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Sample records for 3-hydroxy zinc salt

  1. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-,...

  2. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-,...

  3. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-,...

  4. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-,...

  5. 40 CFR 721.5252 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, zinc salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-methylenebis [3-hydroxy-, zinc salt. 721.5252 Section 721.5252 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-,...

  6. 40 CFR 721.5253 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, strontium salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-methylenebis [3-hydroxy-, strontium salt. 721.5253 Section 721.5253 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, strontium salt. (a) Chemical substance and significant new uses subject to reporting...-, strontium salt (PMN P-99-1341; CAS No. 235083-90-6) is subject to reporting under this section for...

  7. 40 CFR 721.5253 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, strontium salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-methylenebis [3-hydroxy-, strontium salt. 721.5253 Section 721.5253 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, strontium salt. (a) Chemical substance and significant new uses subject to reporting...-, strontium salt (PMN P-99-1341; CAS No. 235083-90-6) is subject to reporting under this section for...

  8. 40 CFR 721.5253 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, strontium salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-methylenebis [3-hydroxy-, strontium salt. 721.5253 Section 721.5253 Protection of Environment ENVIRONMENTAL...′-methylenebis [3-hydroxy-, strontium salt. (a) Chemical substance and significant new uses subject to reporting...-, strontium salt (PMN P-99-1341; CAS No. 235083-90-6) is subject to reporting under this section for...

  9. 40 CFR 721.5253 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, strontium salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...′-methylenebis [3-hydroxy-, strontium salt. (a) Chemical substance and significant new uses subject to reporting...-methylenebis [3-hydroxy-, strontium salt. 721.5253 Section 721.5253 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL...

  10. 40 CFR 721.5253 - 2-Naphthalenecarboxylic acid, 4,4′-methylenebis [3-hydroxy-, strontium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...′-methylenebis [3-hydroxy-, strontium salt. (a) Chemical substance and significant new uses subject to reporting...-methylenebis [3-hydroxy-, strontium salt. 721.5253 Section 721.5253 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL...

  11. 40 CFR 721.10689 - Organo zinc salts (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Organo zinc salts (generic). 721.10689... Substances § 721.10689 Organo zinc salts (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as organo zinc salts (PMN...

  12. Comparative toxicity of a zinc salt, zinc powder and zinc oxide to Eisenia fetida, Enchytraeus albidus and Folsomia candida.

    PubMed

    Lock, Koen; Janssen, Colin R

    2003-12-01

    The pore water zinc concentration and the calcium chloride extracted zinc fraction are higher in the soils spiked with a zinc salt (ZnCl2) compared to soils spiked with zinc oxide or zinc powder. Based on total zinc concentrations in the soil, the acute toxicity of zinc salt to the compost worm Eisenia fetida, the potworm Enchytraeus albidus and the springtail Folsomia candida was lower compared to zinc oxide and zinc powder. However, when expressed on the basis of pore water concentrations or calcium chloride extracted fractions, acute toxicity was higher for zinc salt, which indicated that dermal uptake via the pore water is not the only route of uptake. Chronic toxicity of zinc salt, zinc oxide and zinc powder was similar when based on total concentrations in the soil which again indicates that the pore water route of uptake is not the only route of exposure but that oral uptake is also important.

  13. 40 CFR 180.1285 - Polyoxin D zinc salt; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Polyoxin D zinc salt; exemption from... FOOD Exemptions From Tolerances § 180.1285 Polyoxin D zinc salt; exemption from the requirement of a... zinc salt in or on all food commodities when applied as a fungicide and used in accordance with...

  14. 40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN...

  15. 40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN...

  16. 40 CFR 180.1285 - Polyoxin D zinc salt; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Polyoxin D zinc salt; exemption from... FOOD Exemptions From Tolerances § 180.1285 Polyoxin D zinc salt; exemption from the requirement of a... zinc salt in or on all food commodities when applied as a fungicide and used in accordance with...

  17. 40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN...

  18. 40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN...

  19. 40 CFR 721.3032 - Boric acid (H3BO2), zinc salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid (H3BO2), zinc salt. 721... Substances § 721.3032 Boric acid (H3BO2), zinc salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO2), zinc salt (PMN...

  20. 40 CFR 180.1285 - Polyoxin D zinc salt; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Polyoxin D zinc salt; exemption from... FOOD Exemptions From Tolerances § 180.1285 Polyoxin D zinc salt; exemption from the requirement of a... biochemical pesticide polyoxin D zinc when used as a fungicide on almonds, cucurbit vegetables,...

  1. 40 CFR 180.1285 - Polyoxin D zinc salt; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Polyoxin D zinc salt; exemption from... FOOD Exemptions From Tolerances § 180.1285 Polyoxin D zinc salt; exemption from the requirement of a... biochemical pesticide polyoxin D zinc when used as a fungicide on almonds, cucurbit vegetables,...

  2. 40 CFR 180.1285 - Polyoxin D zinc salt; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Polyoxin D zinc salt; exemption from... FOOD Exemptions From Tolerances § 180.1285 Polyoxin D zinc salt; exemption from the requirement of a... biochemical pesticide polyoxin D zinc when used as a fungicide on almonds, cucurbit vegetables,...

  3. Synergism of organic zinc salts and sulfhydryl compounds (thiols) in the protection of mice against acute ethanol toxicity, and protective effects of various metal salts.

    PubMed

    Floersheim, G L

    1987-06-01

    Organic zinc salts such as zinc aspartate, zinc orotate, zinc histidine and zinc acetate protected mice against the lethality of an acute intraperitoneal challenge with ethanol. A similar activity was also provided by salts of cobalt, zirconium, lithium and magnesium. Organic zinc salts acted synergistically with sulfhydryl compounds in protecting the mice and potentiation between the two categories of agents was seen. The results are in analogy to radioprotective effects by zinc and thiols and imply that organic zinc salts may, alone or in conjunction with thiols, reduce in a wider context tissue injury caused by free radical-mediated mechanisms. PMID:3630856

  4. 40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN...

  5. 40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN...

  6. 40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN...

  7. 40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN...

  8. 40 CFR 721.3031 - Boric acid (H3BO3), zinc salt (2=3).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Boric acid (H3BO3), zinc salt (2=3... Substances § 721.3031 Boric acid (H3BO3), zinc salt (2=3). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as boric acid (H3BO3), zinc salt (2=3) (PMN...

  9. 40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting...

  10. 40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting...

  11. 40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting...

  12. 40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting...

  13. 40 CFR 721.10135 - Phosphinic acid, P,P-diethyl-, zinc salt (2:1).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphinic acid, P,P-diethyl-, zinc... Specific Chemical Substances § 721.10135 Phosphinic acid, P,P-diethyl-, zinc salt (2:1). (a) Chemical... acid, P,P-diethyl-, zinc salt (2:1) (PMN P-05-11; CAS No. 284685-45-6) is subject to reporting...

  14. Zinc Salts Inactivate Clinical Isolates of Herpes Simplex Virus In Vitro

    PubMed Central

    Arens, Max; Travis, Sharon

    2000-01-01

    Using a standard plaque assay and clinical isolates of herpes simplex virus (HSV), we have tested the ability of zinc salts to inactivate HSV. Virus was treated by incubation at 37°C with zinc salts in morpholinepropanesulfonic acid-buffered culture medium and was then diluted and plated onto CV-1 cells for detection and quantitation of remaining infectious virus. Of 10 randomly chosen clinical isolates (five HSV type 1 [HSV-1] isolates and five HSV-2 isolates), seven were inactivated >98% by treatment in vitro with 50 mM zinc gluconate for 2 h and nine were inactivated >97% by treatment with zinc lactate. The effect was concentration dependent. With an HSV-1 isolate, 50 mM zinc gluconate or zinc lactate caused 100% inactivation, 15 mM caused 98 to 99% inactivation, and 5 mM caused 63 to 86% inactivation. With an HSV-2 isolate, 50 and 15 mM zinc gluconate caused 30% inactivation and 5 and 1 mM caused less than 9% inactivation, whereas 50 and 15 mM zinc lactate caused greater than 92% inactivation and 5 and 1 mM caused 37 and 26% inactivation, respectively. The ability of the zinc salts to inactivate HSV was not related to pH in the pH range of 6.1 to 7.6 since inactivation by zinc gluconate or zinc lactate in that pH range was 99.7 to 100% with a 2-h treatment with 50 mM zinc salt. Short (5-min) treatments of selected isolates with zinc gluconate, zinc lactate, zinc acetate, or zinc sulfate yielded inactivation rates of 0 to 55%. PMID:10790094

  15. Cryptococcal 3-Hydroxy Fatty Acids Protect Cells Against Amoebal Phagocytosis.

    PubMed

    Madu, Uju L; Ogundeji, Adepemi O; Mochochoko, Bonang M; Pohl, Carolina H; Albertyn, Jacobus; Swart, Chantel W; Allwood, J William; Southam, Andrew D; Dunn, Warwick B; May, Robin C; Sebolai, Olihile M

    2015-01-01

    We previously reported on a 3-hydroxy fatty acid that is secreted via cryptococcal capsular protuberances - possibly to promote pathogenesis and survival. Thus, we investigated the role of this molecule in mediating the fate of Cryptococcus (C.) neoformans and the related species C. gattii when predated upon by amoebae. We show that this molecule protects cells against the phagocytic effects of amoebae. C. neoformans UOFS Y-1378 (which produces 3-hydroxy fatty acids) was less sensitive toward amoebae compared to C. neoformans LMPE 046 and C. gattii R265 (both do not produce 3-hydroxy fatty acids) and addition of 3-hydroxy fatty acids to C. neoformans LMPE 046 and C. gattii R265 culture media, causes these strains to become more resistant to amoebal predation. Conversely, addition of aspirin (a 3-hydroxy fatty acid inhibitor) to C. neoformans UOFS Y-1378 culture media made cells more susceptible to amoebae. Our data suggest that this molecule is secreted at a high enough concentration to effect intracellular signaling within amoeba, which in turn, promotes fungal survival. PMID:26696972

  16. Cryptococcal 3-Hydroxy Fatty Acids Protect Cells Against Amoebal Phagocytosis

    PubMed Central

    Madu, Uju L.; Ogundeji, Adepemi O.; Mochochoko, Bonang M.; Pohl, Carolina H.; Albertyn, Jacobus; Swart, Chantel W.; Allwood, J. William; Southam, Andrew D.; Dunn, Warwick B.; May, Robin C.; Sebolai, Olihile M.

    2015-01-01

    We previously reported on a 3-hydroxy fatty acid that is secreted via cryptococcal capsular protuberances - possibly to promote pathogenesis and survival. Thus, we investigated the role of this molecule in mediating the fate of Cryptococcus (C.) neoformans and the related species C. gattii when predated upon by amoebae. We show that this molecule protects cells against the phagocytic effects of amoebae. C. neoformans UOFS Y-1378 (which produces 3-hydroxy fatty acids) was less sensitive toward amoebae compared to C. neoformans LMPE 046 and C. gattii R265 (both do not produce 3-hydroxy fatty acids) and addition of 3-hydroxy fatty acids to C. neoformans LMPE 046 and C. gattii R265 culture media, causes these strains to become more resistant to amoebal predation. Conversely, addition of aspirin (a 3-hydroxy fatty acid inhibitor) to C. neoformans UOFS Y-1378 culture media made cells more susceptible to amoebae. Our data suggest that this molecule is secreted at a high enough concentration to effect intracellular signaling within amoeba, which in turn, promotes fungal survival. PMID:26696972

  17. Cryptococcal 3-Hydroxy Fatty Acids Protect Cells Against Amoebal Phagocytosis.

    PubMed

    Madu, Uju L; Ogundeji, Adepemi O; Mochochoko, Bonang M; Pohl, Carolina H; Albertyn, Jacobus; Swart, Chantel W; Allwood, J William; Southam, Andrew D; Dunn, Warwick B; May, Robin C; Sebolai, Olihile M

    2015-01-01

    We previously reported on a 3-hydroxy fatty acid that is secreted via cryptococcal capsular protuberances - possibly to promote pathogenesis and survival. Thus, we investigated the role of this molecule in mediating the fate of Cryptococcus (C.) neoformans and the related species C. gattii when predated upon by amoebae. We show that this molecule protects cells against the phagocytic effects of amoebae. C. neoformans UOFS Y-1378 (which produces 3-hydroxy fatty acids) was less sensitive toward amoebae compared to C. neoformans LMPE 046 and C. gattii R265 (both do not produce 3-hydroxy fatty acids) and addition of 3-hydroxy fatty acids to C. neoformans LMPE 046 and C. gattii R265 culture media, causes these strains to become more resistant to amoebal predation. Conversely, addition of aspirin (a 3-hydroxy fatty acid inhibitor) to C. neoformans UOFS Y-1378 culture media made cells more susceptible to amoebae. Our data suggest that this molecule is secreted at a high enough concentration to effect intracellular signaling within amoeba, which in turn, promotes fungal survival.

  18. The effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in hemodialysis patients.

    PubMed

    Kim, So Mi; Kim, Miyeon; Lee, Eun Kyoung; Kim, Soon Bae; Chang, Jai Won; Kim, Hyun Woo

    2016-07-01

    Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross-sectional study. Zinc deficiency was defined as serum zinc level with below 70 µg/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3-day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non-zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (r = 0.43, P = 0.002). Although, the dietary sodium intake showed a high tendency with no significance (P = 0.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non-zinc deficient group (2.68 ± 1.02 kg vs. 3.18 ± 1.02 kg; P = 0.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients.

  19. The CCCH zinc finger protein gene AtZFP1 improves salt resistance in Arabidopsis thaliana.

    PubMed

    Han, Guoliang; Wang, Mingjie; Yuan, Fang; Sui, Na; Song, Jie; Wang, Baoshan

    2014-10-01

    The CCCH type zinc finger proteins are a super family involved in many aspects of plant growth and development. In this study, we investigated the response of one CCCH type zinc finger protein AtZFP1 (At2g25900) to salt stress in Arabidopsis. The expression of AtZFP1 was upregulated by salt stress. Compared to transgenic strains, the germination rate, emerging rate of cotyledons and root length of wild plants were significantly lower under NaCl treatments, while the inhibitory effect was significantly severe in T-DNA insertion mutant strains. At germination stage, it was mainly osmotic stress when treated with NaCl. Relative to wild plants, overexpression strains maintained a higher K(+), K(+)/Na(+), chlorophyll and proline content, and lower Na(+) and MDA content. Quantitative real-time PCR analysis revealed that the expression of stress related marker genes KIN1, RD29B and RD22 increased more significantly in transgenic strains by salt stress. Overexpression of AtZFP1 also enhanced oxidative and osmotic stress tolerance which was determined by measuring the expression of a set of antioxidant genes, osmotic stress genes and ion transport protein genes such as SOS1, AtP5CS1 and AtGSTU5. Overall, our results suggest that overexpression of AtZFP1 enhanced salt tolerance by maintaining ionic balance and limiting oxidative and osmotic stress.

  20. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, Kenneth N.; Xu, Jide

    1997-01-01

    Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of said chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to said 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities.

  1. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, K.N.; Xu, J.

    1997-04-29

    Disclosed is a series of improved metal chelating agents, which are highly effective upon both injection and oral administration; several of the most effective are of low toxicity. These chelating agents incorporate within their structure 1-hydroxy-2-pyridinone (1,2-HOPO) and 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy or oxo groups of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with its adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provides a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. Also disclosed is a method of making the chelating agents and a method of producing a known compound, 3-hydroxy-1-alkyl-2(1H)pyridinone, used as a precursor to the chelating agent, safely and in large quantities. 2 figs.

  2. Molecular basis of 3-hydroxy-3-methylglutaric aciduria.

    PubMed

    Pie, J; Casals, N; Puisac, B; Hegardt, F G

    2003-12-01

    3-Hydroxy-3-methylglutaric aciduria is a human autosomal recessive metabolic disorder that usually appears within the first year of life. The causes of this aciduria are lethal mutations in the gene encoding for 3-hydroxy-3-methylglutaryl coenzyme A lyase (HL). HL is a mitochondrial matrix enzyme that catalyzes the last step of ketogenesis and leucine catabolism. This gene has been mapped to chromosome 1 at locus 1pter-p33 and its genomic organisation comprises 9 exons whose sizes vary between 64-678 bp. The human cDNA sequence was reported in 1993 with the first genetic study of two Acadian-French Canadian siblings. To date, 24 mutations in 36 patients have been described; most of them are single-base substitutions causing amino acid replacements and a variety of splicing defects. In the population studied two mutations appear predominant: g.122GA (8 patients and 15 alleles) frequent in Saudi Arabia, and g.109GT (6 patients and 12 alleles), prevalent in Spain. At least seven mutations are clustered in the second half of exon 2 affecting aminoacids E37, R41 and D42 and conforming a possible hot spot. The genotype-phenotype correlation is difficult to establish since the probands received different treatments, and the onset of an acute episode frequently depends on external factors such as fasting or acute illness. PMID:15164951

  3. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, Kenneth; Xu, Jide

    1999-01-01

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity.

  4. 3-hydroxy-2(1H)-pyridinone chelating agents

    DOEpatents

    Raymond, K.; Xu, J.

    1999-04-06

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

  5. Zinc

    MedlinePlus

    ... ulcers and promoting weight gain in people with eating disorders such as anorexia nervosa. Some people use zinc ... is abnormal): 25-100 mg zinc. For the eating disorder anorexia nervosa: 100 mg of zinc gluconate daily. ...

  6. 40 CFR 721.1920 - 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. 721.1920 Section 721.1920 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.1920 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. (a) Chemical...

  7. 40 CFR 721.1920 - 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. 721.1920 Section 721.1920 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Specific Chemical Substances § 721.1920 1,4-Bis(3-hydroxy-4-benzoylphenoxy)butane. (a) Chemical...

  8. UV screening of ferulic acid-zinc basic salt nanohybrid with controlled release rate.

    PubMed

    Biswick, Timothy; Park, Dae-Hwan; Shul, Yong-Gun; Hwang, Seong-Ju; Choy, Jin-Ho

    2011-01-01

    Ferulic acid (FA), an organic UV absorber and free radical scavenger, was intercalated into an inorganic zinc basic salt (ZBS) matrix to prepare a UV screening material. FA molecules were vertically oriented bilayer in the ZBS lattice with an expansion of approximately 22.7 angstroms along the c-axis. The FA-ZBS nanohybrid exhibited a superior UV-A approximately UV-B screening ability and an antioxidant activity that was comparable to that of a pure FA molecule. The in vitro release test showed the biphasic release of the FA molecules from the FA-ZBS nanohybrid that consisted of an initial burst, followed by a slow and sustained release. PMID:21446466

  9. Zinc.

    PubMed

    Barceloux, D G

    1999-01-01

    The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound healing. Zinc is a relatively common metal with an average concentration of 50 mg/kg soil and a range of 10-300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recommended daily allowance for adults is 15 mg zinc. The ingestion of 1-2 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and interstitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent. PMID:10382562

  10. Purification, stability, and mineralization of 3-hydroxy-2- formylbenzothiophene, a metabolite of dibenzothiophene.

    PubMed

    Bressler, D C; Fedorak, P M

    2001-02-01

    3-Hydroxy-2-formylbenzothiophene (HFBT) is a metabolite found in many bacterial cultures that degrade dibenzothiophene (DBT) via the Kodama pathway. The fate of HFBT in cultures and in the environment is unknown. In this study, HFBT was produced by a DBT-degrading bacterium and purified by sublimation. When stored in organic solvent or as a crystal, the HFBT slowly decomposed, yielding colored products. Two of these were identified as thioindigo and cis-thioindigo. The supernatant of the DBT-degrading culture contained thioindigo, which has not been reported previously as a product of DBT biodegradation. In mineral salts medium, HFBT was sufficiently stable to allow biodegradation studies with a mixed microbial culture over a 3- to 4-week period. High-performance liquid chromatography analyses showed that HFBT was removed from the medium. 2-Mercaptophenylglyoxalate, detected as benzothiophene-2,3-dione, was found in an HFBT-degrading mixed culture, and the former appears to be a metabolite of HFBT. This mixed culture also mineralized HFBT to CO2. PMID:11157249

  11. Rare earth and zinc layered hydroxide salts intercalated with the 2-aminobenzoate anion as organic luminescent sensitizer

    SciTech Connect

    Cursino, Ana Cristina Trindade; Rives, Vicente; Trujillano, Raquel

    2015-10-15

    Rare earth (RE = Eu, Y and Tb) and zinc layered hydroxide salts intercalated with nitrate anions were synthesized, followed by exchange with 2-aminobenzoate. The UV absorption ability was improved after intercalation/grafting in relation to that shown by the parent material. - Highlights: • Rare earth (RE = Eu, Y and Tb) and zinc layered hydroxide were synthesized. • Intercalated nitrate anions were exchanged by 2-aminobenzoate. • In all the 2-aminobenzoate containing compounds, the grafting reaction was detected. • The UV absorption ability was improved after the exchange reactions. • Rare earth hydroxide salts are potential matrixes to produce luminescent materials. - Abstract: Rare earth (RE = Eu, Y and Tb) and zinc layered hydroxide salts intercalated with nitrate anions were synthesized, followed by exchange with 2-aminobenzoate. The obtained compounds were characterized by powder X-ray diffraction (PXRD), Fourier transform infrared (FTIR) and ultraviolet visible (UV–vis) spectroscopies, fluorescence measurements and thermal analysis (TGA/DTA). The results from FTIR spectroscopy suggest a direct coordination of 2-aminobenzoate to the metal cations of the inorganic layered structure. The organic derivative products from the intercalation reactions absorb a broader range of UV-light in relation to that shown by the parent material; the photoluminescence measurements present a strong violet, blue and green luminescence under UV-light excitation for layered compounds with, Zn, Y and Tb, respectively. Rare earth hydroxide salts (RE-LHS) are potential alternative matrices for the immobilization of organic species to produce luminescent materials.

  12. Homochiral frameworks derived from magnesium, zinc and copper salts of L-tartaric acid

    SciTech Connect

    Rood, Jeffrey A.; Noll, Bruce C.; Henderson, Kenneth W.

    2010-01-15

    Five metal-organic frameworks derived from L-tartarate (L-tart=C{sub 4}H{sub 4}O{sub 6}) and the divalent metal ions magnesium, zinc or copper have been prepared and structurally characterized. The frameworks were prepared from the reaction of potassium L-tartrate [KC{sub 4}H{sub 5}O{sub 6}] with the appropriate metal salt in water solutions. The magnesium compound [Mg(L-tart)(H{sub 2}O) contains 1.5H{sub 2}O], 1, crystallizes as a two-dimensional 6{sup 3} sheet structure. The addition of the divergent linker molecules 4,4'-bipyridine (bipy) or trans-1,2-bispyridylethylene (bpe) to systems involving Zn{sup 2+} and Cu{sup 2+} results in the formation of the homochiral three-dimensional structures [Zn{sub 2}(L-tart)2(biyp)(H{sub 2}O) contains 5.25H{sub 2}O], 2, [Cu(L-tart)(bipy) contains 2.33H{sub 2}O], 3, and [Cu(L-tart)(bpe) contains 8H{sub 2}O], 5. Removal of solvent water molecules from 3 resulted in [Cu(L-tart)(bipy) contains 0.2H{sub 2}O], 4. Similar experiments on 2 and 5 resulted in breakdown of the frameworks, illustrating the dependence of the stability of these structures on the guest water molecules. This study reports the structures of two new topological types of binodal nets. - Five metal-organic frameworks derived from L-tartarate and the divalent metal ions magnesium, zinc or copper have been prepared and structurally characterized. Significant structural diversity is displayed within this set of complexes.

  13. 40 CFR 180.296 - Dimethyl phosphate of 3-hydroxy-N-methyl-cis-crotonamide; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Dimethyl phosphate of 3-hydroxy-N... RESIDUES IN FOOD Specific Tolerances § 180.296 Dimethyl phosphate of 3-hydroxy-N-methyl-cis-crotonamide... phosphate of 3-hydroxy-N-methyl-cis-crotonamide in or on the following raw agricultural...

  14. (Z)-2-(3-hydroxy-4-methoxybenzylidene)-1-azabicyclo[2.2.2]octan-3-one.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2003-11-01

    Crystals of the title compound, C(15)H(17)NO(3), were obtained from a condensation reaction of 3-hydroxy-4-methoxybenzaldehyde with 1-azabicyclo[2.2.2]octan-3-one and subsequent crystallization of the product from methanol. The title compound, containing a double bond that connects the azabicyclic ring system to the 3-hydroxy-4-methoxybenzylidene group, was obtained with Z geometry.

  15. The salt-sensitive structure and zinc inhibition of Borrelia burgdorferi protease BbHtrA.

    PubMed

    Russell, Theresa M; Tang, Xiaoling; Goldstein, Jason M; Bagarozzi, Dennis; Johnson, Barbara J B

    2016-02-01

    HtrA serine proteases are highly conserved and essential ATP-independent proteases with chaperone activity. Bacteria express a variable number of HtrA homologues that contribute to the virulence and pathogenicity of bacterial pathogens. Lyme disease spirochetes possess a single HtrA protease homologue, Borrelia burgdorferi HtrA (BbHtrA). Previous studies established that, like the human orthologue HtrA1, BbHtrA is proteolytically active against numerous extracellular proteins in vitro. In this study, we utilized size exclusion chromatography and blue native polyacrylamide gel electrophoresis (BN-PAGE) to demonstrate BbHtrA oligomeric structures that were substrate independent and salt sensitive. Examination of the influence of transition metals on the activity of BbHtrA revealed that this protease is inhibited by Zn(2+) > Cu(2+) > Mn(2+). Extending this analysis to two other HtrA proteases, E. coli DegP and HtrA1, revealed that all three HtrA proteases were reversibly inhibited by ZnCl2 at all micro molar concentrations examined. Commercial inhibitors for HtrA proteases are not available and physiologic HtrA inhibitors are unknown. Our observation of conserved zinc inhibition of HtrA proteases will facilitate structural and functional studies of additional members of this important class of proteases. PMID:26480895

  16. Lead, zinc, and strontium in limestone cap rock from Tatum salt dome, Mississippi

    SciTech Connect

    Saunders, J.A.

    1988-09-01

    Limestone cap rock at Tatum salt dome, Mississippi, contains disseminated pyrite, sphalerite, and galena, and disseminated to massive amounts of strontianite (SrCO/sub 3/) and celestite (SrSO/sub 4/). Sulfide minerals are locally present in bitumen-rich areas of the upper, massive portion of the limestone cap rock, whereas strontium minerals are disseminated throughout this zone. However, sulfide and strontium minerals are most abundant in the lower banded portion of the limestone cap rock, which consists of alternating subhorizontal light and dark-colored bands. The dark bands are composed of calcite of variable grain size, sulfides, quartz, dolomite, albite, and up to 1% bitumen that apparently formed by the biodegradation of crude oil. Lighter bands are composed of variable amounts of coarsely crystalline, euhedral calcite, strontianite, and celestite resulting in strontium (Sr) contents of up to 30% locally. Banded limestone cap rock at Tatum dome formed at the top of the actively dissolving anhydrite zone by a combination of sulfate reduction and oxidation of liquid hydrocarbons by bacteria to cause the precipitation of calcite and sulfide minerals and the accumulation of insoluble residue from the anhydrite (quartz, albite, dolomite). Lead and zinc in the sulfide minerals could have been derived from the dissolving anhydrite, but the abundance of Sr minerals present requires an external source. Present-day oil field brines in central Mississippi contain up to 3000 ppm Sr, and basin brines of similar composition apparently contributed Sr to the cap-rock environment during formation.

  17. Zinc

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zinc was recognized as an essential trace metal for humans during the studies of Iranian adolescent dwarfs in the early 1960s. Zinc metal existing as Zn2+ is a strong electron acceptor in biological systems without risks of oxidant damage to cells. Zn2+ functions in the structure of proteins and is ...

  18. Zinc

    MedlinePlus

    ... deficiency also causes hair loss, diarrhea, eye and skin sores and loss of appetite. Weight loss, problems ... pneumonia and other infections. Zinc also helps the skin stay healthy. Some people who have skin ulcers ...

  19. Salt tolerance function of the novel C2H2-type zinc finger protein TaZNF in wheat.

    PubMed

    Ma, Xiaoli; Liang, Wenji; Gu, Peihan; Huang, Zhanjing

    2016-09-01

    The expression profile chip of the wheat salt-tolerant mutant RH8706-49 was investigated under salt stress in our laboratory. Results revealed a novel gene induced by salt stress with unknown functions. The gene was named as TaZNF (Triticum aestivum predicted Dof zinc finger protein) because it contains the zf-Dof superfamily and was deposited in GenBank (accession no. KF307327). Further analysis showed that TaZNF significantly improved the salt-tolerance of transgenic Arabidopsis. Various physiological indices of the transgenic plant were improved compared with those of the control after salt stress. Non-invasive micro-test (NMT) detection showed that the root tip of transgenic Arabidopsis significantly expressed Na(+) excretion. TaZNF is mainly localized in the nucleus and exhibited transcriptional activity. Hence, this protein was considered a transcription factor. The TaZNF upstream promoter was then cloned and was found to contain three salts, one jasmonic acid methyl ester (MeJA), and several ABA-responsive elements. The GUS staining and quantitative results of different tissues in the full-length promoter in the transgenic plants showed that the promoter was not tissue specific. The promoter activity in the root, leaf, and flower was enhanced after induction by salt stress. Moreover, GUS staining and quantitative measurement of GUS activity showed that the promoter sequence contained the positive regulatory element of salt and MeJA after their respective elements were mutated in the full-length promoter. RNA-Seq result showed that 2727 genes were differentially expressed; most of these genes were involved in the metabolic pathway and biosynthesis of secondary metabolite pathway. PMID:27156137

  20. The influence of microbial associations on germination of wheat seeds and growth of seedlings under impact of zinc salts

    NASA Astrophysics Data System (ADS)

    Somova, L. A.; Pechurkin, N. S.

    2009-04-01

    The life support systems (LSS) for long-term missions are to use cycling-recycling systems, including biological recycling. Higher plants are the traditional regenerator of air and producer of food. They should be used in many successive generations of their reproduction in LSS. Studies of influence of microbial associations on germination of wheat seeds and on growth of seedlings under impact of heavy metals are necessary because of migration of heavy metals in LSS. Microbial associations are able to stimulate growth of plants, to protect them from pathogenic organisms and from toxicity of heavy metal salts. The goal of this work was to investigate effect of microbial associations on the germination of wheat seeds and on the growth of seedlings under impact of different concentrations of ZnSO4. The results of investigations showed that:Zinc salt had an adverse effect on germination of wheat seeds, beginning with concentrations of 8 MPC (Maximum Permissible Concentration) and higher.Microbial associations (concentrations -104 to 107 cells/ml) were able to decrease (partly or completely) the adverse effect of ZnSO4 on germination of wheat seeds.Concentrations (104-107 cells/ml) of microbial associations were able to decrease partly the adverse effect of zinc salts (intervals: from 1 to 32 MP?) on the growth and development of wheat plantlets during heterotrophic phase.The root system of plants was more sensitive to the adverse effect of ZnSO4 than shoots of plants.

  1. Occurrence of 3-hydroxy acids in microalgae and cyanobacteria and their geochemical significance

    NASA Astrophysics Data System (ADS)

    Matsumoto, Genki I.; Nagashima, Hideyuki

    1984-08-01

    3-Hydroxy acids were detected in pure cultured microalgae: Chlorophyta— Chlamydomonas reinhardtii and Chlorella pyrenoidosa and Rhodophyta— Cyanidium caldarium (two strains), and cyanobacteria (Cyanophyta)— Anacystis nidulans, Phormidium foveolarum, Anabaena variabilis and Oscillatoria sp. Normal and branched (iso and anteiso) 3-hydroxy acids in the ranges of C 8-C 26 were found in all the samples studied at concentrations ranging from 0.036 to 2.3 and 0.000 to 0.12 mg g -1 of dry sample, respectively. The major constituents were generally even-carbon numbered normal acids with carbon chain lengths below C 20. Microalgae and cyanobacteria may be the important sources of 3-hydroxy acids in natural environments.

  2. Central and peripheral antinociceptive activity of 3-(2-oxopropyl)-3-hydroxy-2-oxindoles.

    PubMed

    Giorno, Thais Biondino Sardella; Ballard, Yáskara L L; Cordeiro, Millena Santos; Silva, Bárbara V; Pinto, Angelo C; Fernandes, Patricia Dias

    2015-08-01

    Convolutamydine A has been shown to develop a significant antinociceptive effect. Here we demonstrated that new analogues (5-iodo-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Iisa), 5-fluoro-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Fisa), 5-chloro-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Clisa) and 5-methyl-3-(2-oxopropyl)-3-hydroxy-2-oxindole (5-Meisa)), at 0.1-10mg/kg doses, have significant peripheral and central antinociceptive effects in thermal and chemical models of nociception. Oral administered analogues demonstrated more pronounced antinociceptive effects than that obtained with the classical opioid drug morphine (5mg/kg) in the first and second phases of formalin-induced licking. In the tail flick model, 5-Clisa and 5-Meisa antinociceptive effect was almost twice as that observed with the same dose of morphine. The concomitant administration of diverse antagonists and the analogues indicates that 5-Iisa effects involve the activation of opioid pathway. On the other hand, 5-Fisa and 5-Clisa have the participation of opioid, nitrergic, cholinergic adrenergic and serotoninergic pathways and 5-Meisa has the involvement of opioid, serotoninergic and cholinergic pathways. In conclusion, our results suggest that the new four analogues from Convolutamydine A have significant antinociceptive effects in thermal and chemical induced nociception and could be used in development of new drugs to be used in pain treatment with reduced side effects. PMID:25989045

  3. Discovery of 3-Hydroxy-3-phenacyloxindole Analogues of Isatin as Potential Monoamine Oxidase Inhibitors.

    PubMed

    Tripathi, Rati K P; Krishnamurthy, Sairam; Ayyannan, Senthil R

    2016-01-01

    A series of 3-hydroxy-3-phenacyloxindole analogues of isatin were designed, synthesized, and evaluated in vitro for their inhibitory activity toward monoamine oxidase (MAO) A and B. Most of the synthesized compounds proved to be potent and selective inhibitors of MAO-A rather than MAO-B. 1-Benzyl-3-hydroxy-3-(4'-hydroxyphenacyl)oxindole (compound 18) showed the highest MAO-A inhibitory activity (IC50 : 0.009 ± 0.001 μM, Ki : 3.69 ± 0.003 nM) and good selectivity (selectivity index: 60.44). Kinetic studies revealed that compounds 18 and 16 (1-benzyl-3-hydroxy-3-(4'-bromophenacyl)oxindole) exhibit competitive inhibition against MAO-A and MAO-B, respectively. Structure-activity relationship studies suggested that the 3-hydroxy group is an essential feature for these analogues to exhibit potent MAO-A inhibitory activity. Computational studies revealed the possible molecular interactions between the inhibitors and MAO isozymes. The computational data obtained are congruent with experimental results. Further studies on the lead inhibitors, including co-crystallization of inhibitor-MAO complexes and in vivo evaluations, are essential for their development as potential therapeutic agents for the treatment of MAO-associated neurological disorders.

  4. First total synthesis of (+/-)-3-hydroxy-11-norcytisine: structure confirmation and biological characterization.

    PubMed

    Yohannes, Daniel; Hansen, Camilla P; Akireddy, Srinivasa Rao; Hauser, Terry A; Kiser, Melanie N; Gurnon, Nicholas J; Day, Cynthia S; Bhatti, Balwinder; Caldwell, William S

    2008-12-01

    The first total synthesis of the natural product 3-hydroxy-11-norcytisine (1), structurally related to cytisine (2), a benchmark ligand at neuronal nicotinic acetylcholine receptors (NNRs), has been achieved. The synthesis permits the unambiguous confirmation of the structure originally proposed for 1 and has enabled initial biological characterization of 1 and its related compounds against NNRs.

  5. Evaluation of layered zinc hydroxide nitrate and zinc/nickel double hydroxide salts in the removal of chromate ions from solutions

    NASA Astrophysics Data System (ADS)

    de Oliveira, Henrique Bortolaz; Wypych, Fernando

    2016-11-01

    Layered zinc hydroxide nitrate (ZnHN) and Zn/Ni layered double hydroxide salts were synthesized and used to remove chromate ions from solutions at pH 8.0. The materials were characterized by many instrumental techniques before and after chromate ion removal. ZnHN decomposed after contact with the chromate solution, whereas the layered structure of Zn/Ni hydroxide nitrate (Zn/NiHN) and Zn/Ni hydroxide acetate (Zn/NiHA) remained their layers intact after the topotactic anionic exchange reaction, only changing the basal distances. ZnHN, Zn/NiHN, and Zn/NiHA removed 210.1, 144.8, and 170.1 mg of CrO42-/g of material, respectively. Although the removal values obtained for Zn/NiHN and Zn/NiHA were smaller than the values predicted for the ideal formulas of the solids (194.3 and 192.4 mg of CrO42-/g of material, respectively), the measured capacities were higher than the values achieved with many materials reported in the literature. Kinetic experiments showed the removal reaction was fast. To facilitate the solid/liquid separation process after chromium removal, Zn/Ni layered double hydroxide salts with magnetic supports were also synthesized, and their ability to remove chromate was evaluated.

  6. 3-Hydroxy-3-methylglutaryl-coenzyme A synthase from ox liver. Properties of its acetyl derivative.

    PubMed Central

    Lowe, D M; Tubbs, P K

    1985-01-01

    Ox liver mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5) reacts with acetyl-CoA to form a complex in which the acetyl group is covalently bound to the enzyme. This acetyl group can be removed by addition of acetoacetyl-CoA or CoA. The extent of acetylation and release of CoA were found to be highly temperature-dependent. At temperatures above 20 degrees C, a maximum value of 0.85 mol of acetyl group bound/mol of enzyme dimer was observed. Below this temperature the extent of rapid acetylation was significantly lowered. Binding stoichiometries close to 1 mol/mol of enzyme dimer were also observed when the 3-hydroxy-3-methylglutaryl-CoA synthase activity was titrated with methyl methanethiosulphonate or bromoacetyl-CoA. This is taken as evidence for a 'half-of-the-sites' reaction mechanism for the formation of 3-hydroxy-3-methylglutaryl-CoA by 3-hydroxy-3-methylglutaryl-CoA synthase. The Keq. for the acetylation was about 10. Isolated acetyl-enzyme is stable for many hours at 0 degrees C and pH 7, but is hydrolysed at 30 degrees C with a half-life of 7 min. This hydrolysis is stimulated by acetyl-CoA and slightly by succinyl-CoA, but not by desulpho-CoA. The site of acetylation has been identified as the thiol group of a reactive cysteine residue by affinity-labelling with the substrate analogue bromo[1-14C]acetyl-CoA. PMID:2860896

  7. Enantioselective synthesis of 3-hydroxy oxindoles by ytterbium-catalysed decarboxylative addition of β-ketoacids to isatins.

    PubMed

    Duan, Zhiqiang; Han, Jianlin; Qian, Ping; Zhang, Zirui; Wang, Yi; Pan, Yi

    2013-10-14

    A ytterbium(III)-indapybox catalysed enantioselective decarboxylative addition reaction of β-ketoacids to isatins is described. The biologically important 3-hydroxy oxindoles were obtained in high yields and excellent enantioselectivities.

  8. Catalytic Asymmetric Synthesis of 3-Hydroxy-3-trifluoromethyl Benzofuranones via Tandem Friedel-Crafts/Lactonization Reaction.

    PubMed

    Ren, Hai; Wang, Pan; Wang, Lijia; Tang, Yong

    2015-10-01

    A highly enantioselective and regioselective chiral Lewis acid catalyzed tandem Friedel-Crafts/lactonization reaction is reported, providing direct access to plenty of 3-hydroxy-3-trifluoromethyl benzofuran-2-ones in up to 94% yields with up to >99% ee. Mechanistic study reveals that the interactions between the phenolic hydroxyl group and trifluoropyruvate are the most likely contributing factor to the high enantio- and regioselectivity. Optically pure (-)-BHFF can be obtained in gram-scale with 0.05 mol % catalyst, demonstrating the potentially utility of this method in medicinal chemistry. PMID:26400069

  9. Use of zinc and copper (I) salts to reduce sulfur and nitrogen impurities during the pyrolysis of plastic and rubber waste to hydrocarbons

    DOEpatents

    Wingfield, Jr., Robert C.; Braslaw, Jacob; Gealer, Roy L.

    1984-01-01

    An improvement in a process for the pyrolytic conversion of rubber and plastic waste to hydrocarbon products which results in reduced levels of nitrogen and sulfur impurities in these products. The improvement comprises pyrolyzing the waste in the presence of at least about 1 weight percent of salts, based on the weight of the waste, preferably chloride or carbonate salts, of zinc or copper (I). This invention was made under contract with or subcontract thereunder of the Department of Energy Contract #DE-AC02-78-ER10049.

  10. Synergistic cytotoxic effects of ions released by zinc-aluminum bronze and the metallic salts on osteoblastic cells.

    PubMed

    Grillo, Claudia A; Morales, María L; Mirífico, María V; Fernández Lorenzo de Mele, Mónica A

    2013-07-01

    The use of copper-based alloys for fixed dental crowns and bridges is increasingly widespread in several countries. The aim of this work is to study the dissolution of a zinc-aluminum-bronze and the cytotoxic effects of the ions released on UMR-106 osteoblastic cell line. Two sources of ions were used: (1) ions released by the metal alloy immersed in the cell culture and (2) salts of the metal ions. Conventional electrochemical techniques, atomic absorption spectroscopy [to obtain the average concentration of ions (AC) in solution], and energy dispersive X-ray (EDX) spectroscopy analysis were used to study the corrosion process. Corrosion tests revealed a strong influence of the composition of the electrolyte medium and the immersion time on the electrochemical response. The cytotoxicity was evaluated with (a) individual ions, (b) combinations of two ions, and (c) the mixture of all the ions released by a metal disc of the alloy. Importantly, synergistic cytotoxic effects were found when Al-Zn ion combinations were used at concentration levels lower than the cytotoxic threshold values of the individual ions. Cytotoxic effects in cells in the vicinity of the metal disc were also found. These results were interpreted considering synergistic effects and a diffusion controlled mechanism that yields to concentration levels, in the metal surroundings, several times higher than the measured AC value.

  11. Introduction of Zinc-salt Fixation for Effective Detection of Immune Cell-related Markers by Immunohistochemistry.

    PubMed

    Mori, Hidetoshi; Soonsawad, Pan; Schuetter, Louis; Chen, Qian; Hubbard, Neil E; Cardiff, Robert D; Borowsky, Alexander D

    2015-08-01

    Tissue localization of immune cells is critical to the study of disease processes in mouse models of human diseases. However, immunohistochemistry (IHC) for immune cell phenotyping in mouse tissue sections presents specific technical challenges. For example, CD4 and CD8 have been difficult to detect using IHC on formalin-fixed and paraffin-embedded mouse tissue, prompting alternative methods. We investigated the use of formalin-free zinc-salt fixation (ZN) and optimized IHC protocols for detecting a panel of immune cell-related markers (CD3, CD4, CD8, Foxp3, B220, F4/80, CD68, and major histocompatibility complex [MHC] class-I, MHC class-II, and Gr-1). The IHC results for these markers were compared on mouse spleen tissue treated with neutral buffered formalin (NBF) or ZN with or ZN without antigen retrieval (AR). Whereas CD4 and CD8 were not detected in NBF-treated tissue, all markers were detected in ZN-treated tissue without AR. Thus, the use of ZN treatment for IHC staining can be a good tool for studying immunoreactive lesions in tissues. PMID:26157038

  12. Molecular cloning and characterization of a novel RING zinc-finger protein gene up-regulated under in vitro salt stress in cassava.

    PubMed

    dos Reis, Sávio Pinho; Tavares, Liliane de Souza Conceição; Costa, Carinne de Nazaré Monteiro; Brígida, Aílton Borges Santa; de Souza, Cláudia Regina Batista

    2012-06-01

    Cassava (Manihot esculenta Crantz) is one of the world's most important food crops. It is cultivated mainly in developing countries of tropics, since its root is a major source of calories for low-income people due to its high productivity and resistance to many abiotic and biotic factors. A previous study has identified a partial cDNA sequence coding for a putative RING zinc finger in cassava storage root. The RING zinc finger protein is a specialized type of zinc finger protein found in many organisms. Here, we isolated the full-length cDNA sequence coding for M. esculenta RZF (MeRZF) protein by a combination of 5' and 3' RACE assays. BLAST analysis showed that its deduced amino acid sequence has a high level of similarity to plant proteins of RZF family. MeRZF protein contains a signature sequence motif for a RING zinc finger at its C-terminal region. In addition, this protein showed a histidine residue at the fifth coordination site, likely belonging to the RING-H2 subgroup, as confirmed by our phylogenetic analysis. There is also a transmembrane domain in its N-terminal region. Finally, semi-quantitative RT-PCR assays showed that MeRZF expression is increased in detached leaves treated with sodium chloride. Here, we report the first evidence of a RING zinc finger gene of cassava showing potential role in response to salt stress.

  13. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase modulator: toward age- and sex-personalized medicine.

    PubMed

    Pallottini, Valentina

    2015-01-01

    Cholesterol homeostasis maintenance is regulated by a cellular feedback system that senses cholesterol amount in cellular membranes. 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) plays a pivotal role in cholesterol metabolism as it is the key rate-limiting enzyme of its biosynthetic pathway; its inhibition provokes a feedback response capable of reducing plasma cholesterol content. HMGR inhibition is a keystone in the treatment and prevention of cardiovascular disease and, therefore, statins (HMGR inhibitors) are widely prescribed even though they may sometimes induce side effects. These drugs are prescribed indifferently to both man and women even if there are several well-known differences in cholesterol metabolism depending on the gender and the age. Thus, gender-related differences in cholesterol metabolism should be taken into account to identify new targets for customized pharmacological treatments for hypercholesterolemia. PMID:26135220

  14. Multitasking of the 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor: beyond cardiovascular diseases.

    PubMed

    Calabro, Paolo; Yeh, Edward T H

    2004-01-01

    Statins can profoundly affect cellular metabolism by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is the rate-limiting enzyme responsible for cholesterol synthesis. Many physicians prescribe statins to lower plasma cholesterol levels, which has beneficial effects in both the primary and secondary prevention of coronary artery disease. However, in vitro, in vivo, animal, and clinical studies have all shown that statins may also have important pleiotropic properties. In fact, a number of clinical studies have suggested that statins are involved in modulating diseases such as cancer, osteoporosis, and dementia (including Alzheimer's disease). However, because these studies have been only preliminary and observational in nature, large randomized, placebo-controlled studies are needed to confirm the modulatory role of statins in these important diseases.

  15. BrRZFP1 a Brassica rapa C3HC4-type RING zinc finger protein involved in cold, salt and dehydration stress.

    PubMed

    Jung, Y J; Lee, I H; Nou, I S; Lee, K D; Rashotte, A M; Kang, K K

    2013-03-01

    C3HC4-type RING zinc finger proteins are known to be essential in the regulation of plant processes, including responses to abiotic stress. Here, we identify, clone and examine the first C3HC4-type RING zinc finger protein (BrRZFP1) from Brassica rapa under stress conditions. Phylogenetic analysis of BrRZFP1 revealed strong sequence similarity to C3HC4-type zinc finger proteins from Arabidopsis that are induced by abiotic stresses. Diverse environmental stresses, including salt and cold, were found to induce BrRZFP1 transcripts greater than eightfold in B. rapa. Additional strong induction was shown of the stress hormone abscisic acid, together suggesting that BrRZFP1 could play a role as a general stress modulator. Similar profiles of induction for each of these stresses was found in both root and shoot tissues, although at much higher levels in roots. Constitutive expression of BrRZFP1 in Nicotiana tabacum was conducted to further analyse how changes in gene expression levels would affect plant stress responses. BrRZFP1 overexpression conferred increased tolerance to cold, salt and dehydration stresses. This was observed in several assays examining growth status throughout development, including increased germination, fresh weight and length of shoots and roots, as well as enhanced chlorophyll retention. These results suggest that the transcription factor BrRZFP1 is an important determinant of stress response in plants and that changes in its expression level in plants could increase stress tolerance.

  16. Synthesis of (3-hydroxy-pyrazolin-5-yl)glycine based ligands interacting with ionotropic glutamate receptors.

    PubMed

    Pinto, Andrea; Tamborini, Lucia; Mastronardi, Federica; Ettari, Roberta; Safoz, Yeliz; Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A; De Micheli, Carlo; Conti, Paola

    2014-03-21

    Following the concept that increasing the molecular complexity may enhance the receptor selectivity, we replaced the 3-hydroxy-isoxazoline ring of model compound tricholomic acid with a 3-hydroxy-pyrazoline ring, which could be variously decorated at the N1 position, inserting groups characterized by different electronic and steric properties. Binding assays on rat brain synaptic membranes showed that, depending on the nature of the substituent, some of the new synthesized ligands interacted with either AMPA or KA receptors, with affinities in the mid-micromolar range. PMID:24531228

  17. Influence of exogenous iron, calcium, protein and common salt on the bioaccessibility of zinc from cereals and legumes.

    PubMed

    Hemalatha, Sreeramaiah; Gautam, Smita; Platel, Kalpana; Srinivasan, Krishnapura

    2009-01-01

    We have earlier reported the zinc bioaccessibility from cereals and pulses and documented the influence of heat processing, germination and fermentation on the same. In the present study, we have assessed the influence of exogenous iron and calcium equivalent to their supplemental levels on the bioaccessibility of zinc from food grains that generally are the major components of meal in India. Bioaccessibility measurement was made by a procedure involving equilibrium dialysis during simulated gastrointestinal digestion. Exogenous iron equivalent to therapeutic levels (5mg per 10g of cereal-legume combination) significantly reduced the bioaccessibility of zinc from the food grains tested, the percent reduction being 32.4. Exogenous calcium equivalent to therapeutic levels (83mg per 10g of the cereal-legume combination) also significantly reduced (by 27.4%) the bioaccessibility of zinc from the tested food grains. The negative influence of exogenous iron and calcium was similar in both raw and cooked grains. Such negative influences on the bioaccessibility of zinc were however not seen when exogenous iron and calcium were only moderate (up to four times the intrinsic level). A study of the influence of exogenous protein on the bioaccessibility of zinc from food grains revealed that soy protein isolate added at amounts to result in a total protein content of 20% produced contrasting effects on zinc and iron bioaccessibility from cereals - rice and sorghum. While soy protein had a negative effect on iron bioaccessibility from these food grains, the same produced an enhancing effect on zinc bioaccessibility (an increase of 50% and 90% increase) from raw and cooked grain, respectively). Exogenous sodium chloride (at 5% level) potentiated the positive effect of soy protein on zinc bioaccessibility, and effectively countered its negative effect on iron bioaccessibility. The observed negative influence of supplemental iron and calcium on zinc bioaccessibility suggests that

  18. Biosynthesis of poly(3-hydroxybutyrateco-3-hydroxy-4-methylvalerate) by Strain Azotobacter chroococcum 7B

    PubMed Central

    Bonartsev, A.P.; Bonartseva, G. A.; Myshkina, V. L.; Voinova, V. V.; Mahina, T. K.; Zharkova, I. I.; Yakovlev, S. G.; Zernov, A. L.; Ivanova, E. V.; Akoulina, E. A.; Kuznetsova, E. S.; Zhuikov, V. A.; Alekseeva, S. G.; Podgorskii, V. V.; Bessonov, I. V.; Kopitsyna, M. N.; Morozov, A. S.; Milanovskiy, E. Y.; Tyugay, Z. N.; Bykova, G. S.; Kirpichnikov, M. P.; Shaitan, K. V.

    2016-01-01

    Production of novel polyhydroxyalkanoates (PHAs), biodegradable polymers for biomedical applications, and biomaterials based on them is a promising trend in modern bioengineering. We studied the ability of an effective strain-producer Azotobacter chroococcum 7B to synthesize not only poly(3-hydroxybutyrate) homopolymer (PHB) and its main copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), but also a novel copolymer, poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) (PHB4MV). For the biosynthesis of PHB copolymers, we used carboxylic acids as additional carbon sources and monomer precursors in the chain of synthesized copolymers. The main parameters of these polymers’ biosynthesis were determined: strain-producer biomass yield, polymer yield, molecular weight and monomer composition of the synthesized polymers, as well as the morphology of A. chroococcum 7B bacterial cells. The physico-chemical properties of the polymers were studied using nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), contact angle test, and other methods. In vitro biocompatibility of the obtained polymers was investigated using stromal cells isolated from the bone marrow of rats with the XTT cell viability test. The synthesis of the novel copolymer PHB4MV and its chemical composition were demonstrated by NMR spectroscopy: the addition of 4-methylvaleric acid to the culture medium resulted in incorporation of 3-hydroxy-4-methylvalerate (3H4MV) monomers into the PHB polymer chain (0.6 mol%). Despite the low molar content of 3H4MV in the obtained copolymer, its physico-chemical properties were significantly different from those of the PHB homopolymer: it has lower crystallinity and a higher contact angle, i.e. the physico-chemical properties of the PHB4MV copolymer containing only 0.6 mol% of 3H4MV corresponded to a PHBV copolymer with a molar content ranging from 2.5% to 7.8%. In vitro biocompatibility of the obtained PHB4MV copolymer

  19. Profiling of 3-hydroxy fatty acids as environmental markers of endotoxin using liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Uhlig, Silvio; Negård, Mariell; Heldal, Kari K; Straumfors, Anne; Madsø, Lene; Bakke, Berit; Eduard, Wijnand

    2016-02-19

    3-Hydroxy acids are constituents of the lipid A part of lipopolysaccharides and may potentially be used as chemical markers of endotoxin. While commercial enzymatic assays, such as the widely used Limulus amebocyte lysate (LAL) assay, commonly detect merely the water-soluble fraction of the bioactive endotoxin, the chemical approach aims to estimate the total amount of endotoxin present in a sample. Our objective was to develop a simple method for quantitative profiling of 3-hydroxy fatty acids in occupational and environmental samples based on detection with HPLC-MS/MS. We included eleven 3-hydroxy fatty acids (3-hydroxyoctanoic acid to 3-hydroxyoctadecanoic acid) in the HPLC-MS/MS based method, which involved base hydrolysis of filter samples using 1M sodium hydroxide and removal of the base as well as concentration of the fatty acids using solid-phase extraction on a functionalized polystyrene-divinylbenzene polymer. Recovery trials from spiked glass fiber filters, using threo-9,10-dihydroxyhexadecanoic acid as internal standard, gave an overall recovery of 54-86% for 3-hydroxy fatty acids of medium chain length (3-hydroxynonanoic to 3-hydroxypentadecanoic acid). 3-Hydroxyoctanoic acid and the longer chain fatty acids were more problematic yielding overall spike recoveries of 11-39%. While the 3-hydroxy fatty acid profile of pure lipopolysaccharides was dominated by 3-hydroxydecanoic, 3-hydroxydodecanoic and 3-hydroxytetradecanoic acid the aqueous phase from drilling mud contained in addition relatively high amounts of 3-hydroxyoctanoic and 3-hydroxynonanoic acid. Endotoxin activity as measured by the LAL assay was reasonably correlated (R(2)=0.54) to the sum of 3-hydroxydecanoic acid, 3-hydroxydodecanoic acid and 3-hydroxytetradecanoic acid in these samples. PMID:26818235

  20. Profiling of 3-hydroxy fatty acids as environmental markers of endotoxin using liquid chromatography coupled to tandem mass spectrometry.

    PubMed

    Uhlig, Silvio; Negård, Mariell; Heldal, Kari K; Straumfors, Anne; Madsø, Lene; Bakke, Berit; Eduard, Wijnand

    2016-02-19

    3-Hydroxy acids are constituents of the lipid A part of lipopolysaccharides and may potentially be used as chemical markers of endotoxin. While commercial enzymatic assays, such as the widely used Limulus amebocyte lysate (LAL) assay, commonly detect merely the water-soluble fraction of the bioactive endotoxin, the chemical approach aims to estimate the total amount of endotoxin present in a sample. Our objective was to develop a simple method for quantitative profiling of 3-hydroxy fatty acids in occupational and environmental samples based on detection with HPLC-MS/MS. We included eleven 3-hydroxy fatty acids (3-hydroxyoctanoic acid to 3-hydroxyoctadecanoic acid) in the HPLC-MS/MS based method, which involved base hydrolysis of filter samples using 1M sodium hydroxide and removal of the base as well as concentration of the fatty acids using solid-phase extraction on a functionalized polystyrene-divinylbenzene polymer. Recovery trials from spiked glass fiber filters, using threo-9,10-dihydroxyhexadecanoic acid as internal standard, gave an overall recovery of 54-86% for 3-hydroxy fatty acids of medium chain length (3-hydroxynonanoic to 3-hydroxypentadecanoic acid). 3-Hydroxyoctanoic acid and the longer chain fatty acids were more problematic yielding overall spike recoveries of 11-39%. While the 3-hydroxy fatty acid profile of pure lipopolysaccharides was dominated by 3-hydroxydecanoic, 3-hydroxydodecanoic and 3-hydroxytetradecanoic acid the aqueous phase from drilling mud contained in addition relatively high amounts of 3-hydroxyoctanoic and 3-hydroxynonanoic acid. Endotoxin activity as measured by the LAL assay was reasonably correlated (R(2)=0.54) to the sum of 3-hydroxydecanoic acid, 3-hydroxydodecanoic acid and 3-hydroxytetradecanoic acid in these samples.

  1. The management of pregnancy and delivery in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

    PubMed

    Pipitone, Angela; Raval, Donna B; Duis, Jessica; Vernon, Hilary; Martin, Regina; Hamosh, Ada; Valle, David; Gunay-Aygun, Meral

    2016-06-01

    3-hydroxy-3-methylglutaric (HMG)-CoA lyase is required for ketogenesis and leucine degradation. Patients with HMG-CoA lyase deficiency typically present with hypoketotic hypoglycemia and metabolic acidosis, which can be fatal if untreated. The patient is a 28-year-old female with HMG-CoA lyase deficiency who presented at 4 weeks gestation for prenatal care. Protein intake as well as carnitine supplementation were gradually increased to support maternal and fetal demands up to 65 g per day for protein and 80 mg/kg/day for carnitine. Fetal growth was appropriate. At 36 5/7 weeks, she presented with spontaneous rupture of membranes. Twice maintenance 10% glucose-containing intravenous fluids were initiated. During labor, vomiting and metabolic acidosis developed. Delivery was by cesarean. Preeclampsia developed postpartum. The patient recovered well and was discharged home on postpartum day 5. Stress of pregnancy and labor and delivery can lead to metabolic decompensation in HMG-CoA lyase deficiency. Patients should be monitored closely by a biochemical geneticist, dietitian, and high-risk obstetrician at a tertiary care center during their pregnancy. Fasting should be avoided. Intravenous 10% glucose-containing fluids should be provided to prevent catabolism and metabolic decompensation during labor and delivery. © 2016 Wiley Periodicals, Inc. PMID:26997609

  2. 3-Hydroxy fatty acids in saliva as diagnostic markers in chronic periodontitis.

    PubMed

    Ferrando, Raúl; Szponar, Bogumila; Sánchez, Arturo; Larsson, Lennart; Valero-Guillén, Pedro L

    2005-09-01

    Saturated straight- and branched-chain 3-hydroxy fatty acids (3-OH FAs) of 10-18 carbon chain lengths were determined in saliva from 27 individuals with chronic periodontitis and 18 healthy individuals by using gas chromatography-tandem mass spectrometry. Of the 14 different 3-OH FAs detected, 3-OH-C(i17:0) was the most abundant in the periodontitis samples while 3-OH-C(14:0) was the most abundant in the healthy individuals. Considering the relative percentages of 3-OH-C(12:0), 3-OH-C(14:0), 3-OH-C(i17:0), and 3-OH-C(17:0), 95.6% of all cases were correctly classified as healthy individuals or periodontitis patients by means of discriminant analysis. The sensitivity, specificity, positive predictive value and negative predictive value of 3-OH FA analysis in diagnosing peridontitis were, respectively, 0.92, 1.00, 1.00, and 0.90. The results indicate that 3-OH FA analysis of saliva samples is a useful diagnostic method in chronic periodontitis. PMID:15941605

  3. Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide.

