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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. Urease-independent chemotactic responses of Helicobacter pylori to urea, urease inhibitors, and sodium bicarbonate.

    OpenAIRE

    Mizote, T; Yoshiyama, H; T. Nakazawa

    1997-01-01

    Helicobacter pylori CPY3401 and an isogenic urease-negative mutant, HPT73, showed chemotactic responses to urea, flurofamide (a potent urease inhibitor), and sodium bicarbonate. Since urea and sodium bicarbonate are secreted through the gastric epithelial surface and hydrolysis of urea by urease on the bacterial surface is essential for colonization, the chemotactic response of H. pylori may be crucial for its colonization and persistence in the stomach.

  3. Effect of proton pump inhibitors on the secretion of bicarbonates and pepsinogen induced by chemical stimulation of the gastric mucosa.

    Science.gov (United States)

    Zolotarev, V A; Khropycheva, R P

    2013-02-01

    Proton pump inhibitors were shown to affect the sensitivity of the gastric mucosa to chemical agents. This effect is associated with inhibition of proton back-diffusion and increase in the permeability of the gastric epithelium. We studied the effect of omeprazole on gastric secretion of bicarbonates and pepsinogen induced by irritation of the gastric mucosa in narcotized rats with a hypertonic solution of high acidity (500 mM NaCl, pH 2.0). Irritation of the gastric mucosa increased the basal secretion of bicarbonates and potentiated the secretion of HCO3(-)and pepsinogen induced by electrostimulation of the vagus nerve. Omeprazole stimulated the prostaglandin-induced increase in the basal secretion of HCO3(-)and pepsinogen. By contrast, bicarbonate production in response to vagal stimulation was suppressed in the presence of omeprazole. Our results indicate that proton pump blockade has a modulatory effect on gastric secretion of bicarbonates and pepsinogen induced by chemical stimulation of the gastric mucosa.

  4. 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.

  5. [Hemodiafiltration with on-line production of bicarbonate infusate: 5 years of clinical experience].

    Science.gov (United States)

    Canaud, B; N'Guyen, Q V; Bouloux-Polito, C; Stec, F; Mion, C

    1992-01-01

    Despite its potential advantages HDF has not gained large clinical acceptance among nephrologist due to its technical complexity and to the large quantity of pharmaceutical substitution fluid needed. HDF with on-line production of substitution fluid from dialysate simplifies the procedure and reduces the cost of treatment session. We treated regularly 13 high risk and/or non-compliant patients (9 males, 4 females) with HDF for 46 +/- 17 months. HDF program consisted of 3 sessions weekly lasting 210 +/- 10 mn with blood flow rate 350 +/- 20 ml/mn and fluid volume exchange of 20 liters/session. High flux dialyzers (HF80, Filtral 16) were reused 6 to 13 times automatically on a Renatron machine with peroxyacetic acid solution as sole cleaning and disinfecting agent. Microbiologic quality of infusate was assessed by membrane filtration culturing method and LAL endotoxin determination. 3937 HDF sessions were performed. 57.140 I of substitution fluid were infused IV to patients. Eight pyrogenic reactions were observed: 2 due to septicemia related to catheter infection and 6 from unknown origin. Adequacy of program was achieved in all patients. Blood pressure control was satisfactorily obtained without antihypertensive medication in 12/13 patients. Effective weekly integrated urea clearances was 150 +/- 15 l/wk, KT/V index was 1.50 +/- 0.10, urea TAC 20 +/- 2 mM/l and protein catabolic rate 1.40 +/- 0.10 g/kg/24 h. We conclude that HDF with on-line production of bicarbonate substitution fluid is a safe and highly efficient method cost-competitive with bicarbonate HD, which offers an interesting alternative for renal replacement therapy.

  6. 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.

  7. 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...

  8. 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.

  9. Bicarbonate Test

    Science.gov (United States)

    ... bicarbonate in the blood). They also help monitor treatment until acid-base balance is restored. ^ Back to top When is it ... basic metabolic panels are commonly used to monitor treatment of certain problems, including ... maintaining its acid-base balance , either by failing to remove carbon dioxide through ...

  10. 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

  11. Evolution of a physiological pH 6.8 bicarbonate buffer system: application to the dissolution testing of enteric coated products.

    OpenAIRE

    Liu, Fang; Merchant, Hamid A.; Kulkarni, Rucha P.; Alkademi, Maram; Basit, Abdul W

    2011-01-01

    The use of compendial pH 6.8 phosphate buffer to assess dissolution of enteric coated products gives rise to poor in vitro-in vivo correlations because of the inadequacy of the buffer to resemble small intestinal fluids. A more representative and physiological medium, pH 6.8 bicarbonate buffer, was developed to evaluate the dissolution behaviour of enteric coatings. The bicarbonate system was evolved from pH7.4 Hanks balanced salt solution to produce a pH 6.8 bicarbonate buffer (modified Hank...

  12. 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.

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

    Science.gov (United States)

    Hatzell, Marta C; Ivanov, Ivan; Cusick, Roland D; Zhu, Xiuping; Logan, Bruce E

    2014-01-28

    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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

    and EE in the field. In this study, four Shetland ponies were used to explore the effect of feeding on CO(2) production and EE measured simultaneously by IC and (13)C-BT. The ponies were individually housed in respiration chambers and received either a single oral or intravenous (IV) bolus dose of (13)C......-labelled sodium bicarbonate (NaH(13)CO(3)). The ponies were fed haylage 3 h before (T(-3)), simultaneously with (T(0)) or 3 h after (T(+3)) administration of (13)C-bicarbonate. The CO(2) produced and O(2) consumed by the ponies were measured for 6 h with both administration routes of (13)C...

  1. 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.

  2. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    Science.gov (United States)

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 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 secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p 0.05) duodenal bicarbonate secretion compared 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 of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative.

  3. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

    OpenAIRE

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 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...

  4. Development of effective combined kinetic hydrate inhibitor/corrosion inhibitor (KHI/CI) products

    Energy Technology Data Exchange (ETDEWEB)

    Clark, Len. W.; Anderson, Joh.

    2006-03-15

    Low Dosage Hydrate Inhibitors (LDHIs) are gaining worldwide acceptance as a viable alternative to the more conventional methods of hydrate flow assurance control. Use of this LDHI technology in combination with Corrosion Inhibitors (CI) in production systems such as sub sea developments enables operating companies to further significantly reduce capital costs. CI can have a significant impact of the efficacy of Kinetic Hydrate Inhibitors (KHI). This paper will review the experience of developing combined KHI and CI products (KHI/CI) with the aim of producing effective products whilst also incorporating the goal of the use of more environmentally friendly CI. Relevant KHI/CI product case histories will be considered. The development of KHI to be used in the presence of CI will also be considered in different production scenarios. This relates to the typical situation of continuous CI usage with the seasonal application of KHI. Experience is also shown of how the incorporation of Thermodynamic Hydrate Inhibitors (THI) to KHI/CI products, in order to enable the combined product to control hydrates in higher subcooling systems, can also have a role to play in the influence that the CI has on the efficiency of the KHI. (author) (tk)

  5. 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...

  6. 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.

  7. Production of plant virus inhibitor by Phytolacca americana suspension culture.

    Science.gov (United States)

    Misawa, M; Hayashi, M; Tanaka, H

    1975-09-01

    The inhibitory activity of tobacco mosaic virus (TMV) infection was assayed with the extracts of various callus tissues derived from the intact plants. Phytolacca americana callus was selected as a producer of the virus inhibitor and its cultural conditions in suspension were examined for cell growth and the inhibitor production. A modified liquid medium containing twofold concentrations of all components in that of Murashige and Skoog plus2,4-D (1.0 mg/liter) and sucrose (6%), but without any vitamins and glycine was chosen for production of higher levels of the inhibitor. TMV infections in tobacco, bean, and tomato plants were markedly inhibited by the introduction of the disrupted whole broth of suspension cultured P. americana.

  8. Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1

    Science.gov (United States)

    Pautus, Stéphane; Alami, Mouad; Adam, Fréderic; Bernadat, Guillaume; Lawrence, Daniel A.; de Carvalho, Allan; Ferry, Gilles; Rupin, Alain; Hamze, Abdallah; Champy, Pierre; Bonneau, Natacha; Gloanec, Philippe; Peglion, Jean-Louis; Brion, Jean-Daniel; Bianchini, Elsa P.; Borgel, Delphine

    2016-11-01

    Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of the tissue type and urokinase type plasminogen activators. High levels of PAI-1 are correlated with an increased risk of thrombotic events and several other pathologies. Despite several compounds with in vitro activity being developed, none of them are currently in clinical use. In this study, we evaluated a novel PAI-1 inhibitor, annonacinone, a natural product from the Annonaceous acetogenins group. Annonacinone was identified in a chromogenic screening assay and was more potent than tiplaxtinin. Annonacinone showed high potency ex vivo on thromboelastography and was able to potentiate the thrombolytic effect of tPA in vivo in a murine model. SDS-PAGE showed that annonacinone inhibited formation of PAI-1/tPA complex via enhancement of the substrate pathway. Mutagenesis and molecular dynamics allowed us to identify annonacinone binding site close to helix D and E and β-sheets 2A.

  9. Apparent Bicarbonate Space in Children

    Directory of Open Access Journals (Sweden)

    Horacio A. Repetto

    2006-01-01

    Full Text Available The amount needed to change the concentration of a solute requires the knowledge of its volume of distribution in the solution. Electrolytes that do not participate in active metabolic reactions have a fixed volume of distribution that corresponds to the volume of water in which they solubilize. Bicarbonate infusion is used to correct hyperchloremic metabolic acidosis. Its volume of distribution (bicarbonate space changes with its participation in the blood buffer systems. In other words, it is not a fixed physical volume, like that of other solutes. In this paper, we shall review experimental studies that supported evidence for this knowledge and analyze the basic hypothesis to explain the phenomena. Since we have not found clinical studies in children, we shall report our experience in a group of patients with metabolic acidosis treated with bicarbonate infusion in whom apparent bicarbonate space was measured and compared with data in adults from the literature. Guidelines for amount of bicarbonate needed to increase its concentration according to baseline bicarbonate concentration will be suggested.

  10. 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 secretion (p...

  11. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

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

    1996-01-01

    The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 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...

  12. Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

    Directory of Open Access Journals (Sweden)

    Kyoungho Suk

    2011-01-01

    Full Text Available Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.

  13. 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

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to 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...... States or directly from stakeholders. The food constituents that are the subject of the health claim are carbonate and bicarbonate salts of sodium and potassium. The Panel considers that carbonate and bicarbonate salts of sodium and potassium are sufficiently characterised. The claimed effects are “acid...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Control of red cell volume and pH in trout: Effects of isoproterenol, transport inhibitors, and extracellular pH in bicarbonate/carbon dioxide-buffered media

    DEFF Research Database (Denmark)

    NIKINMAA, M; STEFFENSEN, JF; TUFTS, BL;

    1987-01-01

    The effects of extracellular pH and beta-adrenergic stimula-tion on the volume and pH of rainbow. trout red cells were studied in HCO3-/ CO2 butfered media. A decrease in extracellular pH caused an increase in red cell volume and a decrease in intracellular pH. The pH-induced changes in cell volume...... were inhibited by 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic acid, (DIDS), an inhibitor of the anion exchange pathway, but not by amiloride, an inhibitor of Na+/H+ exchange, indicating that these volume changes are mainly associated with movements of chloride across the red cell membrane...... were enhanced by a decrease in extracellular pH, showing that the adrenergic response is of benefit to stressed animals. DIDS markedly enhanced the effect of isoproterenol on the pHi, but abolished the increase in red cell volume. The effects of furosemide were similar to those of DIDS, suggesting...

  19. A Culture-Based Method for Determining the Production of Secreted Protease Inhibitors

    Science.gov (United States)

    Quintero, David; Bermudes, David

    2014-01-01

    We have developed a culture-based method for determining the production of secreted protease inhibitors. The assay utilizes standard proteolysis detection plates to support microbial growth followed by infiltrating the plate with a protease and subsequently detecting the remaining protein by trichloroacetic acid (TCA) precipitation, or by bromocreosol green (BCG) or Ponseau S (PS) staining. The presence of a protease inhibitor can be observed in the form of a protected zone of protein around the protease inhibitor-producing strain. Using the protease inhibitors α-2-macroglobulin, aprotinin, leupeptin, and bestatin and the primary and secondary forms of Photorhabdus luminescens in combination with the protease trypsin, we were able to demonstrate that the assay is specific for the cognate inhibitor of the protease and for bacteria secreting protease inhibitors. In addition, when casein-containing plates were used, the size of the diffusion zone was inversely correlated with the molecular weight of the inhibitor allowing a relative estimation of the protease inhibitor molecular weight. This assay is useful for detecting the presence of microbial secreted protease inhibitors and may reveal their production by microorganisms that were not previously recognized to produce them. PMID:24632514

  20. Identifying HER2 inhibitors from natural products database.

    Directory of Open Access Journals (Sweden)

    Shun-Chieh Yang

    Full Text Available The relationship between abnormal HER2 expression and cancer is important in cancer therapeutics. Formation and spread of cancer cells may be restricted by inhibiting HER2. We conducted ligand-based and structure-based studies to assess the potency of natural compounds as potential HER2 inhibitors. Multiple linear regression (MLR and support vector machine (SVM models were constructed to predict biological activities of natural compounds, and molecular dynamics (MD was used to assess their stability with HER2 under a dynamic environment. Predicted bioactivities of the natural compounds ranged from 6.014-9.077 using MLR (r(2 = 0.7954 and 5.122-6.950 using SVM (r(2 = 0.8620. Both models were in agreement and suggest bioactivity based on candidate structure. Conformation changes caused by MD favored the formation of stabilizing H-bonds. All candidates had higher stability than Lapinatib, which may be due to the number and spatial distribution of additional H-bonds and hydrophobic interactions. Amino acids Lys724 and Lys736 are critical for binding in HER2, and Thr798, Cys805, and Asp808 are also important for increased stability. Candidates may block the entrance to the ATP binding site located within the inner regions and prevent downstream activation of HER2. Our multidirectional approach indicates that the natural compounds have good ligand efficacy in addition to stable binding affinities to HER2, and should be potent candidates of HER2 inhibitors. With regard to drug design, designing HER2 inhibitors with carboxyl or carbonyl groups available for H-bond formation with Lys724 and Lys736, and benzene groups for hydrophobic contact with Cys805 may improve protein-ligand stability.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to sodium 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...

  6. 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.

  7. 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 expres...

  8. 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...

  9. Identification of baicalein as a ferroptosis inhibitor by natural product library screening.

    Science.gov (United States)

    Xie, Yangchun; Song, Xinxin; Sun, Xiaofang; Huang, Jin; Zhong, Meizuo; Lotze, Michael T; Zeh, Herbert J; Kang, Rui; Tang, Daolin

    2016-05-13

    Ferroptosis, a novel form of regulated cell death, is characterized by oxidative injury from iron accumulation and lipid peroxidation. In a natural product library screening for ferroptosis inhibitor, we found that baicalein is a potent inhibitor of erastin-induced ferroptosis in pancreatic cancer cells. Baicalein (also termed 5,6,7-trihydroxyflavone) is a flavonoid originally obtained from the roots of Scutellaria baicalensis and Scutellaria lateriflora. We showed that baicalein exhibits remarkable anti-ferroptosis activity compared with well-known ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, deferoxamine mesylate, and β-mercaptoethanol. At the biochemistry level, baicalein limits erastin-induced ferrous iron production, glutathione depletion, and lipid peroxidation. At the protein level, baicalein suppresses erastin-mediated degradation of glutathione peroxidase 4, a phospholipid hydroperoxidase that protects cells against membrane lipid peroxidation. Thus, baicalein enhances cellular anti-ferroptosis capacity and could be a potential therapeutic agent for ferroptosis-associated tissue injury.

  10. 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.

  11. 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.

  12. [Involvement of carbonate/bicarbonate ions in the superoxide-generating reaction of adrenaline autoxidation].

    Science.gov (United States)

    Sirota, T V

    2015-01-01

    An important role of carbonate/bicarbonate ions has been recognized in the superoxide generating reaction of adrenaline autooxidation in an alkaline buffer (a model of quinoid adrenaline oxidation in the body). It is suggested that these ions are directly involved not only in formation of superoxide anion radical (О(2)(-)) but also other radicals derived from the carbonate/bicarbonate buffer. Using various buffers it was shown that the rate of accumulation of adrenochrome, the end product of adrenaline oxidation, and the rate of О(2)(-)· formation depend on concentration of carbonate/bicarbonate ions in the buffer and that these ions significantly accelerate adrenaline autooxidation thus demonstrating prooxidant properties. The detectable amount of diformazan, the product of nitro blue tetrazolium (NBT) reduction, was significantly higher than the amount of adrenochrome formed; taking into consideration the literature data on О(2)(-)· detection by NBT it is suggested that adrenaline autooxidation is accompanied by one-electron reduction not only of oxygen dissolved in the buffer and responsible for superoxide formation but possible carbon dioxide also dissolved in the buffer as well as carbonate/bicarbonate buffer components leading to formation of corresponding radicals. The plots of the dependence of the inhibition of adrenochrome and diformazan formation on the superoxide dismutase concentration have shown that not only superoxide radicals are formed during adrenaline autooxidation. Since carbonate/bicarbonate ions are known to be universally present in the living nature, their involvement in free radical processes proceeding in the organism is discussed.

  13. 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)

  14. Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

    Directory of Open Access Journals (Sweden)

    Matthias G. J. Baud

    2013-01-01

    Full Text Available There has been significant interest in the bioactivity of the natural product psammaplin A, most recently as a potent and isoform selective HDAC inhibitor. Here we report our preliminary studies on thioester HDAC inhibitors derived from the active monomeric (thiol form of psammaplin A, as a means to improve compound delivery into cells. We have discovered that such compounds exhibit both potent cytotoxicity and enzymatic inhibitory activity against recombinant HDAC1. The latter effect is surprising since previous SAR suggested that modification of the thiol functionality should detrimentally affect HDAC potency. We therefore also report our preliminary studies on the mechanism of action of this observed effect.

  15. Biofiltration with bicarbonate as dialysate buffer.

    Science.gov (United States)

    Rizzelli, S; Alfonso, L; Corlianò, C; Patruno, P; Sozzo, E; Mastrangelo, F

    1986-12-01

    The biofiltration with bicarbonate as dialysate buffer (BiBF) was used in 10 patients on RDT: the patients were treated for 10 months on standard BF and for 10 months on BiBF. The amount of fluid infused varied between 3 and 5 liters and Na-bicarbonate (100 mEq/h) was infused during BF. The dialytic protocol was 3 hours every other day. Cardiovascular stability, waste molecules and acid-base balance were investigated. No differences in vascular stability and no significant changes in the waste-molecules concentrations were found. Both protocols correct the metabolic acidosis; however, in standard BF 50% of patients showed acute hypocapnia at the end of dialysis.

  16. 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.

  17. 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.

  18. Flocculation causes inhibitor tolerance in Saccharomyces cerevisiae for second-generation bioethanol production.

    Science.gov (United States)

    Westman, Johan O; Mapelli, Valeria; Taherzadeh, Mohammad J; Franzén, Carl Johan

    2014-11-01

    Yeast has long been considered the microorganism of choice for second-generation bioethanol production due to its fermentative capacity and ethanol tolerance. However, tolerance toward inhibitors derived from lignocellulosic materials is still an issue. Flocculating yeast strains often perform relatively well in inhibitory media, but inhibitor tolerance has never been clearly linked to the actual flocculation ability per se. In this study, variants of the flocculation gene FLO1 were transformed into the genome of the nonflocculating laboratory yeast strain Saccharomyces cerevisiae CEN.PK 113-7D. Three mutants with distinct differences in flocculation properties were isolated and characterized. The degree of flocculation and hydrophobicity of the cells were correlated to the length of the gene variant. The effect of different strength of flocculation on the fermentation performance of the strains was studied in defined medium with or without fermentation inhibitors, as well as in media based on dilute acid spruce hydrolysate. Strong flocculation aided against the readily convertible inhibitor furfural but not against less convertible inhibitors such as carboxylic acids. During fermentation of dilute acid spruce hydrolysate, the most strongly flocculating mutant with dense cell flocs showed significantly faster sugar consumption. The modified strain with the weakest flocculation showed a hexose consumption profile similar to the untransformed strain. These findings may explain why flocculation has evolved as a stress response and can find application in fermentation-based biorefinery processes on lignocellulosic raw materials.

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

    OpenAIRE

    2013-01-01

    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...

  20. 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 of form...

  1. 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.

  2. Potential of Natural Products of Herbal Origin as Monoamine Oxidase Inhibitors.

    Science.gov (United States)

    Orhan, Ilkay Erdogan

    2016-01-01

    Monoamine oxidase (MAO, E.C. 1.4.3.4) is a flavin-adenine type of enzyme with two isoforms referred to MAO-A and MAO-B that function for oxidation of monoamines. While MAO-A inhibitors are effective as antidepressant and anxiolytic drugs (e.g. chlorgyline, moclobemide, and lazabemide), inhibitors of MAO-B (e.g. Ldeprenyl, pargyline, and rasagiline) are used against neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Considering the need for novel MAO inhibitors due to side effects of the current ones, natural products have become attractive targets for researchers. Up till now, many studies revealed strong MAO inhibitory activity of flavonoid, xanthone, alkaloid, and coumarin derivatives from herbal sources, which also become good models for the synthetic MAO inhibitors. For this purpose, the present review focuses on examples of in vitro and in vivo MAO-inhibiting natural compounds of plant origin from a wide variety of chemical classes isolated mainly between 2000 - 2015.

  3. Reappraisal of bicarbonate secretion by the human oesophagus

    DEFF Research Database (Denmark)

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

    1997-01-01

    BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosal bicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophageal bicarbonate secretion...... 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...... 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...

  4. Reappraisal of bicarbonate secretion by the human oesophagus.

    OpenAIRE

    Mertz-Nielsen, A; Hillingsø, J; Bukhave, K; Rask-Madsen, J

    1997-01-01

    BACKGROUND AND AIMS: Administration of omeprazole to healthy volunteers was recently reported to increase proximal duodenal mucosal bicarbonate secretion. As human oesophagus also secretes bicarbonate, the hypothesis was tested that omeprazole may stimulate oesophageal bicarbonate secretion 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 segm...

  5. 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.

  6. 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

  7. Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, SAN 05.

    Science.gov (United States)

    2004-01-01

    Santarus Inc. is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers. Acitreltrade mark is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for gastrointestinal (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders. Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results in August 2003 from a phase III trial comparing oral Acitrel (Rapinex 40 mg) with intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of this omeprazole 40 mg powder suspension for an 8-week period. In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

  8. Screening for Small Molecule Inhibitors of Statin-Induced APP C-terminal Toxic Fragment Production

    Science.gov (United States)

    Poksay, Karen S.; Sheffler, Douglas J.; Spilman, Patricia; Campagna, Jesus; Jagodzinska, Barbara; Descamps, Olivier; Gorostiza, Olivia; Matalis, Alex; Mullenix, Michael; Bredesen, Dale E.; Cosford, Nicholas D. P.; John, Varghese

    2017-01-01

    Alzheimer’s disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds – identified here using cells and tissues expressing wt human APP – in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects.

  9. Screening for Small Molecule Inhibitors of Statin-Induced APP C-terminal Toxic Fragment Production.

    Science.gov (United States)

    Poksay, Karen S; Sheffler, Douglas J; Spilman, Patricia; Campagna, Jesus; Jagodzinska, Barbara; Descamps, Olivier; Gorostiza, Olivia; Matalis, Alex; Mullenix, Michael; Bredesen, Dale E; Cosford, Nicholas D P; John, Varghese

    2017-01-01

    Alzheimer's disease (AD) is characterized by neuronal and synaptic loss. One process that could contribute to this loss is the intracellular caspase cleavage of the amyloid precursor protein (APP) resulting in release of the toxic C-terminal 31-amino acid peptide APP-C31 along with the production of APPΔC31, full-length APP minus the C-terminal 31 amino acids. We previously found that a mutation in APP that prevents this caspase cleavage ameliorated synaptic loss and cognitive impairment in a murine AD model. Thus, inhibition of this cleavage is a reasonable target for new therapeutic development. In order to identify small molecules that inhibit the generation of APP-C31, we first used an APPΔC31 cleavage site-specific antibody to develop an AlphaLISA to screen several chemical compound libraries for the level of N-terminal fragment production. This antibody was also used to develop an ELISA for validation studies. In both high throughput screening (HTS) and validation testing, the ability of compounds to inhibit simvastatin- (HTS) or cerivastatin- (validation studies) induced caspase cleavage at the APP-D720 cleavage site was determined in Chinese hamster ovary (CHO) cells stably transfected with wildtype (wt) human APP (CHO-7W). Several compounds, as well as control pan-caspase inhibitor Q-VD-OPh, inhibited APPΔC31 production (measured fragment) and rescued cell death in a dose-dependent manner. The effective compounds fell into several classes including SERCA inhibitors, inhibitors of Wnt signaling, and calcium channel antagonists. Further studies are underway to evaluate the efficacy of lead compounds - identified here using cells and tissues expressing wt human APP - in mouse models of AD expressing mutated human APP, as well as to identify additional compounds and determine the mechanisms by which they exert their effects.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    . Bicarbonate secretion is inhibited by atropine, muscarinic antagonists, alpha-adrenoceptor agonists, indomethacin, bile acids, tobacco smoking, and probably also by infection by Helicobacter pylori. Apart from mucus and bicarbonate, the mucosal defence is supported by a hydrophobic epithelial lining, rapid...

  11. Sodium bicarbonate therapy in patients with metabolic acidosis.

    Science.gov (United States)

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

    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 regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

  12. 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...

  13. Sodium bicarbonate ingestion and boxing performance.

    Science.gov (United States)

    Siegler, Jason C; Hirscher, Kristian

    2010-01-01

    Boxing is a sport that consists of multiple high-intensity bouts separated by minimal recovery time and may benefit from a pre-exercise alkalotic state. The purpose of this study was to observe the ergogenic potential of sodium bicarbonate (NaHCO3) ingestion on boxing performance. Ten amateur boxers volunteered to participate in 2 competitive sparring bouts. The boxers were prematched for weight and boxing ability and consumed either 0.3 g.kg(-1) body weight (BW) of NaHCO3 (BICARB) or 0.045 g.kg(-1) BW of NaCl placebo (PLAC) mixed in diluted low calorie-flavored cordial. The sparring bouts consisted of four 3-minute rounds, each separated by 1-minute seated recovery. Blood acid-base (pH, bicarbonate [HCO3(-)], base excess [BE]), and performance (rates of perceived exertion [RPE], heart rate [HR] [HR(ave) and HR(max)], total punches landed successfully) profiles were analyzed before (where applicable) and after sparring. The results indicated a significant interaction effect for HCO3(-) (p < or = 0.001) and BE (p < 0.001), but not for pH (p = 0.48). Post hoc analysis revealed higher presparring HCO3(-) and BE for the BICARB condition, but no differences between the BICARB and PLAC conditions postsparring. There was a significant increase in punches landed during the BICARB condition (p < 0.001); however, no significant interaction effects for HRave (p = 0.15), HRmax (p = 0.32), or RPE (p = 0.38). The metabolic alkalosis induced by the NaHCO3 loading elevated before and after sparring blood buffering capacity. In practical application, the findings suggest that a standard NaHCO3 loading dose (0.3 g.kg(-1)) improves punch efficacy during 4 rounds of sparring performance.

  14. 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.

  15. Regulation of anterior chamber drainage by bicarbonate-sensitive soluble adenylyl cyclase in the ciliary body.

    Science.gov (United States)

    Lee, Yong S; Tresguerres, Martin; Hess, Kenneth; Marmorstein, Lihua Y; Levin, Lonny R; Buck, Jochen; Marmorstein, Alan D

    2011-12-02

    Glaucoma is a leading cause of blindness affecting as many as 2.2 million Americans. All current glaucoma treatment strategies aim to reduce intraocular pressure (IOP). IOP results from the resistance to drainage of aqueous humor (AH) produced by the ciliary body in a process requiring bicarbonate. Once secreted into the anterior chamber, AH drains from the eye via two pathways: uveoscleral and pressure-dependent or conventional outflow (C(t)). Modulation of "inflow" and "outflow" pathways is thought to occur via distinct, local mechanisms. Mice deficient in the bicarbonate channel bestrophin-2 (Best2), however, exhibit a lower IOP despite an increase in AH production. Best2 is expressed uniquely in nonpigmented ciliary epithelial (NPE) cells providing evidence for a bicarbonate-dependent communicative pathway linking inflow and outflow. Here, we show that bicarbonate-sensitive soluble adenylyl cyclase (sAC) is highly expressed in the ciliary body in NPE cells, but appears to be absent from drainage tissues. Pharmacologic inhibition of sAC in mice causes a significant increase in IOP due to a decrease in C(t) with no effect on inflow. In mice deficient in sAC IOP is elevated, and C(t) is decreased relative to wild-type mice. Pharmacologic inhibition of sAC did not alter IOP or C(t) in sAC-deficient mice. Based on these data we propose that the ciliary body can regulate C(t) and that sAC serves as a critical sensor of bicarbonate in the ciliary body regulating the secretion of substances into the AH that govern outflow facility independent of pressure.

  16. Regulation of Anterior Chamber Drainage by Bicarbonate-sensitive Soluble Adenylyl Cyclase in the Ciliary Body*

    Science.gov (United States)

    Lee, Yong S.; Tresguerres, Martin; Hess, Kenneth; Marmorstein, Lihua Y.; Levin, Lonny R.; Buck, Jochen; Marmorstein, Alan D.

    2011-01-01

    Glaucoma is a leading cause of blindness affecting as many as 2.2 million Americans. All current glaucoma treatment strategies aim to reduce intraocular pressure (IOP). IOP results from the resistance to drainage of aqueous humor (AH) produced by the ciliary body in a process requiring bicarbonate. Once secreted into the anterior chamber, AH drains from the eye via two pathways: uveoscleral and pressure-dependent or conventional outflow (Ct). Modulation of “inflow” and “outflow” pathways is thought to occur via distinct, local mechanisms. Mice deficient in the bicarbonate channel bestrophin-2 (Best2), however, exhibit a lower IOP despite an increase in AH production. Best2 is expressed uniquely in nonpigmented ciliary epithelial (NPE) cells providing evidence for a bicarbonate-dependent communicative pathway linking inflow and outflow. Here, we show that bicarbonate-sensitive soluble adenylyl cyclase (sAC) is highly expressed in the ciliary body in NPE cells, but appears to be absent from drainage tissues. Pharmacologic inhibition of sAC in mice causes a significant increase in IOP due to a decrease in Ct with no effect on inflow. In mice deficient in sAC IOP is elevated, and Ct is decreased relative to wild-type mice. Pharmacologic inhibition of sAC did not alter IOP or Ct in sAC-deficient mice. Based on these data we propose that the ciliary body can regulate Ct and that sAC serves as a critical sensor of bicarbonate in the ciliary body regulating the secretion of substances into the AH that govern outflow facility independent of pressure. PMID:21994938

  17. DNA structures decorated with cathepsin G/secretory leukocyte proteinase inhibitor stimulate IFNI production by plasmacytoid dendritic cells

    DEFF Research Database (Denmark)

    Skrzeczynska-Moncznik, Joanna; Wlodarczyk, Agnieszka; Banas, Magdalena;

    2013-01-01

    psoriasis. Here, we demonstrate that IFNI production in pDCs is stimulated by DNA structures containing the neutrophil serine protease cathepsin G (CatG) and the secretory leukocyte protease inhibitor (SLPI), which is a controlling inhibitor of serine proteases. We also demonstrate the presence...... of neutrophil-derived DNA structures containing CatG and SLPI in lesional skin samples from psoriasis patients. These findings suggest a previously unappreciated role for CatG in psoriasis by linking CatG and its inhibitor SLPI to the IFNI-dependent regulation of immune responses by pDCs in psoriatic skin....

  18. 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.

  19. Intestinal Bicarbonate Secretion in Cystic Fibrosis Mice

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    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

  20. Production of a protease inhibitor from edible mushroom Agaricus bisporus and its statistical optimization by response surface methodology.

    Science.gov (United States)

    Vishvakarma, Reena; Mishra, Abha

    2017-01-31

    The production of a protease inhibitor from Agaricus bisporus through solid state fermentation was studied. The purpose was to produce protease inhibitor from natural, cheap and readily available carbon and nitrogen sources. Solid state fermentation enhanced the mycelia growth and also gave a higher yield of the product. Further, fungal growth and other production parameters were statistically optimized. The specificity of the inhibitor was tested and was effective against trypsin. Screening of significant factors (wheat bran, cyanobacterial biomass, initial pH, temperature, incubation period, and moisture content and inoculum size) was done using Plackett-Burman Design. Central Composite Design was used to determine the optimized values of the significant variables which were found to be temperature (27.5 °C), incubation time (156 hrs.), cyanobacterial biomass (1 g) and moisture content (50%) and gave a statistical yield of 980 PIU/g which was 25.6% higher than experimental yield (780 PIU/g). The inhibitor was purified by ammonium sulphate precipitation and DEAE cellulose chromatography (yield 43.89% and 0.21% respectively) and subjected to Reversed-phase HPLC to validate its identity. Since protease inhibitors act against proteases, finding ample therapeutic roles; the isolated protease inhibitor from A. bisporus can also be a probable medicinal agent after its further characterization.

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

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    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

  2. High-content screening of natural products reveals novel nuclear export inhibitors.

    Science.gov (United States)

    Cautain, Bastien; de Pedro, Nuria; Murillo Garzón, Virginia; Muñoz de Escalona, María; González Menéndez, Victor; Tormo, José R; Martin, Jesús; El Aouad, Noureddine; Reyes, Fernando; Asensio, Francisco; Genilloud, Olga; Vicente, Francisca; Link, Wolfgang

    2014-01-01

    Natural products are considered an extremely valuable source for the discovery of new drugs against diverse pathologies. As yet, we have only explored a fraction of the diversity of bioactive compounds, and opportunities for discovering new natural products leading to new drugs are huge. In the present study, U2nesRELOC, a previously established cell-based imaging assay, was employed to screen a collection of extracts of microbial origin for nuclear export inhibition activity. The fluorescent signal of untreated U2nesRELOC cells localizes predominantly to the cytoplasm. Upon treatment with the nuclear export inhibitor leptomycin B, the fluorescent-tagged reporter proteins appear as speckles in the nucleus. A proprietary collection of extracts from fungi, actinomycetes, and unicellular bacteria that covers an uncommonly broad chemical space was used to interrogate this nuclear export assay system. A two-step image-based analysis allowed us to identify 12 extracts with biological activities that are not associated with previously known active metabolites. The fractionation and structural elucidation of active compounds revealed several chemical structures with nuclear export inhibition activity. Here we show that substrates of the nuclear export receptor CRM1, such as Rev, FOXO3a and NF-κB, accumulate in the nucleus in the presence of the fungal metabolite MDN-0105 with an IC50 value of 3.4 µM. Many important processes in tumor formation and progression, as well as in many viral infections, critically depend on the nucleocytoplasmic trafficking of proteins and RNA molecules. Therefore, the disruption of nuclear export is emerging as a novel therapeutic approach with enormous clinical potential. Our work highlights the potential of applying high-throughput phenotypic imaging on natural product extracts to identify novel nuclear export inhibitors.

  3. 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.

  4. 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.

  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. Metabolomic Responses of Guard Cells and Mesophyll Cells to Bicarbonate.

    Science.gov (United States)

    Misra, Biswapriya B; de Armas, Evaldo; Tong, Zhaohui; Chen, Sixue

    2015-01-01

    Anthropogenic CO2 presently at 400 ppm is expected to reach 550 ppm in 2050, an increment expected to affect plant growth and productivity. Paired stomatal guard cells (GCs) are the gate-way for water, CO2, and pathogen, while mesophyll cells (MCs) represent the bulk cell-type of green leaves mainly for photosynthesis. We used the two different cell types, i.e., GCs and MCs from canola (Brassica napus) to profile metabolomic changes upon increased CO2 through supplementation with bicarbonate (HCO3-). Two metabolomics platforms enabled quantification of 268 metabolites in a time-course study to reveal short-term responses. The HCO3- responsive metabolomes of the cell types differed in their responsiveness. The MCs demonstrated increased amino acids, phenylpropanoids, redox metabolites, auxins and cytokinins, all of which were decreased in GCs in response to HCO3-. In addition, the GCs showed differential increases of primary C-metabolites, N-metabolites (e.g., purines and amino acids), and defense-responsive pathways (e.g., alkaloids, phenolics, and flavonoids) as compared to the MCs, indicating differential C/N homeostasis in the cell-types. The metabolomics results provide insights into plant responses and crop productivity under future climatic changes where elevated CO2 conditions are to take center-stage.

  7. Metabolomic Responses of Guard Cells and Mesophyll Cells to Bicarbonate.

    Directory of Open Access Journals (Sweden)

    Biswapriya B Misra

    Full Text Available Anthropogenic CO2 presently at 400 ppm is expected to reach 550 ppm in 2050, an increment expected to affect plant growth and productivity. Paired stomatal guard cells (GCs are the gate-way for water, CO2, and pathogen, while mesophyll cells (MCs represent the bulk cell-type of green leaves mainly for photosynthesis. We used the two different cell types, i.e., GCs and MCs from canola (Brassica napus to profile metabolomic changes upon increased CO2 through supplementation with bicarbonate (HCO3-. Two metabolomics platforms enabled quantification of 268 metabolites in a time-course study to reveal short-term responses. The HCO3- responsive metabolomes of the cell types differed in their responsiveness. The MCs demonstrated increased amino acids, phenylpropanoids, redox metabolites, auxins and cytokinins, all of which were decreased in GCs in response to HCO3-. In addition, the GCs showed differential increases of primary C-metabolites, N-metabolites (e.g., purines and amino acids, and defense-responsive pathways (e.g., alkaloids, phenolics, and flavonoids as compared to the MCs, indicating differential C/N homeostasis in the cell-types. The metabolomics results provide insights into plant responses and crop productivity under future climatic changes where elevated CO2 conditions are to take center-stage.

  8. Combined creatine and sodium bicarbonate supplementation enhances interval swimming.

    Science.gov (United States)

    Mero, Antti A; Keskinen, Kari L; Malvela, Marko T; Sallinen, Janne M

    2004-05-01

    This study examined the effect of simultaneous supplementation of creatine and sodium bicarbonate on consecutive maximal swims. Sixteen competitive male and female swimmers completed, in a randomized order, 2 different treatments (placebo and a combination of creatine and sodium bicarbonate) with 30 days of washout period between treatments in a double-blind crossover procedure. Both treatments consisted of placebo or creatine supplementation (20 g per day) in 6 days. In the morning of the seventh day, there was placebo or sodium bicarbonate supplementation (0.3 g per kg body weight) during 2 hours before a warm-up for 2 maximal 100-m freestyle swims that were performed with a passive recovery of 10 minutes in between. The first swims were similar, but the increase in time of the second versus the first 100-m swimming time was 0.9 seconds less (p creatine and sodium bicarbonate enhances performance in consecutive maximal swims.

  9. 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.

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

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    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

  11. 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.

  12. Carbonate and Bicarbonate Ion Transport in Alkaline Anion Exchange Membranes

    Science.gov (United States)

    2013-06-25

    Bicarbonate Ion Transport in Alk Block 13: Supplementary Note © 2013 . Published in Journal of the Electrochemical Society , Vol. Ed. 0 160, (9) (2013...for public release; distribution is unlimited. ... 60325.7-CH-II F994 Journal of The Electrochemical Society , 160 (9) F994-F999 (2013) 0013-4651/2013...160(9)/F994/6/$31.00 © The Electrochemical Society Carbonate and Bicarbonate Ion Transport in Alkaline Anion Exchange Membranes Andrew M. Kiss,a

  13. Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East African medicinal plants.

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    Alexander D Crawford

    Full Text Available Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS. Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products.

  14. 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.

  15. 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

  16. Sodium bicarbonated mineral water decreases postprandial lipaemia in postmenopausal women compared to a low mineral water

    OpenAIRE

    S. Schoppen; Pérez Granados, Ana M.; Carbajal, A.; Sarriá, Beatriz; Sánchez-Muniz, F. J.; J. A. Gómez-Gerique; Vaquero, M. Pilar

    2005-01-01

    The role of bicarbonated mineral waters on lipid metabolism and lipoprotein concentrations in man has scarcely been investigated. The present study aimed to investigate whether drinking sodium bicarbonated mineral water affects postprandial cholesterol and triacylglycerol metabolism in postmenopausal women. In a three-way, randomised, crossover study, eighteen healthy postmenopausal women consumed two sodium bicarbonated mineral waters (bicarbonated mineral water 1 and bicarbonated mineral wa...

  17. 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

  18. Production of proteasome inhibitor syringolin A by the endophyte Rhizobium sp. strain AP16.

    Science.gov (United States)

    Dudnik, Alexey; Bigler, Laurent; Dudler, Robert

    2014-06-01

    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.

  19. 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.

  20. 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.

  1. Meta-analysis of the effect of urease and nitrification inhibitors on crop productivity and nitrogen use efficience

    NARCIS (Netherlands)

    Abalos, D.; Jeffery, S.L.; Sanz-Cobena, A.; Guardia, G.; Vallejo, A.

    2014-01-01

    Nitrification and urease inhibitors are proposed as means to reduce nitrogen losses, thereby increasing crop nitrogen use efficiency (NUE). However, their effect on crop yield is variable. A meta-analysis was conducted to evaluate their effectiveness at increasing NUE and crop productivity. Commonly

  2. Different effects of lipopolysaccharide on plasminogen activator inhibitor-1 production in aortic media in vivo and in culture

    NARCIS (Netherlands)

    Leeuwen, R.T.J. van; Quax, P.H.A.; Tippins, J.R.; Antoniw, J.W.; Andreotti, F.; Maseri, A.; Kluft, C.; Sperti, G.

    1996-01-01

    Background: Lipopolysaccharide (endotoxin) has been shown to increase the expression of plasminogen activator inhibitor type-1 (PAI-1) in the vessel wall. Endotoxin is known to increase PAI-1 production in endothelial cells, but its action on smooth muscle cells (SMCs) is presently not clear. In thi

  3. Degradation of Organophosphorus Pesticides in Water during UV/H2O2 Treatment: Role of Sulphate and Bicarbonate Ions

    Directory of Open Access Journals (Sweden)

    Am Fadaei

    2012-01-01

    Full Text Available The photodegradation of two organophosphorus pesticides, malathian and diazinon, by sulfate radicals and bicarbonate radicals in aqueous solution were studied. The effect of the operational parameters such as pH, salt concentration, water type, H2O2 concentration and initial concentration of pesticides was studied. Gas chromatography mass spectroscopy (GC–MS was used for analyses of pesticides. When salt effect was studied, it was found that sodium bicarbonate was the most powerful inhibitor used, while sodium sulfate was the weakest one. The highest degradation in UV/H2O2 process for malathion was found in alkaline condition and for diazinon in acidic condition. The photodegradation in all waters used in this work exhibited first order kinetics. Photodegradation rate in distilled water was higher than real water. The degradation of pesticides increased with increasing of H2O2 concentration.

  4. 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.

  5. 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.

  6. 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.

  7. Effects of alpha-amylase and its inhibitors on acid production from cooked starch by oral streptococci.

    Science.gov (United States)

    Aizawa, S; Miyasawa-Hori, H; Nakajo, K; Washio, J; Mayanagi, H; Fukumoto, S; Takahashi, N

    2009-01-01

    This study evaluated acid production from cooked starch by Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and Streptococcus mitis, and the effects of alpha-amylase inhibitors (maltotriitol and acarbose) and xylitol on acid production. Streptococcal cell suspensions were anaerobically incubated with various carbohydrates that included cooked potato starch in the presence or absence of alpha-amylase. Subsequently, the fall in pH and the acid production rate at pH 7.0 were measured. In addition, the effects of adding alpha-amylase inhibitors and xylitol to the reaction mixture were evaluated. In the absence of alpha-amylase, both the fall in pH and the acid production rate from cooked starch were small. On the other hand, in the presence of alpha-amylase, the pH fell to 3.9-4.4 and the acid production rate was 0.61-0.92 micromol per optical density unit per min. These values were comparable to those for maltose. When using cooked starch, the fall in pH by S. sanguinis and S. mitis was similar to that by S. mutans and S. sobrinus. For all streptococci, alpha-amylase inhibitors caused a decrease in acid production from cooked starch, although xylitol only decreased acid production by S. mutans and S. sobrinus. These results suggest that cooked starch is potentially acidogenic in the presence of alpha-amylase, which occurs in the oral cavity. In terms of the acidogenic potential of cooked starch, S. sanguinis and S. mitis were comparable to S. mutans and S. sobrinus. Alpha-amylase inhibitors and xylitol might moderate this activity.

  8. 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.

  9. 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.

  10. 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.

  11. Characterization of a small molecule inhibitor of tumor necrosis factor-alpha production

    Institute of Scientific and Technical Information of China (English)

    YANG Gao-yun; XIE Zhi-qiang; QIAN Ge; CUI Wen-ying; ZHAO Jun-yin; ZHANG Jian-zhong; LIAN Shi

    2010-01-01

    Background Numerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFα) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes.Methods Peripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 μg/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 μg/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37C, and quantitative determination of TNFα, interleukin-1β(IL-1β), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 μmol/L, 1 μmol/L, 0.1 μmol/L,0.01 μmol/L and 0.001 μmol/L) or dimethyl sulfoxide at 37C for 10 minutes, and then stimulated with LPS or PMA,protein concentrations of p44.42, IKBα, P38 and Jun NH2-terminal kinase were determined by Western blotting. Cyclic adenosine-3',5'-monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech).Results Y316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and

  12. 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

    Many pathogens control production of virulence factors by self-produced signals in a process called quorum sensing (QS). We demonstrate that acyl homoserine lactone (AHL) signals, which enable bacteria to express certain phenotypes in relation to cell density, are produced by a wide spectrum....... 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...

  13. 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.

  14. 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.

  15. 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.

  16. [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.

  17. Role of bicarbonate at the acceptor side of photosystem II

    NARCIS (Netherlands)

    Rensen, van J.J.S.

    2002-01-01

    Besides being the substrate for the carboxylation reaction of photosynthesis, CO2 (bicarbonate) is required for the activity of Photosystem II (water plastoquinone oxido-reductase). It plays a role on the electron donor side as well as the electron acceptor side. In this contribution, attention will

  18. Undisplayed Bicarbonate ion Concentration in Arterial Blood Gas Analysis

    OpenAIRE

    2013-01-01

    Blood bicarbonate ion concentration (BcHCO3-) is a vital parameter in the management of acid base disorders. In an arterial blood gas (ABG) analyzer, the BcHCO3- is calculated from the values of pH and pCO2.

  19. 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.

  20. Regulation of Photosystem II Electron transport by Bicarbonate

    NARCIS (Netherlands)

    Rensen, van J.J.S.

    2012-01-01

    In oxygenic photosynthesis, carbon dioxide is fixed by ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and further reduced to carbohydrates. However, CO2, in the form of carbonate or bicarbonate, is also directly involved in the “light reactions” through structural and regulatory roles wit

  1. 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.

  2. 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

  3. Dynamic volume changes in astrocytes are an intrinsic phenomenon mediated by bicarbonate ion flux.

    Directory of Open Access Journals (Sweden)

    Clare M Florence

    Full Text Available Astrocytes, the major type of non-neuronal cells in the brain, play an important functional role in extracellular potassium ([K(+](o and pH homeostasis. Pathological brain states that result in [K(+](o and pH dysregulation have been shown to cause astrocyte swelling. However, whether astrocyte volume changes occur under physiological conditions is not known. In this study we used two-photon imaging to visualize real-time astrocyte volume changes in the stratum radiatum of the hippocampus CA1 region. Astrocytes were observed to swell by 19.0±0.9% in response to a small physiological increase in the concentration of [K(+](o (3 mM. Astrocyte swelling was mediated by the influx of bicarbonate (HCO(3- ions as swelling was significantly decreased when the influx of HCO(3- was reduced. We found: 1 in HCO(3- free extracellular solution astrocytes swelled by 5.4±0.7%, 2 when the activity of the sodium-bicarbonate cotransporter (NBC was blocked the astrocytes swelled by 8.3±0.7%, and 3 in the presence of an extracellular carbonic anhydrase (CA inhibitor astrocytes swelled by 11.4±0.6%. Because a significant HCO(3- efflux is known to occur through the γ-amino-butyric acid (GABA channel, we performed a series of experiments to determine if astrocytes were capable of HCO(3- mediated volume shrinkage with GABA channel activation. Astrocytes were found to shrink -7.7±0.5% of control in response to the GABA(A channel agonist muscimol. Astrocyte shrinkage from GABA(A channel activation was significantly decreased to -5.0±0.6% of control in the presence of the membrane-permeant CA inhibitor acetazolamide (ACTZ. These dynamic astrocyte volume changes may represent a previously unappreciated yet fundamental mechanism by which astrocytes regulate physiological brain functioning.

  4. Bicarbonate exporting transporters in the ovine ruminal epithelium.

    Science.gov (United States)

    Bilk, S; Huhn, K; Honscha, K U; Pfannkuche, H; Gäbel, G

    2005-07-01

    In order to stabilize the intraruminal pH, bicarbonate secretion by the ruminal epithelium seems to be an important prerequisite. The present study therefore focussed on the characterization of bicarbonate exporting systems in ruminal epithelial cells. Intracellular pH (pH(i)) was measured spectrofluorometrically in primary cultured ruminal epithelial cells loaded with the pH-sensitive fluorescent dye, 2,7-bis(carboxyethyl)-5(6')-carboxyfluorescein acetomethyl ester. Switching from CO2/HCO3- -buffered to HEPES-buffered solution caused a rapid intracellular alkalinization followed by a counter-regulation towards initial pH(i). The recovery of pH(i) was dependent upon extracellular chloride, but independent of extracellular sodium. Adding 500 microM H2DIDS significantly reduced the increase of pH(i). For further characterization of the bicarbonate exporting systems, we tested the ability to reverse the direction from HCO3- export to import in the absence of sodium and chloride. Under sodium and chloride-free conditions, counter-regulation after CO2-induced pH(i) decrease did not differ from pH(i) recovery in the presence of sodium and chloride. Existence of bicarbonate exporting systems in cultured ruminal epithelial cells and intact ruminal epithelium was verified by reverse transcription polymerase chain reaction (RT-PCR). Using RT-PCR and subsequent sequencing, expression of mRNA encoding for AE2, DRA and PAT1 could be found. Bicarbonate exporting systems could therefore be detected both on the functional and structural level.

  5. Addition of sodium bicarbonate to complete pelleted diets fed to dairy calves.

    Science.gov (United States)

    Wheeler, T B; Wangsness, P J; Muller, L D; Griel, L C

    1980-11-01

    During two trials, 35 and 27 Holstein calves were fed ad libitum complete, pelleted diets containing either 35% alfalfa (Trial 1) or 35% grass (Trial 2) hay from birth to 12 wk of age. Calves in Trial 1 were fed one of the following diets: control, control + 3.5% sodium chloride, or control + 5% sodium bicarbonate. In Trial 2, diets were: control, control + 5% sodium bicarbonate, or control + 5% sodium bicarbonate + loose, chopped grass hay. Intake of dry matter, gain in body weight, ruminal pH, or fecal starch did not differ. Calves fed sodium bicarbonate in Trial 1 but not 2 had a reduced feed efficiency compared with control and supplemented diets. In Trial 1 added sodium bicarbonate did not alter intake or digestible energy. Addition of sodium bicarbonate increased concentration of ruminal acetate and butyrate and decreased propionate in both trials. Fecal pH was elevated in calves fed sodium bicarbonate diets during both trials. Sodium chloride increased water intake in Trial 1, and sodium bicarbonate increased water indigestible energy. Addition of sodium bicarbonate increased concentration of ruminal acetate and butyrate and decreased propionate in both trials. Fecal pH was elevated in calves fed sodium bicarbonate diets during both trials. Sodium chloride increased water intake in Trial 1, and sodium bicarbonate increased water indigestible energy. Addition of sodium bicarbonate increased concentration of ruminal acetate and butyrate and decreased propionate in both trials. Fecal pH was elevated in calves fed sodium bicarbonate diets during both trials. Sodium chloride increased water intake in Trial 1, and sodium bicarbonate increased water intake in Trial 2. Incidence of free-gas bloat was higher in calves fed sodium bicarbonate in both trials. Addition of sodium bicarbonate to complete pelleted diets containing 35% alfalfa or 35% grass hay appeared to have no benefit for young, growing dairy calves in performance and health.

  6. Addition of sodium bicarbonate to rations of pre- and postpartum dairy cows.

    Science.gov (United States)

    Kilmer, L H; Muller, L D; Wangsness, P J

    1980-12-01

    Sodium bicarbonate was added to complete mixed rations to evaluate the effect of buffer addition on adaptation to high-energy rations by dairy cows in elderly lactation. Forty-five Holstein cows were assigned to one of three treatment groups: control pre- and postpartum; control prepartum, buffer postpartum; and buffer pre- and postpartum. Rations consisted of 85% chopped grass hay: 15% concentrate prepartum and 60% corn silage:40% concentrate postpartum. On day 4 postpartum, cows were switched abruptly to the postpartum ration for 9 wk. Buffered rations contained .6% sodium bicarbonate prepartum and .7% postpartum. Daily dry matter intake as a percent of body weight for cows fed buffer postpartum (3.51%) was greater than for cows fed no buffer (3.04%) of buffer pre- and postpartum (3.14%). Average production of 4% fat-corrected milk was greater for cows fed buffer postpartum and buffer pre- and postpartum (31.9 kg/day and 31.7 kg/day) than for cows fed no buffer (28.9 kg/day). Milk fat tests were not different. Cows fed the buffered rations lost body weight between wk 1 and 9 as compared to a net gain for cows fed no buffer. Cows fed buffers consumed more dry matter during wk 1 than did cows fed no buffer. Samples of rumen fluid, feces, and serum showed few differences that could be attributed to treatments. Compared to controls, cows fed sodium bicarbonate adapted to rations more rapidly postpartum as indicated by increased feed intake during the first 2 wk and by increased milk production during the first 4 wk of the trial.

  7. Type-1 cannabinoid receptors reduce membrane fluidity of capacitated boar sperm by impairing their activation by bicarbonate.

    Directory of Open Access Journals (Sweden)

    Barbara Barboni

    Full Text Available BACKGROUND: Mammalian spermatozoa acquire their full fertilizing ability (so called capacitation within the female genital tract, where they are progressively exposed to inverse gradients of inhibiting and stimulating molecules. METHODOLOGY/PRINCIPAL FINDINGS: In the present research, the effect on this process of anandamide, an endocannabinoid that can either activate or inhibit cannabinoid receptors depending on its concentration, and bicarbonate, an oviductal activatory molecule, was assessed, in order to study the role exerted by the type 1 cannabinoid receptor (CB1R in the process of lipid membrane remodeling crucial to complete capacitation. To this aim, boar sperm were incubated in vitro under capacitating conditions (stimulated by bicarbonate in the presence or in the absence of methanandamide (Met-AEA, a non-hydrolysable analogue of anandamide. The CB1R involvement was studied by using the specific inhibitor (SR141716 or mimicking its activation by adding a permeable cAMP analogue (8Br-cAMP. By an immunocytochemistry approach it was shown that the Met-AEA inhibits the bicarbonate-dependent translocation of CB1R from the post-equatorial to equatorial region of sperm head. In addition it was found that Met-AEA is able to prevent the bicarbonate-induced increase in membrane disorder and the cholesterol extraction, both preliminary to capacitation, acting through a CB1R-cAMP mediated pathway, as indicated by MC540 and filipin staining, EPR spectroscopy and biochemical analysis on whole membranes (CB1R activity and on membrane enriched fraction (C/P content and anisotropy. CONCLUSIONS/SIGNIFICANCE: Altogether, these data demonstrate that the endocannabinoid system strongly inhibits the process of sperm capacitation, acting as membrane stabilizing agent, thus increasing the basic knowledge on capacitation-related signaling and potentially opening new perspectives in diagnostics and therapeutics of male infertility.

  8. 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.

  9. Effect of preozonation on the characteristic transformation of fulvic acid and its subsequent trichloromethane formation potential: presence or absence of bicarbonate.

    Science.gov (United States)

    Li, Jing; Liu, Huijuan; Zhao, Xu; Qu, Jiuhui; Liu, Ruiping; Ru, Jia

    2008-04-01

    The effects of bicarbonate on the characteristic transformation of fulvic acid (FA) and its subsequent trichloromethane formation potential (TCMFP) were investigated in the process of preozonation. Dissolved organic carbon (DOC) removal rate and the residual aqueous ozone concentration during preozonation were measured with different bicarbonate concentration. The presence of bicarbonate inhibited DOC removal and decreased TCMFP yields in the initial oxidation period. In order to explain these phenomena, the molecular weight (MW) distribution (30 kDa) and corresponding TCMFP were investigated for FA and its subsequent oxidation products. Furthermore, transformation of molecular structure, based on MW distribution, was also characterized with Fourier transform infrared (FTIR) spectrum. Bicarbonate showed different inhibiting effects on TCMFP of organic species with different MW, and more significant TCMFP decrement was observed for the high MW fraction (>30 kDa) than for the low MW fractions. Preozonation led to obvious reduction on DOC and UV254 in most of MW fractions wherever bicarbonate was present or not, demonstrating that ozone contributed to both organics mineralization and structure variation, synchronously. As being indicated from the results of FTIR and gas chromatography-mass spectrometry, the functional groups such as alcohols, epoxides and phenols, the formation of which was promoted with hydroxyl radicals (.OH) and would be remarkably inhibited by bicarbonate, were responsible for the increment of TCM precursor's concentration during ozonation. Results of these studies confirmed low dosage bicarbonate affecting the ozonation pathways, influencing the intermediate species formation and impacting its subsequent TCMFP yields through inhibiting the .OH radicals reactions mainly occurred in high MW fractions.

  10. 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.

  11. Metabolic Acidosis as a Complication of Bicarbonate Haemodialysis

    OpenAIRE

    Irshad Ahmad Sinval, Bassam Bernieh, Ahdulrahman Osman Mohamad, Mohamed Adnan Abbadi,Mossadeque Ahmed, Ahmad Abdelwahab AItabakh

    1999-01-01

    Twelve episodes ofsevere metabolic acidosis were observed among 10 maintenance dialysis patientsusing Bicarbonate Haemodialysis (HDB). Patients were stable at the start of haemodialysis (HO)and became sick during or following the procedure. The main clinical features observed wereabdominal pain and vomiting, hypotension or shock, and CNS manifestations. Laboratoryinvestigations revealed severe metabolic acidosis in all and hyperkalemia in 4 patients. On fouroccasions, dialysate fluid sample a...

  12. 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

  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. 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

  15. An analysis of psychotropic drug sales. Increasing sales of selective serotonin reuptake inhibitors anre closely related to number of products

    DEFF Research Database (Denmark)

    Nielsen, Margrethe; Gøtzsche, Peter C.

    2011-01-01

    by changes in sales of the benzodiazepines and SSRIs. We found a decline in the sales of benzodiazepines after a peak in 1986, likely due to the recognition that they cause dependence. From a low level in 1992, we found that the sales of SSRIs increased almost linearly by a factor of 18, up to 44 DDD per......BACKGROUND: Prescribing of selective serotonin reuptake inhibitors (SSRIs) has increased dramatically. OBJECTIVE: To compare the sales of benzodiazepines and SSRIs within the primary care sector in Denmark and relate changes in usage to number of indications and products on the market. METHODS: We...

  16. Elucidation of the bicarbonate binding site and insights into the carboxylation mechanism of (N(5))-carboxyaminoimidazole ribonucleotide synthase (PurK) from Bacillus anthracis.

    Science.gov (United States)

    Tuntland, Micheal L; Santarsiero, Bernard D; Johnson, Michael E; Fung, Leslie W M

    2014-11-01

    Structures of (N(5))-carboxyaminoimidazole ribonucleotide synthase (PurK) from Bacillus anthracis with various combinations of ATP, ADP, Mg(2+), bicarbonate and aminoimidazole ribonucleotide (AIR) in the active site are presented. The binding site of bicarbonate has only been speculated upon previously, but is shown here for the first time. The binding involves interactions with the conserved residues Arg272, His274 and Lys348. These structures provide insights into each ligand in the active site and allow a possible mechanism to be proposed for the reaction that converts bicarbonate and AIR, in the presence of ATP, to produce (N(5))-carboxyaminoimidazole ribonucleotide. The formation of a carboxyphosphate intermediate through ATP phosphoryl transfer is proposed, followed by carboxylation of AIR to give the product, facilitated by a cluster of conserved residues and an active-site water network.

  17. Bicarbonate-sensing soluble adenylyl cyclase is an essential sensor for acid/base homeostasis.

    Science.gov (United States)

    Tresguerres, Martin; Parks, Scott K; Salazar, Eric; Levin, Lonny R; Goss, Greg G; Buck, Jochen

    2010-01-05

    pH homeostasis is essential for life, yet it remains unclear how animals sense their systemic acid/base (A/B) status. Soluble adenylyl cyclase (sAC) is an evolutionary conserved signaling enzyme that produces the second messenger cAMP in response to bicarbonate ions (HCO(3)(-)). We cloned the sAC ortholog from the dogfish, a shark that regulates blood A/B by absorbing and secreting protons (H(+)) and HCO(3)(-) at its gills. Similar to mammalian sAC, dogfish soluble adenylyl cyclase (dfsAC) is activated by HCO(3)(-) and can be inhibited by two structurally and mechanistically distinct small molecule inhibitors. dfsAC is expressed in the gill epithelium, where the subset of base-secreting cells resides. Injection of inhibitors into animals under alkaline stress confirmed that dfsAC is essential for maintaining systemic pH and HCO(3)(-) levels in the whole organism. One of the downstream effects of dfsAC is to promote the insertion of vacuolar proton pumps into the basolateral membrane to absorb H(+) into the blood. sAC orthologs are present throughout metazoans, and mammalian sAC is expressed in A/B regulatory organs, suggesting that systemic A/B sensing via sAC is widespread in the animal kingdom.

  18. Trametinib, a novel MEK kinase inhibitor, suppresses lipopolysaccharide-induced tumor necrosis factor (TNF)-α production and endotoxin shock.

    Science.gov (United States)

    Du, Shi-lin; Yuan, Xue; Zhan, Sun; Tang, Luo-jia; Tong, Chao-yang

    2015-03-13

    Lipopolysaccharide (LPS), one of the most prominent pathogen-associated molecular patterns (PAMPs), activates macrophages, causing release of toxic cytokines (i.e. tumor necrosis factor (TNF)-α) that may provoke inflammation and endotoxin shock. Here, we tested the potential role of trametinib, a novel and highly potent MAPK/ERK kinase (MEK) inhibitor, against LPS-induced TNF-α response in monocytes, and analyzed the underlying mechanisms. We showed that trametinib, at nM concentrations, dramatically inhibited LPS-induced TNF-α mRNA expression and protein secretion in transformed (RAW 264.7 cells) and primary murine macrophages. In ex-vivo cultured human peripheral blood mononuclear cells (PBMCs), this MEK inhibitor similarly suppressed TNF-α production by LPS. For the mechanism study, we found that trametinib blocked LPS-induced MEK-ERK activation in above monocytes, which accounted for the defective TNF-α response. Macrophages or PBMCs treated with a traditional MEK inhibitor PD98059 or infected with MEK1/2-shRNA lentivirus exhibited a similar defect as trametinib, and nullified the activity of trametinib. On the other hand, introducing a constitutively-active (CA) ERK1 restored TNF-α production by LPS in the presence of trametinib. In vivo, mice administrated with trametinib produced low levels of TNF-α after LPS stimulation, and these mice were protected from LPS-induced endotoxin shock. Together, these results show that trametinib inhibits LPS-induced TNF-α expression and endotoxin shock probably through blocking MEK-ERK signaling.

  19. 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.

  20. Influence of thymol and a urease inhibitor on coliform bacteria, odor, urea, and methane from a swine production manure pit.

    Science.gov (United States)

    Varel, Vincent H; Wells, James E

    2007-01-01

    Pathogens, ammonia, odor, and greenhouse gas emissions are serious environmental concerns associated with swine production. This study was conducted in two manure pits (33,000 L each) to determine the influence of 1.5 or 3.0 g thymol L(-1) and 80 mg L(-1) urease inhibitor amendments on urea accumulation, coliform bacteria, odor, and methane emission. Each experiment lasted 18 or 19 d, during which time 30 to 36 250-mL samples (six per day) were withdrawn from underneath each pit and analyzed for urea, thymol, volatile fatty acids, coliform bacteria, and Campylobacter. At the end of each experiment, six 50-g samples from each pit were placed in serum bottles, and gas volume and composition were determined periodically for 28 d. Compared with the control pit, volatile fatty acids production was reduced 64 and 100% for the thymol amendments of 1.5 and 3.0 g L(-1), respectively. Viable coliform cells were reduced 4.68 and 5.88 log10 colony-forming units kg(-1) of slurry for the 1.5 and 3.0 g thymol L(-1), respectively, and Escherichia coli were reduced 4.67 and 5.01 log10 colony-forming units kg(-1) of slurry, respectively. Campylobacter was not detected in the pits treated with thymol, in contrast to 63% of the samples being positive for the untreated pit. Urea accumulated in the treated pits from Day 3 to 6. Total gas production from serum bottles was reduced 65 and 76% for thymol amendments of 1.5 and 3.0 g L(-1), respectively, and methane was reduced 78 and 93%, respectively. These results suggest that thymol markedly reduces pathogens, odor, and greenhouse gas emissions from a swine production facility. The urease inhibitor produced a temporary response in conserving urea.

  1. 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

  2. Library-based discovery of DYRK1A/CLK1 inhibitors from natural product extracts.

    Science.gov (United States)

    Grabher, Patrick; Durieu, Emilie; Kouloura, Eirini; Halabalaki, Maria; Skaltsounis, Leandros A; Meijer, Laurent; Hamburger, Matthias; Potterat, Olivier

    2012-06-01

    The dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A possesses diverse roles in neuronal development and adult brain physiology, and increased activity has been linked to neurodegenerative diseases. Very few inhibitors of this kinase have been reported up to now. Screening of a library of > 900 plant and fungal extracts afforded 25 extracts with IC₅₀s Larrea tridentata as the active constituents. Active extracts and compounds were also tested on the closely related cdc2-like kinase CLK1. Finally, the selectivity profile of compounds was evaluated by including other members of the DYRKs and CLKs families. While the flavonoids and emodin did not show significant differences in the potency of their activities, harmine (1) was most active against DYRK1A, CLK1, and CLK4, and less potent against the other kinases, with selectivity ranging from 2- to 20-fold.

  3. Isolation of methyl syringate as a specific aflatoxin production inhibitor from the essential oil of Betula alba and aflatoxin production inhibitory activities of its related compounds.

    Science.gov (United States)

    Jermnak, Usuma; Yoshinari, Tomoya; Sugiyama, Yasumasa; Tsuyuki, Rie; Nagasawa, Hiromichi; Sakuda, Shohei

    2012-02-15

    Methyl syringate was isolated from the essential oil of Betula alba as an aflatoxin production inhibitor. It inhibited aflatoxin production of Aspergillus parasiticus and Aspergillus flavus with IC(50) values of 0.9 and 0.8 mM, respectively, without significantly inhibiting fungal growth. Methyl syringate reduced mRNA levels of genes (aflR, pksA, and omtB) [corrected] encoding proteins required for aflatoxin biosynthesis. Methyl gallate, methyl 3,4,5-trimethoxybenzoate, and methyl 3-O-methylgallate inhibited both aflatoxin production and fungal growth of A. parasiticus and A. flavus. However, their acids and syringic acid did not inhibit aflatoxin production and growth of A. parasiticus significantly, although gallic acid inhibited aflatoxin production of A. flavus with selectivity. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of methyl syringate was much weaker than that of gallic acid. These results showed that methyl syringate has a unique inhibitory activity toward aflatoxin production with a different mode of action from that of gallic acid.

  4. 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.

  5. The advanced glycation end product-lowering agent ALT-711 is a low-affinity inhibitor of thiamine diphosphokinase.

    Science.gov (United States)

    Krautwald, Martina; Leech, Dale; Horne, Stacey; Steele, Megan L; Forbes, Josephine; Rahmadi, Anton; Griffith, Renate; Münch, Gerald

    2011-08-01

    Advanced glycation end products (AGEs) are involved in age-related diseases, including the complications of diabetes and chronic renal impairment with arterial stiffening. Alagebrium chloride (ALT-711) is an AGE-lowering agent with beneficial effects in renal structural and functional parameters in diabetes, decreased diabetes-accelerated atherosclerosis, and age-related myocardial stiffening. ALT-711 exhibits a structural homology to thiamine, and it was suggested to interfere with thiamine metabolism. Thiamine is converted to thiamine diphosphate (TDP) by thiamine diphosphokinase (TDPK). TDP is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase. A decreased activity of these enzymes due to TDP deficiency results in disorders such as beriberi and Wernicke-Korsakoff syndrome. Therefore, we investigated whether ALT-711 is an inhibitor of TDPK. Molecular modeling studies showed that ALT-711 fits into the thiamine-binding pocket of TDPK, and there are three interactions between the thiazolium ring and the enzyme, as well as parallel stacking between the phenyl ring and the indole ring of Trp222B. Enzyme kinetic experiments also showed that ALT-711 dose-dependently decreased TDPK activity with K(i)s, calculated by different experiments and fitting models ranging from 0.88 to 1.09 mM. Fitting of the kinetic data favored mixed-mode inhibition with a major role for competitive inhibition. In summary, our results suggest that ALT-711 is a low-affinity inhibitor of TDPK, but is unlikely to interfere with thiamine metabolism at therapeutic concentrations. However, when new AGE-crosslink breakers based on thiamine are designed, care should be taken that they do not act as more potent competitive inhibitors than ALT-711.

  6. Physiological carbon dioxide, bicarbonate, and pH sensing.

    Science.gov (United States)

    Tresguerres, Martin; Buck, Jochen; Levin, Lonny R

    2010-11-01

    In biological systems, carbon dioxide exists in equilibrium with bicarbonate and protons. The individual components of this equilibrium (i.e., CO₂, HCO₃⁻, and H(+)), which must be sensed to be able to maintain cellular and organismal pH, also function as signals to modulate multiple physiological functions. Yet, the molecular sensors for CO₂/HCO₃⁻/pH remained unknown until recently. Here, we review recent progress in delineating molecular and cellular mechanisms for sensing CO₂, HCO₃⁻, and pH.

  7. 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.

  8. [Effect of mild irritants on gastric outputs of bicarbonates and pepsinogen depends on the rate of acid secretion].

    Science.gov (United States)

    Zolotarev, V A; Andreeva, Iu V; Khropycheva, R P

    2012-06-01

    The aggressive luminal content in the stomach activates gastroprotective processes affecting exocrine and endocrine secretion of gastric glands and permeability of the pre-epithelial mucus layer. The aim of the study was to investigate effects of chemical irritants similar to physiological characteristics of digestion (pH 2.0 and/or 500 mM NaCl) on outputs of bicarbonates and pepsinogen as well as assess the role of endogenous acid production in control ofnon-parietal secretion during irritation of the gastric mucosa. In experiments on conscious rats with chronic gastric fistula as well as on anesthetized animals it was demonstrated that luminal infusion of acidic hyperosmotic solution of NaCl enhances basal secretions of bicarbonates and pepsinogen that was fully blocked by indomethacin. Suppression of gastric acid secretion by omeprazole potentiates the stimulative effect of mild irritants likely due to the reduction of pH gradient on the surface of gastric mucosa which causes the growth of sensitivity of the epithelium to chemical stimuli and the increase of synthesis ofprostaglandins. Additionally, mild irritation enhances secretion of HCO3(-) and pepsinogen induced by stimulation of the vagus nerve; and this response does not depend on the action ofprostaglandins. The enhancing effect of irritation on the vagally induced bicarbonate output was eliminated after the treatment with omeprazole.