    PubMed

    Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio E; Anguiano-Robledo, Liliana; Soriano-Ursúa, Marvin A; Correa-Basurto, José; Davood, Asghar; Chamorro-Cevallos, Germán

    2016-01-01

    Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP and Cl-HEPP) with two seizure models, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was examined via the rotarod test. With in silico methods, binding was probed on possible protein targets-GABAA receptors and the sodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6, 87.1, and 62.0 mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5 mg/kg. The HEPP-induced neurotoxic effect, which occurred at twice the ED50 against MES (p < 0.05), did not occur with F-HEPP or Cl-HEPP. Docking studies revealed that all tested ligands bound to GABAA receptors on a site near to the benzodiazepine binding site. However, on the sodium channel open pore Nav1.2, R-HEPP had interactions similar to those reported for phenytoin, while its enantiomer and the ligands F-HEPP and Cl-HEPP reached a site that could disrupt the passage of sodium. Our results show that, as anticonvulsant agents, parahalogen substituted compounds have an advantageous pharmacotoxicological profile compared to their precursor.

  4. Anticonvulsant and Toxicological Evaluation of Parafluorinated/Chlorinated Derivatives of 3-Hydroxy-3-ethyl-3-phenylpropionamide

    PubMed Central

    Garrido-Acosta, Osvaldo; Meza-Toledo, Sergio E.; Anguiano-Robledo, Liliana; Soriano-Ursúa, Marvin A.; Correa-Basurto, José; Davood, Asghar; Chamorro-Cevallos, Germán

    2016-01-01

    Although the anticonvulsant activity of 3-hydroxy-3-ethyl-3-phenylproionamide (HEPP) is well-known, its use is limited by the pharmacotoxicological profile. We herein tested its fluorinated and chlorinated derivatives (F-HEPP and Cl-HEPP) with two seizure models, maximal electroshock seizures (MES), and intraperitoneal pentylenetetrazole (PTZ) administration. Neurotoxicity was examined via the rotarod test. With in silico methods, binding was probed on possible protein targets—GABAA receptors and the sodium channel Nav1.2. The median effective doses (ED50) of HEPP, F-HEPP, and Cl-HEPP in the MES seizure model were 129.6, 87.1, and 62.0 mg/kg, respectively, and 66.4, 43.5, and in the PTZ seizure model 43.5 mg/kg. The HEPP-induced neurotoxic effect, which occurred at twice the ED50 against MES (p < 0.05), did not occur with F-HEPP or Cl-HEPP. Docking studies revealed that all tested ligands bound to GABAA receptors on a site near to the benzodiazepine binding site. However, on the sodium channel open pore Nav1.2, R-HEPP had interactions similar to those reported for phenytoin, while its enantiomer and the ligands F-HEPP and Cl-HEPP reached a site that could disrupt the passage of sodium. Our results show that, as anticonvulsant agents, parahalogen substituted compounds have an advantageous pharmacotoxicological profile compared to their precursor. PMID:27006945

  5. 3-Hydroxy fatty acids in saliva as diagnostic markers in chronic periodontitis.

    PubMed

    Ferrando, Raúl; Szponar, Bogumila; Sánchez, Arturo; Larsson, Lennart; Valero-Guillén, Pedro L

    2005-09-01

    Saturated straight- and branched-chain 3-hydroxy fatty acids (3-OH FAs) of 10-18 carbon chain lengths were determined in saliva from 27 individuals with chronic periodontitis and 18 healthy individuals by using gas chromatography-tandem mass spectrometry. Of the 14 different 3-OH FAs detected, 3-OH-C(i17:0) was the most abundant in the periodontitis samples while 3-OH-C(14:0) was the most abundant in the healthy individuals. Considering the relative percentages of 3-OH-C(12:0), 3-OH-C(14:0), 3-OH-C(i17:0), and 3-OH-C(17:0), 95.6% of all cases were correctly classified as healthy individuals or periodontitis patients by means of discriminant analysis. The sensitivity, specificity, positive predictive value and negative predictive value of 3-OH FA analysis in diagnosing peridontitis were, respectively, 0.92, 1.00, 1.00, and 0.90. The results indicate that 3-OH FA analysis of saliva samples is a useful diagnostic method in chronic periodontitis.

  6. A chemoenzymatic approach to the synthesis of enantiomerically pure (S)-3-hydroxy-gamma-butyrolactone.

    PubMed

    Lee, Sang-Hyun; Park, Oh-Jin; Uh, Hong-Sun

    2008-06-01

    Optically pure (S)-3-hydroxy-gamma-butyrolactone, an important chiral building block in the pharmaceutical industry, was synthesized from L: -malic acid by combining a selective hydrogenation and a lipase-catalyzed hydrolysis. Lipase from Candida rugosa was found to be the most efficient enzyme for the hydrolysis of (S)-beta-benzoyloxy-gamma-butyrolactone. The use of organic solvent-aqueous two-phase system was employed to extract benzoic acid generated from enzymatic hydrolysis of the substrate. Tert-butyl methyl ether as an organic solvent was effective to extract the reaction product, benzoic acid, and stably maintained the enzyme activity of Lipase OF immobilized on polymeric supports Amberlite XAD-7. The immobilization made the recovery of the product simpler and prevented the formation of the emulsion. The pH adjustment was unnecessary with the immobilized Lipase OF. The scale-up of the enzymatic hydrolysis of S-BBL at 1,850-kg scale was carried out without problems to give 728.5 kg of S-HGB at 80% isolated yield. The scale-up results are similar to those of bench scale reactions. Racemic (R,S)-beta-benzoyloxy-gamma-butyrolactone was prepared from D-, L: -malic acid and was found to be hydrolyzed nonselectively by the enzyme. PMID:18446525

  7. Synthesis, Characterization, and Cu(2+) Coordination Studies of a 3-Hydroxy-4-pyridinone Aza Scorpiand Derivative.

    PubMed

    López-Martínez, Luis M; Pitarch-Jarque, Javier; Martínez-Camarena, Àlvar; García-España, Enrique; Tejero, Roberto; Santacruz-Ortega, Hisila; Navarro, Rosa-Elena; Sotelo-Mundo, Rogerio R; Leyva-Peralta, Mario Alberto; Doménech-Carbó, Antonio; Verdejo, Begoña

    2016-08-01

    The synthesis, acid-base behavior, and Cu(2+) coordination chemistry of a new ligand (L1) consisting of an azamacrocyclic core appended with a lateral chain containing a 3-hydroxy-2-methyl-4(1H)-pyridinone group have been studied by potentiometry, cyclic voltammetry, and NMR and UV-vis spectroscopy. UV-vis and NMR studies showed that phenolate group was protonated at the highest pH values [log K = 9.72(1)]. Potentiometric studies point out the formation of Cu(2+) complexes of 1:2, 2:2, 4:3, 1:1, and 2:1 Cu(2+)/L1 stoichiometries. UV-vis analysis and electrochemical studies evidence the implication of the pyridinone moieties in the metal coordination of the 1:2 Cu(2+)/L1 complexes. L1 shows a stronger chelating ability than the reference chelating ligand deferiprone. While L1 shows no cytotoxicity in HeLa and ARPE-19 human cell lines (3.1-25.0 μg/mL), it has significant antioxidant activity, as denoted by TEAC assays at physiological pH. The addition of Cu(2+) diminishes the antioxidant activity because of its coordination to the pyridinone moiety phenolic group.

  8. Targeting and topology in the membrane of plant 3-hydroxy-3-methylglutaryl coenzyme A reductase.

    PubMed Central

    Campos, N; Boronat, A

    1995-01-01

    The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the synthesis of mevalonate. This is the first committed step of isoprenoid biosynthesis. A common feature of all known plant HMGR isoforms is the presence of two highly conserved hydrophobic sequences in the N-terminal quarter of the protein. Using an in vitro system, we showed that the two hydrophobic sequences of Arabidopsis HMGR1S function as internal signal sequences. Specific recognition of these sequences by the signal recognition particle mediates the targeting of the protein to microsomes derived from the endoplasmic reticulum. Arabidopsis HMGR is inserted into the microsomal membrane, and the two hydrophobic sequences become membrane-spanning segments. The N-terminal end and the C-terminal catalytic domain of Arabidopsis HMGR are positioned on the cytosolic side of the membrane, whereas only a short hydrophilic sequence is exposed to the lumen. Our results suggest that the plant HMGR isoforms known to date are primarily targeted to the endoplasmic reticulum and have the same topology in the membrane. This reinforces the hypothesis that mevalonate is synthesized only in the cytosol. The possibility that plant HMGRs might be located in different regions of the endomembrane system is discussed. PMID:8718626

  9. Biosynthesis of 3-hydroxy-5-methyl-o-methyltyrosine in the saframycin/ safracin biosynthetic pathway.

    PubMed

    Fu, Cheng-Yu; Tang, Man-Cheng; Peng, Chao; Li, Lei; He, Yan-Ling; Liu, Wen; Tang, Gong-Li

    2009-05-01

    The biosynthesis study of antibiotics saframycin (SFM) in Streptomyces lavendulae and safracin (SAC) in Pseudomonas fluorescens demonstrated that 3-hydroxy-5-methyl-Omethyltyrosine (3h5mOmTyr), a nonproteinogenic amino acid, is the precursor of the tetrahydroisoquinoline molecular core. In the biosynthetic gene cluster of SAC/SFM, sacD/ sfmD encodes a protein with high homology to each other but no sequence similarity to other known enzymes; sacF/ sfmM2 and sacG/sfmM3 encode methyltransferases for Cmethylation and O-methylation; and sacE/sfmF encodes a small protein with significant sequence similarity to the MbtH-like proteins, which are frequently found in the biosynthetic pathways of nonribosomal peptide antibiotics and siderophores. To address their function, the biosynthetic cassette of 3h5mOmTyr was heterologously expressed in S. coelicolor and P. putida, and an in-frame deletion and complementation in trans were carried out. The results revealed that (i) SfmD catalyzes the hydroxylation of aromatic rings;(ii) sacD/sacF/sacG in the SAC gene cluster and sfmD/sfmM2/sfmM3 in the SFM cluster are sufficient for the biosynthesis of 3h5mOmTyr; and (iii) the mbtH-like gene is not required for the biosynthesis of the 3h5mOmTyr precursor. PMID:19494690

  10. Synthesis, Characterization, and Cu(2+) Coordination Studies of a 3-Hydroxy-4-pyridinone Aza Scorpiand Derivative.

    PubMed

    López-Martínez, Luis M; Pitarch-Jarque, Javier; Martínez-Camarena, Àlvar; García-España, Enrique; Tejero, Roberto; Santacruz-Ortega, Hisila; Navarro, Rosa-Elena; Sotelo-Mundo, Rogerio R; Leyva-Peralta, Mario Alberto; Doménech-Carbó, Antonio; Verdejo, Begoña

    2016-08-01

    The synthesis, acid-base behavior, and Cu(2+) coordination chemistry of a new ligand (L1) consisting of an azamacrocyclic core appended with a lateral chain containing a 3-hydroxy-2-methyl-4(1H)-pyridinone group have been studied by potentiometry, cyclic voltammetry, and NMR and UV-vis spectroscopy. UV-vis and NMR studies showed that phenolate group was protonated at the highest pH values [log K = 9.72(1)]. Potentiometric studies point out the formation of Cu(2+) complexes of 1:2, 2:2, 4:3, 1:1, and 2:1 Cu(2+)/L1 stoichiometries. UV-vis analysis and electrochemical studies evidence the implication of the pyridinone moieties in the metal coordination of the 1:2 Cu(2+)/L1 complexes. L1 shows a stronger chelating ability than the reference chelating ligand deferiprone. While L1 shows no cytotoxicity in HeLa and ARPE-19 human cell lines (3.1-25.0 μg/mL), it has significant antioxidant activity, as denoted by TEAC assays at physiological pH. The addition of Cu(2+) diminishes the antioxidant activity because of its coordination to the pyridinone moiety phenolic group. PMID:27433814

  11. Expanding Mg-Zn hybrid chemistry: inorganic salt effects in addition reactions of organozinc reagents to trifluoroacetophenone and the implications for a synergistic lithium-magnesium-zinc activation.

    PubMed

    Armstrong, David R; Clegg, William; García-Álvarez, Pablo; Kennedy, Alan R; McCall, Matthew D; Russo, Luca; Hevia, Eva

    2011-07-18

    Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl(2) in THF led to the isolation of novel magnesium-zinc hybrids, [{(thf)(2)Mg(μ-Cl)(3)ZnR}(2)] (R=Et, tBu, nBu or o-OMe-C(6)H(4)), which exhibit an unprecedented structural motif in mixed magnesium-zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl(2) reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl(2). This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect. PMID:21656589

  12. Poly-3-hydroxy butyric acid interaction with the transgenic flax fibers: FT-IR and Raman spectra of the composite extracted from a GM flax

    NASA Astrophysics Data System (ADS)

    Wróbel-Kwiatkowska, Magdalena; Żuk, Magdalena; Szopa, Jan; Dymińska, Lucyna; Mączka, Mirosław; Hanuza, Jerzy

    2009-07-01

    The FT-IR and FT-Raman studies have been performed on commercial 3-hydroxy-butyric acid, commercial poly-3-hydroxy butyric acid as well as poly-3-hydroxy butyric acid (PHB) produced by bacteria. The data were compared to those obtained for poly-3-hydroxy butyric acid extracted from natural and genetically modified flax. Genetically modified flax was generated by expression of three bacterial genes coding for synthesis of poly-3-hydroxy butyric acid. Thus transgenic flaxes were enhanced with different amount of the PHB. The discussion of polymer structure and vibrational properties has been done in order to get insight into differences among these materials. The interaction between the cellulose of flax fibers and embedded poly-3-hydroxybutyric acid has been also discussed. The spectroscopic data provide evidences for structural changes in cellulose and in PHB when synthesized in fibers. Based on this data it is suggesting that cellulose and PHB interact by hydrogen and ester bonds.

  13. 3-Hydroxy-2-butanone and the first encounter fight in the male lobster cockroach, Nauphoeta cinerea

    NASA Astrophysics Data System (ADS)

    Kou, Rong; Chen, Shu-Chun; Chen, Ying-Ru; Ho, Hsiao-Yung

    2006-06-01

    Although agonistic behavior in the male lobster cockroach, Nauphoeta cinerea, has been known for more than 40 years, this is the first study to directly collect and quantify the emitted pheromones. In the present study, emitted volatile pheromones were collected from each male pair for 60 min during the first encounter fight and identified and quantified by gas chromatography mass spectrometry. The major compound collected was 3-hydroxy-2-butanone (3H-2B). The strength of the attack by the dominant male was classified into three categories from weakest (C) to strongest (A). Of the 92 pairs, eight (8.7%) showed no agonistic interactions, and the amount of 3H-2B collected was 121.8±37.7 ng/male pair. In the five pairs (5.4%) displaying attack strength C, the amount of 3H-2B collected was 689.6±273.7 ng/male pair, and the attack duration was 9.6±2.4 min. In the 53 pairs (57.6%) showing attack strength B, the corresponding values were 5396.2±449.0 ng/male pair and 22.7±1.6 min, while those for the 26 pairs (28.3%) showing attack strength A were 7910.4±1120.6 ng/male pair and 24.9±2.9 min. For both attack strengths A and B, a linear relationship was found between the amount of 3H-2B collected and attack duration, suggesting that the longer the duration of the attack, the more 3H-2B was emitted. In addition, the rate of 3H-2B emission for attack strength A was significantly higher than that for attack strength B. Using Vaseline-coating, we demonstrated that, in the first encounter fight, the 3H-2B was emitted by the dominant male.

  14. Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential anti-inflammatory properties.

    PubMed

    Chisté, Renan Campos; Ribeiro, Daniela; Freitas, Marisa; Leite, Andreia; Moniz, Tânia; Rangel, Maria; Fernandes, Eduarda

    2016-02-01

    Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (Hmpp) or two methyl groups (Hdmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15μM. Among all the compounds, [Cu(mpp)2] and [Cu(dmpp)2] exhibited the highest scavenging capacity against superoxide radical (O2(-)) (IC50=0.36±0.07 and 0.30±0.06μM, respectively) and against hypochlorous acid (HOCl) (IC50=0.6±0.3 and 0.4±0.1μM, respectively). In the particular case of O2(-), [Fe(mpp)3] and [Fe(dmpp)3] (both at 15μM) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O2(-) nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6-39%). Finally, with exception of [VO(mpp)2] and [VO(dmpp)2], all compounds exhibited scavenging activity against HOCl (39-81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as an useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue.

  15. Subcellular Localization of Arabidopsis 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase1

    PubMed Central

    Leivar, Pablo; González, Víctor M.; Castel, Susanna; Trelease, Richard N.; López-Iglesias, Carmen; Arró, Montserrat; Boronat, Albert; Campos, Narciso; Ferrer, Albert; Fernàndez-Busquets, Xavier

    2005-01-01

    Plants produce diverse isoprenoids, which are synthesized in plastids, mitochondria, endoplasmic reticulum (ER), and the nonorganellar cytoplasm. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyzes the synthesis of mevalonate, a rate-limiting step in the cytoplasmic pathway. Several branches of the pathway lead to the synthesis of structurally and functionally varied, yet essential, isoprenoids. Several HMGR isoforms have been identified in all plants examined. Studies based on gene expression and on fractionation of enzyme activity suggested that subcellular compartmentalization of HMGR is an important intracellular channeling mechanism for the production of the specific classes of isoprenoids. Plant HMGR has been shown previously to insert in vitro into the membrane of microsomal vesicles, but the final in vivo subcellular localization(s) remains controversial. To address the latter in Arabidopsis (Arabidopsis thaliana) cells, we conducted a multipronged microscopy and cell fractionation approach that included imaging of chimeric HMGR green fluorescent protein localizations in transiently transformed cell leaves, immunofluorescence confocal microscopy in wild-type and stably transformed seedlings, immunogold electron microscopy examinations of endogenous HMGR in seedling cotyledons, and sucrose density gradient analyses of HMGR-containing organelles. Taken together, the results reveal that endogenous Arabidopsis HMGR is localized at steady state within ER as expected, but surprisingly also predominantly within spherical, vesicular structures that range from 0.2- to 0.6-μm diameter, located in the cytoplasm and within the central vacuole in differentiated cotyledon cells. The N-terminal region, including the transmembrane domain of HMGR, was found to be necessary and sufficient for directing HMGR to ER and the spherical structures. It is believed, although not directly demonstrated, that these vesicle-like structures are derived from segments of HMGR

  16. Formation of Isobutene from 3-Hydroxy-3-Methylbutyrate by Diphosphomevalonate Decarboxylase▿

    PubMed Central

    Gogerty, David S.; Bobik, Thomas A.

    2010-01-01

    Isobutene is an important commercial chemical used for the synthesis of butyl rubber, terephthalic acid, specialty chemicals, and a gasoline performance additive known as alkylate. Currently, isobutene is produced from petroleum and hence is nonrenewable. Here, we report that the Saccharomyces cerevisiae mevalonate diphosphate decarboxylase (ScMDD) can convert 3-hydroxy-3-methylbutyrate (3-HMB) to isobutene. Whole cells of Escherichia coli producing ScMDD with an N-terminal 6×His tag (His6-ScMDD) formed isobutene from 3-HMB at a rate of 154 pmol h−1 g cells−1. In contrast, no isobutene was detected from control cells lacking ScMDD. His6-ScMDD was purified by nickel affinity chromatography and shown to produce isobutene from 3-HMB at a rate of 1.33 pmol min−1 mg−1 protein. Controls showed that both His6-ScMDD and 3-HMB were required for detectable isobutene formation. Isobutene was identified by gas chromatography (GC) with flame ionization detection as well as by GC-mass spectrometry (MS). ScMDD was subjected to error-prone PCR, and two improved variants were characterized, ScMDD1 (I145F) and ScMDD2 (R74H). Whole cells of E. coli producing ScMDD1 and ScMDD2 produced isobutene from 3-HMB at rates of 3,000 and 5,888 pmol h−1 g cells−1, which are 19- and 38-fold increases compared to rates for cells producing His6-ScMDD. This showed that genetic modifications can be used to increase the rate at which ScMDD converts 3-HMB to isobutene. Because 3-HMB can be produced from l-leucine, ScMDD has a potential application for the production of renewable isobutene. Moreover, isobutene is a gas, which might simplify its purification from a fermentation medium, substantially reducing production costs. PMID:20971863

  17. The Ralstonia solanacearum pathogenicity regulator HrpB induces 3-hydroxy-oxindole synthesis.

    PubMed

    Delaspre, Fabien; Nieto Peñalver, Carlos G; Saurel, Olivier; Kiefer, Patrick; Gras, Emmanuel; Milon, Alain; Boucher, Christian; Genin, Stéphane; Vorholt, Julia A

    2007-10-01

    The transcriptional activator HrpB of the bacterial wilt causing betaproteobacterium Ralstonia solanacearum represents a key regulator for pathogenicity. In particular, it drives expression of hrp genes encoding a type III secretion system (T3SS) as well as effector molecules for delivery into the host cytosol to promote disease. However, the HrpB regulon extends beyond this T3SS. We describe here an HrpB-activated operon of six genes that is responsible for the synthesis of a fluorescent isatin derivative of 149 Amu that we named HDF for HrpB-dependent factor and that we purified from culture supernatants. The structure of the labile molecule was solved by using NMR and CD spectroscopy to be (3S)-3-hydroxy-indolin-2-one and confirmed by its chemical synthesis and MS spectrometry. HDF was found to be present at 20 nM in wild-type cultures grown on minimal medium, and its synthesis increased 15-fold upon overproduction of HrpB, confirming that HrpB activates HDF synthesis. The addition of tryptophan significantly stimulated HDF biosynthesis and was shown to represent the precursor molecule for HDF synthesis. A search for the biological function of the molecule revealed that HDF induces acyl-homoserine lactone receptor-mediated reporter activity of the well studied LuxR transcriptional regulator of Vibrio fischeri. Thus, our results provide evidence that the specificity of acyl-homoserine lactone (acyl-HSL) receptors is clearly broader than previously considered. The failure to detect induction by HDF of the described endogenous quorum-sensing circuits of the pathogen points to a role in interfering with cell-cell signaling of rivalling bacteria. PMID:17890323

  18. Suppression of zinc dendrites in zinc electrode power cells

    NASA Technical Reports Server (NTRS)

    Damjanovic, A.; Diggle, J. W.

    1970-01-01

    Addition of various tetraalkyl quarternary ammonium salts, to alkaline zincate electrolyte of cell, prevents formation of zinc dendrites during charging of zinc electrode. Electrode capacity is not impaired and elimination of dendrites prolongs cell life.

  19. 3-Hydroxy-4-pyridinone derivatives designed for fluorescence studies to determine interaction with amyloid protein as well as cell permeability.

    PubMed

    Telpoukhovskaia, Maria A; Cawthray, Jacqueline F; Rodríguez-Rodríguez, Cristina; Scott, Lauren E; Page, Brent D G; Patrick, Brian O; Orvig, Chris

    2015-09-01

    Finding a cure for Alzheimer's disease is an urgent goal. Multifunctional metal binders are used to elucidate its pathological features and investigated as potential therapeutics. The use of physicochemical and TD-DFT calculations constituted successful strategy in the design of 1-(4-(benzo[d]oxazol-2-yl)phenyl)-3-hydroxy-2-methylpyridin-4(1H)-one (HL21) and 1-(4-(benzo[d]thiazol-2-yl)phenyl)-3-hydroxy-2-methylpyridin-4(1H)-one (HL22). We report the synthesis and full characterization of these compounds, including X-ray crystallography. Using fluorescent signal as the readout, it was determined that HL22 interacts with amyloid-beta protein fibrils, and permeates into bEnd.3 cells used as a mimic of the blood-brain barrier. This provides the first example of direct investigation of our hydroxypyridinone compounds within a biological setting. PMID:26141772

  20. Selective synthesis of 3-hydroxy acids from Meldrum's acids using SmI2-H2O.

    PubMed

    Szostak, Michal; Spain, Malcolm; Procter, David J

    2012-05-01

    The single-step synthesis of 3-hydroxy carboxylic acids from readily available Meldrum's acids involves a selective monoreduction using a SmI(2)-H(2)O complex to give products in high crude purity, and it represents a considerable advancement over other methods for the synthesis of 3-hydroxy acids. The protocol includes a detailed guide to the preparation of a single electron-reducing SmI(2)-H(2)O complex and describes two representative examples of the methodology: monoreduction of a fully saturated Meldrum's acid (5-(4-bromobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione) and tandem conjugate reduction-selective monoreduction of α,β-unsaturated Meldrum's acid (5-(4-methoxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione). The protocol for selective monoreduction of Meldrum's acids takes ∼6 h to complete. PMID:22538848

  1. Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase increases the expression of interferon-responsive genes.

    PubMed

    Yang, Xin; Ouyang, Hongsheng; Chen, Fuwang; Ma, Teng; Dong, Meichen; Wang, Fei; Pang, Daxing; Peng, Zhiyuan; Ren, Linzhu

    2014-12-01

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) pathway is an important metabolic route that is present in almost every organism. However, whether HMGCR affects the expression of interferon (IFN)-responsive genes is unclear. In the present study, expression levels of IFN-responsive genes were monitored by real time polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that expression levels of IFN-responsive genes were significantly increased in HMGCR-downregulated cells and HMGCR inhibitor-treated cells, indicating that inhibition of HMGCR activates the expression of IFN-responsive genes. The result in this study will provide new insight into the role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in antiviral research.

  2. A platform pathway for production of 3-hydroxyacids provides a biosynthetic route to 3-hydroxy-γ-butyrolactone.

    PubMed

    Martin, Collin H; Dhamankar, Himanshu; Tseng, Hsien-Chung; Sheppard, Micah J; Reisch, Christopher R; Prather, Kristala L J

    2013-01-01

    The replacement of petroleum feedstocks with biomass to produce platform chemicals requires the development of appropriate conversion technologies. 3-Hydroxy-γ-butyrolactone has been identified as one such chemical; however, there are no naturally occurring biosynthetic pathways for this molecule or its hydrolyzed form, 3,4-dihydroxybutyric acid. Here we design a novel pathway to produce various chiral 3-hydroxyacids, including 3,4-dihydroxybutyric acid, consisting of enzymes that condense two acyl-CoAs, stereospecifically reduce the resulting β-ketone and hydrolyze the CoA thioester to release the free acid. Acetyl-CoA serves as one substrate for the condensation reaction, whereas the second is produced intracellularly by a pathway enzyme that converts exogenously supplied organic acids. Feeding of butyrate, isobutyrate and glycolate results in the production of 3-hydroxyhexanoate, 3-hydroxy-4-methylvalerate and 3,4-dihydroxybutyric acid+3-hydroxy-γ-butyrolactone, respectively, molecules with potential uses in applications from materials to medicines. We also unexpectedly observe the condensation reaction resulting in the production of the 2,3-dihydroxybutyric acid isomer, a potential value-added monomer.

  3. Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.

    PubMed

    Cardona-Gómez, Gloria Patricia; Arango-Davila, Cesar; Gallego-Gómez, Juan Carlos; Barrera-Ocampo, Alvaro; Pimienta, Hernan; Garcia-Segura, Luis Miguel

    2006-08-21

    During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.

  4. New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones: synthesis and ROS/RNS scavenging activities.

    PubMed

    Sousa, Joana L C; Proença, Carina; Freitas, Marisa; Fernandes, Eduarda; Silva, Artur M S

    2016-08-25

    New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones were prepared and assessed as reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavengers. The synthetic strategy involved the preparation of 2'-hydroxychalcones and 2'-hydroxycinnamylidenoacetophenones from base-catalyzed aldol reaction of appropriate 2'-hydroxyacetophenones and benzaldehydes/cinnamaldehydes, followed by an Algar-Flynn-Oyamada (AFO) reaction to give the polyalkoxy(flavon-3-ols and 3-hydroxy-2-styrylchromones). The last step of this synthetic route consisted in the cleavage of the protecting groups affording the expected polyhydroxylated derivatives. The present work consisted in the study of the in vitro scavenging activities of the synthetized compounds against the most physiologically relevant ROS [superoxide radical (O2(-)), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen ((1)O2) and peroxyl radical (ROO)] and RNS [nitric oxide (NO) and peroxynitrite anion (ONOO(-))]. Generally, all the tested new polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones exhibited scavenging effects dependent on the concentration, and with IC50 values found within the micromolar range. This work allowed the establishment of new structure-activity relationships and brought the knowledge about the selective choice of a structure depending on the targeted reactive species. PMID:27213247

  5. Statins and Myotoxic Effects Associated With Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies

    PubMed Central

    Watanabe, Yurika; Suzuki, Shigeaki; Nishimura, Hiroaki; Murata, Ken-ya; Kurashige, Takashi; Ikawa, Masamichi; Asahi, Masaru; Konishi, Hirofumi; Mitsuma, Satsuki; Kawabata, Satoshi; Suzuki, Norihiro; Nishino, Ichizo

    2015-01-01

    Abstract Statins have a variety of myotoxic effects and can trigger the development of inflammatory myopathies or myasthenia gravis (MG) mediated by immunomodulatory properties. Autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) have been identified in patients with statin-associated myopathy. The purpose of the present study is to develop an enzyme-linked immunosorbent assay (ELISA) of anti-HMGCR antibodies and to elucidate the clinical significance of anti-HMGCR antibodies in Japanese patients with inflammatory myopathies or MG. We enrolled 75 patients with inflammatory myopathies, who were all negative for anti-signal recognition particle and anti-aminoacyl transfer RNA synthetase antibodies. They were referred to Keio University and National Center of Neurology and Psychiatry between October 2010 and September 2012. We also studied 251 patients with MG who were followed at the MG Clinic at Keio University Hospital. Anti-HMGCR antibodies were detected by ELISA. We investigated demographic, clinical, radiological, and histological findings associated with anti-HMGCR antibodies. We established the anti-HMGCR ELISA with the recombinant protein. Protein immunoprecipitation detected autoantigens corresponding to HMGCR. Immunohistochemistry using muscle biopsy specimens revealed regenerating muscle fibers clearly stained by polyclonal anti-HMGCR antibodies and patients’ serum. Anti-HMGCR autoantibodies were specifically detected in 8 patients with necrotizing myopathy. The seropositivity rate in the necrotizing myopathy patients was significantly higher than those in the patients with other histological diagnoses of inflammatory myopathies (31% vs 2%, P = 0.001). Statins were administered in only 3 of the 8 anti-HMGCR-positive patients. Myopathy associated with anti-HMGCR antibodies showed mild limb weakness and favorable response to immunotherapy. All 8 patients exhibited increased signal intensities on short T1 inversion recovery of

  6. One-Pot Synthesis of Organic-Sulfur-Zinc Hybrid Materials via Polycondensation of a Zinc Salt and Thiols Generated in Situ from Cyclic Dithiocarbonates.

    PubMed

    Ochiai, Bungo; Konta, Hirohisa

    2015-08-17

    Soluble organic-sulfur-zinc hybrid polymers were prepared via a one-pot reaction consisting of ring-opening addition and subsequent polycondensation. The first reaction is the nucleophilic ring-opening addition of 2-ethylhexylamine to multifunctional cyclic dithiocarbonates giving multiple thiols in situ. The sequential polycondensation of the in situ generated thiols with Zn(OAc)2 gave the target hybrid polymers. This one-pot method enabled the use of a shorter amine than the previous polycondensation of Zn(OAc)2 and purified thiols, which required octadecylamine to obtain a soluble product. The obtained hybrid polymers may be cast as composite films with polystyrene and poly(methyl methacrylate). Owing to the shorter alkyl chain, the calculated nD values of the products (1.60 or 1.61) are higher than that of the previous product bearing octadecyl chains (1.53).

  7. Cadmium, lead and zinc in growing rats fed corn leaf tissue grown on soil amended with sewage sludge or heavy metal salts.

    PubMed

    Miller, J; Boswell, F C

    1981-12-01

    Rats were fed, from weaning through 11 weeks of age, dried leaf tissue of corn plants grown on soil amended with regular NPK fertilizer (150-22-62), with 33.6 ad 67.2 metric ton/ha of sewage sludge or with salts of cadmium (10kg/ha), lead (25kg/ha), and/or zinc (50kg/ha). A very high proportion of the cadmium (cd) consumed was eliminated in feces. Only in rats fed diets containing leaf tissue from plants grown on soil to which CdCl2 salt or the high level of sludge had been added did the metal accumulate in significantly greater quantity than in rats fed a standard diet without leaf tissue. Most of the carcass accumulation of Cd could be accounted for by that in the liver and kidneys. The proportion of dietary zinc (Zn) that was excreted in feces was less than that for Cd, indicating that more Zn was absorbed into the body. There was no correlation between intake and accumulation of Zn in the tissues, however, so that much of the absorbed Zn must have been eliminated in some way. Fecal elimination did not serve as a way to rid the body of excessive intake of lead (Pb). However, with intakes ranging from 2 to 11 mg total in this study, the carcass load did not exceed 1.1 mg of Pb. Thus absorbed Pb, like Zn, must also be eliminated efficiently. No gross signs of toxicity or of physiological impairment were observed in rats fed any of the plant tissue samples.

  8. Structural characterization of two benzene-1,2-di-amine complexes of zinc chloride: a mol-ecular compound and a co-crystal salt.

    PubMed

    Zick, Patricia L; Geiger, David K

    2016-07-01

    The structures of two zinc complexes containing bidentate benzene-1,2-di-amine ligands are reported. (Benzene-1,2-di-amine-κ(2) N,N')di-chloro-idozinc, [ZnCl2(C6H8N2)], (I), displays a distorted tetra-hedral coordination sphere for the metal cation. The di-amine ligand and the Zn atom reside on a crystallographic mirror plane. In the 1:1 co-crystal salt trans-di-aqua-bis-(4,5-di-methyl-benzene-1,2-di-amine-κ(2) N,N')zinc chloride-4,5-di-methyl-benzene-1,2-di-amine (1/1), [Zn(C8H12N2)2(H2O)2]Cl2·2C8H12N2, (II), the zinc(II) complex cation exhibits a tetra-gonally distorted octa-hedral coordination sphere. The Zn atom sits on a crystallographically imposed inversion center and the di-amine ligands are tilted 30.63 (6)° with respect to the ZnN4 plane. Both complexes exhibit extensive hydrogen bonding. In (I), a stacked-sheet extended structure parallel to (101) is observed. In (II), the co-crystallized di-amine is hydrogen-bonded to the complex cation via O-H⋯N and N-H⋯N linkages. These units are in turn linked into planes along (200) by O-H⋯Cl and N-H⋯Cl hydrogen bonds. PMID:27555958

  9. Structural characterization of two benzene-1,2-di­amine complexes of zinc chloride: a mol­ecular compound and a co-crystal salt

    PubMed Central

    Zick, Patricia L.; Geiger, David K.

    2016-01-01

    The structures of two zinc complexes containing bidentate benzene-1,2-di­amine ligands are reported. (Benzene-1,2-di­amine-κ2 N,N′)di­chloro­idozinc, [ZnCl2(C6H8N2)], (I), displays a distorted tetra­hedral coordination sphere for the metal cation. The di­amine ligand and the Zn atom reside on a crystallographic mirror plane. In the 1:1 co-crystal salt trans-di­aqua­bis­(4,5-di­methyl­benzene-1,2-di­amine-κ2 N,N′)zinc chloride–4,5-di­methyl­benzene-1,2-di­amine (1/1), [Zn(C8H12N2)2(H2O)2]Cl2·2C8H12N2, (II), the zinc(II) complex cation exhibits a tetra­gonally distorted octa­hedral coordination sphere. The Zn atom sits on a crystallographically imposed inversion center and the di­amine ligands are tilted 30.63 (6)° with respect to the ZnN4 plane. Both complexes exhibit extensive hydrogen bonding. In (I), a stacked-sheet extended structure parallel to (101) is observed. In (II), the co-crystallized di­amine is hydrogen-bonded to the complex cation via O—H⋯N and N—H⋯N linkages. These units are in turn linked into planes along (200) by O—H⋯Cl and N—H⋯Cl hydrogen bonds. PMID:27555958

  10. Distribution of 3-hydroxy iC17:0 in subgingival plaque and gingival tissue samples: relationship to adult periodontitis.

    PubMed

    Nichols, F C

    1994-09-01

    Gram-negative organisms incorporate hydroxy fatty acids into the lipid A moiety of lipopolysaccharide (LPS), and in the case of some members of the family Enterobacteriaceae, hydroxy fatty acids are incorporated exclusively into lipid A. However, a limited number of Bacteroides species have been shown to incorporate several classes of 3-hydroxy fatty acids, particularly 3-hydroxy iC17:0, into constitutive lipids as well as LPS. The present study examined the distribution of hydroxy fatty acids in two periodontal pathogens, Prevotella intermedia and Porphyromonas gingivalis, by employing a phospholipid extraction procedure (E. G. Bligh and W. J. Dyer, Can. J. Biochem. Physiol. 37:911-917, 1959) which partitioned constitutive lipids into the organic solvent phase and LPS into the aqueous phase. The distribution of hydroxy fatty acids within organic solvent and aqueous extracts of these bacterial species was then compared with the distribution in subgingival plaque samples isolated from either gingivitis or severe periodontitis sites as well as the distribution in gingival tissue samples. The organic solvent and aqueous extracts were hydrolyzed under strong alkaline conditions, and the free fatty acids were treated to form pentafluorobenzyl-ester, trimethylsilyl-ether derivatives. Hydroxy fatty acid levels were quantified by using gas chromatography-negative-ion chemical ionization-mass spectrometry. By using this approach, the mean values of the 3-hydroxy iC17:0 recovered within organic solvent extracts of P. gingivalis strains ranged from 56 to 63% of total 3-hydroxy iC17:0. Substantially less 3-hydroxy iC17:0 (< 5%) was recovered in organic solvent extracts of P. intermedia. By comparison, 75% of the 3-hydroxy iC17:0 in periodontitis subgingival plaque samples was recovered in organic solvent extracts, while only 43% of the 3-hydroxy iC17:0 in gingivitis plaque samples from the same patients was recovered in organic solvent extracts. However, 3-hydroxy iC17:0 was

  11. Copper, lead and zinc in salt marsh sediments of the Severn Estuary, UK: The potential for their early diagnetic mobility.

    PubMed

    Rae, J E

    1989-12-01

    A detailed lithostratigraphic analysis already exists for salt marsh sediments of the Severn Estuary, which provides an ideal background for an investigation of phase associations of trace elements within sediment depth profiles. The first stages of a detailed investigation are reported in which phase associations of Cu, Pb and Zn are related to early diagenetic processes. PMID:24202421

  12. The effect of calcium salts, ascorbic acid and peptic pH on calcium, zinc and iron bioavailabilities from fortified human milk using an in vitro digestion/Caco-2 cell model.

    PubMed

    Etcheverry, Paz; Wallingford, John Charles; Miller, Dennis Dean; Glahn, Raymond Philip

    2005-05-01

    The calcium, zinc, and iron bioavailabilities of human milk with commercial and noncommercial human milk fortifiers (HMFs) were evaluated under a variety of conditions: peptic digestion at pH 2 and pH 4, supplementation of ascorbic acid, and addition of three calcium salts. The noncommercial HMFs consisted of casein phosphopeptides (CPPs), alpha-lactalbumin, colostrum, and hydrolyzed whey protein concentrate (WPC). They were mixed with human milk (HM) and calcium, zinc, and iron were added. Ascorbic acid (AA) was added in certain studies. The commercial HMFs were Nestlé FM-85, Similac HMF (SHMF), and Enfamil HMF (EHMF). All HMFs were compared to S-26/SMA HMF. Results showed that the peptic pH (2 vs. 4) had no effect on mineral bioavailability. Addition of different calcium salts had no effect on calcium cell uptake and cell ferritin levels (an indicator of iron uptake), however, the addition of calcium glycerophosphate/gluconate increased zinc uptake by Caco-2 cells. Addition of AA significantly increased ferritin levels, with no effect on calcium or zinc uptake. Among the commercial HMFs, FM-85 was significantly lower in zinc uptake than S-26/SMA, and HM+EHMF was significantly higher than HM+S-26/SMA. Cell ferritin levels were significantly higher for HM+S-26/SMA than for all other commercial fortifiers. None of the commercial HMFs were different from HM+S-26/SMA in calcium uptake.

  13. Carnitine biosynthesis. Hydroxylation of N6-trimethyl-lysine to 3-hydroxy-N6-trimethyl-lysine.

    PubMed

    Sachan, D S; Hoppel, C L

    1980-05-15

    Rat kidney homogenates metabolize N6-trimethyl-lysine to N-trimethylammoniobutyrate, but not to carnitine. The first step in this conversion is the hydroxylation of trimethyl-lysine to form 3-hydroxy-N6-trimethyl-lysine. An assay system was developed in which hydroxylation of trimethyl-lysine is linear with respect to both time and homogenate protein concentration. The rate is 5 nmol of 3-hydroxy-N6-trimethyl-lysine formed/min per mg of homogenate protein. The cofactors required are ascorbate, alpha-oxoglutarate, FeSO4, and O2. Catalase and dithiothreitol give a 20% stimulation. Ca2+ produces a 2-fold increase in specific activity and cannot be replaced by Mg2+, Mn2+ or Zn2+. These last three bivalent cations lead to a decreased activity. Subcellular distribution studies demonstrate that trimethyl-lysine hydroxylase activity parallels the distribution profile of succinate dehydrogenase and citrate synthase. Thus trimethyl-lysine hydroxylase has a mitochondrial localization. Distribution of trimethyl-lysine hydroxylase activity between cortex and medulla of kidney if 67 and 33% respectively, similar to mitochondrial distribution.

  14. Novel 1-Phenyl-3-hydroxy-4-pyridinone Derivatives as Multifunctional Agents for the Therapy of Alzheimer's Disease.

    PubMed

    Sheng, Rong; Tang, Li; Jiang, Liu; Hong, Lingjuan; Shi, Ying; Zhou, Naiming; Hu, Yongzhou

    2016-01-20

    A series of novel 1-phenyl-3-hydroxy-4-pyridinone derivatives were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy through incorporation of 3-hydroxy-4-pyridinone moiety from deferiprone into the scaffold of H3 receptor antagonists. Most of these new compounds displayed designed quadruple functions, H3 receptor antagonism, Aβ aggregation inhibition, metal ion chelation, and radical scavenging. Especially, the most promising compound 5c displayed nanomolar IC50 values in H3 receptor antagonism with high selectivity, efficient capability to interrupt the formation of Aβ(1-42) fibrils, good copper and iron chelating properties, and more potent 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) radical cation (ABTS(•+)) scavenging activity than Trolox. Further biological evaluation revealed that it did not show obvious cytotoxicity and hERG potassium channel inhibition at micromolar concentration. In addition, compound 5c demonstrated suitable pharmacokinetic properties and acceptable blood-brain barrier (BBB) permeability in vivo. All these results indicate that compound 5c is a potential multifunctional candidate for AD therapy. PMID:26479744

  15. Novel 1-Phenyl-3-hydroxy-4-pyridinone Derivatives as Multifunctional Agents for the Therapy of Alzheimer's Disease.

    PubMed

    Sheng, Rong; Tang, Li; Jiang, Liu; Hong, Lingjuan; Shi, Ying; Zhou, Naiming; Hu, Yongzhou

    2016-01-20

    A series of novel 1-phenyl-3-hydroxy-4-pyridinone derivatives were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy through incorporation of 3-hydroxy-4-pyridinone moiety from deferiprone into the scaffold of H3 receptor antagonists. Most of these new compounds displayed designed quadruple functions, H3 receptor antagonism, Aβ aggregation inhibition, metal ion chelation, and radical scavenging. Especially, the most promising compound 5c displayed nanomolar IC50 values in H3 receptor antagonism with high selectivity, efficient capability to interrupt the formation of Aβ(1-42) fibrils, good copper and iron chelating properties, and more potent 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) radical cation (ABTS(•+)) scavenging activity than Trolox. Further biological evaluation revealed that it did not show obvious cytotoxicity and hERG potassium channel inhibition at micromolar concentration. In addition, compound 5c demonstrated suitable pharmacokinetic properties and acceptable blood-brain barrier (BBB) permeability in vivo. All these results indicate that compound 5c is a potential multifunctional candidate for AD therapy.

  16. Functional size of rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase as determined by radiation inactivation

    SciTech Connect

    Edwards, P.A.; Kempner, E.S.; Lan, S.F.; Erickson, S.K.

    1985-08-25

    The functional molecular weight of rat liver 3-hydroxy-3-methylglutaryl-CoA reductase was determined by radiation inactivation. Both isolated hepatic microsomes and primary hepatocytes were irradiated with high energy electrons at -135 degrees C, and the residual microsomal enzyme activity was subsequently determined. The loss of enzyme activity in both irradiated microsomes and microsomes isolated from irradiated hepatocytes followed a single exponential decay which corresponded to a molecular mass of 200 kDa. This minimal molecular size of the functional enzyme was unaffected by either addition of cholestyramine to the rat diet or addition of 25-hydroxycholesterol plus mevalonate to the isolated rat hepatocytes. In addition, surviving enzyme protein was determined by immunoprecipitation of radiolabeled enzyme from hepatocytes that had been incubated with (TVS)methionine before irradiation. The target size for loss of the monomer subunits was 98 kDa. The simplest interpretation of these results is that rat liver 3-hydroxy-3-methylglutaryl-CoA reductase in situ is a noncovalently linked dimer of the Mr = 97,200 enzyme subunit.

  17. Double layer structure-based virtual screening reveals 3'-Hydroxy-A-Naphthoflavone as novel inhibitor candidate of human acetylcholinesterase

    NASA Astrophysics Data System (ADS)

    Ichsan, Mochammad; Pangastuti, Ardini; Habibi, Mohammad Wildan; Juliana, Kartika

    2016-03-01

    One of the most effective target for Alzheimer's disease's (AD) treatment is the inhibition of human acetylcholinesterase (hAChE) eventhough it has many side effects. So that, this study was aimed to discover a new candidate of hAChE's inhibitor that has more negative binding affinity than existing drugs. hAChE's 3D model used in this study has a good quality according to its number of residues in most favoured regions (92%), three bad contacts, >50 ERRAT's score (85,870) and successfully passed the VERIFY 3D threshold (>80%). Based on the first layer of SBVS againts more than 12.180.630 ligands, we discovered 11.806 hits and then we found 359 hits from the second layer of SBVS. Based on our previous steps, we found that 3'-Hydroxy-a-Naphthoflavone was the only one candidate, that directly interacted with Trp286 via hydrogen bond and hydrophobic interactions and also has the most negative binding affinity (-10,6 kcal/mol) and also has more negative than existing hAChE's inhibitors, such as tacrine, donepezil, etc. 3'-Hydroxy-a-Naphthoflavone is the best candidate of hAChE's inhibitor based on its binding affinity (-10,6 kcal/mol) that is more negative than existing hAChE's inhibitors, such as tacrine, donepezil, etc.

  18. 3-Hydroxy-3-methylglutaric and 3-methylglutaric acids impair redox status and energy production and transfer in rat heart: relevance for the pathophysiology of cardiac dysfunction in 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency.

    PubMed

    da Rosa, Mateus Struecker; Seminotti, Bianca; Ribeiro, César Augusto João; Parmeggiani, Belisa; Grings, Mateus; Wajner, Moacir; Leipnitz, Guilhian

    2016-09-01

    3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency is characterized by tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), and 3-methylglutaric (MGA) acids. Affected patients present cardiomyopathy, whose pathomechanisms are not yet established. We investigated the effects of HMG and MGA on energy and redox homeostasis in rat heart using in vivo and in vitro models. In vivo experiments showed that intraperitoneal administration of HMG and MGA decreased the activities of the respiratory chain complex II and creatine kinase (CK), whereas HMG also decreased the activity of complex II-III. Furthermore, HMG and MGA injection increased reactive species production and carbonyl formation, and decreased glutathione concentrations. Regarding the enzymatic antioxidant defenses, HMG and MGA increased glutathione peroxidase (GPx) and glutathione reductase (GR) activities, while only MGA diminished the activities of superoxide dismutase (SOD) and catalase, as well as the protein content of SOD1. Pre-treatment with melatonin (MEL) prevented MGA-induced decrease of CK activity and SOD1 levels. In vitro results demonstrated that HMG and MGA increased reactive species formation, induced lipid peroxidation and decreased glutathione. We also verified that reactive species overproduction and glutathione decrease provoked by HMG and MGA were abrogated by MEL and lipoic acid (LA), while only MEL prevented HMG- and MGA-induced lipoperoxidation. Allopurinol (ALP) also prevented reactive species overproduction caused by both metabolites. Our data provide solid evidence that bioenergetics dysfunction and oxidative stress are induced by HMG and MGA in heart, which may explain the cardiac dysfunction observed in HL deficiency, and also suggest that antioxidant supplementation could be considered as adjuvant therapy for affected patients.

  19. Friedel-Crafts alkylations of electron-rich aromatics with 3-hydroxy-2-oxindoles: scope and limitations.

    PubMed

    Kinthada, Lakshmana K; Ghosh, Santanu; Babu, K Naresh; Sharique, Mohd; Biswas, Soumava; Bisai, Alakesh

    2014-11-01

    A Lewis acid-catalyzed nucleophilic addition of electron rich aromatics with 3-hydroxy-2-oxindoles 5 was developed. The reaction is believed to proceed through the 2H-indol-2-one ring system 9, which eventually reacts with various electron-rich aromatics to afford a variety of 2-oxindoles with an all-carbon quaternary center at the pseudobenzylic position (4, 8, 13, and 16) in high yields. The methodology provides an expeditious route to the tetracyclic core (3) of diazonamide (1), and azonazine (2) as well as the tricyclic core of asperazine (6a), idiospermuline (6b), and calycosidine (6c) viz. C(3a)-arylpyrroloindolines 7 having an all-carbon quaternary center on further synthetic elaboration.

  20. Studies on the growth and characterization of a non linear optical crystal: 3 Hydroxy Pyridinium Tartrate Mono Hydrate (3HPTMH).

    PubMed

    Balaji, J; Prabu, S; Srinivasan, P; Srinivasan, T; Velmurugan, D

    2015-06-01

    Single crystals of 3 Hydroxy Pyridinium Tartrate Mono Hydrate (3HPTMH) was synthesised and successfully grown in mixed solvent of ethanol and water by slow evaporation technique at room temperature. 3HPTMH belongs to the orthorhombic crystal system with space group P212121. The lattice parameters of 3HPTMH are a=7.4597(2)Å, b=8.7012(3)Å, c=17.8786(5)Å, V=1160.47(6)Å(3), obtained by single crystal X ray diffraction studies. Hyperpolarizability and HOMO-LUMO analysis were performed for grown crystal using DFT calculations using Gaussian 03 software. Functional groups were identified by FT-IR studies. The lower cut-off wavelength of the 3HPTMH has been identified by UV-Vis study. The thermal behavior has been studied by thermal gravimetric analysis and differential thermal analysis. The powder second harmonic generation efficiency of 3HPTMH was compared with KDP.

  1. Design of a Water Soluble Fluorescent 3-Hydroxy-4-Pyridinone Ligand Active at Physiological pH Values.

    PubMed

    Leite, Andreia; Silva, Ana M G; Coutinho, Catarina; Cunha-Silva, Luís; de Castro, Baltazar; Rangel, Maria

    2016-09-01

    In the present work we report the structure and the spectroscopic characterization of a new fluorescent 3-hydroxy-4-pyridinone ligand D-3,4-HPO. The synthesis of the compound was performed in two steps, which involve the reaction of the commercially available fluorophore dansyl chloride with a 3-hydroxy-4-pyridinone chelating unit and further deprotection. The new fluorescent chelator was characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR, MS, absorption and fluorescence spectroscopies. The analysis of the variation of the absorption spectrum with pH allowed the determination of four pK a values (pK a1  = 3.50, pK a2  = 4.50, pK a3  = 9.60, pK a4  = 10.20) and establishment of the corresponding distribution diagram. The study of the fluorescence properties of the ligand show that in the pH range between 4 and 9 the fluorescence intensity is constant and has its maximum value thus allowing its further use at physiological pH values. The interaction of the ligand with copper(II) was accessed by fluorescence spectroscopy in MOPS buffer and the results show that the presence of copper(II) quenches the fluorescence of the ligand in ca 94 % at a ligand: metal ratio of 2:1. The latter result is consistent with the formation of a copper(II) complex with the bidentate ligand, as confirmed by the EPR spectroscopy. Graphical Abstract New water soluble fluorescent ligand active at physiological pH values. PMID:27357392

  2. Design of a Water Soluble Fluorescent 3-Hydroxy-4-Pyridinone Ligand Active at Physiological pH Values.

    PubMed

    Leite, Andreia; Silva, Ana M G; Coutinho, Catarina; Cunha-Silva, Luís; de Castro, Baltazar; Rangel, Maria

    2016-09-01

    In the present work we report the structure and the spectroscopic characterization of a new fluorescent 3-hydroxy-4-pyridinone ligand D-3,4-HPO. The synthesis of the compound was performed in two steps, which involve the reaction of the commercially available fluorophore dansyl chloride with a 3-hydroxy-4-pyridinone chelating unit and further deprotection. The new fluorescent chelator was characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR, MS, absorption and fluorescence spectroscopies. The analysis of the variation of the absorption spectrum with pH allowed the determination of four pK a values (pK a1  = 3.50, pK a2  = 4.50, pK a3  = 9.60, pK a4  = 10.20) and establishment of the corresponding distribution diagram. The study of the fluorescence properties of the ligand show that in the pH range between 4 and 9 the fluorescence intensity is constant and has its maximum value thus allowing its further use at physiological pH values. The interaction of the ligand with copper(II) was accessed by fluorescence spectroscopy in MOPS buffer and the results show that the presence of copper(II) quenches the fluorescence of the ligand in ca 94 % at a ligand: metal ratio of 2:1. The latter result is consistent with the formation of a copper(II) complex with the bidentate ligand, as confirmed by the EPR spectroscopy. Graphical Abstract New water soluble fluorescent ligand active at physiological pH values.

  3. Effects of replacing a dietary antibacterial agent (zinc bacitracin) with copper salts in Cherry Valley Pekin meat ducks.

    PubMed

    Wu, D W; Wang, L C; Wen, C; Hooge, D M; Liang, C; Zhou, Y M

    2013-01-01

    1. A study was conducted to investigate the effectiveness of high dietary copper concentrations obtained from tribasic copper chloride (TBCC, 58% copper) and copper sulphate pentahydrate (CuSO4, 25% copper) in replacing antibiotic growth promoters (AGP) in duck diets. 2. A total of 960 one-day-old Cherry Valley meat-strain ducks were divided into 3 treatment groups, with 8 replicates per treatment, in a 6-week feeding trial. The ducks were fed a basal diet supplemented with AGP (40 mg zinc bacitracin/kg and 40 mg garlicin/kg of diet) or 150 mg of Cu/kg of diet, given as either CuSO4 or TBCC. 3. The body weight, average daily gain, average daily feed intake and mortality of ducks were not affected by the dietary treatments. However, the feed/gain ratio of ducks that were fed TBCC diets was significantly lower than those of ducks that were fed CuSO4 diets and were similar to those in the AGP group. 4. TBCC increased the Cu content in the liver tissue of ducks compared with the content in those that were fed the diet supplemented with AGP. TBCC also increased the Fe and Zn content in breast muscles compared with that in ducks that were fed the diet supplemented with CuSO4. 5. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly higher in the serum of ducks that received the diet supplemented with TBCC than AGP or CuSO4. TBCC treatment decreased the malondialdehyde (MDA) content in serum of ducks compared with groups supplemented with CuSO4. 6. No significant difference was observed in liver or muscle fat content among the different dietary treatment groups. The serum low-density lipoprotein cholesterol concentration was lower in ducks fed AGP diets than those fed CuSO4 diets. 7. It was concluded that the replacement of AGP with 150 mg of Cu/kg of feed from TBCC improved the feed efficiency, trace mineral deposition and antioxidant status more than when the source of copper was CuSO4.

  4. Cloning, Characterization and Expression Pattern Analysis of a Cytosolic Copper/Zinc Superoxide Dismutase (SaCSD1) in a Highly Salt Tolerant Mangrove (Sonneratia alba)

    PubMed Central

    Yang, Enze; Yi, Shanze; Bai, Fang; Niu, Dewei; Zhong, Junjie; Wu, Qiuhong; Chen, Shufang; Zhou, Renchao; Wang, Feng

    2015-01-01

    Mangroves are critical marine resources for their remarkable ability to tolerate seawater. Antioxidant enzymes play an especially significant role in eliminating reactive oxygen species and conferring abiotic stress tolerance. In this study, a cytosolic copper/zinc superoxide dismutase (SaCSD1) cDNA of Sonneratia alba, a mangrove species with high salt tolerance, was successfully cloned and then expressed in Escherichia coli Rosetta-gami (designated as SaCSD1). SaCSD1 comprised a complete open reading frame (ORF) of 459 bp which encoded a protein of 152 amino acids. Its mature protein is predicted to be 15.32 kDa and the deduced isoelectric point is 5.78. SaCSD1 has high sequence similarity (85%–90%) with the superoxide dismutase (CSD) of some other plant species. SaCSD1 was expressed with 30.6% yield regarding total protein content after being introduced into the pET-15b (Sma I) vector for expression in Rosetta-gami and being induced with IPTG. After affinity chromatography on Ni-NTA, recombinant SaCSD1 was obtained with 3.2-fold purification and a specific activity of 2200 U/mg. SaCSD1 showed good activity as well as stability in the ranges of pH between 3 and 7 and temperature between 25 and 55 °C. The activity of recombinant SaCSD1 was stable in 0.25 M NaCl, Dimethyl Sulphoxide (DMSO), glycerol, and chloroform, and was reduced to a great extent in β-mercaptoethanol, sodium dodecyl sulfate (SDS), H2O2, and phenol. Moreover, the SaCSD1 protein was very susceptive to pepsin digestion. Real-time Quantitative Polymerase Chain Reaction (PCR) assay demonstrated that SaCSD1 was expressed in leaf, stem, flower, and fruit organs, with the highest expression in fruits. Under 0.25 M and 0.5 M salt stress, the expression of SaCSD1 was down-regulated in roots, but up-regulated in leaves. PMID:26703583

  5. Cloning, Characterization and Expression Pattern Analysis of a Cytosolic Copper/Zinc Superoxide Dismutase (SaCSD1) in a Highly Salt Tolerant Mangrove (Sonneratia alba).

    PubMed

    Yang, Enze; Yi, Shanze; Bai, Fang; Niu, Dewei; Zhong, Junjie; Wu, Qiuhong; Chen, Shufang; Zhou, Renchao; Wang, Feng

    2016-01-01

    Mangroves are critical marine resources for their remarkable ability to tolerate seawater. Antioxidant enzymes play an especially significant role in eliminating reactive oxygen species and conferring abiotic stress tolerance. In this study, a cytosolic copper/zinc superoxide dismutase (SaCSD1) cDNA of Sonneratia alba, a mangrove species with high salt tolerance, was successfully cloned and then expressed in Escherichia coli Rosetta-gami (designated as SaCSD1). SaCSD1 comprised a complete open reading frame (ORF) of 459 bp which encoded a protein of 152 amino acids. Its mature protein is predicted to be 15.32 kDa and the deduced isoelectric point is 5.78. SaCSD1 has high sequence similarity (85%-90%) with the superoxide dismutase (CSD) of some other plant species. SaCSD1 was expressed with 30.6% yield regarding total protein content after being introduced into the pET-15b (Sma I) vector for expression in Rosetta-gami and being induced with IPTG. After affinity chromatography on Ni-NTA, recombinant SaCSD1 was obtained with 3.2-fold purification and a specific activity of 2200 U/mg. SaCSD1 showed good activity as well as stability in the ranges of pH between 3 and 7 and temperature between 25 and 55 °C. The activity of recombinant SaCSD1 was stable in 0.25 M NaCl, Dimethyl Sulphoxide (DMSO), glycerol, and chloroform, and was reduced to a great extent in β-mercaptoethanol, sodium dodecyl sulfate (SDS), H₂O2, and phenol. Moreover, the SaCSD1 protein was very susceptive to pepsin digestion. Real-time Quantitative Polymerase Chain Reaction (PCR) assay demonstrated that SaCSD1 was expressed in leaf, stem, flower, and fruit organs, with the highest expression in fruits. Under 0.25 M and 0.5 M salt stress, the expression of SaCSD1 was down-regulated in roots, but up-regulated in leaves. PMID:26703583

  6. Identification of a 3-hydroxy-3-methylglutaryl-CoA reductase gene highly expressed in the root tissue of Taraxacum kok-saghyz

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kazak dandelion (Taraxacum kok-saghyz, Tk) is a rubber-producing plant currently being investigated as a source of natural rubber for industrial applications. Like many other isoprenoids, rubber is a downstream product of the mevalonate pathway. The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) en...