  9. 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.

  10. Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    Xiaochen Yuan; Naifeng Liu

    2011-01-01

    Advanced glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities.Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARΥ) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting,respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARΥ antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2). The ERK kinase inhibitor, UO126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the phosphorylation of ERKi/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARΥ pathways. Our findings suggestedpioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.

  11. Revisiting AI-2 quorum sensing inhibitors: direct comparison of alkyl-DPD analogues and a natural product fimbrolide.

    Science.gov (United States)

    Lowery, Colin A; Abe, Takumi; Park, Junguk; Eubanks, Lisa M; Sawada, Daisuke; Kaufmann, Gunnar F; Janda, Kim D

    2009-11-04

    Quorum sensing (QS) systems have been discovered in a wide variety of bacteria, and mediate both intra- and interspecies communication. The AI-2-based QS system represents the most studied of these proposed interspecies systems and has been shown to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the study of unknown AI-2-based QS systems and the potential treatment of bacterial infections. The fimbrolide class of natural products has exhibited excellent inhibitory activity against AI-2-based QS and as such may be considered the "gold standard" of AI-2 inhibitors. Thus, we sought to include a fimbrolide as a control compound for our recently developed alkyl-DPD panel of AI-2 modulators. Herein, we present a revised synthesis of a commonly studied fimbrolide as well as a direct comparison between the fimbrolide and alkyl-DPD analogues. We demonstrate that our alkyl-DPD analogues are more potent inhibitors of QS in both Vibrio harveyi and Salmonella typhimurium, the two organisms with defined AI-2 QS systems, and in doing so call into question the widely accepted use of fimbrolide-derived compounds as the "gold standard" of AI-2 inhibition.

  12. 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.

  13. 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

    of response along the pathway suggesting that binding, catalysis and product clearance occur along different energy surfaces. Motions in the enzyme with a covalently attached ligand are more complex and occur along several eigenvectors. The magnitudes of the fluctuations in these individual subspaces...... 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 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 hydrogen bond...

  14. 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 2...

  15. Nitrification inhibitors can increase post-harvest nitrous oxide emissions in an intensive vegetable production system

    Science.gov (United States)

    Scheer, Clemens; Rowlings, David; Firrell, Mary; Deuter, Peter; Morris, Stephen; Riches, David; Porter, Ian; Grace, Peter

    2017-03-01

    To investigate the effect of nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and 3-methylpyrazole 1,2,4-triazole (3MP + TZ), on N2O emissions and yield from a typical vegetable rotation in sub-tropical Australia we monitored soil N2O fluxes continuously over an entire year using an automated greenhouse gas measurement system. The temporal variation of N2O fluxes showed only low emissions over the vegetable cropping phases, but significantly higher emissions were observed post-harvest accounting for 50–70% of the annual emissions. NIs reduced N2O emissions by 20–60% over the vegetable cropping phases; however, this mitigation was offset by elevated N2O emissions from the NIs treatments over the post-harvest fallow period. Annual N2O emissions from the conventional fertiliser, the DMPP treatment, and the 3MP + TZ treatment were 1.3, 1.1 and 1.6 (sem = 0.2) kg-N ha‑1 year‑1, respectively. This study highlights that the use of NIs in vegetable systems can lead to elevated N2O emissions by storing N in the soil profile that is available to soil microbes during the decomposition of the vegetable residues. Hence the use of NIs in vegetable systems has to be treated carefully and fertiliser rates need to be adjusted to avoid an oversupply of N during the post-harvest phase.

  16. Nitrification inhibitors can increase post-harvest nitrous oxide emissions in an intensive vegetable production system

    Science.gov (United States)

    Scheer, Clemens; Rowlings, David; Firrell, Mary; Deuter, Peter; Morris, Stephen; Riches, David; Porter, Ian; Grace, Peter

    2017-01-01

    To investigate the effect of nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and 3-methylpyrazole 1,2,4-triazole (3MP + TZ), on N2O emissions and yield from a typical vegetable rotation in sub-tropical Australia we monitored soil N2O fluxes continuously over an entire year using an automated greenhouse gas measurement system. The temporal variation of N2O fluxes showed only low emissions over the vegetable cropping phases, but significantly higher emissions were observed post-harvest accounting for 50–70% of the annual emissions. NIs reduced N2O emissions by 20–60% over the vegetable cropping phases; however, this mitigation was offset by elevated N2O emissions from the NIs treatments over the post-harvest fallow period. Annual N2O emissions from the conventional fertiliser, the DMPP treatment, and the 3MP + TZ treatment were 1.3, 1.1 and 1.6 (sem = 0.2) kg-N ha−1 year−1, respectively. This study highlights that the use of NIs in vegetable systems can lead to elevated N2O emissions by storing N in the soil profile that is available to soil microbes during the decomposition of the vegetable residues. Hence the use of NIs in vegetable systems has to be treated carefully and fertiliser rates need to be adjusted to avoid an oversupply of N during the post-harvest phase. PMID:28266551

  17. Nitrification inhibitors can increase post-harvest nitrous oxide emissions in an intensive vegetable production system.

    Science.gov (United States)

    Scheer, Clemens; Rowlings, David; Firrell, Mary; Deuter, Peter; Morris, Stephen; Riches, David; Porter, Ian; Grace, Peter

    2017-03-07

    To investigate the effect of nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and 3-methylpyrazole 1,2,4-triazole (3MP + TZ), on N2O emissions and yield from a typical vegetable rotation in sub-tropical Australia we monitored soil N2O fluxes continuously over an entire year using an automated greenhouse gas measurement system. The temporal variation of N2O fluxes showed only low emissions over the vegetable cropping phases, but significantly higher emissions were observed post-harvest accounting for 50-70% of the annual emissions. NIs reduced N2O emissions by 20-60% over the vegetable cropping phases; however, this mitigation was offset by elevated N2O emissions from the NIs treatments over the post-harvest fallow period. Annual N2O emissions from the conventional fertiliser, the DMPP treatment, and the 3MP + TZ treatment were 1.3, 1.1 and 1.6 (sem = 0.2) kg-N ha(-1) year(-1), respectively. This study highlights that the use of NIs in vegetable systems can lead to elevated N2O emissions by storing N in the soil profile that is available to soil microbes during the decomposition of the vegetable residues. Hence the use of NIs in vegetable systems has to be treated carefully and fertiliser rates need to be adjusted to avoid an oversupply of N during the post-harvest phase.

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

    DEFF Research Database (Denmark)

    Andersson, Martin Peter; Rodriguez Blanco, Juan Diego; Stipp, Susan Louise Svane

    2016-01-01

    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 calcite, the predicted pKa for deprotonation is 7.5, which is ∼3 pH units lower than in aqueous solution...

  19. 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.

  20. Is Sodium Bicarbonate Therapy Still Up To Date?

    Directory of Open Access Journals (Sweden)

    Hüseyin Kurt

    2015-12-01

    Full Text Available Sodium bicarbonate (SB, which has a vital role in the regulation of acid-base balance of all tissues and organs, is one of the most important buffering systems of the body. SB plays an important role in the treatment of poisoning caused by numerous agents including mainly salicylate and tricyclic antidepressants. In metabolic acidosis (MA occurred in patient with systemic and metabolic diseases, first, the primary disease should be treated and in the case of low bicarbonate levels such as diarrhea and renal tubular acidosis, missing SB should be recovered. As the kidney has an important role in acid-base balance, SB is widely used in the treatment of acute and chronic renal failure. Although there is no conclusive evidence to prevent contrast nephropathy, SB comes to the fore compared to other agents. SB is used due to MA and its effects occurring in acute renal failure. In addition, SB treatment applied to reduce the increased acid levels in chronic kidney failure may reduce mortality. While SB can be used as individualized in lactic acidosis and cardiac arrest cases, it can be used safely as a performance enhancer for athletes. SB is used widely in gastrointestinal tract diseases due to its antacid effects and its routine use is not recommended in diabetic ketoacidosis. These data demonstrate that SB is still popular and it will retain its popularity in the near future.

  1. 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.

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

    Science.gov (United States)

    Cruz, Patricia G.; Auld, Douglas S.; Schultz, Pamela J.; Lovell, Scott; Battaile, Kevin P.; MacArthur, Ryan; Shen, Min; Tamayo-Castillo, Giselle; Inglese, James; Sherman, David H.

    2011-01-01

    The chemical diversity of nature has tremendous potential for discovery of new molecular probes and medicinal agents. However, sensitivity of HTS assays to interfering components of crude extracts derived from plants, macro- and microorganisms has curtailed their use in lead discovery efforts. Here we describe a process for leveraging the concentration-response curves (CRCs) 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 aims to improve the probability that labor-intensive subsequent steps of re-culturing, 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. PMID:22118678

  3. 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.

  4. Effect of crude glycerol-derived inhibitors on ethanol production by Enterobacter aerogenes.

    Science.gov (United States)

    Lee, Sang Jun; Kim, Sung Bong; Kang, Seong Woo; Han, Sung Ok; Park, Chulhwan; Kim, Seung Wook

    2012-01-01

    In this study, ethanol production from pure and crude glycerol using Enterobacter aerogenes ATCC 29007 was evaluated under anaerobic culture conditions. Inhibitory effects of substrate concentrations, pH, and salt concentrations were investigated based on crude glycerol components. Ethanol production was performed with pure glycerol concentrations ranging from 5 to 30 g/L to evaluate the effects of substrate concentration and osmotic pressure. The consumed glycerol was 5-14.33 g/L, and the yield of ethanol was higher than 0.75 mol ethanol/mol glycerol after 24 h of cultivation. To evaluate the inhibitory effects of salts (NaCl and KCl), experiments were performed with 0-20 g/L of each salt. Inhibitory effects of salts were strongest at high salt concentrations. The inhibitory effect of pH was performed in the pH range 4-10, and cell growth and ethanol production were highest at pH 5-6. Also, ethanol production was slightly inhibited at low concentration of crude glycerol comparison with pure glycerol. However, significant inhibitory effects were not observed at 1.5 and 2% crude glycerol which showed higher ethanol production compared to pure glycerol.

  5. Removal of inhibitors from pre-hydrolysis liquor of kraft-based dissolving pulp production process using adsorption and flocculation processes.

    Science.gov (United States)

    Liu, Xin; Fatehi, Pedram; Ni, Yonghao

    2012-07-01

    A process for removing inhibitors from pre-hydrolysis liquor (PHL) of a kraft-based dissolving pulp production process by adsorption and flocculation, and the characteristics of this process were studied. In this process, industrially produced PHL was treated with unmodified and oxidized activated carbon as an absorbent and polydiallyldimethylammonium chloride (PDADMAC) as a flocculant. The overall removal of lignin and furfural in the developed process was 83.3% and 100%, respectively, while that of hemicelluloses was 32.7%. These results confirmed that the developed process can remove inhibitors from PHL prior to producing value-added products, e.g. ethanol and xylitol via fermentation.

  6. Natural Products Screening for the Identification of Selective Monoamine Oxidase-B Inhibitors

    Science.gov (United States)

    Zarmouh, Najla O.; Messeha, Samia S.; Elshami, Faisel M.; Soliman, Karam F. A.

    2016-01-01

    Aims Monoamine oxidase-B inhibitors (MAO-BIs) are used for the initial therapy of Parkinson’s disease. Also, MAO-BIs have shown to be effective neuroprotective agents in several neurodegenerative diseases. However, some concerns exist regarding the long-term use of these compounds. Meanwhile, natural compounds showed potential MAO-B selective inhibitions. To date, few selective natural MAO-BIs have been identified. Therefore, the current study is designed to identify plants with potent and specific MAO-B inhibition. Study Design In this work, we utilized high throughput screening to evaluate the different plants ethanolic extract for their effectiveness to inhibit recombinant human (h)MAO-A and hMAO-B and to determine the relative selectivity of the top MAO-BI. Methodology Recombinant human isozymes were verified by Western blotting, and the 155 plants were screened. A continuous fluorometric screening assay was performed followed by two separate hMAO-A and hMAO-B microtiter screenings and IC50 determinations for the top extracts. Results In the screened plants, 9% of the extracts showed more than 1.5-fold relative inhibition of hMAO-B (RIB) and another 9% showed more than 1.5-fold relative inhibition of hMAO-A. The top extracts with the most potent RIBs were Psoralea corylifolia seeds, Phellodendron amurense bark, Glycyrrhiza uralensis roots, and Ferula assafoetida roots, with the highest RIB of 5.9-fold. Furthermore, extensive maceration of the promising extracts led to increase inhibitory effects with a preserved RIB as confirmed with luminescence assay. The top four extracts hMAO-BIs were equally potent (IC50= 1.3 to 3.8 μg/mL) with highly significant relative selectivities to inhibit hMAO-B (4.1- to 13.4-fold). Conclusion The obtained results indicate that Psoralea corylifolia seeds, Ferula assafoetida, Glycyrrhiza uralensis roots, and Phellodendron amurense ethanolic extracts have selective inhibitions for human MAO-B. Investigating these plant extracts as

  7. Electroantennogram and behavioral responses of Anastrepha suspensa (Diptera: Tephritidae) to putrescine and ammonium bicarbonate lures.

    Science.gov (United States)

    Kendra, Paul E; Montgomery, Wayne S; Epsky, Nancy D; Heath, Robert R

    2009-08-01

    At present, the most effective synthetic lures for pest Anastrepha fruit flies are multicomponent blends that include ammonia and the diamine synergist putrescine (1,4-diaminobutane). Both chemicals generally have been regarded as protein cues that result in female-biased attraction. Using electroantennography (EAG) and flight tunnel bioassays, this study evaluated response of the Caribbean fruit fly, Anastrepha suspensa (Loew) to vapors released from commercial lure formulations of ammonium bicarbonate and putrescine. Over a range of doses tested, EAG response to ammonium bicarbonate was equivalent for both sexes, but female response was significantly greater than male response to putrescine and to a 1:1 mixture of ammonium bicarbonate and putrescine. Amplitude of EAG response to the mixture was approximately equal to the summation of responses to the individual substrates. Using a fixed dose of substrate, EAG measurements from females 1-14 d old indicated that antennal sensitivity to both lures varied according to physiological state of the fly. Peak response to ammonium bicarbonate was recorded from immature females, peak response to putrescine from sexually mature females. In bioassays, more females were captured with ammonium bicarbonate plus putrescine than with ammonium bicarbonate alone. This difference was not observed in males, resulting in a higher female to male ratio in captures with ammonium bicarbonate plus putreseine (3:1) versus ammonium bicarbonate alone (1:1). Results suggest that separate olfactory receptors are involved in detection of the two semiochemicals, and that the putrescine component is primarily responsible for the female-biased attraction.

  8. 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...

  9. Treatment with Potassium Bicarbonate Lowers Calcium Excretion and Bone Resorption in Older Men and Women

    Science.gov (United States)

    Bicarbonate has been implicated in bone health in older subjects on acid-producing diets in short-term studies. The objective of this study was to determine the effects of potassium bicarbonate and its components on changes in bone resorption and calcium excretion over 3 months in older men and wom...

  10. 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...

  11. 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

  12. 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)

    Ichiro Miki

    2007-09-01

    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.

  13. 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.

  14. Identification of Bicarbonate as a Trigger and Genes Involved with Extracellular DNA Export in Mycobacterial Biofilms.

    Science.gov (United States)

    Rose, Sasha J; Bermudez, Luiz E

    2016-12-06

    Extracellular DNA (eDNA) is an integral biofilm matrix component of numerous pathogens, including nontuberculous mycobacteria (NTM). Cell lysis is the source of eDNA in certain bacteria, but the source of eDNA remains unidentified for NTM, as well as for other eDNA-containing bacterial species. In this study, conditions affecting eDNA export were examined, and genes involved with the eDNA export mechanism were identified. After a method for monitoring eDNA in real time in undisturbed biofilms was established, different conditions affecting eDNA were investigated. Bicarbonate positively influenced eDNA export in a pH-independent manner in Mycobacterium avium, M. abscessus, and M. chelonae The surface-exposed proteome of M. avium in eDNA-containing biofilms revealed abundant carbonic anhydrases. Chemical inhibition of carbonic anhydrases with ethoxzolamide significantly reduced eDNA export. An unbiased transposon mutant library screen for eDNA export in M. avium identified many severely eDNA-attenuated mutants, including one not expressing a unique FtsK/SpoIIIE-like DNA-transporting pore, two with inactivation of carbonic anhydrases, and nine with inactivation of genes belonging to a unique genomic region, as well as numerous mutants involved in metabolism and energy production. Complementation of nine mutants that included the FtsK/SpoIIIE and carbonic anhydrase significantly restored eDNA export. Interestingly, several attenuated eDNA mutants have mutations in genes encoding proteins that were found with the surface proteomics, and many more mutations are localized in operons potentially encoding surface proteins. Collectively, our data strengthen the evidence of eDNA export being an active mechanism that is activated by the bacterium responding to bicarbonate.

  15. Effects of RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts

    NARCIS (Netherlands)

    Westra, J; Limburg, PC; de Boer, Peter; van Rijswijk, Martin

    2004-01-01

    Objective: To investigate the effect of the p38 mitogen activated protein kinase ( MAPK) inhibitor RWJ 67657 on inflammatory mediator production by rheumatoid synovial fibroblasts (RSF). Methods: RSF were pretreated with RWJ 67657 and stimulated with TNFalpha and/or IL-1beta. Protein levels and mRNA

  16. ONO 3403, a synthetic serine protease inhibitor, inhibits lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production and protects mice from lethal endotoxic shock

    NARCIS (Netherlands)

    Tumurkhuu, Gantsetseg; Koide, Naoki; Hiwasa, Takaki; Ookoshi, Motohiro; Dagvadorj, Jargalsaikhan; Noman, Abu Shadat Mohammod; Iftakhar-E-Khuda, Imtiaz; Naiki, Yoshikazu; Komatsu, Takayuki; Yoshida, Tomoaki; Yokochi, Takashi

    2011-01-01

    ONO 3403, a new synthetic serine protease inhibitor, is a derivative of camostat mesilate and has a higher protease-inhibitory activity. The effect of ONO 3403 on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha and nitric oxide (NO) production in RAW 264.7 macrophage-like cells wa

  17. Inhibitory effect of presenilin inhibitor LY411575 on maturation of hepatitis C virus core protein, production of the viral particle and expression of host proteins involved in pathogenicity.

    Science.gov (United States)

    Otoguro, Teruhime; Tanaka, Tomohisa; Kasai, Hirotake; Yamashita, Atsuya; Moriishi, Kohji

    2016-11-01

    Hepatitis C virus (HCV) core protein is responsible for the formation of infectious viral particles and induction of pathogenicity. The C-terminal transmembrane region of the immature core protein is cleaved by signal peptide peptidase (SPP) for maturation of the core protein. SPP belongs to the family of presenilin-like aspartic proteases. Some presenilin inhibitors are expected to suppress HCV infection and production; however, this anti-HCV effect has not been investigated in detail. In this study, presenilin inhibitors were screened to identify anti-HCV compounds. Of the 13 presenilin inhibitors tested, LY411575 was the most potent inhibitor of SPP-dependent cleavage of HCV core protein. Production of intracellular core protein and supernatant infectious viral particles from HCV-infected cells was significantly impaired by LY411575 in a dose-dependent manner (half maximum inhibitory concentration = 0.27 μM, cytotoxic concentration of the extracts to cause death to 50% of viable cells > 10 μM). No effect of LY411575 on intracellular HCV RNA in the subgenomic replicon cells was detected. LY411575 synergistically promoted daclatasvir-dependent inhibition of viral production, but not that of viral replication. Furthermore, LY411575 inhibited HCV-related production of reactive oxygen species and expression of NADPH oxidases and vascular endothelial growth factor. Taken together, our data suggest that LY411575 suppresses HCV propagation through SPP inhibition and impairs host gene expressions related to HCV pathogenicity.

  18. Regulatory substances produced by lymphocytes. V. Production of inhibitor of DNA synthesis (IDS) by proliferating T lymphocytes.

    Science.gov (United States)

    Namba, Y; Jegasothy, B V; Waksman, B H

    1977-04-01

    The conditions neccessary for production of inhibitor of DNA synthesis (IDS) by rat lymphocytes were investigated. In concanavalin A (Con A)-stimulated lymph node cell (LNC) cultures, IDS production was not detected in the culture supernatant during the first 24 hr, and it increased gradually after that to reach a maximum at 3 to 4 days. When the cells were pretreated with mitomycin C, IDS was not produced, suggesting that DNA synthesis of LNC or a LNC subpopulation is necessary for IDS production. In contrast, Con A-stimulated spleen cells priduced a high level of IDS within 24 hr, and its production fell off sharply thereafter. Con A-stimulated rat thymocytes also produced IDS reaching a maximum at 2 to 3 dyas. However, thymus cells from rats treated with hydrocortisone 48 hr previously did not produce IDS. This finding implies that cortisol-sensitive (cortical) thymocytes are capable of producing IDS and cortisol-resistant (medullary) thymocytes are not. IDS production by lymphoblasts was proportional to cell number and unaffected eith by cell density (1 to 10 x 106/ml) or by the concomitant presence of normal cells from spleen, lymph node, or thymus. Thus Con A-stimulated cells, after becoming blasts, appear to produce IDS automatically wihtout affecting or being affected by other cells. Both spleen and thymus cells from rats injected with a large dose of antigen (ovalbumin, 100 mg, i.p.) 24 hr in advance produced substantial amounts of IDS in culture within 24 hr in the absence of mitogen or additional antigen, but not the cells from rats injected with an immunizing dose (1 mg) of the same antigen. The cells producing IDS in the spleen were shown to be adherent to glass wool, and those in the thymus were partially so. IDS production by antigen-stimulated spleen cells was abrogated by injecting rats with bromodexyuridine (BUdR) at 0 and 12 hr after the ovalbumin. These findings suggest that a subpopulation ofadherent spleen cells (possibly resembling cortical

  19. Effect of TNF-α production inhibitors on the production of pro-inflammatory cytokines by peripheral blood mononuclear cells from HTLV-1-infected individuals.

    Science.gov (United States)

    Luna, T; Santos, S B; Nascimento, M; Porto, M A F; Muniz, A L; Carvalho, E M; Jesus, A R

    2011-11-01

    Human T lymphotropic virus type 1 (HTLV-1) is the causal agent of myelopathy/tropical spastic paraparesis (HAM/TSP), a disease mediated by the immune response. HTLV-1 induces a spontaneous proliferation and production of pro-inflammatory cytokines by T cells, and increasing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels are potentially involved in tissue damage in diseases related to HTLV-1. This exaggerated immune response is also due to an inability of the natural regulatory mechanisms to down-modulate the immune response in this group of patients. TNF-α inhibitors reduce inflammation and have been shown to improve chronic inflammatory diseases in clinical trials. The aim of this study was to evaluate the ability of pentoxifylline, forskolin, rolipram, and thalidomide to decrease in vitro production of TNF-α and IFN-γ in cells of HTLV-1-infected subjects. Participants of the study included 19 patients with HAM/TSP (mean age, 53 ± 11; male:female ratio, 1:1) and 18 HTLV-1 carriers (mean age, 47 ± 11; male:female ratio, 1:2.6). Cytokines were determined by ELISA in supernatants of mononuclear cell cultures. Pentoxifylline inhibited TNF-α and IFN-γ synthesis with the minimum dose used (50 µM). The results with forskolin were similar to those observed with pentoxifylline. The doses of rolipram used were 0.01-1 µM and the best inhibition of TNF-α production was achieved with 1 µM and for IFN-γ production it was 0.01 µM. The minimum dose of thalidomide used (1 µM) inhibited TNF-α production but thalidomide did not inhibit IFN-γ production even when the maximum dose (50 µM) was used. All drugs had an in vitro inhibitory effect on TNF-α production and, with the exception of thalidomide, all of them also decreased IFN-γ production.

  20. 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; 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

  1. New inhibitors of nitric oxide production from the seeds of Myristica fragrans.

    Science.gov (United States)

    Cao, Gui-Yun; Yang, Xiu-Wei; Xu, Wei; Li, Fei

    2013-12-01

    Six dihydrobenzofuran type neolignans were isolated from the dried ripe seeds of Myristica fragrans Houtt. (family: Myristicaceae) and their chemical structures were identified as licarin B (1), 3'-methoxylicarin B (2), myrisfrageal A (3), isodihydrocainatidin (4), dehydrodiisoeugenol (5), and myrisfrageal B (6), respectively, on the basis of spectroscopic data analyses. Among them, compounds 3 and 6 are new compounds. Compounds 1-6 showed inhibition of nitric oxide production in lipopolysaccharide-activated murine monocyte-macrophage RAW264.7 with IC50 values of 53.6, 48.7, 76.0, 36.0, 33.6, and 45.0 μM, respectively. These values were compared to those of the positive controls, indomethacin and L-N(6)-(1-iminoethyl)-lysine, which have IC50 values of 65.3 and 27.1 μM, respectively. Further compounds 3, 5 and 6 suppressed LPS-induced iNOS mRNA expression in a does-dependent manner in RAW 264.7 cells assayed by real-time RT-PCR. Compounds 3, 5 and 6 may inhibit NO overproduction via inhibition of iNOS mRNA expression. The results provided valuable information for further investigation of compounds 1-6 as anti-inflammatory and chemopreventive agents.

  2. 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.

  3. A randomized, crossover pharmacodynamic study of immediate‐release omeprazole/sodium bicarbonate and delayed‐release lansoprazole in healthy adult volunteers

    OpenAIRE

    Pratha, Vijayalakshmi S.; McGraw, Thomas; Tobin, William

    2016-01-01

    Abstract 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, o...

  4. 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.

  5. Mitochondrial Respiratory Chain Inhibitors Involved in ROS Production Induced by Acute High Concentrations of Iodide and the Effects of SOD as a Protective Factor

    Directory of Open Access Journals (Sweden)

    Lingyan Wang

    2015-01-01

    Full Text Available A major source of reactive oxygen species (ROS generation is the mitochondria. By using flow cytometry of the mitochondrial fluorescent probe, MitoSOX Red, western blot of mitochondrial ROS scavenger Peroxiredoxin (Prx 3 and fluorescence immunostaining, ELISA of cleaved caspases 3 and 9, and TUNEL staining, we demonstrated that exposure to 100 μM KI for 2 hours significantly increased mitochondrial superoxide production and Prx 3 protein expression with increased expressions of cleaved caspases 3 and 9. Besides, we indicated that superoxide dismutase (SOD at 1000 unit/mL attenuated the increase in mitochondrial superoxide production, Prx 3 protein expression, and lactate dehydrogenase (LDH release and improved the relative cell viability at 100 μM KI exposure. However, SOD inhibitor diethyldithiocarbamic acid (DETC (2 mM, Rotenone (0.5 μM, a mitochondrial complex I inhibitor, and Antimycin A (10 μM, a complex III inhibitor, caused an increase in mitochondrial superoxide production, Prx 3 protein expression, and LDH release and decreased the relative cell viability. We conclude that the inhibitors of mitochondrial respiratory chain complex I or III may be involved in oxidative stress caused by elevated concentrations of iodide, and SOD demonstrates its protective effect on the Fischer rat thyroid cell line (FRTL cells.

  6. Enhanced short-cut nitrification in an airlift reactor by CaCO3 attachment on biomass under high bicarbonate condition.

    Science.gov (United States)

    Ali, Mohammad; Chai, Li-Yuan; Wang, Hai-Ying; Tang, Chong-Jian; Min, Xiao-Bo; Yan, Xu; Peng, Cong; Song, Yu-Xia; Zheng, Ping

    2016-06-01

    The short-cut nitrification (SCN) performance of an airlift reactor (ALR) was investigated under increasing bicarbonate condition. The sequential increase of bicarbonate from 2.5 to 7.0 g/L accelerated the nitrite accumulation and improved the NAP to 99 %. With the increase of bicarbonate dose to 11 g/L, the ammonium removal efficiency and the ammonium removal rate (ARR) were improved to 95.1 % and 0.57 kg/m(3)/day, respectively. However, the elevation of bicarbonate concentration from 11.0 to 14.0 g/L gradually depreciated the nitrite accumulation percentage to 62.5 %. Then, the reactor was operated in increasing ammonium strategy to increase the nitrogen loading rate (NLR) to 1.1 kg/m(3)/day under 700 mg/L influent ammonium concentration. The ARR and nitrite production rate were elevated to 1.1 and 0.9 kg/m(3)/day, respectively. The SCN performance was improved to 1.8 kg/m(3)/day (NLR) by the subsequent progressive shortening of HRT to 4.8 h at ammonium concentration of 350 mg/L, which was 1.6 times higher than that of the increasing ammonium strategy. Chemical analysis with EDS, FTIR and XRD confirmed the presence of CaCO3 precipitates on biomass surface during the long-term operation under high bicarbonate conditions. The attachment of precipitates to the SCN sludge helped to improve the biomass settleability and finally enhanced the SCN performance of the ALR.

  7. TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors.

    Science.gov (United States)

    Gao, Xiaofei; Lee, Hsiang-Ying; da Rocha, Edroaldo Lummertz; Zhang, Cheng; Lu, Yi-Fen; Li, Dandan; Feng, Yuxiong; Ezike, Jideofor; Elmes, Russell R; Barrasa, M Inmaculada; Cahan, Patrick; Li, Hu; Daley, George Q; Lodish, Harvey F

    2016-12-08

    Burst-forming unit erythroid progenitors (BFU-Es) are so named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of "bursts" of smaller erythroid colonies derived from the later colony-forming unit erythroid progenitor erythropoietin (Epo)-dependent progenitors. "Early" BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do "late" BFU-Es forming small colonies, but the mechanism underlying this heterogeneity remains unknown. We show that the type III transforming growth factor β (TGF-β) receptor (TβRIII) is a marker that distinguishes early and late BFU-Es. Transient elevation of TβRIII expression promotes TGF-β signaling during the early BFU-E to late BFU-E transition. Blocking TGF-β signaling using a receptor kinase inhibitor increases early BFU-E cell self-renewal and total erythroblast production, suggesting the usefulness of this type of drug in treating Epo-unresponsive anemias.

  8. Radioprotective effects of combination broncho-vaxom, a macrophage activator, and indomethacin, an inhibitor of prostaglandin production. Relationship to myelopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Fedorocko, P.; Mackova, N.O. [Safarik Univ., Faculty ofSciences, Dept. of Cellular and Molecular Biology, Kosice (Slovakia)

    1996-01-01

    The effects of the bacterial extract broncho-vaxom (BV; radioprotective immunomodulator; 500 {mu}g/mouse i.p., -24 h) and indomethacin (INDO; inhibitor of prostaglandin production; 2x40 {mu}g/mouse i.m., - 24 h and - 3 h) on the post-irradiation recovery of hemopoietic functions in mice were investigated. Both agents were administered either alone or in combination. Endogenous spleen colony formation was increased in all treatment groups, with combination-treated mice exhibiting the greatest effects. Similarly, 24 h after combined administration of BV and INDO (i.e. at the time of presumed irradiation) to the non-irradiated mice granulocyte-macrophage colony-forming cell (GM-CFC) numbers were greater in the bone marrow and spleen. Also, as determined by hydroxyurea injection, there was an increase in the number of GM-CFC in the S-phase of the cell cycle in the bone marrow. However, GM-CFC in the spleen of combination pretreated mice was not stimulated to significant proliferation as compared to GM-CFC in the spleen of mice injected with BV alone. Combined modality treatment was also more effective than single agent treatments in accelerating bone marrow cellularity and GM-CFC regeneration, but not in accelerating GM-CFC regeneration in the spleen. Combined administration of BV and INDO to mice prior to lethal irradiation exerted and additional radioprotective effect and protected 95% of the C57B1/6 mice. (au) 42 refs.

  9. Intrahypothalamic corticotropin-releasing factor elevates gastric bicarbonate and inhibits stress ulcers in rats.

    Science.gov (United States)

    Gunion, M W; Kauffman, G L; Taché, Y

    1990-01-01

    The effects of intrahyopthalamic microinfusions of corticotropin-releasing factor (CRF) on gastric bicarbonate, acid, and pepsin content and on cold restraint-induced gastric lesion formation were tested in three experiments. Bilateral microinfusions of CRF into the hypothalamic ventromedial nucleus (0.86 nmol/rat) significantly increased both gastric bicarbonate concentration and total bicarbonate output. These effects were observed irrespective of whether rats were pretreated with the acid antisecretory drug omeprazole. In nonomeprazole-pretreated rats, CRF microinfusions also significantly reduced acid secretion and raised pH. The increase in bicarbonate content accounted for half of the observed decrease in acid output, suggesting that CRF microinfusions activated separable bicarbonate-stimulating and acid-inhibiting hypothalamic systems. In non-omeprazole-pretreated rats, CRF microinfusions significantly increased serum gastrin, whereas pepsin output was unchanged. Gastric mucosal damage produced by 4 h of cold restraint was significantly diminished by CRF microinfusion into the ventromedial hypothalamus. These data demonstrate that ventromedial hypothalamic microinfusions of CRF increase bicarbonate content, decrease gastric acid content, and confer protection against cold restraint-induced gastric mucosal damage. Hypothalamic CRF neuronal terminals and receptors may be involved in the central regulation of gastric bicarbonate secretion as well as acid secretion.

  10. 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.

  11. 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.

  12. Chronic administration of phosphodiesterase type 5 inhibitor suppresses renal production of endothelin-1 in dogs with congestive heart failure.

    Science.gov (United States)

    Yamamoto, Takashi; Wada, Atsuyuki; Ohnishi, Masato; Tsutamoto, Takayoshi; Fujii, Masanori; Matsumoto, Takehiro; Takayama, Tomoyuki; Wang, Xinwen; Kurokawa, Kiyoshi; Kinoshita, Masahiko

    2002-08-01

    Endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) play important roles in the regulation of body fluid balance in congestive heart failure (CHF). Renal production of ET-1 increases in CHF and it is a significant independent predictor of sodium excretion. ANP inhibits the ET system through cGMP, a second messenger of ANP. However, in severe CHF, plasma cGMP levels reached a plateau despite the activation of ANP secretion. Thus, ANP does not seem to sufficiently oppose exaggerated ET-1 actions in severe CHF, partially due to the accelerated degradation of cGMP, through phosphodiesterase type 5 (PDE5). We examined the chronic effects of a PDE5 inhibitor, T-1032 (1 mg/kg per day, n=5), on renal function and renal production of ET-1 in dogs with CHF induced by rapid ventricular pacing (270 beats/min). Vehicle dogs were given a placebo (n=5) and normal dogs (n=5) served as normal controls without pacing. In this experimentally produced CHF, plasma levels of ET-1, ANP and cGMP were elevated and renal production of cGMP was increased compared with the normal group, associated with increases in renal expression of preproET-1 mRNA and the number of ET-1-positive cells in glomeruli. In the T-1032 group, systemic and renal production of cGMP were further increased compared with the vehicle group despite no significant difference in plasma ANP levels between the two groups. Subsequently, the agent significantly improved urine flow rate, sodium excretion rate and glomerular filtration rate (GFR) associated with reductions in renal expression of preproET-1 mRNA and the number of ET-1-positive cells compared with the vehicle group. Moreover, there was a significant negative correlation between the number of ET-1-positive cells and GFR (r=-0.802 and Prenal ANP and ET-1 through the cGMP pathway, subsequently preventing renal dysfunction during the progression of CHF.

  13. Influence of proliferation signal inhibitors on vascular endothelial growth factor production in heart transplant recipients - preliminary report.

    Science.gov (United States)

    Kamieńska, Natalia; Zakliczyński, Michał; Kasperska-Zając, Alicja; Szewczyk, Marta; Trybunia-Orzeszek, Dominika; Nożyński, Jerzy; Pijet, Marta; Hrapkowicz, Tomasz; Zembala, Marian

    2014-06-01

    Proliferation signal inhibitors (PSI) are especially beneficial for heart transplant recipients, but are rarely used due to frequent side effects. As they may be caused by vascular endothelial growth factor (VEGF), we performed a prospective cross-sectional pilot study to assess the influence of PSI and/or calcineurin inhibitors (CNI) presence in immunosuppressive protocols of heart transplant recipients on VEGF secretion. All electively screened heart transplant recipients willing to participate were enrolled in the study. The preliminary report was based on the results of the first 89 serum samples. The study group (n = 84) consisted of the PSI group (n = 14) further divided into the PSI + CNI subgroup (n = 10) and PSIw/oCNI subgroup (n = 4) based on concomitant CNI use, and the CNIw/oPSI group (n = 70) receiving CNI without PSI. The control group (n = 5) consisted of patients not requiring immunosuppression. VEGF was present in serum of 70 (83%) study group patients: median (range) 18 (0-316) pg/mL, mean 35 ± 57 pg/mL; in 13 (93%) PSI group patients: 22 (0-110) pg/mL, 28 ± 28 pg/mL, with 19 (8-20) pg/mL, 16 ± 6 pg/mL in the PSI + CNI subgroup, and 29 (0-110) pg/mL, 32 ± 32 pg/mL in the PSIw/oCNI subgroup. In the CNIw/oPSI group VEGF was present in 57 (81%) patients: 16 (0-316) pg/mL, 37 ± 62 pg/mL, and in the control group in 3 (60%) patients: 4 (0-110) pg/mL, 32 ± 48 pg/mL. None of the differences observed between any compared groups and/or subgroups was significant (χ(2) and Mann-Whitney U test). In conclusion, differences of VEGF concentration observed among groups imply the influence of PSI and CNI on VEGF production, but further studies involving higher numbers of participants are needed to prove it.

  14. Influence of proliferation signal inhibitors on vascular endothelial growth factor production in heart transplant recipients – preliminary report

    Science.gov (United States)

    Kamieńska, Natalia; Kasperska-Zając, Alicja; Szewczyk, Marta; Trybunia-Orzeszek, Dominika; Nożyński, Jerzy; Pijet, Marta; Hrapkowicz, Tomasz; Zembala, Marian

    2014-01-01

    Proliferation signal inhibitors (PSI) are especially beneficial for heart transplant recipients, but are rarely used due to frequent side effects. As they may be caused by vascular endothelial growth factor (VEGF), we performed a prospective cross-sectional pilot study to assess the influence of PSI and/or calcineurin inhibitors (CNI) presence in immunosuppressive protocols of heart transplant recipients on VEGF secretion. All electively screened heart transplant recipients willing to participate were enrolled in the study. The preliminary report was based on the results of the first 89 serum samples. The study group (n = 84) consisted of the PSI group (n = 14) further divided into the PSI + CNI subgroup (n = 10) and PSIw/oCNI subgroup (n = 4) based on concomitant CNI use, and the CNIw/oPSI group (n = 70) receiving CNI without PSI. The control group (n = 5) consisted of patients not requiring immunosuppression. VEGF was present in serum of 70 (83%) study group patients: median (range) 18 (0-316) pg/mL, mean 35 ± 57 pg/mL; in 13 (93%) PSI group patients: 22 (0-110) pg/mL, 28 ± 28 pg/mL, with 19 (8-20) pg/mL, 16 ± 6 pg/mL in the PSI + CNI subgroup, and 29 (0-110) pg/mL, 32 ± 32 pg/mL in the PSIw/oCNI subgroup. In the CNIw/oPSI group VEGF was present in 57 (81%) patients: 16 (0-316) pg/mL, 37 ± 62 pg/mL, and in the control group in 3 (60%) patients: 4 (0-110) pg/mL, 32 ± 48 pg/mL. None of the differences observed between any compared groups and/or subgroups was significant (χ2 and Mann-Whitney U test). In conclusion, differences of VEGF concentration observed among groups imply the influence of PSI and CNI on VEGF production, but further studies involving higher numbers of participants are needed to prove it. PMID:26336417

  15. Toward an in vivo dissolution methodology: a comparison of phosphate and bicarbonate buffers.

    Science.gov (United States)

    Sheng, Jennifer J; McNamara, Daniel P; Amidon, Gordon L

    2009-01-01

    The purpose of this research was to evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin, to illustrate the dependence of buffer differential on biopharmaceutical properties of BCS II weak acids, and to recommend phosphate buffers equivalent to bicarbonates. The intrinsic dissolution rates of ketoprofen and indomethacin were experimentally measured using a rotating disk method at 37 degrees C in USP SIF/FaSSIF and various concentrations of bicarbonates. Theoretical models including an improved reaction plane model and a film model were applied to estimate the surrogate phosphate buffers equivalent to the bicarbonates. Experimental results show that the intrinsic dissolution rates of ketoprofen and indomethacin in USP and FaSSIF phosphate buffers are 1.5-3.0 times that in the 15 mM bicarbonates. Theoretical analysis demonstrates that the buffer differential is largely dependent on the drug pK(a) and second on solubility, and weakly dependent on the drug diffusivity. Further, in accordance with the drug pK(a), solubility and diffusivity, a simple phosphate surrogate was proposed to match an average bicarbonate value (15 mM) of the upper gastrointestinal region. Specifically, phosphate buffers of 13-15 mM and 3-4 mM were recommended for ketoprofen and indomethacin, respectively. For both ketoprofen and indomethacin, the intrinsic dissolution using the phosphate surrogate buffers closely approximated the 15 mM bicarbonate buffer. This work demonstrates the substantial difference between pharmaceutical phosphates and physiological bicarbonates in determining the drug intrinsic dissolution rates of BCS II weak acids, such as ketoprofen and indomethacin. Surrogate phosphates were recommended in order to closely reflect the in vivo dissolution of ketoprofen and indomethacin in gastrointestinal bicarbonates, which has significant implications for defining buffer systems for

  16. 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.

  17. 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.

  18. Physiological Sensing of Carbon Dioxide/Bicarbonate/pH via Cyclic Nucleotide Signaling

    Directory of Open Access Journals (Sweden)

    Lonny R. Levin

    2011-02-01

    Full Text Available Carbon dioxide (CO2 is produced by living organisms as a byproduct of metabolism. In physiological systems, CO2 is unequivocally linked with bicarbonate (HCO3− and pH via a ubiquitous family of carbonic anhydrases, and numerous biological processes are dependent upon a mechanism for sensing the level of CO2, HCO3, and/or pH. The discovery that soluble adenylyl cyclase (sAC is directly regulated by bicarbonate provided a link between CO2/HCO3/pH chemosensing and signaling via the widely used second messenger cyclic AMP. This review summarizes the evidence that bicarbonate-regulated sAC, and additional, subsequently identified bicarbonate-regulate nucleotidyl cyclases, function as evolutionarily conserved CO2/HCO3/pH chemosensors in a wide variety of physiological systems.

  19. Serum Bicarbonate And Survival In Peritoneal Dialysis (Pd: Comparison With Hemodialysis (Hd

    Directory of Open Access Journals (Sweden)

    Tania Sharma

    2012-06-01

    Full Text Available Correction of metabolic acidosis is one of the goals of effective dialysis. The KDOQI guidelines recommend serum bicarbonate >22 meq/L irrespective of dialysis modality. Since the measured bicarbonate reflects the steady state in PD patients and the lowest inter-dialytic value in HD patients, we compared the survival predictability of serum bicarbonate 10,400 PD and 110,951 HD patients treated in DaVita facilities from 7/2001-6/2006 with follow-up through 6/2007. PD patients were substantially less likely to have lower serum bicarbonate (adjusted odds, 22 meq/L for all end-stage renal disease irrespective of dialysis modality.fx1

  20. Remediation of uranium contaminated soils with bicarbonate extraction and microbial U(VI) reduction

    Science.gov (United States)

    Philips , Elizabeth J.P.; Landa, Edward R.; Lovely, Derek R.

    1995-01-01

    A process for concentrating uranium from contaminated soils in which the uranium is first extracted with bicarbonate and then the extracted uranium is precipitated with U(VI)-reducing microorganisms was evaluated for a variety of uranuum-contaminated soils. Bicarbonate (100 mM) extracted 20–94% of the uranium that was extracted with nitric acid. The U(VI)-reducing microorganism,Desulfovibrio desulfuricans reduced the U(VI) to U(IV) in the bicarbonate extracts. In some instances unidentified dissolved extracted components, presumably organics, gave the extract a yellow color and inhibited U(VI) reduction and/or the precipitation of U(IV). Removal of the dissolved yellow material with the addition of hydrogen peroxide alleviated this inhibition. These results demonstrate that bicarbonate extraction of uranium from soil followed by microbial U(VI) reduction might be an effective mechanism for concentrating uranium from some contaminated soils.

  1. Abnormal production of tumor necrosis factor (TNF) -- alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome [corrected].

    Science.gov (United States)

    Cortis, Elisabetta; De Benedetti, Fabrizio; Insalaco, Antonella; Cioschi, Stefania; Muratori, Flaminia; D'Urbano, Leila E; Ugazio, Alberto G

    2004-12-01

    We report a family with pyogenic sterile arthritis, pyoderna and acne syndrome (PAPA). The proband presented several episodes of sterile pyogenic arthritis and became unresponsive to glucocorticoids. After treatment with the tumor necrosis factor inhibitor etanercept, the disease underwent rapid and sustained clinical remission. Production of tumor necrosis factor-alpha by mononuclear cells of the proband and of the affected relatives was abnormally elevated.

  2. 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.

  3. 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.

  4. 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.

  5. Probing the bioactive conformation of an archetypal natural product HDAC inhibitor with conformationally homogeneous triazole-modified cyclic tetrapeptides.

    Science.gov (United States)

    Horne, W Seth; Olsen, Christian A; Beierle, John M; Montero, Ana; Ghadiri, M Reza

    2009-01-01

    Fooling enzymes with mock amides: Analogues of apicidin, a cyclic-tetrapeptide inhibitor of histone deacetylase (HDAC), were designed with a 1,4- or 1,5-disubstituted 1,2,3-triazole in place of a backbone amide bond to fix the bond in question in either a trans-like or a cis-like configuration. Thus, the binding affinity of distinct peptide conformations (see picture) could be probed. One analogue proved in some cases to be superior to apicidin as an HDAC inhibitor.

  6. Rational design and synthesis of new quorum-sensing inhibitors derived from acylated homoserine lactones and natural products from garlic

    DEFF Research Database (Denmark)

    Persson, T.; Rasmussen, Thomas Bovbjerg; Skindersoe, M.

    2005-01-01

    with similarity both to sulfides 10a-s and to bioactive structures from garlic. Design and biological screening of all compounds presented in this work targeted inhibition of quorum-sensing comprising competitive inhibition of transcriptional regulators LuxR and LasR. The design was based on critical interactions...... within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-L-homoserine lactone (10c) was identified. Together with data collected for the other...

  7. Effect of nitrification inhibitors (DMPP and 3MP+TZ) on soil nitrous oxide emissions from a sub-tropical vegetable production system in Queensland, Australia

    Science.gov (United States)

    Scheer, Clemens; Deuter, Peter; Firrell, Mary; Rowlings, David; Grace, Peter

    2015-04-01

    The use of nitrification inhibitors, in combination with ammonium based fertilisers, has been promoted recently as an effective method to reduce nitrous oxide (N2O) emissions from fertilised agricultural fields, whilst increasing yield and nitrogen use efficiency. Vegetable cropping systems are often characterised by high inputs of nitrogen fertiliser and consequently elevated emissions of nitrous oxide (N2O) can be expected. However, to date only limited data is available on the use of nitrification inhibitors in sub-tropical vegetable systems. A field experiment investigated the effect of the nitrification inhibitors (DMPP & 3MP+TZ) on N2O emissions and yield from a typical vegetable production system in sub-tropical Australia. Soil N2O fluxes were monitored continuously over an entire year with a fully automated system. Measurements were taken from three subplots for each treatment within a randomized complete blocks design. There was a significant inhibition effect of DMPP and 3MP+TZ on N2O emissions and soil mineral N content directly following the application of the fertiliser over the vegetable cropping phase. However this mitigation was offset by elevated N2O emissions from the inhibitor treatments over the post-harvest fallow period. Cumulative annual N2O emissions amounted to 1.22 kg-N/ha, 1.16 kg-N/ha, 1.50 kg-N/ha and 0.86 kg-N/ha in the conventional fertiliser (CONV), the DMPP treatment, the 3MP+TZ treatment and the zero fertiliser (0N) respectively. Corresponding fertiliser induced emission factors (EFs) were low with only 0.09 - 0.20% of the total applied fertiliser lost as N2O. There was no significant effect of the nitrification inhibitors on yield compared to the CONV treatment for the three vegetable crops (green beans, broccoli, lettuce) grown over the experimental period. This study highlights that N2O emissions from such vegetable cropping system are primarily controlled by post-harvest emissions following the incorporation of vegetable crop

  8. Intravenous bicarbonate and sodium chloride both prolong endurance during intense cycle ergometer exercise.

    Science.gov (United States)

    Mitchell, T H; Abraham, G; Wing, S; Magder, S A; Cosio, M G; Deschamps, A; Marliss, E B

    1990-08-01

    To determine the effects of neutralizing exercise systemic acidosis via the intravenous route upon endurance and metabolic responses, eight lean, normal, postabsorptive men exercised to exhaustion at about 80% of their VO2 max (69 +/- 3%, mean +/- SEM, of maximum power output) on a cycle ergometer. Exercise studies were performed either with no infusion (control) or with a total infusion volume of about 1.5 L, mainly as 1.3% sodium bicarbonate or as 0.9% sodium chloride (NaCl), infused (double-blind) throughout exercise. The sodium bicarbonate was to prevent acid-base change, the sodium chloride was as a control for the volume infused. Arterialized venous blood and breath-by-breath analysis of expired gases were obtained. [H+] (nmol.L-1) and [HCO3-] (mmol.L-1) at exhaustion were similar in control and NaCl (46.5 +/- 1.8, 19.9 +/- 0.9), but remained unchanged from rest values with bicarbonate (38.4 +/- 0.9, 24.8 +/- 1.5, p less than 0.005 vs control and NaCl). At exhaustion, VO2, VCO2, RER, heart rate, and systolic BP as well as FFA, glycerol, alanine, insulin, norepinephrine, and epinephrine did not differ among protocols. Endurance was markedly prolonged (p less than 0.01) with bicarbonate (31.9 +/- 5.8 min) and NaCl (31.8 +/- 4.1 min) compared with the control (19.0 +/- 2.9 min) condition. Plasma glucose at exhaustion was higher (p less than 0.025) in the control compared to bicarbonate and NaCl experiments, while lactate was higher (p less than 0.025) in the bicarbonate than in the control and NaCl experiments. Thus, the prolonged endurance with sodium bicarbonate infusion could not be explained either by its effect of maintaining blood acid-base equilibrium or concomitant metabolic changes.

  9. 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.

  10. Effects of combined creatine and sodium bicarbonate supplementation on repeated sprint performance in trained men.

    Science.gov (United States)

    Barber, James J; McDermott, Ann Y; McGaughey, Karen J; Olmstead, Jennifer D; Hagobian, Todd A

    2013-01-01

    Creatine and sodium bicarbonate supplementation independently increase exercise performance, but it remains unclear whether combining these 2 supplements is more beneficial on exercise performance. The purpose of this study was to evaluate the impact of combining creatine monohydrate and sodium bicarbonate supplementation on exercise performance. Thirteen healthy, trained men (21.1 ± 0.6 years, 23.5 ± 0.5 kg·m(-2), 66.7 ± 5.7 ml·(kg·m)(-1) completed 3 conditions in a double-blinded, crossover fashion: (a) Placebo (Pl; 20 g maltodextrin + 0.5 g·kg(-1) maltodextrin), (b) Creatine (Cr; 20 g + 0.5 g·kg(-1) maltodextrin), and (c) Creatine plus sodium bicarbonate (Cr + Sb; 20 g + 0.5 g·kg(-1) sodium bicarbonate). Each condition consisted of supplementation for 2 days followed by a 3-week washout. Peak power, mean power, relative peak power, and bicarbonate concentrations were assessed during six 10-second repeated Wingate sprint tests on a cycle ergometer with a 60-second rest period between each sprint. Compared with Pl, relative peak power was significantly higher in Cr (4%) and Cr + Sb (7%). Relative peak power was significantly lower in sprints 4-6, compared with that in sprint 1, in both Pl and Cr. However, in Cr + Sb, sprint 6 was the only sprint significantly lower compared with sprint 1. Pre-Wingate bicarbonate concentrations were significantly higher in Cr + Sb (10%), compared with in Pl and Cr, and mean concentrations remained higher after sprint 6, although not significantly. Combining creatine and sodium bicarbonate supplementation increased peak and mean power and had the greatest attenuation of decline in relative peak power over the 6 repeated sprints. These data suggest that combining these 2 supplements may be advantageous for athletes participating in high-intensity, intermittent exercise.

  11. The microbial production of amylase inhibitor and its application. I. Isolation and cultivation of Streptomyces nigrifaciens NTU-3314.

    Science.gov (United States)

    Su, Y C; Chiu, R J; Yu, N; Chang, W R

    1984-10-01

    In the course of screening amylase inhibitor producing, microorganisms, a strain identified as Streptomyces nigrifaciens NTU-3314 was found to have the highest inhibitor-producing ability among the other isolated strains. This strain was aerobically cultured at 30 degrees C in a 5l jar fermentor with a working volume of 2l. The optimum cultural medium consisted of defatted soybean flake 3.0%, potato starch 4.0%, casein 0.6%, sucrose 0.6%, serine 0.02% and NaCl 0.8% (pH 7.0). With an aeration rate of 1.5 vvm, an agitation speed of 300 rpm and an inoculum of 15% seed (previously grown in seed medium 3), the highest amount of inhibitor was obtained after 24 hours of cultivation. The amylase inhibitor produced had inhibitory effects on both alpha-amylase and glucoamylase, but not on beta-amylase, alpha-glucosidase, beta-glucosidase or dextranase. It was quite stable in 0.1M phosphate buffer (pH 7.0) and nearly 100% of its activity was retained even after boiling at 100 degrees C for 20 min.

  12. 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.

  13. 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.

  14. Application research of sweetness inhibitor in chocolate products%甜味抑制剂在巧克力制品中的应用研究

    Institute of Scientific and Technical Information of China (English)

    杨恒; 郑建仙

    2011-01-01

    Adding sweetness inhibitor into chocolate products was studied, which discussed the comprehensive senses influence of sweetness inhibitor, sucrose and coco butter on the chocolate products. And the response surface methodology was conducted to optimize the conditions based on the single - factor test. The best conditions were found as follows; the total dosage of coco butter was 30. 55% , the dosage of sucrose was 55. 2% and the dosage of sweetness inhibitor was 0. 2054. And after added sweetness inhibitor, it not only reduced the energy and sweet greasy degree of chocolate, but also cut down the cost.%对甜味抑制剂在巧克力制品中的应用进行了研究,探讨了甜味抑制剂添加量、蔗糖用量、可可脂用量对巧克力制品综合感官的影响,并在单因素实验的基础上采用响应面分析法选出最佳工艺条件,即可可脂总用量为30.55%、蔗糖用量为55.2%、甜味抑制剂添加量为0.2054‰时,巧克力的综合感官评分最好,且添加甜味抑制剂后不仅降低了巧克力的能量和甜腻度,还减少了其生产成本.

  15. Interactions of a family 18 chitinase with the designed inhibitor HM508 and its degradation product, chitobiono-delta-lactone.

    Science.gov (United States)

    Vaaje-Kolstad, Gustav; Vasella, Andrea; Peter, Martin G; Netter, Catharina; Houston, Douglas R; Westereng, Bjørge; Synstad, Bjørnar; Eijsink, Vincent G H; van Aalten, Daan M F

    2004-01-30

    We describe enzymological and structural analyses of the interaction between the family 18 chitinase ChiB from Serratia marcescens and the designed inhibitor N,N'-diacetylchitobionoxime-N-phenylcarbamate (HM508). HM508 acts as a competitive inhibitor of this enzyme with a K(i) in the 50 microM range. Active site mutants of ChiB show K(i) values ranging from 1 to 200 microM, providing insight into some of the interactions that determine inhibitor affinity. Interestingly, the wild type enzyme slowly degrades HM508, but the inhibitor is essentially stable in the presence of the moderately active D142N mutant of ChiB. The crystal structure of the D142N-HM508 complex revealed that the two sugar moieties bind to the -2 and -1 subsites, whereas the phenyl group interacts with aromatic side chains that line the +1 and +2 subsites. Enzymatic degradation of HM508, as well as a Trp --> Ala mutation in the +2 subsite of ChiB, led to reduced affinity for the inhibitor, showing that interactions between the phenyl group and the enzyme contribute to binding. Interestingly, a complex of enzymatically degraded HM508 with the wild type enzyme showed a chitobiono-delta-lactone bound in the -2 and -1 subsites, despite the fact that the equilibrium between the lactone and the hydroxy acid forms in solution lies far toward the latter. This shows that the active site preferentially binds the (4)E conformation of the -1 sugar, which resembles the proposed transition state of the reaction.

  16. Improved bio-hydrogen production from glucose by adding a specific methane inhibitor to microbial electrolysis cells with a double anode arrangement.

    Science.gov (United States)

    Zhang, Jingnan; Bai, Yanxia; Fan, Yaoting; Hou, Hongwei

    2016-10-01

    Improved hydrogen production from glucose was achieved by adding a specific methane inhibitor (such as chloroform) to repress the activity of methanogens in a single-chamber microbial electrolysis cells (MECs) with a double anode arrangement. A maximum hydrogen production of 8.4±0.2 mol H2/mol-G (G represents glucose), a hydrogen production rate of 2.39±0.3 m(3) H2/m3/d and a high energy efficiency (relative to the electrical input) of ηE=165±5% had been recorded from 1 g/L glucose at a low dosage of chloroform (5‰, v:v) and an applied voltage of 0.8 V. Almost all of the glucose was removed within 4 h, with 66% of the electrons in intermediates (mainly including acetate and ethanol), and methane gas was not detected in the MECs through 11 batch cycles. The experimental results confirmed that chloroform was an effective methane inhibitor that improved hydrogen production from glucose in the MECs. In addition, the cyclic voltammetry tests demonstrated that the electron transfer in the MECs was mainly due to the biofilm-bound redox compounds rather than soluble electron shuttles.

  17. Regulation of duodenal bicarbonate secretion during stress by corticotropin-releasing factor and beta-endorphin.

    Science.gov (United States)

    Lenz, H J

    1989-02-01

    Proximal duodenal mucosal bicarbonate secretion is an important factor in the pathogenesis of duodenal ulcer disease. To examine the central nervous system regulation of duodenal bicarbonate secretion, an animal model was developed that allowed cerebroventricular and intravenous injections as well as collection of duodenal perfusates in awake, freely moving rats. The hypothalamic peptide corticotropin-releasing factor (CRF) and stress (physical restraint) significantly stimulated duodenal bicarbonate secretion. These responses were abolished by pretreatment of the animals with the CRF receptor antagonist alpha-helical CRF-(9-41), hypophysectomy, and naloxone. In contrast, blockade of autonomic efferents by surgical and pharmacological means did not prevent the stimulatory effects of stress and CRF. Intravenous, but not cerebroventricular, administration of beta-endorphin that produced plasma concentrations of beta-endorphin that were similar to those produced by exogenous CRF and stress significantly stimulated duodenal bicarbonate secretion. These results indicate that endogenous CRF released during stress and exogenously administered CRF stimulate duodenal bicarbonate secretion by release of beta-endorphin from the pituitary, thus, demonstrating a functional hypothalamus-pituitary-gut axis.

  18. Interactive Effects of the Carbon Paper, Sodium Bicarbonate and Oral Contraceptive Pills on Morphine Urine Test

    Directory of Open Access Journals (Sweden)

    Solhi, H

    2010-01-01

    Full Text Available Background and objectives: A major problem for labs. esp. medicolegal centers is drug test false positive and negative results. Using carbonpaper, sodium bicarbonate or oral contraceptive pills (OCP are commonamong addict people to make the results negative. Therefore, we decidedto evaluate the effect of carbon paper, sodium bicarbonate or OCP onmorphine urine test.Material and Methods: We performed this pre-experimental study onthe urine samples of all people referred to narcotic drug laboratory ofMarkazi province during May of 2005. Of 2110 urine samples, theMorphine Rapid Test of 208 samples was positive. Then by means ofTLC method, we confirmed the presence of morphine metabolites in 150urine samples. After that, we divided these samples into three equalgroups for adding carbon paper, sodium bicarbonate or OCP.Results: The results show that in carbon paper group, 41 cases arepositive and nine cases unclear. In sodium bicarbonate group, 45 samplesare positive and 5 cases unclear. In estrogen conjugate group, all 50samples are positive.Conclusion: According to this study, adding carbon paper, sodiumbicarbonate or oral contraceptive pills cannot make negative theMorphine Rapid Test result.Key words: Morphine Rapid Test, Carbon paper, Sodium bicarbonate,Oral contraceptive pill.

  19. Mechanisms behind changes in gastric acid and bicarbonate outputs during the human interdigestive motility cycle.

    Science.gov (United States)

    Dalenbäck, J; Fändriks, L; Olbe, L; Sjövall, H

    1996-01-01

    Human gastric interdigestive acid and bicarbonate outputs vary cyclically in association with the migrating motor complex (MMC). These phenomena were studied in 26 healthy volunteers by constant-flow gastric perfusion, with continuous recording of pH and Pco2 in mixed gastric effluent and concomitant open-tip manometry of gastroduodenal motility. Stable acid and bicarbonate outputs were registered during less than 50% of the MMC cycle. Acid secretion started to increase 71 +/- 3% into the cycle, with maximum output during antral phase III. Bicarbonate output increased biphasically 1) 40 +/- 5% into the cycle, coinciding with reflux of bile, and 2) at the end of duodenal phase III when the aspirate was devoid of bile. The bicarbonate peak associated with phase III was abolished by atropine (0.01 mg/kg iv, n = 8) and by pyloric occlusion (n = 9) but remained unchanged after omeprazole (n = 10). The acid peak was abolished by both atropine and omeprazole. It is concluded that the MMC-related changes in acid and alkaline outputs represent two different and independent phenomena. Acid secretion cyclicity is due to periodical variations in cholinergic stimulation of the parietal cells. In contrast, the phase III-associated increase in bicarbonate output is due to duodenogastric reflux.

  20. Sulphate-bicarbonate mineral waters in the treatment of biliary and digestive tract diseases.

    Science.gov (United States)

    Fraioli, A; Menunni, G; Petraccia, L; Fontana, M; Nocchi, S; Grassi, M

    2010-01-01

    The authors point out the therapeutic properties of sulphate-bicarbonate mineral waters. After summarizing the general mechanism of action of mineral waters, the main indications of such waters in thermal treatment are examined including: biliary sand, biliary dyskinesia, functional dyspepsia, irritable colon, chronic primitive constipation. The dysfunctions of biliary and digestive tracts are growing, mainly in the affluent world, because of the increase for stress, dietary habits, modern life style. Now they affect from 2,4% of general population to 7% of men and 20% of women, according to different studies. Mineral waters can improve symptoms and care some physiopathological underlying mechanisms. Authors stress the efficacy of sulphate-bicarbonate mineral waters in the therapy of biliary dyskinesias, namely gallbladder hypokinesia and Oddi's sphincter spasm, caused by their content in SO4 = anion and Mg++ cation and related effects on paracrine-endocrine gastrointestinal system. In addition, they report the effects of sulphate-bicarbonate mineral waters in the lithogenic bile (sand bile), because of their diluting and washing activity. Among the sulphate-bicarbonate mineral waters, the Authors outline the well-documented therapeutic activity of Acqua Santa and Fucoli of Chianciano Terme. Acqua Santa has stimulating effect on cholecystis's motility, as proved by controlled clinical trials. Finally, the therapeutic use of sulphate-bicarbonate mineral water is discussed in functional dyspepsia, chronic primitive constipation and irritable bowel syndrome.

  1. Differential Responses of Two Lactuca sativa Varieties to Bicarbonate-Induced Iron Deficiency

    Directory of Open Access Journals (Sweden)

    Mohamed Chebbi

    2013-11-01

    Full Text Available Iron chlorosis induced by bicarbonate is very common in calcareous soils, where bicarbonate (HCO3- ions are present at high concentrations. In this study, morpho-physiological and biochemical responses of two Lactuca sativa varieties (Romaine and Vista to bicarbonate induced iron deficiency were investigated. The culture was conducted on nutrient solution containing 5 µM Fe and 10 mM NaHCO3, in a growth chamber with controlled conditions. After 14 days of bicarbonate treatment, the two varieties seedling showed a slight yellowing of young leaves associated with a significant decline of plant biomass, leaf number and area. Furthermore, the concentrations of the nutrient elements (potassium, magnesium, iron and calcium in leaves and roots of two lettuce varieties were modified. In roots of bicarbonate treated plants, the Fe-chelate reductase activity was increased as compared to control in both varieties. PEPC activity was enhanced only in Vista variety. Moreover, Fe deficiency induced a small change in the photosynthetic parameters and chlorophyll fluorescence, especially in Romaine variety. These changes are accompanied by decreases in ribulose 1.5-bisphosphate carboxylase/oxygenase (Rubisco activity. These findings indicated that Vista variety could survive at low iron supply.

  2. Effect of sodium bicarbonate and varying concentrations of sodium chloride in brine on the liquid retention of fish (Pollachius virensL.) muscle

    DEFF Research Database (Denmark)

    Åsli, Magnus; Ofstad, Ragni; Böcker, Ulrike

    2016-01-01

    BACKGROUND Negative health effects associated with excessive sodium (Na) intake have increased the demand for tasty low-Na products (<2% NaCl) rather than traditional heavily salted fish products (∼20% NaCl). This study investigates the causes of improved yield and liquid retention of fish muscle...... in greater intracellular space at 30 and 60 g kg−1 NaCl. CONCLUSION Sodium bicarbonate addition to low-salt solutions can improve yield and flesh quality of fish muscle owing to altered water mobility and wider space between the muscle cells...

  3. 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.

  4. 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.

  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. 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.

  7. Exchange equilibria between bicarbonate, carbonate, chloride and bromide on dowex 1 x 8.

    Science.gov (United States)

    Lundström, U; Olin, A

    1984-07-01

    The exchange reaction 2R(+)HCO(3)(2-) + CO(3)(2-) right harpoon over left harpoon R(2)(+) CO(3)(2-) + 2HCO(3)(2-) has been studied on Dowex 1 x 8 in the presence of bicarbonate solution in equilibrium with atmospheric carbon dioxide (open system). The experiments showed, as theory predicts, that the composition of the resin phase is independent of the concentration of the bicarbonate solution. The mole fraction of carbonate at equilibrium is about 0.4 and the equilibrium constant is 0.15M at 20 degrees . With this value of the constant, the composition of the ion-exchanger for various bicarbonate concentrations has been calculated for a closed system. At [HCO(3)(-)] Chromatographie enrichment of bromide from fresh water.

  8. A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening.

    Science.gov (United States)

    Bruccoleri, Rebecca E; Burns, Michele M

    2016-03-01

    Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants.

  9. Isotope composition of bicarbonate carbon in bed waters of oil and gas deposits

    Energy Technology Data Exchange (ETDEWEB)

    Golyshev, S.I.; Cherepnin, A.V.; Ivanov, V.G.; Manylova, L.S.

    1981-01-01

    A study is made of the isotope composition of bicarbonate carbon in bed waters of the Jurassic water complex in southeast West Siberia. It has been established that waters of empty and transcontour structures have isotope composition of carbon 5/sup 0//oo, while in waters which contact the hydrocarbon formations, the isotope composition of carbon is lighter on the average by 5-8/sup 0//oo. The isotope composition of bicarbonate carbon in bed waters reflects both the conditions for primary sedimentation, and secondary processes associated with organic matter transformation.

  10. 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.

  11. 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.

  12. Restoration of camptothecine production in attenuated endophytic fungus on re-inoculation into host plant and treatment with DNA methyltransferase inhibitor.

    Science.gov (United States)

    Vasanthakumari, M M; Jadhav, S S; Sachin, Naik; Vinod, G; Shweta, Singh; Manjunatha, B L; Kumara, P Mohana; Ravikanth, G; Nataraja, Karaba N; Uma Shaanker, R

    2015-10-01

    Fungal endophytes inhabit living tissues of plants without any apparent symptoms and in many cases are known to produce secondary metabolites similar to those produced by their respective host plants. However on sub-culture, the endophytic fungi gradually attenuate their ability to produce the metabolites. Attenuation has been a major constraint in realizing the potential of endophytic fungi as an alternative source of plant secondary metabolites. In this study, we report attempts to restore camptothecine (CPT) production in attenuated endophytic fungi isolated from CPT producing plants, Nothapodytes nimmoniana and Miquelia dentata when they are passed through their host plant or plants that produce CPT and when treated with a DNA methyl transferase inhibitor. Attenuated endophytic fungi that traversed through their host tissue or plants capable of synthesizing CPT, produced significantly higher CPT compared to the attenuated fungi. Attenuated fungus cultured in the presence of 5-azacytidine, a DNA methyltransferase inhibitor, had an enhanced CPT content compared to untreated attenuated fungus. These results indicate that the attenuation of CPT production in endophytic fungi could in principle be reversed by eliciting some signals from plant tissue, most likely that which prevents the methylation or silencing of the genes responsible for CPT biosynthesis.

  13. 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...

  14. 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

    BACKGROUND: Caffeine and sodium bicarbonate ingestion have been suggested to improve high-intensity intermittent exercise, but it is unclear if these ergogenic substances affect performance under provoked metabolic acidification. To study the effects of caffeine and sodium bicarbonate on intense ...

  15. The Use of Sodium Bicarbonate in the Treatment of Acidosis in Sepsis: A Literature Update on a Long Term Debate

    Directory of Open Access Journals (Sweden)

    Dimitrios Velissaris

    2015-01-01

    Full Text Available Introduction. Sepsis and its consequences such as metabolic acidosis are resulting in increased mortality. Although correction of metabolic acidosis with sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding the role of bicarbonates as a therapeutic option. Methods. We conducted a PubMed literature search in order to identify published literature related to the effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The search included all articles published in English in the last 35 years. Results. There is ongoing debate regarding the use of bicarbonates for the treatment of acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis patients with arterial blood gas pH>7.15. Conclusions. Routine use of bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is subject of controversy, and current opinion does not favor routine use of bicarbonates. However, available evidence is inconclusive, and more studies are required to determine the potential benefit, if any, of bicarbonate therapy in the sepsis patient with acidosis.

  16. 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.

  17. 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。

  18. Enhanced offspring production in Daphnia magna clones exposed to serotonin reuptake inhibitors and 4-nonylphenol. Stage- and food-dependent effects.