  7. Induction mechanism of 3-hydroxy-3-methylglutaryl-CoA reductase in potato tuber and sweet potato root tissues.

    PubMed

    Kondo, Katsuyoshi; Uritani, Ikuzo; Oba, Kazuko

    2003-05-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR, EC1.1.1.34), the key enzyme in isoprenoid biosynthesis, was purified from microsomes of potato tuber tissue, and a polyclonal antibody and two monoclonal antibodies against the purified enzyme were prepared. HMGR protein content was measured by immunotitration and radioimmunoassay using these antibodies. HMGR activity was very low in the fresh tissues of both potato tuber and sweet potato root. The activity in potato tuber was increased by cutting and further by additional fungal infection of the cut tissues. In sweet potato root tissue, the activity was scarcely increased after cutting alone, but was markedly increased by additional fungal infection or chemical treatment. The HMGR protein contents in both fresh potato tuber and sweet potato root tissues were also very low, and increased markedly in response to cutting and fungal infection. From these results, we proposed a hypothesis on the induction mechanism of HMGR after cutting and fungal infection in potato tuber and sweet potato root tissues.

  8. Sequence comparison of a segment of the gene for 3-hydroxy-3-methylglutaryl-coenzyme A reductase in zygomycetes.

    PubMed

    Burmester, A; Czempinski, K

    1994-03-01

    In this paper we compare the sequences of a segment of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase gene, isolated from eleven different strains belonging to four species of the fungal order Mucorales, Parasitella parasitica, Absidia glauca, Mucor mucedo (Mucoraceae) and Blakeslea trispora (Choanephoraceae). The segment was obtained by polynucleotide-chain-reaction amplification with primers derived from conservative regions of the gene. For the species M. mucedo and P. parasitica we have obtained evidence for two different types of HMG-CoA reductase genes by hybridization of genomic DNA with the amplified fragment and by cloning and sequencing of two different fragments. The different genes from one species show a sequence similarity of around 80% at the protein sequence level, whereas sequences of the same type from different species show similarity ranging between 91-96%. The highest similarity was found between the genes of type 1 from B. trispora and M. mucedo, although these species belong to different families. Southern-blot analysis of A. glauca DNA and B. trispora DNA revealed a second copy of the genes.

  9. Modulation of dendritic cell immunobiology via inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase.

    PubMed

    Leuenberger, Tina; Pfueller, Caspar F; Luessi, Felix; Bendix, Ivo; Paterka, Magdalena; Prozorovski, Timour; Treue, Denise; Luenstedt, Sarah; Herz, Josephine; Siffrin, Volker; Infante-Duarte, Carmen; Zipp, Frauke; Waiczies, Sonia

    2014-01-01

    The maturation status of dendritic cells determines whether interacting T cells are activated or if they become tolerant. Previously we could induce T cell tolerance by applying a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor (HMGCRI) atorvastatin, which also modulates MHC class II expression and has therapeutic potential in autoimmune disease. Here, we aimed at elucidating the impact of this therapeutic strategy on T cell differentiation as a consequence of alterations in dendritic cell function. We investigated the effect of HMGCRI during differentiation of peripheral human monocytes and murine bone marrow precursors to immature DC in vitro and assessed their phenotype. To examine the stimulatory and tolerogenic capacity of these modulated immature dendritic cells, we measured proliferation and suppressive function of CD4+ T cells after stimulation with the modulated immature dendritic cells. We found that an HMGCRI, atorvastatin, prevents dendrite formation during the generation of immature dendritic cells. The modulated immature dendritic cells had a diminished capacity to take up and present antigen as well as to induce an immune response. Of note, the consequence was an increased capacity to differentiate naïve T cells towards a suppressor phenotype that is less sensitive to proinflammatory stimuli and can effectively inhibit the proliferation of T effector cells in vitro. Thus, manipulation of antigen-presenting cells by HMGCRI contributes to an attenuated immune response as shown by promotion of T cells with suppressive capacities.

  10. Involvement of tristetraprolin in transcriptional activation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase by insulin

    SciTech Connect

    Ness, Gene C.; Edelman, Jeffrey L.; Brooks, Patricia A.

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer siRNAs to tristetraprolin blocks transcription of HMGR in vivo in rat liver. Black-Right-Pointing-Pointer siRNAs to tristetraprolin inhibits insulin activation of HMGR transcription. Black-Right-Pointing-Pointer Insulin acts to rapidly increase tristetraprolin in liver nuclear extracts. -- Abstract: Several AU-rich RNA binding element (ARE) proteins were investigated for their possible effects on transcription of hepatic 3-hydroxy-3-methyglutaryl coenzyme A reductase (HMGR) in normal rats. Using in vivo electroporation, four different siRNAs to each ARE protein were introduced together with HMGR promoter (-325 to +20) luciferase construct and compared to saline controls. All four siRNAs to tristetraprolin (TTP) completely eliminated transcription from the HMGR promoter construct. Since insulin acts to rapidly increase hepatic HMGR transcription, the effect of TTP siRNA on induction by insulin was tested. The 3-fold stimulation by insulin was eliminated by this treatment. In comparison, siRNA to AU RNA binding protein/enoyl coenzyme A hydratase (AUH) had no effect. These findings indicate a role for TTP in the insulin-mediated activation of hepatic HMGR transcription.

  11. Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase

    SciTech Connect

    Sarver, Ronald W.; Bills, Elizabeth; Bolton, Gary; Bratton, Larry D.; Caspers, Nicole L.; Dunbar, James B.; Harris, Melissa S.; Hutchings, Richard H.; Kennedy, Robert M.; Larsen, Scott D.; Pavlovsky, Alexander; Pfefferkorn, Jeffrey A.; Bainbridge, Graeme

    2008-10-02

    Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2--7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC{sub 50} = 7.9 nM) inhibitor with excellent hepatoselectivity (>1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a {Delta}H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

  12. Cloning and functional characterization of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Withania somnifera: an important medicinal plant.

    PubMed

    Akhtar, Nehal; Gupta, Parul; Sangwan, Neelam Singh; Sangwan, Rajender Singh; Trivedi, Prabodh Kumar

    2013-04-01

    Withania somnifera (L.) Dunal is one of the most valuable medicinal plants synthesizing a large number of pharmacologically active secondary metabolites known as withanolides, the C28-steroidal lactones derived from triterpenoids. Though the plant has been well characterized in terms of phytochemical profiles as well as pharmaceutical activities, not much is known about the biosynthetic pathway and genes responsible for biosynthesis of these compounds. In this study, we have characterized the gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) catalyzing the key regulatory step of the isoprenoid biosynthesis. The 1,728-bp full-length cDNA of Withania HMGR (WsHMGR) encodes a polypeptide of 575 amino acids. The amino acid sequence homology and phylogenetic analysis suggest that WsHMGR has typical structural features of other known plant HMGRs. The relative expression analysis suggests that WsHMGR expression varies in different tissues as well as chemotypes and is significantly elevated in response to exposure to salicylic acid, methyl jasmonate, and mechanical injury. The functional color assay in Escherichia coli showed that WsHMGR could accelerate the biosynthesis of carotenoids, establishing that WsHMGR encoded a functional protein and may play a catalytic role by its positive influence in isoprenoid biosynthesis.

  13. Comparison of regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in hepatoma cells grown in vivo and in vitro.

    PubMed Central

    Beirne, O R; Watson, J A

    1976-01-01

    Unlike the normal liver, numerous transplantable rodent and human hepatomas are unable to alter their rate of sterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-GoA) reductase [mevalonate: NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] activity in response to a dietary cholesterol challenge. It has been suggested that this metabolic defect is linked to the process of malignant transformation. Hepatoma 7288C "lacks" feedback regulation of cholesterol synthesis when grown in vivo but expresses this regulatory property when grown in vitro (then called HTC). Therefore, it was used as a model system to answer whether an established hepatoma cell line that modulates its rate of cholesterol synthesis in vitro can express this property when grown in vivo, and whether cells reisolated from the tumor mass have the same regulatory phenotype as before transplantation. Our results show that long-term growth of hepatoma 7288C in tissue culture has not caused a biotransformation that permits feedback regulation of HMG-CoA reductase when the cells are transplanted back into host animals. In addition, HTC cells reisolated from the tumor mass and established in tissue culture continue to have the ability to regulate HMG-CoA reductase activity. Therefore, malignant transformation is not categorically linked to the loss of the cellular components necessary to regulate sterol synthesis and HMG-CoA reductase activity. Images PMID:183207

  14. (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, a potent and selective inhibitor of human cytomegalovirus replication.

    PubMed Central

    Snoeck, R; Sakuma, T; De Clercq, E; Rosenberg, I; Holy, A

    1988-01-01

    From a series of phosphonylmethoxyalkylpurine and -pyrimidine derivatives, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] emerged as a particularly potent and selective inhibitor of the replication of human cytomegalovirus (CMV). Its potency against CMV was similar to that of the structurally related adenine derivative (S)-HPMPA but higher than that of the reference compounds phosphonoformate and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG). The minimum concentrations of phosphonoformate, DHPG, (S)-HPMPA, and (S)-HPMPC required to inhibit CMV plaque formation by 50% were 15, 0.7, 0.1, and 0.07 microgram/ml, respectively. The selectivity indices of phosphonoformate, DHPG, (S)-HPMPA, and (S)-HPMPC, as determined by the ratio of the 50% inhibitory concentration for cell growth to the 50% inhibitory concentration for plaque formation for CMV (AD-169 strain), were 14, 150, 200 and 1,500, respectively. Corresponding values for the CMV Davis strain were 20, 200, 100, and 1,000, respectively. (S)-HPMPC was inhibitory to CMV plaque formation even when added to the cells at 24 or 48 h postinfection. When (S)-HPMPC was added immediately postinfection, a 24- or 48-h incubation time sufficed to obtain a marked inhibitory effect on CMV replication. Such limited incubation time was insufficient for DHPG to achieve any protection against CMV. PMID:2854454

  15. Dual Targeting of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Histone Deacetylase as a Therapy for Colorectal Cancer.

    PubMed

    Wei, Tzu-Tang; Lin, Yi-Ting; Chen, Wen-Shu; Luo, Ping; Lin, Yu-Chin; Shun, Chia-Tung; Lin, Yi-Hsin; Chen, Jhih-Bin; Chen, Nai-Wei; Fang, Jim-Min; Wu, Ming-Shiang; Yang, Kai-Chien; Chang, Li-Chun; Tai, Kang-Yu; Liang, Jin-Tung; Chen, Ching-Chow

    2016-08-01

    Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) inhibitors decreasing serum cholesterol and have shown promise in cancer prevention. In this study, we demonstrated the oncogenic role of HMGR in colorectal cancer (CRC) by disclosing increased HMGR activity in CRC patients and its enhancement of anti-apoptosis and stemness. Our previous studies showed that statins containing carboxylic acid chains possessed activity against histone deacetylases (HDACs), and strengthened their anti-HDAC activity through designing HMGR-HDAC dual inhibitors, JMF compounds. These compounds exerted anti-cancer effect in CRC cells as well as in AOM-DSS and Apc(Min/+) CRC mouse models. JMF mostly regulated the genes related to apoptosis and inflammation through genome-wide ChIP-on-chip analysis, and Ingenuity Pathways Analysis (IPA) predicted their respective regulation by NR3C1 and NF-κB. Furthermore, JMF inhibited metastasis, angiogenesis and cancer stemness, and potentiated the effect of oxaliplatin in CRC mouse models. Dual HMGR-HDAC inhibitor could be a potential treatment for CRC. PMID:27448759

  16. Iron speciation in natural waters by sequential injection analysis with a hexadentate 3-hydroxy-4-pyridinone chelator as chromogenic agent.

    PubMed

    Miranda, Joana L A; Mesquita, Raquel B R; Nunes, Ana; Rangel, Maria; Rangel, António O S S

    2016-02-01

    A sequential injection method for iron speciation in various types of natural waters was developed using a synthesised hexadentate 3-hydroxy-4-pyridinone chelator (CP256). The denticity of the ligand that allow formation of the corresponding iron(III) complex in a 1:1 stoichiometry proved to be highly advantageous, in comparison with parent bidentate, hydroxy-4-piridinone chelators, with a two fold increase of reaction sensitivity and over 65% decrease of the LOD. A solid phase extraction approach was employed to attain matrix elimination, facilitating iron(III) determination and application to high salinity waters. The combination with the total iron determination obtained by the direct reaction of the ligand resulted in iron speciation. Two detection spectrophotometric cells were tested, a conventional flow cell (CFC) and a liquid waveguide capillary cell (LWCC). The dynamic concentration ranges were 0.1-2 mg/L with the CFC detection and 0.005-0.1 mg/L with the LWCC, with limit of detection of 30 µg/L and 6 µg/L, respectively. The developed method was successfully applied to a variety of natural waters.

  17. Characterization of wetland quorum quenching Pseudomonas aeruginosa strain 2SW8 and its 2-heptyl-3-hydroxy-4-quinolone production.

    PubMed

    Wong, Cheng-Siang; Yin, Wai-Fong; Sam, Choon-Kook; Koh, Chong-Lek; Chan, Kok-Gan

    2012-01-01

    Most Proteobacteria produce N-acylhomoserine lactones for bacterial cell-to-cell communication, a process called quorum sensing. Interference of quorum sensing, commonly known as quorum quenching, represents an important way to control quorum sensing. This work reports the isolation of quorum quenching bacterium strain 2WS8 from Malaysia tropical wetland water (2°11'8"N, 102°15'2"E, in 2007) by using a modified version of a previously reported KG medium. Strain 2WS8 was isolated based on its ability to utilize N-(3-oxohexanoyl)-L-homoserine lactone (3-oxo-C6-HSL) as the sole source of energy. This bacterium clustered closely to Pseudomonas aeruginosa PAO1. Strain 2SW8 possesses both quiP and pvdQ homologue acylase genes. Rapid Resolution Liquid Chromatography analysis confirmed that strain 2SW8 preferentially degraded N-acylhomoserine lactones with 3-oxo group substitution but not those with unsubstituted groups at C3 position in the acyl side chain. Strain 2SW8 also showed 2-heptyl-3-hydroxy-4-quinolone production.

  18. Growth and characterization of novel organic 3-Hydroxy Benzaldehyde-N-methyl 4 Stilbazolium Tosylate crystals for NLO applications

    NASA Astrophysics Data System (ADS)

    Jagannathan, K.; Umarani, P.; Ratchagar, V.; Ramesh, V.; Kalainathan, S.

    2016-01-01

    The 3-Hydroxy Benzaldehyde-N-methyl 4-Stilbazolium Tosylate (3- HBST) is a new organic NLO crystal and it is a new derivative in stilbazolium tosylate family. In this work we have synthesized 3-HBST and the single crystal was grown by conventional slow cooling method. The structure and lattice parameters of the grown crystal were determined by the single crystal X-ray diffraction (XRD) technique and it is exhibiting good crystalline nature which is observed from the powder XRD. In order to check the crystalline quality the rocking curve was recorded using multi crystal X-ray diffractometer. The functional groups were identified from both FTIR and NMR spectral analyses. The π-π* and n-π* optical transition energy levels were estimated from the absorption peaks. The NLO property was confirmed by measuring relative SHG efficiency by Kurtz powder test; it shows 24 times higher SHG efficiency than that of urea. In order to test the mechanical stability the Vickers and Knoop micro hardness measurement were carried out and found that the micro hardness number decreases with increasing load. The melting point was determined from Differential Scanning Colorimetry (DSC).

  19. Growth and characterization of novel organic 3-Hydroxy Benzaldehyde-N-methyl 4 Stilbazolium Tosylate crystals for NLO applications.

    PubMed

    Jagannathan, K; Umarani, P; Ratchagar, V; Ramesh, V; Kalainathan, S

    2016-01-15

    The 3-Hydroxy Benzaldehyde-N-methyl 4-Stilbazolium Tosylate (3- HBST) is a new organic NLO crystal and it is a new derivative in stilbazolium tosylate family. In this work we have synthesized 3-HBST and the single crystal was grown by conventional slow cooling method. The structure and lattice parameters of the grown crystal were determined by the single crystal X-ray diffraction (XRD) technique and it is exhibiting good crystalline nature which is observed from the powder XRD. In order to check the crystalline quality the rocking curve was recorded using multi crystal X-ray diffractometer. The functional groups were identified from both FTIR and NMR spectral analyses. The π-π* and n-π* optical transition energy levels were estimated from the absorption peaks. The NLO property was confirmed by measuring relative SHG efficiency by Kurtz powder test; it shows 24 times higher SHG efficiency than that of urea. In order to test the mechanical stability the Vickers and Knoop micro hardness measurement were carried out and found that the micro hardness number decreases with increasing load. The melting point was determined from Differential Scanning Colorimetry (DSC).

  20. Genome-Based Analysis and Gene Dosage Studies Provide New Insight into 3-Hydroxy-4-Methylvalerate Biosynthesis in Ralstonia eutropha

    PubMed Central

    Ushimaru, Kazunori; Mizuno, Shoji

    2015-01-01

    Recombinant Ralstonia eutropha strain PHB−4 expressing the broad-substrate-specificity polyhydroxyalkanoate (PHA) synthase 1 from Pseudomonas sp. strain 61-3 (PhaC1Ps) synthesizes a PHA copolymer containing the branched side-chain unit 3-hydroxy-4-methylvalerate (3H4MV), which has a carbon backbone identical to that of leucine. Mutant strain 1F2 was derived from R. eutropha strain PHB−4 by chemical mutagenesis and shows higher levels of 3H4MV production than does the parent strain. In this study, to understand the mechanisms underlying the enhanced production of 3H4MV, whole-genome sequencing of strain 1F2 was performed, and the draft genome sequence was compared to that of parent strain PHB−4. This analysis uncovered four point mutations in the 1F2 genome. One point mutation was found in the ilvH gene at amino acid position 36 (A36T) of IlvH. ilvH encodes a subunit protein that regulates acetohydroxy acid synthase III (AHAS III). AHAS catalyzes the conversion of pyruvate to 2-acetolactate, which is the first reaction in the biosynthesis of branched amino acids such as leucine and valine. Thus, the A36T IlvH mutation may show AHAS tolerance to feedback inhibition by branched amino acids, thereby increasing carbon flux toward branched amino acid and 3H4MV biosynthesis. Furthermore, a gene dosage study and an isotope tracer study were conducted to investigate the 3H4MV biosynthesis pathway. Based on the observations in these studies, we propose a 3H4MV biosynthesis pathway in R. eutropha that involves a condensation reaction between isobutyryl coenzyme A (isobutyryl-CoA) and acetyl-CoA to form the 3H4MV carbon backbone. PMID:25645560

  1. Characterization of endotoxin and 3-hydroxy fatty acid levels in air and settled dust from commercial aircraft cabins.

    PubMed

    Hines, C J; Waters, M A; Larsson, L; Petersen, M R; Saraf, A; Milton, D K

    2003-06-01

    Endotoxin was measured in air and dust samples collected during four commercial aircraft flights. Samples were analyzed for endotoxin biological activity using the Limulus assay. 3-hydroxy fatty acids (3-OH FA) of carbon chain lengths C10:0-C18:0 were determined in dust by gas chromatography-ion trap tandem mass spectrometry. The geometric mean (geometric standard deviation) endotoxin air level was 1.5 EU/m3 (1.9, n = 28); however, significant differences were found by flight within aircraft type. Mean endotoxin levels were significantly higher in carpet dust than in seat dust (140 +/- 81 vs. 51 +/- 25 EU/mg dust, n = 32 each, P < 0.001). Airborne endotoxin levels were not significantly related to either carpet or seat dust endotoxin levels. Mean 3-OH FA levels were significantly higher in carpet dust than in seat dust for C10:2, C12:0, and C14:0 (P < 0.001 for each), while the mean level of C16:0 was significantly higher in seat dust than in carpet dust (P < 0.01). Carpet dust endotoxin was significantly, but moderately, correlated with 3-OH-C12:0 and 3-OH-C14:0 (Pearson r = 0.52 and 0.48, respectively), while correlation of seat dust endotoxin with individual 3-OH FAs depended on the test statistic used. Mean endotoxin potency was significantly higher for carpet dust than for seat dust (6.3 +/- 3.0 vs. 3.0 +/- 1.4 EU/pmol LPS, P < 0.0001). Mean endotoxin levels in the air and dust of commercial aircraft cabins were generally higher than mean levels reported in homes and office buildings. These results suggest that exposure route and dust source are important considerations when relating endotoxin exposure to specific health outcomes.

  2. Novel cis-selective and non-epimerisable C3 hydroxy azapodophyllotoxins targeting microtubules in cancer cells.

    PubMed

    Kandil, Sahar; Wymant, Jennifer M; Kariuki, Benson M; Jones, Arwyn T; McGuigan, Christopher; Westwell, Andrew D

    2016-03-01

    Podophyllotoxin (PT) and its clinically used analogues are known to be powerful antitumour agents. These compounds contain a trans fused strained γ-lactone system, a feature that correlates to the process of epimerisation, whereby the trans γ-lactone system of ring D opens and converts to the more thermodynamically stable cis epimer. Since these cis epimers are known to be either less active or lacking antitumour activity, epimerisation is an undesirable feature from a chemotherapeutic point of view. To circumvent this problem, considerable efforts have been reported, amongst which is the synthesis of azapodophyllotoxins where the stereocentres at C2 and C3 are removed in order to preclude epimerisation. Herein we report the identification of a novel C3 hydroxy, cis-selective γ-lactone configuration of ring C in the azapodophyllotoxin scaffold, through an efficient stereoselective multicomponent reaction (MCR) involving fluorinated and non-fluorinated aldehydes. This configuration releases the highly strained trans γ-lactone system in podophyllotoxin analogues into the more thermodynamically stable cis γ-lactone motif and yet retains significantly potent activity. These compounds were evaluated against the human cancer lines MCF-7 and 22Rv1 in vitro. Fourteen out of the seventeen tested compounds exhibited sub-micromolar activity with IC50 values in the range of 0.11-0.91 μM, which is comparable and in some cases better than the activity profile of etoposide in this assay. Interestingly, we obtained strong evidence from spectroscopic and X-ray data analyses that the previously reported structure of similar analogues is not accurate. Molecular modelling performed using the podophyllotoxin binding site on β tubulin revealed a novel binding mode of these analogues. Furthermore, sub-cellular study of our compounds using immunolabelling and confocal microscopy analyses showed strong microtubule disruptive activity, particularly in dividing cells.

  3. Novel cis-selective and non-epimerisable C3 hydroxy azapodophyllotoxins targeting microtubules in cancer cells

    PubMed Central

    Kandil, Sahar; Wymant, Jennifer M.; Kariuki, Benson M.; Jones, Arwyn T.; McGuigan, Christopher; Westwell, Andrew D.

    2016-01-01

    Podophyllotoxin (PT) and its clinically used analogues are known to be powerful antitumour agents. These compounds contain a trans fused strained γ-lactone system, a feature that correlates to the process of epimerisation, whereby the trans γ-lactone system of ring D opens and converts to the more thermodynamically stable cis epimer. Since these cis epimers are known to be either less active or lacking antitumour activity, epimerisation is an undesirable feature from a chemotherapeutic point of view. To circumvent this problem, considerable efforts have been reported, amongst which is the synthesis of azapodophyllotoxins where the stereocentres at C2 and C3 are removed in order to preclude epimerisation. Herein we report the identification of a novel C3 hydroxy, cis-selective γ-lactone configuration of ring C in the azapodophyllotoxin scaffold, through an efficient stereoselective multicomponent reaction (MCR) involving fluorinated and non-fluorinated aldehydes. This configuration releases the highly strained trans γ-lactone system in podophyllotoxin analogues into the more thermodynamically stable cis γ-lactone motif and yet retains significantly potent activity. These compounds were evaluated against the human cancer lines MCF-7 and 22Rv1 in vitro. Fourteen out of the seventeen tested compounds exhibited sub-micromolar activity with IC50 values in the range of 0.11–0.91 μM, which is comparable and in some cases better than the activity profile of etoposide in this assay. Interestingly, we obtained strong evidence from spectroscopic and X-ray data analyses that the previously reported structure of similar analogues is not accurate. Molecular modelling performed using the podophyllotoxin binding site on β tubulin revealed a novel binding mode of these analogues. Furthermore, sub-cellular study of our compounds using immunolabelling and confocal microscopy analyses showed strong microtubule disruptive activity, particularly in dividing cells. PMID

  4. Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells.

    PubMed

    Sidaway, James E; Davidson, Robert G; McTaggart, Fergus; Orton, Terry C; Scott, Robert C; Smith, Graham J; Brunskill, Nigel J

    2004-09-01

    Renal proximal tubule cells are responsible for the reabsorption of proteins that are present in the tubular lumen. This occurs by receptor-mediated endocytosis, a process that has a requirement for some GTP-binding proteins. Statins are inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase used for the therapeutic reduction of cholesterol-containing plasma lipoproteins. However, they can also reduce intracellular levels of isoprenoid pyrophosphates that are derived from the product of the enzyme, mevalonate, and are required for the prenylation and normal function of GTP-binding proteins. The hypothesis that inhibition of HMG-CoA reductase in renal proximal tubule cells could reduce receptor mediated-endocytosis was therefore tested. Five different statins inhibited the uptake of FITC-labeled albumin by the proximal tubule-derived opossum kidney cell line in a dose-dependent manner and in the absence of cytotoxicity. The reduction in albumin uptake was related to the degree of inhibition of HMG-CoA reductase. Simvastatin (e.g., statin) inhibited receptor-mediated endocytosis of both FITC-albumin and FITC-beta(2)-microglobulin to similar extents but without altering the binding of albumin to the cell surface. The effect on albumin endocytosis was prevented by mevalonate and by the isoprenoid geranylgeranyl pyrophosphate but not by cholesterol. Finally, evidence that the inhibitory effect of statins on endocytosis of proteins may be caused by reduced prenylation and thereby decreased function of one or more GTP-binding proteins is provided. These data establish the possibility in principle that inhibition of HMG-CoA reductase by statins in proximal tubule cells may reduce tubular protein reabsorption. PMID:15339975

  5. Purification and characterization of a Galactomyces reessii hydratase that converts 3-methylcrotonic acid to 3-hydroxy-3-methylbutyric acid.

    PubMed

    Dhar, A; Dhar, K; Rosazza, J P N

    2002-02-01

    Cell free extracts of Galactomyces reessii contain a hydratase as the key enzyme for the transformation of 3-methylcrotonic acid to 3-hydroxy-3-methylbutyric acid. Highest levels of hydratase activity were obtained during growth on isovaleric acid. The enzyme, an enoyl CoA hydratase, was purified 147-fold by precipitation with ammonium sulphate and successive chromatography over columns of DE-52, Blue Sepharose CL-6B and Sephacryl S-200. During purification, hydratase activity was measured spectrophotometrically (OD change at 263 nm) for 3-methylcrotonyl CoA and crotonyl CoA as substrates. The enzyme displayed highest activity with crotonyl CoA with a Kcat of 1,050,000 min(-1). The ratio of crotonyl CoA to 3-methylcrotonyl CoA activities was constant (20:1) during all steps of purification. The Kcat for crotonyl CoA was also about 20 times greater than the Kcat for 3-methylcrotonyl CoA (51,700 min(-1). The enzyme had pH and temperature optima at 7.0 and 35 degrees C, a native Mr of 260 +/- 4.5 kDa and a subunit Mr of 65 kDa, suggesting that the enzyme was a homotetramer. The pI of the purified hydratase was 5.5, and the N-terminal amino acid sequence was VPEGYAEDLLKGKMMRFFDS. Hydratase activity for 3-methylcrotonyl CoA was competitively inhibited by acetyl CoA, propionyl CoA and acetoacetyl CoA.

  6. Cellular Plasticity Induced by Anti–α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) Receptor Encephalitis Antibodies

    PubMed Central

    Peng, Xiaoyu; Hughes, Ethan G; Moscato, Emilia H; Parsons, Thomas D; Dalmau, Josep; Balice-Gordon, Rita J

    2015-01-01

    Objective Autoimmune-mediated anti–α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis is a severe but treatment-responsive disorder with prominent short-term memory loss and seizures. The mechanisms by which patient antibodies affect synapses and neurons leading to symptoms are poorly understood. Methods The effects of patient antibodies on cultures of live rat hippocampal neurons were determined with immunostaining, Western blot, and electrophysiological analyses. Results We show that patient antibodies cause a selective decrease in the total surface amount and synaptic localization of GluA1- and GluA2-containing AMPARs, regardless of receptor subunit binding specificity, through increased internalization and degradation of surface AMPAR clusters. In contrast, patient antibodies do not alter the density of excitatory synapses, N-methyl-D-aspartate receptor (NMDAR) clusters, or cell viability. Commercially available AMPAR antibodies directed against extracellular epitopes do not result in a loss of surface and synaptic receptor clusters, suggesting specific effects of patient antibodies. Whole-cell patch clamp recordings of spontaneous miniature postsynaptic currents show that patient antibodies decrease AMPAR-mediated currents, but not NMDAR-mediated currents. Interestingly, several functional properties of neurons are also altered: inhibitory synaptic currents and vesicular γ-aminobutyric acid transporter (vGAT) staining intensity decrease, whereas the intrinsic excitability of neurons and short-interval firing increase. Interpretation These results establish that antibodies from patients with anti-AMPAR encephalitis selectively eliminate surface and synaptic AMPARs, resulting in a homeostatic decrease in inhibitory synaptic transmission and increased intrinsic excitability, which may contribute to the memory deficits and epilepsy that are prominent in patients with this disorder. PMID:25369168

  7. Synthesis, crystal growth, structural and physicochemical studies of novel binary organic complex: 4-chloroaniline-3-hydroxy-4-methoxybenzaldehyde

    SciTech Connect

    Sharma, K.P.; Reddi, R.S.B.; Bhattacharya, S.; Rai, R.N.

    2012-06-15

    The solid-state reaction, which is solvent free and green synthesis, has been adopted to explore the novel compound. The phase diagram of 4-chloroaniline (CA) and 3-hydroxy-4-methoxybenzaldehyde (HMB) system shows the formation of a novel 1:1 molecular complex, and two eutectics on either sides of complex. Thermochemical studies of complex and eutectics have been carried out for various properties such as heat of fusion, entropy of fusion, Jackson's parameters, interfacial energy and excess thermodynamic functions. The formation of molecular complex was also studied by IR, NMR, elemental analysis and UV-Vis absorption spectra. The single crystal of molecular complex was grown and its XRD study confirms the formation of complex and identifies the crystal structure and atomic packing of crystal of complex. Transmission spectra of grown crystal of the complex show 70% transmittance efficiency with cut off wavelength 412 nm. The band gap and refractive index of the crystal of complex have also been studied. - Graphical abstarct: Exploiting phase diagram study and solvent free synthesis a novel compound was synthesized and its single crystal growth, atomic packing, energy band gap and refractive index were studied. Highlights: Black-Right-Pointing-Pointer Novel organic complex was synthesized using Green or solvent free synthesis. Black-Right-Pointing-Pointer Phase diagram study provided the information to identify the worthy composition of novel complex. Black-Right-Pointing-Pointer The single crystal of the sufficient size was grown from the ethanol solution. Black-Right-Pointing-Pointer Crystal analysis suggested that the covalent bond is formed between the two parent compounds. Black-Right-Pointing-Pointer The transmittance of the crystal was found to be 70% and it was transparent from 412 to 850 nm.

  8. Determination of ketone body kinetics using a D-(-)-3-hydroxy(4,4,4-/sub 2/H/sup 3/)butyrate tracer

    SciTech Connect

    Bougneres, P.F.; Balasse, E.O.; Ferre, P.; Bier, D.M.

    1986-02-01

    In studies where D-(-)-3-hydroxy(4,4,4-/sub 2/H/sup 3/)butyrate is employed as isotopic tracer in vivo, we have described a selected ion monitoring, gas-liquid chromatography-mass spectrometry micromethod which measures (/sub 2/H/sup 3/) tracer enrichment in 3-hydroxybutyrate and acetoacetate from 300-microliters blood samples. For plasma samples in the physiologic range, intra- and interassay precisions for each ketone averaged better than +/- 1% and +/- 2%, respectively. The use of the method was validated by comparing kinetic data obtained with the above tracer with simultaneous flux data obtained with conventional D-(-)-3-hydroxy(3-/sup 14/C)butyrate tracer in five fasted rats.

  9. 40 CFR 721.10594 - Hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane and 1,1â²- bis , iso-Bu alc.-blocked, compds. with triethylamine. 721.10594 Section...

  10. 40 CFR 721.10594 - Hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane and 1,1â²- bis , iso-Bu alc.-blocked, compds. with triethylamine. 721.10594 Section...

  11. Crystallization and diffraction data of 1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase: a cofactor-free oxygenase of the α/β-hydrolase family

    SciTech Connect

    Qi, Ruhu; Fetzner, Susanne; Oakley, Aaron J.

    2007-05-01

    Preliminary crystallographic data for 1H-3-hydroxy-4-oxoquinoline 2,4-dioxygenase from P. putida 33/1 are reported. 1H-3-Hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO) from Pseudomonas putida 33/1 catalyses the oxygenolysis of 1H-3-hydroxy-4-oxoquinoline to form N-formylanthranilic acid and carbon monoxide without the aid of cofactors. Both N-terminally His{sub 6}-tagged and native QDO were overexpressed in Escherichia coli and purified by conventional chromatographic procedures. Untagged QDO, but not His{sub 6}-tagged QDO, was crystallized by the vapour-diffusion method, giving hexagonal bipyramid crystals belonging to space group P6{sub 1}22. Selenomethionine-containing native QDO was prepared and crystallized under identical conditions. The unit-cell parameters were a = b = 90.1, c = 168.6 Å, α = β = 90, γ = 120°. Using synchrotron radiation, these crystals diffract to 2.5 Å. The expression, purification and crystallization of QDO are reported here.

  12. Zinc Enzymes.

    ERIC Educational Resources Information Center

    Bertini, I.; And Others

    1985-01-01

    Discusses the role of zinc in various enzymes concerned with hydration, hydrolysis, and redox reactions. The binding of zinc to protein residues, properties of noncatalytic zinc(II) and catalytic zinc, and the reactions catalyzed by zinc are among the topics considered. (JN)

  13. Zinc oxide varistors and/or resistors

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    Varistors and/or resistors that includes doped zinc oxide gel microspheres. The doped zinc oxide gel microspheres preferably have from about 60 to about 95% by weight zinc oxide and from about 5 to about 40% by weight dopants based on the weight of the zinc oxide. The dopants are a plurality of dopants selected from silver salts, boron oxide, silicon oxide and hydrons oxides of aluminum, bismuth, cobalt, chromium, manganese, nickel, and antimony.

  14. Zinc oxide varistors and/or resistors

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-07-27

    Varistors and/or resistors are described that include doped zinc oxide gel microspheres. The doped zinc oxide gel microspheres preferably have from about 60 to about 95% by weight zinc oxide and from about 5 to about 40% by weight dopants based on the weight of the zinc oxide. The dopants are a plurality of dopants selected from silver salts, boron oxide, silicon oxide and hydrons oxides of aluminum, bismuth, cobalt, chromium, manganese, nickel, and antimony.

  15. Preparation of silver-activated zinc sulfide thin films

    NASA Technical Reports Server (NTRS)

    Feldman, C.; Swindells, F. E.

    1968-01-01

    Silver improves luminescence and reduces contamination of zinc sulfide phosphors. The silver is added after the zinc sulfide phosphors are deposited in thin films by vapor evaporation, but before calcining, by immersion in a solution of silver salt.

  16. Zinc poisoning

    MedlinePlus

    ... other materials to make industrial items such as paint, dyes, and more. These combination substances can be ... Compounds used to make paint, rubber, dyes, wood preservatives, and ... Zinc chloride Zinc oxide (relatively nonharmful) Zinc ...

  17. DESCRIPTIVE ANALYSIS OF DIVALENT SALTS

    PubMed Central

    YANG, HEIDI HAI-LING; LAWLESS, HARRY T.

    2005-01-01

    Many divalent salts (e.g., calcium, iron, zinc), have important nutritional value and are used to fortify food or as dietary supplements. Sensory characterization of some divalent salts in aqueous solutions by untrained judges has been reported in the psychophysical literature, but formal sensory evaluation by trained panels is lacking. To provide this information, a trained descriptive panel evaluated the sensory characteristics of 10 divalent salts including ferrous sulfate, chloride and gluconate; calcium chloride, lactate and glycerophosphate; zinc sulfate and chloride; and magnesium sulfate and chloride. Among the compounds tested, iron compounds were highest in metallic taste; zinc compounds had higher astringency and a glutamate-like sensation; and bitterness was pronounced for magnesium and calcium salts. Bitterness was affected by the anion in ferrous and calcium salts. Results from the trained panelists were largely consistent with the psychophysical literature using untrained judges, but provided a more comprehensive set of oral sensory attributes. PMID:16614749

  18. History of Zinc in Agriculture12

    PubMed Central

    Nielsen, Forrest H.

    2012-01-01

    Zinc was established as essential for green plants in 1926 and for mammals in 1934. However, >20 y would pass before the first descriptions of zinc deficiencies in farm animals appeared. In 1955, it was reported that zinc supplementation would cure parakeratosis in swine. In 1958, it was reported that zinc deficiency induced poor growth, leg abnormalities, poor feathering, and parakeratosis in chicks. In the 1960s, zinc supplementation was found to alleviate parakeratosis in grazing cattle and sheep. Within 35 y, it was established that nearly one half of the soils in the world may be zinc deficient, causing decreased plant zinc content and production that can be prevented by zinc fertilization. In many of these areas, zinc deficiency is prevented in grazing livestock by zinc fertilization of pastures or by providing salt licks. For livestock under more defined conditions, such as poultry, swine, and dairy and finishing cattle, feeds are easily supplemented with zinc salts to prevent deficiency. Today, the causes and consequences of zinc deficiency and methods and effects of overcoming the deficiency are well established for agriculture. The history of zinc in agriculture is an outstanding demonstration of the translation of research into practical application. PMID:23153732

  19. A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals[S

    PubMed Central

    Nagao, Akihiko; Maoka, Takashi; Ono, Hiroshi; Kotake-Nara, Eiichi; Kobayashi, Miyuki; Tomita, Mie

    2015-01-01

    We previously found that mice fed lutein accumulated its oxidative metabolites (3′-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3′-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD+, (3′R,6′R)-3′-hydroxy-β,ε-caroten-3-one and (6RS,3′R,6′R)-3′-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products. The former accumulated only at the early stage and was assumed to be an intermediate, followed by isomerization to the latter. The configuration at the C3′ and C6′ of the ε-end group in lutein was retained in the two oxidation products. These results indicate that the 3-hydroxy β-end group in lutein was preferentially oxidized to a 3-oxo ε-end group via a 3-oxo β-end group. Other xanthophylls such as β-cryptoxanthin and zeaxanthin, which have a 3-hydroxy β-end group, were also oxidized in the same manner as lutein. These keto-carotenoids, derived from dietary xanthophylls, were confirmed to be present in plasma of normal human subjects, and β,ε-caroten-3′-one was significantly increased by the ingestion of β-cryptoxanthin. Thus, humans as well as mice have oxidative activity to convert the 3-hydroxy β-end group of xanthophylls to a 3-oxo ε-end group. PMID:25502844

  20. Comparative pharmacokinetics of (/sup 65/Zn)zinc sulfate and (/sup 65/Zn)zinc pantothenate injected intravenously in rabbits

    SciTech Connect

    Guillard, O.; Courtois, P.; Murai, P.; Ducassou, D.; Reiss, D.

    1984-11-01

    The pharmacokinetics of zinc sulfate were compared with those of a new zinc salt, pantothenate, in rabbits. Each salt was administered at a dosage of 3.3 microCi of zinc-65/kg of body weight. The measured pharmacokinetics of the two compounds responded to a two-compartment open model. The urinary elimination of the two salts was similar, as was their localization in the skin and fur, but zinc pantothenate was fixed by the liver to a lesser extent than was zinc sulfate.

  1. Enhanced Production of a Plant Monoterpene by Overexpression of the 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Catalytic Domain in Saccharomyces cerevisiae▿ †

    PubMed Central

    Rico, Juan; Pardo, Ester; Orejas, Margarita

    2010-01-01

    Linalool production was evaluated in different Saccharomyces cerevisiae strains expressing the Clarkia breweri linalool synthase gene (LIS). The wine strain T73 was shown to produce higher levels of linalool than conventional laboratory strains (i.e., almost three times the amount). The performance of this strain was further enhanced by manipulating the endogenous mevalonate (MVA) pathway: deregulated overexpression of the rate-limiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) doubled linalool production. In a haploid laboratory strain, engineering of this key step also improved linalool yield. PMID:20675444

  2. Designing the ideal uranyl ligand: a sterically induced speciation change in complexes with thiophene-bridged bis(3-hydroxy-n-methylpyridin-2-one).

    PubMed

    Szigethy, Géza; Raymond, Kenneth N

    2009-12-21

    Structural characterization of a mononuclear uranyl complex with a tetradentate, thiophene-linked bis(3-hydroxy-N-methylpyridin-2-one) ligand reveals the most planar coordination geometry yet observed with this ligand class. The introduction of ethylsulfanyl groups onto the thiophene linker disrupts this planar, conjugated ligand arrangement, resulting in the formation of dimeric (UO(2))(2)L(2) species in which each ligand spans two uranyl centers. Relative energy calculations reveal that this tendency toward dimer formation is the result of steric interference between ethylsulfanyl substitutents and linking amides. PMID:19928845

  3. Designing the Ideal Uranyl Ligand: a Sterically-Induced Speciation Change in Complexes with Thiophene-Bridged Bis(3-hydroxy-N-methylpyridin-2-one)

    SciTech Connect

    Szigethy, Geza; Raymond, Kenneth N.

    2009-09-11

    Structural characterization of a mononuclear uranyl complex with a tetradentate, thiophene-linked bis(3-hydroxy-N-methylpyridin-2-one) ligand reveals the most planar coordination geometry yet observed with this ligand class. The introduction of ethylsulfanyl groups onto the thiophene linker disrupts this planar, conjugated ligand arrangement, resulting in the formation of dimeric (UO{sub 2}){sub 2}L{sub 2} species in which each ligand spans two uranyl centers. Relative energy calculations reveal that this tendency toward dimer formation is the result of steric interference between ethylsulfanyl substituents and linking amides.

  4. Is the Reaction Catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase a Rate-Limiting Step for Isoprenoid Biosynthesis in Plants?

    PubMed Central

    Chappell, J.; Wolf, F.; Proulx, J.; Cuellar, R.; Saunders, C.

    1995-01-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the irreversible conversion of 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate and is considered a key regulatory step controlling isoprenoid metabolism in mammals and fungi. The rate-limiting nature of this enzyme for isoprenoid biosynthesis in plants remains controversial. To investigate whether HMGR activity could be limiting in plants, we introduced a constitutively expressing hamster HMGR gene into tabacco (Nicotiana tabaccum L.) plants to obtain unregulated HMGR activity. The impact of the resulting enzyme activity on the biosynthesis and accumulation of particular isoprenoids was evaluated. Expression of the hamster HMGR gene led to a 3- to 6-fold increase in the total HMGR enzyme activity. Total sterol accumulation was consequently increased 3- to 10-fold, whereas end-product sterols such as sitosterol, campesterol, and stigmasterol were increased only 2-fold. The level of cycloartenol, a sterol biosynthetic intermediate, was increased more than 100-fold. Although the synthesis of total sterols appears to be limited normally by HMGR activity, these results indicate that the activity of one or more later enzyme(s) in the pathway must also be involved in determining the relative accumulation of end-product sterols. The levels of other isoprenoids such as carotenoids, phytol chain of chlorophyll, and sesquiterpene phytoalexins were relatively unaltered in the transgenic plants. It appears from these results that compartmentation, channeling, or other rate-determining enzymes operate to control the accumulation of these other isoprenoid end products. PMID:12228673

  5. Novel 1,5,7-trihydroxy-3-hydroxy methyl anthraquinone isolated from terrestrial Streptomyces sp. (eri-26) with antimicrobial and molecular docking studies.

    PubMed

    Duraipandiyan, V; Al-Dhabi, N A; Balachandran, C; Raj, M Karunai; Arasu, M Valan; Ignacimuthu, S

    2014-11-01

    Streptomyces sp. isolate ERI-26 was obtained from the Nilgiris forest soil of Western Ghats, Tamil Nadu, India. Novel anthraquinone compound was isolated from the active fraction 5; it was identified by spectroscopical data using UV, IR, NMR and MASS. The isolated compound 1,5,7-trihydroxy-3-hydroxy methyl anthraquinone was tested against bacteria and fungi at minimum inhibitory concentration level. The compound showed significant antimicrobial activity against bacteria, Staphylococcus aureus at 125 μg/ml, Staphylococcus epidermidis at 62.5 μg/m, Bacillus subtilis at 31.25 μg/ml, fungi; Epidermophyton floccosum at 62.5 μg/ml, Aspergillus niger at 31.25 μg/ml, Aspergiller flavus at 31.25 μg/ml, Trichophyton rubrum at 62.5 μg/ml and Botrytis cinerea at 62.5 μg/ml. The isolated compound was subjected to molecular docking studies for the inhibition of TtgR, topoisomerase IV and AmpC β-lactamase enzymes which are targets for antimicrobials. Docking studies of the compound showed low docking energy indicating its usefulness as antimicrobial agent. 1,5,7-Trihydroxy-3-hydroxy methyl anthraquinone is new, and its antimicrobial and molecular docking properties are reported for the first time. PMID:25149455

  6. Phytoextraction potential of wild type and 35S-gshI transgenic poplar trees (Populus x Canescens) for environmental pollutants herbicide paraquat, salt sodium, zinc sulfate and nitric oxide in vitro.

    PubMed

    Gyulai, G; Bittsánszky, A; Szabó, Z; Waters, L; Gullner, G; Kampfl, G; Heltai, G; Komíves, T

    2014-01-01

    Phytoextraction potentials of two transgenic (TR) poplar (Populus x canescens) clones TRggs11 and TRlgl6 were compared with that of wild-type (WT) following exposure to paraquat, zinc sulfate, common salt and nitric oxide (NO), using a leaf-disc system incubated for 21 days on EDTA-containing nutritive WPM media in vitro. Glutathione (GSH) contents of leaf discs of TRlgl6 and TRggs11 showed increments to 296% and 190%, respectively, compared with WT. NO exposure led to a twofold GSH content in TRlgl6, which was coupled with a significantly increased sulfate uptake when exposed to 10(-3) M ZnSO4. The highest mineral contents of Na, Zn, Mn, Cu, and Mo was observed in the TRggs11 clone. Salt-induced activity of catalase enzyme increased in both TR clones significantly compared with WT under NaCl (0.75% and 1.5%) exposure. The in silico sequence analyses of gsh1 genes revealed that P. x canadensis and Salix sachalinensis show the closest sequence similarity to that of P. x canescens, which predicted an active GSH production with high phytoextraction potentials of these species with indication for their use where P. x canescens can not be grown.

  7. Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.

    PubMed

    Moezzi, Amir; Cortie, Michael; McDonagh, Andrew

    2016-04-25

    Thermal decomposition of layered zinc hydroxide double salts provides an interesting alternative synthesis for particles of zinc oxide. Here, we examine the sequence of changes occurring as zinc hydroxide chloride monohydrate (Zn5(OH)8Cl2·H2O) is converted to crystalline ZnO by thermal decomposition. The specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A complicating and important factor in this process is that the thermal decomposition of zinc hydroxide chloride is also accompanied by the formation of volatile zinc-containing species under certain conditions. We show that this volatile compound is anhydrous ZnCl2 and its formation is moisture dependent. Therefore, control of atmospheric moisture is an important consideration that affects the overall efficiency of ZnO production by this process. PMID:27030646

  8. Zinc-catalyzed depolymerization of artificial polyethers.

    PubMed

    Enthaler, Stephan; Weidauer, Maik

    2012-02-13

    Recycling polymers: In the present study, the efficient zinc-catalyzed depolymerization of a variety of artificial polyethers has been investigated. Chloroesters were obtained as the depolymerization products, which are suitable precursors for new polymers. By using straightforward zinc salts, extraordinary catalyst activities and selectivities were feasible (see scheme). PMID:22253040

  9. Zinc Absorption by Young Adults from Supplemental Zinc Citrate Is Comparable with That from Zinc Gluconate and Higher than from Zinc Oxide123

    PubMed Central

    Wegmüller, Rita; Tay, Fabian; Zeder, Christophe; Brnić, Marica; Hurrell, Richard F.

    2014-01-01

    The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with 67Zn and 70Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6–71.0) and was not different from that from zinc gluconate with 60.9% (50.6–71.7). Absorption from zinc oxide at 49.9% (40.9–57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627. PMID:24259556

  10. Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide.

    PubMed

    Wegmüller, Rita; Tay, Fabian; Zeder, Christophe; Brnic, Marica; Hurrell, Richard F

    2014-02-01

    The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with (67)Zn and (70)Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6-71.0) and was not different from that from zinc gluconate with 60.9% (50.6-71.7). Absorption from zinc oxide at 49.9% (40.9-57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627.

  11. Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide.

    PubMed

    Wegmüller, Rita; Tay, Fabian; Zeder, Christophe; Brnic, Marica; Hurrell, Richard F

    2014-02-01

    The water-soluble zinc salts gluconate, sulfate, and acetate are commonly used as supplements in tablet or syrup form to prevent zinc deficiency and to treat diarrhea in children in combination with oral rehydration. Zinc citrate is an alternative compound with high zinc content, slightly soluble in water, which has better sensory properties in syrups but no absorption data in humans. We used the double-isotope tracer method with (67)Zn and (70)Zn to measure zinc absorption from zinc citrate given as supplements containing 10 mg of zinc to 15 healthy adults without food and compared absorption with that from zinc gluconate and zinc oxide (insoluble in water) using a randomized, double-masked, 3-way crossover design. Median (IQR) fractional absorption of zinc from zinc citrate was 61.3% (56.6-71.0) and was not different from that from zinc gluconate with 60.9% (50.6-71.7). Absorption from zinc oxide at 49.9% (40.9-57.7) was significantly lower than from both other supplements (P < 0.01). Three participants had little or no absorption from zinc oxide. We conclude that zinc citrate, given as a supplement without food, is as well absorbed by healthy adults as zinc gluconate and may thus be a useful alternative for preventing zinc deficiency and treating diarrhea. The more insoluble zinc oxide is less well absorbed when given as a supplement without food and may be minimally absorbed by some individuals. This trial was registered at clinicaltrials.gov as NCT01576627. PMID:24259556

  12. Altered trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) in the striatum leads to behavioral changes in emotional responses.

    PubMed

    Lee, Young; Lee, Hojin; Kim, Hyung-Wook; Yoon, Bong-June

    2015-01-01

    The striatum receives and integrates multiple inputs from diverse areas in the brain and plays a critical role in the regulation of motor activity. However, whether the striatum is involved in the alteration of behavior in the presence of emotional challenges is unknown. Here, we examined whether alterations in the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) in the dorsal striatum would affect anxiety-related behaviors. We found that the transient expression of G1CT or G2CT, AMPAR-derived peptides, in the dorsomedial striatum led to decreased mobility in high-anxiety circumstances; however, the expression of these peptides in the dorsolateral striatum did not affect anxiety-related behavior. These data suggest that excitatory connections within the dorsomedial striatum play important roles in the control of motor actions in the presence of emotional challenges.

  13. Systematic comparison of the mono-, dimethyl- and trimethyl 3-hydroxy-4(1H)-pyridones - Attempted optimization of the orally active iron chelator, deferiprone.

    PubMed

    Xie, Yuan-Yuan; Lu, Zidong; Kong, Xiao-Le; Zhou, Tao; Bansal, Sukhi; Hider, Robert

    2016-06-10

    A range of close analogues of deferiprone have been synthesised. The group includes mono-, di- and tri-methyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe(3+) values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NH-containing hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis. PMID:27014847

  14. The antiviral agent cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine] has pronounced activity against nasopharyngeal carcinoma grown in nude mice.

    PubMed

    Neyts, J; Sadler, R; De Clercq, E; Raab-Traub, N; Pagano, J S

    1998-02-01

    The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir) on the EBV-associated tumor nasopharyngeal carcinoma (NPC) was evaluated in NPC xenografts in athymic mice. Intratumoral injection arrested tumor growth within 1 week, and by 4 weeks, tumors regressed to 8-75% (39 +/- 33%) of the original size, whereas control tumors injected with PBS grew to 282 +/- 25% of the original size. Ganciclovir slowed but did not arrest or cause regression of tumor growth. A striking antitumor effect was also produced by systemic administration; at 4 weeks, tumors were 79 +/- 49% of the original size, compared with 635 +/- 91% for the controls. Widespread apoptosis was detected after treatment for 2-6 days in C15 as well as two other NPC xenografts, C17 and C18; the latter NPCs have mutations in the p53 gene. These data indicate that cidofovir induces rapid cell death through apoptosis in EBV-transformed epithelial cells.

  15. NMR spectral study of some 2r,6c-diarylpiperidin-4-one (3'-hydroxy-2'-naphthoyl)hydrazones with special reference to γ-syn effect

    NASA Astrophysics Data System (ADS)

    Sylvestre, S.; Pandiarajan, K.

    2011-01-01

    1H and 13C NMR spectra have been recorded for 2r,6c-diarylpiperidin-4-one (3'-hydroxy-2'-naphthoyl)hydrazones 10-17 and 3,3-dimethyl-2r,6c-bis(p-methoxyphenyl)piperidin-4-one ( 5). For selected compounds 2D NMR spectra have been recorded. The spectral data along with those reported for related compounds are used to study the effect of a heteroatom X on the 13C chemical shift of a γ-carbon with X C α C β C γ torsional angle close to 0°, termed as γ-syn effect. Also γ-gauche and δ-effects of the alkyl groups at C-3 on the carbons of the aryl group at C-2 have been studied. The chemical shifts for the naphthalene ring are in accord with the mesomeric and steric effects of the carbonyl and hydroxy groups.

  16. Influence of human saliva on odorant concentrations. 2. aldehydes, alcohols, 3-alkyl-2-methoxypyrazines, methoxyphenols, and 3-hydroxy-4,5-dimethyl-2(5H)-furanone.

    PubMed

    Buettner, Andrea

    2002-11-20

    The influence of human whole saliva on selected alcohols, aldehydes, 3-alkyl-2-methoxypyrazines, and phenols in food-relevant concentrations was investigated. At pH 7.5-8 it was found that the alcohols, methoxyphenols, methoxypyrazines, and 3-hydroxy-4,5-dimethyl-2(5H)-furanone remained unmodified by saliva, whereas aldehydes were reduced to their corresponding alcohols. Generally, the processes were found to be dependent on the salivary activity of the panelists as well as on the concentration of the applied odorants. Reduction of the aldehydes did not occur after thermal treatment of the saliva. These investigations are aimed at finding an explanation for longer lasting aftertaste in humans, as it is induced by some odor-active compounds after the consumption of food materials.

  17. The Influence of the Linker Geometry in Bis(3-hydroxy-N-methyl-pyridin-2-one) Ligands on Solution-Phase Uranyl Affinity

    SciTech Connect

    Szigethy, Geza; Raymond, Kenneth

    2010-08-12

    Seven water-soluble, tetradentate bis(3-hydroxy-N-methyl-pyridin-2-one) (bis-Me-3,2-HOPO) ligands were synthesized that vary only in linker geometry and rigidity. Solution phase thermodynamic measurements were conducted between pH 1.6 and pH 9.0 to determine the effects of these variations on proton and uranyl cation affinity. Proton affinity decreases by introduction of the solubilizing triethylene glycol group as compared to un-substituted reference ligands. Uranyl affinity was found to follow no discernable trends with incremental geometric modification. The butyl-linked 4Li-Me-3,2-HOPO ligand exhibited the highest uranyl affinity, consistent with prior in vivo decorporation results. Of the rigidly-linked ligands, the o-phenylene linker imparted the best uranyl affinity to the bis-Me-3,2-HOPO ligand platform.

  18. Theoretical study on the influence of water for the tautomerization of 3-hydroxy-2(1H)-pyridinethione in the solution

    NASA Astrophysics Data System (ADS)

    Du, Benni; Zhang, Weichao

    2016-09-01

    The isomerization processes of 3-hydroxy-2(1H)-pyridinethione with water or water cluster in the aqueous solution were explored at B3LYP-D3/6-311++G(3df,3pd) level of theory. The results suggest that the formation of P2 dominates over that of P1 in the isolated reaction, whereas the barrier difference of transition states between them will decrease gradually with increasing of water number from one to three and the production of P1 will be competitive to that of P2 with water dimer or water trimer. Furthermore, the location of water or water cluster between N and S is more suitable for the formation of active component P1.

  19. Structural basis for the design of potent and species-specific inhibitors of 3-hydroxy-3-methylglutaryl CoA synthases.

    PubMed

    Pojer, Florence; Ferrer, Jean-Luc; Richard, Stéphane B; Nagegowda, Dinesh A; Chye, Mee-Len; Bach, Thomas J; Noel, Joseph P

    2006-08-01

    3-Hydroxy-3-methylglutaryl CoA synthase (HMGS) catalyzes the first committed step in the mevalonate metabolic pathway for isoprenoid biosynthesis and serves as an alternative target for cholesterol-lowering and antibiotic drugs. We have determined a previously undescribed crystal structure of a eukaryotic HMGS bound covalently to a potent and specific inhibitor F-244 [(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecadienenoic acid]. Given the accessibility of synthetic analogs of the F-244 natural product, this inhibited eukaryotic HMGS structure serves as a necessary starting point for structure-based methods that may improve the potency and species-specific selectivity of the next generation of F-244 analogs designed to target particular eukaryotic and prokaryotic HMGS.

  20. Discovery of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides active against efflux-mediated resistant Streptococcus pneumoniae.

    PubMed

    Bukvić Krajačić, Mirjana; Dumić, Miljenko; Novak, Predrag; Cindrić, Mario; Koštrun, Sanja; Fajdetić, Andrea; Alihodžić, Sulejman; Brajša, Karmen; Kujundžić, Nedjeljko

    2011-01-15

    A series of novel ureas and thioureas of 3-decladinosyl-3-hydroxy 15-membered azalides, were discovered, structurally characterized and biologically evaluated. They have shown good antibacterial activity against selected Gram-positive and Gram-negative bacterial strains. These include N″ substituted 9a-(N'-carbamoyl-γ-aminopropyl)- (6a,c), 9a-(N'-thiocarbamoyl-γ-aminopropyl)- (7a,e), 9a-[N'-(β-cyanoethyl)-N'-(carbamoyl-γ-aminopropyl)]- (9a-c, 9g) 9a-[N'-(β-cyanoethyl)-N'-(thiocarbamoyl-γ-aminopropyl)]-derivatives (10d-f) of 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3). Among the synthesized compounds thiourea 7a and urea 9b have shown substantially improved activity comparable to azithromycin (1) and significantly better activity than the 3-decladinosyl-azithromycin (2) and the parent 3-cladinosyl analogues against efflux-mediated resistant S. pneumoniae.

  1. Prevention of leucaena toxicosis of cattle in Florida by ruminal inoculation with 3-hydroxy-4-(1H)-pyridone-degrading bacteria.

    PubMed

    Hammond, A C; Allison, M J; Williams, M J; Prine, G M; Bates, D B

    1989-12-01

    Ruminal microorganisms in cattle at a Florida agriculture research station did not have the ability to detoxify leucaena by degradation of 3-hydroxy-4(1H)-pyridone (3,4,-DHP), but a DHP isomer (2,3-DHP) was degraded in some cattle. Cattle with microorganisms that degraded 2,3-DHP were mostly Senepol cattle imported from St. Croix, US Virgin Islands, where leucaena is an indigenous species. Hereford cattle at the research station in Florida generally did not degrade 3,4-DHP or 2,3-DHP. An experiment was conducted in which a pure culture of 3,4-DHP-degrading bacteria was inoculated into Hereford cattle (with ruminal fistula) grazing leucaena. The bacteria successfully colonized the rumen of recipient cattle and persisted through the following winter when there was no leucaena in the diet. PMID:2610447

  2. Structural Basis for the Design of Potent and Species-specific Inhibitors of 3-hydroxy-3-methylglutaryl CoA Synthases

    SciTech Connect

    Pojer,F.; Ferrer, J.; Richard, S.; Nagegowda, D.; Chye, M.; Bach, T.; Noel, J.