    Science.gov (United States)

    Campos, B; Piña, B; Fernández-Sanjuán, M; Lacorte, S; Barata, C

    2012-03-01

    Risk assessment of emerging pollutants requires the development of bioassays able to detect and understand novel mechanisms of action. This study tested the hypothesis that the increase of offspring production in Daphnia magna induced by certain pollutants may be mediated through different mechanisms, depending on development stages, clones and food rations The study included two selective serotonin reuptake inhibitors (SSRIs), fluoxetine and fluvoxamine, and the detergent metabolite 4-nonylphenol. Organisms were exposed from birth to adulthood or only during adulthood at low and high food ration levels. Results indicated that low exposure levels of the three studied substances increased offspring production and/or juvenile developmental rates similarly for all studied clones, but the responses differed among life-stages and food rations. When individuals were exposed to the studied chemicals from birth, enhanced offspring production per female was observed only at low and intermediate food rations. On the contrary, when exposures started in gravid females most treatments increased offspring production. Results obtained with SSRIs support previous findings, where it was stated that these compounds may amplify serotoninergic signaling in D. magna. Nonylphenol effects may be related to the reported alteration of this compound in Daphnia ecdysteroid metabolism. Further investigations are necessary to resolve the biochemical mechanism of SSRI and nonylphenol enhancing offspring production.

  19. Inhibitor of apoptosis proteins (IAPs) and their antagonists regulate spontaneous and tumor necrosis factor (TNF)-induced proinflammatory cytokine and chemokine production.

    Science.gov (United States)

    Kearney, Conor J; Sheridan, Clare; Cullen, Sean P; Tynan, Graham A; Logue, Susan E; Afonina, Inna S; Vucic, Domagoj; Lavelle, Ed C; Martin, Seamus J

    2013-02-15

    Inhibitor of apoptosis proteins (IAPs) play a major role in determining whether cells undergo apoptosis in response to TNF as well as other stimuli. However, TNF is also highly proinflammatory through its ability to trigger the secretion of multiple inflammatory cytokines and chemokines, which is arguably the most important role of TNF in vivo. Indeed, deregulated production of TNF-induced cytokines is a major driver of inflammation in several autoimmune conditions such as rheumatoid arthritis. Here, we show that IAPs are required for the production of multiple TNF-induced proinflammatory mediators. Ablation or antagonism of IAPs potently suppressed TNF- or RIPK1-induced proinflammatory cytokine and chemokine production. Surprisingly, IAP antagonism also led to spontaneous production of chemokines, particularly RANTES, in vitro and in vivo. Thus, IAPs play a major role in influencing the production of multiple inflammatory mediators, arguing that these proteins are important regulators of inflammation in addition to apoptosis. Furthermore, small molecule IAP antagonists can modulate spontaneous as well as TNF-induced inflammatory responses, which may have implications for use of these agents in therapeutic settings.

  20. 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

    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...

  1. The anaerobic conversion of methanol under thermophilic conditions: pH and bicarbonate dependence

    NARCIS (Netherlands)

    Paulo, P.L.; Villa, G.; Lier, van J.B.; Lettinga, G.

    2003-01-01

    The thermophilic (55degreesC) anaerobic conversion of methanol was studied in an unbuffered medium (pH 4 +/- 0.2) and in a phosphate buffered medium (pH 6.4 +/- 0.1), in both cases without bicarbonate addition. Our cultivated sludge consortium was unable to degrade methanol under acidic conditions.

  2. 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.

  3. 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

  4. Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients.

    Science.gov (United States)

    Bossola, Maurizio; Giungi, Stefania; Tazza, Luigi; Luciani, Giovanna

    2007-01-01

    Metabolic acidosis, a frequent event in hemodialysis patients, has been implicated as a potential cause of protein-energy malnutrition. Unfortunately, correction of metabolic acidosis by means of high bicarbonate concentration in the dialysate does not seem to lead to significant changes in nutritional parameters. The project was a single-arm, open-label, 12-month pilot study at a university-based tertiary care center aimed at evaluating whether correction of metabolic acidosis through long-term oral sodium bicarbonate supplementation improves serum albumin levels and other nutritional parameters in patients undergoing maintenance hemodialysis. Twenty highly acidotic hemodialysis patients patients were invited to consume an oral supplementation of sodium bicarbonate (1 g, thrice daily), for 12 months. Patients were followed at baseline and every month, until month 12. At each follow-up visit, dry body weight, BMI, blood pressure, presence of edema, venous bicarbonate, and serum albumin were measured. Total lymphocyte count, fasting total cholesterol and C-reactive protein were assessed every 2 months. At baseline and at 12 months, the subjective global assessment of nutritional status and the protein equivalent of nitrogen appearance normalized to actual body weight were determined. Plasma bicarbonate level rose from 18.1 +/- 2.7 to 22.1 +/- 4.5 mmol/l after 10 months (p = 0.001). Mean serum albumin levels were 3.8 +/- 0.2 mg/dl at baseline and 3.9 +/- 0.2 at the end of the study. Repeated measure ANOVA showed that there was no significant effect of bicarbonate treatment on serum albumin levels (p = 0.29), dry weight (p = 0.1), serum total cholesterol (p = 0.97), total lymphocyte count (p = 0.69), or C-reactive protein (p = 0.85). Mean subjective global assessment score was 4.53 +/- 0.37 at baseline and 4.58 +/- 0.54 at 12 months (p = 0.1). Mean nPNA (g/kg/day) was 0.86 +/- 0.05 at baseline and 0.85 +/- 0.08 at month 12. The present study demonstrates that long

  5. 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.

  6. Phenolic compounds: Strong inhibitors derived from lignocellulosic hydrolysate for 2,3-butanediol production by Enterobacter aerogenes.

    Science.gov (United States)

    Lee, Sang Jun; Lee, Ju Hun; Yang, Xiaoguang; Kim, Sung Bong; Lee, Ja Hyun; Yoo, Hah Young; Park, Chulhwan; Kim, Seung Wook

    2015-12-01

    Lignocellulosic biomass are attractive feedstocks for 2,3-butanediol production due to their abundant supply and low price. During the hydrolysis of lignocellulosic biomass, various byproducts are formed and their effects on 2,3-butanediol production were not sufficiently studied compared to ethanol production. Therefore, the effects of compounds derived from lignocellulosic biomass (weak acids, furan derivatives and phenolics) on the cell growth, the 2,3-butanediol production and the enzymes activity involved in 2,3-butanediol production were evaluated using Enterobacter aerogenes ATCC 29007. The phenolic compounds showed the most toxic effects on cell growth, 2,3-butanediol production and enzyme activity, followed by furan derivatives and weak acids. The significant effects were not observed in the presence of acetic acid and formic acid. Also, feasibility of 2,3-butanediol production from lignocellulosic biomass was evaluated using Miscanthus as a feedstock. In the fermentation of Miscanthus hydrolysate, 11.00 g/L of 2,3-butanediol was obtained from 34.62 g/L of reducing sugar. However, 2,3-butanediol was not produced when the concentration of total phenolic compounds in the hydrolysate increased to more than 1.5 g/L. The present study provides useful information to develop strategies for biological production of 2,3-butanediol and to establish biorefinery for biochemicals from lignocellulosic biomass.

  7. The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    Agnieszka E. Laudy

    2017-01-01

    Full Text Available The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs, against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC value determination in the presence of 1 mM MgSO4. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100–800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.

  8. The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis.

    Science.gov (United States)

    Ori, Yaacov; Zingerman, Boris; Bergman, Michael; Bessler, Hanna; Salman, Hertzel

    2015-04-01

    The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4-5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134±10-116±8 mg/dl, P=0.002), potassium decreased (5.1±0.4-4.8±0.1 mequiv./l, P=0.064), pH increased (7.29±0.01-7.33±0.01, P=0.008), and serum bicarbonate increased (18.6±0.4 mequiv./l to 21.3±0.3 mequiv./l, P=0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75±0.25 ng/ml to 2.29±0.21 ng/ml, P=0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1β, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.

  9. A low serum bicarbonate concentration as a risk factor for mortality in peritoneal dialysis patients.

    Directory of Open Access Journals (Sweden)

    Tae Ik Chang

    Full Text Available BACKGROUND AND AIM: Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD patients. METHODS: This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients. RESULTS: Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR, while it was negatively associated with albumin, C-reactive protein (CRP levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001. In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively. CONCLUSIONS: This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.

  10. 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.

  11. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells.

    Science.gov (United States)

    Shimomura, Tomoko; Nakano, Tomoyuki; Goto, Kaoru; Wakabayashi, Ichiro

    2017-02-01

    Although diacylglycerol kinase (DGK) is known to be expressed in vascular smooth muscle cell, its functional significance remains to be clarified. We hypothesized that DGK is involved in the pathway of cytokine-induced nitric oxide (NO) production in vascular smooth muscle cells. The purpose of this study was to investigate the effects of R59949, a diacylglycerol kinase inhibitor, on inducible nitric oxide production in vascular smooth muscle cell. Cultured rat aortic smooth muscle cells (RASMCs) were used to elucidate the effects of R59949 on basal and interleukin-1β (IL-1β)-induced NO production. The effects of R59949 on protein and mRNA expression of induced nitric oxide synthase (iNOS) and on transplasmalemmal L-arginine uptake were also evaluated using RASMCs. Treatment of RASMCs with R59949 (10 μM) inhibited IL-1β (10 ng/ml)-induced NO production but not basal NO production. Neither protein nor mRNA expression level of iNOS after stimulation with IL-1β was significantly affected by R59949. Estimated enzymatic activities of iNOS in RASMCs were comparable in the absence and presence of R59949. Stimulation of RASMCs with IL-1β caused a marked increase in transplasmalemmal L-arginine uptake into RASMCs. L-Arginine uptake in the presence of IL-1β was markedly inhibited by R59949, while basal L-arginine uptake was not significantly affected by R59949. Both IL-1β-induced NO production and L-arginine uptake were abolished in the presence of cycloheximide (1 μM). The results indicate that R59949 inhibits inducible NO production through decreasing transplasmalemmal L-arginine uptake. DGK is suggested to be involved in cytokine-stimulated L-arginine transport and regulate its intracellular concentration in vascular smooth muscle cell.

  12. Synthesis and evaluation of chalcone derivatives as inhibitors of neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species.

    Science.gov (United States)

    Bukhari, Syed N A; Tajuddin, Yasmin; Benedict, Vannessa J; Lam, Kok W; Jantan, Ibrahim; Jalil, Juriyati; Jasamai, Malina

    2014-02-01

    Inhibitory effects on neutrophils' chemotaxis, phagocytosis and production of reactive oxygen species (ROS) are among the important targets in developing anti-inflammatory agents and immunosuppressants. Eight series of chalcone derivatives including five newly synthesized series were assessed for their inhibitory effects on chemotaxis, phagocytosis and ROS production in human polymorphonuclear neutrophils (PMNs). Inhibition of PMNs' chemotaxis and phagocytosis abilities were investigated using the Boyden chamber technique and the Phagotest kit, respectively, while ROS production was evaluated using luminol- and lucigenin-based chemiluminescence assay. The new derivatives (4d and 8d), which contain 4-methylaminoethanol functional group were active in all the assays performed. It was also observed that some of the compounds were active in inhibiting chemotaxis while others suppressed phagocytosis and ROS production. The information obtained gave new insight into chalcone derivatives with the potential to be developed as immunomodulators.

  13. Augmentation of Cationic Antimicrobial Peptide Production with Histone Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Roshan D. Yedery

    2015-01-01

    Full Text Available The emergence of antibiotic resistance seriously threatens our ability to treat many common and medically important bacterial infections. Novel therapeutics are needed that can be used alone or in conjunction with antibiotics. Cationic antimicrobial peptides (CAMPs are important effectors of the host innate defense that exhibit broad-spectrum activity against a wide range of microorganisms. CAMPs are carried within phagocytic granules and are constitutively or inducibly expressed by multiple cell types, including epithelial cells. The role of histone modification enzymes, specifically the histone deacetylases (HDAC, in down-regulating the transcription of CAMP-encoding genes is increasingly appreciated as is the capacity of HDAC inhibitors (HDACi to block the action of HDACs to increase CAMP expression. The use of synthetic and natural HDACi molecules to increase CAMPs on mucosal surfaces, therefore, has potential therapeutic applications. Here, we review host and pathogen regulation of CAMP expression through the induction of HDACs and assess the therapeutic potential of natural and synthetic HDACi based on evidence from tissue culture systems, animal models, and clinical trials.

  14. Natural Products from Microalgae with Potential against Alzheimer’s Disease: Sulfolipids Are Potent Glutaminyl Cyclase Inhibitors

    Directory of Open Access Journals (Sweden)

    Stephanie Hielscher-Michael

    2016-11-01

    Full Text Available In recent years, many new enzymes, like glutaminyl cyclase (QC, could be associated with pathophysiological processes and represent targets for many diseases, so that enzyme-inhibiting properties of natural substances are becoming increasingly important. In different studies, the pathophysiology connection of QC to various diseases including Alzheimer’s disease (AD was described. Algae are known for the ability to synthesize complex and highly-diverse compounds with specific enzyme inhibition properties. Therefore, we screened different algae species for the presence of QC inhibiting metabolites using a new “Reverse Metabolomics” technique including an Activity-correlation Analysis (AcorA, which is based on the correlation of bioactivities to mass spectral data with the aid of mathematic informatics deconvolution. Thus, three QC inhibiting compounds from microalgae belonging to the family of sulfolipids were identified. The compounds showed a QC inhibition of 81% and 76% at concentrations of 0.25 mg/mL and 0.025 mg/mL, respectively. Thus, for the first time, sulfolipids are identified as QC inhibiting compounds and possess substructures with the required pharmacophore qualities. They represent a new lead structure for QC inhibitors.

  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. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Goulding, A.; McIntosh, J.; Campbell, D.

    1984-04-01

    Metabolic balance studies were undertaken to determine whether sodium bicarbonate (NaHCO/sub 3/) 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)/sub 2/D/sub 3//day). Feeding bicarbonate lowered urinary Ca but raised fecal Ca so that Ca balance became less positive. However, 1,25(OH)/sub 2/D/sub 3/ 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)/sub 2/D/sub 3/. Changes in net Ca absorption induced by bicarbonate may occur at a point in the gut distal to the duodenum since duodenal /sup 45/Ca 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)/sub 2/D/sub 3/ metabolism because it is manifest in animals receiving high doses of 1,25(OH)/sub 2/D/sub 3/, which stimulate alimentary Ca absorption maximally, and because bicarbonate-fed rats are able to respond normally to exogenous 1,25(OH)/sub 2/D/sub 3/ by increasing their net absorption of Ca and P. In view of this demonstration that NaHCO/sub 3/ 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.

  18. 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.

  19. 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

  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. 碳酸氢铵为氮源对螺旋藻培养的影响%Effect of Ammonium Bicarbonate as Nitrogen Source on Spirulina platensis Cultivation

    Institute of Scientific and Technical Information of China (English)

    鲍亦璐; 刘明; 丛威; 卢运明; 宁正祥

    2012-01-01

    以碳酸氢铵作为氮源,研究在分批培养及流加培养条件下其对螺旋藻生长的影响。结果表明:当培养液中碳酸氢铵浓度小于5mmol/L时,螺旋藻生长正常;碳酸氢铵浓度超过5mmol/L时,螺旋藻生长受到抑制,解体死亡。采用生物量反馈补料的流加策略可以使培养液中螺旋藻生物量达到3.08g/L,产率达到0.26g/(L.d),藻体中蛋白质及叶绿素含量分别达到65.06%和13.37mg/g,结果证实了碳酸氢铵为氮源高密度培养螺旋藻的可行性。%The batch and fed-batch cultivations of Spirulina platensis were studied using ammonium bicarbonate as the nitrogen source. The results showed that Spirulinaplatensis could grow well when ammonium concentration in the medium was less than 5 mmol/L. However, when the concentration of ammonium bicarbonate was higher than 5 retool/L, cell growth was inhibited and disintegrated. The fed-batch cultivation using biomass-based feeding method could yield a dry cell concentration of 3.08 g/L, and a productivity of 0.26 g/(L· d). Moreover, the contents of protein and chlorophyll could reach up to 65.06% and 13.37 mg/g, respectively. Therefore, bicarbonate ammonium is a suitable nitrogen source for high cell density culture of Spirulina platensis.

  3. 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.

  4. Bicarbonate ingestion has no ergogenic effect on consecutive all out sprint tests in BMX elite cyclists.

    Science.gov (United States)

    Zabala, Mikel; Peinado, Ana B; Calderón, Francisco J; Sampedro, Javier; Castillo, Manuel J; Benito, Pedro J

    2011-12-01

    The aim of the present study was to examine the effect of sodium bicarbonate ingestion on consecutive "all out" sprint tests, analyzing the acid-base status and its influence on performance and perceived effort. Ten elite bicycle motocross (BMX) riders (20.7 ± 1.4 years, training experience 8-12 years) participated in this study which consisted of two trials. Each trial consisted of three consecutive Wingate tests (WTs) separated by 15 min recovery. Ninety minutes prior to exercise subjects ingested either NaHCO(3) (-) (0.3 g kg(-1) body weight) or placebo. Blood samples were collected for the assessment of blood acid-base status: bicarbonate concentration ([HCO(3) (-)]), pH, base excess (BE) and blood lactate concentration ([La(-)]). Performance variables of peak power (PP), mean power (MP), time to peak power and fatigue index were calculated for each sprint. Significant differences (p BMX cyclists.

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

    DEFF Research Database (Denmark)

    Brodersen, Knud Erik

    2003-01-01

    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 ofthe 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. Thecementitious 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 migratingions is taken into account. Example calculations demonstrate effects of parameter variations on distribution of precipitated calcite in the crack...

  6. Effect of bicarbonate supplementation on renal function and nutritional indices in predialysis advanced chronic kidney disease.

    Science.gov (United States)

    Jeong, Jiwon; Kwon, Soon Kil; Kim, Hye-Young

    2014-12-01

    Current practice guidelines recommend alkali therapy in patients with chronic kidney disease (CKD) and metabolic acidosis to prevent complications. This study aims to investigate the effect of oral sodium bicarbonate supplementation on the progression of renal function and nutritional indices in patients with predialysis advanced CKD. Forty patients with predialysis stage 5 CKD(estimated glomerular filtration rate, eGFR total lymphocyte count (TLC), and Ondodera's prognostic nutritional index (OPNI) during the study between the two groups. In stage 5 CKD, there were significant differences in the changes of TLC and OPNI between the two groups. In conclusion, our results demonstrate that bicarbonate supplementation slows the rate of decline of renal function in stage 4 CKD and improves nutritional indices in stage 5 CKD. Alkali therapy in advanced CKD may have beneficial effect on renal function and malnutrition.

  7. Transformation of Sodium Bicarbonate and CO2 into Sodium Formate over NiPd Nanoparticle Catalyst

    Directory of Open Access Journals (Sweden)

    Mengnan eWang

    2013-09-01

    Full Text Available The present research systematically investigated, for the first time, the transformation of sodium bicarbonate and CO2 into sodium formate over a series of Ni based metal nanoparticles (NPs. Ni NPs and eight NiM (M stands for a second metal NPs were prepared by a facile wet chemical process and then their catalytic performance were evaluated in sodium bicarbonate hydrogenation. Bimetallic NiPd NPs with a composition of 7:3 were found to be superior for this reaction, which are more active than both pure Ni and Pd NPs. Hot filtration experiment suggested the NPs to be the truly catalytic active species and kinetic analysis indicated the reaction mechanism to be different than most homogeneous catalysts. The enhanced activity of the bimetallic nanoparticles may be attributed to their smaller size and improved stability.

  8. 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....

  9. The regulation of interferon production by aspirin, other inhibitors of the cyclooxygenase pathway and agents influencing calcium channel flux.

    OpenAIRE

    1989-01-01

    Interferon is a family of potent antiviral agents which can activate macrophages, enhance cell surface markers, or influence antibody production. Three major types of human interferon are known to exist and have been designated interferons alpha, beta, and gamma. Because of its unique antiviral properties and its ability to influence the immune response, interferon has long been considered a potential therapeutic intervention in the treatment of infections and possibly neoplastic diseases. Tw...

  10. 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.

  11. Temperature and Particle Size Dependence of Sodium Bicarbonate Inhibition of Methane/Air Flames.

    Science.gov (United States)

    1982-11-03

    43 7 Particle mess flow rate in fluidized bed feeder as a function of pressure drop in mercury manometer . . 46 8 Attenuated Us~e laser peak upon... mercury manometer , attached to the fluidized feeder housing, was used to find the value of mass flow rate on the calibration curve. Sodium bicarbonate was...front without further refinement. 45 3.2 Particle Feed Rate Measurements LI A mercury manometer was attached to the fluidized feeder housing and a

  12. 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

  13. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

    Science.gov (United States)

    Zippin, Jonathan H.; Farrell, Jeanne; Huron, David; Kamenetsky, Margarita; Hess, Kenneth C.; Fischman, Donald A.; Levin, Lonny R.; Buck, Jochen

    2004-01-01

    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation. PMID:14769862

  14. Bicarbonate-responsive “soluble” adenylyl cyclase defines a nuclear cAMP microdomain

    OpenAIRE

    2004-01-01

    Bicarbonate-responsive “soluble” adenylyl cyclase resides, in part, inside the mammalian cell nucleus where it stimulates the activity of nuclear protein kinase A to phosphorylate the cAMP response element binding protein (CREB). The existence of this complete and functional, nuclear-localized cAMP pathway establishes that cAMP signals in intracellular microdomains and identifies an alternate pathway leading to CREB activation.

  15. 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.

  16. Influence of colostrum preservation and sodium bicarbonate on performance of dairy calves.

    Science.gov (United States)

    Jenny, B F; Hodge, S E; O'Dell, G D; Ellers, J E

    1984-02-01

    Forty-eight Holstein calves were fed one of four liquid diets from 3 to 30 days of age to compare sodium benzoate, propionic acid, and formaldehyde as preservatives for colostrum. Colostrum batches were fermented at temperatures of 20 degrees C or higher. Diets were 2.73 kg of 1) naturally fermented colostrum, or colostrum treated with 2) sodium benzoate (.5% by weight), 3) propionic acid (1.0% by weight), or 4) formaldehyde (.05% by weight). Colostrum diets were diluted with .91 kg water. Prior to feeding, 25 g. sodium bicarbonate was added to liquid diets of one-half the calves on each treatment. Liquid diets were fed once daily. Water and a 15% crude protein complete starter were offered for ad libitum consumption. Calves were weaned abruptly at 30 days of age and received only water and starter from 31 to 44 days of age. Daily gain from 0 to 4 wk and 0 to 6 wk favored calves fed colostrum treated with sodium benzoate or propionic acid. Gains from 0 to 6 wk were .33, .44, .45, and .32 kg/day for the four diets, and feed efficiencies (kg dry matter intake/kg gain) were 3.23, 2.36, 2.76, and 2.89 during the same period. Addition of sodium bicarbonate to colostrum diets improved intake during the 1st wk of feeding. Gain and feed efficiency were similar during wk 0 to 4 but favored slightly calves not receiving sodium bicarbonate during the overall study, wk 0 to 6. Daily gain and efficiencies during wk 0 to 6 were .41 and 2.53 for calves without .36 and 3.01 with sodium bicarbonate added to colostrum diets.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Interactions between bicarbonate, potassium, and magnesium, and sulfur-dependent induction of luminescence in Vibrio fischeri.

    Science.gov (United States)

    Tabei, Yosuke; Era, Mariko; Ogawa, Akane; Morita, Hiroshi

    2012-06-01

    In spite of its central importance in research efforts, the relationship between seawater compounds and bacterial luminescence has not previously been investigated in detail. Thus, in this study, we investigated the effect of cations (Na(+) , K(+) , NH(4) (+) , Mg(2+) , and Ca(2+) ) and anions (Cl(-) , HCO(3) (-) , CO(3) (2-) , and NO(3) (-) ) on the induction of both inorganic (sulfate, sulfite, and thiosulfate) and organic (L-cysteine and L-cystine) sulfur-dependent luminescence in Vibrio fischeri. We found that HCO(3) (-) (bicarbonate) and CO(3) (2-) (carbonate), in the form of various compounds, had a stimulatory effect on sulfur-dependent luminescence. The luminescence induced by bicarbonate was further promoted by the addition of magnesium. Potassium also increased sulfur-dependent luminescence when sulfate or thiosulfate was supplied as the sole sulfur source, but not when sulfite, L-cysteine, or L-cystine was supplied. The positive effect of potassium was accelerated by the addition of magnesium and/or calcium. Furthermore, the additional supply of magnesium improved the induction of sulfite- or L-cysteine-dependent luminescence, but not the l-cystine-dependent type. These results suggest that sulfur-dependent luminescence of V. fischeri under nutrient-starved conditions is mainly controlled by bicarbonate, carbonate, and potassium. In addition, our results indicate that an additional supply of magnesium is effective for increasing V. fischeri luminescence.

  18. 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.

  19. Characterization of basolateral chloride/bicarbonate exchange in macula densa cells.

    Science.gov (United States)

    Komlosi, Peter; Frische, Sebastian; Fuson, Amanda L; Fintha, Attila; Zsembery, Akos; Peti-Peterdi, Janos; Bell, P Darwin

    2005-02-01

    Functional and immunohistological studies were performed to identify basolateral chloride/bicarbonate exchange in macula densa cells. Using the isolated, perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pH(i)) was measured with fluorescence microscopy and BCECF. For these experiments, basolateral chloride was reduced, resulting in reversible macula densa cell alkalinization. Anion exchange activity was assessed by measuring the maximal net base efflux on readdition of bath chloride. Anion exchange activity required the presence of bicarbonate, was independent of changes in membrane potential, did not require the presence of sodium, and was inhibited by high concentrations of DIDS. Inhibition of macula densa anion exchange activity by basolateral DIDS increased luminal NaCl concentration-induced elevations in pH(i). Immunohistochemical studies using antibodies against AE2 demonstrated expression of AE2 along the basolateral membrane of macula densa cells of rabbit kidney. These results suggest that macula densa cells functionally and immunologically express a chloride/bicarbonate exchanger at the basolateral membrane. This transporter likely participates in the regulation of pH(i) and might be involved in macula densa signaling.

  20. Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.

    Science.gov (United States)

    Guttu, K; Røsok, B; Gislason, H; Fändriks, L; Svanes, K; Grønbech, J E

    1991-04-01

    In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.

  1. 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.

  2. Improvement of ethanol productivity and energy efficiency by degradation of inhibitors using recombinant Zymomonas mobilis (pHW20a-fdh).

    Science.gov (United States)

    Dong, Hong-Wei; Fan, Li-Qiang; Luo, Zichen; Zhong, Jian-Jiang; Ryu, Dewey D Y; Bao, Jie

    2013-09-01

    Toxic compounds, such as formic acid, furfural, and hydroxymethylfurfural (HMF) generated during pretreatment of corn stover (CS) at high temperature and low pH, inhibit growth of Zymomonas mobilis and lower the conversion efficiency of CS to biofuel and other products. The inhibition of toxic compounds is considered as one of the major technical barriers in the lignocellulose bioconversion. In order to detoxify and/or degrade these toxic compounds by the model ethanologenic strain Z. mobilis itself in situ the fermentation medium, we constructed a recombinant Z. mobilis ZM4 (pHW20a-fdh) strain that is capable of degrading toxic inhibitor, formate. This is accomplished by cloning heterologous formate dehydrogenase gene (fdh) from Saccharomyces cerevisiae and by coupling this reaction of NADH regeneration reaction system with furfural and HMF degradation in the recombinant Z. mobilis strain. The NADH regeneration reaction also improved both the energy efficiency and cell physiological activity of the recombinant organism, which were definitely confirmed by the improved cell growth, ethanol yield, and ethanol productivity during fermentation with CS hydrolysate.

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

    OpenAIRE

    Marriott, Matthaus; Krustrup, Peter; Mohr, Magni

    2015-01-01

    BACKGROUND: Caffeine and sodium bicarbonate ingestion have been suggested to improve high-intensity intermittent exercise, but it is unclear if these ergogenic substances affect performance under provoked metabolic acidification. To study the effects of caffeine and sodium bicarbonate on intense 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,...

  4. 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.

  5. Monocyte intracellular cytokine production during human endotoxaemia with or without a second in vitro LPS challenge : effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness

    NARCIS (Netherlands)

    Faas, MM; Moes, H; Fijen, JW; Kobold, ACM; Tulleken, JE; Zijlstra, JG

    2002-01-01

    In the present study, we investigated the effect of RWJ-67657, a p38 MAP kinase inhibitor, upon in vivo LPS-induced monocyte cytokine production and upon monocyte LPS-hyporesponsiveness. Thirty minutes before a single injection of LPS (4 ng/kg BW), healthy male volunteers received a single oral dose

  6. 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.

  7. 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

    Alkaline wet oxidation (WO) (using water, 6.5 g/L sodium carbonate and 12 bar oxygen at 195degreesC) was used as pretreatment method for wheat straw (60 g/L), resulting in a hydrolysate and a cellulosic solid fraction. The hydrolysate consisted of soluble hemicellulose (8 g/L), low......-molecular-weight carboxylic acids (3.9 g/L), phenols (0.27 g/L = 1.7 mM) and 2-furoic acid (0.007 g/L). The wet oxidized wheat straw hydrolysate caused no inhibition of ethanol production by Saccharomyces cerevisiae ATCC 96581. Nine phenols and 2-furoic acid, identified to be present in the hydrolysate, were each tested...

  8. 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.

  9. 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

  10. [ROLES OF CONSTITUTIVE SYNTHASES OF NITRIC OXIDE IN THE REGULATION OF GASTRIC BICARBONATE SECRETION INDUCED BY MILD IRRITATION OF THE MUCOSA].

    Science.gov (United States)

    Zolotarev, V A; Andreeva, Yu V; Vershinina, E A; Kropycheva, R P

    2015-04-01

    Roles of isoforms of constitutive synthase of nitric oxide, neuronal or endothelial (nNOS or eNOS), in control of gastric bicarbonate secretion induced by mild irritation of the gastric mucosa was assessed at the normoacid state or after blockade of gastric acid secretion with omeprazole. In anesthetized rats, the concentration of HCO3- in luminal perfusate was calculated basing on measurements of pH/PCO2. Mucosal irritation during 20 min with acidic hypertonic solution (1 M NaCl, pH 2.0) caused marked and omeprazole-independent increase of HCO-secretion. Selective blocker ofnNOS in vivo 7-nitroindazole (7-NI), and the nonselective blocker ofnNOS and eNOS, N(G)-nitro-L-arginine (L-NNA), were applied either intravenously (10 mg/kg), or locally via retrograde injection into the splenic artery (1 mg/kg). At the normo-acid state, the irritation-induced secretion of was suppressed by 7-NI, but was not affected by L-NNA. After administration of omeprazole, both 7-NI and L-NNA equally inhibited HCO3- output. The effect of 7-NI (but not L-NNA) was abolished by cyclooxygenase (COX) inhibitor, indomethacin, which by itself suppressed irritation-induced secretion of HCO3-. Additionally, bicarbonate output was substantially reduced by the blocker of soluble guanylate cyclase (GC), methylene blue. We conclude that irritation-induced secretion of HCO3- is largely mediated by intramural nNOS and depends on GC-COX interaction. As it was theoretically estimated, eNOS activity caused a reduction of HCO3- output in the normo-acid stomach. Omeprazole abolished the effect of eNOS.

  11. 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.

  12. 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

    2015-01-01

    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 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. PMID:26621630

  13. 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.

  14. 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.

  15. 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

  16. Whey protein with potassium bicarbonate supplement attenuates the reduction in muscle oxidative capacity during 19 days of bed rest.

    Science.gov (United States)

    Bosutti, Alessandra; Salanova, Michele; Blottner, Dieter; Buehlmeier, Judith; Mulder, Edwin; Rittweger, Jörn; Yap, Moi Hoon; Ganse, Bergita; Degens, Hans

    2016-10-01

    The effectiveness of whey protein plus potassium bicarbonate-enriched diet (WP+KHCO3) in mitigating disuse-induced changes in muscle fiber oxidative capacity and capillarization was investigated in a 21-day crossover design bed rest study. Ten healthy men (31 ± 6 yr) once received WP+KHCO3 and once received a standardized isocaloric diet. Muscle biopsies were taken 2 days before and during the 19th day of bed rest (BR) from the soleus (SOL) and vastus lateralis (VL) muscle. Whole-body aerobic power (V̇o2 max), muscle fatigue, and isometric strength of knee extensor and plantar flexor muscles were monitored. Muscle fiber types and capillaries were identified by immunohistochemistry. Fiber oxidative capacity was determined as the optical density (OD) at 660 nm of succinate dehydrogenase (SDH)-stained sections. The product of fiber cross-sectional area and SDH-OD (integrated SDH) indicated the maximal oxygen consumption of that fiber. The maximal oxygen consumption supported by a capillary was calculated as the integrated SDH in its supply area. BR reduced isometric strength of knee extensor muscles (P capacity (P capacity in both muscles (P capacity is proportionally larger than the loss of capillaries. WP+KHCO3 appears to attenuate disuse-induced reductions in fiber oxidative capacity.

  17. Effects of sources of carbon and nitrogen on production of α-glucosidase inhibitor by a newly isolated strain of Bacillus subtilis B2.

    Science.gov (United States)

    Zhu, Yun-Ping; Yin, Li-Jun; Cheng, Yong-Qiang; Yamaki, Kohji; Mori, Yutaka; Su, Yi-Cheng; Li, Li-Te

    2008-08-15

    This study examined production of α-glucosidase inhibitors by Bacillus subtilis B2 in Luria-Bertani (LB) fermentation with okara, soy powder, starch or pectin as additional source of carbon and nitrogen. All the fermentation broths of B. subtilis B2 exhibited gradual increase in α-glucosidase inhibitory activity during the fermentation process with or without supplemented source of carbon or nitrogen. Addition of okara into the LB medium greatly enhanced the strength (nearly twice as much of that without okara supplement) of α-glucosidase inhibitory activity of fermentation broth. The α-glucosidase inhibitory activity of B. subtilis B2 fermentation broth was positively correlated (pprocess and were both reduced drastically in media containing okara, soy powder, starch or pectin after 6days of fermentation. The fermented LB medium containing okara by B. subtilis B2 possessed very strong α-glucosidase inhibitory activity and contained little glucose and sucrose, suggesting that fermentation of B. subtilis B2 in LB added with okara might be considered as a strategy for preparing functional foods for diabetic patients.

  18. [Non-peptide furin inhibitors based on amidinohydrazones of diarylaldehydes].

    Science.gov (United States)

    Kibirev, V K; Osadchuk, T V; Kozachenko, A P; Vadziuk, O B; Brovarets, V S

    2013-01-01

    A series of novel non-peptidic furin inhibitors containing amidinohydrazone moieties has been synthesized under interaction of dialdehydes, the derivatives of ethylene diethylvanillin ethers, with aminoguanidine bicarbonate. Two aryl cycles were bridged by 1,2-ethylene-, 1,4-buthylene- or 1,4-dimethylenebenzene-group. The compounds have been found to inhibit furin. The antifurin activity was shown to grow with the increase of the length and/or hydrophobicity of the bridge. The most potent compound, containing in the bridge the lypophylic benzene cycle was found to inhibit the activity of furin with Ki = 0.51 microM.

  19. Research Progress on Natural Products as Corrosion Inhibitor in Acid, Neutral and Alkaline Mediums%酸性、中性、碱性介质中植物型缓蚀剂的研究进展

    Institute of Scientific and Technical Information of China (English)

    郑杰; 王亚娜; 章柏林; 杨婷; 焦学敏; 何勇

    2011-01-01

    Plant extracts have become important as an environmentally acceptable, readily available and renewable source for wide range of inhibitors. In general, the plant extracts are of inhibitors with high inhibition efficiency and of non toxicant. This article summarizes the reaction mechanism and gives a vivid account of natural products which are used as corrosion inhibitors in acid, neutral and alkaline mediums. The prospects of the development trend are also discussed.%植物型缓蚀剂具有成本低,来源广,无毒,高效等特点,是未来缓蚀剂的发展方向.本文概括介绍了植物型缓蚀剂的作用机理,总结了植物型缓蚀剂在酸性、中性和碱性介质中的研究进展,并对今后的研究提出了展望.