    2006-01-01

    3-Hydroxy-3-methylglutaryl CoA synthase (HMGS) catalyzes the first committed step in the mevalonate metabolic pathway for isoprenoid biosynthesis and serves as an alternative target for cholesterol-lowering and antibiotic drugs. We have determined a previously undescribed crystal structure of a eukaryotic HMGS bound covalently to a potent and specific inhibitor F-244 [(E,E)-11-[3-(hydroxymethyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4-undecadienenoic acid]. Given the accessibility of synthetic analogs of the F-244 natural product, this inhibited eukaryotic HMGS structure serves as a necessary starting point for structure-based methods that may improve the potency and species-specific selectivity of the next generation of F-244 analogs designed to target particular eukaryotic and prokaryotic HMGS.

  3. Prion protein facilitates uptake of zinc into neuronal cells

    PubMed Central

    Watt, Nicole T.; Taylor, David R.; Kerrigan, Talitha L.; Griffiths, Heledd H.; Rushworth, Jo V.; Whitehouse, Isobel J.; Hooper, Nigel M.

    2012-01-01

    Zinc is released into the synaptic cleft upon exocytotic stimuli, although the mechanism for its reuptake into neurons is unresolved. Here we show that the cellular prion protein enhances the uptake of zinc into neuronal cells. This prion-protein-mediated zinc influx requires the octapeptide repeats and amino-terminal polybasic region in the prion protein, but not its endocytosis. Selective antagonists of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors block the prion protein-mediated zinc uptake, and the prion protein co-immunoprecipitates with both GluA1 and GluA2 AMPA receptor subunits. Zinc-sensitive intracellular tyrosine phosphatase activity is decreased in cells expressing prion protein and increased in the brains of prion-protein-null mice, providing evidence of a physiological consequence of this process. Prion protein-mediated zinc uptake is ablated in cells expressing familial associated mutants of the protein and in prion-infected cells. These data suggest that alterations in the cellular prion protein-mediated zinc uptake may contribute to neurodegeneration in prion and other neurodegenerative diseases. PMID:23072804

  4. Inhibition of Squalene Synthase and Squalene Epoxidase in Tobacco Cells Triggers an Up-Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase

    PubMed Central

    Wentzinger, Laurent F.; Bach, Thomas J.; Hartmann, Marie-Andrée

    2002-01-01

    To get some insight into the regulatory mechanisms controlling the sterol branch of the mevalonate pathway, tobacco (Nicotiana tabacum cv Bright Yellow-2) cell suspensions were treated with squalestatin-1 and terbinafine, two specific inhibitors of squalene synthase (SQS) and squalene epoxidase, respectively. These two enzymes catalyze the first two steps involved in sterol biosynthesis. In highly dividing cells, SQS was actively expressed concomitantly with 3-hydroxy-3-methylglutaryl coenzyme A reductase and both sterol methyltransferases. At nanomolar concentrations, squalestatin was found to inhibit efficiently sterol biosynthesis as attested by the rapid decrease in SQS activity and [14C]radioactivity from acetate incorporated into sterols. A parallel dose-dependent accumulation of farnesol, the dephosphorylated form of the SQS substrate, was observed without affecting farnesyl diphosphate synthase steady-state mRNA levels. Treatment of tobacco cells with terbinafine is also shown to inhibit sterol synthesis. In addition, this inhibitor induced an impressive accumulation of squalene and a dose-dependent stimulation of the triacylglycerol content and synthesis, suggesting the occurrence of regulatory relationships between sterol and triacylglycerol biosynthetic pathways. We demonstrate that squalene was stored in cytosolic lipid particles, but could be redirected toward sterol synthesis if required. Inhibition of either SQS or squalene epoxidase was found to trigger a severalfold increase in enzyme activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, giving first evidence for a positive feedback regulation of this key enzyme in response to a selective depletion of endogenous sterols. At the same time, no compensatory responses mediated by SQS were observed, in sharp contrast to the situation in mammalian cells. PMID:12226513

  5. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  6. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  7. 46 CFR 148.330 - Zinc ashes; zinc dross; zinc residues; zinc skimmings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Zinc ashes; zinc dross; zinc residues; zinc skimmings... Materials § 148.330 Zinc ashes; zinc dross; zinc residues; zinc skimmings. (a) The shipper must inform the cognizant Coast Guard Captain of the Port in advance of any cargo transfer operations involving zinc...

  8. Zinc Therapy in Dermatology: A Review

    PubMed Central

    Mahajan, Vikram K.; Mehta, Karaninder S.; Chauhan, Pushpinder S.

    2014-01-01

    Zinc, both in elemental or in its salt forms, has been used as a therapeutic modality for centuries. Topical preparations like zinc oxide, calamine, or zinc pyrithione have been in use as photoprotecting, soothing agents or as active ingredient of antidandruff shampoos. Its use has expanded manifold over the years for a number of dermatological conditions including infections (leishmaniasis, warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders (melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc is well-established in human zinc deficiency syndromes including acrodermatitis enteropathica, it is only in recent years that importance of zinc as a micronutrient essential for infant growth and development has been recognized. The paper reviews various dermatological uses of zinc. PMID:25120566

  9. Zinc therapy in dermatology: a review.

    PubMed

    Gupta, Mrinal; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S

    2014-01-01

    Zinc, both in elemental or in its salt forms, has been used as a therapeutic modality for centuries. Topical preparations like zinc oxide, calamine, or zinc pyrithione have been in use as photoprotecting, soothing agents or as active ingredient of antidandruff shampoos. Its use has expanded manifold over the years for a number of dermatological conditions including infections (leishmaniasis, warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders (melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc is well-established in human zinc deficiency syndromes including acrodermatitis enteropathica, it is only in recent years that importance of zinc as a micronutrient essential for infant growth and development has been recognized. The paper reviews various dermatological uses of zinc. PMID:25120566

  10. 3-Methylglutaconyl-CoA hydratase, 3-methylcrotonyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA lyase deficiencies: a coupled enzyme assay useful for their detection.

    PubMed

    Narisawa, K; Gibson, K M; Sweetman, L; Nyhan, W L

    1989-09-15

    A coupled assay has been developed using 3-methylcrotonyl-CoA and NaH14CO3 which permits the detection of deficiencies of 3-methylcrotonyl-CoA carboxylase, 3-methylglutaconyl-CoA hydratase and 3-hydroxy-3-methylglutaryl CoA-lyase. The products of the reaction were analyzed by high performance liquid chromatography. Using this method the site of the defect was documented in a patient with deficiency of 3-methylcrotonyl-CoA carboxylase, 2 patients with deficiency of 3-methyl-glutaconyl-CoA hydratase, and 2 patients with deficiency of 3-hydroxy-3-methyl-glutaryl-CoA lyase.

  11. Suppressing the dendritic growth of zinc in an ionic liquid containing cationic and anionic zinc complexes for battery applications.

    PubMed

    Liu, Zhen; Pulletikurthi, Giridhar; Lahiri, Abhishek; Cui, Tong; Endres, Frank

    2016-05-10

    Metallic zinc is a promising negative electrode for high energy rechargeable batteries due to its abundance, low-cost and non-toxic nature. However, the formation of dendritic zinc and low Columbic efficiency in aqueous alkaline solutions during charge/discharge processes remain a great challenge. Here we demonstrate that the dendritic growth of zinc can be effectively suppressed in an ionic liquid electrolyte containing highly concentrated cationic and anionic zinc complexes obtained by dissolving zinc oxide and zinc trifluoromethylsulfonate in a protic ionic liquid, 1-ethylimidazolium trifluoromethylsulfonate. The presence of both cationic and anionic zinc complexes alters the interfacial structure at the electrode/electrolyte interface and influences the nucleation and growth of zinc, leading to compact, homogeneous and dendrite-free zinc coatings. This study also provides insights into the development of highly concentrated metal salts in ionic liquids as electrolytes to deposit dendrite-free zinc as an anode material for energy storage applications. PMID:27080261

  12. Dissolution of different zinc salts and zn uptake by Sedum alfredii and maize in mono- and co-cropping under hydroponic culture.

    PubMed

    Jiang, Cheng'ai; Wu, Qitang; Zeng, Shucai; Chen, Xian; Wei, Zebin; Long, Xinxian

    2013-09-01

    Previous soil pot and field experiments demonstrated that co-cropping the hyperaccumulator Sedum alfredii with maize increased Zn phytoextraction by S. alfredii and decreased Zn uptake by maize shoots. This hydroponic experiment was conducted to investigate whether the facilitation of Zn phytoextraction by S. alfredii resulted from improved dissolution in this co-cropping system and its relation to root exudates. S. alfredii and maize were mono- and co-cropped (without a root barrier) in nutrient solution spiked with four Zn compounds, ZnS, ZnO, Zn3(PO4)2 and 5ZnO x 2CO3-4H2O (represented as ZnCO3) at 1000 mg/L Zn for 15 days without renewal of nutrient solution after pre-culture. The root exudates were collected under incomplete sterilization and analyzed. The results indicated that the difference in Zn salts had a greater influence on the Zn concentration in maize than for S. alfredii, varying from 210-2603 mg/kg for maize shoots and 6445-12476 mg/kg for S. alfredii in the same order: ZnCO3 > ZnO > Zn3(PO4)2 > ZnS. For the four kinds of Zn sources in this experiment, co-cropping with maize did not improve Zn phytoextraction by S. alfredii. In most cases, compared to co-cropped and mono-cropped maize, mono-cropped S. alfredii resulted in the highest Zn2+ concentration in the remaining nutrient solution, and also had a higher total concentration of low molecular weight organic acids (LMWOA) and lower pH of root exudation. Root exudates did partly influence Zn hyperaccumulation in S. alfredii.

  13. Dissolution of different zinc salts and zn uptake by Sedum alfredii and maize in mono- and co-cropping under hydroponic culture.

    PubMed

    Jiang, Cheng'ai; Wu, Qitang; Zeng, Shucai; Chen, Xian; Wei, Zebin; Long, Xinxian

    2013-09-01

    Previous soil pot and field experiments demonstrated that co-cropping the hyperaccumulator Sedum alfredii with maize increased Zn phytoextraction by S. alfredii and decreased Zn uptake by maize shoots. This hydroponic experiment was conducted to investigate whether the facilitation of Zn phytoextraction by S. alfredii resulted from improved dissolution in this co-cropping system and its relation to root exudates. S. alfredii and maize were mono- and co-cropped (without a root barrier) in nutrient solution spiked with four Zn compounds, ZnS, ZnO, Zn3(PO4)2 and 5ZnO x 2CO3-4H2O (represented as ZnCO3) at 1000 mg/L Zn for 15 days without renewal of nutrient solution after pre-culture. The root exudates were collected under incomplete sterilization and analyzed. The results indicated that the difference in Zn salts had a greater influence on the Zn concentration in maize than for S. alfredii, varying from 210-2603 mg/kg for maize shoots and 6445-12476 mg/kg for S. alfredii in the same order: ZnCO3 > ZnO > Zn3(PO4)2 > ZnS. For the four kinds of Zn sources in this experiment, co-cropping with maize did not improve Zn phytoextraction by S. alfredii. In most cases, compared to co-cropped and mono-cropped maize, mono-cropped S. alfredii resulted in the highest Zn2+ concentration in the remaining nutrient solution, and also had a higher total concentration of low molecular weight organic acids (LMWOA) and lower pH of root exudation. Root exudates did partly influence Zn hyperaccumulation in S. alfredii. PMID:24520733

  14. Species-specific expansion and molecular evolution of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) gene family in plants.

    PubMed

    Li, Wei; Liu, Wei; Wei, Hengling; He, Qiuling; Chen, Jinhong; Zhang, Baohong; Zhu, Shuijin

    2014-01-01

    The terpene compounds represent the largest and most diverse class of plant secondary metabolites which are important in plant growth and development. The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) is one of the key enzymes contributed to terpene biosynthesis. To better understand the basic characteristics and evolutionary history of the HMGR gene family in plants, a genome-wide analysis of HMGR genes from 20 representative species was carried out. A total of 56 HMGR genes in the 14 land plant genomes were identified, but no genes were found in all 6 algal genomes. The gene structure and protein architecture of all plant HMGR genes were highly conserved. The phylogenetic analysis revealed that the plant HMGRs were derived from one ancestor gene and finally developed into four distinct groups, two in the monocot plants and two in dicot plants. Species-specific gene duplications, caused mainly by segmental duplication, led to the limited expansion of HMGR genes in Zea mays, Gossypium raimondii, Populus trichocarpa and Glycine max after the species diverged. The analysis of Ka/Ks ratios and expression profiles indicated that functional divergence after the gene duplications was restricted. The results suggested that the function and evolution of HMGR gene family were dramatically conserved throughout the plant kingdom. PMID:24722776

  15. Theoretical study on the HIV-1 integrase inhibitor 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2 H-tetrazol-5-yl)-propenone (5CITEP)

    NASA Astrophysics Data System (ADS)

    Nunthaboot, Nadtanet; Pianwanit, Somsak; Parasuk, Vudhichai; Kokpol, Sirirat; Wolschann, Peter

    2007-11-01

    1-(5-Chloroindol-3-yl)-3-hydroxy-3-(2 H-tetrazol-5-yl)-propenone (5CITEP) is an inhibitor of the HIV-1 integrase (IN). Theoretical studies were performed on the interaction of this inhibitor with surrounding amino acids. Density functional theory (DFT) calculations were conducted to identify the protonation state of HIV-1 integrase (IN), in particular, residues Lys156 and Lys159 and 5CITEP inhibitor. The results indicate that the both lysine residues are in protonated forms while 5CITEP is in de-protonated form. The binding energy of 5CITEP and its six surrounding amino acids, i.e., Thr66, Gln148, Glu152, Asn155, Lys156, and Lys159 is -41.33 kcal/mol. In addition, conformation analysis of 5CITEP was carried out to determine conformational minima of this compound. The calculations reveal that the lowest energy conformation of 5CITEP is close to that of X-ray conformation, as evidenced by energy difference of 1.5 kcal/mol only.

  16. The 3-hydroxy-3-methylglutaryl coenzyme-A reductases from fungi: a proposal as a therapeutic target and as a study model.

    PubMed

    Andrade-Pavón, Dulce; Sánchez-Sandoval, Eugenia; Rosales-Acosta, Blanca; Ibarra, José Antonio; Tamariz, Joaquín; Hernández-Rodríguez, César; Villa-Tanaca, Lourdes

    2014-01-01

    The enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzes the conversion of HMG-Co-A into mevalonate. This step is the limiting point for the synthesis of cholesterol in mammals and ergosterol in fungi. We describe in this article the genome organization of HMGR coding genes and those deduced from different fungi, recount the evidence showing statins as HMGR inhibitors for ergosterol synthesis and its effect in yeast viability, and propose fungal HMGR (HMGRf) as a model to study the use of pharmaceutical compounds to inhibit cholesterol and ergosterol synthesis. Bibliographical search and bioinformatic analyses were performed and discussed. HMGRfs belong to the class I with a high homology in the catalytic region. The sterol biosynthetic pathway in humans and fungi share many enzymes in the initial steps (such as the HMGR enzyme), but in the last steps enzymes are different rendering the two final products: cholesterol in mammals and ergosterol in fungi. With regards to inhibitors such as statins and other compounds, these affect also fungal viability. Since HMGR from Schizosaccharomyces pombe and Ustilago maydis are very similar to the human HMGR in the catalytic regions, we propose that fungal enzymes can be used to test inhibitors for a potential use in humans. We consider that HMGRf is a good therapeutic target to design and test new antifungal compounds. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24270073

  17. Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons.

    PubMed

    Wang, H; Yu, L C; Li, Y C

    2016-01-01

    This study was performed to investigate the modulation effect of protein tyrosine kinase on postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons. The cultured neurons were exposed to 1% O2 and the expression of AMPA receptor subunit GluR2 on the cell surface was significantly increased, while total GluR2 was not markedly changed. Furthermore, the hypoxia-induced increase in GluR2 expression on the cell surface was partially blocked by the protein tyrosine kinase membrane-permeable inhibitor genistein. In contrast, both the protein tyrosine kinase agonist nerve growth factor and protein tyrosine phosphatase inhibitor vanadate promoted the hypoxia-induced increase of GluR2 expression on cell surface. Moreover, GluR2 could be phosphorylated by tyrosine under normoxia and hypoxia conditions in vitro on brainstem neurons, and tyrosine phosphorylation of GluR2 was significantly stronger under hypoxia conditions. Our results indicate that acute hypoxia induces the AMPA receptor subunit GluR2 to rapidly migrate to the cell membrane to modify the strength of the synapse. This study indicates that tyrosine phosphorylation of the receptor is an important pathway regulating the rapid migration of GluR2 in the postsynaptic domain induced by hypoxia. PMID:27525851

  18. The Pseudomonas aeruginosa liuE gene encodes the 3-hydroxy-3-methylglutaryl coenzyme A lyase, involved in leucine and acyclic terpene catabolism.

    PubMed

    Chávez-Avilés, Mauricio; Díaz-Pérez, Alma Laura; Reyes-de la Cruz, Homero; Campos-García, Jesús

    2009-07-01

    The enzymes involved in the catabolism of leucine are encoded by the liu gene cluster in Pseudomonas aeruginosa PAO1. A mutant in the liuE gene (ORF PA2011) of P. aeruginosa was unable to utilize both leucine/isovalerate and acyclic terpenes as the carbon source. The liuE mutant grown in culture medium with citronellol accumulated metabolites of the acyclic terpene pathway, suggesting an involvement of liuE in both leucine/isovalerate and acyclic terpene catabolic pathways. The LiuE protein was expressed as a His-tagged recombinant polypeptide purified by affinity chromatography in Escherichia coli. LiuE showed a mass of 33 kDa under denaturing and 79 kDa under nondenaturing conditions. Protein sequence alignment and fingerprint sequencing suggested that liuE encodes 3-hydroxy-3-methylglutaryl-coenzyme A lyase (HMG-CoA lyase), which catalyzes the cleavage of HMG-CoA to acetyl-CoA and acetoacetate. LiuE showed HMG-CoA lyase optimal activity at a pH of 7.0 and 37 degrees C, an apparent K(m) of 100 microM for HMG-CoA and a V(max) of 21 micromol min(-1) mg(-1). These results demonstrate that the liuE gene of P. aeruginosa encodes for the HMG-CoA lyase, an essential enzyme for growth in both leucine and acyclic terpenes.

  19. (S)-3-hydroxy-3-methylglutaryl coenzyme A reductase, a product of the mva operon of Pseudomonas mevalonii, is regulated at the transcriptional level.

    PubMed Central

    Wang, Y L; Beach, M J; Rodwell, V W

    1989-01-01

    We have cloned and sequenced a 505-base-pair (bp) segment of DNA situated upstream of mvaA, the structural gene for (S)-3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.88) of Pseudomonas mevalonii. The DNA segment that we characterized includes the promoter region for the mva operon. Nuclease S1 mapping and primer extension analysis showed that mvaA is the promoter-proximal gene of the mva operon. Transcription initiates at -56 bp relative to the first A (+1) of the translation start site. Transcription in vivo was induced by mevalonate. Structural features of the mva promoter region include an 80-bp A + T-rich region, and -12, -24 consensus sequences that resemble sequences of sigma 54 promoters in enteric organisms. The relative amplitudes of catalytic activity, enzyme protein, and mvaA mRNA are consistent with a model of regulation of this operon at the transcriptional level. Images PMID:2477360

  20. Glutamate regulates Oct-2 DNA-binding activity through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in cultured chick Bergmann glia cells.

    PubMed

    Méndez, J Alfredo; López-Bayghen, Esther; Rojas, Fausto; Hernández, María Elena; Ortega, Arturo

    2004-02-01

    Ionotropic glutamate receptors in cerebellar Bergmann glial cells are linked to transcriptional regulation and, by these means, are thought to play an important role in plasticity, learning and memory and in several neuropathologies. Within the CNS, the transcription factors of the POU family bind their target DNA sequences after a growth factor-dependent phosphorylation-dephosphorylation cascade. Exposure of cultured Bergmann glial cells to glutamate leads to a time- and dose-dependent increase in Oct-2 DNA-binding activity. The use of specific pharmacological tools established the involvement of Ca2+-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors. Furthermore, the signaling cascade includes phosphatidyl inositol 3-kinase as well as protein kinase C activation. Interestingly, transcriptional as well as translational inhibitors abolish the glutamate effect, suggesting a transcriptional up-regulation of the oct-2 gene. These data demonstrate that Oct-2 expression is not restricted to neurons and further strengthen the notion that the glial glutamate receptors participate in the modulation of glutamatergic cerebellar neurotransmission.

  1. Effect of tris(3-hydroxy-4-pyridinonate) iron(III) complexes on iron uptake and storage in soybean (Glycine max L.).

    PubMed

    Santos, Carla S; Carvalho, Susana M P; Leite, Andreia; Moniz, Tânia; Roriz, Mariana; Rangel, António O S S; Rangel, Maria; Vasconcelos, Marta W

    2016-09-01

    Iron deficiency chlorosis (IDC) is a serious environmental problem affecting the growth of several crops in the world. The application of synthetic Fe(III) chelates is still one of the most common measures to correct IDC and the search for more effective Fe chelates remains an important issue. Herein, we propose a tris(3-hydroxy-4-pyridinonate) iron(III) complex, Fe(mpp)3, as an IDC corrector. Different morphological, biochemical and molecular parameters were assessed as a first step towards understanding its mode of action, compared with that of the commercial fertilizer FeEDDHA. Plants treated with the pyridinone iron(III) complexes were significantly greener and had increased biomass. The total Fe content was measured using ICP-OES and plants treated with pyridinone complexes accumulated about 50% more Fe than those treated with the commercial chelate. In particular, plants supplied with compound Fe(mpp)3 were able to translocate iron from the roots to the shoots and did not elicit the expression of the Fe-stress related genes FRO2 and IRT1. These results suggest that 3,4-HPO iron(III) chelates could be a potential new class of plant fertilizing agents.

  2. Arabidopsis thaliana contains two differentially expressed 3-hydroxy-3-methylglutaryl-CoA reductase genes, which encode microsomal forms of the enzyme.

    PubMed Central

    Enjuto, M; Balcells, L; Campos, N; Caelles, C; Arró, M; Boronat, A

    1994-01-01

    The enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR; EC 1.1.1.34) catalyzes the first rate-limiting step in plant isoprenoid biosynthesis. Arabidopsis thaliana contains two genes, HMG1 and HMG2, that encode HMGR. We have cloned these two genes and analyzed their structure and expression. HMG1 and HMG2 consist of four exons and three small introns that interrupt the coding sequence at equivalent positions. The two genes share sequence similarity in the coding regions but not in the 5'- or 3'-flanking regions. HMG1 mRNA is detected in all tissues, whereas the presence of HMG2 mRNA is restricted to young seedlings, roots, and inflorescences. The similarity between the two encoded proteins (HMGR1 and HMGR2) is restricted to the regions corresponding to the membrane and the catalytic domains. Arabidopsis HMGR2 represents a divergent form of the enzyme that has no counterpart among plant HMGRs characterized so far. By using a coupled in vitro transcription-translation assay, we show that both HMGR1 and HMGR2 are cotranslationally inserted into endoplasmic reticulum-derived microsomal membranes. Our results suggest that the endoplasmic reticulum is the only cell compartment for the targeting of HMGR in Arabidopsis and support the hypothesis that in higher plants the formation of mevalonate occurs solely in the cytosol. Images PMID:8302869

  3. Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

    SciTech Connect

    Massicotte, G.; Baudry, M. ); Vanderklish, P.; Lynch, G. )

    1991-03-01

    The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

  4. Metabolically regulated endoplasmic reticulum-associated degradation of 3-hydroxy-3-methylglutaryl-CoA reductase: evidence for requirement of a geranylgeranylated protein.

    PubMed

    Leichner, Gil S; Avner, Rachel; Harats, Dror; Roitelman, Joseph

    2011-09-16

    In mammalian cells, the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), which catalyzes the rate-limiting step in the mevalonate pathway, is ubiquitylated and degraded by the 26 S proteasome when mevalonate-derived metabolites accumulate, representing a case of metabolically regulated endoplasmic reticulum-associated degradation (ERAD). Here, we studied which mevalonate-derived metabolites signal for HMGR degradation and the ERAD step(s) in which these metabolites are required. In HMGR-deficient UT-2 cells that stably express HMGal, a chimeric protein between β-galactosidase and the membrane region of HMGR, which is necessary and sufficient for the regulated ERAD, we tested inhibitors specific to different steps in the mevalonate pathway. We found that metabolites downstream of farnesyl pyrophosphate but upstream to lanosterol were highly effective in initiating ubiquitylation, dislocation, and degradation of HMGal. Similar results were observed for endogenous HMGR in cells that express this protein. Ubiquitylation, dislocation, and proteasomal degradation of HMGal were severely hampered when production of geranylgeranyl pyrophosphate was inhibited. Importantly, inhibition of protein geranylgeranylation markedly attenuated ubiquitylation and dislocation, implicating for the first time a geranylgeranylated protein(s) in the metabolically regulated ERAD of HMGR.

  5. Up-regulation of an N-terminal truncated 3-hydroxy-3-methylglutaryl CoA reductase enhances production of essential oils and sterols in transgenic Lavandula latifolia.

    PubMed

    Muñoz-Bertomeu, Jesús; Sales, Ester; Ros, Roc; Arrillaga, Isabel; Segura, Juan

    2007-11-01

    Spike lavender (Lavandula latifolia) essential oil is widely used in the perfume, cosmetic, flavouring and pharmaceutical industries. Thus, modifications of yield and composition of this essential oil by genetic engineering should have important scientific and commercial applications. We generated transgenic spike lavender plants expressing the Arabidopsis thaliana HMG1 cDNA, encoding the catalytic domain of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR1S), a key enzyme of the mevalonic acid (MVA) pathway. Transgenic T0 plants accumulated significantly more essential oil constituents as compared to controls (up to 2.1- and 1.8-fold in leaves and flowers, respectively). Enhanced expression of HMGR1S also increased the amount of the end-product sterols, beta-sitosterol and stigmasterol (average differences of 1.8- and 1.9-fold, respectively), but did not affect the accumulation of carotenoids or chlorophylls. We also analysed T1 plants derived from self-pollinated seeds of T0 lines that flowered after growing for 2 years in the greenhouse. The increased levels of essential oil and sterols observed in the transgenic T0 plants were maintained in the progeny that inherited the HMG1 transgene. Our results demonstrate that genetic manipulation of the MVA pathway increases essential oil yield in spike lavender, suggesting a contribution for this cytosolic pathway to monoterpene and sesquiterpene biosynthesis in leaves and flowers of the species.

  6. Simultaneous spectrophotometric determination of Cu2+, Hg2+, and Cd2+ ions using 2-(3-hydroxy-1-methylbut-2-enylideneamino)pyridine-3-ol.

    PubMed

    Tarighat, Maryam Abbasi; Mohammadi, Khosro

    2015-04-01

    New complexes of Cu2+, Hg2+, and Cd2+ with a recently synthesized Schiff base derived from 2-(3-hydroxy-1-methylbut-2-enylideneamino)pyridine-3-ol were applied for their simultaneous determination with artificial neural networks. A new analytical method using principal component-feed forward neural networks (PC-FFNNs) and principal component-radial basis function networks (PC-RBFNs) was used. Spectral data was reduced using principal component analysis and subjected to ANNs. The data obtained from synthetic mixtures of metal ions were processed by PC-FFNNs and PC-RBFNs. Performances of the proposed methods were tested with regard to relative standard error of prediction. Limit of detections and limit of quantifications were determined. The results obtained by PC-FFNNs and PC-RBFNs were compared to each other. Under the working conditions, the proposed methods were successfully applied to simultaneous determination of Hg2+, Cu2+, and Cd2+ in different water and soil samples. Concentrations of metal ions in the samples were also determined by flame atomic absorption spectrometry (FAAS) and standard addition method. The amounts of metal ions obtained by the proposed methods were in good agreement with those obtained by FAAS and standard addition method. PMID:25792026

  7. Laser videofluorometer system for real-time characterization of high-performance liquid chromatographic eluate. [3-hydroxy-benzo(a)pyrene

    SciTech Connect

    Skoropinski, D.B.; Callis, J.B.; Danielson, J.D.S.; Christian, G.D.

    1986-11-01

    A second generation videofluorometer has been developed for real-time characterization of high-performance liquid chromatographic eluate. The instrument features a nitrogen-laser-pumped dye laser as excitation source and quarter meter polychromator/microchannel plate-intensified diode array as fluorescence detector. The dye laser cavity is tuned with a moving-iron galvanometer scanner grating drive, permitting the laser output to be changed to any wavelength in its range in less than 40 ms. Thus, the optimum excitation wavelength can be chosen for each chromatographic region. A minimum detection limit of 13 pptr has been obtained for 3-hydroxy-benzo(a)pyrene in a conventional fluorescence cuvette with a 30-s data acquisition. For the same substance eluted chromatographically, a minimum detection limit of 50 pg has been obtained, and a linear dynamic range of greater than 3 orders of magnitude observed. An extract of soil that had been contaminated with polyaromatic hydrocarbons was analyzed as a practical test of the system, permitting the quantitation of three known species, and the identification and quantitation of a previously unknown fourth compound.

  8. Expression of the Hevea brasiliensis (H.B.K.) Mull. Arg. 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase 1 in Tobacco Results in Sterol Overproduction.

    PubMed Central

    Schaller, H.; Grausem, B.; Benveniste, P.; Chye, M. L.; Tan, C. T.; Song, Y. H.; Chua, N. H.

    1995-01-01

    A genomic fragment encoding one (HMGR1) of the three 3-hydroxy-3-methylglutaryl coenzyme A reductases (HMGRs) from Hevea brasiliensis (H.B.K.) Mull. Arg. (M.-L. Chye, C.-T. Tan, N.-H. Chua [1992] Plant Mol Biol 19: 473-484) was introduced into Nicotiana tabacum L. cv xanthi via Agrobacterium transformation to study the influence of the hmg1 gene product on plant isoprenoid biosynthesis. Transgenic plants were morphologically indistinguishable from control wild-type plants and displayed the same developmental pattern. Transgenic lines showed an increase in the level of total sterols up to 6-fold, probably because of an increased expression level of hmg1 mRNA and a corresponding increased enzymatic activity for HMGR, when compared with the level of total sterols from control lines not expressing the hmg1 transgene. In addition to the pathway end products, campesterol, sitosterol, and stigmasterol, some biosynthetic intermediates such as cycloartenol also accumulated in transgenic tissues. Most of the overproduced sterols were detected as steryl-esters and were likely to be stored in cytoplasmic lipid bodies. These data strongly support the conclusion that plant HMGR is a key limiting enzyme in phytosterol biosynthesis. PMID:12228630

  9. Enhancement of Ganoderic Acid Accumulation by Overexpression of an N-Terminally Truncated 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene in the Basidiomycete Ganoderma lucidum

    PubMed Central

    Xu, Jun-Wei; Xu, Yi-Ning

    2012-01-01

    Ganoderic acids produced by Ganoderma lucidum, a well-known traditional Chinese medicinal mushroom, exhibit antitumor and antimetastasis activities. Genetic modification of G. lucidum is difficult but critical for the enhancement of cellular accumulation of ganoderic acids. In this study, a homologous genetic transformation system for G. lucidum was developed for the first time using mutated sdhB, encoding the iron-sulfur protein subunit of succinate dehydrogenase, as a selection marker. The truncated G. lucidum gene encoding the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) was overexpressed by using the Agrobacterium tumefaciens-mediated transformation system. The results showed that the mutated sdhB successfully conferred carboxin resistance upon transformation. Most of the integrated transfer DNA (T-DNA) appeared as a single copy in the genome. Moreover, deregulated constitutive overexpression of the HMGR gene led to a 2-fold increase in ganoderic acid content. It also increased the accumulation of intermediates (squalene and lanosterol) and the upregulation of downstream genes such as those of farnesyl pyrophosphate synthase, squalene synthase, and lanosterol synthase. This study demonstrates that transgenic basidiomycete G. lucidum is a promising system to achieve metabolic engineering of the ganoderic acid pathway. PMID:22941092

  10. Preparation of optically active (2RS,3SR)-2-amino-3-hydroxy-3-phenylpropanoic acid (threo-beta-phenylserine) via optical resolutions by replacing and preferential crystallization.

    PubMed

    Shiraiwa, Tadashi; Kawashima, Yuka; Ikaritani, Atsushi; Suganuma, Yumiko; Saijoh, Reiichi

    2006-08-01

    To obtain optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (1) via optical resolutions by replacing and preferential crystallization, the racemic structure of (2RS,3SR)-1 hydrochloride [(2RS,3SR)-1.HCl] was examined based on the melting point, solubility, and infrared spectrum. (2RS,3SR)-1.HCl was indicated to exist as a conglomerate at room temperature, although it forms a racemic compound at the melting point. When, in optical resolution by replacing crystallization, L-phenylalanine methyl ester hydrochloride (L-2) was used as the optically active co-solute, (2R,3S)-1.HCl was preferentially crystallized from the supersaturated racemic solution; the use of D-2 as the co-solute afforded (2S,3R)-1.HCl with an optical purity of 95%. In addition, optical resolution by preferential crystallization was successfully achieved to give successively (2R,3S)- and (2S,3R)-1.HCl with optical purities of 90-92%. The (2R,3S)- and (2S,3R)-1.HCl purified by recrystallization from 1-propanol were treated with triethylamine in methanol to give optically pure (2R,3S)- and (2S,3R)-1.

  11. The 3-hydroxy-3-methylglutaryl coenzyme-A reductases from fungi: a proposal as a therapeutic target and as a study model.

    PubMed

    Andrade-Pavón, Dulce; Sánchez-Sandoval, Eugenia; Rosales-Acosta, Blanca; Ibarra, José Antonio; Tamariz, Joaquín; Hernández-Rodríguez, César; Villa-Tanaca, Lourdes

    2014-01-01

    The enzyme 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) catalyzes the conversion of HMG-Co-A into mevalonate. This step is the limiting point for the synthesis of cholesterol in mammals and ergosterol in fungi. We describe in this article the genome organization of HMGR coding genes and those deduced from different fungi, recount the evidence showing statins as HMGR inhibitors for ergosterol synthesis and its effect in yeast viability, and propose fungal HMGR (HMGRf) as a model to study the use of pharmaceutical compounds to inhibit cholesterol and ergosterol synthesis. Bibliographical search and bioinformatic analyses were performed and discussed. HMGRfs belong to the class I with a high homology in the catalytic region. The sterol biosynthetic pathway in humans and fungi share many enzymes in the initial steps (such as the HMGR enzyme), but in the last steps enzymes are different rendering the two final products: cholesterol in mammals and ergosterol in fungi. With regards to inhibitors such as statins and other compounds, these affect also fungal viability. Since HMGR from Schizosaccharomyces pombe and Ustilago maydis are very similar to the human HMGR in the catalytic regions, we propose that fungal enzymes can be used to test inhibitors for a potential use in humans. We consider that HMGRf is a good therapeutic target to design and test new antifungal compounds. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

  12. Effect of tris(3-hydroxy-4-pyridinonate) iron(III) complexes on iron uptake and storage in soybean (Glycine max L.).

    PubMed

    Santos, Carla S; Carvalho, Susana M P; Leite, Andreia; Moniz, Tânia; Roriz, Mariana; Rangel, António O S S; Rangel, Maria; Vasconcelos, Marta W

    2016-09-01

    Iron deficiency chlorosis (IDC) is a serious environmental problem affecting the growth of several crops in the world. The application of synthetic Fe(III) chelates is still one of the most common measures to correct IDC and the search for more effective Fe chelates remains an important issue. Herein, we propose a tris(3-hydroxy-4-pyridinonate) iron(III) complex, Fe(mpp)3, as an IDC corrector. Different morphological, biochemical and molecular parameters were assessed as a first step towards understanding its mode of action, compared with that of the commercial fertilizer FeEDDHA. Plants treated with the pyridinone iron(III) complexes were significantly greener and had increased biomass. The total Fe content was measured using ICP-OES and plants treated with pyridinone complexes accumulated about 50% more Fe than those treated with the commercial chelate. In particular, plants supplied with compound Fe(mpp)3 were able to translocate iron from the roots to the shoots and did not elicit the expression of the Fe-stress related genes FRO2 and IRT1. These results suggest that 3,4-HPO iron(III) chelates could be a potential new class of plant fertilizing agents. PMID:27156133

  13. Characterization and expression of two cDNA encoding 3-Hydroxy-3-methylglutaryl coenzyme A reductase isoforms in coffee (Coffea arabica L.).

    PubMed

    Tiski, Iris; Marraccini, Pierre; Pot, David; Vieira, Luiz Gonzaga Esteves; Pereira, Luiz Filipe Protasio

    2011-10-01

    In higher plants there are two independent pathways for isoprenoid biosynthesis, located in the cytosol (mevalonic acid or MVA pathway) or in the plastids [methylerythritol phosphate (MEP) pathway]. The 3-hydroxy-3-methyglutaryl-CoA reductase (HMGR) is the first committed step in the MVA pathway. Using the information available from the Brazilian Coffee Genome Project, we found 13 ESTs that originated two isoforms, CaHMGR1 and CaHMGR2, for the enzyme HMGR of Coffea arabica. A complementary DNA encoding the isoform CaHMGR1 was cloned, and its complete nucleotide sequence determined. The full-length cDNA of CaHMGR1 was 2,242 bp containing a 1,812-bp ORF encoding 604 amino acids. Bioinformatic analyses revealed that the deduced CaHMGR1 had extensive homology with other plant HMGRs and contained two transmembrane domains and two putative HMGR binding sites and two NADP(H)-binding sites. Under normal growth conditions, transcripts of isoform CaHMRG1 were detected in fruit tissues (pulp, perisperm, and endosperm) only at the initial stages of development, flower buds and leaves. CaHMRG2 was expressed in all tissues and during all fruit development stages examined. These results suggest a constitutive expression of isoform CaHMGR2, while the isoform CaHMGR1 shows temporal and tissue-specific transcriptional activation.

  14. Molecular cloning of mevalonate pathway genes from Taraxacum brevicorniculatum and functional characterisation of the key enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

    PubMed

    van Deenen, Nicole; Bachmann, Anne-Lena; Schmidt, Thomas; Schaller, Hubert; Sand, Jennifer; Prüfer, Dirk; Schulze Gronover, Christian

    2012-04-01

    Taraxacum brevicorniculatum is known to produce high quality rubber. The biosynthesis of rubber is dependent on isopentenyl pyrophosphate (IPP) precursors derived from the mevalonate (MVA) pathway. The cDNA sequences of seven MVA pathway genes from latex of T. brevicorniculatum were isolated, including three cDNA sequences encoding for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases (TbHMGR1-3). Expression analyses indicate an important role of TbHMGR1 as well as for the HMG-CoA synthase (TbHMGS), the diphosphomevalonate decarboxylase and the mevalonate kinase in the provision of precursors for rubber biosynthesis. The amino acid sequences of the TbHMGRs show the typical motifs described for plant HMGRs such as two transmembrane domains and a catalytic domain containing two HMG-CoA and two NADP(H) binding sites. The functionality of the HMGRs was demonstrated by complementation assay using an IPP auxotroph mutant of Escherichia coli. Furthermore, the transient expression of the catalytic domains of TbHMGR1 and TbHMGR2 in Nicotiana benthamiana resulted in a strong accumulation of sterol precursors, one of the major groups of pathway end-products.

  15. Regulation of GluA1 α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Function by Protein Kinase C at Serine-818 and Threonine-840

    PubMed Central

    Jenkins, Meagan A.; Wells, Gordon; Bachman, Julia; Snyder, James P.; Jenkins, Andrew; Huganir, Richard L.; Oswald, Robert E.

    2014-01-01

    Three residues within the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit GluA1 C terminus (Ser818, Ser831, Thr840) can be phosphorylated by Ca2+/phospholipid-dependent protein kinase (PKC). Here, we show that PKC phosphorylation of GluA1 Ser818 or Thr840 enhances the weighted mean channel conductance without altering the response time course or agonist potency. These data support the idea that these residues constitute a hyper-regulatory domain for the AMPA receptor. Introduction of phosphomimetic mutations increases conductance only at these three sites within the proximal C terminus, consistent with a structural model with a flexible linker connecting the distal C-terminal domain to the more proximal domain containing a helix bracketed by Ser831 and Thr840. NMR spectra support this model and raise the possibility that phosphorylation can alter the configuration of this domain. Our findings provide insight into the structure and function of the C-terminal domain of GluA1, which controls AMPA receptor function and trafficking during synaptic plasticity in the central nervous system. PMID:24452473

  16. Farnesol-Induced Cell Death and Stimulation of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Activity in Tobacco cv Bright Yellow-2 Cells12

    PubMed Central

    Hemmerlin, Andréa; Bach, Thomas J.

    2000-01-01

    Growth inhibition of tobacco (Nicotiana tabacum L. cv Bright Yellow-2) cells by mevinolin, a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) could be partially overcome by the addition of farnesol. However, farnesol alone inhibited cell division and growth as measured by determination of fresh weight increase. When 7-d-old tobacco cv Bright Yellow-2 cells were diluted 40-fold into fresh culture, the cells exhibited a dose-dependent sensitivity to farnesol, with 25 μm sufficient to cause 100% cell death, as measured by different staining techniques, cytometry, and monitoring of fragmentation of genomic DNA. Cells were less sensitive to the effects of farnesol when diluted only 4-fold. Farnesol was absorbed by the cells, as examined by [1-3H]farnesol uptake, with a greater relative enrichment by the more diluted cells. Both mevinolin and farnesol treatments stimulated apparent HMGR activity. The stimulation by farnesol was also reflected in corresponding changes in the steady-state levels of HMGR mRNA and enzyme protein with respect to HMGR gene expression and enzyme protein accumulation. PMID:10938345

  17. The Influence of Linker Geometry on Uranyl Complexation by Rigidly-Linked Bis(3-hydroxy-N-methyl-pyridin-2-one)

    SciTech Connect

    Szigethy, Geza; Raymond, Kenneth

    2010-04-22

    A series of bis(3-hydroxy-N-methyl-pyridin-2-one) ligands was synthesized, and their respective uranyl complexes were characterized by single crystal X-ray diffraction analyses. These structures were inspected for high-energy conformations and evaluated using a series of metrics to measure co-planarity of chelating moieties with each other and the uranyl coordination plane, as well as to measure coordinative crowding about the uranyl dication. Both very short (ethyl, 3,4-thiophene and o-phenylene) and very long ({alpha},{alpha}{prime}-m-xylene and 1,8-fluorene) linkers provide optimal ligand geometries about the uranyl cation, resulting in planar, unstrained molecular arrangements. The planarity of the rigid linkers also suggests there is a degree of pre-organization for a planar coordination mode that is ideal for uranyl-selective ligand design. Comparison of intramolecular N{sub amide}-O{sub phenolate} distances and {sup 1}H NMR chemical shifts of amide protons supports earlier results that short linkers provide the optimal geometry for intramolecular hydrogen bonding.

  18. Species-Specific Expansion and Molecular Evolution of the 3-hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Plants

    PubMed Central

    Li, Wei; Liu, Wei; Wei, Hengling; He, Qiuling; Chen, Jinhong; Zhang, Baohong; Zhu, Shuijin

    2014-01-01

    The terpene compounds represent the largest and most diverse class of plant secondary metabolites which are important in plant growth and development. The 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34) is one of the key enzymes contributed to terpene biosynthesis. To better understand the basic characteristics and evolutionary history of the HMGR gene family in plants, a genome-wide analysis of HMGR genes from 20 representative species was carried out. A total of 56 HMGR genes in the 14 land plant genomes were identified, but no genes were found in all 6 algal genomes. The gene structure and protein architecture of all plant HMGR genes were highly conserved. The phylogenetic analysis revealed that the plant HMGRs were derived from one ancestor gene and finally developed into four distinct groups, two in the monocot plants and two in dicot plants. Species-specific gene duplications, caused mainly by segmental duplication, led to the limited expansion of HMGR genes in Zea mays, Gossypium raimondii, Populus trichocarpa and Glycine max after the species diverged. The analysis of Ka/Ks ratios and expression profiles indicated that functional divergence after the gene duplications was restricted. The results suggested that the function and evolution of HMGR gene family were dramatically conserved throughout the plant kingdom. PMID:24722776

  19. Contribution of Accelerated Degradation to Feedback Regulation of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase and Cholesterol Metabolism in the Liver.

    PubMed

    Hwang, Seonghwan; Hartman, Isamu Z; Calhoun, Leona N; Garland, Kristina; Young, Gennipher A; Mitsche, Matthew A; McDonald, Jeffrey; Xu, Fang; Engelking, Luke; DeBose-Boyd, Russell A

    2016-06-24

    Accumulation of sterols in endoplasmic reticulum membranes stimulates the ubiquitination of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which catalyzes a rate-limiting step in synthesis of cholesterol. This ubiquitination marks HMGCR for proteasome-mediated degradation and constitutes one of several mechanisms for feedback control of cholesterol synthesis. Mechanisms for sterol-accelerated ubiquitination and degradation of HMGCR have been elucidated through the study of cultured mammalian cells. However, the extent to which these reactions modulate HMGCR and contribute to control of cholesterol metabolism in whole animals is unknown. Here, we examine transgenic mice expressing in the liver the membrane domain of HMGCR (HMGCR (TM1-8)), a region necessary and sufficient for sterol-accelerated degradation, and knock-in mice in which endogenous HMGCR harbors mutations that prevent sterol-induced ubiquitination. Characterization of transgenic mice revealed that HMGCR (TM1-8) is appropriately regulated in the liver of mice fed a high cholesterol diet or chow diet supplemented with the HMGCR inhibitor lovastatin. Ubiquitination-resistant HMGCR protein accumulates in the liver and other tissues disproportionately to its mRNA, indicating that sterol-accelerated degradation significantly contributes to feedback regulation of HMGCR in vivo Results of these studies demonstrate that HMGCR is subjected to sterol-accelerated degradation in the liver through mechanisms similar to those established in cultured cells. Moreover, these studies designate sterol-accelerated degradation of HMGCR as a potential therapeutic target for prevention of atherosclerosis and associated cardiovascular disease. PMID:27129778

  20. 3'-hydroxy-3,4,5,4'-tetramethoxystilbene, the metabolite of resveratrol analogue DMU-212, inhibits ovarian cancer cell growth in vitro and in a mice xenograft model.

    PubMed

    Piotrowska-Kempisty, Hanna; Ruciński, Marcin; Borys, Sylwia; Kucińska, Małgorzata; Kaczmarek, Mariusz; Zawierucha, Piotr; Wierzchowski, Marcin; Łażewski, Dawid; Murias, Marek; Jodynis-Liebert, Jadwiga

    2016-01-01

    In screening studies, the cytotoxic activity of four metabolites of resveratrol analogue 3,4,5,4'-tetramethoxystilbene (DMU-212) against A-2780 and SKOV-3 ovarian cancer cells was investigated. The most active metabolite, 3'-hydroxy-3,4,5,4'-tetramethoxystilbene (DMU-214), was chosen for further studies. The cytotoxicity of DMU-214 was shown to be higher than that of the parent compound, DMU-212, in both cell lines tested. Since DMU-212 was supposed to undergo metabolic activation through its conversion to DMU-214, an attempt was made to elucidate the mechanism of its anti-proliferative activity. We found that in SKOV-3 cells lacking p53, DMU-214 induced receptor-mediated apoptosis. In A-2780 cell line with expression of wild-type p53, DMU-214 modulated the expression pattern of p53-target genes driving intrinsic and extrinsic apoptosis pathways, as well as DNA repair and damage prevention. Regardless of the up-regulation of p48, p53R2, sestrins and Gaad45 genes involved in cancer cell DNA repair, we demonstrated the stronger anti-proliferative and pro-apoptotic effects of DMU-214 in A-2780 cells when compared to those in SKOV-3. Hence we verified DMU-214 activity in the xenograft model using SCID mice injected with A-2780 cells. The strong anti-proliferative activity of DMU-214 in the in vivo model allowed to suggest the tested compound as a potential therapeutic in ovarian cancer treatment. PMID:27585955

  1. The synthesis of 3-hydroxy-2,4,8-trimethyldec-8-enolides and an approach to 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide.

    PubMed

    Botubol-Ares, J M; Durán-Peña, M J; Macías-Sánchez, A J; Hanson, J R; Collado, I G; Hernández-Galán, R

    2015-01-14

    The synthesis of several derivatives of 3-hydroxy-2,4,8-trimethyldec-8-enolide and attempts at the synthesis of 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (1), a structure which has been assigned to a metabolite of the phytopathogenic fungus, Botrytis cinerea, gave products whose spectroscopic data had significant differences from those reported for the natural product 1. The rare 11-membered lactone rings were constructed by ring-closing metathesis reactions. The increase in conformational restrictions imposed by the substituents has a high influence on the stereochemistry of the ring-closing metathesis reaction and gives rise to a decrease in the yield for the synthesis of 11-membered lactones. The predominant alkene which was obtained was the (Z)-isomer. The observed spectroscopic differences between the synthesized lactones and the natural product and the spectroscopic data of its acetylated derivative 26a allowed us to revise the structure 1 to that of the γ-butyrolactone 26.

  2. Partial cloning, tissue distribution and effects of epigallocatechin gallate on hepatic 3-hydroxy-3-methylglutaryl-CoA reductase mRNA transcripts in goldfish (Carassius auratus).

    PubMed

    Cocci, Paolo; Mosconi, Gilberto; Palermo, Francesco Alessandro

    2014-07-25

    Epigallocatechin gallate (EGCG), the major active component of the green tea, has recently been found to inhibit 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) activity in vitro and to modulate lipogenesis in vivo. In this study we have evaluated the effects of short-term in vivo exposure to EGCG (6 μg g(-1) BW or 9 μg g(-1) BW) on hepatic HMGCoAR gene expression of goldfish (Carassius auratus). We initially characterized a partial sequence of goldfish HMGCoAR suggesting that the obtained fragment shares high similarity (>92%) with other fish HMGCoAR sequences. Further, the HMGCoAR transcript was detected in all goldfish tissues (except muscle) but primarily in liver, brain and gonads; on the contrary, low expression levels were found in intestine, heart, gill, and kidney. Both EGCG doses significantly decreased hepatic HMGCoAR mRNA levels 180 min post-injection. HMGCoAR was also significantly down-regulated at 90 min after injection in fish treated with the highest dose of EGCG. Our results demonstrate that hepatic HMGCoAR gene expression is acutely responsive to short-term EGCG exposure in goldfish. This finding suggests a potential role of EGCG in transcriptional regulation of the rate-limiting enzyme in cholesterol synthesis.

  3. Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes.

    PubMed

    Klette, K L; Anderson, C J; Poch, G K; Nimrod, A C; ElSohly, M A

    2000-10-01

    The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

  4. Simultaneous spectrophotometric determination of Cu2+, Hg2+, and Cd2+ ions using 2-(3-hydroxy-1-methylbut-2-enylideneamino)pyridine-3-ol.

    PubMed

    Tarighat, Maryam Abbasi; Mohammadi, Khosro

    2015-04-01

    New complexes of Cu2+, Hg2+, and Cd2+ with a recently synthesized Schiff base derived from 2-(3-hydroxy-1-methylbut-2-enylideneamino)pyridine-3-ol were applied for their simultaneous determination with artificial neural networks. A new analytical method using principal component-feed forward neural networks (PC-FFNNs) and principal component-radial basis function networks (PC-RBFNs) was used. Spectral data was reduced using principal component analysis and subjected to ANNs. The data obtained from synthetic mixtures of metal ions were processed by PC-FFNNs and PC-RBFNs. Performances of the proposed methods were tested with regard to relative standard error of prediction. Limit of detections and limit of quantifications were determined. The results obtained by PC-FFNNs and PC-RBFNs were compared to each other. Under the working conditions, the proposed methods were successfully applied to simultaneous determination of Hg2+, Cu2+, and Cd2+ in different water and soil samples. Concentrations of metal ions in the samples were also determined by flame atomic absorption spectrometry (FAAS) and standard addition method. The amounts of metal ions obtained by the proposed methods were in good agreement with those obtained by FAAS and standard addition method.

  5. Chronic oral toxicity of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the dog.

    PubMed

    Otabe, A; Fujieda, T; Masuyama, T

    2011-11-01

    Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate), an N-substituted analog of aspartame, has been developed as a high-intensity sweetener. Groups of 4 dogs of each sex were treated at 0, 2000, 10,000, or 50,000 ppm of advantame in the diet for 52 weeks. Additional groups of 2 dogs/sex at the control, and mid- and high-dose groups were treated for 52 weeks followed by a 6-week recovery period. There was no effect of treatment on mortality, body weight, organ weights, food consumption, or the results of ophthalmological, electrocardiographic, haematological, clinical chemistry or urinalysis examinations. No histopathological changes were associated with advantame treatment. The NOAEL was considered to be 50,000 ppm, the highest concentration tested, which was equivalent to 2057 and 2139 mg/kg body weight/day in males, and females, respectively. The results of the study support the safety of advantame for use as a high-intensity sweetener.

  6. Expression of the Arabidopsis HMG2 gene, encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, is restricted to meristematic and floral tissues.

    PubMed Central

    Enjuto, M; Lumbreras, V; Marín, C; Boronat, A

    1995-01-01

    The synthesis of mevalonate, which is considered the first rate-limiting step in isoprenoid biosynthesis, is catalyzed by the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR; EC 1.1.1.34). In Arabidopsis, HMGR is encoded by two differentially expressed genes (HMG1 and HMG2). The transcriptional activity of the HMG2 gene was studied after fusing different regions of its 5' flanking region to the beta-glucuronidase (GUS) reporter gene and transforming the resulting constructs into tobacco plants. The spatial and temporal expression directed by the HMG2 promoter in the transgenic plants is consistent with the expression pattern previously established by RNA analysis using an HMG2-specific probe. HMG2 expression is restricted to meristematic (root tip and shoot apex) and floral (secretory zone of the stigma, mature pollen grains, gynoecium vascular tissue, and fertilized ovules) tissues. Deletion analysis of the HMG2 5' flanking region was conducted in transgenic plants and transfected protoplasts. The region containing nucleotides -857 to +64 of the HMG2 gene was sufficient to confer high levels of expression in both floral and meristematic tissues, although deletion to nucleotide -503 resulted in almost complete loss of expression. Sequences contained within the 5' transcribed, untranslated region are also important for gene expression. The biological significance of the restricted pattern of expression of HMG2 is also discussed. PMID:7780305

  7. Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

    SciTech Connect

    Rodriguez-Concepcion, M.; Gruissem, W.

    1999-01-01

    Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression of HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.

  8. Isolation of pig mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene promoter: characterization of a peroxisome proliferator-responsive element.

    PubMed Central

    Ortiz, J A; Mallolas, J; Nicot, C; Bofarull, J; Rodríguez, J C; Hegardt, F G; Haro, D; Marrero, P F

    1999-01-01

    Low expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene during development correlates with an unusually low hepatic ketogenic capacity and lack of hyperketonaemia in piglets. Here we report the isolation and characterization of the 5' end of the pig mitochondrial HMG-CoA synthase gene. The 581 bp region proximal to the transcription start site permits transcription of a reporter gene, confirming the function of the promoter. The pig mitochondrial HMG-CoA synthase promoter is trans-activated by the peroxisomal proliferator-activated receptor (PPAR), and a functional response element for PPAR (PPRE) has been localized in the promoter region. Pig PPRE is constituted by an imperfect direct repeat (DR-1) and a downstream sequence, both of which are needed to confer PPAR-sensitivity to a thymidine kinase promoter and to form complexes with PPAR.retinoid X receptor heterodimers. A role of PPAR trans-activation in starvation-associated induction of gene expression is suggested. PMID:9882632

  9. [Use of metal salts for radioprotection of plants during radioactive pollution of the territory].

    PubMed

    Gudkov, I N; Kitsno, V E; Grisiuk, S N; Tkachenko, G M; Ivanova, E A; Saenko, K V; Gural'chuk, Zh Z

    1999-01-01

    The applying salts of some metals to radionuclide contaminated soddy-podzolic soil in the zone of Chernobyl nuclear power station or the spraying of plants by its solutions are showing the radioprotective effect (salts of iron, zinc, cobalt and manganese) and decreasing the uptake of 90Sr and 137Cs through roots (salts of zinc, manganese, boron, lithium, cobalt and copper). PMID:10366969

  10. Preparation of ionic membranes for zinc/bromine storage batteries

    NASA Astrophysics Data System (ADS)

    Assink, R. A.; Arnold, C., Jr.

    Zinc/bromine flow batteries are being developed for vehicular and utility load leveling applications. During charge, an aqueous zinc bromide salt is electrolyzed to zinc metal and molecular bromine. During discharge, the zinc and bromine react to again form the zinc bromide salt. One serious disadvantage of the microporous separators presently used in the zinc/bromine battery is that modest amounts of bromine and negatively charged bromine moieties permeate through these materials and react with the zinc anode. This results in partial self-discharge of the battery and low coulombic efficiencies. Our approach to this problem is to impregnate the microporous separators with a soluble cationic polyelectrolyte. In laboratory screening tests a sulfonated polysulfone resin and fully fluorinated sulfonic acid polymer substantially reduced bromine permeation with only modest increases in the area resistance.

  11. 40 CFR 721.5288 - Chromate(2-), [3-hydroxy-4-[(2-hydroxy-1-naphthenyl)azo]-7-nitro-1-substituted][N-[7-hydroxy-8...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...] -1-substituted]-, salt (generic). 721.5288 Section 721.5288 Protection of Environment ENVIRONMENTAL...-substituted]-, salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as chromate(2-), -7- nitro-1-substituted] -1-substituted]-,...

  12. 40 CFR 721.5288 - Chromate(2-), [3-hydroxy-4-[(2-hydroxy-1-naphthenyl)azo]-7-nitro-1-substituted][N-[7-hydroxy-8...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-substituted]-, salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The...] -1-substituted]-, salt (generic). 721.5288 Section 721.5288 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL...

  13. 40 CFR 721.5288 - Chromate(2-), [3-hydroxy-4-[(2-hydroxy-1-naphthenyl)azo]-7-nitro-1-substituted][N-[7-hydroxy-8...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-substituted]-, salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The...] -1-substituted]-, salt (generic). 721.5288 Section 721.5288 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL...

  14. 40 CFR 721.5288 - Chromate(2-), [3-hydroxy-4-[(2-hydroxy-1-naphthenyl)azo]-7-nitro-1-substituted][N-[7-hydroxy-8...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-substituted]-, salt (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The...] -1-substituted]-, salt (generic). 721.5288 Section 721.5288 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL...

  15. Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

    DOEpatents

    Adler, T.C.; McLarnon, F.R.; Cairns, E.J.

    1994-04-12

    An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing KOH and a combination of KF and K[sub 2]CO[sub 3] salts which inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics. 8 figures.

  16. Rechargeable zinc cell with alkaline electrolyte which inhibits shape change in zinc electrode

    DOEpatents

    Adler, Thomas C.; McLarnon, Frank R.; Cairns, Elton J.

    1994-01-01

    An improved rechargeable zinc cell is described comprising a zinc electrode and another electrode such as, for example, a nickel-containing electrode, and having an electrolyte containing KOH and a combination of KF and K.sub.2 CO.sub.3 salts which inhibits shape change in the zinc electrode, i.e., the zinc electrode exhibits low shape change, resulting in an improved capacity retention of the cell over an number of charge-discharge cycles, while still maintaining high discharge rate characteristics.

  17. Surface modification of anatase nanoparticles with fused ring salicylate-type ligands (3-hydroxy-2-naphthoic acids): a combined DFT and experimental study of optical properties

    NASA Astrophysics Data System (ADS)

    Savić, Tatjana D.; Šaponjić, Zoran V.; Čomor, Mirjana I.; Nedeljković, Jovan M.; Dramićanin, Miroslav D.; Nikolić, Marko G.; Veljković, Dušan Ž.; Zarić, Snežana D.; Janković, Ivana A.

    2013-07-01

    The surface modification of nanocrystalline TiO2 particles (45 Å) with salicylate-type ligands consisting of an extended aromatic ring system, specifically 3-hydroxy-2-naphthoic acid, 3,5-dihydroxy-2-naphthoic acid and 3,7-dihydroxy-2-naphthoic acid, was found to alter the optical properties of nanoparticles in a similar way to salicylic acid. The formation of the inner-sphere charge-transfer (CT) complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites and a reduction in the band gap upon the increase in the electron delocalization when including an additional ring. The investigated ligands have the optimal geometry for binding to surface Ti atoms, resulting in ring coordination complexes of a salicylate-type (binuclear bidentate binding-bridging) thus restoring the six-coordinated octahedral geometry of surface Ti atoms. From both absorption measurements in methanol/water = 90/10 solutions and steady-state quenching measurements of modifier fluorescence upon binding to TiO2 in aqueous solutions, stability constants in the order of 103 M-1 have been determined at pH 2 and pH 3. Fluorescence lifetime measurements, in the presence and absence of colloidal TiO2 nanoparticles, indicated that the fluorescence quenching process is primarily static quenching, thus proving the formation of a nonfluorescent CT complex. The binding structures were investigated by using FTIR spectroscopy. Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain the vibrational frequencies of charge transfer complexes, and the calculated values were then compared with the experimental data.The surface modification of nanocrystalline TiO2 particles (45 Å) with salicylate-type ligands consisting of an extended aromatic ring system, specifically 3-hydroxy-2-naphthoic acid, 3,5-dihydroxy-2-naphthoic acid and 3,7-dihydroxy-2-naphthoic acid, was found to alter the optical properties of

  18. Inhibition of 3-Hydroxy-3-Methylglutaryl–Coenzyme A Reductase and Application of Statins as a Novel Effective Therapeutic Approach against Acanthamoeba Infections

    PubMed Central

    Lorenzo-Morales, Jacob; Machin, Rubén P.; López-Arencibia, Atteneri; García-Castellano, José Manuel; de Fuentes, Isabel; Loftus, Brendan; Maciver, Sutherland K.; Valladares, Basilio; Piñero, José E.

    2013-01-01

    Acanthamoeba is an opportunistic pathogen in humans, whose infections most commonly manifest as Acanthamoeba keratitis or, more rarely, granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of Acanthamoeba, they are generally lengthy and/or have limited efficacy. Therefore, there is a requirement for the identification, validation, and development of novel therapeutic targets against these pathogens. Recently, RNA interference (RNAi) has been widely used for these validation purposes and has proven to be a powerful tool for Acanthamoeba therapeutics. Ergosterol is one of the major sterols in the membrane of Acanthamoeba. 3-Hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase is an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, one of the precursors for the production of cholesterol in humans and ergosterol in plants, fungi, and protozoa. Statins are compounds which inhibit this enzyme and so are promising as chemotherapeutics. In order to validate whether this enzyme could be an interesting therapeutic target in Acanthamoeba, small interfering RNAs (siRNAs) against HMG-CoA were developed and used to evaluate the effects induced by the inhibition of Acanthamoeba HMG-CoA. It was found that HMG-CoA is a potential drug target in these pathogenic free-living amoebae, and various statins were evaluated in vitro against three clinical strains of Acanthamoeba by using a colorimetric assay, showing important activities against the tested strains. We conclude that the targeting of HMG-CoA and Acanthamoeba treatment using statins is a novel powerful treatment option against Acanthamoeba species in human disease. PMID:23114753

  19. Gas chromatography/electron-capture negative ion mass spectrometry for the quantitative determination of 2- and 3-hydroxy fatty acids in bovine milk fat.

    PubMed

    Jenske, Ramona; Vetter, Walter

    2008-07-23

    2- and 3-hydroxy fatty acids (2- and 3-OH-FAs) are bioactive substances reported in sphingolipids and bacteria. Little is known of their occurrence in food. For this reason, a method suitable for the determination of OH-FAs at trace levels in bovine milk fat was developed. OH-FAs (and conventional fatty acids in samples) were converted into methyl esters and the hydroxyl group was derivatized with pentafluorobenzoyl (PFBO) chloride to give PFBO- O-FA methyl esters. These derivatives with strong electron affinity were determined by gas chromatography interfaced to mass spectrometry using electron-capture negative ion in the selected ion monitoring mode (GC/ECNI-MS-SIM). This method proved to be highly sensitive and selective for PFBO-O-FA methyl esters. For the analysis of samples, two internal standards were used. For this purpose, 9,10-dideutero-2-OH-18:0 methyl ester (ISTD-1) from 2-OH-18:1(9 c) methyl ester as well as the ethyl ester of 3-PFBO-O-12:0 (ISTD-2) was synthesized. ISTD-1 served as a recovery standard whereas ISTD-2 was used for GC/MS measurements. The whole-sample cleanup consisted of accelerated solvent extraction of dry bovine milk, addition of ISTD 1, saponification, conversion of fatty acids into methyl esters by use of boron trifluoride, separation of the methyl esters of OH-FAs from nonsubstituted FAs on activated silica, conversion of OH-FAs methyl esters into PFBO-O-FA methyl esters, addition of ISTD-2, and measurement by GC/ECNI-MS-SIM. By this method, ten OH-FAs were quantified in bovine milk fat with high precision in the range from 0.02 +/- 0.00 to 4.49 +/- 0.29 mg/100 g of milk fat.

  20. α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor activation protects against phencyclidine-induced caspase-3 activity by activating voltage-gated calcium channels.

    PubMed

    Timpe, Jennifer M; Wang, Cheng Z; Kim, Jisoo; Johnson, Kenneth M

    2014-12-01

    Phencyclidine (PCP) is a noncompetitive, open channel blocker of the N-methyl-D-aspartate (NMDA) receptor-ion channel complex. When administered to immature animals, it is known to cause apoptotic neurodegeneration in several regions, and this is followed by olanzapine-sensitive, schizophrenia-like behaviors in late adolescence and adulthood. Clarification of its mechanism of action could yield data that would help to inform the treatment of schizophrenia. In our initial experiments, we found that α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) inhibited PCP-induced apoptosis in organotypic neonatal rat brain slices in a concentration-dependent and 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive manner. Calcium signaling pathways are widely implicated in apoptosis, and PCP prevents calcium influx through NMDA receptor channels. We therefore hypothesized that AMPA could protect against this effect by activation of voltage-dependent calcium channels (VDCCs). In support of this hypothesis, pretreatment with the calcium channel blocker cadmium chloride eliminated AMPA-mediated protection against PCP. Furthermore, the L-type VDCC inhibitor nifedipine (10 µM) fully abrogated the effects of AMPA, suggesting that L-type VDCCs are required for AMPA-mediated protection against PCP-induced neurotoxicity. Whereas the P/Q-type inhibitor ω-agatoxin TK (200 nM) reduced AMPA protection by 51.7%, the N-type VDCC inhibitor ω-conotoxin (2 µM) had no effect. Decreased AMPA-mediated protection following cotreatment with K252a, a TrkB inhibitor, suggests that brain-derived neurotrophic factor signaling plays an important role. By analogy, these results suggest that activation of L-type, and to a lesser extent P/Q-type, VDCCs might be advantageous in treating conditions associated with diminished NMDAergic activity during early development. PMID:24995437

  1. Proliferation and Morphogenesis of the Endoplasmic Reticulum Driven by the Membrane Domain of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Plant Cells.

    PubMed

    Ferrero, Sergi; Grados-Torrez, Ricardo Enrique; Leivar, Pablo; Antolín-Llovera, Meritxell; López-Iglesias, Carmen; Cortadellas, Nuria; Ferrer, Joan Carles; Campos, Narciso

    2015-07-01

    The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) has a key regulatory role in the mevalonate pathway for isoprenoid biosynthesis and is composed of an endoplasmic reticulum (ER)-anchoring membrane domain with low sequence similarity among eukaryotic kingdoms and a conserved cytosolic catalytic domain. Organized smooth endoplasmic reticulum (OSER) structures are common formations of hypertrophied tightly packed ER membranes devoted to specific biosynthetic and secretory functions, the biogenesis of which remains largely unexplored. We show that the membrane domain of plant HMGR suffices to trigger ER proliferation and OSER biogenesis. The proliferating membranes become highly enriched in HMGR protein, but they do not accumulate sterols, indicating a morphogenetic rather than a metabolic role for HMGR. The N-terminal MDVRRRPP motif present in most plant HMGR isoforms is not required for retention in the ER, which was previously proposed, but functions as an ER morphogenic signal. Plant OSER structures are morphologically similar to those of animal cells, emerge from tripartite ER junctions, and mainly build up beside the nuclear envelope, indicating conserved OSER biogenesis in high eukaryotes. Factors other than the OSER-inducing HMGR construct mediate the tight apposition of the proliferating membranes, implying separate ER proliferation and membrane association steps. Overexpression of the membrane domain of Arabidopsis (Arabidopsis thaliana) HMGR leads to ER hypertrophy in every tested cell type and plant species, whereas the knockout of the HMG1 gene from Arabidopsis, encoding its major HMGR isoform, causes ER aggregation at the nuclear envelope. Our results show that the membrane domain of HMGR contributes to ER morphogenesis in plant cells.

  2. Diurnal variation in the fraction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the active form in the mammary gland of the lactating rat.

    PubMed Central

    Smith, R A; Middleton, B; West, D W

    1986-01-01

    'Expressed' and 'total' activities of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) were measured in freeze-clamped samples of mammary glands from lactating rats at intervals throughout the 24 h light/dark cycle. 'Expressed' activities were measured in microsomal fractions isolated and assayed in the presence of 100 mM-KF. 'Total' activities were determined in microsomal preparations from the same homogenates but washed free of KF and incubated with exogenously added sheep liver phosphoprotein phosphatase before assay. Both 'expressed' and 'total' activities of HMG-CoA reductase underwent a diurnal cycle, which had a major peak 6 h into the light phase and a nadir 15 h later, i.e. 9 h into the dark period. Both activities showed a secondary peak of activity (around 68% of the maximum activity) at the time of changeover from dark to light, with a trough in the value of the 'expressed' activity that was close to the nadir value. 'Expressed' activity was lower than 'total' at all time points, indicating the presence of enzyme molecules inactivated by covalent phosphorylation. Nevertheless the 'expressed'/'total' activity ratio was comparatively constant and varied only between 43% and 75%. Immunotitration of enzyme activity, with antiserum raised in sheep against purified rat liver HMG-CoA reductase, confirmed the presence of both active and inactive forms of the enzyme and indicated that at the peak and nadir the variation in 'expressed' HMG-CoA reductase activity resulted from changes in the total number of enzyme molecules rather than from covalent modification. The sample obtained after 3 h of the light phase exhibited an anomalously low 'total' HMG-CoA reductase activity, which could be increased when Cl- replaced F- in the homogenization medium. The result suggests that at that time the activity of the enzyme could be regulated by mechanisms other than covalent phosphorylation or degradation. PMID:3814075

  3. Masou salmon (Oncorhynchus masou) ethanol extract decreases 3-hydroxy-3-methylglutaryl coenzyme A reductase expression in diet-induced obese mice.

    PubMed

    Oh, Hyun-Taek; Chung, Mi Ja; Kim, Soo-Hyun; Choi, Hyun-Jin; Ham, Seung-Shi

    2009-02-01

    This study was designed to evaluate the hypocholesterolemic effects of masou salmon 70% ethanol extract (MSE) and to determine the molecular mechanism by which MSE exerts its effects in high-fat (HF) diet-induced obese mice. We hypothesize that the MSE may contain abundant n-3 fatty acids, so a diet containing MSE may also have hypolipidemic effects by assessing several key gene expressions in cholesterol metabolism such as the low-density lipoprotein (LDL) receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and cholesterol 7alpha-hydroxylase (CYP7A1). To test this hypothesis, C57BL/6J mice were fed a 40% HF diet for 5 weeks, after which time the animals were fed an HF diet containing 0 mg/kg, 75 mg/kg, or 150 mg/kg MSE (HF, HF + MSE 1, and HF + MSE 2 groups, respectively) for an additional 4 weeks (n = 8 in each group, for a total of 24 mice). We found that feeding MSE with an HF diet prevented hypercholesterolemia in diet-induced obese mice; daily MSE feeding reduced total cholesterol levels in plasma and liver by 12.3% and 16.2%, respectively. Furthermore, we examined the expression of key cholesterol metabolism genes by reverse transcription-polymerase chain reaction and found that messenger RNA levels of HMG-CoA reductase were decreased by up to 5-fold, but the expression of both LDL receptor and CYP7A1 did not change. Thus, MSE may exert its hypocholesterolemic effect by altering the expression of HMG-CoA reductase. PMID:19285603

  4. Proliferation and Morphogenesis of the Endoplasmic Reticulum Driven by the Membrane Domain of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Plant Cells1[OPEN

    PubMed Central

    Ferrero, Sergi; Grados-Torrez, Ricardo Enrique; Antolín-Llovera, Meritxell; López-Iglesias, Carmen; Cortadellas, Nuria; Ferrer, Joan Carles

    2015-01-01

    The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) has a key regulatory role in the mevalonate pathway for isoprenoid biosynthesis and is composed of an endoplasmic reticulum (ER)-anchoring membrane domain with low sequence similarity among eukaryotic kingdoms and a conserved cytosolic catalytic domain. Organized smooth endoplasmic reticulum (OSER) structures are common formations of hypertrophied tightly packed ER membranes devoted to specific biosynthetic and secretory functions, the biogenesis of which remains largely unexplored. We show that the membrane domain of plant HMGR suffices to trigger ER proliferation and OSER biogenesis. The proliferating membranes become highly enriched in HMGR protein, but they do not accumulate sterols, indicating a morphogenetic rather than a metabolic role for HMGR. The N-terminal MDVRRRPP motif present in most plant HMGR isoforms is not required for retention in the ER, which was previously proposed, but functions as an ER morphogenic signal. Plant OSER structures are morphologically similar to those of animal cells, emerge from tripartite ER junctions, and mainly build up beside the nuclear envelope, indicating conserved OSER biogenesis in high eukaryotes. Factors other than the OSER-inducing HMGR construct mediate the tight apposition of the proliferating membranes, implying separate ER proliferation and membrane association steps. Overexpression of the membrane domain of Arabidopsis (Arabidopsis thaliana) HMGR leads to ER hypertrophy in every tested cell type and plant species, whereas the knockout of the HMG1 gene from Arabidopsis, encoding its major HMGR isoform, causes ER aggregation at the nuclear envelope. Our results show that the membrane domain of HMGR contributes to ER morphogenesis in plant cells. PMID:26015445

  5. Ketanserin, an antidepressant, exerts its antileishmanial action via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) enzyme of Leishmania donovani.

    PubMed

    Singh, Sushma; Dinesh, Neeradi; Kaur, Preet Kamal; Shamiulla, Baigadda

    2014-06-01

    Leishmaniasis is one of the major health problems existing globally. The current chemotherapy for leishmaniasis presents several drawbacks like toxicity and increased resistance to existing drugs, and hence, there is a necessity to look out for the novel drug targets and new chemical entities. Current trend in drug discovery arena is the "repurposing" of old drugs for the treatment of diseases. In the present study, an antidepressant, ketanserin, was found lethal to both Leishmania donovani promastigotes and intracellular amastigotes with no apparent toxicity to the cells. Ketanserin killed promastigotes and amastigotes with an IC50 value of 37 μM and 28 μM respectively, in a dose-dependent manner. Ketanserin was found to inhibit L. donovani recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) enzyme with an IC50 value of 43 μM. Ketanserin treated promastigotes were exogenously supplemented with sterols like ergosterol and cholesterol to rescue cell death. Ergosterol could recover the inhibition partially, whereas cholesterol supplementation completely failed to rescue the inhibited parasites. Further, HMGR-overexpressing parasites were generated by transfecting Leishmania promastigotes with an episomal pspα hygroα-HMGR construct. Wild-type and HMGR overexpressors of L. donovani were used to study the effect and mode of action of this inhibitor. The HMGR overexpressors showed twofold resistance to ketanserin. These observations suggest that the lethal effect of ketanserin is due to inhibition of HMGR, the rate-limiting enzyme of the ergosterol biosynthetic pathway. Since targeting of the sterol biosynthetic pathway enzymes may be useful therapeutically, the present study may have implications in treatment of leishmaniasis.

  6. Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) by recombinant Escherichia coli expressing leucine metabolism-related enzymes derived from Clostridium difficile.

    PubMed

    Saika, Azusa; Watanabe, Yoriko; Sudesh, Kumar; Tsuge, Takeharu

    2014-06-01

    An obligate anaerobic bacterium Clostridium difficile has a unique metabolic pathway to convert leucine to 4-methylvalerate, in which 4-methyl-2-pentenoyl-CoA (4M2PE-CoA) is an intermediate of this pathway. 4M2PE-CoA is also able to be converted to 3-hydroxy-4-methylvalerate (3H4MV), a branched side chain monomer unit, for synthesis of polyhydroxyalkanoate (PHA) copolymer. In this study, to synthesize 3H4MV-containing PHA copolymer from leucine, the leucine metabolism-related enzymes (LdhA and HadAIBC) derived from C. difficile and PHA biosynthesis enzymes (PhaPCJAc and PhaABRe) derived from Aeromonas caviae and Ralstonia eutropha were co-expressed in the codon usage-improved Escherichia coli. Under microaerobic culture conditions, this E. coli was able to synthesize P(3HB-co-12.2 mol% 3H4MV) from glucose with the supplementation of 1 g/L leucine. This strain also produced P(3HB-co-12.6 mol% 3H4MV) using the culture supernatant of leucine overproducer E. coli strain NS1391 as the medium for PHA production, achieving 3H4MV copolymer synthesis only from glucose. Furthermore, we tested the feasibility of the 3H4MV copolymer synthesis in E. coli strain NS1391 from glucose. The recombinant E. coli NS1391 was able to synthesize P(3HB-co-3.0 mol% 3H4MV) from glucose without any leucine supplementation. This study demonstrates the potential of the new metabolic pathway for 3H4MV synthesis using leucine metabolism-related enzymes from C. difficile.

  7. Insulin treatment restores glutamate (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function in the hippocampus of diabetic rats.

    PubMed

    Viswaprakash, Nilmini; Vaithianathan, Thirumalini; Viswaprakash, Ajitan; Judd, Robert; Parameshwaran, Kodeeswaran; Suppiramaniam, Vishnu

    2015-09-01

    Type 1 diabetes is associated with cognitive dysfunction. Cognitive processing, particularly memory acquisition, depends on the regulated enhancement of expression and function of glutamate receptor subtypes in the hippocampus. Impairment of memory was been detected in rodent models of type 1 diabetes induced by streptozotocin (STZ). This study examines the functional properties of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the expression of synaptic molecules that regulate glutamatergic synaptic transmission in the hippocampus of STZ-diabetic rats. The AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) and single-channel properties of synaptosomal AMPA receptors were examined after 4 weeks of diabetes induction. Results show that amplitude and frequency of mEPSCs recorded from CA1 pyramidal neurons were decreased in diabetic rats. In addition, the single-channel properties of synaptic AMPA receptors from diabetic rat hippocampi were different from those of controls. These impairments in synaptic currents gated by AMPA receptors were accompanied by decreased protein levels of AMPA receptor subunit GluR1, the presynaptic protein synaptophysin, and the postsynaptic anchor protein postsynaptic density protein 95 in the hippocampus of diabetic rats. Neural cell adhesion molecule (NCAM), an extracellular matrix molecule abundantly expressed in the brain, and the polysialic acid (PSA) attached to NCAM were also downregulated in the hippocampus of diabetic rats. Insulin treatment, when initiated at the onset of diabetes induction, reduced these effects. These findings suggest that STZ-induced diabetes may result in functional deteriorations in glutamatergic synapses in the hippocampus of rats and that these effects may be reduced by insulin treatment. PMID:25807926

  8. Mevalonate regulates polysome distribution and blocks translation-dependent suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA: relationship to translational control.

    PubMed

    Peffley, D M; Gayen, A K

    1995-05-01

    We reported previously that 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis is regulated at the translational level by mevalonate. To determine at what stage mevalonate affects reductase synthesis, we examined the distribution of reductase mRNA in polysomes from cells treated with lovastatin alone; lovastatin and 25-hydroxycholesterol; or lovastatin, 25-hydroxycholesterol, and mevalonate. In lovastatin-treated cells, reductase mRNA was primarily associated with heavy polysome fractions. When 25-hydroxycholesterol was added to lovastatin-treated cells, reductase mRNA levels were reduced approximately fourfold in all polysome fractions, with no accompanying redistribution of reductase mRNA into lighter polysome fractions. However, addition of both 25-hydroxycholesterol and mevalonate to lovastatin-treated cells shifted reductase mRNA from heavier to lighter polysome fractions. No change in the distribution of control beta-actin or ribosomal protein S17 mRNA occurred with any of the treatments. These results suggest that mevalonate suppresses reductase synthesis at the level of initiation. When the translation inhibitor cycloheximide was added to all three regimens, reductase mRNA shifted into heavy polysome fractions. Treatment with either lovastatin alone or lovastatin plus 25-hydroxycholesterol resulted in a 50% greater loss of reductase mRNA from the heavy polysome fractions compared to the same fractions from noncycloheximide-treated cells. No loss of reductase mRNA occurred when cycloheximide was added to cells treated with both 25-hydroxycholesterol and mevalonate. beta-Actin mRNA levels and polysome distribution were not significantly changed by cycloheximide under any of these conditions. Translationally mediated suppression of reductase mRNA did not occur when protein synthesis was inhibited with puromycin. Our results indicate that regulation of reductase mRNA levels is translation-dependent and is linked to the rate of elongation.

  9. Bivalent transition metal complexes of o-hydroxyacetophenone [N-(3-hydroxy-2-naphthoyl)] hydrazone: Spectroscopic, antibacterial, antifungal activity and thermogravimetric studies

    NASA Astrophysics Data System (ADS)

    Zaky, R. R.; Ibrahim, K. M.; Gabr, I. M.

    2011-10-01

    Schiff base complexes of Cu(II), Ni(II) and Zn(II) with the o-hydroxyacetophenone [N-(3-hydroxy-2-naphthoyl)] hydrazone (H 2o-HAHNH) containing N and O donor sites have been synthesized. Both ligand and its metal complexes were characterized by different physicochemical methods, elemental analysis, molar conductivity ( 1H NMR, 13C NMR, IR, UV-visible, ESR, MS spectra) and also thermal analysis (TG and DTG) techniques. The discussion of the outcome data of the prepared complexes indicates that the ligand behave as a bidentate and/or tridentate ligand. The electronic spectra of the complexes as well as their magnetic moments suggest octahedral geometries for all isolated complexes. The room temperature solid state ESR spectrum of the Cu(II) complex shows d x2- y2 as a ground state, suggesting tetragonally distorted octahedral geometry around Cu(II) centre. The molar conductance measurements proved that the complexes are non-electrolytes. The kinetic thermodynamic parameters such as: E#, Δ H#, Δ G#, Δ S# are calculated from the DTG curves, for the [Ni(H O-HAHNH) 2] and [Zn(H 2 O-HAHNH)(OAc) 2]·H 2O complexes using the Coats-Redfern equation. Also, the antimicrobial properties of all compounds were studied using a wide spectrum of bacterial and fungal strains. The [Cu(H o-HAHNH)(OAc)(H 2O) 2] complex was the most active against all strains, including Aspergillus sp., Stemphylium sp. and Trichoderma sp. Fungi; E. coli and Clostridium sp. Bacteria.

  10. Cloning, Expression Profiling and Functional Analysis of CnHMGS, a Gene Encoding 3-hydroxy-3-Methylglutaryl Coenzyme A Synthase from Chamaemelum nobile.

    PubMed

    Cheng, Shuiyuan; Wang, Xiaohui; Xu, Feng; Chen, Qiangwen; Tao, Tingting; Lei, Jing; Zhang, Weiwei; Liao, Yongling; Chang, Jie; Li, Xingxiang

    2016-01-01

    Roman chamomile (Chamaemelum nobile L.) is renowned for its production of essential oils, which major components are sesquiterpenoids. As the important enzyme in the sesquiterpenoid biosynthesis pathway, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS) catalyze the crucial step in the mevalonate pathway in plants. To isolate and identify the functional genes involved in the sesquiterpene biosynthesis of C. nobile L., a HMGS gene designated as CnHMGS (GenBank Accession No. KU529969) was cloned from C. nobile. The cDNA sequence of CnHMGS contained a 1377 bp open reading frame encoding a 458-amino-acid protein. The sequence of the CnHMGS protein was highly homologous to those of HMGS proteins from other plant species. Phylogenetic tree analysis revealed that CnHMGS clustered with the HMGS of Asteraceae in the dicotyledon clade. Further functional complementation of CnHMGS in the mutant yeast strain YSC6274 lacking HMGS activity demonstrated that the cloned CnHMGS cDNA encodes a functional HMGS. Transcript profile analysis indicated that CnHMGS was preferentially expressed in flowers and roots of C. nobile. The expression of CnHMGS could be upregulated by exogenous elicitors, including methyl jasmonate and salicylic acid, suggesting that CnHMGS was elicitor-responsive. The characterization and expression analysis of CnHMGS is helpful to understand the biosynthesis of sesquiterpenoid in C. nobile at the molecular level and also provides molecular wealth for the biotechnological improvement of this important medicinal plant. PMID:27005600

  11. Immune-mediated myopathy related to anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies as an emerging cause of necrotizing myopathy induced by statins.

    PubMed

    Lahaye, Clément; Beaufrére, Anne Marie; Boyer, Olivier; Drouot, Laurent; Soubrier, Martin; Tournadre, Anne

    2014-01-01

    Immune-mediated necrotizing myopathy (IMNM) associated with statin use and anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody is a new and emerging entity that supports a link between statin use and IMNM and raises the questions of distinct clinical phenotypes and treatment strategy. We describe the clinical and histopathological characteristics of a patient and discuss the spectrum of IMNM and statin-induced myopathies. A 65-year-old man was suffering from proximal muscle weakness and elevated CK levels, following exposure to statin therapy. The symptoms worsened despite discontinuation of the drug. At that point, no myositis-specific or -associated antibodies were detected. Malignancy screening did not reveal abnormalities. Muscle biopsy demonstrated a predominantly necrotizing myopathy with minimal lymphocytic infiltrates, MHC class I expression in necrotic muscle fibers, and complement deposition on scattered non-necrotic muscle fibers. Muscle protein analysis by western blot was normal. The patient did not improve with steroid and methotrexate and required monthly intravenous immunoglobulin (IVIG) therapy. Muscle strength gradually improved, CK levels normalized and IVIG were stopped 1 year later. Screening for anti-HMGCR antibodies, not available at the time of presentation, was highly positive. Identification of anti-HMGCR antibodies in statin-exposed patients with myopathy appears to be helpful both for differential diagnosis and for treatment strategy. In patients who did not improve after discontinuation of the statin treatment, a muscle biopsy should be performed as well as screening for anti-HMGCR antibodies. Patients with this disorder require aggressive immunosuppressive treatment.

  12. 3-hydroxy-3-methyl glutaryl coenzyme A reductase: an essential actor in the biosynthesis of cantharidin in the blister beetle Epicauta chinensis Laporte.

    PubMed

    Lü, S; Jiang, M; Huo, T; Li, X; Zhang, Y

    2016-02-01

    Cantharidin (C(10)H(12)O(4)) is a monoterpene defensive toxin in insects involved in chemical defence as well as in courtship and mating behaviours. It is relatively well known in the medical literature because of its high anticancer activity and as an effective therapy for molluscum contagiosum. However, little is known about its biosynthesis pathway in vivo, and no enzyme involved in cantharidin biosynthesis has been identified. The purpose of this study was to identify the crucial enzyme that is involved in the biosynthesis of cantharidin. Using the homology cloning method, a 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) gene, the rate-limiting enzyme in the mevalonate pathway, was cloned from the blister beetle Epicauta chinensis. Quantitative reverse transcription PCR and gas chromatography methods revealed that the HMGR transcripts had a positive correlation with cantharidin production in the beetles (R = 0.891). RNA interference (RNAi) knockdown of HMGR mRNA expression was achieved by microinjection of a specific double-stranded RNA with more than 90% RNAi efficiency, and an apparent decrease of cantharidin production was observed. Furthermore, the HMGR mRNA was greatly upregulated by exogenous juvenile hormone III (JH III), and cantharidin production was also raised in males; however, when injecting the JH III with RNAi of HMGR mRNA at the same time, cantharidin production did not rise. These results demonstrate that HMGR is an essential enzyme in cantharidin biosynthesis in the blister beetle E. chinensis, which further verifies previous research results demonstrating that cantharidin is synthesized de novo by the mevalonate pathway in blister beetles.

  13. Distinctive EPR signals provide an understanding of the affinity of bis-(3-hydroxy-4-pyridinonato) copper(II) complexes for hydrophobic environments.

    PubMed

    Rangel, Maria; Leite, Andreia; Silva, André M N; Moniz, Tânia; Nunes, Ana; Amorim, M João; Queirós, Carla; Cunha-Silva, Luís; Gameiro, Paula; Burgess, John

    2014-07-01

    In this work we report the synthesis and characterization of a set of 3-hydroxy-4-pyridinone copper(ii) complexes with variable lipophilicity. EPR spectroscopy was used to characterize the structure of copper(ii) complexes in solution, and as a tool to gain insight into solvent interactions. EPR spectra of solutions of the [CuL2] complexes recorded in different solvents reveal the presence of two copper species whose ratio depends on the nature of the solvent. Investigation of EPR spectra in the pure solvents methanol, dimethylsulfoxide, dichloromethane and their 50% (v/v) mixtures with toluene allowed the characterization of two types of copper signals (gzz = 2.30 and gzz = 2.26) whose spin-Hamiltonian parameters are consistent with solvated and non-solvated square-planar copper(ii) complexes. Regarding the potential biological application of ligands and complexes and to get insight into the partition properties in water-membrane interfaces, EPR spectra were also obtained in water-saturated octanol, an aqueous solution buffered at pH = 7.4 and liposome suspensions, for three compounds representative of different hydro-lipophilic balances. Analysis of the EPR spectra obtained in liposomes allowed establishment of the location of the complexes in the water and lipid phases. In view of the results of this work we put forward the use of EPR spectroscopy to assess the affinity of copper(ii) complexes for a hydrophobic environment and also to obtain indirect information about the lipophilicity of the ligands and similar EPR silent complexes.

  14. Simultaneous determination of LSD and 2-oxo-3-hydroxy LSD in hair and urine by LC-MS/MS and its application to forensic cases.

    PubMed

    Jang, Moonhee; Kim, Jihyun; Han, Inhoi; Yang, Wonkyung

    2015-11-10

    Lysergic acid diethylamide (LSD) is administered in low dosages, which makes its detection in biological matrices a major challenge in forensic toxicology. In this study, two sensitive and reliable methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) were established and validated for the simultaneous determination of LSD and its metabolite, 2-oxo-3-hydroxy-LSD (O-H-LSD), in hair and urine. Target analytes in hair were extracted using methanol at 38°C for 15h and analyzed by LC-MS/MS. For urine sample preparation, liquid-liquid extraction was performed. Limits of detection (LODs) in hair were 0.25pg/mg for LSD and 0.5pg/mg for O-H-LSD. In urine, LODs were 0.01 and 0.025ng/ml for LSD and O-H-LSD, respectively. Method validation results showed good linearity and acceptable precision and accuracy. The developed methods were applied to authentic specimens from two legal cases of LSD ingestion, and allowed identification and quantification of LSD and O-H-LSD in the specimens. In the two cases, LSD concentrations in hair were 1.27 and 0.95pg/mg; O-H-LSD was detected in one case, but its concentration was below the limit of quantification. In urine samples collected from the two suspects 8 and 3h after ingestion, LSD concentrations were 0.48 and 2.70ng/ml, respectively, while O-H-LSD concentrations were 4.19 and 25.2ng/ml, respectively. These methods can be used for documenting LSD intake in clinical and forensic settings. PMID:26188861

  15. Expression of a 3-hydroxy-3-methylglutaryl coenzyme A reductase gene from Camptotheca acuminata is differentially regulated by wounding and methyl jasmonate.

    PubMed Central

    Burnett, R J; Maldonado-Mendoza, I E; McKnight, T D; Nessler, C L

    1993-01-01

    We have isolated a gene, hmg1, for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) from Camptotheca acuminata, a Chinese tree that produces the anti-cancer monoterpenoid indole alkaloid camptothecin (CPT). HMGR supplies mevalonate for the synthesis of the terpenoid component of CPT as well as for the formation of many other primary and secondary metabolites. In Camptotheca, hmg1 transcripts were detected only in young seedlings and not in vegetative organs of older plants. Regulation of the hmg1 promoter was studied in transgenic tobacco using three translational fusions (-1678, -1107, -165) with the beta-glucuronidase (GUS) reporter gene. Histochemical analysis of plants containing each of the three promoter fusions showed similar developmental and spatial expression patterns. In vegetative tissues, GUS staining was localized to the epidermis of young leaves and stems, particularly in glandular trichomes. Roots showed intense staining in the cortical tissues in the elongation zone and light staining in the cortex of mature roots. hmg1::GUS expression was also observed in sepals, petals, pistils, and stamens of developing flowers, with darkest staining in the ovary wall, ovules, stigmas, and pollen. Leaf discs from plants containing each of the translational fusions showed a 15- to 20-fold wound induction of hmg1::GUS expression over 72 h; however, this increase in GUS activity was completely suppressed by treatment with methyl jasmonate. Taken together, these data show that a 165-bp fragment of Camptotheca hmg1 promoter is sufficient to confer developmental regulation as well as wound induction and methyl jasmonate suppression of GUS expression in transgenic tobacco. PMID:8208857

  16. Metabolic Control of Avocado Fruit Growth (Isoprenoid Growth Regulators and the Reaction Catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase).

    PubMed

    Cowan, A. K.; Moore-Gordon, C. S.; Bertling, I.; Wolstenholme, B. N.

    1997-06-01

    The effect of isoprenoid growth regulators on avocado (Persea americana Mill. cv Hass) fruit growth and mesocarp 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity was investigated during the course of fruit ontogeny. Both normal and small-fruit phenotypes were used to probe the interaction between the end products of isoprenoid biosynthesis and the activity of HMGR in the metabolic control of avocado fruit growth. Kinetic analysis of the changes in both cell number and size revealed that growth was limited by cell number in phenotypically small fruit. In small fruit a 70% reduction in microsomal HMGR activity was associated with an increased mesocarp abscisic acid (ABA) concentration. Application of mevastatin, a competitive inhibitor of HMGR, reduced the growth of normal fruit and increased mesocarp ABA concentration. These effects were reversed by co-treatment of fruit with mevalonic acid lactone, isopentenyladenine, or N-(2-chloro-4-pyridyl)-N-phenylurea, but were not significantly affected by either gibberellic acid or stigmasterol. However, stigmasterol appeared to partially restore fruit growth when co-injected with mevastatin in either phase II or III of fruit growth. In vivo application of ABA reduced fruit growth and mesocarp HMGR activity and accelerated fruit abscission, effects that were reversed by co-treatment with isopentenyladenine. Together, these observations indicate that ABA accumulation down-regulates mesocarp HMGR activity and fruit growth, and that in situ cytokinin biosynthesis modulates these effects during phase I of fruit ontogeny, whereas both cytokinins and sterols seem to perform this function during the later phases.

  17. Metabolic Control of Avocado Fruit Growth (Isoprenoid Growth Regulators and the Reaction Catalyzed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase).

    PubMed Central

    Cowan, A. K.; Moore-Gordon, C. S.; Bertling, I.; Wolstenholme, B. N.

    1997-01-01

    The effect of isoprenoid growth regulators on avocado (Persea americana Mill. cv Hass) fruit growth and mesocarp 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity was investigated during the course of fruit ontogeny. Both normal and small-fruit phenotypes were used to probe the interaction between the end products of isoprenoid biosynthesis and the activity of HMGR in the metabolic control of avocado fruit growth. Kinetic analysis of the changes in both cell number and size revealed that growth was limited by cell number in phenotypically small fruit. In small fruit a 70% reduction in microsomal HMGR activity was associated with an increased mesocarp abscisic acid (ABA) concentration. Application of mevastatin, a competitive inhibitor of HMGR, reduced the growth of normal fruit and increased mesocarp ABA concentration. These effects were reversed by co-treatment of fruit with mevalonic acid lactone, isopentenyladenine, or N-(2-chloro-4-pyridyl)-N-phenylurea, but were not significantly affected by either gibberellic acid or stigmasterol. However, stigmasterol appeared to partially restore fruit growth when co-injected with mevastatin in either phase II or III of fruit growth. In vivo application of ABA reduced fruit growth and mesocarp HMGR activity and accelerated fruit abscission, effects that were reversed by co-treatment with isopentenyladenine. Together, these observations indicate that ABA accumulation down-regulates mesocarp HMGR activity and fruit growth, and that in situ cytokinin biosynthesis modulates these effects during phase I of fruit ontogeny, whereas both cytokinins and sterols seem to perform this function during the later phases. PMID:12223724

  18. Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD.

    PubMed

    Poch, G K; Klette, K L; Hallare, D A; Manglicmot, M G; Czarny, R J; McWhorter, L K; Anderson, C J

    1999-03-01

    Seventy-four urine specimens previously found to contain lysergic acid diethylamide (LSD) by gas chromatography-mass spectrometry (GC-MS) were analyzed by a new procedure for the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) using a Finnigan LC-MS-MS system. This procedure proved to be less complex, shorter to perform and provides cleaner chromatographic characteristics than the method currently utilized by the Navy Drug Screening Laboratories for the extraction of LSD from urine by GC-MS. All of the specimens used in the study screened positive for LSD by radioimmunoassay (Roche Abuscreen). Analysis by GC-MS revealed detectable amounts of LSD in all of the specimens. In addition, isolysergic diethylamide (iso-LSD), a byproduct of LSD synthesis, was quantitated in 64 of the specimens. Utilizing the new LC-MS-MS method, low levels of N-desmethyl-LSD (nor-LSD), another identified LSD metabolite, were detected in some of the specimens. However, all 74 specimens contained O-H-LSD at significantly higher concentrations than LSD, iso-LSD, or nor-LSD alone. The O-H-LSD concentration ranged from 732 to 112 831 pg/ml (mean, 16340 pg/ml) by quantification with an internal standard. The ratio of O-H-LSD to LSD ranged from 1.1 to 778.1 (mean, 42.9). The presence of O-H-LSD at substantially higher concentrations than LSD suggests that the analysis for O-H-LSD as the target analyte by employing LC-MS-MS will provide a much longer window of detection for the use of LSD than the analysis of the parent compound, LSD.

  19. Simultaneous determination of LSD and 2-oxo-3-hydroxy LSD in hair and urine by LC-MS/MS and its application to forensic cases.

    PubMed

    Jang, Moonhee; Kim, Jihyun; Han, Inhoi; Yang, Wonkyung

    2015-11-10

    Lysergic acid diethylamide (LSD) is administered in low dosages, which makes its detection in biological matrices a major challenge in forensic toxicology. In this study, two sensitive and reliable methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) were established and validated for the simultaneous determination of LSD and its metabolite, 2-oxo-3-hydroxy-LSD (O-H-LSD), in hair and urine. Target analytes in hair were extracted using methanol at 38°C for 15h and analyzed by LC-MS/MS. For urine sample preparation, liquid-liquid extraction was performed. Limits of detection (LODs) in hair were 0.25pg/mg for LSD and 0.5pg/mg for O-H-LSD. In urine, LODs were 0.01 and 0.025ng/ml for LSD and O-H-LSD, respectively. Method validation results showed good linearity and acceptable precision and accuracy. The developed methods were applied to authentic specimens from two legal cases of LSD ingestion, and allowed identification and quantification of LSD and O-H-LSD in the specimens. In the two cases, LSD concentrations in hair were 1.27 and 0.95pg/mg; O-H-LSD was detected in one case, but its concentration was below the limit of quantification. In urine samples collected from the two suspects 8 and 3h after ingestion, LSD concentrations were 0.48 and 2.70ng/ml, respectively, while O-H-LSD concentrations were 4.19 and 25.2ng/ml, respectively. These methods can be used for documenting LSD intake in clinical and forensic settings.

  20. Cloning and characterization of an elicitor-responsive gene encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase involved in 20-hydroxyecdysone production in cell cultures of Cyanotis arachnoidea.

    PubMed

    Wang, Qiu Jun; Zheng, Li Ping; Zhao, Pei Fei; Zhao, Yi Lu; Wang, Jian Wen

    2014-11-01

    Cyanotis arachnoidea contains a rich source of bioactive phytoecdysteroids (i.e. analogues of insect steroid hormones). 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) supplies mevalonate for the synthesis of many secondary metabolites including 20-hydroxyecdysone (20E), one of metabolism-enhancing phytoecdysteroids. In this study, in order to develop a sustainable source of 20E, cell suspension cultures were established from shoot cultures of C. arachnoidea, and a full length cDNA encoding HMGR (designated as CaHMGR) was cloned and characterized. The cDNA contained 2037 nucleotides with a complete open reading frame (ORF) of 1800 nucleotides, which was predicted to encode a peptide of 599 amino acids. Expression analysis by real-time PCR revealed that CaHMGR mRNA was abundant in C. arachnoidea stems, roots and leaves. When cultivated in Murashige & Skoog medium supplemented with 0.2 mg L(-1) 1-naphthlcetic acid (NAA) and 3.0 mg L(-1) 6-benzyladenine (6-BA), C. arachnoidea cells in suspension culture grew rapidly, yielding 20E (124.14 μg L(-1)) after 12 days. The content of 20E in cell cultures elicited by 0.2 mM methyl jasmonate (MeJA), 100 mg L(-1) yeast elicitor (YE) or 25 μM AgNO3 was increased 8-, 2-, and 6-fold over the control, respectively. Quantitative real-time PCR analysis showed that CaHMGR was expressed at a higher level under the treatment of MeJA or Ag(+) elicitor. Our results suggested that 20E accumulation may be the result of the expression up-regulation of CaHMGR involved in the biosynthesis under the treatment of various elicitors.

  1. Functional Analysis of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Encoding Genes in Triterpene Saponin-Producing Ginseng1[C][W

    PubMed Central

    Kim, Yu-Jin; Lee, Ok Ran; Oh, Ji Yeon; Jang, Moon-Gi; Yang, Deok-Chun

    2014-01-01

    Ginsenosides are glycosylated triterpenes that are considered to be important pharmaceutically active components of the ginseng (Panax ginseng ‘Meyer’) plant, which is known as an adaptogenic herb. However, the regulatory mechanism underlying the biosynthesis of triterpene saponin through the mevalonate pathway in ginseng remains unclear. In this study, we characterized the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) concerning ginsenoside biosynthesis. Through analysis of full-length complementary DNA, two forms of ginseng HMGR (PgHMGR1 and PgHMGR2) were identified as showing high sequence identity. The steady-state mRNA expression patterns of PgHMGR1 and PgHMGR2 are relatively low in seed, leaf, stem, and flower, but stronger in the petiole of seedling and root. The transcripts of PgHMGR1 were relatively constant in 3- and 6-year-old ginseng roots. However, PgHMGR2 was increased five times in the 6-year-old ginseng roots compared with the 3-year-old ginseng roots, which indicates that HMGRs have constant and specific roles in the accumulation of ginsenosides in roots. Competitive inhibition of HMGR by mevinolin caused a significant reduction of total ginsenoside in ginseng adventitious roots. Moreover, continuous dark exposure for 2 to 3 d increased the total ginsenosides content in 3-year-old ginseng after the dark-induced activity of PgHMGR1. These results suggest that PgHMGR1 is associated with the dark-dependent promotion of ginsenoside biosynthesis. We also observed that the PgHMGR1 can complement Arabidopsis (Arabidopsis thaliana) hmgr1-1 and that the overexpression of PgHMGR1 enhanced the production of sterols and triterpenes in Arabidopsis and ginseng. Overall, this finding suggests that ginseng HMGRs play a regulatory role in triterpene ginsenoside biosynthesis. PMID:24569845

  2. The Potential for Zinc Stable Isotope Techniques and Modelling to Determine Optimal Zinc Supplementation

    PubMed Central

    Tran, Cuong D.; Gopalsamy, Geetha L.; Mortimer, Elissa K.; Young, Graeme P.

    2015-01-01

    It is well recognised that zinc deficiency is a major global public health issue, particularly in young children in low-income countries with diarrhoea and environmental enteropathy. Zinc supplementation is regarded as a powerful tool to correct zinc deficiency as well as to treat a variety of physiologic and pathologic conditions. However, the dose and frequency of its use as well as the choice of zinc salt are not clearly defined regardless of whether it is used to treat a disease or correct a nutritional deficiency. We discuss the application of zinc stable isotope tracer techniques to assess zinc physiology, metabolism and homeostasis and how these can address knowledge gaps in zinc supplementation pharmacokinetics. This may help to resolve optimal dose, frequency, length of administration, timing of delivery to food intake and choice of zinc compound. It appears that long-term preventive supplementation can be administered much less frequently than daily but more research needs to be undertaken to better understand how best to intervene with zinc in children at risk of zinc deficiency. Stable isotope techniques, linked with saturation response and compartmental modelling, also have the potential to assist in the continued search for simple markers of zinc status in health, malnutrition and disease. PMID:26035248

  3. Zinc-rich coatings: A market survey

    NASA Technical Reports Server (NTRS)

    Lizak, R.

    1975-01-01

    Zinc-rich coatings with both organic and inorganic binders were considered for coastal bridges which require more corrosion protection than inland bridges because of exposure to salt spray and fog. Inorganics give longer protection and may be applied without a finish coat; those currently available are harder to apply than organics. The NASA potassium silicate/zinc - dust coating appears to provide longer protection, resist thermal shock, and overcome the application problem. Panels coated with the formulation withstood 5308 hours in a salt spray chamber with no rusting or blistering.

  4. Cleanup of plutonium oxide reduction black salts

    SciTech Connect

    Giebel, R.E.; Wing, R.O.

    1986-12-17

    This work describes pyrochemical processes employed to convert direc oxide reduction (DOR) black salts into discardable white salt and plutonium metal. The DOR process utilizes calcium metal as the reductant in a molten calcium chloride solvent salt to convert plutonium oxide to plutonium metal. An insoluble plutonium-rich dispersion called black salt sometimes forms between the metal phase and the salt phase. Black salts accumulated for processing were treated by one of two methods. One method utilized a scrub alloy of 70 wt % magnesium/30 wt % zinc. The other method utilized a pool of plutonium metal to agglomerate the metal phase. The two processes were similar in that calcium metal reductant and calcium chloride solvent salt were used in both cases. Four runs were performed by each method, and each method produced greater than 93% conversion of the black salt.

  5. Avian 3-hydroxy-3-methylglutaryl-CoA lyase: sensitivity of enzyme activity to thiol/disulfide exchange and identification of proximal reactive cysteines.

    PubMed Central

    Hruz, P. W.; Miziorko, H. M.

    1992-01-01

    Catalysis by purified avian 3-hydroxy-3-methylglutaryl-CoA lyase is critically dependent on the reduction state of the enzyme, with less than 1% of optimal activity being observed with the air-oxidized enzyme. The enzyme is irreversibly inactivated by sulfhydryl-directed reagents with the rate of this inactivation being highly dependent upon the redox state of a critical cysteine. Methylation of reduced avian lyase with 1 mM 4-methylnitrobenzene sulfonate results in rapid inactivation of the enzyme with a k(inact) of 0.178 min-1. The oxidized enzyme is inactivated at a sixfold slower rate (k(inact) = 0.028 min-1). Inactivation of the enzyme with the reactive substrate analog 2-butynoyl-CoA shows a similar dependence upon the enzyme's redox state, with a sevenfold difference in k(inact) observed with oxidized vs. reduced forms of the enzyme. Chemical cross-linking of the reduced enzyme with stoichiometric amounts of the bifunctional reagents 1,3-dibromo-2-propanone (DBP) or N,N'-ortho-phenylene-dimaleimide (PDM) coincides with rapid inactivation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of enzyme treated with bifunctional reagent reveals a band of twice the molecular weight of the lyase monomer, indicating that an intersubunit cross-link has been formed. Differential labeling of native and cross-linked protein with [1-14C]iodoacetate has identified as the primary cross-linking target a cysteine within the sequence VSQAACR, which maps at the carboxy-terminus of the cDNA-deduced sequence of the avian enzyme (Mitchell, G.A., et al., 1991, Am. J. Hum. Genet. 49, 101). In contrast, bacterial HMG-CoA lyase, which contains no corresponding cysteine, is not cross-linked by comparable treatment with bifunctional reagent. These results provide evidence for a potential regulatory mechanism for the eukaryotic enzyme via thiol/disulfide exchange and identify a cysteinyl residue with the reactivity and juxtaposition required for participation in disulfide

  6. Control of 3-Hydroxy-3-Methylglutaryl-CoA Reductase Activity in Cultured Human Fibroblasts by Very Low Density Lipoproteins of Subjects with Hypertriglyceridemia

    PubMed Central

    Gianturco, Sandra H.; Gotto, Antonio M.; Jackson, Richard L.; Patsch, Josef R.; Sybers, Harley D.; Taunton, O. David; Yeshurun, Daniel L.; Smith, Louis C.

    1978-01-01

    Very low density lipoproteins (VLDL) and low density lipoproteins (LDL) from human normolipemic plasma, and the VLDL, the intermediate density lipoprotein (IDL), and LDL from patients with Type III hyperlipoproteinemic plasma were tested for their abilities to suppress the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in cultured human fibroblasts from normal subjects and a Type III patient. Regulation of cholesterol synthesis in the fibroblasts of a patient with Type III hyperlipoproteinemia appears to be normal. VLDL from normal subjects, isolated by angle head ultracentrifugation (d < 1.006) or by gel filtration on BioGel A-5m, were about 5 times less effective than LDL in suppressing HMG-CoA reductase activity, based on protein content, in agreement with previous reports with normal fibroblasts. Zonal centrifugation of normal VLDL isolated by both methods showed that the VLDL contained IDL. Normal VLDL from the angle head rotor, refractionated by the zonal method, had little, if any, ability to suppress the HMG-CoA reductase activity in either normal or Type III fibroblasts. VLDL, IDL, and LDL fractionated by zonal ultracentrifugation from Type III plasma gave half-maximum inhibition at 0.2-0.5 μg of protein/ml, indistinguishable from the suppression caused by normal LDL. Type III VLDL did not suppress HMG-CoA reductase in mutant LDL receptor-negative fibroblasts. Zonally isolated VLDL obtained from one Type IV and one Type V patient gave half-maximal suppression at 5 and 0.5 μg of protein/ml, respectively. Molecular diameters and apoprotein compositions of the zonally isolated normal and Type III VLDL were similar; the major difference in composition was that Type III VLDL contained more cholesteryl esters and less triglyceride than did normal VLDL. The compositions and diameters of the Type IV and Type V VLDL were similar to normal VLDL. These findings show that the basic defect in Type III hyperlipoproteinemia is qualitatively

  7. Isomer-selective distribution of 3-n-butylphthalide (NBP) hydroxylated metabolites, 3-hydroxy-NBP and 10-hydroxy-NBP, across the rat blood-brain barrier

    PubMed Central

    Diao, Xing-xing; Zhong, Kan; Li, Xiu-li; Zhong, Da-fang; Chen, Xiao-yan

    2015-01-01

    Aim: To investigate the mechanisms underlying the isomer-selective distribution of 3-n-butylphthalide (NBP) hydroxylated metabolites, 3-hydroxy-NBP (3-OH-NBP) and 10-hydroxy-NBP (10-OH-NBP), across the blood brain barrier (BBB). Methods: After oral administration of NBP (20 mg/kg) to rats, the pharmacokinetics of two major hydroxylated metabolites, 3-OH-NBP and 10-OH-NBP, in plasma and brains were investigated. Plasma and brain protein binding of 3-OH-NBP and 10-OH-NBP was also assessed. To evaluate the influences of major efflux transporters, rats were pretreated with the P-gp inhibitor tariquidar (10 mg/kg, iv) and BCRP inhibitor pantoprazole (40 mg/kg, iv), then received 3-OH-NBP (12 mg/kg, iv) or 10-OH-NBP (3 mg/kg, iv). The metabolic profile of NBP was investigated in rat brain homogenate. Results: After NBP administration, the plasma exposure of 3-OH-NBP was 4.64 times that of 10-OH-NBP, whereas the brain exposure of 3-OH-NBP was only 11.8% of 10-OH-NBP. In the rat plasma, 60%±5.2% of 10-OH-NBP was unbound to proteins versus only 22%±2.3% of 3-OH-NBP being unbound, whereas in the rat brain, free fractions of 3-OH-NBP and 10-OH-NBP were 100%±9.7% and 49.9%±14.1%, respectively. In the rats pretreated with tariquidar and pantoprazole, the unbound partition coefficient Kp,uu of 3-OH-NBP was significantly increased, while that of 10-OH-NBP showed a slight but not statistically significant increase. Incubation of rat brain homogenate with NBP yielded 3-OH-NBP but not 10-OH-NBP. Conclusion: The isomer-selective distribution of 10-OH-NBP and 3-OH-NBP across the BBB of rats is mainly attributed to the differences in plasma and brain protein binding and the efflux transport of 3-OH-NBP. The abundant 10-OH-NBP is not generated in rat brains. PMID:26567730

  8. Pharmacological characterization of cGMP regulation by the biarylpropylsulfonamide class of positive, allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.

    PubMed

    Ryder, John W; Falcone, Julie F; Manro, Jason R; Svensson, Kjell A; Merchant, Kalpana M

    2006-10-01

    The biarylpropylsulfonamide class of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) potentiators represented by N-2-(4-(4-cyanophenol)phenol)propyl-2-propanesulfonamide (LY404187) and (R)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide (LY503430) are positive, allosteric AMPA receptor activators, which enhance AMPA receptor-mediated neurotransmission by reducing desensitization of the ion channel. Although these compounds have efficacy in in vivo rodent models of cognition, depression, and Parkinson's disease, little is known about biochemical pathways activated by these agents. Given the well established regulation of the nitric oxide/cGMP pathway by excitatory neurotransmission, the current study characterized AMPA receptor potentiator-mediated cGMP response in mouse cerebellum. Acute treatment by both LY404187 and LY503430 [2.0, 5.0, or 10 mg/kg subcutaneously (s.c.)] elevated basal cerebellar cGMP levels in a dose-dependent manner. Pretreatment with the noncompetitive, allosteric AMPA receptor-selective antagonist 7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine-7-carboxamide, 5-(4-aminophenyl)-8,9-dihydro-N,8-dimethyl-monohydrochloride-(9CI) (GYKI 53655) [3.0 mg/kg intraperitoneally (i.p.)], completely blocked the effect of LY404187, demonstrating that activation of AMPA receptors induces cGMP levels. Interestingly, pretreatment with the N-methyl-d-aspartate (NMDA) open channel blocker dizocilpine (0.3 and 1.0 mg/kg i.p.) also abolished the AMPA receptor potentiator-mediated cGMP accumulation, indicating that activation of AMPA receptors leads to NMDA receptor-mediated transmission involved in cGMP regulation. Pharmacological augmentation of the endogenous glutamate tone via the alkaloid harmaline (20-60 mg/kg i.p.) synergized with AMPA potentiator activity and provided further direct evidence of in vivo allosteric activation of AMPA receptors by LY404187. The synergism between harmaline and LY404187 was

  9. Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein.

    PubMed Central

    Hampton, R Y; Gardner, R G; Rine, J

    1996-01-01

    3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), a key enzyme of sterol synthesis, is an integral membrane protein of the endoplasmic reticulum (ER). In both humans and yeast, HMG-R is degraded at or in the ER. The degradation of HMG-R is regulated as part of feedback control of the mevalonate pathway. Neither the mechanism of degradation nor the nature of the signals that couple the degradation of HMG-R to the mevalonate pathway is known. We have launched a genetic analysis of the degradation of HMG-R in Saccharomyces cerevisiae using a selection for mutants that are deficient in the degradation of Hmg2p, an HMG-R isozyme. The underlying genes are called HRD (pronounced "herd"), for HMG-CoA reductase degradation. So far we have discovered mutants in three genes: HRD1, HRD2, and HRD3. The sequence of the HRD2 gene is homologous to the p97 activator of the 26S proteasome. This p97 protein, also called TRAP-2, has been proposed to be a component of the mature 26S proteasome. The hrd2-1 mutant had numerous pleiotropic phenotypes expected for cells with a compromised proteasome, and these phenotypes were complemented by the human TRAP-2/p97 coding region. In contrast, HRD1 and HRD3 genes encoded previously unknown proteins predicted to be membrane bound. The Hrd3p protein was homologous to the Caenorhabditis elegans sel-1 protein, a negative regulator of at least two different membrane proteins, and contained an HRD3 motif shared with several other proteins. Hrd1p had no full-length homologues, but contained an H2 ring finger motif. These data suggested a model of ER protein degradation in which the Hrd1p and Hrd3p proteins conspire to deliver HMG-R to the 26S proteasome. Moreover, our results lend in vivo support to the proposed role of the p97/TRAP-2/Hrd2p protein as a functionally important component of the 26S proteasome. Because the HRD genes were required for the degradation of both regulated and unregulated substrates of ER degradation, the HRD genes are the

  10. 5,7-dihydroxy-2-(3-hydroxy-4, 5-dimethoxy-phenyl)-chromen-4-one-a flavone from Bruguiera gymnorrhiza displaying anti-inflammatory properties

    PubMed Central

    Barik, Rajib; Sarkar, Ratul; Biswas, Prova; Bera, Rammohan; Sharma, Soma; Nath, Suvadeep; Karmakar, Sanmoy; Sen, Tuhinadri

    2016-01-01

    Objective: Bruguiera gymnorrhiza (BRG) (L.) Lamk (Rhizophoraceae), a mangrove species, is widely distributed in the Pacific region, eastern Africa, Indian subcontinent, and subtropical Australia. The leaves of this plant are traditionally used for treating burns and inflammatory lesions. This study isolates the bioactive compound from the methanol extract of BRG leaves and evaluates the possible mechanisms of anti-inflammatory activity involved. Materials and Methods: Bioassay-guided fractionation of BRG was performed to identify the bioactive fraction (displaying inhibition of cyclooxygenase 2 [COX2] - 5-lipoxygenase (5-LOX) activities and tumor necrosis factor-alpha (TNF-α) production at the tested concentrations of 100 and 10 μg/ml). The fractionation was performed by solvent extraction and preparative high-performance liquid chromatography. The bioactive compound was characterized by ultraviolet–visible, liquid chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. The antioxidant potential was evaluated by electron spin resonance spectrum of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical at 250 μM. The effect of the compound was also studied on TNF-α converting enzyme and nuclear factor kappa B (NF-κB) activities at the concentrations 100, 10 and 1 μg/ml. Results: Bioassay-guided purification of BRG revealed the presence of a flavone (5,7-dihydroxy-2- [3-hydroxy-4,5-dimethoxy-phenyl]-chromen-4-one) of molecular weight 330Da. It demonstrated more than 80% inhibition against COX2, 5-LOX activities and TNF-α production at 100 μg/ml. It also displayed 40% inhibition against DPPH radical at the tested concentration along with 23.1% inhibition of NF-κB activity at 100 μg/ml. Conclusions: The isolated methoxy-flavone may play a predominant role in the anti-inflammatory properties displayed by BRG leaves. Such activity may involve multiple mechanisms, namely (a) modulation of oxidative stress (b) inhibition of arachidonic acid

  11. The 3-hydroxy fatty acids as biomarkers for quantification and characterization of endotoxins and Gram-negative bacteria in atmospheric aerosols in Hong Kong

    NASA Astrophysics Data System (ADS)

    Lee, Alex K. Y.; Chan, Chak K.; Fang, Ming; Lau, Arthur P. S.

    Endotoxins from Gram-negative bacteria have received much attention because they could elicit strong pro-inflammatory responses in the human respiratory tract. In this study, 3-hydroxy fatty acids (3-OH FAs) with carbon chain lengths from 10 to 18 (C10-C18) were employed as biomarkers to quantify and characterize the endotoxins and Gram-negative bacterial community in atmospheric aerosols. Gas chromatography-mass spectrometry (GC-MS) was utilized for quantification of this biomarker in fine (PM 2.5) and coarse (PM 2.5-10) particulates collected by high volume samplers simultaneously at a rural and an urban site in Hong Kong. The geometric mean concentrations of the endotoxins were 5.5 and 1.35 ng m -3 in fine and coarse particulates at the rural site, respectively. At the urban site, the corresponding concentrations were 9.4 and 2.80 ng m -3 in fine and coarse particulates, respectively. It is found that 70-80% of the total endotoxins are associated with the fine particulates. Significant higher endotoxin levels at the urban site were observed throughout the 8-month study period. This could possibly relate to the heavier human activities in the urban areas. The distribution patterns of the 3-OH FAs with respect to carbon number are similar between the rural and urban sites regardless of particle sizes. The C10 and C16 were predominant and accounted for about 40-50% of the total 3-OH FAs. Furthermore, the odd carbon chain length 3-OH FAs constituted a non-negligible fraction (15-25%) of the total 3-OH FAs. The biologically active endotoxins estimated as the sum of C12 and C14 portions in this study ranged from 0.6-3.7 and 1.9-4.8 ng m -3 at the rural and urban sites, respectively. Applying the biomarker-to-microbial mass conversion factors, the dry mass loading of the Gram-negative bacteria are in the order of 10-10 2 ng m -3 in atmospheric aerosol. This study also demonstrates that the biomarker (3-OH FAs) approach yields much more quantitative information such as

  12. Zinc phosphide

    Integrated Risk Information System (IRIS)

    Zinc phoshide ; CASRN 1314 - 84 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  13. Zinc cyanide

    Integrated Risk Information System (IRIS)

    Zinc cyanide ; CASRN 557 - 21 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effe

  14. Preparation and Purification of Zinc Sulphinate Reagents for Organic Synthesis

    PubMed Central

    O’Hara, Fionn; Baxter, Ryan D.; O’Brien, Alexander G.; Collins, Michael R.; Dixon, Janice A.; Fujiwara, Yuta; Ishihara, Yoshihiro; Baran, Phil S.