  20. Regulation of granulosa cell cocaine and amphetamine regulated transcript (CART) binding and effect of CART signaling inhibitor on granulosa cell estradiol production during dominant follicle selection in cattle.

    Science.gov (United States)

    Folger, Joseph K; Jimenez-Krassel, Fermin; Ireland, James J; Lv, Lihua; Smith, George W

    2013-12-01

    We previously established a potential role for cocaine and amphetamine regulated transcript (CARTPT) in dominant follicle selection in cattle. CARTPT expression is elevated in subordinate versus dominant follicles, and treatment with the mature form of the CARTPT peptide (CART) decreases follicle-stimulating hormone (FSH)-stimulated granulosa cell estradiol production in vitro and follicular fluid estradiol and granulosa cell CYP19A1 mRNA in vivo. However, mechanisms that regulate granulosa cell CART responsiveness are not understood. In this study, we investigated hormonal regulation of granulosa cell CART-binding sites in vitro and temporal regulation of granulosa cell CART-binding sites in bovine follicles collected at specific stages of a follicular wave. We also determined the effect of inhibition of CART receptor signaling in vivo on estradiol production in future subordinate follicles. Granulosa cell CART binding in vitro was increased by FSH, and this induction was blocked by estrogen receptor antagonist treatment. In follicles collected in vivo at specific stages of a follicular wave, granulosa cell CART binding in the F2 (second largest), future subordinate follicle increased during dominant follicle selection. Injection into the F2 follicle (at onset of diameter deviation) of an inhibitor of the o/i subclass of G proteins (previously shown to block CART actions in vitro) resulted in increased follicular fluid estradiol concentrations in vivo. Collectively, results demonstrate hormonal regulation of granulosa cell CART binding in vitro and temporal regulation of CART binding in subordinate follicles during dominant follicle selection. Results also suggest that CART signaling may help suppress estradiol-producing capacity of the F2 (subordinate) follicle during this time period.

  1. 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.

  2. Association between Low Serum Bicarbonate Concentrations and Cardiovascular Disease in Patients in the End-Stage of Renal Disease

    Directory of Open Access Journals (Sweden)

    Vaia D. Raikou

    2016-11-01

    Full Text Available Background: Metabolic acidosis, a common condition particularly in the end-stage of renal disease patients, results in malnutrition, inflammation and oxidative stress. In this study, we focused on the association between low serum bicarbonate and cardiovascular disease in patients on intermittent dialysis. Methods: We studied 52 on-line-pre-dilution hemodiafiltration (on-l HDF patients, 32 males and 20 females, with a mean age of 58.01 ± 15.4 years old. Metabolic acidosis was determined by serum bicarbonate concentrations less than 22 mmol/L. Residual renal function (RRF was defined by interdialytic urine volume. Kaplan–Meier curves and Cox regression models were performed to predict coronary artery disease (CAD, defined by ejection fraction <50%, or diastolic dysfunction congestive heart failure (CHF and peripheral vascular disease (PVD. Results: Kaplan–Meier analyses showed that a lower or higher than 22 mmol/L serum bicarbonate metabolic acidosis status was significantly associated with both PVD and diastolic dysfunction (log-rank = 5.07, p = 0.02 and log-rank = 5.84, p = 0.01, respectively. A similar prevalence of serum bicarbonate on CAD or CHF by low ejection fraction was not shown. The RRF was associated with PVD event and serum bicarbonate less than 22 mmol/L (log-rank = 5.49, p = 0.01 and log-rank = 3.9, p = 0.04, respectively. Cox regression analysis revealed that serum bicarbonate and RRF were significant risk factors for PVD after adjustment for confounders. Furthermore, RRF adjusted for covariates was shown to be a significant risk factor for diastolic dysfunction. Conclusion: Low serum bicarbonate was associated with peripheral vascular disease and diastolic dysfunction in intermittent dialysis. The residual renal function may impact patients’ outcomes through its relationship with metabolic acidosis status, particularly for peripheral vascular disease manifestation.

  3. 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.

  4. Nitric oxide content is associated with tolerance to bicarbonate-induced chlorosis in micropropagated Prunus explants.

    Science.gov (United States)

    Cellini, Antonio; Corpas, Francisco Javier; Barroso, Juan Bautista; Masia, Andrea

    2011-09-01

    Iron (Fe) chlorosis is a common nutritional deficiency in fruit trees grown in calcareous soils. Grafting on tolerant rootstocks is the most efficient practice to cope with it. In the present work, three Prunus hybrid genotypes, commonly used as peach rootstocks, and one peach cultivar were cultivated with bicarbonate in the growth medium. Parameters describing oxidative stress and the metabolism of reactive nitrogen species were studied. Lower contents of nitric oxide and a decreased nitrosoglutathione reductase activity were found in the most sensitive genotypes, characterized by higher oxidative stress and reduced antioxidant defense. In the peach cultivar, which behaved as a tolerant genotype, a specifically nitrated polypeptide was found.

  5. High serum bicarbonate level within the normal range prevents the progression of chronic kidney disease in elderly chronic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Kanda Eiichiro

    2013-01-01

    Full Text Available Abstract Background Metabolic acidosis leads to chronic kidney disease (CKD progression. The guidelines recommend a lower limit of serum bicarbonate level, but no upper limit. For serum bicarbonate level to be clinically useful as a therapeutic target marker, it is necessary to investigate the target serum bicarbonate level within the normal range to prevent CKD progression. Methods One hundred and thirteen elderly CKD patients, whose serum bicarbonate level was controlled within the normal range, were enrolled in this retrospective cohort study in Ibaraki, Japan. Outcome was defined as a decrease of 25% or more in estimated glomerular filtration rate (eGFR or starting dialysis. We used Cox proportional hazard models adjusted for patients’ characteristics to examine the association between serum bicarbonate level and the outcome. Results Female patients were 36.3%: average age (SD, 70.4 (6.6 years; eGFR, 25.7 (13.6 ml/min/1.73 m2; serum bicarbonate level, 27.4 (3.2 mEq/l. Patients with the lowest quartile of serum bicarbonate levels [23.4 (1.8 mEq/l] showed a high risk of CKD progression compared with patients with high serum bicarbonate levels [28.8 (2.3 mEq/l]: adjusted hazard ratio (HR, 3.511 (95% CI, 1.342-9.186. A 1 mEq/l increase in serum bicarbonate level was associated with a low risk of CKD progression: adjusted HR, 0.791 [95% confidence interval (CI, 0.684-0.914]. Conclusions In elderly CKD patients, our findings suggest that serum bicarbonate level is independently associated with CKD progression, and that a high serum bicarbonate level is associated with a low risk of CKD progression. A high target serum bicarbonate level within the normal range may be effective for preventing CKD progression.

  6. 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.

  7. 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...

  8. Efficient degradation of organic pollutants in aqueous solution with bicarbonate-activated hydrogen peroxide.

    Science.gov (United States)

    Xu, Aihua; Li, Xiaoxia; Xiong, Hui; Yin, Guochuan

    2011-02-01

    Bicarbonate anion is an efficient activator for hydrogen peroxide to generate many active oxygen species including peroxymonocarbonate (HCO(4)(-)), superoxide ion (O(2)(-)) and singlet oxygen ((1)O(2)). This study aims to understand the oxidative degradation of organic pollutants including methyl blue, methyl orange, rhodamine B, and 4-chlorophenol, with H(2)O(2) activated by sodium bicarbonate at room temperature. The obtained results indicate that such a method is apparently efficient in versatile pollutant degradation. Compared with using H(2)O(2) alone under similar pH conditions, the degradation rates of the pollutants were greatly enhanced through adding NaHCO(3). Through LC-MS, FT-IR and the TOC analysis, the degradation of methylene blue was revealed to proceed by the transformation of dimethylamino group in methylene blue to methylamino, aldehyde and nitro group, and the opening of phenyl ring into small molecular compounds and CO(2). The studies using the (1)O(2) scavenger sodium azide and the O(2)(-) indicator nitro blue tetrazolium suggest that the active O(2)(-) intermediate, generated from HCO(4)(-) decomposition, rather than (1)O(2) was involved in the pollutant degradation.

  9. 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.

  10. 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.

  11. 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 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.

  12. 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)

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

    Science.gov (United States)

    Pimenta, R. S.; Silva, J. F. M.; Coelho, C. M.; Morais, P. B.; Rosa, C. A.; Corrêa Jr, A.

    2010-01-01

    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. PMID:24031511

  14. 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.

  15. 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.

  16. 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...

  17. Structural modifications of the salivary conditioning film upon exposure to sodium bicarbonate: implications for oral lubrication and mouthfeel.

    Science.gov (United States)

    Ash, A; Wilde, P J; Bradshaw, D J; King, S P; Pratten, J R

    2016-03-14

    The salivary conditioning film (SCF) that forms on all surfaces in the mouth plays a key role in lubricating the oral cavity. As this film acts as an interface between tongue, enamel and oral mucosa, it is likely that any perturbations to its structure could potentially lead to a change in mouthfeel perception. This is often experienced after exposure to oral hygiene products. For example, consumers that use dentifrice that contain a high concentration of sodium bicarbonate (SB) often report a clean mouth feel after use; an attribute that is clearly desirable for oral hygiene products. However, the mechanisms by which SB interacts with the SCF to alter lubrication in the mouth is unknown. Therefore, saliva and the SCF was exposed to high ionic strength and alkaline solutions to elucidate whether the interactions observed were a direct result of SB, its high alkalinity or its ionic strength. Characteristics including bulk viscosity of saliva and the viscoelasticity of the interfacial salivary films that form at both the air/saliva and hydroxyapatite/saliva interfaces were tested. It was hypothesised that SB interacts with the SCF in two ways. Firstly, the ionic strength of SB shields electrostatic charges of salivary proteins, thus preventing protein crosslinking within the film and secondly; the alkaline pH (≈8.3) of SB reduces the gel-like structure of mucins present in the pellicle by disrupting disulphide bridging of the mucins via the ionization of their cysteine's thiol group, which has an isoelectric point of ≈8.3.

  18. Facile and Efficient Acetylation of Primary Alcohols and Phenols with Acetic Anhydride Catalyzed by Dried Sodium Bicarbonate

    Directory of Open Access Journals (Sweden)

    Fulgentius Nelson Lugemwa

    2013-12-01

    Full Text Available A variety of primary alcohols and phenols were reacted with acetic anhydride at room temperature in the presence of sodium bicarbonate to produce corresponding esters in good to excellent yields. The acetylation of 4-nitrobenzyl alcohol was also carried out using other bicarbonates and carbonates. The reaction in the presence of cesium bicarbonate and lithium carbonate gave 4-nitrobenzyl acetate in excellent yield, while in the presence of Na2CO3, K2CO3, Cs2CO3, or KHCO3 the yield was in the range of 80%–95%. Calcium carbonate and cobaltous carbonate did not promote the acetylation of 4-ntirobenzyl alcohol using acetic anhydride. The acetylation of 4-nitrobenzyl alcohol was carried out using ethyl acetate, THF, toluene, diethyl ether, dichloromethane and acetonitrile, and gave good yields ranging from 75%–99%. Toluene was the best solvent for the reaction, while diethyl ether was the poorest.

  19. Effect of Tris-Hydroxymethyl Aminomethane on intracellular pH depends on the extracellular non-bicarbonate buffering capacity.

    Science.gov (United States)

    Giunti, Carine; Priouzeau, Fabrice; Allemand, Denis; Levraut, Jacques

    2007-12-01

    The effect of Tris-Hydroxymethyl Aminomethane (THAM) on intracellular pH (pHi) is unknown. We previously demonstrated that the effect of sodium bicarbonate on pHi depends on the non-bicarbonate buffering system. First, human hepatocytes from hepatocytes cell culture (HepG2) were perfused with an acidotic artificial medium containing 5-mmol/L (H5) or 30-mmol/L (H30) concentrations of 4-(2-hydroxyethyl)-1-piperazineethane sulfonic acid (HEPES), a non-bicarbonate buffer. We studied the effect of THAM on the pHi in both conditions. We repeated the same protocol using an acidotic human blood with a 5% or 40% hematocrit. The pHi was measured with the pH-sensitive fluorescent dye bis-carboxyethyl carboxy-fluorescein (BCECF). Gas analysis was performed before and during the alkaline infusion. The results showed that THAM caused an intracellular alkalization that was higher when the non-bicarbonate buffer concentration was low (0.45 +/- 0.21 and 0.22 +/- 0.14 pH units with H5 and H30, respectively). A significant relationship was found between changes in pHi and changes in PCO(2). Similar results were obtained with the human blood. In conclusion, the intracellular alkalizing effect of THAM is caused by the induced decrease of PCO(2) linked to the extracellular non-bicarbonate buffer capacity: The smaller the concentration of extracellular non-bicarbonate buffer, the higher the PCO(2) decrease caused by THAM.

  20. Effect of 10% sodium bicarbonate on bond strength of enamel and dentin after bleaching with 38% hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Fernanda Medeiros Darzé

    Full Text Available AbstractIntroductionBy-products of hydrogen peroxide degradation released during dental bleaching influence the polymerization of adhesive systems and composite resins, causing a reduction in shear bond strength to the tooth.Objectivethe aim of this article was to evaluate the effect of 10% sodium bicarbonate (SB, applied for different lengths of time, on the shear bond strength to enamel and dentin after bleaching.Material and methodEnamel and dentin blocks were divided into groups (n=10: (1 control: no bleaching; (2 immediate: bleaching immediately followed by restoration; (3 14-day: bleaching, restoration 14 days later; (4 SB for 10 minutes: bleaching, SB gel for 10 minutes, immediately followed by restoration; (5 SB for 20 minutes: bleaching, SB gel for 20 minutes, immediately followed by restoration. A 38% hydrogen peroxide gel (Opalescence Boost/Ultradent was used. After application of the adhesive system, composite resin cylinders were mounted on the surface of the substrates in order to test shear bond strength. Result: ANOVA and Tukey tests showed significantly higher mean enamel bond strength values for the 14-day follow-up group and without significant differences for control group. Mean bond strength values obtained for the other groups were intermediate. When testing dentin, the Tukey test revealed a significantly higher mean bond strength value for the 14-day follow-up group when compared with application of SB for 20 minutes.ConclusionSB gel applied was unable to reverse the low bond strength to enamel and dentin after bleaching treatment.

  1. 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.

  2. 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

  3. 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.

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

    Science.gov (United States)

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

    2008-09-26

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

  5. 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

  6. 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

  7. Evaluation of smear layer removal by bicarbonate soda, ethylenediamine tetraacetic acid with cetrimide and sodium hypochlorite with a new model.

    Science.gov (United States)

    Leow, Natalie; Abbott, Paul; Castro Salgado, Jacqueline; Firth, Laura

    2012-12-01

    Various methods are used to evaluate irrigants. The primary aim was to develop a model for preliminary testing of potential irrigants. The second aim was to investigate the effect of bicarbonate soda on smear layer by comparing it with ethylenediamine tetraacetic acid with cetrimide (EDTAC) and sodium hypochlorite (NaOCl). Extracted human single-canal teeth were halved, and a uniform filing method was used to create smear layer. The following solutions were then applied - distilled water (control), 1% NaOCl, 17% EDTAC and bicarbonate soda at concentrations of 1%, 5%, 10% and 15%. Some samples had multiple solutions in different sequences. Samples were examined by scanning electron microscopy. Representative images were scored based on the degree of smear layer remaining. Results were analysed with the SAS system, using the GENMOD procedure. Complete smear layer was found in samples treated with all solutions except EDTAC used alone. There were no significant differences between the sequences, EDTAC/NaOCl/EDTAC and NaOCl/EDTAC/NaOCl. There were no significant differences between groups with and without bicarbonate soda. In conclusion, the model was effective for testing chemical effects on solutions on smear layer. Bicarbonate soda did not remove smear layer and provided no additional cleaning effects after EDTAC and NaOCl.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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,...

  13. 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.E.; Cnubben, N.H.P.; Sudhölter, E.J.R.; Rietjens, I.M.C.M.; Beek, T.A. van

    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

  14. 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

  15. Receptor-based modeling and 3D-QSAR for a quantitative production of the butyrylcholinesterase inhibitors based on genetic algorithm.

    Science.gov (United States)

    Zaheer-ul, Haq; Uddin, Reaz; Yuan, Hongbin; Petukhov, Pavel A; Choudhary, M Iqbal; Madura, Jeffry D

    2008-05-01

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of structurally related steroidal alkaloids as butyrylcholinesterase (BuChE) inhibitors. Docking studies were employed to position the inhibitors into the BuChE active site to determine the most probable binding mode. The strategy was to explore multiple inhibitor conformations in producing a more reliable 3D-QSAR model. These multiple conformations were derived using the FlexS program. The conformation selection step for CoMFA was done by genetic algorithm. The genetic algorithm based CoMFA approach was found to be the best. Both CoMFA and CoMSIA yielded significant cross-validated q(2) values of 0.701 and 0.627 and the r(2) values of 0.979 and 0.982, respectively. These statistically significant models were validated by a test set of five compounds. Comparison of CoMFA and CoMSIA contour maps helped to identify structural requirements for the inhibitors and serves as a basis for the design of the next generation of the inhibitor analogues. The results demonstrate that the combination of ligand-based and receptor-based modeling with use of a genetic algorithm is a powerful approach to build 3D-QSAR models. These data can be used for the lead optimization process with respect to inhibition enhancement which is important for the drug discovery and development for Alzheimer's disease.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate Buffer on the Dissolution of Weak Acids and Weak Bases.

    Science.gov (United States)

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

    2015-09-01

    Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pKa can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O ← H2 CO3 , the transport analysis can accurately predict rotating disk dissolution of weak acid and weak base drugs in bicarbonate buffer. The predictions show that matching the dissolution of weak acid and weak base drugs in phosphate and bicarbonate buffer is possible. The phosphate buffer concentration necessary to match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug solubility and pKa .

  2. Role of CCK-A receptor in the regulation of pancreatic bicarbonate secretion in conscious rats: a study in naturally occurring CCK-A receptor gene knockout rats.

    Science.gov (United States)

    Miyasaka, K; Suzuki, S; Kanai, S; Masuda, M; Funakoshi, A

    1999-10-01

    Whether cholecystokinin (CCK) has a direct action on duct cells and the role of CCK-A receptor in bicarbonate secretion were examined by comparing the results obtained from OLETF (CCK-A receptor-deficient rats) and control (LETO) rats. Rats were prepared with cannulae for draining bile and pancreatic juice separately, with two duodenal cannulae and an external jugular vein cannula. The experiments were conducted without anesthesia. The responses of bicarbonate secretion to intravenous infusion of CCK, acetyl-beta-methylcholine (Ach), and 2-deoxy-D-glucose (2DG), and to intraduodenal infusion of HCl and a liquid meal were examined. To examine the synergistic effect between CCK and secretin, the effect of CCK during a background secretin infusion was examined in LETO rats. CCK did not stimulate bicarbonate secretion in either strain, nor in LETO rats with secretin infusion. When gastric acid secretion was prevented by administration of omeprazole, Ach did not increase bicarbonate secretion, but 2DG did in both strains. Intraduodenal infusion of HCI and a liquid meal significantly increased bicarbonate secretion in both strains; however, the responses were much less in OLETF than LETO rats. In conclusion, intravenous injection of CCK did not stimulate bicarbonate secretion, and the lack of CCK-A receptor decreased bicarbonate secretion in response to luminal stimulants.

  3. Cafestol, a coffee-specific diterpene, is a novel extracellular signal-regulated kinase inhibitor with AP-1-targeted inhibition of prostaglandin E2 production in lipopolysaccharide-activated macrophages.

    Science.gov (United States)

    Shen, Ting; Lee, Jaehwi; Lee, Eunji; Kim, Seong Hwan; Kim, Tae Woong; Cho, Jae Youl

    2010-01-01

    Coffee is a popular beverage worldwide with various nutritional benefits. Diterpene cafestol, one of the major components of coffee, contributes to its beneficial effects through various biological activities such as chemopreventive, antitumorigenic, hepatoprotective, antioxidative and antiinflammatory effects. In this study, we examined the precise molecular mechanism of the antiinflammatory activity of cafestol in terms of prostaglandin E(2) (PGE(2)) production, a critical factor involved in inflammatory responses. Cafestol inhibited both PGE(2) production and the mRNA expression of cyclooxygenase (COX)-2 from lipopolysaccharide (LPS)-treated RAW264.7 cells. Interestingly, this compound strongly decreased the translocation of c-Jun into the nucleus and AP-1 mediated luciferase activity. In kinase assays using purified extracellular signal-regulated kinase 2 (ERK2) or immunoprecipitated ERK prepared from LPS-treated cells in the presence or absence of cafestol, it was found that this compound can act as an inhibitor of ERK2 but not of ERK1 and mitogen-activated protein kinase kinase 1 (MEK 1). Therefore our data suggest that cafestol may be a novel ERK inhibitor with AP-1-targeted inhibitory activity against PGE(2) production in LPS-activated RAW264.7 cells.

  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. 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

  6. 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.

  7. Variability of Acid-Base Status in Acetate-Free Biofiltration 84% versus Bicarbonate Dialysis

    Directory of Open Access Journals (Sweden)

    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.

  8. 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

  9. 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.

  10. Inhibition of cobalt active dissolution by benzotriazole in slightly alkaline bicarbonate aqueous media

    Energy Technology Data Exchange (ETDEWEB)

    Gallant, Danick [Departement de Chimie, Universite Laval, Quebec (Canada); Departement de Biologie, Chimie et Geographie, Universite du Quebec a Rimouski, 300, Allee des Ursulines, Rimouski, Quebec (Canada); E-mail: danick.gallant.1@ulaval.ca; Pezolet, Michel [Departement de Chimie, Universite Laval, Quebec (Canada)]. E-mail: michel.pezolet@chm.ulaval.ca; Simard, Stephan [Departement de Chimie, Universite Laval, Quebec (Canada); Departement de Biologie, Chimie et Geographie, Universite du Quebec a Rimouski, 300, Allee des Ursulines, Rimouski, Quebec (Canada); E-mail: stephan_simard@uqar.qc.ca

    2007-04-20

    The efficiency of benzotriazole as inhibiting agent for the corrosion of cobalt was probed at pH ranging from 8.3 to 10.2 in a sodium bicarbonate solution, chosen to simulate mild natural environments. From electrochemical, Raman spectroscopy, atomic force microscopy and ellipsometry experiments, we have demonstrated that benzotriazole markedly affects the electrodissolution reactions, which become modeled by the formation of a [Co(II)(BTA){sub 2}.H{sub 2}O] {sub n} film according to two different mechanisms. Surface-enhanced Raman spectroscopy has shown that the polarization of a cobalt electrode at cathodic potentials with respect to its potential of zero charge allows a mechanism of specific adsorption of the neutral form of benzotriazole to take place through a suspected metal-to-molecule electron transfer and which follows Frumkin's adsorption isotherms. At the onset of the anodic dissolution, some experimental evidence suggests that these adsorbed neutral benzotriazole molecules deprotonate to yield a very thin [Co(II)(BTA){sub 2}.H{sub 2}O] {sub n} polymer-like and water-insoluble protective film, responsible for the inhibition of active dissolution processes occurring at slightly more anodic potentials. In the anodic dissolution region, deprotonated benzotriazole species present in the bulk solution favors the formation of a multilayered [Co(II)(BTA){sub 2}.H{sub 2}O] {sub n} film, which also contributes to the inhibition of any further cobalt dissolution usually observed at higher electrode potentials.

  11. 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.

  12. 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.

  13. Does bicarbonated mineral water rich in sodium change insulin sensitivity of postmenopausal women?

    Directory of Open Access Journals (Sweden)

    S. Schoppen

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Geochemistry of fly ash from desulphurisation process performed by sodium bicarbonate

    Energy Technology Data Exchange (ETDEWEB)

    Raclavska, Helena; Matysek, Dalibor; Raclavsky, Konstantin; Juchelkova, Dagmar [VSB - Technical University Ostrava, 17. listopadu 15, 708 33 Ostrava, Poruba (Czech Republic)

    2010-02-15

    The application of NEUTREC {sup registered} technology - desulphurisation by means of sodium bicarbonate - has been tested at the Trebovice coal-fired power plant (Ostrava, Czech Republic). This technology significantly influences the chemical composition of fly ash and the leachability of total dissolved substances (TDS), e.g., sulphates, fluorides and oxyanions (Se, Sb, Cr, As), which are monitored according to the Council of the European Union Decision 2003/33/EC. An increase of TDS in the water leachate from the fly ash obtained at 60% desulphurisation was influenced by sodium content, which is present in the form of Na{sup +} ions (85-90%). The percentages of sodium sulphate and sodium carbonate were between 5 and 10% of the total sodium content. In order to decrease the leachability of TDS, sodium, sulphates and oxyanion mixtures were prepared containing a sorbent (60% bentonite) and mixed with desulphurised and non-desulphurised fly ash in various ratios. The addition of CaO resulted in the formation of a new mineral phase, burkeite. None of the applied technologies tested for the processed fly ash resulted in the preparation of a water leachate which complied in all monitored parameters to the requirements of Council Decision 2003/33 EC for nonhazardous wastes. (author)

  16. Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase.

    Science.gov (United States)

    Choi, Hyun B; Gordon, Grant R J; Zhou, Ning; Tai, Chao; Rungta, Ravi L; Martinez, Jennifer; Milner, Teresa A; Ryu, Jae K; McLarnon, James G; Tresguerres, Martin; Levin, Lonny R; Buck, Jochen; MacVicar, Brian A

    2012-09-20

    Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO₃⁻) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO₃⁻ entry via the electrogenic NaHCO₃ cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K⁺](ext) and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons.

  17. 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.

  18. 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

  19. 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

  20. 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

    2012-10-01

    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.

  1. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine

    OpenAIRE

    Koestler, Benjamin J.; Waters, Christopher M.

    2015-01-01

    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 ...

  2. 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.

  3. 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.

  4. 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.

  5. The OECD validation program of the H295R steroidogenesis assay for the identification of in vitro inhibitors and inducers of testosterone and estradiol production. Phase 2: Inter-laboratory pre-validation studies

    DEFF Research Database (Denmark)

    Hecker, Markus; Hollert, Henner; Cooper, Ralph

    2007-01-01

    related to one laboratory there were unexplained minor uncertainties related to the inter-laboratory hormone production variation. Based on the findings from this Phase 2 prevalidation study, the H295R Steroidogenesis Assay protocol is currently being refined. The next phase of the OECD validation program...... their potential to interact with the endocrine system of vertebrates. Study Design. Six laboratories from five countries participated in the pre-validation studies. Each laboratory tested the effects of three model chemicals on the production of testosterone (T) and estradiol (E2) using the H295R Steroidogenesis...... Assay. Chemicals tested were well described inducers or inhibitors of steroidogenic pathways (forskolin, prochloraz and fadrozole). All experiments were conducted in 24 well plates following standard protocols. Six different doses per compound were analyzed in triplicate per plate. A quality control (QQ...

  6. [Application of process engineering to remove lignocellulose fermentation inhibitors].

    Science.gov (United States)

    Wang, Lan; Xia, Menglei; Chen, Hongzhang

    2014-05-01

    Fermentation inhibitors are toxic to cells, which is one of the bottlenecks for lignocellulose bio-refinery process. How to remove those inhibitors serves a key role in the bioconversion of lignocellulose. This article reviews the sources and the types of the inhibitors, especially the updated removal strategies including physical methods, chemical methods, biological methods and inhibitor-tolerant strain construction strategies. Based on these, we introduce a new bio-refinery model named "fractional conversion", which reduces the production of inhibitors at pretreatment stage, and a novel in situ detoxification method named "fermentation promoter exploitation technology". This review could provide new research ideas on the removal of fermentation inhibitors.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Mechanisms involved in ketone body release by rat liver cells: influence of pH and bicarbonate

    Energy Technology Data Exchange (ETDEWEB)

    Fafournoux, P.; Demigne, C.; Remesy, C.

    1987-02-01

    The aim of the present work is to study the intra- and extracellular concentration gradient of ketone bodies across the hepatic cell membrane, ketone bodies released by liver cells, and the effects of changes in acid-base status on these processes. Ketone bodies appeared to be released by liver cells against a concentration gradient both in vivo and in vitro. In vitro, a decrease in external pH and bicarbonate gradient measured with ( UC)- and (TH)-labelled compounds, and efflux rates. Analysis of the distribution ratio of ketone bodies as a function of pH across the cell membrane indicates that additional factors must be invoked to account for the observed distribution ratios. These data along with measurement of ketone body efflux are consistent with the existence of a system promoting the efflux of ketone bodies from liver cells, which is trans-stimulated by external bicarbonate. In vivo, ketogenesis was also inhibited by acidosis, and slightly enhanced by bicarbonate infusion, although this was not solely due to effects on transfer across the cell membrane. The study indicates that the hepatic release of ketone bodies might be auto-limited by ketoacidosis.

  13. 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.

  14. 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

    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...... volunteers the rates of gastroduodenal bicarbonate secretion and the release of PGE2 were not influenced by H. pylori status. In inactive DU patients the rates of basal (704 +/- 84 versus 356 +/- 40 mumol/h; mean +/- SEM) and vagally stimulated (modified sham feeding) (1724 +/- 376 versus 592 +/- 52 mumol...... 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....

  15. 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

    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...... volunteers the rates of gastroduodenal bicarbonate secretion and the release of PGE(2), were not influenced by H. pylori status. In inactive DU patients the rates of basal (704 +/- 84 versus 356 +/- 40 mu mol/h: mean +/- SEM) and vagally stimulated (modified sham feeding) (1724 +/- 376 versus 592 +/- 52 mu...... 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....

  16. 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

  17. 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.

  18. Effect of Chewing Bicarbonate-containing Sugar-free Gum on the Salivary pH: An in vivo Study.

    Science.gov (United States)

    Ballal, Raksha K; Bhat, Sham S; Ramdas, Shenoy Shailesh; Ballal, Shrinidhi

    2016-01-01

    The objective of the study was to evaluate the effect of chewing gum on the salivary pH and to compare the effect of chewing bicarbonate-containing sugar-free gum on salivary pH against that of standard sugar-free gum. The experiment was carried out on 30 volunteers aged 20-22 years (mean age = 21 years) who fulfilled the inclusion criteria. The test gum was sugar-free greenmint-flavored bicarbonate-containing gum and the standard control was sugar-free spearmint-flavored gum. The pH was measured immediately using pH strips. According to statistical analysis, the mean salivary pH of the bicarbonate gum at 0, 5, 10, 15 and 20 minutes is 6.9713, 6.5667, 6.4267, 6.3867 and 6.3233 respectively. There is decrease in pH from 0 to 20 minutes. According to Bonferroni, there was no significant difference in pH from 0 to 20 minutes, 10 to 20 minutes and 15 to 20 minutes, but there was a significant difference in salivary pH from 5 to 20 minutes (p = 0.014). The mean salivary pH of the standard gum at 0, 5, 10, 15 and 20 minutes is 6.8767, 6.6067, 6.4200, 6.4027 and 6.3000 respectively. There is decrease in pH from 0 to 20 minutes. According to Bonferroni, there was no significant difference in pH from 0 to 20 minutes, 5 to 20 minutes, 10 to 20 minutes and 15 to 20 minutes. Thus, the higher salivary pH achieved with chewing bicarbonate gum compared with a standard sugar-free gum may have important oral health implications. How to cite this article: Ballal RK, Bhat SS, Ramdas SS, Ballal S. Effect of Chewing Bicarbonate-containing Sugar-free Gum on the Salivary pH: An in vivo Study. Int J Clin Pediatr Dent 2016;9(1):35-38.

  19. 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 ...

  20. Review article: immediate-release proton-pump inhibitor therapy--potential advantages.

    Science.gov (United States)

    Howden, C W

    2005-12-01

    The absorption of most oral proton-pump inhibitors is delayed by the enteric coating required to protect the acid-labile proton-pump inhibitor from degradation in the stomach and, as a result, antisecretory effect is also delayed. This article provides an overview of the pharmacokinetics and pharmacodynamics of a new immediate-release omeprazole [(IR-OME) Zegerid power for oral suspension; Santarus Inc., San Diego, CA, USA] and its potential advantages over delayed-release proton-pump inhibitors. Immediate-release omeprazole has a higher mean peak plasma omeprazole concentration (C(max)) and a significantly shorter mean time to reach C(max) (t(max)) than delayed-release omeprazole. Immediate-release omeprazole 40 mg has a prolonged antisecretory effect with median intragastric pH above 4.0 for 18.6 h/day at steady-state, after 7 days of once daily dosing. The sodium bicarbonate in immediate-release omeprazole protects the uncoated omeprazole from degradation by gastric acid. The accelerated antisecretory action of immediate-release omeprazole compared with delayed-release omeprazole may be due to the activation of proton pumps by the rapid neutralization of intragastric acid by the sodium bicarbonate. The faster onset of action seen with immediate-release omeprazole is not achieved by using an antacid with a delayed-release proton-pump inhibitor, because administering antacids with conventional delayed-release proton-pump inhibitors does not significantly enhance absorption of the proton-pump inhibitor. In conclusion, immediate-release omeprazole is associated with rapid absorption of omeprazole and rapid onset of antisecretory effect, without compromising the duration of acid suppression.

  1. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands.

    Science.gov (United States)

    Abdulnour-Nakhoul, Solange; Nakhoul, Hani N; Kalliny, Medhat I; Gyftopoulos, Alex; Rabon, Edd; Doetjes, Rienk; Brown, Karen; Nakhoul, Nazih L

    2011-07-01

    The esophageal submucosal glands (SMG) secrete HCO(3)(-) and mucus into the esophageal lumen, where they contribute to acid clearance and epithelial protection. This study characterized the ion transport mechanisms linked to HCO(3)(-) secretion in SMG. We localized ion transporters using immunofluorescence, and we examined their expression by RT-PCR and in situ hybridization. We measured HCO(3)(-) secretion by using pH stat and the isolated perfused esophagus. Using double labeling with Na(+)-K(+)-ATPase as a marker, we localized Na(+)-coupled bicarbonate transporter (NBCe1) and Cl(-)-HCO(3)(-) exchanger (SLC4A2/AE2) to the basolateral membrane of duct cells. Expression of cystic fibrosis transmembrane regulator channel (CFTR) was confirmed by immunofluorescence, RT-PCR, and in situ hybridization. We identified anion exchanger SLC26A6 at the ducts' luminal membrane and Na(+)-K(+)-2Cl(-) (NKCC1) at the basolateral membrane of mucous and duct cells. pH stat experiments showed that elevations in cAMP induced by forskolin or IBMX increased HCO(3)(-) secretion. Genistein, an activator of CFTR, which does not increase intracellular cAMP, also stimulated HCO(3)(-) secretion, whereas glibenclamide, a Cl(-) channel blocker, and bumetanide, a Na(+)-K(+)-2Cl(-) blocker, decreased it. CFTR(inh)-172, a specific CFTR channel blocker, inhibited basal HCO(3)(-) secretion as well as stimulation of HCO(3)(-) secretion by IBMX. This is the first report on the presence of CFTR channels in the esophagus. The role of CFTR in manifestations of esophageal disease in cystic fibrosis patients remains to be determined.

  2. 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.