    2014-01-01

    SUMMARY The present protocol details the synthesis of zinc bis(alkanesulphinate)s that can be used as general reagents for the formation of radical species. The zinc sulphinates described herein have been generated from the corresponding sulphonyl chlorides by treatment with zinc dust. The products may be used crude, or a simple purification procedure may be performed to minimize incorporation of water and zinc chloride. Elemental analysis has been conducted in order to confirm the purity of the zinc sulphinate reagents; reactions with caffeine have also been carried out to verify the reactivity of each batch that has been synthesized. Although the synthesis of the zinc sulphinate salts generally proceeds within 3 h, workup can take up to 24 h and purification can take up to 3 h. Following the steps in this protocol would enable the user to generate a small toolkit of zinc sulphinate reagents over the course of one week. PMID:23640168

  15. (3S,4R)-4-(4-Fluoro­phen­yl)-3-(hydroxy­meth­yl)piperidinium chloride1

    PubMed Central

    Nirmala, M; Sreekanth, B. R.; Vishweshwar, Peddy; Moses Babu, J.; Anjaneyulu, Y

    2008-01-01

    The title compound, C12H17FNO+·Cl−, is a degradation impurity of paroxetine hydro­chloride hemihydrate (PAXIL), an anti­depressant belonging to the group of drugs called selective serotonin reuptake inhibitors (SSRIs). Similar to the paroxetine hydro­chloride salt with protonation having taken place on the basic piperidine ring, the degradation impurity also exists as the hydro­chloride salt. The cyclic six-membered piperidinium ring adopts a chair conformation with the hydroxy­methyl and 4-fluoro­phenyl groups in the equatorial positions. The ions form a tape along the b axis through charge-assisted N+—H⋯Cl− hydrogen bonds; these tapes are connected by O—H⋯Cl− hydrogen bonds along the a axis. PMID:21202292

  16. Crosstalk between Zinc Status and Giardia Infection: A New Approach.

    PubMed

    Astiazarán-García, Humberto; Iñigo-Figueroa, Gemma; Quihui-Cota, Luis; Anduro-Corona, Iván

    2015-06-03

    Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal illness worldwide which causes disturbances in zinc metabolism of infected children, representing a risk factor for zinc deficiency. How zinc metabolism is compromised by Giardia is not well understood; zinc status could be altered by intestinal malabsorption, organ redistribution or host-pathogen competition. The potential metal-binding properties of Giardia suggest unusual ways that the parasite may interact with its host. Zinc supplementation was recently found to reduce the rate of diarrhea caused by Giardia in children and to upregulate humoral immune response in Giardia-infected mice; in vitro and in vivo, zinc-salts enhanced the activity of bacitracin in a zinc-dose-dependent way, and this was not due to zinc toxicity. These findings reflect biological effect of zinc that may impact significantly public health in endemic areas of infection. In this paper, we shall explore one direction of this complex interaction, discussing recent information regarding zinc status and its possible contribution to the outcome of the encounter between the host and Giardia.

  17. Crosstalk between Zinc Status and Giardia Infection: A New Approach

    PubMed Central

    Astiazarán-García, Humberto; Iñigo-Figueroa, Gemma; Quihui-Cota, Luis; Anduro-Corona, Iván

    2015-01-01

    Zinc supplementation has been shown to reduce the incidence and prevalence of diarrhea; however, its anti-diarrheal effect remains only partially understood. There is now growing evidence that zinc can have pathogen-specific protective effects. Giardiasis is a common yet neglected cause of acute-chronic diarrheal illness worldwide which causes disturbances in zinc metabolism of infected children, representing a risk factor for zinc deficiency. How zinc metabolism is compromised by Giardia is not well understood; zinc status could be altered by intestinal malabsorption, organ redistribution or host-pathogen competition. The potential metal-binding properties of Giardia suggest unusual ways that the parasite may interact with its host. Zinc supplementation was recently found to reduce the rate of diarrhea caused by Giardia in children and to upregulate humoral immune response in Giardia-infected mice; in vitro and in vivo, zinc-salts enhanced the activity of bacitracin in a zinc-dose-dependent way, and this was not due to zinc toxicity. These findings reflect biological effect of zinc that may impact significantly public health in endemic areas of infection. In this paper, we shall explore one direction of this complex interaction, discussing recent information regarding zinc status and its possible contribution to the outcome of the encounter between the host and Giardia. PMID:26046395

  18. Development and validation a LC-MS/MS method for the simultaneous determination of agomelatine and its metabolites, 7-desmethyl-agomelatine and 3-hydroxy-agomelatine in human plasma: Application to a bioequivalence study.

    PubMed

    Li, Meizhen; Tang, Fang; Xie, Feifan; Lv, Yisha; Yu, Peng; Liu, Zhi; Cheng, Zeneng

    2015-10-15

    A novel sensitive and selective LC-MS/MS method for the determination of agomelatine, 7-desmethyl-agomelatine and 3-hydroxy-agomelatine in human plasma was developed and validated. After simple protein precipitation, the analytes were separated on a Phenomenex ODS3 column (4.6×150 mm, 5μm, Phenomenex, USA) with mobile phase consisted of methanol and 5mM ammonium formate solution (containing 0.2% formic acid) at a ratio of 70:30 (v/v) with a flow rate of 0.8mL/min. The MS acquisition was performed in multiple reactions monitoring (MRM) mode with a positive electrospray ionization source. The mass transitions monitored were m/z 244.1→185.1, m/z 230.1→171.1, m/z 260.1→201.1 and m/z 180.1→110.1 for agomelatine, 7-desmethyl-agomelatine, 3-hydroxy-agomelatine and internal standard (phenacetin), respectively. The method was validated for specificity, linearity and lower limit of quantification, precision and accuracy, extraction recovery, matrix effect and stability. The calibration curves for agomelatine, 7-desmethyl-agomelatine and 3-hydroxy-agomelatine in human plasma were linear over concentration ranges of 0.0457-100ng/mL, 0.1372-300ng/mL and 0.4572-1000ng/mL, respectively. Intra- and inter-day precisions and accuracies data met the acceptance criteria of FDA guideline for bioanalytical method validation. The developed method has been successfully applied to a bioequivalence study in healthy Chinese volunteers. PMID:26409931

  19. Ring-closing metathesis-based synthesis of (3R,4R,5S)-4-acetylamino-5-amino-3-hydroxy- cyclohex-1-ene-carboxylic acid ethyl ester: a functionalized cycloalkene skeleton of GS4104.

    PubMed

    Cong, Xin; Yao, Zhu-Jun

    2006-07-01

    (3R,4R,5S)-4-Acetylamino-5-amino-3-hydroxy-cyclohex-1-ene-carboxylic acid ethyl ester, a functionalized cyclohexene skeleton of GS4104, was diastereoselectively synthesized. A major advantage of this synthesis is the use of readily available L-serine to replace frequently used (-)-shikimic acid or (-)-quinic acid as the starting material. Ring-closing metathesis and diastereoselective Grignard reactions successfully served as the key steps. Absolute configurations of the key intermediates were confirmed by corresponding two-dimensional NMR studies.

  20. New methodology for the preparation of 3-hydroxy-2-pyridinone (3,2-HOPO) chelators - Reaction of amines with a novel electrophilic 3,2-HOPO precursor

    PubMed Central

    Lambert, Timothy N.; Chittamuru, Sumathi; Jacobs, Hollie K.; Gopalan, Aravamudan S.

    2012-01-01

    The preparation of the new electrophilic iminium ester mesylate salt 5 and its reaction with primary and secondary amines have been investigated. Aniline, t-butylamine, and secondary amines react with 5 via ring opening to give the corresponding HOPO derivatives in high yields. The usefulness of this methodology has been demonstrated by the preparation of two new di-HOPO derivatives 19 and 21. This method allows the introduction of the HOPO ligand onto a variety of amine platforms without the concomitant formation of an amide bond and provides access to HOPO chelators of increased water solubility. PMID:23125467

  1. Molecular insight into amyloid oligomer destabilizing mechanism of flavonoid derivative 2-(4' benzyloxyphenyl)-3-hydroxy-chromen-4-one through docking and molecular dynamics simulations.

    PubMed

    Kumar, Akhil; Srivastava, Swati; Tripathi, Shubhandra; Singh, Sandeep Kumar; Srikrishna, Saripella; Sharma, Ashok

    2016-06-01

    Aggregation of amyloid peptide (Aβ) has been shown to be directly related to progression of Alzheimer's disease (AD). Aβ is neurotoxic and its deposition and aggregation ultimately lead to cell death. In our previous work, we reported flavonoid derivative (compound 1) showing promising result in transgenic AD model of Drosophila. Compound 1 showed prevention of Aβ-induced neurotoxicity and neuroprotective efficacy in Drosophila system. However, mechanism of action of compound 1 and its effect on the amyloid is not known. We therefore performed molecular docking and atomistic, explicit-solvent molecular dynamics simulations to investigate the process of Aβ interaction, inhibition, and destabilizing mechanism. Results showed different preferred binding sites of compound 1 and good affinity toward the target. Through the course of 35 ns molecular dynamics simulation, conformations_5 of compound 1 intercalates into the hydrophobic core near the salt bridge and showed major structural changes as compared to other conformations. Compound 1 showed interference with the salt bridge and thus reducing the inter strand hydrogen bound network. This minimizes the side chain interaction between the chains A-B leading to disorder in oligomer. Contact map analysis of amino acid residues between chains A and B also showed lesser interaction with adjacent amino acids in the presence of compound 1 (conformations_5). The study provides an insight into how compound 1 interferes and disorders the Aβ peptide. These findings will further help to design better inhibitors for aggregation of the amyloid oligomer.

  2. 3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients

    SciTech Connect

    Wang, S.P.; Robert, M.F.; Mitchell, G.A.

    1996-04-01

    3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither a TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.

  3. Crystallization and preliminary X-ray analysis of 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase from Arthrobacter nitroguajacolicus Rü61a: a cofactor-devoid dioxygenase of the α/β-hydrolase-fold superfamily

    SciTech Connect

    Steiner, Roberto A.; Frerichs-Deeken, Ursula; Fetzner, Susanne

    2007-05-01

    Preliminary crystallographic data are reported for 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) from A. nitroguajacolicus Rü61a. 1H-3-Hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) is a cofactor-devoid dioxygenase that is involved in the anthranilate pathway of quinaldine degradation. HOD has been proposed to belong to the α/β-hydrolase-fold superfamily of enzymes. N-terminally His{sub 6}-tagged HOD has been crystallized by the hanging-drop vapour-diffusion method using sodium/potassium tartrate as a precipitant and CuCl{sub 2} as an additive. The structure was solved by the single anomalous dispersion (SAD) technique using data collected to 3.5 Å resolution at the Cu absorption peak wavelength. The crystals belong to the primitive tetragonal space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 153.788, c = 120.872 Å.

  4. Use of (2-/sup 14/C)mevalonate and saponin-bound (/sup 14/C)-3-hydroxy-3-methylglutaric acid for the biosynthesis of terpenoids in leaves of Dioscorea deltoidea

    SciTech Connect

    Gurielidze, K.G.; Paseshnichenko, V.A.; Vasil'eva, I.S.

    1986-03-20

    After the introduction of (2-/sup 14/C)acetate into leaves of Dioscorea deltoidea, a radioactive furonanalog of deltafolin - protodeltofolin, containing two-thirds of the label in the 3-hydroxy-3-methylglutaryl portion - was isolated from them. Radioactive ..beta..-careotene and sterols were isolated from cut young leaves of Dioscorea 24 h after the introduction of (/sup 14/C) protodeltofolin into them, using chromatography on a column of silica gel and precipitation of sterols in the form of digitonins for this purpose. The incorporation of radioactivity from (/sup 14/C)-3-hydroxy-3-methyl-glutaric acid, bound in the form of a saponin, and ..beta..-carotene came to 0.18-0.80%, while incorporation into sterols came to 0.07-2.86% of the radioactivity of the alcohol extract. Thereby it was shown that 3-hydroxyl-3-methylglutaric acid, bound in the form of the saponin, can be used to form terpenoids in Dioscorea leaves. It was suggested that the binding of hydroxymethylglutaric acid to saponin represents one of the mechanisms of regulation of the rate of terpenoid biosynthesis in Dioscorea leaves.

  5. Finger millet (Eleucine coracana) flour as a vehicle for fortification with zinc.

    PubMed

    Tripathi, Bhumika; Platel, Kalpana

    2010-01-01

    Millets, being less expensive compared to cereals and the staple for the poorer sections of population, could be the choice for fortification with micronutrients such as zinc. In view of this, finger millet, widely grown and commonly consumed in southern India, was explored as a vehicle for fortification with zinc in this investigation. Finger millet flour fortified with either zinc oxide or zinc stearate so as to provide 50mg zinc per kg flour, was specifically examined for the bioaccessibility of the fortified mineral, as measured by in vitro simulated gastrointestinal digestion procedure and storage stability. Addition of the zinc salts increased the bioaccessible zinc content by 1.5-3 times that of the unfortified flour. Inclusion of EDTA along with the fortified salt significantly enhanced the bioaccessibility of zinc from the fortified flours, the increase being three-fold. Inclusion of citric acid along with the zinc salt and EDTA during fortification did not have any additional beneficial effect on zinc bioaccessiblity. Moisture and free fatty acid contents of the stored fortified flours indicated the keeping quality of the same, up to 60 days. Both zinc oxide and zinc stearate were equally effective as fortificants, when used in combination with EDTA as a co-fortificant. The preparation of either roti or dumpling from the fortified flours stored up to 60 days did not result in any significant compromise in the bioaccessible zinc content. Thus, the present study has revealed that finger millet flour can effectively be used as a vehicle for zinc fortification to derive additional amounts of bioaccessible zinc, with reasonably good storage stability, to combat zinc deficiency.

  6. Zinc and zinc transporters in prostate carcinogenesis

    PubMed Central

    Kolenko, Vladimir; Teper, Ervin; Kutikov, Alexander; Uzzo, Robert

    2013-01-01

    The healthy human prostate accumulates the highest level of zinc of any soft tissue in the body. This unique property is retained in BPH, but is lost in prostatic malignancy, which implicates changes in zinc and its transporters in carcinogenesis. Indeed, zinc concentrations diminish early in the course of prostate carcinogenesis, preceding histopathological changes, and continue to decline during progression toward castration-resistant disease. Numerous studies suggest that increased zinc intake might protect against progression of prostatic malignancy. Despite increased dietary intake, zinc accumulation might be limited by the diminished expression of zinc uptake transporters, resulting in decreased intratumoural zinc levels. This finding can explain the conflicting results of various epidemiological studies evaluating the role of zinc supplementation on primary and secondary prostate cancer prevention. Overall, more research into the mechanisms of zinc homeostasis are needed to fully understand its impact on prostate carcinogenesis. Only then can the potential of zinc and zinc transport proteins be harnessed in the diagnosis and treatment of men with prostate cancer. PMID:23478540

  7. Production of zinc pellets

    DOEpatents

    Cooper, John F.

    1996-01-01

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries.

  8. Production of zinc pellets

    DOEpatents

    Cooper, J.F.

    1996-11-26

    Uniform zinc pellets are formed for use in batteries having a stationary or moving slurry zinc particle electrode. The process involves the cathodic deposition of zinc in a finely divided morphology from battery reaction product onto a non-adhering electrode substrate. The mossy zinc is removed from the electrode substrate by the action of gravity, entrainment in a flowing electrolyte, or by mechanical action. The finely divided zinc particles are collected and pressed into pellets by a mechanical device such as an extruder, a roller and chopper, or a punch and die. The pure zinc pellets are returned to the zinc battery in a pumped slurry and have uniform size, density and reactivity. Applications include zinc-air fuel batteries, zinc-ferricyanide storage batteries, and zinc-nickel-oxide secondary batteries. 6 figs.

  9. Dietary phytate, zinc and hidden zinc deficiency.

    PubMed

    Sandstead, Harold H; Freeland-Graves, Jeanne H

    2014-10-01

    Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency.

  10. Contactin-associated Protein 1 (Caspr1) Regulates the Traffic and Synaptic Content of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA)-type Glutamate Receptors*

    PubMed Central

    Santos, Sandra D.; Iuliano, Olga; Ribeiro, Luís; Veran, Julien; Ferreira, Joana S.; Rio, Pedro; Mulle, Christophe; Duarte, Carlos B.; Carvalho, Ana Luísa

    2012-01-01

    Glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type mediate fast excitatory synaptic transmission in the CNS. Synaptic strength is modulated by AMPA receptor binding partners, which regulate receptor synaptic targeting and functional properties. We identify Contactin-associated protein 1 (Caspr1) as an AMPA receptor interactor. Caspr1 is present in synapses and interacts with AMPA receptors in brain synaptic fractions. Coexpression of Caspr1 with GluA1 increases the amplitude of glutamate-evoked currents. Caspr1 overexpression in hippocampal neurons increases the number and size of synaptic GluA1 clusters, whereas knockdown of Caspr1 decreases the intensity of synaptic GluA1 clusters. Hence, Caspr1 is a regulator of the trafficking of AMPA receptors to synapses. PMID:22223644

  11. Contactin-associated protein 1 (Caspr1) regulates the traffic and synaptic content of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors.

    PubMed

    Santos, Sandra D; Iuliano, Olga; Ribeiro, Luís; Veran, Julien; Ferreira, Joana S; Rio, Pedro; Mulle, Christophe; Duarte, Carlos B; Carvalho, Ana Luísa

    2012-02-24

    Glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type mediate fast excitatory synaptic transmission in the CNS. Synaptic strength is modulated by AMPA receptor binding partners, which regulate receptor synaptic targeting and functional properties. We identify Contactin-associated protein 1 (Caspr1) as an AMPA receptor interactor. Caspr1 is present in synapses and interacts with AMPA receptors in brain synaptic fractions. Coexpression of Caspr1 with GluA1 increases the amplitude of glutamate-evoked currents. Caspr1 overexpression in hippocampal neurons increases the number and size of synaptic GluA1 clusters, whereas knockdown of Caspr1 decreases the intensity of synaptic GluA1 clusters. Hence, Caspr1 is a regulator of the trafficking of AMPA receptors to synapses. PMID:22223644

  12. Zinc and vegetarian diets.

    PubMed

    Saunders, Angela V; Craig, Winston J; Baines, Surinder K

    2013-08-19

    Well planned vegetarian diets can provide adequate amounts of zinc from plant sources. Vegetarians appear to adapt to lower zinc intakes by increased absorption and retention of zinc. Good sources of zinc for vegetarians include whole grains, tofu, tempeh, legumes, nuts and seeds, fortified breakfast cereals and dairy products. The inhibitory effects of phytate on absorption of zinc can be minimised by modern food-processing methods such as soaking, heating, sprouting, fermenting and leavening. Absorption of zinc can be improved by using yeast-based breads and sourdough breads, sprouts, and presoaked legumes. Studies show vegetarians have similar serum zinc concentrations to, and no greater risk of zinc deficiency than, non-vegetarians (despite differences in zinc intake).

  13. Transient neonatal zinc deficiency.

    PubMed

    Krieger, I; Alpern, B E; Cunnane, S C

    1986-06-01

    We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA. PMID:3717070

  14. Zinc: the neglected nutrient.

    PubMed

    Shambaugh, G E

    1989-03-01

    Zinc was first recognized as essential for animals at the University of Illinois School of Agriculture in 1916, when it was found that zinc-deficient baby pigs were runty, developed dermatitis on their legs, and were sterile. Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit 26 years ago when he measured serum and hair zinc levels in young male Egyptian dwarfs who had failed to mature and were small in stature. By simply adding zinc to their regular diet, they grew in height and became sexually mature. It is now recognized that dwarfism in males is frequent around the Mediterranean, where wheat is the staple of life and has been grown for 4,000 years on the same soil, thereby resulting in the depletion of zinc. Professor Robert Henkin first suggested that zinc deficiency might cause hearing-nerve impairment. Assay of the soft tissues of the cochlea and vestibule revealed a zinc level higher than that of any other part of the body. Previously, the eye was considered to have the highest level of zinc of any organ. To diagnose zinc deficiency clinically, we use serum zinc assays made at the Mayo Clinic Trace Element Laboratory. With zinc supplementation in patients who are marginally zinc deficient, there has been improvement in tinnitus and sensorineural hearing loss in about one-third of elderly adults. We believe zinc deficiency is one causation of presbycusis; by recognizing and correcting it, a progressive hearing loss can be arrested.

  15. Zinc: the neglected nutrient.

    PubMed

    Shambaugh, G E

    1989-03-01

    Zinc was first recognized as essential for animals at the University of Illinois School of Agriculture in 1916, when it was found that zinc-deficient baby pigs were runty, developed dermatitis on their legs, and were sterile. Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit 26 years ago when he measured serum and hair zinc levels in young male Egyptian dwarfs who had failed to mature and were small in stature. By simply adding zinc to their regular diet, they grew in height and became sexually mature. It is now recognized that dwarfism in males is frequent around the Mediterranean, where wheat is the staple of life and has been grown for 4,000 years on the same soil, thereby resulting in the depletion of zinc. Professor Robert Henkin first suggested that zinc deficiency might cause hearing-nerve impairment. Assay of the soft tissues of the cochlea and vestibule revealed a zinc level higher than that of any other part of the body. Previously, the eye was considered to have the highest level of zinc of any organ. To diagnose zinc deficiency clinically, we use serum zinc assays made at the Mayo Clinic Trace Element Laboratory. With zinc supplementation in patients who are marginally zinc deficient, there has been improvement in tinnitus and sensorineural hearing loss in about one-third of elderly adults. We believe zinc deficiency is one causation of presbycusis; by recognizing and correcting it, a progressive hearing loss can be arrested. PMID:2786676

  16. Zinc-Permeable Ion Channels: Effects on Intracellular Zinc Dynamics and Potential Physiological/Pathophysiological Significance

    PubMed Central

    Inoue, Koichi; O'Bryant, Zaven; Xiong, Zhi-Gang

    2015-01-01

    Zinc (Zn2+) is one of the most important trace metals in the body. It is necessary for the normal function of a large number of proteins including enzymes and transcription factors. While extracellular fluid may contain up to micromolar Zn2+, intracellular Zn2+ concentration is generally maintained at a subnanomolar level; this steep gradient across the cell membrane is primarily attributable to Zn2+ extrusion by Zn2+ transporting systems. Interestingly, systematic investigation has revealed that activities, previously believed to be dependent on calcium (Ca2+), may be partially mediated by Zn2+. This is also supported by new findings that some Ca2+-permeable channels such as voltage-dependent calcium channels (VDCCs), N-methyl-D-aspartate receptors (NMDA), and amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPA-Rs) are also permeable to Zn2+. Thus, the importance of Zn2+ in physiological and pathophysiological processes is now more widely appreciated. In this review, we describe Zn2+-permeable membrane molecules, especially Zn2+-permeable ion channels, in intracellular Zn2+dynamics and Zn2+ mediated physiology/pathophysiology. PMID:25666796

  17. Measurements of plasma zinc

    PubMed Central

    Davies, I. J. T.; Musa, M.; Dormandy, T. L.

    1968-01-01

    Zinc is an essential trace element. Previous methods of measuring zinc in clinical material have been difficult and reported findings must be treated with caution. Using atomic absorption spectroscopy it has been established that plasma zinc is one of the most uniform biochemical characteristics of normal adult blood. Sex and age differences in adult life are insignificant. Increased metabolic activity, on the other hand, induces a marked, immediate fall in plasma zinc level. The possible implications of this are discussed. Zinc levels in patients with diabetes mellitus, cardiovascular disease, and anaemia due to acute blood loss have been within normal limits. Plasma zinc is low in certain types of liver disease. PMID:5303355

  18. Is zinc a neuromodulator?

    PubMed

    Kay, Alan R; Tóth, Katalin

    2008-01-01

    The vesicles of certain glutamatergic terminals in the mammalian forebrain are replete with ionic zinc. It is believed that during synaptic transmission zinc is released, binds to receptors on the pre- or postsynaptic membranes, and hence acts as a neuromodulator. Although exogenous zinc modulates a wide variety of channels, whether synaptic zinc transits across the synaptic cleft and alters the response of channels has been difficult to establish. We will review the evidence for zinc as a neuromodulator and propose diagnostic criteria for establishing whether it is indeed one. Moreover, we will delineate alternative ways in which zinc might act at synapses.

  19. Sensitivity of Anabaena spiroides to zinc and cobalt

    SciTech Connect

    Kostyayev, V. Ya.; Yagodka, S.N.; Sokolov, V.A.

    1980-01-01

    The influence of zinc and cobalt chlorous salts on destruction, nitrogen fixation photosynthesis, and Na/sup +/ and K/sup +/-ion concentrations in the cells was studied for the blue-green alga Anabaena spiroides. Stability of A. spiroides depends on the developmental stage. The algae are most sensitive to cobalt at the beginning of the growth lag-phase, and they are least sensitive to it at the end of this phase. Cobalt ions are more toxic for A. spiroides than zinc ions. Salts of heavy metals inhibit active ion transport, which results in a sharp decrease of K and Na ions concentration in the algae cells.

  20. Zinc oxide overdose

    MedlinePlus

    Zinc oxide is an ingredient in many products. Some of these are certain creams and ointments used ... prevent or treat minor skin burns and irritation. Zinc oxide overdose occurs when someone eats one of ...

  1. Bacitracin zinc overdose

    MedlinePlus

    ... Small amounts of bacitracin zinc are dissolved in petroleum jelly to create antibiotic ointments. Bacitracin zinc overdose ... is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation ...

  2. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  3. Phosphate salts

    MedlinePlus

    ... taken by mouth or used as enemas. Indigestion. Aluminum phosphate and calcium phosphate are FDA-permitted ingredients ... Phosphate salts containing sodium, potassium, aluminum, or calcium are LIKELY SAFE for most people when taken by mouth short-term, when sodium phosphate is inserted into the ...

  4. Development and validation of a rapid turboflow LC-MS/MS method for the quantification of LSD and 2-oxo-3-hydroxy LSD in serum and urine samples of emergency toxicological cases.

    PubMed

    Dolder, Patrick C; Liechti, Matthias E; Rentsch, Katharina M

    2015-02-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of the present study is to develop a quantitative turboflow LC-MS/MS method that can be used for rapid quantification of LSD and its main metabolite 2-oxo-3-hydroxy LSD (O-H-LSD) in serum and urine in emergency toxicological cases without time-consuming extraction steps. The method was developed on an ion-trap LC-MS/MS instrument coupled to a turbulent-flow extraction system. The validation data showed no significant matrix effects and no ion suppression has been observed in serum and urine. Mean intraday accuracy and precision for LSD were 101 and 6.84%, in urine samples and 97.40 and 5.89% in serum, respectively. For O-H-LSD, the respective values were 97.50 and 4.99% in urine and 107 and 4.70% in serum. Mean interday accuracy and precision for LSD were 100 and 8.26% in urine and 101 and 6.56% in serum, respectively. For O-H-LSD, the respective values were 101 and 8.11% in urine and 99.8 and 8.35% in serum, respectively. The lower limit of quantification for LSD was determined to be 0.1 ng/ml. LSD concentrations in serum were expected to be up to 8 ng/ml. 2-Oxo-3-hydroxy LSD concentrations in urine up to 250 ng/ml. The new method was accurate and precise in the range of expected serum and urine concentrations in patients with a suspected LSD intoxication. Until now, the method has been applied in five cases with suspected LSD intoxication where the intake of the drug has been verified four times with LSD concentrations in serum in the range of 1.80-14.70 ng/ml and once with a LSD concentration of 1.25 ng/ml in urine. In serum of two patients, the O-H-LSD concentration was determined to be 0.99 and 0.45 ng/ml. In the urine of a third patient, the O-H-LSD concentration was 9.70 ng/ml. PMID:25542574

  5. Development and validation of a rapid turboflow LC-MS/MS method for the quantification of LSD and 2-oxo-3-hydroxy LSD in serum and urine samples of emergency toxicological cases.

    PubMed

    Dolder, Patrick C; Liechti, Matthias E; Rentsch, Katharina M

    2015-02-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of the present study is to develop a quantitative turboflow LC-MS/MS method that can be used for rapid quantification of LSD and its main metabolite 2-oxo-3-hydroxy LSD (O-H-LSD) in serum and urine in emergency toxicological cases without time-consuming extraction steps. The method was developed on an ion-trap LC-MS/MS instrument coupled to a turbulent-flow extraction system. The validation data showed no significant matrix effects and no ion suppression has been observed in serum and urine. Mean intraday accuracy and precision for LSD were 101 and 6.84%, in urine samples and 97.40 and 5.89% in serum, respectively. For O-H-LSD, the respective values were 97.50 and 4.99% in urine and 107 and 4.70% in serum. Mean interday accuracy and precision for LSD were 100 and 8.26% in urine and 101 and 6.56% in serum, respectively. For O-H-LSD, the respective values were 101 and 8.11% in urine and 99.8 and 8.35% in serum, respectively. The lower limit of quantification for LSD was determined to be 0.1 ng/ml. LSD concentrations in serum were expected to be up to 8 ng/ml. 2-Oxo-3-hydroxy LSD concentrations in urine up to 250 ng/ml. The new method was accurate and precise in the range of expected serum and urine concentrations in patients with a suspected LSD intoxication. Until now, the method has been applied in five cases with suspected LSD intoxication where the intake of the drug has been verified four times with LSD concentrations in serum in the range of 1.80-14.70 ng/ml and once with a LSD concentration of 1.25 ng/ml in urine. In serum of two patients, the O-H-LSD concentration was determined to be 0.99 and 0.45 ng/ml. In the urine of a third patient, the O-H-LSD concentration was 9.70 ng/ml.

  6. Zinc oxyfluoride transparent conductor

    SciTech Connect

    Gordon, R.G.

    1991-02-05

    Transparent, electrically conductive and infrared-reflective films of zinc oxyfluoride are produced by chemical vapor deposition from vapor mixtures of zinc, oxygen and fluorine-containing compounds. The substitution of fluorine for some of the oxygen in zinc oxide results in dramatic increases in the electrical conductivity. For example, diethyl zinc, ethyl alcohol and hexafluoropropene vapors are reacted over a glass surface at 400 C to form a visibly transparent, electrically conductive, infrared reflective and ultraviolet absorptive film of zinc oxyfluoride. Such films are useful in liquid crystal display devices, solar cells, electrochromic absorbers and reflectors, energy-conserving heat mirrors, and antistatic coatings. 8 figures.

  7. Zinc oxyfluoride transparent conductor

    DOEpatents

    Gordon, Roy G.

    1991-02-05

    Transparent, electrically conductive and infrared-reflective films of zinc oxyfluoride are produced by chemical vapor deposition from vapor mixtures of zinc, oxygen and fluorine-containing compounds. The substitution of fluorine for some of the oxygen in zinc oxide results in dramatic increases in the electrical conductivity. For example, diethyl zinc, ethyl alcohol and hexafluoropropene vapors are reacted over a glass surface at 400.degree. C. to form a visibly transparent, electrically conductive, infrared reflective and ultraviolet absorptive film of zinc oxyfluoride. Such films are useful in liquid crystal display devices, solar cells, electrochromic absorbers and reflectors, energy-conserving heat mirrors, and antistatic coatings.

  8. [Zinc and gastrointestinal disorders].

    PubMed

    Higashimura, Yasuki; Takagi, Tomohisa; Naito, Yuji

    2016-07-01

    Zinc, an essential trace element, affects immune responses, skin metabolism, hormone composition, and some sensory function, so that the deficiency presents various symptoms such as immunodeficiency and taste obstacle. Further, the zinc deficiency also considers as a risk of various diseases. Recent reports demonstrated that -20% of the Japanese population was marginally zinc deficiency, and over 25% of the global population is at high risk of zinc deficiency. In gastrointestinal disorders, zinc plays an important role in the healing of mucosal and epithelial damage. In fact, polaprezinc, a chelate compound of zinc and L-carnosine, has been used for the treatment of gastric ulcer and gastritis. We describe here the therapeutic effect of zinc on gastrointestinal disorders. PMID:27455800

  9. Novel synthesis of Bis (N-oxopyridine-2-thionato) zinc (II) using solid precursors

    NASA Astrophysics Data System (ADS)

    Jo, Won-Young; Paek, Seung-Min; Park, Man; Hwang, Seong-Ju; Choy, Jin-Ho

    2006-05-01

    Unprecedented solid-transchelation reaction has been established for the synthesis of zinc pyrithione nanoparticles to control particle size within sub-micron range through direct reaction between insoluble layered zinc basic salts and aqueous sodium pyrithione solution at room temperature under ambient atmosphere. The change in crystalline phases upon reaction time clearly reveals that insoluble zinc precursors transform into zinc pyrithione nanoparticles within very short reaction time. Distinguished from usual precipitation reactions, the resulting zinc pyrithione nanoparticles exhibit a narrow size distribution. This unprecedented reaction would leads to a new route for efficient preparation of zinc pyrithione nanoparticles. And it is expected that nanosized zinc pyrithione leads to a great expansion of its application fields.

  10. Equilibrium and structure of the Al(III)-ethylenediamine-N,N'-bis(3-hydroxy-2-propionate) (EDBHP) complex. A multi-method study by potentiometry, NMR, ESI MS and X-ray diffraction.

    PubMed

    Jószai, Róbert; Kerekes, Imola; Satoshi, Igarashi; Sawada, Kiyoshi; Zékány, László; Tóth, Imre

    2006-07-14

    The equilibrium and structure of the complex formed by Al(III) and ethylenediamine-N,N'-bis(3-hydroxy-2-propionate) (EDBHP2-) have been studied using pH-potentiometry, 1H and 27Al NMR, ESI MS and single crystal X-ray diffraction methods. The EDBHP ligand is a strong Al-binder in aqueous solution for pH between 4 and 8 and for c(Al) = c(EDBHP)> or = 0.1 mmol dm(-3). The dominating complex identified by ESI MS and potentiometry is a neutral dimer, Al2L2(OH)2, with logbeta(22-2) = 14.16 +/- 0.03. In the solid Al2(EDBHP)2(OH)2.2H2O the Al(III) ions are connected through a double hydroxo bridge. Both four-dentate organic ligands are coordinated terminally through two carboxylate groups and two N-donors forming three five-membered chelate rings. The hydroxyl groups of the ligand EDBHP remain protonated and are not coordinated to the aluminium ions. The structure and composition of the dimer are very likely the same in solution and the solid state.

  11. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells.

    PubMed Central

    Hernández-Perera, O; Pérez-Sala, D; Navarro-Antolín, J; Sánchez-Pascuala, R; Hernández, G; Díaz, C; Lamas, S

    1998-01-01

    Endothelial dysfunction associated with atherosclerosis has been attributed to alterations in the L-arginine-nitric oxide (NO)-cGMP pathway or to an excess of endothelin-1 (ET-1). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to ameliorate endothelial function. However, the physiological basis of this observation is largely unknown. We investigated the effects of Atorvastatin and Simvastatin on the pre-proET-1 mRNA expression and ET-1 synthesis and on the endothelial NO synthase (eNOS) transcript and protein levels in bovine aortic endothelial cells. These agents inhibited pre-proET-1 mRNA expression in a concentration- and time-dependent fashion (60-70% maximum inhibition) and reduced immunoreactive ET-1 levels (25-50%). This inhibitory effect was maintained in the presence of oxidized LDL (1-50 microg/ml). No significant modification of pre-proET-1 mRNA half-life was observed. In addition, mevalonate, but not cholesterol, reversed the statin-mediated decrease of pre-proET-1 mRNA levels. eNOS mRNA expression was reduced by oxidized LDL in a dose-dependent fashion (up to 57% inhibition), whereas native LDL had no effect. Statins were able to prevent the inhibitory action exerted by oxidized LDL on eNOS mRNA and protein levels. Hence, these drugs might influence vascular tone by modulating the expression of endothelial vasoactive factors. PMID:9637705

  12. In vitro effects of bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), or VO(dmpp)2, on insulin secretion in pancreatic islets of type 2 diabetic Goto-Kakizaki rats.

    PubMed

    Pelletier, Julien; Domingues, Neuza; Castro, M Margarida C A; Östenson, Claes-Göran

    2016-01-01

    Vanadium compounds have been explored as therapy of diabetes, and most studies have focussed on insulin mimetic effects, i.e. reducing hyperglycemia by improving glucose sensitivity and thus glucose uptake in sensitive tissues. We have recently shown that bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp)2, has promising effects when compared to another vanadium compound, bis(maltolato)oxidovanadium(IV), BMOV, and insulin itself, in isolated adipocytes and in vivo in Goto-Kakizaki (GK) rats, an animal model of hereditary type 2 diabetes (T2D).We now have investigated in GK rats whether VO(dmpp)2 also modulates another important defect in T2D, impaired insulin secretion. VO(dmpp)2, but not BMOV, stimulated insulin secretion from isolated GK rat pancreatic islets at high, 16.7mM, but not at low–normal, 3.3 mM, glucose concentration. Mechanistic studies demonstrate that the insulin releasing effect of VO(dmpp)2 is due to its interaction with several steps in the stimulus-secretion coupling for glucose, including islet glucose metabolism and K-ATP channels, L-type Ca2+ channels, modulation by protein kinases A and C, as well as the exocytotic machinery. In conclusion, VO(dmpp)2 exhibits properties of interest for treatment of the insulin secretory defect in T2D, in addition to its well-described insulin mimetic activity.

  13. The Arabidopsis FLAKY POLLEN1 gene encodes a 3-hydroxy-3-methylglutaryl-coenzyme A synthase required for development of tapetum-specific organelles and fertility of pollen grains.

    PubMed

    Ishiguro, Sumie; Nishimori, Yuka; Yamada, Miho; Saito, Hiroko; Suzuki, Toshiya; Nakagawa, Tsuyoshi; Miyake, Hiroshi; Okada, Kiyotaka; Nakamura, Kenzo

    2010-06-01

    The pollen coat is a surface component of pollen grains required for fertilization. To study how the pollen coat is produced, we identified and characterized a recessive and conditional male-sterile Arabidopsis mutant, flaky pollen1-1 (fkp1-1), whose pollen grains lack functional pollen coats. FKP1 is a single-copy gene in the Arabidopsis genome and encodes 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMG-CoA synthase), an enzyme of the mevalonate (MVA) pathway involved in biosynthesis of isoprenoids such as sterols. We found that fkp1-1 possesses a T-DNA insertion 550 bp upstream of the initiation codon. RT-PCR and promoter analyses revealed that fkp1-1 results in knockdown of FKP1 predominantly in tapetum. Electron microscopy showed that the mutation affected the development of tapetum-specific lipid-containing organelles (elaioplast and tapetosome), causing the deficient formation of fkp1-1 pollen coats. These results suggest that both elaioplasts, which accumulate vast amount of sterol esters, and tapetosomes, which are unique oil-accumulating structures, require the MVA pathway for development. Null alleles of fkp1 were male-gametophyte lethal upon pollen tube elongation, whereas female gametophytes were normal. These results show that the MVA pathway is essential, at least in tapetal cells and pollen grains, for the development of tapetum-specific organelles and the fertility of pollen grains.

  14. LC-ESI-MS/MS on an ion trap for the determination of LSD, iso-LSD, nor-LSD and 2-oxo-3-hydroxy-LSD in blood, urine and vitreous humor.

    PubMed

    Favretto, Donata; Frison, Giampietro; Maietti, Sergio; Ferrara, Santo Davide

    2007-07-01

    A method has been developed for the simultaneous determination of lysergic acid diethylamide (LSD), its epimer iso-LSD, and its main metabolites nor-LSD and 2-oxo-3-hydroxy LSD in blood, urine, and, for the first time, vitreous humor samples. The method is based on liquid/liquid extraction and liquid chromatography-multiple mass spectrometry detection in an ion trap mass spectrometer, in positive ion electrospray ionization conditions. Five microliter of sample are injected and analysis time is 12 min. The method is specific, selective and sensitive, and achieves limits of quantification of 20 pg/ml for both LSD and nor-LSD in blood, urine, and vitreous humor. No significant interfering substance or ion suppression was identified for LSD, iso-LSD, and nor-LSD. The interassay reproducibilities for LSD at 20 pg/ml and 2 ng/ml in urine were 8.3 and 5.6%, respectively. Within-run precision using control samples at 20 pg/ml and 2 ng/ml was 6.9 and 3.9%. Mean recoveries of two concentrations spiked into drug free samples were in the range 60-107% in blood, 50-105% in urine, and 65-105% in vitreous humor. The method was successfully applied to the forensic determination of postmortem LSD levels in the biological fluids of a multi drug abuser; for the first time, LSD could be detected in vitreous humor.

  15. Application of multiplex ligation-dependent probe amplification, and identification of a heterozygous Alu-associated deletion and a uniparental disomy of chromosome 1 in two patients with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

    PubMed

    Aoyama, Yuka; Yamamoto, Toshiyuki; Sakaguchi, Naomi; Ishige, Mika; Tanaka, Toju; Ichihara, Tomoko; Ohara, Katsuaki; Kouzan, Hiroko; Kinosada, Yasutomi; Fukao, Toshiyuki

    2015-06-01

    Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) deficiency is an autosomal recessive disorder affecting the leucine catabolic pathway and ketone body synthesis, and is clinically characterized by metabolic crises with hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. In the present study, we initially used PCR with genomic followed by direct sequencing to investigate the molecular genetic basis of HMGCL deficiency in two patients clinically diagnosed with the condition. Although we identified a mutation in each patient, the inheritance patterns of these mutations were not consistent with disease causation. Therefore, we investigated HMGCL using multiplex ligation-dependent probe amplification (MLPA) to determine the copy numbers of all exons. A heterozygous deletion that included exons 2-4 was identified in one of the patients. MLPA revealed that the other patient had two copies for all HMGCL exons. Paternal uniparental isodisomy of chromosome 1 was confirmed in this patient by microarray analysis. These findings indicate that MLPA is useful for the identification of genomic aberrations and mutations other than small-scale nucleotide alterations. To the best of our knowledge, this is the first study describing HMGCL deficiency caused by uniparental disomy. PMID:25872961

  16. In vitro and in vivo assessment of the mutagenic activity of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame).

    PubMed

    Otabe, A; Fujieda, T; Masuyama, T

    2011-11-01

    Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate), an N-substituted analogue of aspartame, has been developed as a high-intensity sweetener. It is approximately 100 and 20,000 times sweeter than aspartame and sucrose, respectively. In this study the safety of advantame has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell mutation, and mouse micronucleus tests. Advantame did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at concentrations of up to 5000 μg/plate. In the mammalian cell mutation assay, advantame did not induce mutation at the Hprt locus of L5178Y mouse lymphoma cells in two independent experiments, either in the absence or presence of S9. In vivo, there was no effect on the incidence of micronucleated immature or mature erythrocytes in bone marrow after oral administration of the test substance at any dose level (up to 2000 mg/kg body weight) or sampling time (24 and 48 h). The results of these studies demonstrate that advantame is without genotoxic potential.

  17. The Structure of LiuC, a 3-Hydroxy-3-Methylglutaconyl CoA Dehydratase Involved in Isovaleryl-CoA Biosynthesis in Myxococcus xanthus, Reveals Insights into Specificity and Catalysis.

    PubMed

    Bock, Tobias; Reichelt, Joachim; Müller, Rolf; Blankenfeldt, Wulf

    2016-09-01

    Myxobacteria are able to produce the important metabolite isovaleryl coenzyme A by a route other than leucine degradation. The first step into this pathway is mediated by LiuC, a member of the 3-methylglutaconyl CoA hydratases (MGCH). Here we present crystal structures refined to 2.05 and 1.1 Å of LiuC in the apo form and bound to coenzyme A, respectively. By using simulated annealing we modeled the enzyme substrate complex and identified residues potentially involved in substrate binding, specificity, and catalysis. The dehydration of 3-hydroxy-3-methylglutaconyl CoA to 3-methylglutaconyl CoA catalyzed by LiuC involves Glu112 and Glu132 and likely employs the typical crotonase acid-base mechanism. In this, Tyr231 and Arg69 are key players in positioning the substrate to enable catalysis. Surprisingly, LiuC shows higher sequence and structural similarity to human MGCH than to bacterial forms, although they convert the same substrate. This study provides structural insights into the alternative isovaleryl coenzyme A biosynthesis pathway and might open a path for biofuel research, as isovaleryl-CoA is a source for isobutene, a precursor for renewable fuels and chemicals. PMID:27271456

  18. Influence of zinc on the calcium carbonate biomineralization of Halomonas halophila

    PubMed Central

    2012-01-01

    Background The salt tolerance of halophilic bacteria make them promising candidates for technical applications, like isolation of salt tolerant enzymes or remediation of contaminated saline soils and waters. Furthermore, some halophilic bacteria synthesize inorganic solids resulting in organic–inorganic hybrids. This process is known as biomineralization, which is induced and/or controlled by the organism. The adaption of the soft and eco-friendly reaction conditions of this formation process to technical syntheses of inorganic nano materials is desirable. In addition, environmental contaminations can be entrapped in biomineralization products which facilitate the subsequent removal from waste waters. The moderately halophilic bacteria Halomonas halophila mineralize calcium carbonate in the calcite polymorph. The biomineralization process was investigated in the presence of zinc ions as a toxic model contaminant. In particular, the time course of the mineralization process and the influence of zinc on the mineralized inorganic materials have been focused in this study. Results H. halophila can adapt to zinc contaminated medium, maintaining the ability for biomineralization of calcium carbonate. Adapted cultures show only a low influence of zinc on the growth rate. In the time course of cultivation, zinc ions accumulated on the bacterial surface while the medium depleted in the zinc contamination. Intracellular zinc concentrations were below the detection limit, suggesting that zinc was mainly bound extracellular. Zinc ions influence the biomineralization process. In the presence of zinc, the polymorphs monohydrocalcite and vaterite were mineralized, instead of calcite which is synthesized in zinc-free medium. Conclusions We have demonstrated that the bacterial mineralization process can be influenced by zinc ions resulting in the modification of the synthesized calcium carbonate polymorph. In addition, the shape of the mineralized inorganic material is chancing

  19. DNA binding in high salt: analysing the salt dependence of replication protein A3 from the halophile Haloferax volcanii.

    PubMed

    Winter, Jody A; Patoli, Bushra; Bunting, Karen A

    2012-01-01

    Halophilic archaea maintain intracellular salt concentrations close to saturation to survive in high-salt environments and their cellular processes have adapted to function under these conditions. Little is known regarding halophilic adaptation of the DNA processing machinery, particularly intriguing since protein-DNA interactions are classically salt sensitive. To investigate such adaptation, we characterised the DNA-binding capabilities of recombinant RPA3 from Haloferax volcanii (HvRPA3). Under physiological salt conditions (3 M KCl), HvRPA3 is monomeric, binding 18 nucleotide ssDNA with nanomolar affinity, demonstrating that RPAs containing the single OB-fold/zinc finger architecture bind with broadly comparable affinity to two OB-fold/zinc finger RPAs. Reducing the salt concentration to 1 M KCl induces dimerisation of the protein, which retains its ability to bind DNA. On circular ssDNA, two concentration-dependent binding modes are observed. Conventionally, increased salt concentration adversely affects DNA binding but HvRPA3 does not bind DNA in 0.2 M KCl, although multimerisation may occlude the binding site. The single N-terminal OB-fold is competent to bind DNA in the absence of the C-terminal zinc finger, albeit with reduced affinity. This study represents the first quantitative characterisation of DNA binding in a halophilic protein in extreme salt concentrations.

  20. Formation of zinc protoporphyrin IX in Parma-like ham without nitrate or nitrite.

    PubMed

    Wakamatsu, Jun-ichi; Uemura, Juichi; Odagiri, Hiroko; Okui, Jun; Hayashi, Nobutaka; Hioki, Shoji; Nishimura, Takanori; Hattori, Akihito

    2009-04-01

    Zinc protoporphyrin IX (ZPP) is a characteristic red pigment in meat products that are manufactured without the addition of a curing agent such as nitrate or nitrite. To examine the effects of impurities such as mineral components in sea salt on the formation of ZPP, we manufactured Parmatype dry-cured hams that were salted with refined salt or sea salt and examined the involvement of oxidation-reduction potential (ORP) in the formation of ZPP. The content of ZPP was increased drastically after 40 weeks. Microscopic observation showed strong fluorescence caused by ZPP muscle fiber after 40 weeks. Conversely, heme content varied considerably during processing. ORP increased during processing. However, there was no obvious difference between ham salted with refined salt and that salted with sea salt. Therefore, it was concluded that impurities in sea salt were not involved in the formation of ZPP.

  1. The effect of zinc in the form of erythromycin-zinc complex (Zineryt lotion) and zinc acetate on metallothionein expression and distribution in hamster skin.

    PubMed

    Morgan, A J; Lewis, G; Van den Hoven, W E; Akkerboom, P J

    1993-11-01

    The occurrence of zinc-induced synthesis of metallothionein in skin after topical application of the anti-acne drug Zineryt lotion was investigated in hamster ears. The dinitrophenyl hapten-sandwich immunohistochemical method involving a monoclonal anti-metallothionein (MT) antibody (E9) was used to detect and localize zinc-binding MT in the 'treated' and untreated hamster skin. Atomic absorption spectrophotometry and dithizone histochemistry indicated that zinc penetrated the skin more readily, and accumulated more efficiently within the sebaceous glands, when applied to the skin surface as the organo-zinc complex, rather than as the inorganic zinc salt. MT and zinc had similar distributions in hamster skin exposed to the metal. Thus, MT immunoreactivity was especially intense in the sebaceous glands of Zineryt lotion-treated skin, with evidence of nuclear distribution in some cells. Zinc delivered to the sebaceous glands, and released from the organo-complex under the prevailing aqueous conditions, certainly induced MT synthesis; the cysteine-rich protein may protect the pilosebaceous units during the inflammatory phase of acne by scavenging generated oxyradical species.

  2. Improved zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, P.N. Jr.

    1988-06-21

    The invention comprises an improved rechargeable zinc-air cell/battery having recirculating alkaline electrolyte and a zinc electrode comprising a porous foam support material which carries the active zinc electrode material. 5 figs.

  3. [Zinc and autophagy].

    PubMed

    Qiaoyun, Liu; Hanming, Shen; Dajing, Xia

    2016-05-25

    Autophagy refers to a catabolic process,in which the damaged organelles or biological macromolecules, such as protein aggregates, are degraded via lysosome. The completion of autophagy depends on a series of autophagy-related genes (Atgs) and many upstream regulatory molecules. Zinc is an essential trace element, and plays an important role in the process of autophagy as a component of enzymes and structural proteins like zinc transporters or zinc finger protein. The regulation of autophagy is closely associated with the zinc ion homeostasis. In addition, many studies suggest that the protective effects of zinc on cells are likely to be done by autophagy. This review aims to summarize the current research progress and discuss the reciprocal regulation mechanism between zinc and autophagy, which may provide insights into the intricate roles of autophagy in diseases and find novel strategies for treatment and prevention of human diseases. PMID:27651198

  4. Eight salts constructed from 4-phenylthiazol-2-amine and carboxylic acid derivatives through combination of strong hydrogen bonding and weak noncovalent interactions

    NASA Astrophysics Data System (ADS)

    Jin, Shouwen; Zhu, Qiaowang; Wei, ShuaiShuai; Wang, Daqi

    2013-10-01

    Eight crystalline organic salts derived from 4-phenylthiazol-2-amine and carboxylic acid derivatives (2-chloronicotinic acid, 3-hydroxy-2-naphthoic acid, p-nitrobenzoic acid, 2-hydroxy-5-(phenyldiazenyl)benzoic acid, 5-nitrosalicylic acid, 5-sulfosalicylic acid, oxalic acid, and L-malic acid) were prepared and characterized by X-ray diffraction analysis, IR, mp, and elemental analysis. In all of the salts except 6, 7, and 8, the 4-phenylthiazol-2-amine and carboxylic acid components are held together by two fused heterosynthons: a R22(7) heterosynthon and a R22(8) heterosynthon. All supramolecular architectures of the organic salts 1-8 involve extensive Nsbnd H⋯O hydrogen bonds as well as other noncovalent interactions. The role of weak and strong noncovalent interactions in the crystal packing is ascertained. The salts displayed 2D/3D framework structure under these weak interactions.

  5. Zinc electrode and rechargeable zinc-air battery

    SciTech Connect

    Ross, P.N. Jr.

    1989-06-27

    This patent describes an improved zinc electrode for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed.

  6. Zinc in Entamoeba invadens.

    NASA Technical Reports Server (NTRS)

    Morgan, R. S.; Sattilaro, R. F.

    1972-01-01

    Atomic absorption spectroscopy, electron microprobe analysis, and dithizone staining of trophozoites and cysts of Entamoeba invadens demonstrate that these cells have a high concentration of zinc (approximately one picogram per cell or 1% of their dry weight). In the cysts of this organism, the zinc is confined to the chromatoid bodies, which previous work has shown to contain crystals of ribosomes. The chemical state and function of this zinc are unknown.

  7. Zinc: An Essential Micronutrient

    PubMed Central

    SAPER, ROBERT B.; RASH, REBECCA

    2009-01-01

    Zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression. Patients with malnutrition, alcoholism, inflammatory bowel disease, and malabsorption syndromes are at an increased risk of zinc deficiency. Symptoms of zinc deficiency are nonspecific, including growth retardation, diarrhea, alopecia, glossitis, nail dystrophy, decreased immunity, and hypogonadism in males. In developing countries, zinc supplementation may be effective for the prevention of upper respiratory infection and diarrhea, and as an adjunct treatment for diarrhea in malnourished children. Zinc in combination with antioxidants may be modestly effective in slowing the progression of intermediate and advanced age-related macular degeneration. Zinc is an effective treatment for Wilson disease. Current data do not support zinc supplementation as effective for upper respiratory infection, wound healing, or human immunodeficiency virus. Zinc is well tolerated at recommended dosages. Adverse effects of long-term high-dose zinc use include suppressed immunity, decreased high-density lipoprotein cholesterol levels, anemia, copper deficiency, and possible genitourinary complications. PMID:20141096

  8. Zinc and Chlamydia trachomatis

    SciTech Connect

    Sugarman, B.; Epps, L.R.

    1985-07-01

    Zinc was noted to have significant effects upon the infection of McCoy cells by each of two strains of Chlamydia trachomatis. With a high or low Chlamydia inoculant, the number of infected cells increased up to 200% utilizing supplemental zinc (up to 1 x 10/sup -4/ M) in the inoculation media compared with standard Chlamydia cultivation media (8 x 10/sup -6/ M zinc). Ferric chloride and calcium chloride did not effect any such changes. Higher concentrations of zinc, after 2 hr of incubation with Chlamydia, significantly decreased the number of inclusions. This direct effect of zinc on the Chlamydia remained constant after further repassage of the Chlamydia without supplemental zinc, suggesting a lethal effect of the zinc. Supplemental zinc (up to 10/sup -4/ M) may prove to be a useful addition to inoculation media to increase the yield of culturing for Chlamydia trachomatis. Similarly, topical or oral zinc preparations used by people may alter their susceptibility to Chamydia trachomatis infections.

  9. Mechanochemical synthesis of layered hydroxy salts

    SciTech Connect

    Thomas, Nygil

    2012-11-15

    Highlights: ► Ultrafast synthesis method was developed for the synthesis of layered hydroxy salts. ► Preparation of hydroxy single salt by this method requires only one minute. ► Hydroxy salts with variable Ni/Zn ratio could be synthesized by varying the metal contents of the starting mixture. ► This synthesis method is solvent free and environment friendly. -- Abstract: A simple one minute synthesis method was adapted for the preparation of layered hydroxy salts of copper, zinc, nickel and cadmium by grinding the metal salts with sodium hydroxide in a mortar. This solvent free method is environment friendly and fast. This method could be extended to the preparation of Ni/Zn hydroxy double salts. The Ni/Zn ratio could be varied from 1.2 to 1.9 by varying the metal contents of the precursor salts without the formation of any impurities in the sample. The prepared compounds had similar characteristics as that of the samples prepared by precipitation route. No sign of carbonate contamination was observed in any of the prepared samples.

  10. Chelators for investigating zinc metalloneurochemistry.

    PubMed

    Radford, Robert J; Lippard, Stephen J

    2013-04-01

    The physiology and pathology of mobile zinc signaling has become an important topic in metalloneurochemistry. To study the action of mobile zinc effectively, specialized tools are required that probe the temporal and positional changes of zinc ions within live tissue and cells. In the present article we describe the design and implementation of selective zinc chelators as antagonists to interrogate the function of mobile zinc, with an emphasis on the pools of vesicular zinc in the terminals of hippocampal mossy fiber buttons.

  11. Conversion of acetyl-coenzyme A into 3-hydroxy-3-methylglutaryl-coenzyme A in radish seedlings. Evidence of a single monomeric protein catalyzing a FeII/quinone-stimulated double condensation reaction.

    PubMed

    Weber, T; Bach, T J

    1994-02-10

    We solubilized from radish membranes and purified to apparent homogeneity a monomeric protein (55.5 kDa) capable of catalyzing the two-step conversion of acetyl-CoA into 3-hydroxy-3-methylglutaryl(HMG)-CoA. Unlike the situation described for other eukaryotes (yeast, animals), both enzyme activities needed for HMG-CoA synthesis (acetoacetyl-CoA thiolase, AACT and HMG-CoA synthase, HMGS) appear to be localized on a single polypeptide. Thus, the enzyme system is further referred to as AACT/HMGS. The reaction as catalyzed by purified AACT/HMGS is strongly stimulated in vitro in presence of FeII-chelates (namely EDTA) and of quinone cofactors with pyrroloquinoline quinone (PQQ) being by far the most effective one studied so far. Whereas the FeII stimulation is apparently due to a Vmax effect, PQQ increases the affinity of the enzyme system towards acetyl-CoA (1.9 microM vs. 5.9 microM, at 50 microM FeII, 100 microM EDTA, 20 microM PQQ). Stimulation by naphthoquinone (NQ) can be overcome in the presence of halogenated NQ-derivatives, while activation by PQQ remains unaffected, possibly indicating a much more specific-binding of the latter cofactor. Gel filtration experiments of enzyme after preincubation in presence of PQQ indicate that there is no covalent-binding of the quinone cofactor to the enzyme. As is also shown with partially purified enzyme from maize membranes, phenylhydrazine, known to react with PQQ as the prosthetic group of quinoproteins (see van der Meer et al. (1987) FEBS Lett. 221, 299-304), efficiently inhibits the reaction. The data lead us to suggest a reaction mechanism that involves radical formation by the redox couple FeII/PQQ, thereby possibly facilitating the energetically unfavorable Claisen condensation as catalyzed during the first partial (AACT) reaction.

  12. Gender-specific differences between the concentrations of nonvolatile (R)/(S)-3-methyl-3-sulfanylhexan-1-Ol and (R)/(S)-3-hydroxy-3-methyl-hexanoic acid odor precursors in axillary secretions.

    PubMed

    Troccaz, Myriam; Borchard, Gerrit; Vuilleumier, Christine; Raviot-Derrien, Sophie; Niclass, Yvan; Beccucci, Sabine; Starkenmann, Christian

    2009-03-01

    The volatile fatty acid, (R)/(S)-3-hydroxy-3-methylhexanoic acid ((R)/(S)-HMHA), and the human specific volatile thiol, (R)/(S)-3-methyl-3-sulfanylhexan-1-ol ((R)/(S)-MSH), were recently identified as major components of human sweat malodor. Their 2 corresponding precursors were subsequently isolated from sterile and odorless axillary secretions. The purpose of this work was to analyze these 2 odor precursors in 49 male and female volunteers over a period of 3 years to elucidate to which extent they are implicated in the gender-specific character of body odor. Surprisingly, the ratio between the acid precursor 1, a glutamine conjugate, and the "sulfur" precursor 2, a cysteinylglycine-S-conjugate, was 3 times higher in men than in women with no correlation with either the sweat volume or the protein concentration. Indeed, women have the potential to liberate significantly more (R)/(S)-MSH, which has a tropical fruit- and onion-like odor than (R)/(S)-HMHA (possibly transformed into (E)/(Z)-3-methyl-2-hexenoic acid) that has a cheesy, rancid odor. Parallel to this work, sensory analysis on sweat incubated with isolated skin bacteria (Staphylococcus epidermidis Ax3, Corynebacterium jeikeium American Type Culture Collection 43217, or Staphylococcus haemolyticus Ax4) confirmed that intrinsic composition of sweat is important for the development of body odors and may be modulated by gender differences in bacterial compositions. Sweat samples having the highest sulfur intensity were also found to be the most intense and the most unpleasant. PMID:19147808

  13. Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. I. Rodent cerebral white matter and cortex.

    PubMed

    Talos, Delia M; Fishman, Rachel E; Park, Hyunkyung; Folkerth, Rebecca D; Follett, Pamela L; Volpe, Joseph J; Jensen, Frances E

    2006-07-01

    This is the first part of a two-part study to investigate the cellular distribution and temporal regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunits in the developing white matter and cortex in rat (part I) and human (part II). Western blot and immunocytochemistry were used to evaluate the differential expression of AMPAR subunits on glial and neuronal subtypes during the first 3 postnatal weeks in the Long Evans and Sprague Dawley rat strains. In Long Evans rats during the first postnatal week, GluR2-lacking AMPARs were expressed predominantly on white matter cells, including radial glia, premyelinating oligodendrocytes, and subplate neurons, whereas, during the second postnatal week, these AMPARs were highly expressed on cortical neurons, coincident with decreased expression on white matter cells. Immunocytochemical analysis revealed that cell-specific developmental changes in AMPAR expression occurred 2-3 days earlier by chronological age in Sprague Dawley rats compared with Long Evans rats, despite overall similar temporal sequencing. In both white and gray matter, the periods of high GluR2 deficiency correspond to those of regional susceptibility to hypoxic/ischemic injury in each of the two rat strains, supporting prior studies suggesting a critical role for Ca2+-permeable AMPARs in excitotoxic cellular injury and epileptogenesis. The developmental regulation of these receptor subunits strongly suggests that Ca2+ influx through GluR2-lacking AMPARs may play an important role in neuronal and glial development and injury in the immature brain. Moreover, as demonstrated in part II, there are striking similarities between rat and human in the regional and temporal maturational regulation of neuronal and glial AMPAR expression.

  14. Developmental regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit expression in forebrain and relationship to regional susceptibility to hypoxic/ischemic injury. II. Human cerebral white matter and cortex.

    PubMed

    Talos, Delia M; Follett, Pamela L; Folkerth, Rebecca D; Fishman, Rachel E; Trachtenberg, Felicia L; Volpe, Joseph J; Jensen, Frances E

    2006-07-01

    This report is the second of a two-part evaluation of developmental differences in alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit expression in cell populations within white matter and cortex. In part I, we reported that, in rat, developmental expression of Ca2+-permeable (GluR2-lacking) AMPARs correlated at the regional and cellular level with increased susceptibility to hypoxia/ischemia (H/I), suggesting an age-specific role of these receptors in the pathogenesis of brain injury. Part II examines the regional and cellular progression of AMPAR subunits in human white matter and cortex from midgestation through early childhood. Similarly to the case in the rodent, there is a direct correlation between selective vulnerability to H/I and expression of GluR2-lacking AMPARs in human brain. For midgestational cases aged 20-24 postconceptional weeks (PCW) and for premature infants (25-37 PCW), we found that radial glia, premyelinating oligodendrocytes, and subplate neurons transiently expressed GluR2-lacking AMPARs. Notably, prematurity represents a developmental window of selective vulnerability for white matter injury, such as periventricular leukomalacia (PVL). During term (38-42 PCW) and postterm neonatal (43-46 PCW) periods, age windows characterized by increased susceptibility to cortical injury and seizures, GluR2 expression was low in the neocortex, specifically on cortical pyramidal and nonpyramidal neurons. This study indicates that Ca2+-permeable AMPAR blockade may represent an age-specific therapeutic strategy for potential use in humans. Furthermore, these data help to validate specific rodent maturational stages as appropriate models for evaluation of H/I pathophysiology.

  15. Effects of 15-oxa-32-vinyl-lanost-8-ene-3 beta,32 diol on the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and low density lipoprotein receptor in rat liver.

    PubMed

    Ness, G C; Lopez, D; Chambers, C M; Zhao, Z; Beach, D L; Ko, S S; Trzaskos, J M

    1998-09-15

    The mechanisms by which oxylanosterols regulate expression of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and lower serum cholesterol levels were examined by using a novel nonmetabolizable oxylanosterol mimic, 15-oxa-32-vinyl-lanost-8-ene-3 beta, 32 diol (DMP 565). This compound, unlike other nonmetabolizable oxylanosterols, is not a substrate for lanosterol 14 alpha-methyl demethylase. Feeding rats a diet supplemented with 0.02% DMP 565 markedly decreased HMG-CoA reductase immunoreactive protein and enzyme activity levels without affecting mRNA levels. The rate of reductase protein degradation was unaffected. However, the rate of translation was reduced to less than 20% of control. Thus, DMP 565 appears to regulate hepatic HMG-CoA reductase gene expression primarily at the level of translation. The pronounced inhibition of HMG-CoA reductase by DMP 565 resulted in a compensatory increase in the functioning of the hepatic low density lipoprotein (LDL) receptor, possibly by increased cycling, as evidenced by a marked increase in the rate of degradation of the LDL receptor. The half-life of the receptor was decreased from over 7 h to only 1 h in animals receiving DMP 565. This increase in the rate of degradation occurred without a change in the steady state level of the receptor. Addition of dietary cholesterol attenuated the increased turnover of the LDL receptor. These effects on the hepatic LDL receptor have also been observed with HMG-CoA reductase inhibitors (G. C. Ness et al., 1996, Arch. Biochem, Biophys. 325, 242-248). However, the effect of DMP 565 on the rate of degradation of the hepatic LDL receptor was of a greater magnitude when equal doses of the drugs were used. These regulatory actions of DMP 565 provide, in part, an explanation for the observed hypocholesterolemic action of this compound.

  16. Asian plantain (Plantago asiatica) essential oils suppress 3-hydroxy-3-methyl-glutaryl-co-enzyme A reductase expression in vitro and in vivo and show hypocholesterolaemic properties in mice.

    PubMed

    Chung, Mi Ja; Park, Kuen Woo; Kim, Kyoung Heon; Kim, Cheong-Tae; Baek, Jun Pill; Bang, Kyong-Hwan; Choi, Young-Mi; Lee, Sung-Joon

    2008-01-01

    Asian plantain (Plantago asiatica) essential oil (PAEO) contains multiple bioactive compounds, but its potential effects on lipid metabolism have not been examined. PAEO was found to be mostly composed of oxygenated monoterpenes, with linalool as the major component (82.5 %, w/w), measured using GC-MS. Incubation of 0-200 microg PAEO/ml with HepG2 cells for 24 h resulted in no significant toxicity. Incubation with 0.2 mg PAEO/ml altered the expression of LDL receptor (+83 %; P < 0.05) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase ( - 37 %; P < 0.05), as assessed using RT-PCR. LDL oxidation was markedly inhibited by PAEO treatment due to the prevalence of linalool compounds in PAEO. Oral administration of PAEO for 3 weeks in C57BL/6 mice significantly reduced plasma total cholesterol and TAG concentrations by 29 and 46 %, respectively. The mRNA (+58 %; P < 0.05), but not protein, levels of the LDL receptor were significantly higher, whereas both mRNA and protein levels of HMG-CoA reductase were significantly lower ( - 46 and - 11 %, respectively; P < 0.05) in the liver of PAEO-fed than of control mice. The mRNA levels of CYP7A1 were marginally reduced in HepG2 cells, but not in mouse liver after PAEO treatment. Thus, PAEO may have hypocholesterolaemic effects by altering the expression of HMG-CoA reductase. Reduced TAG and oxidised LDL may provide additional cardiovascular protective benefits. PMID:17697428

  17. Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA contents in human hepatoma cell line Hep G2 by distinct classes of mevalonate-derived metabolites.

    PubMed Central

    Cohen, L H; Griffioen, M

    1988-01-01

    Hep G2 cells were incubated under conditions known to influence the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity, e.g. in the presence of compactin (a competitive inhibitor of HMG-CoA reductase itself) and U18666A (a squalene-2,3-epoxide cyclase inhibitor). We studied the effects of these conditions both on the HMG-CoA reductase activity and on the reductase mRNA content. In the presence of compactin the mRNA content increased, but less than the enzyme activity, as determined after removal of the inhibitor. The increase in mRNA could be prevented by addition of mevalonate or by a combination of low-density lipoprotein (LDL) plus a low concentration of mevalonate. LDL alone prevented the compactin-induced increases in mRNA and activity only partially. The effect of U18666A on reductase mRNA content and activity was biphasic, i.e. a slight decrease at low (0.3-0.5 microM) concentrations, with a concomitant formation of polar sterols [Boogaard, Griffioen & Cohen (1987) Biochem. J. 241, 345-351], and an increase at high (20-30 microM) concentrations, with complete blockage of sterol formation. At these high concentrations of U18666A, additional compactin (2 microM) increased the reductase activity, but not the mRNA content. We conclude that non-sterol metabolites of mevalonate regulate exclusively at the enzyme level, whereas sterol metabolites regulate at the reductase mRNA level. In the latter group of regulators we distinguish mevalonate metabolites which can, and metabolites which cannot, be replaced by exogenous LDL. Images Fig. 1. PMID:2848511

  18. H2O-mediated isatin spiro-epoxide ring opening with NaCN: Synthesis of novel 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids and their anticancer evaluation.

    PubMed

    Sharma, Pankaj; Senwar, Kishna Ram; Jeengar, Manish Kumar; Reddy, T Srinivasa; Naidu, V G M; Kamal, Ahmed; Shankaraiah, Nagula

    2015-11-01

    A simple method for isatin spiro-epoxide ring-opening by sodium cyanide in water to obtain a variety of isatin hydroxy nitriles has been developed. Further, these intermediates have been converted into new 3-tetrazolylmethyl-3-hydroxy-oxindole hybrids via azide-nitrile cycloaddition reaction in a sealed tube. These compounds were evaluated for their in vitro anticancer activity on five human cancer cell lines i.e. breast (BT549 and MDA MB-231), prostate (PC-3 and DU-145) and ovarian (PA-1). The compounds 6d and 6r showed potent anticancer activity against DU-145 cell line with IC50 values in the range of 7.01 ± 0.91 and 4.26 ± 0.09 μM respectively. The compounds 6d, 6g, 6q and 6r were also tested on human normal prostate epithelial (RWPE-1) cells and found to be safer with lesser cytotoxicity. The morphology and long term clonogenic survival of DU-145 cells were severely affected by compound 6r. Cell cycle analysis revealed that the compounds arrest the cells in G2/M phase. Acridine orange/ethidium bromide (AO/EB) staining, DAPI staining, annexin-V binding assay and DNA fragmentation analysis showed that cell proliferation was inhibited through induction of apoptosis. Moreover, one of the compounds 6r treatment led to collapse of the mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) in DU-145 cells. PMID:26413726

  19. A study of the oligomeric state of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring glutamate receptors in the synaptic junctions of porcine brain.

    PubMed Central

    Wu, T Y; Liu, C I; Chang, Y C

    1996-01-01

    The number of the subunits in an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring L-glutamate receptor in the synaptic junctions of porcine brain was investigated in this study. Upon incubation of the synaptic junctions with three cross-linking regents, dimethyl adipimidate (DMA), dimethyl suberimidate (DMS) and N-succinimidyl-(4-azidophenyl)-1,3'-dithiopropionate (SADP), AMPA receptor subunits in higher-molecular-mass aggregates were detected by immunoblotting. These aggregates migrated as proteins of approx. 200, 300 and 400 kDa. The number and identity of the subunits in a solubilized AMPA receptor were also investigated here. Two samples, W1 and W2, enriched in AMPA receptors were prepared from synaptic junctions by a combination of detergent-solubilization, anion-exchange chromatography and wheatgerm agglutinin affinity chromatography. Hydrodynamic behaviour analyses revealed that the majority of the AMPA receptors in either one of these samples were asymmetrical detergent-surrounded particles with a protein mass around 350 kDa. SDS/PAGE analysis revealed that the majority of AMPA receptors in the W1 sample were comprised of dimers of 106 kDa subunits which were covalently linked by disulphide bonds. Cross-linking these receptors with SADP yielded a new band of approx. 400 kDa. The results obtained here, either from the studies of AMPA receptors embedding in synaptic junctions or from those of detergent-solubilized and partially purified receptors, suggest that AMPA receptors contain a basic core structure comprising of four 106 kDa subunits. PMID:8920974

  20. Zinc Inhibits Hedgehog Autoprocessing

    PubMed Central

    Xie, Jian; Owen, Timothy; Xia, Ke; Singh, Ajay Vikram; Tou, Emiley; Li, Lingyun; Arduini, Brigitte; Li, Hongmin; Wan, Leo Q.; Callahan, Brian; Wang, Chunyu

    2015-01-01

    Zinc is an essential trace element with wide-ranging biological functions, whereas the Hedgehog (Hh) signaling pathway plays crucial roles in both development and disease. Here we show that there is a mechanistic link between zinc and Hh signaling. The upstream activator of Hh signaling, the Hh ligand, originates from Hh autoprocessing, which converts the Hh precursor protein to the Hh ligand. In an in vitro Hh autoprocessing assay we show that zinc inhibits Hh autoprocessing with a Ki of 2 μm. We then demonstrate that zinc inhibits Hh autoprocessing in a cellular environment with experiments in primary rat astrocyte culture. Solution NMR reveals that zinc binds the active site residues of the Hh autoprocessing domain to inhibit autoprocessing, and isothermal titration calorimetry provided the thermodynamics of the binding. In normal physiology, zinc likely acts as a negative regulator of Hh autoprocessing and inhibits the generation of Hh ligand and Hh signaling. In many diseases, zinc deficiency and elevated level of Hh ligand co-exist, including prostate cancer, lung cancer, ovarian cancer, and autism. Our data suggest a causal relationship between zinc deficiency and the overproduction of Hh ligand. PMID:25787080

  1. Preparation of zinc orthotitanate

    NASA Technical Reports Server (NTRS)

    Gates, D. W.; Gilligan, J. E.; Harada, Y.; Logan, W. R.

    1977-01-01

    Use of decomposable precursors to enhance zinc oxide-titanium dioxide reaction and rapid fixing results in rapid preparation of zinc orthotitanate powder pigment. Preparation process allows production under less stringent conditions. Elimination of powder grinding results in purer that is less susceptible to color degradation.

  2. Metals Electroprocessing in Molten Salts

    NASA Technical Reports Server (NTRS)

    Sadoway, D. R.

    1985-01-01

    The present study seeks to explain the poor quality of solid electrodeposits in molten salts through a consideration of the effects of fluid flow of the electrolyte. Transparent cells allow observation of electrolyte circulation by a laser schlieren optical technique during the electrodeposition of solid zinc from the molten salt electrolyte, ZnCl2 - LiCl-KCl. Experimental variables are current, density, electrolyte composition, and cell geometry. Based on the results of earlier electrodeposition studies as well as reports in the literature, these parameters are identified as having the primary influence on cell performance and deposit quality. Experiments are conducted to measure the fluid flow patterns and the electrochemical cell characteristics, and to correlate this information with the morphology of the solid electrodeposit produced. Specifically, cell voltage, cell current, characteristic time for dendrite evolution, and dendrite growth directions are noted. Their relationship to electrolyte flow patterns and the morphology of the resulting electrodeposit are derived. Results to date indicate that laser schlieren imaging is capable of revealing fluid flow patterns in a molten salt electrolyte.

  3. Exploring zinc coordination in novel zinc battery electrolytes.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2014-06-14

    The coordination of zinc ions by tetraglyme has been investigated here to support the development of novel electrolytes for rechargeable zinc batteries. Zn(2+) reduction is electrochemically reversible from tetraglyme. The spectroscopic data, molar conductivity and thermal behavior as a function of zinc composition, between mole ratios [80 : 20] and [50 : 50] [tetraglyme : zinc chloride], all suggest that strong interactions take place between chloro-zinc complexes and tetraglyme. Varying the concentration of zinc chloride produces a range of zinc-chloro species (ZnClx)(2-x) in solution, which hinder full interaction between the zinc ion and tetraglyme. Both the [70 : 30] and [50 : 50] mixtures are promising electrolyte candidates for reversible zinc batteries, such as the zinc-air device.

  4. Exploring zinc coordination in novel zinc battery electrolytes.

    PubMed

    Kar, Mega; Winther-Jensen, Bjorn; Forsyth, Maria; MacFarlane, Douglas R

    2014-06-14

    The coordination of zinc ions by tetraglyme has been investigated here to support the development of novel electrolytes for rechargeable zinc batteries. Zn(2+) reduction is electrochemically reversible from tetraglyme. The spectroscopic data, molar conductivity and thermal behavior as a function of zinc composition, between mole ratios [80 : 20] and [50 : 50] [tetraglyme : zinc chloride], all suggest that strong interactions take place between chloro-zinc complexes and tetraglyme. Varying the concentration of zinc chloride produces a range of zinc-chloro species (ZnClx)(2-x) in solution, which hinder full interaction between the zinc ion and tetraglyme. Both the [70 : 30] and [50 : 50] mixtures are promising electrolyte candidates for reversible zinc batteries, such as the zinc-air device. PMID:24760367

  5. Zinc Bromide Combustion: Implications for the Consolidated Incinerator Facility

    SciTech Connect

    Oji, L.N.

    1998-12-16

    In the nuclear industry, zinc bromide (ZnBr2) is used for radiation shielding. At Savannah River Site (SRS) zinc bromide solution, in appropriate configurations and housings, was used mainly for shielding in viewing windows in nuclear reactor and separation areas. Waste stream feeds that will be incinerated at the CIF will occasionally include zinc bromide solution/gel matrices.The CIF air pollution systems control uses a water-quench and steam atomizer scrubber that collects salts, ash and trace metals in the liquid phase. Water is re-circulated in the quench unit until a predetermined amount of suspended solids or dissolved salts are present. After reaching the threshold limit, "dirty liquid", also called "blowdown", is pumped to a storage tank in preparation for treatment and disposal. The air pollution control system is coupled to a HEPA pre-filter/filter unit, which removes particulate matter from the flue gas stream (1).The objective of this report is to review existing literature data on the stability of zinc bromide (ZnBr2) at CIF operating temperatures (>870 degrees C (1600 degrees F) and determine what the combustion products are in the presence of excess air. The partitioning of the combustion products among the quencher/scrubber solution, bottom ash and stack will also be evaluated. In this report, side reactions between zinc bromide and its combustion products with fuel oil were not taken into consideration.

  6. Interstitial zinc clusters in zinc oxide

    NASA Astrophysics Data System (ADS)

    Gluba, M. A.; Nickel, N. H.; Karpensky, N.

    2013-12-01

    Doped zinc oxide (ZnO) exhibits anomalous Raman modes in the range of 270 to 870 cm-1. Commonly, the resonance at 275 cm-1 is attributed to the local vibration of Zn atoms in the vicinity of extrinsic dopants. We revisit this assignment by investigating the influence of isotopically purified zinc oxide thin films on the frequency of the vibrational mode around 275 cm-1. For this purpose, undoped and nitrogen-doped ZnO thin-films with Zn isotope compositions of natural Zn, 64Zn, 68Zn, and a 1:1 mixture of 64Zn and 68Zn were grown by pulsed laser deposition. The isotopic shift and the line shape of the Raman resonance around 275 cm-1 are analyzed in terms of three different microscopic models, which involve the vibration of (i) interstitial zinc atoms bound to extrinsic defects, (ii) interstitial diatomic Zn molecules, and (iii) interstitial zinc clusters. The energy diagram of interstitial Zn-Zn bonds in a ZnO matrix is derived from density functional theory calculations. The interstitial Zn-Zn bond is stabilized by transferring electrons from the antibonding orbital into the ZnO conduction band. This mechanism facilitates the formation of interstitial Zn clusters and fosters the common n-type doping asymmetry of ZnO.

  7. Designing hydrolytic zinc metalloenzymes.

    PubMed

    Zastrow, Melissa L; Pecoraro, Vincent L

    2014-02-18

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  8. Designing Hydrolytic Zinc Metalloenzymes

    PubMed Central

    2015-01-01

    Zinc is an essential element required for the function of more than 300 enzymes spanning all classes. Despite years of dedicated study, questions regarding the connections between primary and secondary metal ligands and protein structure and function remain unanswered, despite numerous mechanistic, structural, biochemical, and synthetic model studies. Protein design is a powerful strategy for reproducing native metal sites that may be applied to answering some of these questions and subsequently generating novel zinc enzymes. From examination of the earliest design studies introducing simple Zn(II)-binding sites into de novo and natural protein scaffolds to current studies involving the preparation of efficient hydrolytic zinc sites, it is increasingly likely that protein design will achieve reaction rates previously thought possible only for native enzymes. This Current Topic will review the design and redesign of Zn(II)-binding sites in de novo-designed proteins and native protein scaffolds toward the preparation of catalytic hydrolytic sites. After discussing the preparation of Zn(II)-binding sites in various scaffolds, we will describe relevant examples for reengineering existing zinc sites to generate new or altered catalytic activities. Then, we will describe our work on the preparation of a de novo-designed hydrolytic zinc site in detail and present comparisons to related designed zinc sites. Collectively, these studies demonstrate the significant progress being made toward building zinc metalloenzymes from the bottom up. PMID:24506795

  9. Crystal structures of two bacterial 3-hydroxy-3-methylglutaryl-CoA lyases suggest a common catalytic mechanism among a family of TIM barrel metalloenzymes cleaving carbon-carbon bonds.

    PubMed

    Forouhar, Farhad; Hussain, Munif; Farid, Ramy; Benach, Jordi; Abashidze, Mariam; Edstrom, William C; Vorobiev, Sergey M; Xiao, Rong; Acton, Thomas B; Fu, Zhuji; Kim, Jung-Ja P; Miziorko, Henry M; Montelione, Gaetano T; Hunt, John F

    2006-03-17

    The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 A resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name "DRE-TIM metallolyases" for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis results and can

  10. Crystal Structures of Two Bacterial 3-Hydroxy-3-methylglutaryl-CoA Lyases Suggest a Common Catalytic Mechanism among a Family of TIM Barrel Metalloenzymes Cleaving Carbon-Carbon Bonds

    SciTech Connect

    Forouhar,F.; Hussain, M.; Farid, R.; Benach, J.; Abashidze, M.; Edstrom, W.; Vorobiev, S.; Montelione, G.; Hunt, J.; et al.

    2006-01-01

    The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase catalyzes the terminal steps in ketone body generation and leucine degradation. Mutations in this enzyme cause a human autosomal recessive disorder called primary metabolic aciduria, which typically kills victims because of an inability to tolerate hypoglycemia. Here we present crystal structures of the HMG-CoA lyases from Bacillus subtilis and Brucella melitensis at 2.7 and 2.3 {angstrom} resolution, respectively. These enzymes share greater than 45% sequence identity with the human orthologue. Although the enzyme has the anticipated triose-phosphate isomerase (TIM) barrel fold, the catalytic center contains a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel, contrary to the predictions of homology models. Surprisingly, the residues forming this cation-binding site and most of their interaction partners are shared with three other TIM barrel enzymes that catalyze diverse carbon-carbon bond cleavage reactions believed to proceed through enolate intermediates (4-hydroxy-2-ketovalerate aldolase, 2-isopropylmalate synthase, and transcarboxylase 5S). We propose the name 'DRE-TIM metallolyases' for this newly identified enzyme family likely to employ a common catalytic reaction mechanism involving an invariant Asp-Arg-Glu (DRE) triplet. The Asp ligates the divalent cation, while the Arg probably stabilizes charge accumulation in the enolate intermediate, and the Glu maintains the precise structural alignment of the Asp and Arg. We propose a detailed model for the catalytic reaction mechanism of HMG-CoA lyase based on the examination of previously reported product complexes of other DRE-TIM metallolyases and induced fit substrate docking studies conducted using the crystal structure of human HMG-CoA lyase (reported in the accompanying paper by Fu, et al. (2006) J. Biol. Chem. 281, 7526-7532). Our model is consistent with extensive mutagenesis results and

  11. Ubiquitin is conjugated by membrane ubiquitin ligase to three sites, including the N terminus, in transmembrane region of mammalian 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for sterol-regulated enzyme degradation.

    PubMed

    Doolman, Ram; Leichner, Gil S; Avner, Rachel; Roitelman, Joseph

    2004-09-10

    The stability of the endoplasmic reticulum (ER) glycoprotein 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), the key enzyme in cholesterol biosynthesis, is negatively regulated by sterols. HMGR is anchored in the ER via its N-terminal region, which spans the membrane eight times and contains a sterol-sensing domain. We have previously established that degradation of mammalian HMGR is mediated by the ubiquitin-proteasome system (Ravid, T., Doolman, R., Avner, R., Harats, D., and Roitelman, J. (2000) J. Biol. Chem. 275, 35840-35847). Here we expressed in HEK-293 cells an HA-tagged-truncated version of HMGR that encompasses all eight transmembrane spans (350 N-terminal residues). Similar to endogenous HMGR, degradation of this HMG(350)-3HA protein was accelerated by sterols, validating it as a model to study HMGR turnover. The degradation of HMG(240)-3HA, which lacks the last two transmembrane spans yet retains an intact sterol-sensing domain, was no longer accelerated by sterols. Using HMG(350)-3HA, we demonstrate that transmembrane region of HMGR is ubiquitinated in a sterol-regulated fashion. Through site-directed Lys --> Arg mutagenesis, we pinpoint Lys(248) and Lys(89) as the internal lysines for ubiquitin attachment, with Lys(248) serving as the major acceptor site for polyubiquitination. Moreover, the data indicate that the N terminus is also ubiquitinated. The degradation rates of the Lys --> Arg mutants correlates with their level of ubiquitination. Notably, lysine-less HMG(350)-3HA is degraded faster than wild-type protein, suggesting that lysines other than Lys(89) and Lys(248) attenuate ubiquitination at the latter residues. The ATP-dependent ubiquitination of HMGR in isolated microsomes requires E1 as the sole cytosolic protein, indicating that ER-bound E2 and E3 enzymes catalyze this modification. Polyubiquitination of HMGR is correlated with its extraction from the ER membrane, a process likely to be assisted by cytosolic p97/VCP/Cdc48p-Ufd1-Npl

  12. Reduction of circulating and selective limbic brain levels of (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) following forced swim stress in C57BL/6J mice

    PubMed Central

    Maldonado-Devincci, Antoniette M.; Beattie, Matthew C.; Morrow, Danielle H.; McKinley, Raechel E.; Cook, Jason B.; O’Buckley, Todd K.

    2014-01-01

    Rationale Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, and GABAergic neuroactive steroids contribute to homeostatic regulation of this circuitry. Acute forced swim stress (FSS) increases plasma, cortical, and hypothalamic (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) levels in rats. However, there have not been systemic investigations of acute stress on changes in plasma and brain levels of 3α,5α-THP in mouse models. Objectives The present experiments aimed to assess circulating and local brain levels of 3α,5α-THP following acute FSS in C57BL/6J mice. Methods Mice were exposed to FSS (10 min), and 50 min later, blood and brains were collected. Circulating pregnenolone and 3α,5α-THP levels were assessed in serum. Free-floating brain sections (40 µm, four to five sections/region) were immunostained and analyzed in cortical and limbic brain structures. Results FSS decreased circulating 3α,5α-THP (−41.6± 10.4 %) and reduced 3α,5α-THP immunolabeling in the paraventricular nucleus of the hypothalamus (−15.2±5.7 %), lateral amygdala (LA, −31.1±13.4 %), and nucleus accumbens (NAcc) shell (−31.9±14.6). Within the LA, vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter were localized in 3α,5α-THP-positively stained cells, while in the NAcc shell, only VGLUT1 was localized in 3α,5α-THP-positively stained cells, suggesting that both glutamatergic and GABAergic cells within the LA are 3α,5α-THP-positive, while in the NAcc shell, 3α,5α-THP only localizes to glutamatergic cells. Conclusions The decrease in circulating and brain levels of 3α,5α-THP may be due to alterations in the biosynthesis/ metabolism or changes in the regulation of the HPA axis following FSS. Changes in GABAergic neuroactive steroids in response to stress likely mediate functional adaptations in neuronal activity. This may provide a potential targeted therapeutic avenue to address maladaptive stress responsivity. PMID:24744202

  13. Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway.

    PubMed

    Hu, Hai-Jie; Luo, Xue-Gang; Dong, Qing-Qing; Mu, Ai; Shi, Guo-Long; Wang, Qiu-Tong; Chen, Xiao-Ying; Zhou, Hao; Zhang, Tong-Cun; Pan, Li-Wen

    2016-03-01

    Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the high-fat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factor-kappa B (NF-κB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the

  14. midD-encoded 'rhizomimosinase' from Rhizobium sp. strain TAL1145 is a C-N lyase that catabolizes L-mimosine into 3-hydroxy-4-pyridone, pyruvate and ammonia.

    PubMed

    Negi, Vishal Singh; Bingham, Jon-Paul; Li, Qing X; Borthakur, Dulal

    2013-06-01

    Rhizobium sp. strain TAL1145 catabolizes mimosine, which is a toxic non-protein amino acid present in Leucaena leucocephala (leucaena). The objective of this investigation was to study the biochemical and catalytic properties of the enzyme encoded by midD, one of the TAL1145 genes involved in mimosine degradation. The midD-encoded enzyme, MidD, was expressed in Escherichia coli, purified and used for biochemical and catalytic studies using mimosine as the substrate. The reaction products in the enzyme assay were analyzed by HPLC and mass spectrometry. MidD has a molecular mass of ~45 kDa and its catalytic activity was found to be optimal at 37 °C and pH 8.5. The major product formed in the reaction had the same retention time as that of synthetic 3-hydroxy-4-pyridone (3H4P). It was confirmed to be 3H4P by MS/MS analysis of the HPLC-purified product. The K m, V max and K cat of MidD were 1.27 × 10(-4) mol, 4.96 × 10(-5) mol s(-1) mg(-1), and 2,256.05 s(-1), respectively. Although MidD has sequence similarities with aminotransferases, it is not an aminotransferase because it does not require a keto acid as the co-substrate in the degradation reaction. It is a pyridoxal-5'-phosphate (PLP)-dependent enzyme and the addition of 50 μM hydroxylamine completely inhibited the reaction. However, the supplementation of the reaction with 0.1 μM PLP restored the catalytic activity of MidD in the reaction containing 50 μM hydroxylamine. The catalytic activity of MidD was found to be specific to mimosine, and the presence of its structural analogs including L-tyrosine, L-tryptophan and L-phenylalanine did not show any competitive inhibition. In addition to 3H4P, we also identified pyruvate and ammonia as other degradation products in equimolar quantities of the substrate used. The degradation of mimosine into a ring compound, 3H4P with the release of ammonia indicates that MidD of Rhizobium sp. strain TAL1145 is a C-N lyase. PMID:23462928

  15. Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway.

    PubMed

    Hu, Hai-Jie; Luo, Xue-Gang; Dong, Qing-Qing; Mu, Ai; Shi, Guo-Long; Wang, Qiu-Tong; Chen, Xiao-Ying; Zhou, Hao; Zhang, Tong-Cun; Pan, Li-Wen

    2016-03-01

    Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the high-fat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factor-kappa B (NF-κB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the

  16. Ethanol extract of Zhongtian hawthorn lowers serum cholesterol in mice by inhibiting transcription of 3-hydroxy-3-methylglutaryl-CoA reductase via nuclear factor-kappa B signal pathway

    PubMed Central

    Hu, Hai-Jie; Dong, Qing-Qing; Mu, Ai; Shi, Guo-Long; Wang, Qiu-Tong; Chen, Xiao-Ying; Zhou, Hao; Zhang, Tong-Cun

    2016-01-01

    Hawthorn is a berry-like fruit from the species of Crataegus. In China, it has another more famous name, Shan-Zha, which has been used to improve digestion as a traditional Chinese medicine or food for thousands of years. Moreover, during the last decades, hawthorn has received more attention because of its potential to treat cardiovascular diseases. However, currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included as Shan-Zha in the Chinese Pharmacopoeia. In this study, our results showed that the ethanol extract of Zhongtian hawthorn, a novel grafted cultivar of C. cuneata (wild Shan-Zha), could markedly reduce body weight and levels of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, and liver cholesterol of hyperlipidemia mice. It could suppress the stimulation effect of high-fat diet on the transcription of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and p65, and counteract the downregulation of CYP7A1 and LDLR. In addition, the results of luciferase reporter assay and Western blot showed that the transcriptional activity of HMGCR promoter was inhibited by Zhongtian hawthorn ethanol extract in a dose-dependent manner, while overexpression of p65 could reverse this transcriptional repression effect. These results suggested that Zhongtian hawthorn could provide health benefits by counteracting the high-fat diet-induced hypercholesteolemic and hyperlipidemic effects in vivo, and the mechanism underlying this event was mainly dependent on the suppressive effect of Zhongtian hawthorn ethanol extract on the transcription of HMGCR via nuclear factor-kappa B (NF-κB) signal pathway. Therefore, this novel cultivar of hawthorn cultivar which has much bigger fruits, early bearing, high yield, cold resistance, and drought resistance, might be considered as a good alternative to Shan-Zha and has great value in the food and medicine industry. In addition, to our best knowledge, this is also the first report that the

  17. Downregulation of stargazin inhibits the enhanced surface delivery of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunit in rat dorsal horn and ameliorates postoperative pain

    PubMed Central

    Guo, Ruijuan; Zhao, Yujie; Zhang, Meijuan; Wang, Yue; Shi, Rong; Liu, Yang; Xu, Jie; Wu, Anshi; Yue, Yun; Wu, Jing; Guan, Yun; Wang, Yun

    2014-01-01

    Background Stargazin is the first transmembrane protein known to regulate synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Yet, it is unclear whether regulation of the surface delivery of spinal AMPA receptor subunits by stargazin contributes to postoperative pain development. Methods Western blot analysis was used to examine changes in the surface delivery of AMPA receptor subunits GluR1 and GluR2 in rat dorsal horn. The interaction between stargazin and GluR1 and GluR2 was examined by coimmunoprecipitation. Expression of stargazin was suppressed by intrathecal administration of small interfering ribonucleic acid (siRNA)311. Results Membrane-bound GluR1, but not GluR2, in ipsilateral dorsal horn was increased at 3 h (1.49±0.15-fold of β-tubulin, mean±SEM) and 1 day (1.03±0.25) after incision, as compared to that in control rats (naïve, 0.63±0.23, P < 0.05, n=6/group). The amount of GluR1 coimmunoprecipitated with stargazin was greater at 3 h after incision (1.48±0.31-fold of input) than in control animals (0.45±0.24, P < 0.05, n=6/group). Importantly, the increase in membrane GluR1 at 3 h after incision was normalized to near control level (0.72±0.20-fold of β-tubulin) by pretreatment with intrathecal stargazin siRNA311 (0.87±0.09), but not scrambled siRNA (1.48±0.24) or vehicle (1.25±0.13, P < 0.05, n=6/group). Stargazin siRNA311 pretreatment prevented the increase in stargazin–GluR1 interaction and decreased postoperative pain after incision. Conclusions This study suggests a critical role of stargazin-mediated surface delivery of GluR1 subunit in the development of postoperative pain. A better therapeutic strategy for postoperative pain may involve selectively downregulating spinal stargazin to inhibit synaptic targeting of GluR1 subunit. PMID:25093662

  18. Chronic Intermittent Ethanol Exposure Alters Stress Effects on (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) Immunolabeling of Amygdala Neurons in C57BL/6J Mice.

    PubMed

    Maldonado-Devincci, Antoniette M; Kampov-Polevoi, Alexander; McKinley, Raechel E; Morrow, Danielle H; O'Buckley, Todd K; Morrow, A Leslie

    2016-01-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) is decreased in various brain regions of C57BL/6J mice following exposure to an acute stressor or chronic intermittent ethanol (CIE) exposure and withdrawal. It is well established that there are complex interactions between stress and ethanol drinking, with mixed literature regarding the effects of stress on ethanol intake. However, there is little research examining how chronic ethanol exposure alters stress responses. The present work examined the impact of CIE exposure and withdrawal on changes in brain levels of 3α,5α-THP, as well as hormonal and behavioral responses to forced swim stress (FSS). Adult male C57BL/6J mice were exposed to four cycles of CIE to induce ethanol dependence. Following 8 h or 72 h withdrawal, mice were subjected to FSS for 10 min, and 50 min later brains were collected for immunohistochemical analysis of cellular 3α,5α-THP. Behavioral and circulating corticosterone responses to FSS were quantified. Following 8 h withdrawal, ethanol exposure potentiated the corticosterone response to FSS. Following 72 h withdrawal, this difference was no longer observed. Following 8 h withdrawal, stress-exposed mice showed no differences in immobility, swimming or struggling behavior. However, following 72 h withdrawal, ethanol-exposed mice showed less immobility and greater swimming behavior compared to air-exposed mice. Interestingly, cellular 3α,5α-THP levels were increased in the lateral amygdala 8 h and 72 h post-withdrawal in stressed ethanol-exposed mice compared to ethanol-exposed/non-stressed mice. In the paraventricular nucleus of the hypothalamus, stress exposure decreased 3α,5α-THP levels compared to controls following 72 h withdrawal, but no differences were observed 8 h post-withdrawal. There were no differences in cellular 3α,5α-THP levels in the nucleus accumbens shell at either withdrawal time point. These data suggest that

  19. Chronic Intermittent Ethanol Exposure Alters Stress Effects on (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) Immunolabeling of Amygdala Neurons in C57BL/6J Mice

    PubMed Central

    Maldonado-Devincci, Antoniette M.; Kampov-Polevoi, Alexander; McKinley, Raechel E.; Morrow, Danielle H.; O’Buckley, Todd K.; Morrow, A. Leslie

    2016-01-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) is decreased in various brain regions of C57BL/6J mice following exposure to an acute stressor or chronic intermittent ethanol (CIE) exposure and withdrawal. It is well established that there are complex interactions between stress and ethanol drinking, with mixed literature regarding the effects of stress on ethanol intake. However, there is little research examining how chronic ethanol exposure alters stress responses. The present work examined the impact of CIE exposure and withdrawal on changes in brain levels of 3α,5α-THP, as well as hormonal and behavioral responses to forced swim stress (FSS). Adult male C57BL/6J mice were exposed to four cycles of CIE to induce ethanol dependence. Following 8 h or 72 h withdrawal, mice were subjected to FSS for 10 min, and 50 min later brains were collected for immunohistochemical analysis of cellular 3α,5α-THP. Behavioral and circulating corticosterone responses to FSS were quantified. Following 8 h withdrawal, ethanol exposure potentiated the corticosterone response to FSS. Following 72 h withdrawal, this difference was no longer observed. Following 8 h withdrawal, stress-exposed mice showed no differences in immobility, swimming or struggling behavior. However, following 72 h withdrawal, ethanol-exposed mice showed less immobility and greater swimming behavior compared to air-exposed mice. Interestingly, cellular 3α,5α-THP levels were increased in the lateral amygdala 8 h and 72 h post-withdrawal in stressed ethanol-exposed mice compared to ethanol-exposed/non-stressed mice. In the paraventricular nucleus of the hypothalamus, stress exposure decreased 3α,5α-THP levels compared to controls following 72 h withdrawal, but no differences were observed 8 h post-withdrawal. There were no differences in cellular 3α,5α-THP levels in the nucleus accumbens shell at either withdrawal time point. These data suggest that

  20. Ornithine cyclodeaminase/μ-crystallin homolog from the hyperthermophilic archaeon Thermococcus litoralis functions as a novel Δ1-pyrroline-2-carboxylate reductase involved in putative trans-3-hydroxy-l-proline metabolism

    PubMed Central

    Watanabe, Seiya; Tozawa, Yuzuru; Watanabe, Yasuo

    2014-01-01

    l-Ornithine cyclodeaminase (OCD) is involved in l-proline biosynthesis and catalyzes the unique deaminating cyclization of l-ornithine to l-proline via a Δ1-pyrroline-2-carboxyrate (Pyr2C) intermediate. Although this pathway functions in only a few bacteria, many archaea possess OCD-like genes (proteins), among which only AF1665 protein (gene) from Archaeoglobus fulgidus has been characterized as an NAD+-dependent l-alanine dehydrogenase (AfAlaDH). However, the physiological role of OCD-like proteins from archaea has been unclear. Recently, we revealed that Pyr2C reductase, involved in trans-3-hydroxy-l-proline (T3LHyp) metabolism of bacteria, belongs to the OCD protein superfamily and catalyzes only the reduction of Pyr2C to l-proline (no OCD activity) [FEBS Open Bio (2014) 4, 240–250]. In this study, based on bioinformatics analysis, we assumed that the OCD-like gene from Thermococcus litoralis DSM 5473 is related to T3LHyp and/or proline metabolism (TlLhpI). Interestingly, TlLhpI showed three different enzymatic activities: AlaDH; N-methyl-l-alanine dehydrogenase; Pyr2C reductase. Kinetic analysis suggested strongly that Pyr2C is the preferred substrate. In spite of their similar activity, TlLhpI had a poor phylogenetic relationship to the bacterial and mammalian reductases for Pyr2C and formed a close but distinct subfamily to AfAlaDH, indicating convergent evolution. Introduction of several specific amino acid residues for OCD and/or AfAlaDH by site-directed mutagenesis had marked effects on both AlaDH and Pyr2C reductase activities. The OCC_00387 gene, clustered with the TlLhpI gene on the genome, encoded T3LHyp dehydratase, homologous to the bacterial and mammalian enzymes. To our knowledge, this is the first report of T3LHyp metabolism from archaea. PMID:25161870

  1. Positive allosteric modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors differentially modulates the behavioural effects of citalopram in mouse models of antidepressant and anxiolytic action.

    PubMed

    Fitzpatrick, Ciarán M; Larsen, Maria; Madsen, Louise H; Caballero-Puntiverio, Maitane; Pickering, Darryl S; Clausen, Rasmus P; Andreasen, Jesper T

    2016-09-01

    Drugs that increase monoamine neurotransmission are effective in both anxiety and depression. The therapeutic effects of monoamine-based antidepressant drugs may involve indirect effects on neurotransmission through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPAR). Thus, chronic antidepressant treatment increases AMPAR-mediated neurotransmission and AMPAR-positive allosteric modulators have shown antidepressant-like efficacy in rodents. Here, the effect of enhanced AMPAR neurotransmission on the antidepressant-like and anxiolytic-like actions of the selective serotonin reuptake inhibitor citalopram (0-10 mg/kg) was investigated in mice using the AMPAR-positive allosteric modulator LY451646 (0-3 mg/kg). Antidepressant-like effects were assessed using the forced-swim test (FST), whereas anxiolytic-like effects were tested using the elevated zero maze (EZM) and the marble burying test. LY451646 (3 mg/kg) increased swim distance in the FST and a subactive dose of LY451646 (1 mg/kg) enhanced the effect of citalopram in the FST. In the EZM, LY451646 (3 mg/kg) did not show anxiogenic effects alone, but blocked the anxiolytic-like action of citalopram in the EZM, as reflected by an increase in the latency to enter the open areas and a decrease in the number of entries and time spent in the open areas in citalopram-treated mice. In the marble burying test, LY451646 (3 mg/kg) showed no effect alone, but significantly attenuated the anxiolytic-like effect of citalopram (1.25-2.5 mg/kg) by increasing the number of marbles buried in citalopram-treated mice. These results suggest that AMPAR neurotransmission plays opposite roles in anxiety and depression as AMPAR potentiation facilitated the antidepressant-like effects of citalopram while attenuating its anxiolytic-like effect. These findings have ramifications in the search for AMPAR-based novel anxiolytic and antidepressant treatments. PMID:27341500

  2. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, T.

    1997-02-18

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate {alpha}-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal. 33 figs.

  3. Zinc phosphate conversion coatings

    DOEpatents

    Sugama, Toshifumi

    1997-01-01

    Zinc phosphate conversion coatings for producing metals which exhibit enhanced corrosion prevention characteristics are prepared by the addition of a transition-metal-compound promoter comprising a manganese, iron, cobalt, nickel, or copper compound and an electrolyte such as polyacrylic acid, polymethacrylic acid, polyitaconic acid and poly-L-glutamic acid to a phosphating solution. These coatings are further improved by the incorporation of Fe ions. Thermal treatment of zinc phosphate coatings to generate .alpha.-phase anhydrous zinc phosphate improves the corrosion prevention qualities of the resulting coated metal.

  4. Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains.

    PubMed Central

    Vallee, B L; Coleman, J E; Auld, D S

    1991-01-01

    We now recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a "zinc cluster" akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is approximately 3.5 A. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is approximately 13 A, and in this instance, a "zinc twist" is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native "zinc fingers," structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent. Images PMID:1846973

  5. Control of zinc transfer between thionein, metallothionein, and zinc proteins

    PubMed Central

    Jacob, Claus; Maret, Wolfgang; Vallee, Bert L.

    1998-01-01

    Metallothionein (MT), despite its high metal binding constant (KZn = 3.2 × 1013 M−1 at pH 7.4), can transfer zinc to the apoforms of zinc enzymes that have inherently lower stability constants. To gain insight into this paradox, we have studied zinc transfer between zinc enzymes and MT. Zinc can be transferred in both directions—i.e., from the enzymes to thionein (the apoform of MT) and from MT to the apoenzymes. Agents that mediate or enhance zinc transfer have been identified that provide kinetic pathways in either direction. MT does not transfer all of its seven zinc atoms to an apoenzyme, but apparently contains at least one that is more prone to transfer than the others. Modification of thiol ligands in MT zinc clusters increases the total number of zinc ions released and, hence, the extent of transfer. Aside from disulfide reagents, we show that selenium compounds are potential cellular enhancers of zinc transfer from MT to apoenzymes. Zinc transfer from zinc enzymes to thionein, on the other hand, is mediated by zinc-chelating agents such as Tris buffer, citrate, or glutathione. Redox agents are asymmetrically involved in both directions of zinc transfer. For example, reduced glutathione mediates zinc transfer from enzymes to thionein, whereas glutathione disulfide oxidizes MT with enhanced release of zinc and transfer of zinc to apoenzymes. Therefore, the cellular redox state as well as the concentration of other biological chelating agents might well determine the direction of zinc transfer and ultimately affect zinc distribution. PMID:9520393

  6. Diphosphonate thin films on zinc: Preparation, structure characterization and corrosion protection effects

    NASA Astrophysics Data System (ADS)

    Pilbáth, A.; Bertóti, I.; Sajó, I.; Nyikos, L.; Kálmán, E.

    2008-12-01

    The reaction of water-based solution of 1,5-diphosphono-pentane (DPP) and 1,7-diphosphono-heptane (DPH) with high purity polycrystalline zinc surface was investigated at room temperature. XRD and XPS studies evidenced the formation of crystalline zinc-phosphonate film on the metal surface. The formed layers give hydrophilic properties to the surface. A conversion-type interaction of diphosphonic acid compounds with the oxidized zinc surface was unambiguously shown by XPS analysis. Conclusive results were obtained by synthesized zinc-diphosphonate model compounds imitating the ones developed on the zinc surface, revealing a simple, closely 1:1 ratio of the phosphonate groups with zinc. Reactions with both diphosphonates resulted in significant protective effect of zinc against corrosion, although the structure and quality of the formed layers exhibit marked differences. The in-depth distribution of the composition and dissimilarity of the layer thickness were determined by glow discharge optical emission spectrometry (GD-OES). The corrosion inhibition was explained by the formation of insoluble zinc-phosphonate salt on the zinc surface, blocking the zinc dissolution process.

  7. Effect of zinc treatment on intestinal motility in experimentally induced diarrhea in rats.

    PubMed

    Adeniyi, O S; Akomolafe, R O; Ojabo, C O; Eru, E U; Olaleye, S B

    2014-01-01

    Zinc supplementation is a critical new intervention for treating diarrheal episodes in children. Recent studies suggest that administration of zinc along with new low osmolarity oral rehydration solutions / salts (ORS) can reduce the duration and severity of diarrheal episodes for up to three months. Several mechanisms of action of zinc has been proposed, however there is dearth of information about the effect of zinc on intestinal motility during diarrhea. Male albino Wistar rats (80-100g) were used. The effect of different doses of zinc sulphate (25, 50, 100, 150 mg/Kg) on the number of wet faeces was investigated. Intestinal motility during castor oil induced diarrhea was assessed using activated charcoal meal and the mechanisms of action of zinc sulphate on motility were investigated. The effective dose of zinc sulphate (100mg/Kg) significantly reduced (p< 0.001) the number of wet faeces (3.0 ± 0.00) compared with control (6.8 ± 0.25) during diarrhea. This antidiarrheal effect of zinc was abolished by propranolol and nifedipine. Zinc sulphate significantly reduced (p< 0.05) intestinal transit time (60.7 ± 7.13%) compared with control (85.7 ± 2.35%). It is concluded that zinc sulphate reduces the frequency of wet faeces output and intestinal motility during diarrhea via activation of β adrenergic receptor and L-type Ca2+ channel.

  8. Inhibitory zinc sites in enzymes.

    PubMed

    Maret, Wolfgang

    2013-04-01

    Several pathways increase the concentrations of cellular free zinc(II) ions. Such fluctuations suggest that zinc(II) ions are signalling ions used for the regulation of proteins. One function is the inhibition of enzymes. It is quite common that enzymes bind zinc(II) ions with micro- or nanomolar affinities in their active sites that contain catalytic dyads or triads with a combination of glutamate (aspartate), histidine and cysteine residues, which are all typical zinc-binding ligands. However, for such binding to be physiologically significant, the binding constants must be compatible with the cellular availability of zinc(II) ions. The affinity of inhibitory zinc(II) ions for receptor protein tyrosine phosphatase β is particularly high (K i = 21 pM, pH 7.4), indicating that some enzymes bind zinc almost as strongly as zinc metalloenzymes. The competitive pattern of zinc inhibition for this phosphatase implicates its active site cysteine and nearby residues in the coordination of zinc. Quantitative biophysical data on both affinities of proteins for zinc and cellular zinc(II) ion concentrations provide the basis for examining the physiological significance of inhibitory zinc-binding sites in proteins and the role of zinc(II) ions in cellular signalling. Regulatory functions of zinc(II) ions add a significant level of complexity to biological control of metabolism and signal transduction and embody a new paradigm for the role of transition metal ions in cell biology.

  9. Zinc in diet

    MedlinePlus

    ... Zinc is also needed for the senses of smell and taste. During pregnancy, infancy, and childhood the ... sense of taste Problems with the sense of smell Skin sores Slow growth Trouble seeing in the ...

  10. Zinc electrode and rechargeable zinc-air battery

    DOEpatents

    Ross, Jr., Philip N.

    1989-01-01

    An improved zinc electrode is disclosed for a rechargeable zinc-air battery comprising an outer frame and a porous foam electrode support within the frame which is treated prior to the deposition of zinc thereon to inhibit the formation of zinc dendrites on the external surface thereof. The outer frame is provided with passageways for circulating an alkaline electrolyte through the treated zinc-coated porous foam. A novel rechargeable zinc-air battery system is also disclosed which utilizes the improved zinc electrode and further includes an alkaline electrolyte within said battery circulating through the passageways in the zinc electrode and an external electrolyte circulation means which has an electrolyte reservoir external to the battery case including filter means to filter solids out of the electrolyte as it circulates to the external reservoir and pump means for recirculating electrolyte from the external reservoir to the zinc electrode.

  11. Electrolyte salts for power sources

    DOEpatents

    Doddapaneni, N.; Ingersoll, D.

    1995-11-28

    Electrolyte salts are disclosed for power sources comprising salts of phenyl polysulfonic acids and phenyl polyphosphonic acids. The preferred salts are alkali and alkaline earth metal salts, most preferably lithium salts. 2 figs.

  12. Electrolyte salts for power sources

    DOEpatents

    Doddapaneni, Narayan; Ingersoll, David

    1995-01-01

    Electrolyte salts for power sources comprising salts of phenyl polysulfonic acids and phenyl polyphosphonic acids. The preferred salts are alkali and alkaline earth metal salts, most preferably lithium salts.

  13. Zinc deficiency in elderly patients.

    PubMed

    Prasad, A S; Fitzgerald, J T; Hess, J W; Kaplan, J; Pelen, F; Dardenne, M

    1993-01-01

    Zinc is needed for growth and development, DNA synthesis, neurosensory functions, and cell-mediated immunity. Although zinc intake is reduced in elderly people, its deficiency and effects on cell-mediated immunity of the elderly have not been established. Subjects enrolled in "A Model Health Promotion and Intervention Program for Urban Middle Aged and Elderly Americans" were assessed for nutrition and zinc status. One hundred eighty healthy subjects were randomly selected for the study. Their mean dietary zinc intake was 9.06 mg/day, whereas the recommended dietary allowance is 15 mg/day. Plasma zinc was normal, but zinc in granulocytes and lymphocytes were decreased compared with younger control subjects. Of 118 elderly subjects in whom zinc levels in both granulocytes and lymphocytes were available, 36 had deficient levels. Plasma copper was increased, and interleukin 1 (IL-1) production was significantly decreased. Reduced response to the skin-test antigen panel and decreased taste acuity were observed. Thirteen elderly zinc-deficient subjects were supplemented with zinc, and various variables were assessed before and after zinc supplementation. Zinc supplementation corrected zinc deficiency and normalized plasma copper levels. Serum thymulin activity, IL-1 production, and lymphocyte ecto-5'-nucleotidase increased significantly after supplementation. Improvement in response to skin-test antigens and taste acuity was observed after zinc supplementation. A mild zinc deficiency appears to be a significant clinical problem in free-living elderly people. PMID:8353362

  14. Treatment of zinc deficiency without zinc fortification

    PubMed Central

    Oberleas, Donald; Harland, Barbara F.

    2008-01-01

    Zinc (Zn) deficiency in animals became of interest until the 1950s. In this paper, progresses in researches on physiology of Zn deficiency in animals, phytate effect on bioavailability of Zn, and role of phytase in healing Zn deficiency of animals were reviewed. Several studies demonstrated that Zn is recycled via the pancreas; the problem of Zn deficiency was controlled by Zn homeostasis. The endogenous secretion of Zn is considered as an important factor influencing Zn deficiency, and the critical molar ratio is 10. Phytate (inositol hexaphosphate) constituted up to 90% of the organically bound phosphorus in seeds. Great improvement has been made in recent years on isolating and measuring phytate, and its structure is clear. Phytate is considered to reduce Zn bioavailability in animal. Phytase is the enzyme that hydrolyzes phytate and is present in yeast, rye bran, wheat bran, barley, triticale, and many bacteria and fungi. Zinc nutrition and bioavailability can be enhanced by addition of phytase to animal feeds. Therefore, using phytase as supplements, the most prevalent Zn deficiency in animals may be effectively corrected without the mining and smelting of several tons of zinc daily needed to correct this deficiency by fortification worldwide. PMID:18357621

  15. High temperature electrolysis: zinc from zinc oxide using a solar furnace

    SciTech Connect

    MacDonald, F.J.

    1986-01-01

    Exploratory research was conducted in high temperature metal extraction using a concentrating solar furnace for process heat. Electrolysis of zinc oxide was performed using various molten salts as electrolytes; 13% AlF/sub 3//87% NaF, 45% AlF/sub 3//55% NaF, 33% ZnF/sub 2//67% NaF and NaOH. The temperature range investigated was 600 to 1400 K. Several materials were tried as crucibles and electrodes with the best being graphite for the cathode and crucible, and platinum for the anode. Experiments were performed where the zinc produced was collected and the current and voltage were measured. From this data, current efficiencies were calculated and decomposition potentials were determined.

  16. Endogenous zinc in neurological diseases.

    PubMed

    Koh, Jae-Yong

    2005-10-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized.

  17. Endogenous Zinc in Neurological Diseases

    PubMed Central

    2005-01-01

    The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'. Here neurobiological roles of endogenous zinc is summarized. PMID:20396459

  18. Simple colorimetric method for seminal plasma zinc assay.

    PubMed

    Fuentes, J; Miró, J; Riera, J

    1982-01-01

    Zinc concentration in seminal plasma is one of the best biochemical parameters with which to assess prostatic function in the study of male infertility. Nevertheless, this parameter is not determined in many laboratories because of technical difficulties. In this paper a simple colorimetric method for seminal plasma zinc assay is presented. This assay is performed with only one reagent solution making deproteinization and extraction with organic solvents unnecessary. The method is based on the reaction between 1-(2-pyridylazo)-2-naphthol and zinc which yields a coloured complex, that is soluble in the reagent solution when dodecyl hydrogen sulfate sodium salt is present. The solubilized complex has an absorbance peak at 560 nm. The accuracy of this method is proved by statistical comparison with atomic absorption spectrophotometry. Furthermore, the method has a good precision and is free of interference. PMID:7125243

  19. ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    ZINC ROUGHER CELLS ON LEFT, ZINC CLEANER CELLS ON RIGHT, LOOKING NORTH. NOTE ONE STYLE OF DENVER AGITATOR IN LOWER RIGHT CELL. - Shenandoah-Dives Mill, 135 County Road 2, Silverton, San Juan County, CO

  20. Nanocrystalline zinc oxide: Pyrolytic synthesis and spectroscopic characteristics

    SciTech Connect

    Demyanets, L. N. Li, L. E.; Lavrikov, A. S.; Nikitin, S. V.

    2010-01-15

    Nanocrystalline and microcrystalline ZnO powders are synthesized by the pyrolysis of organic zinc salts in the presence of a reducing catalyst represented by a porous cellulose carrier. The specimens obtained are characterized by X-ray powder diffraction, energy dispersive analysis, scanning electron microscopy, and pulse cathodoluminescence. Lasing characteristics of the specimens are studied. The synthesis conditions, under which specimens with the crystallite morphology optimal for a low-threshold lasing are obtained, are found.

  1. Structural Basis for Autoregulation of the Zinc Transporter YiiP

    SciTech Connect

    Lu, M.; Chai, J; Fu, D

    2009-01-01

    Zinc transporters have crucial roles in cellular zinc homeostatic control. The 2.9-A resolution structure of the zinc transporter YiiP from Escherichia coli reveals a richly charged dimer interface stabilized by zinc binding. Site-directed fluorescence resonance energy transfer (FRET) measurements and mutation-activity analysis suggest that zinc binding triggers hinge movements of two electrically repulsive cytoplasmic domains pivoting around four salt bridges situated at the juncture of the cytoplasmic and transmembrane domains. These highly conserved salt bridges interlock transmembrane helices at the dimer interface, where they are well positioned to transmit zinc-induced interdomain movements to reorient transmembrane helices, thereby modulating coordination geometry of the active site for zinc transport. The cytoplasmic domain of YiiP is a structural mimic of metal-trafficking proteins and the metal-binding domains of metal-transporting P-type ATPases. The use of this common structural module to regulate metal coordination chemistry may enable a tunable transport activity in response to cytoplasmic metal fluctuations.

  2. Clinical manifestations of zinc deficiency.

    PubMed

    Prasad, A S

    1985-01-01

    The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal diseases, following uses of certain drugs such as penicillamine for Wilson's disease and diuretics in some cases, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. In pregnancy and during periods of growth the requirement of zinc is increased. The clinical manifestations in severe cases of zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males; it is fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. Its deficiency adversely affects growth in many animal species and humans. Inasmuch as zinc is needed for protein and DNA synthesis and for cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Whether or not zinc is required for the metabolism of somatomedin needs to be investigated in the future. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level; the hypothalamic-pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in cell division, its deficiency may adversely affect testicular size and thus affect its functions. Zinc is required for the functions of several enzymes and whether or not it has an enzymatic role in steroidogenesis is not known at present

  3. Salt tectonics on Venus

    SciTech Connect

    Wood, C.A.; Amsbury, D.

    1986-05-01

    The discovery of a surprisingly high deuterium/hydrogen ratio on Venus immediately led to the speculation that Venus may have once had a volume of surface water comparable to that of the terrestrial oceans. The authors propose that the evaporation of this putative ocean may have yielded residual salt deposits that formed various terrain features depicted in Venera 15 and 16 radar images. By analogy with models for the total evaporation of the terrestrial oceans, evaporite deposits on Venus should be at least tens to hundreds of meters thick. From photogeologic evidence and in-situ chemical analyses, it appears that the salt plains were later buried by lava flows. On Earth, salt diapirism leads to the formation of salt domes, anticlines, and elongated salt intrusions - features having dimensions of roughly 1 to 100 km. Due to the rapid erosion of salt by water, surface evaporite landforms are only common in dry regions such as the Zagros Mountains of Iran, where salt plugs and glaciers exist. Venus is far drier than Iran; extruded salt should be preserved, although the high surface temperature (470/sup 0/C) would probably stimulate rapid salt flow. Venus possesses a variety of circular landforms, tens to hundreds of kilometers wide, which could be either megasalt domes or salt intrusions colonizing impact craters. Additionally, arcurate bands seen in the Maxwell area of Venus could be salt intrusions formed in a region of tectonic stress. These large structures may not be salt features; nonetheless, salt features should exist on Venus.