  3. 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

  4. Effects of sodium bicarbonate, caffeine, and their combination on repeated 200-m freestyle performance.

    Science.gov (United States)

    Pruscino, Cathryn L; Ross, Megan L R; Gregory, John R; Savage, Bernard; Flanagan, Troy R

    2008-04-01

    The purpose of this study was to investigate the effects of sodium bicarbonate (NaHCO(3)), caffeine, and their combination on repeated 200-m freestyle performance. Six elite male freestyle swimmers ingested NaHCO(3) (0.3 g/kg; B), caffeine (6.2 +/- 0.3 mg/kg; C), a combination of both (B+C), and placebo (P) on 4 separate occasions before completing 2 maximal 200-m freestyle time trials (TT1 and TT2) separated by 30 min. No significant differences (p = .06) were observed for performance in TT1 (B 2:03.01 +/- 0:03.68 min, C 2:02.42 +/- 0:03.17 min, B+C 2:01.69 +/- 0:03.19 min, P 2:03.77 +/- 0:03.21 min) or TT2 (B 2:02.62 +/- 0:04.16 min, C 2:03.90 +/- 0:03.58 min, B+C 2:01.70 +/- 0:02.84 min, P 2:04.22 +/- 0:03.75 min). The drop-off in performance time from TT1 to TT2, however, was significantly greater when C was ingested than with B (-1.5%, p = .002) or B+C (-1.2%, p = .024). This is likely because of the lower blood pH and slower recovery of blood HCO(3) post-TT1 after C ingestion. These findings suggest that the ergogenic benefit of taking C alone for repeated 200-m swimming performance appears limited. When combined with NaHCO(3), however, its negative impact on repeated maximal exercise performance is reversed.

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

    Science.gov (United States)

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

    2012-11-01

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

  6. 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.

  7. Bicarbonate blocks iron translocation from cotyledons inducing iron stress responses in Citrus roots.

    Science.gov (United States)

    Martínez-Cuenca, Mary-Rus; Legaz, Francisco; Forner-Giner, M Ángeles; Primo-Millo, Eduardo; Iglesias, Domingo J

    2013-07-01

    The effect of bicarbonate ion (HCO3(-)) on the mobilization of iron (Fe) reserves from cotyledons to roots during early growth of citrus seedlings and its influence on the components of the iron acquisition system were studied. Monoembryonic seeds of Citrus limon (L.) were germinated "in vitro" on two iron-deprived media, supplemented or not with 10mM HCO3(-) (-Fe+Bic and -Fe, respectively). After 21d of culture, Fe concentration in seedling organs was measured, as well as gene expression and enzymatic activities. Finally, the effect of Fe resupply on the above responses was tested in the presence and absence of HCO3(-) (+Fe+Bic or +Fe, respectively). -Fe+Bic seedlings exhibited lower Fe concentration in shoots and roots than -Fe ones but higher in cotyledons, associated to a significative inhibition of NRAMP3 expression. HCO3(-) upregulated Strategy I related genes (FRO1, FRO2, HA1 and IRT1) and FC-R and H(+)-ATPase activities in roots of Fe-starved seedlings. PEPC1 expression and PEPCase activity were also increased. When -Fe+Bic pre-treated seedlings were transferred to Fe-containing media for 15d, Fe content in shoots and roots increased, although to a lower extent in the +Fe+Bic medium. Consequently, the above-described root responses became markedly repressed, however, this effect was less pronounced in +Fe+Bic seedlings. In conclusion, it appears that HCO3(-) prevents Fe translocation from cotyledons to shoot and root, therefore reducing their Fe levels. This triggers Fe-stress responses in the root, enhancing the expression of genes related with Fe uptake and the corresponding enzymatic activities.

  8. Comparative evaluation of 13 yeast species in the Yarrowia clade on lignocellulosic biomass hydrolysate and genetic engineering of inhibitor tolerant strains for lipid and biofuel production

    Science.gov (United States)

    Yarrowia lipolytica is an oleaginous yeast that has garnered interest for commercial production of single cell oil and other fatty acid-derived chemicals because of its GRAS status and genetic tractability. Three recent peer-reviewed studies have highlighted the possibility of lipid production by th...

  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. 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...

  11. Upregulation of Salmonella-Induced IL-6 Production in Caco-2 Cells by PJ-34, PARP-1 Inhibitor: Involvement of PI3K, p38 MAPK, ERK, JNK, and NF-κB

    Directory of Open Access Journals (Sweden)

    Fu-Chen Huang

    2009-01-01

    Full Text Available Following Salmonella invasion, intestinal epithelial cells release a distinct array of proinflammatory cytokines. Interleukin (IL-6 produced by enterocytes may have anti-inflammatory and cell-protective effects, and may counteract some of the injurious effects of sepsis and endotoxemia. Recent studies in a variety of rodent models of experimental colitis by using PJ-34, a potent poly (ADP-ribose polymerase-1 (PARP-1 inhibitor, support the concept that the marked beneficial effect of PJ-34 can be exploited to treat human inflammatory diseases. The present study was to investigate the effect of PJ-34 on Salmonella-induced enterocyte IL-6 production and its mechanisms. We found that PJ-34 enhanced Salmonella-induced IL-6 production in Caco-2 cells, either secreted protein or mRNA expression. PJ-34 treatment enhanced the activity of NF-κB in Salmonella-infected Caco-2 cells. Besides, the involvement of PJ-34 in up-regulating IL-6 production in S. typhimurium-infected Caco-2 cells might be also through the ERK but not p38 MAPK, JNK or PI3K/Akt pathways, as demonstrated by Western blot of phosphorylated ERK, p38, JNK and Akt proteins. It suggests that PJ-34 may exert its protective effect on intestinal epithelial cells against invasive Salmonella infection by up-regulating IL-6 production through ERK and NF-κB but not P38 MAPK, JNK or PI3K/Akt signal pathways.

  12. 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.

  13. Controlled leaching with prolonged activity for Co-LDH supported catalyst during treatment of organic dyes using bicarbonate activation of hydrogen peroxide.

    Science.gov (United States)

    Jawad, Ali; Li, Yibing; Lu, Xiaoyan; Chen, Zhuqi; Liu, Weidong; Yin, Guochuan

    2015-05-30

    The effluents from industries are commonly non-biodegradable and produce various hazardous intermediate products by chemical reactions that have direct impact on environment. In the present investigation, a series of Co-Mg/AL ternary LDH catalysts with fixed Mg/Al ratio were prepared by co-precipitation method. The effect of Co on the activity of the catalyst was monitored on the degradation of methylene blue (MB) as model compound at batch level using bicarbonate activation of H2O2 (BAP) system. On bench level, the best CoMgAl-4 catalyst can completely decolorize both methylene blue (MB) and methylene orange (MO) in short time, while in fixed bed, the catalyst was found stable for over 300 h with nearly 100% decolorization and excellent chemical oxygen demand (COD) removal. No leaching of Co was detected for the entire fixed experiment which may be accounted for long life stability and good activity of the catalyst. The ternary LDH catalysts were characterized by AES, XRD, FTIR, BET, and SEM for its compositional, phase structure, optical properties, textural, and surface morphology respectively. The XRD analysis confirmed characteristic pattern of hydrotalcite like structures without impurity phases. The formation of superoxide and hydroxyl radical as ROS was proposed with CoMgAl-4 by radical's scavengers.

  14. Magnesium bicarbonate and carbonate interactions in aqueous solutions: An infrared spectroscopic and quantum chemical study

    Science.gov (United States)

    Stefánsson, Andri; Lemke, Kono H.; Bénézeth, Pascale; Schott, Jacques

    2017-02-01

    The interaction of magnesium with bicarbonate and carbonate ions in aqueous solutions was studied using infrared spectroscopy and quantum chemical calculations. Using the infrared vibrational bands for HCO3- and CO32- at 1200-1450 cm-1 (δC-OH, vS and v3) together with their molar absorptivity (ε), the concentrations of the HCO3- and CO32- ions and the corresponding Mg ion pairs have been determined. In the absence of Mg2+, measured spectra were accurately reproduced assuming that only HCO3- and CO32- were present in solution. Upon addition of Mg2+ at fixed pH, infrared spectra were observed to shift indicating presence of the MgHCO3+ and MgCO3 (aq) ion pairs. From measurements, the second ionization constant of carbonic acid and the MgHCO3+ and MgCO3 (aq) ion pair formation constants have been obtained, these being logK2 = -10.34 ± 0.04, logKMgHCO3+ = 1.12 ± 0.11 and logKMgCO3 = 2.98 ± 0.06, respectively. To support our experimental infrared measurements and to gain further insight into the molecular nature of the ion pair formation, density functional theory (DFT) calculations with VPT2 anharmonic correction were conducted. The most stable geometries predicted for the MgHCO3+ and MgCO3 (aq) ion pairs were a bi-dentate [MgHCO3]+(H2O)n and a monodentate [MgHCO3]+(OH)(H2O)n complexes, respectively. The predicted frequencies for HCO3-, CO32- and MgHCO3+ were found to shift toward those experimentally measured with an increasing H2O solvation number where possible band shifts were predicted for MgCO3 (aq) relative to CO32-, this being dependent on the exact structure and hydration of the bulk MgCO3 (aq) ion pair. Experimentally, the ion pair formations were found to have insignificant effects on the δC-OH, vS and v3 vibrational frequencies. The speciation of dissolved inorganic carbon may be significantly influenced by ion pair formation, particularly in alkaline solutions where they may be the predominant species.

  15. The effect of sodium bicarbonate ingestion on back squat and bench press exercise to failure.

    Science.gov (United States)

    Duncan, Michael J; Weldon, Anthony; Price, Michael J

    2014-05-01

    This study examined the acute effects of NaHCO3 ingestion on repetitions to failure and rating of perceived exertion in the back squat and bench press in trained men. Eight resistance-trained men took part in this double-blind, randomized crossover experimental study whereby they ingested NaHCO3 (0.3 g·kg(-1) body mass) or placebo (sodium chloride NaCl: 0.045 g·kg(-1) body mass) solution 60 minutes before completing a bout of resistance exercise (3 sets of bench press and back squat exercise to failure at an intensity of 80% 1 repetition maximum). Experimental conditions were separated by at least 48 hours. Participants completed more repetitions to failure in the back squat after NaHCO3 ingestion (p = 0.04) but not for bench press (p = 0.679). Mean ± SD of total repetitions was 31.3 ± 15.3 and 24.6 ± 16.2 for back squat and 28.7 ± 12.2 and 26.7 ± 10.2 for bench press in NaHCO3 and placebo conditions, respectively. Repetitions to failure decreased as set increased for the back squat and bench press (p = 0.001, both). Rating of perceived exertion significantly increased with set for the back squat and bench press (p = 0.002, both). There was no significant change in blood lactate across time or between conditions. There were however treatment × time interactions for blood pH (p = 0.014) and blood HCO3 concentration (p = 0.001). After ingestion, blood pH and HCO3 (p = 0.008) concentrations were greater for the NaHCO3 condition compared with the placebo condition (p < 0.001). The results of this study suggest that sodium bicarbonate ingestion can enhance resistance exercise performance using a repetition to failure protocol in the first exercise in a resistance exercise session.

  16. 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.

  17. 高抗逆高丁比拜氏梭菌的选育及其性能考察%Screening of Clostridium beijerinckii mutant with high inhibitor tolerance and high proportions of butanol for butanol production

    Institute of Scientific and Technical Information of China (English)

    贺爱永; 尹春燕; 孔祥平; 陈佳楠; 姜岷; 吴昊

    2014-01-01

    以抗逆突变株Clostridium beijerinckii IB4为出发菌株,通过常压室温等离子体诱变( ARTP ),刃天青平板初筛,摇瓶发酵复筛,筛选出1株高抗逆高丁比的突变菌株C.beijerinckii IT111。发酵结果表明:该突变菌株利用多种C源时均展现其高丁醇比的特性,以玉米芯酸解糖液为C源时,溶剂产量达到10.5 g/L,丁醇8.0 g/L,丁醇比高达76%。抑制物抗逆性测试结果显示:糠醛和酸类对C.beijerinckii发酵影响较小,酚类物质对C.beijerinckii抑制作用较强,其中以香草醛为最。综上所述,C.beijerinckii IT111是1株极具潜力的利用木质纤维原料制备丁醇的菌株。%Clostridium beijerinckii IT111,a tolerance mutant strain with high proportions of butanol,was obtained by atmospheric and room temperature plasma ( ARTP ) and high-throughput screening.Fermentation results showed that the mutant had a high butanol proportions using a variety of carbon sources.When non-detoxified hemicellulosic hydrolysate of corn fiber treated with dilute sulfuric acid ( SAHHC) was used as a substrate,total solvent( ABE) and butanol production of 10.5 g/L and 8.0 g/L were obtained,respectively.The butanol proportion was up to 76%.The results of toxicity evaluation of model inhibitors showed that acetates,furfural and 5-HMF were not inhibitory to ABE production,while phenolic compounds were potent inhibitors of growth and ABE production, especially vanillin.C.beijerinckii IT111 was a promising strain for ABE production from lignocellulosic materials.

  18. 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.

    Science.gov (United States)

    Swartz, Kenneth; Zhang, Yiguan; Valeriote, Frederick; Chen, Ben; Shaw, Jiajiu

    2013-12-01

    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 samples were quenched by acetonitrile, vortexed, and centrifuged. The supernatants were then analyzed by reversed-phase HPLC (using a C18 column). The retention times and UV/vis spectra of individual peaks were compared to those of UTL-5g and its two postulated enzymatic products; thus the enzymatic products of UTL-5g were tentatively identified. Secondly, a different HPLC method (providing different retentions times) was used to cross-check and to confirm the identities of the two enzymatic products. Based on the observations, it was concluded that under the treatment of PLE, the major enzymatic products of UTL-5g were 5-methyliosxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA). Treatment of UTL-5g by RLE also provided the same enzymatic products of UTL-5g from esterase. These results indicate that the peptide bond in UTL-5g was cleaved by PLE/RLE. Michaelis-Menten kinetics showed that the Km values of UTL-5g were 2.07mM with PLE and 0.37mM with RLE indicating that UTL-5g had a higher affinity with RLE. In summary, by a simple HPLC approach, we have concluded that the peptide bond in UTL-5g was cleaved by esterase from either porcine liver or rabbit liver in vitro and afforded DCA (at a mole ratio of 1:1) and ISOX. However, further studies are needed in order to determine whether UTL-5g is metabolized by microsomal enzymes to produce ISOX and DCA.

  19. 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.

  20. 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

    2016-02-01

    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.

  1. 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

    2016-02-23

    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.

  2. Effects of some organic materials on bicarbonate extractable phosphate content of soils having different pH

    Directory of Open Access Journals (Sweden)

    Nutullah Özdemir

    2016-10-01

    Full Text Available This study was carried out to determine the effects of rice husk compost (RC, town waste compost (TW and tobacco waste (TB on bicarbonate extractable phosphate content (P in soils having different pH levels under greenhouse conditions. Soil samples used in this study were taken from surfaces (0-20 cm of agricultural fields around Samsun, Northern Anatolia. The experiment was conducted according to split plot design with four doses of organic matterials (0, 2.5, 5.0 and 7.5, %. After a month of mixing organic matterials into soils, lettuce were grown in the medias. According to the results, RC, TW and TB applications into acidic (Tepecik, neutral (Kampüs and alkaline (Çetinkaya soils increased extractable P content. It was observed that effectiveness of organic matterials changed depend on soil reaction, type and dose of organic matterials. All organic wastes were more effective on increment of bicarbonate extractable phosphate content in neutral soil pH when compared the other soil pH levels.

  3. 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.

  4. 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...

  5. 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.

  6. / 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.

  7. Identification of fermentation inhibitors in wood hydrolyzates and removal of inhibitors by ion exchange and liquid-liquid extraction

    Science.gov (United States)

    Luo, Caidian

    1998-12-01

    Common methods employed in the ethanol production from biomass consist of chemical or enzymatic degradation of biomass into sugars and then fermentation of sugars into ethanol or other chemicals. However, some degradation products severely inhibit the fermentation processes and substantially reduce the efficiency of ethanol production. How to remove inhibitors from the reaction product mixture and increase the production efficiency are critical in the commercialization of any processes of energy from biomass. The present study has investigated anion exchange and liquid-liquid extraction as potential methods for inhibitor removal. An analytical method has been developed to identify the fermentation inhibitors in a hydrolyzate. The majority of inhibitors present in hybrid poplar hydrolyzate have positively been identified. Ion exchange with weak basic Dowex-MWA-1 resin has been proved to be an effective mean to remove fermentation inhibitors from hybrid poplar hydrolyzate and significantly increase the fermentation productivity. Extraction with n-butanol might be a preferred way to remove inhibitors from wood hydrolyzates and improve the fermentability of sugars in the hydrolyzates. n-Butanol also removes some glucose, mannose and xylose from the hydrolyzate. Inhibitor identification reveals that lignin and sugar degradation compounds including both aromatic and aliphatic aldehydes and carboxylic acids formed in hydrolysis, plus fatty acids and other components from wood extractives are major fermentation inhibitors in Sacchromyces cerevisiae fermentation. There are 35 components identified as fermentation inhibitors. Among them, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid, syringic acid, syringaldehyde, and ferulic acid are among the most abundant aromatic inhibitors in hybrid poplar hydrolyzate. The conversion of aldehyde groups into carboxylic acid groups in the nitric acid catalyzed hydrolysis reduces the toxicity of the hydrolyzate. A wide spectrum of

  8. 21 CFR 347.50 - Labeling of skin protectant drug products.

    Science.gov (United States)

    2010-04-01

    ...) For products containing any ingredient in § 347.10(b), (c), (j), (s), (t), and (u). “Poison ivy, oak... products containing any ingredient in § 347.10(b), (c), (f), (j), (o), (s), (t), and (u). “Poison ivy, oak...’ ‘ poison ivy, oak, or sumac’ ‘ insect bites’].” (5) For products containing sodium bicarbonate...

  9. 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

    Alkaline wet oxidation (WO) (using water, 6.5 g/L sodium carbonate and 12 bar oxygen at 195degreesC) was used as pretreatment method for wheat straw (60 g/L), resulting in a hydrolysate and a cellulosic solid fraction. The hydrolysate consisted of soluble hemicellulose (8 g/L), low......-molecular-weight carboxylic acids (3.9 g/L), phenols (0.27 g/L = 1.7 mM) and 2-furoic acid (0.007 g/L). The wet oxidized wheat straw hydrolysate caused no inhibition of ethanol production by Saccharomyces cerevisiae ATCC 96581. Nine phenols and 2-furoic acid, identified to be present in the hydrolysate, were each tested...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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)

  15. Determination of a novel ACE inhibitor in the presence of alkaline and oxidative degradation products using smart spectrophotometric and chemometric methods

    Institute of Scientific and Technical Information of China (English)

    Maha Abdel-Monem Hegazy; Maya Shaaban Eissa; Osama Ibrahim Abd El-Sattar; Mohamed Mohamed Abd El-Kawy

    2014-01-01

    Simple, accurate, sensitive and validated UV spectrophotometric and chemometric methods were developed for the determination of imidapril hydrochloride (IMD) in the presence of both its alkaline (AKN) and oxidative (OXI) degradation products and in its pharmaceutical formulation. Method A is the fourth derivative spectra (D4) which allows the determination of IMD in the presence of both AKN and OXD, in pure form and in tablets by measuring the peak amplitude at 243.0 nm. Methods B, C and D, manipulating ratio spectra, were also developed. Method B is the double divisor-ratio difference spectrophotometric one (DD-RD) by computing the difference between the amplitudes of IMD ratio spectra at 232 and 256.3 nm. Method C is the double divisor-first derivative of ratio spectra method (DD-DR1) at 243.2 nm, while method D is the mean centering of ratio spectra (MCR) at 288.0 nm. Methods A, B, C and D could successfully determine IMD in a concentration range of 4.0-32.0 mg/mL. Methods E and F are principal component regression (PCR) and partial least-squares (PLS), respectively, for the simultaneous determination of IMD in the presence of both AKN and OXI, in pure form and in its tablets. The developed methods have the advantage of simultaneous determination of the cited components without any pre-treatment. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared with those of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

  16. 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.

  17. Bicarbonate concentration and osmolality are key determinants in the inhibition of CHO cell polysialylation under elevated pCO(2) or pH.

    Science.gov (United States)

    Zanghi, J A; Schmelzer, A E; Mendoza, T P; Knop, R H; Miller, W M

    1999-10-20

    Accumulation of CO(2) in animal cell cultures can be a significant problem during scale-up and production of recombinant glycoprotein biopharmaceuticals. By examining the cell-surface polysialic acid (PSA) content, we show that elevated CO(2) partial pressure (pCO(2)) can alter protein glycosylation. PSA is a high-molecular-weight polymer attached to several complex N-linked oligosaccharides on the neural cell adhesion molecule (NCAM), so that small changes in either core glycosylation or in polysialylation are amplified and easily measured. Flow-cytometric analysis revealed that PSA levels on Chinese hamster ovary (CHO) cells decrease with increasing pCO(2) in a dose-dependent manner, independent of any change in NCAM content. The results are highly pH-dependent, with a greater decrease in PSA at higher pH. By manipulating medium pH and pCO(2), we showed that decreases in PSA correlate well with bicarbonate concentration ([HCO(3)(-)]). In fact, it was possible to offset a 60% decrease in PSA content at 120 mm Hg pCO(2) by decreasing the pH from 7.3 to 6.9, such that [HCO(3)(-)] was lowered to that of control (38 mm Hg pCO(2)). When the increase in osmolality associated with elevated [HCO(3)(-)] was offset by decreasing the basal medium [NaCl], elevated [HCO(3)(-)] still caused a decrease in PSA, although less extensive than without osmolality control. By increasing [NaCl], we show that hyperosmolality alone decreases PSA content, but to a lesser extent than for the same osmolality increase due to elevated [NaHCO(3)]. In conclusion, we demonstrate the importance of pH and pCO(2) interactions, and show that [HCO(3)(-)] and osmolality can account for the observed changes in PSA content over a wide range of pH and pCO(2) values.

  18. Review article: similarities and differences among delayed-release proton-pump inhibitor formulations.

    Science.gov (United States)

    Horn, J R; Howden, C W

    2005-12-01

    Proton-pump inhibitors are acid-labile, and require an enteric coating to protect them from degradation in the stomach when given orally. However, this leads to delayed absorption and onset of action of the proton-pump inhibitor. This article aims to review the similarities and differences between the various formulations of delayed release proton-pump inhibitors. Delayed-release omeprazole and delayed-release lansoprazole have been suspended in sodium bicarbonate for tube administration; however, for omeprazole, absorption is further impaired and antisecretory effects are disappointing. Although such formulations may be more convenient for clinical use in certain patient groups, absorption of the proton-pump inhibitor is still influenced by residual enteric coating. There are few differences among the currently available delayed-release proton-pump inhibitors with respect to their pharmacodynamic effects during chronic administration. There are minor formulation-based pharmacokinetic differences among these agents, primarily reflected in their bioavailability following the first few doses. Differences in bioavailability may explain slight differences in the rate of onset of maximal antisecretory effect. However, minor pharmacodynamic and pharmacokinetic differences are not associated with meaningful differences in clinical outcomes.

  19. 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 ...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Microbial methane production in deep aquifer associated with the accretionary prism in Japan.

    Science.gov (United States)

    Kimura, Hiroyuki; Nashimoto, Hiroaki; Shimizu, Mikio; Hattori, Shohei; Yamada, Keita; Koba, Keisuke; Yoshida, Naohiro; Kato, Kenji

    2010-04-01

    To identify the methanogenic pathways present in a deep aquifer associated with an accretionary prism in Southwest Japan, a series of geochemical and microbiological studies of natural gas and groundwater derived from a deep aquifer were performed. Stable carbon isotopic analysis of methane in the natural gas and dissolved inorganic carbon (mainly bicarbonate) in groundwater suggested that the methane was derived from both thermogenic and biogenic processes. Archaeal 16S rRNA gene analysis revealed the dominance of H(2)-using methanogens in the groundwater. Furthermore, the high potential of methane production by H(2)-using methanogens was shown in enrichments using groundwater amended with H(2) and CO(2). Bacterial 16S rRNA gene analysis showed that fermentative bacteria inhabited the deep aquifer. Anaerobic incubations using groundwater amended with organic substrates and bromoethanesulfonate (a methanogen inhibitor) suggested a high potential of H(2) and CO(2) generation by fermentative bacteria. To confirm whether or not methane is produced by a syntrophic consortium of H(2)-producing fermentative bacteria and H(2)-using methanogens, anaerobic incubations using the groundwater amended with organic substrates were performed. Consequently, H(2) accumulation and rapid methane production were observed in these enrichments incubated at 55 and 65 degrees C. Thus, our results suggested that past and ongoing syntrophic biodegradation of organic compounds by H(2)-producing fermentative bacteria and H(2)-using methanogens, as well as a thermogenic reaction, contributes to the significant methane reserves in the deep aquifer associated with the accretionary prism in Southwest Japan.

  7. The activity of SN33638, an inhibitor of AKR1C3, on testosterone and 17β-estradiol production and function in castration-resistant prostate cancer and ER-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Yarong Diana eYin

    2014-06-01

    Full Text Available AKR1C3 is a novel therapeutic target in castration-resistant prostate cancer (CRPC and ER-positive breast cancer because of its ability to produce testosterone and 17β-estradiol intratumorally, thus promoting nuclear receptor signaling and tumor progression. A panel of CRPC, ER-positive breast cancer and high/low AKR1C3-expressing cell lines were treated with SN33638, a selective inhibitor of AKR1C3, in the presence of hormone or prostaglandin precursors, prior to evaluation of cell proliferation and levels of 11β-prostaglandin F2α (11β-PGF2α, testosterone, 17β-estradiol and prostate-specific antigen (PSA. A meta-analysis of AKR1C3 mRNA expression in patient samples was also conducted, which revealed that AKR1C3 mRNA was upregulated in CRPC, but downregulated in ER-positive breast cancer. 11β-PGF2α and testosterone levels in the cell line panel correlated with AKR1C3 protein expression. SN33638 prevented 11β-PGF2α formation in cell lines that expressed AKR1C3, but partially inhibited testosterone formation and subsequently cell proliferation and/or PSA expression only in high (LAPC4 AKR1C3-overexpressing cells or moderate (22RV1 AKR1C3-expressing cell lines. SN33638 had little effect on 17β-estradiol production or estrone-stimulated cell proliferation in ER-positive breast cancer cell lines. Although SN33638 could prevent 11β-PGF2α formation, its ability to prevent testosterone and 17β-estradiol production and their roles in CRPC and ER-positive breast cancer progression was limited due to AKR1C3-independent steroid hormone production, except in LAPC4 AKR1C3 cells where the majority of testosterone was AKR1C3-dependent. These results suggest that inhibition of AKR1C3 is unlikely to produce therapeutic benefit in CRPC and ER-positive breast cancer patients, except possibly in the small subpopulation of CRPC patients with tumors that have upregulated AKR1C3 expression and are dependent on AKR1C3 to produce the testosterone required

  8. 141 BOVINE EMBRYO DEVELOPMENT RATES ARE AFFECTED WHEN OOCYTES ARE MATURED IN DIFFERENT VIALS CONTAINING HEPES/BICARBONATE BUFFERED MEDIUM.

    Science.gov (United States)

    Hashem, N; Secher, J O; Pryor, J H; Long, C R; Looney, C R; Avery, B; Hyttel, P; Stroebech, L

    2016-01-01

    Laboratory ware for the in vitro-produced embryos is generally made from embryo-tested plastic instead of glass. The quality of the plastic is crucial for the outcome because plastic is often toxic to gametes (Nijs et al. 2009 Fertil. Steril. 92, 527-535). In addition, gas molecules permeate through the plastic at a rate that depends on a variety of factors, such as diffusion coefficient and thickness of the plastic. In an incubator with appropriate concentration of CO2 and vented culture vessels, the gas permeability of the plastic is not important. When oocytes are transported outside a controlled atmosphere, gas permeability, toxicity, and oocyte cumulus cell CO2 metabolism could perturb the outcome. Medium containing bicarbonate buffer increases pH outside of a controlled atmosphere within minutes, whereas medium buffered with HEPES maintains suitable pH for hours. Previously, we tested that gas permeability differs among plastic vials and glass vials with no cumulus-oocyte complexes (COC) by measuring pH after 2, 5, and 24h at the same temperature. The objective of this study was to compare pH post-maturation, blastocyst development rates on Day 8 post-IVF (Day 0=IVF) between 2 different 1.2-mL polypropylene cryovials (A: VWR DK, 479-1219; B: Sigma-Aldrich, St. Louis, MO, USA, CLS430289), glass vial (VWR DK, NSCAC4015-96), and 4-well plate (4WP) as control (Thermo Fisher Scientific, Waltham, MA, USA, 144444). A total of 1135 abattoir-derived COC in Exp. 1 and 133 in Exp. 2 were divided equally between the treatments (20-25 COC per vessel). Vials/4WP contained 0.8/0.5mL of BO-IVM HEPES, a HEPES/bicarbonate medium (IVF Bioscience; BO-HEPES-IVM, UK). Maturation lasted 22 to 24h at 38.8°C in an incubator with either a humidified atmosphere of 5.5% CO2 in air (Exp. 1) or with no CO2 contact (Exp. 2). In Exp. 1, oocyte vials were matured without a vial lid while in Exp. 2 vial lids were closed. Statistical analysis was performed with chi-square and mean±SD. In Exp

  9. Effect of glandular kallikrein on distal bicarbonate transport. Role of basolateral Cl-/HCO3- exchanger and vacuolar H(+)-ATPase.

    Science.gov (United States)

    Manucha, W; Vallés, P

    1999-12-01

    The luminal membrane of collecting duct cells, specially the intercalated cells, is normally exposed to active kallikrein. This is due to the specific localization of renal kallikrein in the connecting tubule cells. We have previously reported inhibition of distal bicarbonate secretion by renal kallikrein. The present study was performed to evaluate the participation of basolateral Cl-/HCO3- exchanger and luminal H(+)-ATPase activity of cortical collecting duct segments (CCD) in the mechanism involved in the inhibition of bicarbonate secretion induced by the enzyme. The effect of orthograde injections of 1 microgram/ml (250 U/6.3 mg) pig pancreatic kallikrein, in the absence and presence of 1 mM DIDS (stilbene-disulfonic acid) in the renal tubule system, was evaluated. Urine fractions were collected after two-minutes stop-flow. Changes in the urine fraction (Fr) related to those in free-flow urine samples (Ff) were related to the respective polyfructosan (Inutest) ratio. Renal kallikrein activity (Fr:Ff kallikrein/Fr:Ff polyfructosan) increased significantly in the first 120 microliters urine fraction collected after glandular 1 microgram/ml kallikrein, P Bicarbonate secretion rate (Fr:Ff HCO3-/Fr:Ff polyfructosan) of collecting ducts was significantly reduced in the first 120 microliters urine fraction collected, related to control, during the first and second stop-flow periods. No difference was shown in bicarbonate excretion between the first 120 microliters urine fractions collected after administration of glandular kallikrein and glandular kallikrein plus DIDS. To measure H(+)-ATPase activity, rat microdissected cortical collector tubules (CCD) were incubated in the presence of increasing glandular kallikrein doses (A: 93, B: 187 and C: 375 mU/200 microL) in the presence of ouabain (4 microM) and omeprazole (100 microM) to inhibit Na(+)-K(+)-ATPase and H(+)-K(+)-ATPase, respectively. In CCD, bafilomycin-sensitive H(+)-ATPase activity (pmol/mm/min) after

  10. 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

  11. Decreased pCO(2) accumulation by eliminating bicarbonate addition to high cell-density cultures.

    Science.gov (United States)

    Goudar, Chetan T; Matanguihan, Ricaredo; Long, Edward; Cruz, Christopher; Zhang, Chun; Piret, James M; Konstantinov, Konstantin B

    2007-04-15

    High-density perfusion cultivation of mammalian cells can result in elevated bioreactor CO(2) partial pressure (pCO(2)), a condition that can negatively influence growth, metabolism, productivity, and protein glycosylation. For BHK cells in a perfusion culture at 20 x 10(6) cells/mL, the bioreactor pCO(2) exceeded 225 mm Hg with approximate contributions of 25% from cellular respiration, 35% from medium NaHCO(3), and 40% from NaHCO(3) added for pH control. Recognizing the limitations to the practicality of gas sparging for CO(2) removal in perfusion systems, a strategy based on CO(2) reduction at the source was investigated. The NaHCO(3) in the medium was replaced with a MOPS-Histidine buffer, while Na(2)CO(3) replaced NaHCO(3) for pH control. These changes resulted in 63-70% pCO(2) reductions in multiple 15 L perfusion bioreactors, and were reproducible at the manufacturing-scale. Bioreactor pCO(2) values after these modifications were in the 68-85 mm Hg range, pCO(2) reductions consistent with those theoretically expected. Low bioreactor pCO(2) was accompanied by both 68-123% increased growth rates and 58-92% increased specific productivity. Bioreactor pCO(2) reduction and the resulting positive implications for cell growth and productivity were brought about by process changes that were readily implemented and robust. This philosophy of pCO(2) reduction at the source through medium and base modification should be readily applicable to large-scale fed-batch cultivation of mammalian cells.

  12. Myeloperoxidase Inhibitors as Potential Drugs.

    Science.gov (United States)

    Lazarević-Pasti, Tamara; Leskovac, Andreja; Vasić, Vesna

    2015-01-01

    Myeloperoxidase (MPO) is an important member of the haem peroxidase - cyclooxygenase superfamily. This enzyme is physiologically expressed in circulating neutrophils, monocytes and some tissue macrophages including microglia. MPO plays an essential role in the antimicrobial and antiviral system of humans. The microbicidal activity of MPO exists due to its capability to oxidize halide and pseudohalide ions (CI(-), Br(-), I(-) and SCN(-)) by H2O2, thereby producing respective hypohalous acids (HOX). During the phagocytosis of pathogens, azurophilic granules release their content together with MPO into phagolysosomes. On the other hand, MPO can be discharged outside the phagocytes. Due to this, tissue damage during inflammation is greatly promoted by MPO-derived oxidants. Regarding its activity, MPO is a key factor in a great number of conditions within the group of cardiovascular diseases, inflammatory diseases, neurodegenerative diseases, kidney diseases and immune-mediated diseases. Therefore, MPO and its downstream inflammatory pathways might be attractive targets for both prognostic and therapeutic intervention in the prophylaxis of all mentioned illnesses. Nowadays, structure and reaction mechanism of MPO are known, which enable rational strategy in the development of specific MPO inhibitors that still preserve MPO activity during host defense from bacteria, but hinder pathophysiologically persistent activation of MPO. Various methods for MPO activity inhibition and unfavorable effects of MPO-derived oxidants remodeling will be discussed. Emphasis will be put on various known inhibitors, as well as on newly investigated natural products, which can also inhibit MPO activity.

  13. Thrombin inhibitor design.

    Science.gov (United States)

    Sanderson, P E; Naylor-Olsen, A M

    1998-08-01

    Recently, iv formulated direct thrombin inhibitors have been shown to be safe and efficacious alternatives to heparin. These results have fueled the hopes for an orally active compound. Such a compound could be a significant advance over warfarin if it had predictable pharmacokinetics and a duration of action sufficient for once or twice a day dosing. In order to develop an orally active compound which meets these criteria, the deficiencies of the prototype inhibitor efegatran have had to be addressed. First, using a combination of structure based design and empirical structure optimization, more selective compounds have been identified by modifying the P1 group or by incorporating different peptidomimetic P2/P3 scaffolds. Secondly, this optimization has resulted in the development of potent and selective non-covalent inhibitors, thus bypassing the liabilities of the serine trap. Thirdly, oral bioavailability has been achieved while maintaining selectivity and efficacy through the incorporation of progressively less basic P1 groups. The duration of action of these compounds remains to be optimized. Other advances in thrombin inhibitor design have included the development of uncharged P1 groups and the discovery of two non-peptide templates.

  14. ACE inhibitors and proteinuria

    NARCIS (Netherlands)

    Gansevoort, RT; deZeeuw, D; deJong, PE

    1996-01-01

    This review discusses the clinical consequences of urinary protein loss and the effects of inhibitors of the angiotensin converting enzyme (ACE) on this clinical finding. Proteinuria appears to be an important risk factor for renal function deterioration and for cardiovascular mortality. ACE inhibit

  15. Transglutaminase inhibitor from milk

    NARCIS (Netherlands)

    Jong, G.A.H. de; Wijngaards, G.; Koppelman, S.J.

    2003-01-01

    Cross-linking experiments of skimmed bovine milk with bacterial transglutaminase isolated from Streptoverticillium mobaraense showed only some degree of formation of high-molecular-weight casein polymers. Studies on the nature of this phenomenon revealed that bovine milk contains an inhibitor of tra

  16. 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...

  17. 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...

  18. Effects of sodium bicarbonate ingestion on performance and perceptual responses in a laboratory-simulated BMX cycling qualification series.

    Science.gov (United States)

    Zabala, Mikel; Requena, Bernardo; Sánchez-Muñoz, Cristóbal; González-Badillo, Juan José; García, Inmaculada; Oöpik, Vahur; Pääsuke, Mati

    2008-09-01

    The objective of this study was to examine the effect of sodium bicarbonate (NaHCO3-) ingestion on performance and perceptual responses in a laboratory-simulated bicycle motocross (BMX) qualification series. Nine elite BMX riders volunteered to participate in this study. After familiarization, subjects undertook two trials involving repeated sprints (3 x Wingate tests [WTs] separated by 30 minutes of recovery; WT1, WT2, WT3). Ninety minutes before each trial, subjects ingested either NaHCO3- or placebo in a counterbalanced, randomly assigned, double-blind manner. Each trial was separated by 4 days. Performance variables of peak power, mean power, time to peak power, and fatigue index were calculated for each sprint. Ratings of perceived exertion were obtained after each sprint, and ratings of perceived readiness were obtained before each sprint. No significant differences were observed in performance variables between successive sprints or between trials. For the NaHCO3- trial, peak blood lactate during recovery was greater after WT2 (p BMX qualification series, possibly because of the short duration of each effort and the long recovery time used between the three WTs. On the contrary, NaHCO3- ingestion improved perceived readiness before each WT.

  19. Bicarbonate-sensing soluble adenylyl cyclase is present in the cell cytoplasm and nucleus of multiple shark tissues.

    Science.gov (United States)

    Roa, Jinae N; Tresguerres, Martin

    2017-01-01

    The enzyme soluble adenylyl cyclase (sAC) is directly stimulated by bicarbonate (HCO3(-)) to produce the signaling molecule cyclic adenosine monophosphate (cAMP). Because sAC and sAC-related enzymes are found throughout phyla from cyanobacteria to mammals and they regulate cell physiology in response to internal and external changes in pH, CO2, and HCO3(-), sAC is deemed an evolutionarily conserved acid-base sensor. Previously, sAC has been reported in dogfish shark and round ray gill cells, where they sense and counteract blood alkalosis by regulating the activity of V-type H(+)- ATPase. Here, we report the presence of sAC protein in gill, rectal gland, cornea, intestine, white muscle, and heart of leopard shark Triakis semifasciata Co-expression of sAC with transmembrane adenylyl cyclases supports the presence of cAMP signaling microdomains. Furthermore, immunohistochemistry on tissue sections, and western blots and cAMP-activity assays on nucleus-enriched fractions demonstrate the presence of sAC protein in and around nuclei. These results suggest that sAC modulates multiple physiological processes in shark cells, including nuclear functions.

  20. Measurement of Total Free Iron in Soils by H2S Chemisorption and Comparison with the Citrate Bicarbonate Dithionite Method

    Directory of Open Access Journals (Sweden)

    Shui-Sheng Fan

    2016-01-01

    Full Text Available Free iron is one of the major analytical items for soil basic properties. It is also an important indicator for understanding the genesis of soil, soil classification, and soil distribution behavior. In this study, an alternative analytical method (chemisorption based on thermodynamic knowledge was proposed for measurement of total free iron oxides in soils. Several representative soil samples belonging to alfisols, ultisols, inceptisols, and entisols were collected from Taiwan and tested by the chemisorption, and the estimated total free iron oxides were compared with those measured from the traditional citrate bicarbonate dithionite (CBD method. Experimental results showed that the optimal operating temperature was found to be at 773 K and the carbon monoxide (CO is the best gaseous reagent to promote the formation of FeS. The estimated total free iron oxides for soil samples determined from the chemisorption in the presence of CO were very close to those from the CBD technique. The result of regression indicates that the estimated total free iron is strongly correlated with the CBD-Fe content (R2=0.999 in the presence of CO.

  1. Evaluation of strength-enhancing factors of a ductile binder in direct compression of sodium bicarbonate and calcium carbonate powders.

    Science.gov (United States)

    Mattsson, S; Nyström, C

    2000-03-01

    This study evaluated the effectiveness of a ductile binder in direct compression of sodium bicarbonate and calcium carbonate powders. Properties associated with both the binder and the compound were studied. The addition of binder materials, such as polyethylene glycols (PEGs) of differing molecular weights or microcrystalline cellulose, generally resulted in an increase in the axial tensile strength of the corresponding compacts. The increase in tablet strength was generally greater with the PEGs than with microcrystalline cellulose. The results indicate that the improvement in tablet strength caused by the binder is dependent on properties of both the binder and the compound. By utilising different methods it was established that the fracture during tablet strength testing mainly occurred around the compound particles. As a consequence of this, it appears that the ability of the binder to fill the voids between the compound particles is a determinative factor for increasing tablet strength. The binder appeared to have less effect when added to compounds that fragmented during compaction. Characteristics of the binder resulting in the greatest decrease in porosity, and thus the greatest increase in the tensile strength of the compound, included a high degree of plastic deformation with a limited elastic component and a small particle size. Obviously, the amount of binder added to the mixture also affected the results.

  2. [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.

  3. Measurement of Total Free Iron in Soils by H2S Chemisorption and Comparison with the Citrate Bicarbonate Dithionite Method

    Science.gov (United States)

    Fan, Shui-Sheng; Chang, Feng-Hsiang

    2016-01-01

    Free iron is one of the major analytical items for soil basic properties. It is also an important indicator for understanding the genesis of soil, soil classification, and soil distribution behavior. In this study, an alternative analytical method (chemisorption) based on thermodynamic knowledge was proposed for measurement of total free iron oxides in soils. Several representative soil samples belonging to alfisols, ultisols, inceptisols, and entisols were collected from Taiwan and tested by the chemisorption, and the estimated total free iron oxides were compared with those measured from the traditional citrate bicarbonate dithionite (CBD) method. Experimental results showed that the optimal operating temperature was found to be at 773 K and the carbon monoxide (CO) is the best gaseous reagent to promote the formation of FeS. The estimated total free iron oxides for soil samples determined from the chemisorption in the presence of CO were very close to those from the CBD technique. The result of regression indicates that the estimated total free iron is strongly correlated with the CBD-Fe content (R2 = 0.999) in the presence of CO. PMID:28116218

  4. Effects of feeding virginiamycin and sodium bicarbonate to grazing lactating dairy cows.

    Science.gov (United States)

    Clayton, E H; Lean, I J; Rowe, J B; Cox, J W

    1999-07-01

    The effects of virginiamycin, an agent active against Gram-positive lactic acid-producing bacteria, and NaHCO3 on ruminal and fecal pH, rumen volatile fatty acid proportions, blood metabolites, and milk production and composition were assessed. This study was conducted over 28 d and involved 71 dairy cows that grazed predominantly ryegrass, oats, and clover, and that were fed 10 kg of concentrate pellets/d per head. The pellets contained (per kilogram) no dietary additive, 30 mg of virginiamycin, 20 g of NaHCO3, or 30 mg of virginiamycin and 20 g of NaHCO3 on a DM basis. Ruminal pH tended to be higher in cows fed pellets containing virginiamycin (7.0 vs. 6.9; SED = 0.16). The results of in vitro incubation of ruminal fluid with glucose found the potential for L-lactic acid accumulation in ruminal fluid to be significantly lower in cows fed virginiamycin (15.5 vs. 35.3 mmol/L; SED = 2.98). Cows fed virginiamycin had significantly higher fecal pH (6.72 vs. 6.57; SED = 0.08) and produced more milk (23.94 vs. 23.32 kg/d) and more lactose than those not fed virginiamycin. No effects of NaHCO3 on fecal pH, in vitro potential for L-lactic acid accumulation in ruminal fluid, or milk production were observed, but ruminal pH tended to be higher and ruminal acetate proportion was greater for cows fed NaHCO3. Milk fat and milk protein percentage did not differ significantly as a result of dietary treatment. These data suggest that the inclusion of virginiamycin in the diet will reduce L-lactic acid accumulation in ruminal fluid and increase fecal pH in grazing dairy cattle fed concentrate supplements.

  5. Achievements, challenges and unmet needs for haemophilia patients with inhibitors

    Science.gov (United States)

    DARGAUD, Y.; PAVLOVA, A.; LACROIX-DESMAZES, S.; FISCHER, K.; SOUCIE, M.; CLAEYSSENS, S.; SCOTT, D.W.; d’OIRON, R.; LAVIGNE-LISSALDE, G.; KENET, G.; ETTINGSHAUSEN, C. ESCURIOLA; BOREL-DERLON, A.; LAMBERT, T.; PASTA, G.; NÉGRIER, C.

    2016-01-01

    Summary Over the past 20 years, there have been many advances in haemophilia treatment that have allowed patients to take greater control of their disease. However, the development of factor VIII (FVIII) inhibitors is the greatest complication of the disease and a challenge in the treatment of haemophilia making management of bleeding episodes difficult and surgical procedures very challenging. A meeting to discuss the unmet needs of haemophilia patients with inhibitors was held in Paris on 20 November 2014. Topics discussed were genetic and non-genetic risk factors for the development of inhibitors, immunological aspects of inhibitor development, FVIII products and inhibitor development, generation and functional properties of engineered antigen-specific T regulatory cells, suppression of immune responses to FVIII, prophylaxis in haemophilia patients with inhibitors, epitope mapping of FVIII inhibitors, current controversies in immune tolerance induction therapy, surgery in haemophilia patients with inhibitors and future perspectives for the treatment of haemophilia patients with inhibitors. A summary of the key points discussed is presented in this paper. PMID:26728503

  6. Urease Inhibitors of Agricultural Interest Inspired by Structures of Plant Phenolic Aldehydes

    OpenAIRE

    Lívia P. Horta; Mota,Yane C. C.; Barbosa,Gisele Maria; Taniris C. Braga; Marriel,Ivanildo E.; Fátima,Ângelo de; Modolo, Luzia V.

    2016-01-01

    The plant phenolic natural products (PNPs) protocatechuic aldehyde, syringaldehyde and vanillin were used as platforms for obtaining four urease inhibitors. Urea (urease substrate) or thiourea (urease inhibitor) core was added to the structure of newly synthesized compounds to provide inhibitors up to 230-fold more active than the PNPs they originated from. The PNP derivatives are mixed inhibitors with higher affinity to urease active site. Two compounds were as efficient as N-(butyl)thiophos...

  7. 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.

  8. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.

    Science.gov (United States)

    Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee; Wesson, Donald E

    2014-11-01

    Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.

  9. Intravenous Lipid Emulsion Therapy Does Not Improve Hypotension Compared to Sodium Bicarbonate for Tricyclic Antidepressant Toxicity: A Randomized, Controlled Pilot Study in a Swine Model

    Science.gov (United States)

    2014-11-01

    amitriptyline-induced hypotension. The objective was to determine if ILE improved hypotension (defined by a mean arterial pressure [MAP] < 60% baseline...more effective in improving hypotension (defined by a mean arterial pressure [MAP] < 60% baseline) compared to sodium bicarbon- ate for treatment of...amitriptyline overdose in a critically ill swine model. METHODS Study Design Using a porcine model of amitriptyline-induced hypo- tension , we used a

  10. 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.

  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. Effects of sodium bicarbonate and ammonium chloride pre-treatments on PEPT2 (SLC15A2) mediated renal clearance of cephalexin in healthy subjects.

    Science.gov (United States)

    Liu, Rui; Tang, Audrey May Yi; Tan, Yen Ling; Limenta, Lie Michael George; Lee, Edmund Jon Deoon

    2011-01-01

    PEPT2 mediates the H(+) gradient-driving reabsorption of di- and tri-peptides, and various peptidomimetic compounds in the kidney. This study examines the influence of urinary pH modification through sodium bicarbonate and ammonium chloride pre-treatments on the function of PEPT2 in healthy subjects, using cephalexin as the probe drug. Sixteen male subjects received a single oral dose of 1000 mg cephalexin under ammonium chloride and sodium bicarbonate treatment, respectively, with a wash-out period of one week. The study subjects were genotyped for PEPT2 polymorphic variants. Cephalexin concentrations in plasma and urine were determined by high performance liquid chromatography. The mean renal clearance of cephalexin was significantly higher under ammonium chloride treatment than that under sodium bicarbonate treatment (P < 0.01). This difference was significant for PEPT2*2/*2 (P = 0.017) but not for PEPT2*1/*1 (P = 0.128). No differences were observed for other pharmacokinetic parameters. The findings of this study suggest that urinary pH changes may alter the pharmacokinetics of PEPT2's substrates. This effect was more obvious for the PEPT2*2/*2.

  13. 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.

  14. Heterotrophic bicarbonate assimilation is the main process of de novo organic carbon synthesis in hadal zone of the Hellenic Trench, the deepest part of Mediterranean Sea.

    Science.gov (United States)

    Yakimov, Michail M; La Cono, Violetta; Smedile, Francesco; Crisafi, Francesca; Arcadi, Erika; Leonardi, Marcella; Decembrini, Franco; Catalfamo, Maurizio; Bargiela, Rafael; Ferrer, Manuel; Golyshin, Peter N; Giuliano, Laura

    2014-12-01

    Ammonium-oxidizing chemoautotrophic members of Thaumarchaea are proposed to be the key players in the assimilation of bicarbonate in the dark (ABD). However, this process may also involve heterotrophic metabolic pathways, such as fixation of carbon dioxide (CO2) via various anaplerotic reactions. We collected samples from the depth of 4900 m at the Matapan-Vavilov Deep (MVD) station (Hellenic Trench, Eastern Mediterranean) and used the multiphasic approach to study the ABD mediators in this deep-sea ecosystem. At this depth, our analysis indicated the occurrence of actively CO2-fixing heterotrophic microbial assemblages dominated by Gammaproteobacteria with virtually no Thaumarchaea present. [14C]-bicarbonate incorporation experiments combined with shotgun [14C]-proteomic analysis identified a series of proteins of gammaproteobacterial origin. More than quarter of them were closely related with Alteromonas macleodii ‘deep ecotype’ AltDE, the predominant organism in the microbial community of MVD. The present study demonstrated that in the aphotic/hadal zone of the Mediterranean Sea, the assimilation of bicarbonate is associated with both chemolithoauto- and heterotrophic ABD. In some deep-sea areas, the latter may predominantly contribute to the de novo synthesis of organic carbon which points at the important and yet underestimated role heterotrophic bacterial populations can play the in global carbon cycle/sink in the ocean interior.

  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. Synergistic antitumor effects of in vivo production of human endostatin and tissue inhibitor of metalloproteinase-1 in mice after subcutaneous implantation of primary fibroblasts transfected by adenovirus-mediated gene delivery

    Institute of Scientific and Technical Information of China (English)

    SHEN Wei-gan; ZHU Jun; ZHANG Yu; SU Qing

    2010-01-01

    Background Tissue inhibitor of metalloproteinase (TIMP)-1 is a multifunctional protein. The aim of the study was to examine the feasibility of using a combination of adenovirus-mediated gene delivery of TIMP-1 plus endostatin and cell transplantation techniques to treat tumor growth and metastasis in mouse melanoma.Methods A enzyme-linked immunosorbent assay (ELISA) was used to detect the level of TIMP-1 and endostatin in vitro and in vivo. A tumor bearing mouse model and an experimental lung metastasis model in animal experiments were used to explore the therapeutic effect of in vivo production of human TIMP-1 and endostatin after the implantation of primary fibroblasts infected with the indicated adenovirus into tumor-bearing mice and a cytochemical method was used to observe histopathological changes of the tumor. An experimental lung metastasis model was established by injecting B16BL6 cells into the tail vein of mice and adenovirus-infected primary fibroblasts were subcutaneously implanted into the mice 24 hours later. Twenty-one days after tumor cell injection, mice were sacrificed to examine the effect on nodules visible as black forms on the surface of the lungs in B16BL6 cells.Results TIMP-1 and endostatin were secreted into the supernatants of cultures of Ad-TIMP-1 and Ad-End-infected mouse primary fibroblasts. We also observed that implantation of fibroblasts infected with Ad-TIMP-1 alone, Ad-End alone, or Ad-TIMP-1 plus Ad-End resulted in detectable blood levels which may clearly inhibit the tumor growth and metastasis in a murine melanoma model.Conclusion These results suggest the high capacity of transfection for the delivery of TIMP-1 or endostatin gene constructs into primary fibroblasts, and demonstrate that the implantation of TIMP-1 and endostatin producing fibroblasts at a site in vivo where direct secretion of TIMP-1 and endostatin into the blood is possible represented a promising approach for the development of cancer therapy.

  17. Benzoylurea Chitin Synthesis Inhibitors.

    Science.gov (United States)

    Sun, Ranfeng; Liu, Chunjuan; Zhang, Hao; Wang, Qingmin

    2015-08-12

    Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low toxicity to mammals and predatory insects. In the past decades, a large number of benzoylurea derivatives have been synthesized, and 15 benzoylurea chitin synthesis inhibitors have been commercialized. This review focuses on the history of commercial benzolyphenylureas (BPUs), synthetic methods, structure-activity relationships (SAR), action mechanism research, environmental behaviors, and ecotoxicology. Furthermore, their disadvantages of high risk to aquatic invertebrates and crustaceans are pointed out. Finally, we propose that the para-substituents at anilide of benzoylphenylureas should be the functional groups, and bipartite model BPU analogues are discussed in an attempt to provide new insight for future development of BPUs.

  18. Sequencing of aromatase inhibitors

    OpenAIRE

    2005-01-01

    Since the development of the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, these agents have been the subject of intensive research to determine their optimal use in advanced breast cancer. Not only have they replaced progestins in second-line therapy and challenged the role of tamoxifen in first-line, but there is also evidence for a lack of cross-resistance between the steroidal and nonsteroidal AIs, meaning that they may be used in sequence to obtain p...

  19. Simultaneous measurement of pH and membrane potential in rat dorsal vagal motoneurons during normoxia and hypoxia: a comparison in bicarbonate and HEPES buffers.

    Science.gov (United States)

    Cowan, A I; Martin, R L

    1995-12-01

    1. The effects of oxygenated and hypoxic bicarbonate/CO2, 10 and 25 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered artificial cerebrospinal fluid (ACSF) have been studied in a rat brain slice preparation. Double-barreled pH-selective microelectrodes were used to measure intracellular pH (pHi) and membrane potential in dorsal vagal motoneurons (DVMs) and to measure extracellular pH (pHe) in the dorsal vagal motonucleus. 2. In bicarbonate ACSF, pHi averaged 7.24 +/- 0.05 (mean +/- SE, n = 21) and ranged from 6.86 to 7.79 pH units. pHe averaged 7.13 +/- 0.08 (n = 10). 3. On changing from oxygenated bicarbonate ACSF to either 10 or 25 mM HEPES ACSF, pHi decreased by 0.13-0.15 units, and the membrane depolarized by 10-11 mV. pHe also decreased in 10 mM HEPES ACSF (pHe 6.89 +/- 0.02, n = 8) but not in 25 mM HEPES ACSF (pHe 7.15 +/- 0.06, n = 3). In most neurons changes in pHi preceded changes in membrane potential. 4. In bicarbonate ACSF and in 25 mM HEPES ACSF, there was a significant linear relationship between prehypoxic pHi and the direction and amplitude of the hypoxia-induced membrane potential change (either an hyperpolarization or a depolarization). 5. In 10 mM HEPES ACSF, hypoxia always induced a depolarization; there was no correlation between prehypoxic pHi and the membrane potential response. 6. In bicarbonate ACSF and in 10 and 25 mM HEPES ACSF, hypoxia resulted in intracellular and extracellular acidification. However, the extracellular acidification in hypoxic 10 mM HEPES buffer was most pronounced (pH 6.40 +/- 0.11, n = 8), reflecting a preexisting extracellular acidification in oxygenated 10 mM HEPES buffer. 7. Various hypotheses that could give rise to a relationship between changes in membrane potential and pH are discussed; arguments are presented in favor of the concept that modulation of ion channels by either pHi or pHe, or both, is responsible for the observed correlations.

  20. 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

  1. Role of bicarbonate as a pH buffer and electron sink in microbial dechlorination of chloroethenes

    Directory of Open Access Journals (Sweden)

    Delgado Anca G

    2012-09-01

    Full Text Available Abstract Background Buffering to achieve pH control is crucial for successful trichloroethene (TCE anaerobic bioremediation. Bicarbonate (HCO3− is the natural buffer in groundwater and the buffer of choice in the laboratory and at contaminated sites undergoing biological treatment with organohalide respiring microorganisms. However, HCO3− also serves as the electron acceptor for hydrogenotrophic methanogens and hydrogenotrophic homoacetogens, two microbial groups competing with organohalide respirers for hydrogen (H2. We studied the effect of HCO3− as a buffering agent and the effect of HCO3−-consuming reactions in a range of concentrations (2.5-30 mM with an initial pH of 7.5 in H2-fed TCE reductively dechlorinating communities containing Dehalococcoides, hydrogenotrophic methanogens, and hydrogenotrophic homoacetogens. Results Rate differences in TCE dechlorination were observed as a result of added varying HCO3− concentrations due to H2-fed electrons channeled towards methanogenesis and homoacetogenesis and pH increases (up to 8.7 from biological HCO3− consumption. Significantly faster dechlorination rates were noted at all HCO3− concentrations tested when the pH buffering was improved by providing 4-(2-hydroxyethyl-1-piperazineethanesulfonic acid (HEPES as an additional buffer. Electron balances and quantitative PCR revealed that methanogenesis was the main electron sink when the initial HCO3− concentrations were 2.5 and 5 mM, while homoacetogenesis was the dominant process and sink when 10 and 30 mM HCO3− were provided initially. Conclusions Our study reveals that HCO3− is an important variable for bioremediation of chloroethenes as it has a prominent role as an electron acceptor for methanogenesis and homoacetogenesis. It also illustrates the changes in rates and extent of reductive dechlorination resulting from the combined effect of electron donor competition stimulated by HCO3− and the changes in pH exerted by

  2. Effectiveness of sodium bicarbonate combined with hydrogen peroxide and CPP-ACPF in whitening and microhardness of enamel

    Science.gov (United States)

    Hasanzadeh, Nadia; Rajabi, Omid; Forouzannejad, Zakiyeh

    2017-01-01

    Background This study investigated the effects of sodium bicarbonate (NaHCO3) combined with 1.5% hydrogen peroxide (H2O2) and casein phosphopeptide amorphous calcium phosphate fluoride (CPP-ACPF) on color and microhardness of enamel. Material and Methods Seventy-five bovine incisors were immersed in a tea solution for 7.5 days. The specimens were randomly divided into five groups according to the whitening agent applied: 1) 94% NaHCO3, 2) a blend of 94% NaHCO3 and CPP-ACPF, 3) a blend of 94% NaHCO3 and 1.5% H2O2, 4) a blend of 94% NaHCO3, 1.5% H2O2 and CPP-ACPF, 5) control. The whitening procedure was performed for 10 times over 10 days. At each day, the buccal surfaces were covered with whitening agents for 5 minutes and then brushed for 30 seconds. After the 10 days, the teeth were again immersed in a tea solution for 10 minutes. Color assessment was performed at baseline (T1), after the first staining process (T2), after the whitening procedure (T3), and after the second staining process (T4). Finally, the specimens were subjected to microhardness test. Results There was a statistically significant difference in the color change between T2 and T3 stages among the study groups (p<0.05), with the greatest improvement observed in group 4. Microhardness was significantly greater in groups 2 and 4, as compared to the other groups (p<0.05). Conclusions The combination of 94% NaHCO3, 1.5% H2O2 and CPP-ACPF was effective in improving color and microhardness of teeth with extrinsic stains and could be recommended in the clinical situation.

  3. The ergogenic effect of beta-alanine combined with sodium bicarbonate on high-intensity swimming performance.

    Science.gov (United States)

    Painelli, Vitor de Salles; Roschel, Hamilton; Jesus, Flávia de; Sale, Craig; Harris, Roger Charles; Solis, Marina Yázigi; Benatti, Fabiana Braga; Gualano, Bruno; Lancha, Antonio Herbert; Artioli, Guilherme Giannini

    2013-05-01

    We investigated the effect of beta-alanine (BA) alone (study A) and in combination with sodium bicarbonate (SB) (study B) on 100- and 200-m swimming performance. In study A, 16 swimmers were assigned to receive either BA (3.2 g·day(-1) for 1 week and 6.4 g·day(-1) for 4 weeks) or placebo (PL; dextrose). At baseline and after 5 weeks of supplementation, 100- and 200-m races were completed. In study B, 14 were assigned to receive either BA (3.2 g·day(-1) for 1 week and 6.4 g·day(-1) for 3 weeks) or PL. Time trials were performed once before and twice after supplementation (with PL and SB), in a crossover fashion, providing 4 conditions: PL-PL, PL-SB, BA-PL, and BA-SB. In study A, BA supplementation improved 100- and 200-m time-trial performance by 2.1% (p = 0.029) and 2.0% (p = 0.0008), respectively. In study B, 200-m time-trial performance improved in all conditions, compared with presupplementation, except the PL-PL condition (PL-SB, +2.3%; BA-PL, +1.5%; BA-SB, +2.13% (p supplementation. The probability of BA having a positive effect was 65.2%; when SB was added to BA, the probability was 71.8%. BA and SB supplementation improved 100- and 200-m swimming performance. The coingestion of BA and SB induced a further nonsignificant improvement in performance.

  4. Profiling of differentially expressed genes in haemophilia A with inhibitor.

    Science.gov (United States)

    Hwang, S H; Lim, J A; Kim, M J; Kim, H C; Lee, H W; Yoo, K Y; You, C W; Lee, K S; Kim, H S

    2012-05-01

    Inhibitor development is the most significant complication in the therapy of haemophilia A (HA) patients. In spite of many studies, not much is known regarding the mechanism underlying inhibitor development. To understand the mechanism, we analysed profiles of differentially expressed genes (DEGs) between inhibitor and non-inhibitor HA via a microarray technique. Twenty unrelated Korean HAs were studied: 11 were non-inhibitor and nine were HA with inhibitor (≥5 BU mL(-1)). Microarray analysis was conducted using a Human Ref-8 expression Beadchip system (Illumina) and the data were analysed using Beadstudio software. We identified 545 DEGs in inhibitor HA as compared with the non-inhibitor patients; 384 genes were up-regulated and 161 genes were down-regulated. Among them, 75 genes whose expressions were altered by at least two-fold (>+2 or genes differed significantly in the two groups. For validation of the DEGs, semi-quantitative RT-PCR (semi-qRT-PCR) was conducted with the six selected DEGs. The results corresponded to the microarray data, with the exception of one gene. We also examined the expression of the genes associated with the antigen presentation process via real-time PCR. The average levels of IL10, CTLA4 and TNFα slightly reduced, whereas that of IFNγ increased in the inhibitor HA group. We are currently unable to explain whether this phenomenon is a function of the inhibitor-inducing factor or is an epiphenomenon of antibody production. Nevertheless, our results provide a possible explanation for inhibitor development.

  5. Corrosion inhibitors for intermediate cooling systems

    Energy Technology Data Exchange (ETDEWEB)

    Falk, I.; Suhr, L.

    1985-04-01

    The selected inhibitors were tested for heat and radiation stability and corrosion protection on the bench scale. Based on the results from these tests two of the products were selected, Bycoguard 81 and Bycoguard MP4S for continuing corrosion tests in an autoclave loop at 90 degrees C and 120 degrees C. Oxygen saturated deionized water with an addition of 1 ppm chloride was recirculated in the loop. Samples of copper and carbon steel were exposed to the water in the autoclave for periods up to 10 weeks. The purpose of this project was to find a substitute for hydrazine and chromates. Besides good corrosion protection qualities the toxic and environmental effect of the inhibitors should be minimal. The investigation has shown that the copper inhibitor BTA (benzotriazole) loses its corrosion protection qualities at a water temperature of 120 degrees C. The protection effects at 90 degrees C were satisfactory for both of the materials. The corrosion rates measured were 0.01 mm/y or less for the copper and carbon steel samples. The environment in the autoclave during the testing was more corrosive than is to be found in intermediate cooling systems. Due to the low corrosion rates measured the two inhibitors are to be recommended as alternatives to hydrazine and chromates.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 = <2.5 and Ωar = 1.1-1.5, where calcification of new 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

  11. 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

  12. 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.

  13. 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.

  14. Production of ribitol by alginate-immobilized

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, E.C.; Molina, M.C.; Pedrosa, M.M.; Solas, M.T.; vicente, C.; Legaz, M.E. [Laboratorio de Fisiologia, Facultad de Biologia, Madrid (Spain)

    1995-12-01

    Cells of the lichen Cladonia verticillatis have been immobilized in calcium alginate and incubated for 15 days in light on different con centrations of sodium bicarbonate in order to produce lichen polyols. Sugars and polyols secreted to the medium were extracted and analyzed by HPLC. Production and secretion of both ribitol and glucose were very high by entrapped cells incubated on 10 mM sodium bicarbonate but the replacement of calcium by sodium in the alginate matrix produced the disorganization of the immobilized system in a period no longer tan 5 days. however, incubation of the entrapped cells on 1 mM sodium bicarbonate preserved the structure of the innert matrix although only ribitol was produced and secreted to the medium. Entrapment in sodium alginate maintained cell vitality although chloroplast disorganization of the phycobiont became evident. Moreover, contact between myco- and phycobiont has also been altered during immobilization since algal ribitol was not converted into mannitol by the fungal partner. 19 refs.

  15. 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.

  16. 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.

  17. 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−.

  18. Use of potassium bicarbonate (Armicarb) on the control of powdery mildew (Sphaerotheca mors-uvae) of gooseberry (Ribes uva-crispa).

    Science.gov (United States)

    Wenneker, M; Kanne, J

    2010-01-01

    Powdery mildew (Sphaerotheca mors-uvae) severely infects young shoots, stems and fruits of gooseberry (Ribes uva-crispa). Environmental friendly and biological control measures are being sought throughout the world. Especially in organic gooseberry growing effective control measures are needed, because powdery mildew infections may result in a total loss of the crop. In organic currant growing the number of adequate control methods is very limited. Sulphur as a fungicide against powdery mildew in e.g. gooseberry or table grape growing is not recommendable due to possible bleaching of berries and scorching of tender shoots. Various bicarbonate salts are suggested as a good option to control powdery mildew. In a field trial the effect of potassium bicarbonate (Armicarb) on the on the control of powdery mildew of gooseberry was evaluated. Four treatments; i.e. two preventive strategies and two curative strategies, were applied. PLants were sprayed until runoff. The percent of infected fruits and disease severity were assessed. In the unsprayed control plots very high disease incidences were observed; on average more than 90% of the berries were infected with powdery mildew. The weekly (preventive) spray applications with potassium carbonate reduced the disease incidences on fruits significantly. On average approximately 10% of the fruits were affected by powdery mildew. However, the number of spray applications was high. In conclusion, our results indicate that applications of potassium bicarbonate (as Armicarb) are effective in reducing the incidence and severity of American powdery mildew in gooseberry. Early spray applications are necessary to protect berries against powdery mildew infections. Future research will focus on reducing the number of applications, e.g. warning models based on powdery mildew of rose (Sphaerotheca pannosa).

  19. A five way crossover human volunteer study to compare the pharmacokinetics of paracetamol following oral administration of two commercially available paracetamol tablets and three development tablets containing paracetamol in combination with sodium bicarbonate or calcium carbonate.

    Science.gov (United States)

    Grattan, T; Hickman, R; Darby-Dowman, A; Hayward, M; Boyce, M; Warrington, S

    2000-05-01

    This report concerns a single dose randomized five way crossover study to compare the pharmacokinetics of paracetamol from two commercially available paracetamol (500 mg) tablets and three different development paracetamol (500 mg) tablet formulations containing either sodium bicarbonate (400 mg), sodium bicarbonate (630 mg) or calcium carbonate (375 mg). The results demonstrated that addition of sodium bicarbonate (630 mg) to paracetamol tablets, increased the rate of absorption of paracetamol relative to conventional paracetamol tablets and soluble paracetamol tablets. Addition of sodium bicarbonate (400 mg) to paracetamol tablets increased the absorption rate of paracetamol relative to conventional paracetamol tablets, but there was no difference in the rate of absorption compared to soluble paracetamol tablets. Inclusion of calcium carbonate (375 mg) to paracetamol tablets had no effect on absorption kinetics compared to the conventional paracetamol tablet. The faster absorption observed for the sodium bicarbonate formulations may be as a result of an increase in gastric emptying rate leading to faster transport of paracetamol to the small intestine where absorption takes place.

  20. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    OpenAIRE

    Čolović, Mirjana B.; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are appl...

  1. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.;

    2004-01-01

    Proteins that inhibit alpha-amylases have been isolated from plants and microorganisms. These inhibitors can have natural roles in the control of endogenous a-amylase activity or in defence against pathogens and pests; certain inhibitors are reported to be antinutritional factors. The alpha-amylase...... inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha-amylases...... in complex with inhibitors from five families. These structures indicate major diversity but also some similarity in the structural basis of alpha-amylase inhibition. Mutational analysis of the mechanism of inhibition was performed in a few cases and various protein engineering and biotechnological...

  2. Proteinase inhibitors in Brazilian leguminosae

    Directory of Open Access Journals (Sweden)

    C. A. M. Sampaio

    1991-01-01

    Full Text Available Serine proteinase inhitors, in the seeds of several Leguminosae from the Pantanal region (West Brazil, were studied using bovine trypsin, a digestive enzyme, Factor XIIa and human plasma Kallikrein, two blood clotting factors. The inhibitors were purified from Enterolobium contortisiliquum (Mr=23,000, Torresea cearensis (Mr = 13,000, Bauhinia pentandra (Mr = 20,000 and Bauhinia bauhinioides (Mr = 20,000. E. contortisiliquum inhibitor inactivates all three enzymes, whereas the T. cearensis inhibitor inactivates trypsin and Factor XSSa, but does nor affect plasma kallikrein; both Bauhinia inhibitors, on the other hand, inactivate trypsin and plasma kallikrein but only the Bpentandra inhibitor affects Factor XIIa. Ki values were calculated between 10 [raised to the power of] -7 and 10 [raised to the power of] -8 M.

  3. Ménage-à-trois: The ratio of bicarbonate to CO2 and the pH regulate the capacity of neutrophils to form NETs

    Directory of Open Access Journals (Sweden)

    Christian Maueröder

    2016-12-01

    Full Text Available In this study we identified and characterized the potential of a high ratio of bicarbonate to CO2 and a moderately alkaline pH to render neutrophils prone to undergo neutrophil extracellular trap (NET formation. Both experimental settings increased the rate of spontaneous NET release and potentiated the NET-inducing capacity of phorbol esters (PMA, ionomycin, monosodium urate and LPS. In contrast, an acidic environment impaired neutrophil extracellular trap formation both spontaneous and induced. Our findings indicate that intracellular alkalinization of neutrophils in response to an alkaline environment leads to an increase of intracellular calcium and neutrophil activation. We further found that the anion channel blocker DIDS strongly reduced NET formation induced by bicarbonate. This finding suggests that the effects observed are due to a molecular program that renders neutrophils susceptible to neutrophil extracellular trap formation. Inflammatory foci are characterized by an acidic environment. Our data indicates that NET formation is favored by the higher pH at the border regions of inflamed areas. Moreover our findings highlight the necessity for strict pH control during assays of neutrophil extracellular trap formation.

  4. Influences of Temperature and pH Value on the Corrosion Behaviors of X80 Pipeline Steel in Carbonate/Bicarbonate Buffer Solution