  4. Zinc titanate sorbents

    DOEpatents

    Gupta, Raghubir P.; Gangwal, Santosh K.; Jain, Suresh C.

    1998-01-01

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750.degree. C. to about 950.degree. C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 .mu., and about 1 part titanium dioxide having a median particle size of less than about 1 .mu.. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  5. Zinc titanate sorbents

    DOEpatents

    Gupta, R.P.; Gangwal, S.K.; Jain, S.C.

    1998-02-03

    The present invention provides a zinc titanate sorbent material useful in desulfurization applications. The zinc titanate material is in the form of generally spherical particles of substantially uniform chemical distribution. The sorbent material is capable of absorbing sulfur compounds from a gaseous feed in an amount of at least about 15 weight percent based on the weight of the sorbent. The sorbent material is prepared by a process including: (a) forming a zinc oxide/titanium dioxide dry blend, (b) preparing a substantially uniform aqueous slurry comprising the zinc oxide/titanium dioxide dry blend, organic binder, and at least about 1 weight percent inorganic binder based on the solids weight of the slurry, (c) spray drying the slurry to produce substantially spherical particles, and (d) calcining the particles at a temperature of between about 750 to about 950 C. The dry blend is formed by mixing between about 0.5 to about 2 parts zinc oxide having a median particle size of less than about 0.5 microns, and about 1 part titanium dioxide having a median particle size of less than about 1 micron. The slurry contains substantially no free silica and may be prepared by the process including (1) preparing an aqueous solution of organic binder, (2) adding the dry blend to the aqueous solution of organic binder, and (3) adding the inorganic binder to the solution of organic binder, and blend. Additional reagents, such as a surfactant, may also be incorporated into the sorbent material. The present invention also provides a process for desulfurizing a gaseous stream. The process includes passing a gaseous stream through a reactor containing an attrition resistant zinc titanate sorbent material of the present invention.

  6. PySALT: SALT science pipeline

    NASA Astrophysics Data System (ADS)

    Crawford, S. M.; Still, M.; Schellart, P.; Balona, L.; Buckley, D. A. H.; Gulbis, A. A. S.; Kniazev, A.; Kotze, M.; Loaring, N.; Nordsieck, K. H.; Pickering, T. E.; Potter, S.; Romero Colmenero, E.; Vaisanen, P.; Wiliams, T.; Zietsman, E.

    2012-07-01

    The PySALT user package contains the primary reduction and analysis software tools for the SALT telescope. Currently, these tools include basic data reductions for RSS and SALTICAM in both imaging, spectroscopic, and slot modes. Basic analysis software for slot mode data is also provided. These tools are primarily written in python/PyRAF with some additional IRAF code.

  7. Comparison of proteome response to saline and zinc stress in lettuce.

    PubMed

    Lucini, Luigi; Bernardo, Letizia

    2015-01-01

    Zinc salts occurring in soils can exert an osmotic stress toward plants. However, being zinc a heavy metal, some more specific effects on plant metabolisms can be forecast. In this work, lettuce has been used as a model to investigate salt and zinc stresses at proteome level through a shotgun tandem MS proteomic approach. The effect of zinc stress in lettuce, in comparison with NaCl stress, was evaluated to dissect between osmotic/oxidative stress related effects, from those changes specifically related to zinc. The analysis of proteins exhibiting a fold change of 3 as minimum (on log 2 normalized abundances), revealed the involvement of photosynthesis (via stimulation of chlorophyll synthesis and enhanced role of photosystem I) as well as stimulation of photophosphorylation. Increased glycolytic supply of energy substrates and ammonium assimilation [through formation of glutamine synthetase (GS)] were also induced by zinc in soil. Similarly, protein metabolism (at both transcriptional and ribosomal level), heat shock proteins, and proteolysis were affected. According to their biosynthetic enzymes, hormones appear to be altered by both the treatment and the time point considered: ethylene biosynthesis was enhanced, while production of abscisic acid was up-regulated at the earlier time point to decrease markedly and gibberellins were decreased at the later one. Besides aquaporin PIP2 synthesis, other osmotic/oxidative stress related compounds were enhanced under zinc stress, i.e., proline, hydroxycinnamic acids, ascorbate, sesquiterpene lactones, and terpenoids biosynthesis. Although the proteins involved in the response to zinc stress and to salinity were substantially the same, their abundance changed between the two treatments. Lettuce response to zinc was more prominent at the first sampling point, yet showing a faster adaptation than under NaCl stress. Indeed, lettuce plants showed an adaptation after 30 days of stress, in a more pronounced way in the case of

  8. Comparison of proteome response to saline and zinc stress in lettuce

    PubMed Central

    Lucini, Luigi; Bernardo, Letizia

    2015-01-01

    Zinc salts occurring in soils can exert an osmotic stress toward plants. However, being zinc a heavy metal, some more specific effects on plant metabolisms can be forecast. In this work, lettuce has been used as a model to investigate salt and zinc stresses at proteome level through a shotgun tandem MS proteomic approach. The effect of zinc stress in lettuce, in comparison with NaCl stress, was evaluated to dissect between osmotic/oxidative stress related effects, from those changes specifically related to zinc. The analysis of proteins exhibiting a fold change of 3 as minimum (on log 2 normalized abundances), revealed the involvement of photosynthesis (via stimulation of chlorophyll synthesis and enhanced role of photosystem I) as well as stimulation of photophosphorylation. Increased glycolytic supply of energy substrates and ammonium assimilation [through formation of glutamine synthetase (GS)] were also induced by zinc in soil. Similarly, protein metabolism (at both transcriptional and ribosomal level), heat shock proteins, and proteolysis were affected. According to their biosynthetic enzymes, hormones appear to be altered by both the treatment and the time point considered: ethylene biosynthesis was enhanced, while production of abscisic acid was up-regulated at the earlier time point to decrease markedly and gibberellins were decreased at the later one. Besides aquaporin PIP2 synthesis, other osmotic/oxidative stress related compounds were enhanced under zinc stress, i.e., proline, hydroxycinnamic acids, ascorbate, sesquiterpene lactones, and terpenoids biosynthesis. Although the proteins involved in the response to zinc stress and to salinity were substantially the same, their abundance changed between the two treatments. Lettuce response to zinc was more prominent at the first sampling point, yet showing a faster adaptation than under NaCl stress. Indeed, lettuce plants showed an adaptation after 30 days of stress, in a more pronounced way in the case of

  9. Comparison of proteome response to saline and zinc stress in lettuce.

    PubMed

    Lucini, Luigi; Bernardo, Letizia

    2015-01-01

    Zinc salts occurring in soils can exert an osmotic stress toward plants. However, being zinc a heavy metal, some more specific effects on plant metabolisms can be forecast. In this work, lettuce has been used as a model to investigate salt and zinc stresses at proteome level through a shotgun tandem MS proteomic approach. The effect of zinc stress in lettuce, in comparison with NaCl stress, was evaluated to dissect between osmotic/oxidative stress related effects, from those changes specifically related to zinc. The analysis of proteins exhibiting a fold change of 3 as minimum (on log 2 normalized abundances), revealed the involvement of photosynthesis (via stimulation of chlorophyll synthesis and enhanced role of photosystem I) as well as stimulation of photophosphorylation. Increased glycolytic supply of energy substrates and ammonium assimilation [through formation of glutamine synthetase (GS)] were also induced by zinc in soil. Similarly, protein metabolism (at both transcriptional and ribosomal level), heat shock proteins, and proteolysis were affected. According to their biosynthetic enzymes, hormones appear to be altered by both the treatment and the time point considered: ethylene biosynthesis was enhanced, while production of abscisic acid was up-regulated at the earlier time point to decrease markedly and gibberellins were decreased at the later one. Besides aquaporin PIP2 synthesis, other osmotic/oxidative stress related compounds were enhanced under zinc stress, i.e., proline, hydroxycinnamic acids, ascorbate, sesquiterpene lactones, and terpenoids biosynthesis. Although the proteins involved in the response to zinc stress and to salinity were substantially the same, their abundance changed between the two treatments. Lettuce response to zinc was more prominent at the first sampling point, yet showing a faster adaptation than under NaCl stress. Indeed, lettuce plants showed an adaptation after 30 days of stress, in a more pronounced way in the case of

  10. Observations of interstellar zinc

    NASA Technical Reports Server (NTRS)

    Jura, M.; York, D.

    1981-01-01

    The International Ultraviolet Explorer observations of interstellar zinc toward 10 stars are examined. It is found that zinc is at most only slightly depleted in the interstellar medium; its abundance may serve as a tracer of the true metallicity in the gas. The local interstellar medium has abundances that apparently are homogeneous to within a factor of two, when integrated over paths of about 500 pc, and this result is important for understanding the history of nucleosynthesis in the solar neighborhood. The intrinsic errors in detecting weak interstellar lines are analyzed and suggestions are made as to how this error limit may be lowered to 5 mA per target observation.

  11. Photovoltaic cells employing zinc phosphide

    DOEpatents

    Barnett, Allen M.; Catalano, Anthony W.; Dalal, Vikram L.; Masi, James V.; Meakin, John D.; Hall, Robert B.

    1984-01-01

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  12. Recovering Zinc From Discarded Tires

    NASA Technical Reports Server (NTRS)

    Du Fresne, E. R.

    1984-01-01

    Zinc sulfate monohydrate sold at profit. Shredded tire material steeped in three sulfuric acid baths to extract zinc. Final product removed by evaporating part of solution until product crystallizes out. Recovered as zinc sulfate monohydrate and sold as fertilizer or for general use.

  13. Photovoltaic cells employing zinc phosphide

    SciTech Connect

    Barnett, A.M.; Catalano, A.W.; Dalal, V.L.; Hall, R.B.; Masi, J.V.; Meakin, J.D.

    1984-10-16

    A photovoltaic cell having a zinc phosphide absorber. The zinc phosphide can be a single or multiple crystal slice or a thin polycrystalline film. The cell can be a Schottky barrier, heterojunction or homojunction device. Methods for synthesizing and crystallizing zinc phosphide are disclosed as well as a method for forming thin films.

  14. Metabolism of leucine in fibroblasts from patients with deficiencies in each of the major catabolic enzymes: branched-chain ketoacid dehydrogenase, isovaleryl-CoA dehydrogenase, 3-methylcrotonyl-CoA carboxylase, 3-methylglutaconyl-CoA hydratase, and 3-hydroxy-3-methylglutaryl-CoA lyase.

    PubMed

    Yoshida, I; Søvik, O; Sweetman, L; Nyhan, W L

    1985-12-01

    The metabolism of leucine was studied in cultured human fibroblasts derived from patients with defects in each of the major steps in the catabolism of the amino acid. Intact fibroblasts were incubated with [U-14C]leucine and the organic acid products were isolated by liquid partition chromatography. In control fibroblasts the major product of leucine was 3-hydroxyisovaleric acid. This was also the case for fibroblasts with deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase, 3-methylcrotonyl-CoA carboxylase and 3-methylglutaconyl-CoA hydratase. There was little or no accumulation of the compound with fibroblasts from patients with maple syrup urine disease and isovaleric acidemia.

  15. Low-salt diet

    MedlinePlus

    ... away from foods that are always high in salt. Some common ones are: Processed foods, such as cured or smoked meats, bacon, hot dogs, sausage, bologna, ham, and salami ... salt with other seasonings. Pepper, garlic, herbs, and lemon ...

  16. The fluids in salt.

    USGS Publications Warehouse

    Roedder, E.

    1984-01-01

    The characteristics of fluid inclusions in salt, the geological processes through which these fluids evolve, and the possible problems such inclusions pose for nuclear waste disposal in salt beds or domes are reviewed.-J.A.Z.

  17. What Are Bath Salts?

    MedlinePlus

    ... Are bath salts becoming more popular? Marsha Lopez Hi, Lauren. Nope! Actually quite the opposite! This family ... and how dangerous for your body? Michelle Rankin Hi ParkerPanella - Bath salts are drugs known as synthetic ...

  18. Utah: Salt Lake Region

    Atmospheric Science Data Center

    2014-05-15

    article title:  Winter and Summer Views of the Salt Lake Region     View Larger Image Magnificent views of the region surrounding Salt Lake City, Utah are captured in these winter and summer images from the ...

  19. Molten salt electrolyte separator

    DOEpatents

    Kaun, Thomas D.

    1996-01-01

    A molten salt electrolyte/separator for battery and related electrochemical systems including a molten electrolyte composition and an electrically insulating solid salt dispersed therein, to provide improved performance at higher current densities and alternate designs through ease of fabrication.

  20. Quantitative separation of zinc traces from cadmium matrices by solid-phase extraction with polyurethane foam.

    PubMed

    Santiago de Jesus, D; Souza de Carvalho, M; Spínola Costa, A C; Costa Ferreira, S L

    1998-08-01

    A system for separation of zinc traces from large amounts of cadmium is proposed in this paper. It is based on the solid-phase extraction of the zinc in the form of thiocyanate complexes by the polyurethane foam. The following parameters were studied: effect of pH and of the thiocyanate concentration on the zinc extraction, shaking time required for quantitative extraction, amount of PU foam necessary for complete extraction, conditions for the separation of zinc from cadmium, influence of other cations and anions on the zinc sorption by PU foam, and required conditions for back extraction of zinc from the PU foam. The results show that zinc traces can be separated from large amounts of cadmium at pH 3.0+/-0.50, with the range of thiocyanate concentration from 0.15 to 0.20 mol l(-1), and the shaking time of 5 min. The back extraction of zinc can be done by shaking it with water for 10 min. Calcium, barium, strontium, magnesium, aluminum, nickel and iron(II) are efficiently separated. Iron(III), copper(II) and cobalt(II) are extracted simultaneously with zinc, but the iron reduction with ascorbic acid and the use of citrate to mask copper(II) and cobalt(II) increase the selectivity of the zinc extraction. The anions nitrate, chloride, sulfate, acetate, thiosulphate, tartarate, oxalate, fluoride, citrate, and carbonate do not affect the zinc extraction. Phosphate and EDTA must be absent. The method proposed was applied to determine zinc in cadmium salts using 4-(2-pyridylazo)-resorcinol (PAR) as a spectrophotometric reagent. The result achieved did not show significant difference in the accuracy and precision (95% confidence level) with those obtained by ICP-AES analysis. PMID:18967283

  1. Molten salt technology

    SciTech Connect

    Lovering, D.G.

    1982-01-01

    In this volume, the historical background, scope, problems, economics, and future applications of molten salt technologies are discussed. Topics presented include molten salts in primary production of aluminum, general principles and handling and safety of the alkali metals, first-row transition metals, group VIII metals and B-group elements, solution electrochemistry, transport phenomena, corrosion in different molten salts, cells with molten salt electrolytes and reactants, fuel cell design, hydrocracking and liquefaction, heat storage in phase change materials, and nuclear technologies.

  2. Retrospective salt tectonics

    SciTech Connect

    Jackson, M.P.A.

    1996-12-31

    The conceptual breakthroughs in understanding salt tectonics can be recognized by reviewing the history of salt tectonics, which divides naturally into three parts: the pioneering era, the fluid era, and the brittle era. The pioneering era (1856-1933) featured the search for a general hypothesis of salt diapirism, initially dominated by bizarre, erroneous notions of igneous activity, residual islands, in situ crystallization, osmotic pressures, and expansive crystallization. Gradually data from oil exploration constrained speculation. The effects of buoyancy versus orogeny were debated, contact relations were characterized, salt glaciers were discovered, and the concepts of downbuilding and differential loading were proposed as diapiric mechanisms. The fluid era (1933-{approximately}1989) was dominated by the view that salt tectonics resulted from Rayleigh-Taylor instabilities in which a dense fluid overburden having negligible yield strength sinks into a less dense fluid salt layer, displacing it upward. Density contrasts, viscosity contrasts, and dominant wavelengths were emphasized, whereas strength and faulting of the overburden were ignored. During this era, palinspastic reconstructions were attempted; salt upwelling below thin overburdens was recognized; internal structures of mined diapirs were discovered; peripheral sinks, turtle structures, and diapir families were comprehended; flow laws for dry salt were formulated; and contractional belts on divergent margins and allochthonous salt sheets were recognized. The 1970s revealed the basic driving force of salt allochthons, intrasalt minibasins, finite strains in diapirs, the possibility of thermal convection in salt, direct measurement of salt glacial flow stimulated by rainfall, and the internal structure of convecting evaporites and salt glaciers. The 1980`s revealed salt rollers, subtle traps, flow laws for damp salt, salt canopies, and mushroom diapirs.

  3. Zinc requirements and zinc intakes of breast-fed infants.

    PubMed

    Krebs, N F; Hambidge, K M

    1986-02-01

    Longitudinal changes in dietary zinc requirements for infants at different levels of net absorption were estimated using a factorial approach. Apart from variations in net absorption, the zinc needed for new lean body mass is the major determinant of requirements. As growth velocity declines progressively, estimated zinc requirements for growth and for replacement of urine and sweat losses decrease from a high for male infants of 780 micrograms/day at 1 mo to 480 micrograms/day in the 5th mo and then remain quite constant through the 1st yr. Calculated percentage absorption of zinc from human milk necessary to meet estimated requirements increases with duration of lactation. For infants of mothers whose zinc intake approximated 25 mg/day the calculated percentage absorption remained within plausible limits. It is suggested that the progressive decrease in milk zinc concentrations provides a mechanism for conserving maternal zinc while meeting infant needs. PMID:3946293

  4. 21 CFR 100.155 - Salt and iodized salt.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Salt and iodized salt. 100.155 Section 100.155... FOR HUMAN CONSUMPTION GENERAL Specific Administrative Rulings and Decisions § 100.155 Salt and iodized salt. (a) For the purposes of this section, the term iodized salt or iodized table salt is...

  5. 21 CFR 100.155 - Salt and iodized salt.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Salt and iodized salt. 100.155 Section 100.155... FOR HUMAN CONSUMPTION GENERAL Specific Administrative Rulings and Decisions § 100.155 Salt and iodized salt. (a) For the purposes of this section, the term iodized salt or iodized table salt is...

  6. 21 CFR 100.155 - Salt and iodized salt.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Salt and iodized salt. 100.155 Section 100.155... FOR HUMAN CONSUMPTION GENERAL Specific Administrative Rulings and Decisions § 100.155 Salt and iodized salt. (a) For the purposes of this section, the term iodized salt or iodized table salt is...

  7. 21 CFR 100.155 - Salt and iodized salt.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Salt and iodized salt. 100.155 Section 100.155... FOR HUMAN CONSUMPTION GENERAL Specific Administrative Rulings and Decisions § 100.155 Salt and iodized salt. (a) For the purposes of this section, the term iodized salt or iodized table salt is...

  8. 21 CFR 100.155 - Salt and iodized salt.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Salt and iodized salt. 100.155 Section 100.155... FOR HUMAN CONSUMPTION GENERAL Specific Administrative Rulings and Decisions § 100.155 Salt and iodized salt. (a) For the purposes of this section, the term iodized salt or iodized table salt is...

  9. Homoleptic and heteroleptic N-alkylimidazole zinc(ii)-containing ionic liquids for high current density electrodeposition.

    PubMed

    Steichen, Marc; Brooks, Neil R; Van Meervelt, Luc; Fransaer, Jan; Binnemans, Koen

    2014-08-28

    New homoleptic and heteroleptic zinc(ii)-containing liquid metal salts with N-alkylimidazole (AlkIm) ligands and bis(trifluoromethylsulfonyl)imide (Tf2N(-)) anions are described. The general formulae of the complexes are [Zn(AlkIm)6][Tf2N]2 and [Zn(AlkIm)6-x(AlkIm')x][Tf2N]2. Single-crystal X-ray diffraction revealed that, in the solid state, the cations consist of octahedral zinc(ii) centres. The heteroleptic complexes contain two different N-alkylimidazole ligands. The melting points of the liquid metal salts are below or slightly above room temperature. The dependence of the melting points, viscosity and crystal structure on the alkyl chain length of the N-alkylimidazole ligand for the homoleptic complexes and on the ratio of the two N-alkylimidazole ligands AlkIm and AlkIm' for the heteroleptic compounds is discussed. The possibility of incongruent melting and the presence of a mixture of the four-coordinate zinc(ii) centre and neutral ligands is discussed. The new zinc(ii)-containing liquid metal salts have been used as non-aqueous electrolytes for electrodeposition of zinc. A highly reversible deposition-stripping behaviour was found. Zinc electroplating was possible at very high current densities of more than -200 mA cm(-2) in unstirred solutions. Compact and highly crystalline zinc deposits were obtained.

  10. Imaging Mobile Zinc in Biology

    PubMed Central

    Tomat, Elisa; Lippard, Stephen J.

    2009-01-01

    Summary Trafficking and regulation of mobile zinc pools influence cellular functions and pathological conditions in multiple organs, including brain, pancreas, and prostate. The quest for a dynamic description of zinc distribution and mobilization in live cells fuels the development of increasingly sophisticated probes. Detection systems that respond to zinc binding with changes of their fluorescence emission properties have provided sensitive tools for mobile zinc imaging, and fluorescence microscopy experiments have afforded depictions of zinc distribution within live cells and tissues. Both small-molecule and protein-based fluorescent probes can address complex imaging challenges, such as analyte quantification, site-specific sensor localization, and real-time detection. PMID:20097117

  11. Zinc and Compounds

    Integrated Risk Information System (IRIS)

    Zinc and Compounds ; CASRN 7440 - 66 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  12. Creep Resistant Zinc Alloy

    SciTech Connect

    Frank E. Goodwin

    2002-12-31

    This report covers the development of Hot Chamber Die Castable Zinc Alloys with High Creep Strengths. This project commenced in 2000, with the primary objective of developing a hot chamber zinc die-casting alloy, capable of satisfactory service at 140 C. The core objectives of the development program were to: (1) fill in missing alloy data areas and develop a more complete empirical model of the influence of alloy composition on creep strength and other selected properties, and (2) based on the results from this model, examine promising alloy composition areas, for further development and for meeting the property combination targets, with the view to designing an optimized alloy composition. The target properties identified by ILZRO for an improved creep resistant zinc die-casting alloy were identified as follows: (1) temperature capability of 1470 C; (2) creep stress of 31 MPa (4500 psi); (3) exposure time of 1000 hours; and (4) maximum creep elongation under these conditions of 1%. The project was broadly divided into three tasks: (1) Task 1--General and Modeling, covering Experimental design of a first batch of alloys, alloy preparation and characterization. (2) Task 2--Refinement and Optimization, covering Experimental design of a second batch of alloys. (3) Task 3--Creep Testing and Technology transfer, covering the finalization of testing and the transfer of technology to the Zinc industry should have at least one improved alloy result from this work.

  13. Doped zinc oxide microspheres

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

  14. Doped zinc oxide microspheres

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-12-14

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

  15. Zinc sulfide liquefaction catalyst

    DOEpatents

    Garg, Diwakar

    1984-01-01

    A process for the liquefaction of carbonaceous material, such as coal, is set forth wherein coal is liquefied in a catalytic solvent refining reaction wherein an activated zinc sulfide catalyst is utilized which is activated by hydrogenation in a coal derived process solvent in the absence of coal.

  16. Intercalation studies of zinc hydroxide chloride: Ammonia and amino acids

    SciTech Connect

    Arizaga, Gregorio Guadalupe Carbajal

    2012-01-15

    Zinc hydroxide chloride (ZHC) is a layered hydroxide salt with formula Zn{sub 5}(OH){sub 8}Cl{sub 2}{center_dot}2H{sub 2}O. It was tested as intercalation matrix for the first time and results were compared with intercalation products of the well-known zinc hydroxide nitrate and a Zn/Al layered double hydroxide. Ammonia was intercalated into ZHC, while no significant intercalation occurred in ZHN. Aspartic acid intercalation was only achieved by co-precipitation at pH=10 with ZHC and pH=8 with zinc hydroxide nitrate. Higher pH resistance in ZHC favored total deprotonation of both carboxylic groups of the Asp molecule. ZHC conferred more thermal protection against Asp combustion presenting exothermic peaks even at 452 Degree-Sign C while the exothermic event in ZHN was 366 Degree-Sign C and in the LDH at 276 Degree-Sign C. - Graphical abstract: The zinc hydroxide chloride (ZHC) with formula Zn{sub 5}(OH){sub 8}Cl{sub 2}{center_dot}2H{sub 2}O was tested as intercalation matrix. In comparison with the well-known zinc hydroxide nitrate (ZHN) and layered double hydroxides (LDH), ZHC was the best matrix for thermal protection of Asp combustion, presenting exothermic peaks even at 452 Degree-Sign C, while the highest exothermic event in ZHN was at 366 Degree-Sign C, and in the LDH it was at 276 Degree-Sign C. Highlights: Black-Right-Pointing-Pointer Zinc hydroxide chloride (ZHC) was tested as intercalation matrix for the first time. Black-Right-Pointing-Pointer ZHC has higher chemical and thermal stability than zinc hydroxide nitrate and LDH. Black-Right-Pointing-Pointer NH{sub 3} molecules can be intercalated into ZHC. Black-Right-Pointing-Pointer The amino group of amino acids limits the intercalation by ion-exchange.

  17. Zinc, the brain and behavior.

    PubMed

    Pfeiffer, C C; Braverman, E R

    1982-04-01

    The total content of zinc in the adult human body averages almost 2 g. This is approximately half the total iron content and 10 to 15 times the total body copper. In the brain, zinc is with iron, the most concentrated metal. The highest levels of zinc are found in the hippocampus in synaptic vesicles, boutons, and mossy fibers. Zinc is also found in large concentrations in the choroid layer of the retina which is an extension of the brain. Zinc plays an important role in axonal and synaptic transmission and is necessary for nucleic acid metabolism and brain tubulin growth and phosphorylation. Lack of zinc has been implicated in impaired DNA, RNA, and protein synthesis during brain development. For these reasons, deficiency of zinc during pregnancy and lactation has been shown to be related to many congenital abnormalities of the nervous system in offspring. Furthermore, in children insufficient levels of zinc have been associated with lowered learning ability, apathy, lethargy, and mental retardation. Hyperactive children may be deficient in zinc and vitamin B-6 and have an excess of lead and copper. Alcoholism, schizophrenia, Wilson's disease, and Pick's disease are brain disorders dynamically related to zinc levels. Zinc has been employed with success to treat Wilson's disease, achrodermatitis enteropathica, and specific types of schizophrenia.

  18. Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.

    PubMed

    Holland, Tai C; Killilea, David W; Shenvi, Swapna V; King, Janet C

    2015-12-01

    A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.

  19. Interaction Between Yeasts and Zinc

    NASA Astrophysics Data System (ADS)

    Nicola, Raffaele De; Walker, Graeme

    Zinc is an essential trace element in biological systems. For example, it acts as a cellular membrane stabiliser, plays a critical role in gene expression and genome modification and activates nearly 300 enzymes, including alcohol dehydrogenase. The present chapter will be focused on the influence of zinc on cell physiology of industrial yeast strains of Saccharomyces cerevisiae, with special regard to the uptake and subsequent utilisation of this metal. Zinc uptake by yeast is metabolism-dependent, with most of the available zinc translocated very quickly into the vacuole. At cell division, zinc is distributed from mother to daughter cells and this effectively lowers the individual cellular zinc concentration, which may become zinc depleted at the onset of the fermentation. Zinc influences yeast fermentative performance and examples will be provided relating to brewing and wine fermentations. Industrial yeasts are subjected to several stresses that may impair fermentation performance. Such stresses may also impact on yeast cell zinc homeostasis. This chapter will discuss the practical implications for the correct management of zinc bioavailability for yeast-based biotechnologies aimed at improving yeast growth, viability, fermentation performance and resistance to environmental stresses

  20. Zinc hydroxide sulphate and its transformation to crystalline zinc oxide.

    PubMed

    Moezzi, Amir; Cortie, Michael B; McDonagh, Andrew M

    2013-10-28

    The thermal transformation of zinc hydroxide sulphate hydrate to zinc oxide has been examined using synchrotron X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, and surface area measurements. By collecting X-ray diffraction data in situ, we found that the dehydration of zinc hydroxide sulphate pentahydrate proceeded in discrete steps to form anhydrous zinc hydroxide sulphate. This compound then decomposed to a mixture of zinc oxide and a compound tentatively identified as Zn3(OH)2(SO4)2 at ~235 °C. At ~360 °C, the final dehydroxylation occurred with the formation of zinc oxy-sulphate, Zn3O(SO4)2, which then decomposed to ZnO at about ~800 °C. Interruption of the dehydration process can be used to synthesize the intermediate compounds.

  1. Experimental phasing using zinc anomalous scattering

    SciTech Connect

    Cha, Sun-Shin; An, Young Jun; Jeong, Chang-Sook; Kim, Min-Kyu; Lee, Sung-Gyu; Lee, Kwang-Hoon; Oh, Byung-Ha

    2012-09-01

    The surface of proteins can be charged with zinc ions and the anomalous signals from these zinc ions can be used for structure determination of proteins. Zinc is a suitable metal for anomalous dispersion phasing methods in protein crystallography. Structure determination using zinc anomalous scattering has been almost exclusively limited to proteins with intrinsically bound zinc(s). Here, it is reported that multiple zinc ions can easily be charged onto the surface of proteins with no intrinsic zinc-binding site by using zinc-containing solutions. Zn derivatization of protein surfaces appears to be a largely unnoticed but promising method of protein structure determination.

  2. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  3. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  4. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  5. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  6. 21 CFR 73.1991 - Zinc oxide.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Zinc oxide. 73.1991 Section 73.1991 Food and Drugs... ADDITIVES EXEMPT FROM CERTIFICATION Drugs § 73.1991 Zinc oxide. (a) Identity. (1) The color additive zinc... indirect process whereby zinc metal isolated from the zinc-containing ore is vaporized and then...

  7. An investigation of the electrochemical action of the epoxy zinc-rich coatings containing surface modified aluminum nanoparticle

    NASA Astrophysics Data System (ADS)

    Jalili, M.; Rostami, M.; Ramezanzadeh, B.

    2015-02-01

    Aluminum nanoparticle was modified with amino trimethylene phosphonic acid (ATMP). The surface characterization of the nanoparticles was done by X-ray photo electron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis. The influence of the replacement of 2 wt% of zinc dust in the standard zinc-rich epoxy coating by nanoparticles on the electrochemical action of the coating was studied by electrochemical impedance spectroscopy (EIS) and salt spray tests. The morphology and phase composition of the zinc rich paints were evaluated by X-ray diffraction (XRD) and filed-emission scanning electron microscopy (FE-SEM). Results showed that the ATMP molecules successfully adsorbed on the surface of Al nanoparticles. Results obtained from salt spray and electrochemical measurements revealed that the addition of surface modified nanoparticles to the zinc rich coating enhanced its galvanic action and corrosion protection properties.

  8. Observations of interstellar zinc

    NASA Technical Reports Server (NTRS)

    York, D. G.; Jura, M.

    1982-01-01

    IUE observations toward 10 stars have shown that zinc is not depleted in the interstellar medium by more than a factor of two, suggesting that its abundance may serve as a tracer of the true metallicity in the gas. A result pertinent to the history of nucleosynthesis in the solar neighborhood is that the local interstellar medium has abundances that appear to be homogeneous to within a factor of two, when integrated over paths of about 500 pc.

  9. Novel waste printed circuit board recycling process with molten salt.

    PubMed

    Riedewald, Frank; Sousa-Gallagher, Maria

    2015-01-01

    The objective of the method was to prove the concept of a novel waste PCBs recycling process which uses inert, stable molten salts as the direct heat transfer fluid and, simultaneously, uses this molten salt to separate the metal products in either liquid (solder, zinc, tin, lead, etc.) or solid (copper, gold, steel, palladium, etc.) form at the operating temperatures of 450-470 °C. The PCB recovery reactor is essentially a U-shaped reactor with the molten salt providing a continuous fluid, allowing molten salt access from different depths for metal recovery. A laboratory scale batch reactor was constructed using 316L as suitable construction material. For safety reasons, the inert, stable LiCl-KCl molten salts were used as direct heat transfer fluid. Recovered materials were washed with hot water to remove residual salt before metal recovery assessment. The impact of this work was to show metal separation using molten salts in one single unit, by using this novel reactor methodology. •The reactor is a U-shaped reactor filled with a continuous liquid with a sloped bottom representing a novel reactor concept.•This method uses large PCB pieces instead of shredded PCBs as the reactor volume is 2.2 L.•The treated PCBs can be removed via leg B while the process is on-going.

  10. Novel waste printed circuit board recycling process with molten salt

    PubMed Central

    Riedewald, Frank; Sousa-Gallagher, Maria

    2015-01-01

    The objective of the method was to prove the concept of a novel waste PCBs recycling process which uses inert, stable molten salts as the direct heat transfer fluid and, simultaneously, uses this molten salt to separate the metal products in either liquid (solder, zinc, tin, lead, etc.) or solid (copper, gold, steel, palladium, etc.) form at the operating temperatures of 450–470 °C. The PCB recovery reactor is essentially a U-shaped reactor with the molten salt providing a continuous fluid, allowing molten salt access from different depths for metal recovery. A laboratory scale batch reactor was constructed using 316L as suitable construction material. For safety reasons, the inert, stable LiCl–KCl molten salts were used as direct heat transfer fluid. Recovered materials were washed with hot water to remove residual salt before metal recovery assessment. The impact of this work was to show metal separation using molten salts in one single unit, by using this novel reactor methodology. • The reactor is a U-shaped reactor filled with a continuous liquid with a sloped bottom representing a novel reactor concept. • This method uses large PCB pieces instead of shredded PCBs as the reactor volume is 2.2 L. • The treated PCBs can be removed via leg B while the process is on-going. PMID:26150977

  11. Novel waste printed circuit board recycling process with molten salt.

    PubMed

    Riedewald, Frank; Sousa-Gallagher, Maria

    2015-01-01

    The objective of the method was to prove the concept of a novel waste PCBs recycling process which uses inert, stable molten salts as the direct heat transfer fluid and, simultaneously, uses this molten salt to separate the metal products in either liquid (solder, zinc, tin, lead, etc.) or solid (copper, gold, steel, palladium, etc.) form at the operating temperatures of 450-470 °C. The PCB recovery reactor is essentially a U-shaped reactor with the molten salt providing a continuous fluid, allowing molten salt access from different depths for metal recovery. A laboratory scale batch reactor was constructed using 316L as suitable construction material. For safety reasons, the inert, stable LiCl-KCl molten salts were used as direct heat transfer fluid. Recovered materials were washed with hot water to remove residual salt before metal recovery assessment. The impact of this work was to show metal separation using molten salts in one single unit, by using this novel reactor methodology. •The reactor is a U-shaped reactor filled with a continuous liquid with a sloped bottom representing a novel reactor concept.•This method uses large PCB pieces instead of shredded PCBs as the reactor volume is 2.2 L.•The treated PCBs can be removed via leg B while the process is on-going. PMID:26150977

  12. Surface energy of zinc

    SciTech Connect

    Bilello, J.C.; Dew-Hughes, D.; Pucino, A.T.

    1983-04-01

    The influence of temperature and associated dislocation microstructure on the energetics of basal plane cleavage in zinc crystals has been investigated using the method of Hull, Beardmore, and Valentine (HBV). A marked temperature dependence was observed in the zinc surface energy, over the range 77--298 /sup 0/K, contrary to previous expectations. Plastic relaxation was associated with crack initiation at 77 /sup 0/K, but not propagation; while at room temperature a plastic zone of 1200--1500 ..mu..m in depth was produced by crack extension. The surface energy could be estimated, independent of the usual Griffith analysis, by measuring the energy dissipation in a fully relaxed deformed zone associated with an explosively formed precursor crack. This method yielded surface energies of 0.066 to 0.079 J m/sup -2/ which was in good agreement with previous work. It is demonstrated that the cleavage surface energy of zinc is well below the thermodynamic surface energy and that this discrepancy is not related to plastic deformation.

  13. Photochemistry of triarylsulfonium salts

    SciTech Connect

    Dektar, J.L.; Hacker, N.P. )

    1990-08-01

    The photolysis of triphenylsulfonium, tris(4-methylphenyl)sulfonium, tris(4-chlorophenyl)sulfonium, several monosubstituted (4-F, 4-Cl, 4-Me, 4-MeO, 4-PhS, and 4-PhCO), and disubstituted (4,4{prime}-Me{sub 2} and 4,4{prime}-(MeO){sub 2}) triphenylsulfonium salts was examined in solution. It was found that direct irradiation of triphenylsulfonium salts produced new rearrangement products, phenylthiobiphenyls, along with diphenyl sulfide, which had been previously reported. Similarly, the triarylsulfonium salts, with the exception of the (4-(phenylthio)phenyl)diphenylsulfonium salts produced new rearrangement products, phenylthiobiphenyls, along with diphenyl sulfide, which had been previously reported. Similarly, the triarylsulfonium salts, with the exception of the (4-(phenylthio)phenyl)diphenylsulfonium salts, gave the new rearrangement products. The mechanism for direct photolysis is proposed to occur from the singlet excited states to give a predominant heterolytic cleavage along with some homolytic cleavage.

  14. A history of salt.

    PubMed

    Cirillo, M; Capasso, G; Di Leo, V A; De Santo, N G

    1994-01-01

    The medical history of salt begins in ancient times and is closely related to different aspects of human history. Salt may be extracted from sea water, mineral deposits, surface encrustations, saline lakes and brine springs. In many inland areas, wood was used as a fuel source for evaporation of brine and this practice led to major deafforestation in central Europe. Salt played a central role in the economies of many regions, and is often reflected in place names. Salt was also used as a basis for population censuses and taxation, and salt monopolies were practised in many states. Salt was sometimes implicated in the outbreak of conflict, e.g. the French Revolution and the Indian War of Independence. Salt has also been invested with many cultural and religious meanings, from the ancient Egyptians to the Middle Ages. Man's innate appetite for salt may be related to his evolution from predominantly vegetarian anthropoids, and it is noteworthy that those people who live mainly on protein and milk or who drink salty water do not generally salt their food, whereas those who live mainly on vegetables, rice and cereals use much more salt. Medicinal use tended to emphasize the positive aspects of salt, e.g. prevention of putrefaction, reduction of tissue swelling, treatment of diarrhea. Evidence was also available to ancient peoples of its relationship to fertility, particularly in domestic animals. The history of salt thus represents a unique example for studying the impact of a widely used dietary substance on different important aspects of man's life, including medical philosophy.

  15. Iodised salt is safe.

    PubMed

    Ranganathan, S

    1995-01-01

    Iodine deficiency disorders are prevalent in all the States and Union Territories in India. Under the National Iodine Deficiency Disorders control programme, the Government of India has adopted a strategy to iodisation of all edible salt in the country which is a long term and sustainable preventive solution to eliminate iodine deficiency disorders. The benefits to be derived from universal salt iodisation are more to the population. Iodised salt is safe and does not cause any side effect. PMID:8690505

  16. Dosimetry using silver salts

    DOEpatents

    Warner, Benjamin P.

    2003-06-24

    The present invention provides a method for detecting ionizing radiation. Exposure of silver salt AgX to ionizing radiation results in the partial reduction of the salt to a mixture of silver salt and silver metal. The mixture is further reduced by a reducing agent, which causes the production of acid (HX) and the oxidized form of the reducing agent (R). Detection of HX indicates that the silver salt has been exposed to ionizing radiation. The oxidized form of the reducing agent (R) may also be detected. The invention also includes dosimeters employing the above method for detecting ionizing radiation.

  17. Depleted zinc: Properties, application, production.

    PubMed

    Borisevich, V D; Pavlov, A V; Okhotina, I A

    2009-01-01

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  18. Nutrition intervention strategies to combat zinc deficiency in developing countries.

    PubMed

    Gibson, R S; Ferguson, E L

    1998-06-01

    Widespread zinc deficiency is likely to exist in developing countries where staple diets are predominantly plant based and intakes of animal tissues are low. The severe negative consequences of zinc deficiency on human health in developing countries, however, have only recently been recognized. An integrated approach employing targeted supplementation, fortification and dietary strategies must be used to maximize the likelihood of eliminating zinc deficiency at a national level in developing countries. Supplementation is appropriate only for populations whose zinc status must be improved over a relatively short time period, and when requirements cannot be met from habitual dietary sources. As well, the health system must be capable of providing consistent supply, distribution, delivery and consumption of the zinc supplement to the targeted groups. Uncertainties still exist about the type, frequency, and level of supplemental zinc required for prevention and treatment of zinc deficiency. Salts that are readily absorbed and at levels that will not induce antagonistic nutrient interactions must be used. At a national level, fortification with multiple micronutrients could be a cost effective method for improving micronutrient status, including zinc, provided that a suitable food vehicle which is centrally processed is available. Alternatively, fortification could be targeted for certain high risk groups (e.g. complementary foods for infants). Efforts should be made to develop protected fortificants for zinc, so that potent inhibitors of zinc absorption (e.g. phytate) present either in the food vehicle and/or indigenous meals do not compromise zinc absorption. Fortification does not require any changes in the existing food beliefs and practices for the consumer and, unlike supplementation, does not impose a burden on the health sector. A quality assurance programme is required, however, to ensure the quality of the fortified food product from production to consumption

  19. Innovative uses for zinc in dermatology.

    PubMed

    Bae, Yoon Soo; Hill, Nikki D; Bibi, Yuval; Dreiher, Jacob; Cohen, Arnon D

    2010-07-01

    Severe zinc deficiency states, such as acrodermatitis enteropathica, are associated with a variety of skin manifestations, such as perioral, acral, and perineal dermatitis. These syndromes can be reversed with systemic zinc repletion. In addition to skin pathologies that are clearly zinc-dependent, many dermatologic conditions (eg, dandruff, acne, and diaper rash) have been associated and treated with zinc. Success rates for treatment with zinc vary greatly depending on the disease, mode of administration, and precise zinc preparation used. With the exception of systemic zinc deficiency states, there is little evidence that convincingly demonstrates the efficacy of zinc as a reliable first-line treatment for most dermatologic conditions. However, zinc may be considered as an adjunctive treatment modality. Further research is needed to establish the indications for zinc treatment in dermatology, optimal mode of zinc delivery, and best type of zinc compound to be used. PMID:20510767

  20. Comparative effects of zinc-nano complexes, zinc-sulphate and zinc-methionine on performance in broiler chickens.

    PubMed

    Mohammadi, V; Ghazanfari, S; Mohammadi-Sangcheshmeh, A; Nazaran, M H

    2015-01-01

    Micronutrients, especially zinc, have an important role in normal metabolism and growth of broilers. Using novel technologies helps to synthesise novel zinc complexes to deliver this micronutrient more efficiently. In the present study, the effects of different zinc complexes and nano complexes on broiler performance were compared. Broilers in 6 groups were given basal diet (without zinc) and basal diet supplemented with zinc-sulphate, zinc-methionine, zinc-nano-sulphate, zinc-nano-methionine and zinc-nano-max (that was synthesised based on nanochelating technology) at a concentration of 80 mg/kg of diet. At 1-42 d of age, dietary zinc-nano-sulphate supplementation decreased weight gain and feed intake. However, feed conversion ratio was not influenced by treatments. Carcass yield (%) of birds in the zinc-nano-sulphate and control groups were dramatically reduced at 42 d of age and abdominal fat (%) increased in these groups. Relative to the control group, the antibody titre, spleen and bursa of Fabricius (%) were significantly higher in groups supplemented with zinc. Heterophil (%) was also significantly higher in the zinc-nano-methionine group in blood on d 42 compared to the control, zinc-sulphate and zinc-nano-sulphate. Compared to the controls, the mean malondialdehyde content in thigh tissue was significantly reduced in groups supplemented with zinc at the time 0, 50, 100 and 150 min after oxidation. Tibia zinc concentration in nanoparticle zinc samples was significantly higher relative to the control and zinc-sulphate groups. Taken together, our data indicate that delivery of zinc in the structure of zinc-nano-methionine and zinc-nano-max at concentrations of 80 mg/kg of diet improves growth performance. However, dietary zinc-nano-sulphate decreased growth performance in broilers.

  1. Uptake and partitioning of zinc in Lemnaceae.

    PubMed

    Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

    2011-11-01

    Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility. PMID:21755349

  2. Increased levels of hepatic and renal metallothionein in the rat and guinea pig after percutaneous application of zinc chloride

    SciTech Connect

    Wormser, U.; BenZakine, S. )

    1991-02-01

    Metallothionein (MT) is a cytoplasmic, low molecular weight, cysteine rich, heat stable protein. It was detected in various organs including liver, spleen, pancreas, testes, lung, intestine, brain, heart, adrenal, lacrimal and parotid glands. The most powerful inducers of metallothionein are cadmium and zinc. Water soluble zinc salts are common contaminants of the environment. In the present study dose-response relationship and the cumulative effect of topically applied zinc chloride have been demonstrated. For comparison, metal-binding protein induction by the same route of exposure has been also tested in the guinea pig.

  3. Progress in Studying Salt Secretion from the Salt Glands in Recretohalophytes: How Do Plants Secrete Salt?

    PubMed Central

    Yuan, Fang; Leng, Bingying; Wang, Baoshan

    2016-01-01

    To survive in a saline environment, halophytes have evolved many strategies to resist salt stress. The salt glands of recretohalophytes are exceptional features for directly secreting salt out of a plant. Knowledge of the pathway(s) of salt secretion in relation to the function of salt glands may help us to change the salt-tolerance of crops and to cultivate the extensive saline lands that are available. Recently, ultrastructural studies of salt glands and the mechanism of salt secretion, particularly the candidate genes involved in salt secretion, have been illustrated in detail. In this review, we summarize current researches on salt gland structure, salt secretion mechanism and candidate genes involved, and provide an overview of the salt secretion pathway and the asymmetric ion transport of the salt gland. A new model recretohalophyte is also proposed. PMID:27446195

  4. SALT for Language Acquisition.

    ERIC Educational Resources Information Center

    Bancroft, W. Jane

    1996-01-01

    Discusses Schuster's Suggestive-Accelerative Learning Techniques (SALT) Method, which combines Lozanov's Suggestopedia with such American methods as Asher's Total Physical Response and Galyean's Confluent Education. The article argues that students trained with the SALT Method have higher achievement scores and better attitudes than others. (14…

  5. Hydroxycarboxylic acids and salts

    DOEpatents

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  6. Utah: Salt Lake City

    Atmospheric Science Data Center

    2014-05-15

    ... backdrops for the 2002 Winter Olympics, to be held in Salt Lake City, Utah. The mountains surrounding Salt Lake City are renowned for ... western edge of the Rocky Mountains and eastern rim of the Great Basin. This early-winter image pair was acquired by the Multi-angle ...

  7. Molten salt electrolyte separator

    DOEpatents

    Kaun, T.D.

    1996-07-09

    The patent describes a molten salt electrolyte/separator for battery and related electrochemical systems including a molten electrolyte composition and an electrically insulating solid salt dispersed therein, to provide improved performance at higher current densities and alternate designs through ease of fabrication. 5 figs.

  8. Integrated Salt Studies

    NASA Astrophysics Data System (ADS)

    Urai, Janos L.; Kukla, Peter A.

    2015-04-01

    The growing importance of salt in the energy, subsurface storage, and chemical and food industries also increases the challenges with prediction of geometries, kinematics, stress and transport in salt. This requires an approach, which integrates a broader range of knowledge than is traditionally available in the different scientific and engineering disciplines. We aim to provide a starting point for a more integrated understanding of salt, by presenting an overview of the state of the art in a wide range of salt-related topics, from (i) the formation and metamorphism of evaporites, (ii) rheology and transport properties, (iii) salt tectonics and basin evolution, (iv) internal structure of evaporites, (v) fluid flow through salt, to (vi) salt engineering. With selected case studies we show how integration of these domains of knowledge can bring better predictions of (i) sediment architecture and reservoir distribution, (ii) internal structure of salt for optimized drilling and better cavern design, (iii) reliable long-term predictions of deformations and fluid flow in subsurface storage. A fully integrated workflow is based on geomechanical models, which include all laboratory and natural observations and links macro- and micro-scale studies. We present emerging concepts for (i) the initiation dynamics of halokinesis, (ii) the rheology and deformation of the evaporites by brittle and ductile processes, (iii) the coupling of processes in evaporites and the under- and overburden, and (iv) the impact of the layered evaporite rheology on the structural evolution.

  9. Hydrothermal synthesis of zinc oxide nanoparticles using rice as soft biotemplate

    PubMed Central

    2013-01-01

    Background Rice as a renewable, abundant bio-resource with unique characteristics can be used as a bio-template to synthesize various functional nanomaterials. Therefore, the effect of uncooked rice flour as bio-template on physico-chemical properties, especially the morphology of zinc oxide nanostructures was investigated in this study. The ZnO particles were synthesized through hydrothermal-biotemplate method using zinc acetate-sodium hydroxide and uncooked rice flour at various ratios as precursors at 120°C for 18 hours. Results The results indicate that rice as a bio-template can be used to modify the shape and size of zinc oxide particles. Different morphologies, namely flake-, flower-, rose-, star- and rod-like structures were obtained with particle size at micro- and nanometer range. Pore size and texture of the resulting zinc oxide particles were found to be template-dependent and the resulting specific surface area enhanced compared to the zinc oxide synthesized without rice under the same conditions. However, optical property particularly the band gap energy is generally quite similar. Conclusion Pure zinc oxide crystals were successfully synthesized using rice flour as biotemplate at various ratios of zinc salt to rice. The size- and shape-controlled capability of rice to assemble the ZnO particles can be employed for further useful practical applications. PMID:23919386

  10. Position on zinc delivery to olfactory nerves in intranasal insulin phase I-III clinical trials.

    PubMed

    Hamidovic, A

    2015-11-01

    Zinc in pancreatic insulin is essential for processing and action of the peptide, while in commercial preparations zinc promotes hexameric structure and prevents aggregate formation. In 2002, for the first time, insulin was delivered to humans intranasally with resulting cerebrospinal fluid insulin increases, but steady peripheral insulin levels. The novel method of increasing brain insulin levels without changes in the periphery resulted in an expansion of brain insulin research in clinical trials. As pre-clinical research has shown that brain insulin modulates a number functions, including food cravings and eating behavior, learning and memory functions, stress and mood regulation; realization of beneficial effects of insulin in modulating these functions in clinical populations became a possibility with the new direct-to-brain insulin delivery methodology. However, zinc, being integral to insulin structure and function, is neurotoxic, and has resulted in adverse effects to human health. In the last century, intranasal zinc was given preventively during the time of polio outbreak, and in the 21st century intranasal zinc was widely used over the counter to prevent common cold. In both cases, patients experienced partial or complete loss of smell. This paper is the first one to analyze zinc salts and concentrations of those two epidemiological adversities and directly compare formulations distributed to the public with animal toxicity data. The information gained from animal and epidemiological data provides a foundation for the formation of opinion given in this paper regarding safety of intranasal zinc in emerging clinical trials with intranasal insulin.

  11. [Salt and cancer].

    PubMed

    Strnad, Marija

    2010-05-01

    Besides cardiovascular disease, a high salt intake causes other adverse health effects, i.e., gastric and some other cancers, obesity (risk factor for many cancer sites), Meniere's disease, worsening of renal disease, triggering an asthma attack, osteoporosis, exacerbation of fluid retention, renal calculi, etc. Diets containing high amounts of food preserved by salting and pickling are associated with an increased risk of cancers of the stomach, nose and throat. Because gastric cancer is still the most common cancer in some countries (especially in Japan), its prevention is one of the most important aspects of cancer control strategy. Observations among Japanese immigrants in the U.S.A. and Brazil based on the geographic differences, the trend in cancer incidence with time, and change in the incidence patterns indicate that gastric cancer is closely associated with dietary factors such as the intake of salt and salted food. The findings of many epidemiological studies suggest that high dietary salt intake is a significant risk factor for gastric cancer and this association was found to be strong in the presence of Helicobacter (H.) pylori infection with atrophic gastritis. A high-salt intake strips the lining of the stomach and may make infection with H. pylori more likely or may exacerbate the infection. Salting, pickling and smoking are traditionally popular ways of preparing food in Japan and some parts of Asia. In addition to salt intake, cigarette smoking and low consumption of fruit and vegetables increase the risk of stomach cancer. However, it is not known whether it is specifically the salt in these foods or a combination of salt and other chemicals that can cause cancer. One study identified a mutagen in nitrite-treated Japanese salted fish, and chemical structure of this mutagen suggests that it is derived from methionine and that salt and nitrite are precursors for its formation. Working under conditions of heat stress greatly increased the workers

  12. Effect of anions on the electrochemistry of zinc tetraphenylporphyrin

    SciTech Connect

    Seely, G.R.; Gust, D.; Moore, T.A.; Moore, A.L. )

    1994-10-13

    Accurate measurements of porphyrin redox potentials are essential for the prediction and rationalization of the rates of electron transfer reactions involving these biologically important electron-donating and accepting chromophores. The present work describes a survey of redox potentials of zinc tetraphenylporphyrin obtained by cyclic voltammetry in dichloromethane, with tetrabutylammonium salts containing a variety of anions as electrolytes. Of the anions tested, hexafluorophosphate appears to have the least ability to ligate the metal, so that potentials measured in its presence as electrolyte should most closely approach those of the unligated porphyrin. With perchlorate electrolyte, the potential for one-electron oxidation is approximately 80 mV lower, enough to affect the interpretation of photochemical electron transfer rates. In general, anions bind much more strongly to the cation radical than to zinc tetraphenylporphyrin itself. The use of reference redox systems based on thymoquinone and ferrocene carboxylate enabled comparison of potentials measured with different electrolytes. 30 refs., 2 tabs.

  13. Arsenic doped zinc oxide

    SciTech Connect

    Volbers, N.; Lautenschlaeger, S.; Leichtweiss, T.; Laufer, A.; Graubner, S.; Meyer, B. K.; Potzger, K.; Zhou Shengqiang

    2008-06-15

    As-doping of zinc oxide has been approached by ion implantation and chemical vapor deposition. The effect of thermal annealing on the implanted samples has been investigated by using secondary ion mass spectrometry and Rutherford backscattering/channeling geometry. The crystal damage, the distribution of the arsenic, the diffusion of impurities, and the formation of secondary phases is discussed. For the thin films grown by vapor deposition, the composition has been determined with regard to the growth parameters. The bonding state of arsenic was investigated for both series of samples using x-ray photoelectron spectroscopy.

  14. Zinc Oxide Nanophotonics

    NASA Astrophysics Data System (ADS)

    Choi, Sumin; Aharonovich, Igor

    2015-12-01

    The emerging field of nanophotonics initiated a dedicated study of single photon sources and optical resonators in new class of materials. One such material is zinc oxide (ZnO) that has been long considered only for classical light-emitting applications. However, it recently showed promise for quantum photonics technologies. In this review, we highlight the recent advances in studying single emitters in ZnO, engineering of optical cavities and practical nanophotonics devices including nanolasers and electrically triggered devices. We finalize with an outlook at this promising area, as well as provide perspectives and open questions in solid state nanophotonics employing ZnO.

  15. Hydrometallurgical process for zinc recovery from electric arc furnace dust (EAFD). Part II: Downstream processing and zinc recovery by electrowinning.

    PubMed

    Tsakiridis, P E; Oustadakis, P; Katsiapi, A; Agatzini-Leonardou, S

    2010-07-15

    The characterization and the agitation leaching of electric arc furnace dust (EAFD) by diluted sulphuric acid have been studied in Part I, as a separate article. The aim of the present research work (Part II) is the development of a purification process of the leach liquor for the recovery of high-purity zinc by electrowinning. The proposed hydrometallurgical process consists of the following four (4) unit operations: (1) Removal of iron as easily filterable crystalline basic sulphate salt of the jarosite type, at atmospheric pressure, by chemical precipitation at pH: 3.5 and 95 degrees C. (2) Zinc solvent extraction by Cyanex 272 at pH: 3.5, T: 40 degrees C, with 25% extractant concentration. (3) Stripping of the loaded organic phase by zinc spent electrolyte (62.5 g/L Zn(2+)) at T: 40 degrees C with diluted H(2)SO(4) (3 mol/L). (4) Zinc electrowinning from sulphate solutions (at 38 degrees C) using Al as cathode and Pb as anode. The acidity of the electrolyte was fixed at 180 g/L H(2)SO(4), while the current density was kept constant at 500 A/m(2). PMID:20434263

  16. Hydrometallurgical process for zinc recovery from electric arc furnace dust (EAFD). Part II: Downstream processing and zinc recovery by electrowinning.

    PubMed

    Tsakiridis, P E; Oustadakis, P; Katsiapi, A; Agatzini-Leonardou, S

    2010-07-15

    The characterization and the agitation leaching of electric arc furnace dust (EAFD) by diluted sulphuric acid have been studied in Part I, as a separate article. The aim of the present research work (Part II) is the development of a purification process of the leach liquor for the recovery of high-purity zinc by electrowinning. The proposed hydrometallurgical process consists of the following four (4) unit operations: (1) Removal of iron as easily filterable crystalline basic sulphate salt of the jarosite type, at atmospheric pressure, by chemical precipitation at pH: 3.5 and 95 degrees C. (2) Zinc solvent extraction by Cyanex 272 at pH: 3.5, T: 40 degrees C, with 25% extractant concentration. (3) Stripping of the loaded organic phase by zinc spent electrolyte (62.5 g/L Zn(2+)) at T: 40 degrees C with diluted H(2)SO(4) (3 mol/L). (4) Zinc electrowinning from sulphate solutions (at 38 degrees C) using Al as cathode and Pb as anode. The acidity of the electrolyte was fixed at 180 g/L H(2)SO(4), while the current density was kept constant at 500 A/m(2).

  17. Associations among dietary zinc intakes and biomarkers of zinc status before and after a zinc supplementation program in Guatemalan schoolchildren

    PubMed Central

    Bui, Vinh Q.; Marcinkevage, Jessica; Ramakrishnan, Usha; Flores-Ayala, Rafael C.; Ramirez-Zea, Manuel; Villalpando, Salvador; Martorell, Reynaldo; DiGirolamo, Ann M.; Stein, Aryeh D.

    2015-01-01

    Background The associations among dietary zinc intakes and biomarkers of zinc status are unknown in apparently healthy children at high risk for zinc deficiency. Objective To assess associations among zinc-related parameters in a sample of Guatemalan school-aged children. Methods We assessed total dietary intakes and biomarkers of zinc status before and after receiving 6 months of zinc supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years. Most of the children also received zinc-fortified milk from a government program that started shortly after the trial began. We assessed associations between zinc intakes and serum zinc, alkaline phosphatase (ALP), and albumin. Results At baseline, the prevalence of serum zinc < 65 μg/dL and dietary zinc intake below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9 and ≥ 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson correlations between serum zinc concentration and dietary zinc intake, serum ALP, and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes were observed in 1.2% and 0.0% of children in the zinc-supplemented group and 4.0% and 34.1% in the placebo group, respectively. Pearson correlations between serum zinc concentration and total zinc intake, serum ALP, and serum albumin were 0.10, 0.06, and −0.11 in the zinc-supplemented group and −0.04, 0.05, and 0.01 in the placebo group, respectively. Conclusions Zinc intake was inconsistently associated with markers of serum zinc concentration. Zinc fortification or supplementation attenuated the associations. PMID:23964387

  18. Methanol conversion over metal salts of 12-tungstophosphoric acid

    SciTech Connect

    Hayashi, H.; Moffat, J.B.

    1983-05-01

    The sodium, boron, calcium, magnesium, zinc, aluminum, and zirconium salts of 12-tungstophosphoric acid have been prepared and characterized using x-ray diffraction, mercury porosimetry, the chemisorption of ammonia, and Hammett indicators. Methanol conversion at 350/sup 0/C and a variety of residence times produced hydrocarbons ranging from C/sub 1/ to C/sub 5/ in amounts which varied with the cation. The more strongly acidic salts produced the higher yields of hydrocarbons. The maximum yield of the major product C/sub 4/ was found with the aluminum salt. The activities were related to the partial change on the oxygen atoms in the various catalysts. 3 figures, 1 table.

  19. Water purification using organic salts

    DOEpatents

    Currier, Robert P.

    2004-11-23

    Water purification using organic salts. Feed water is mixed with at least one organic salt at a temperature sufficiently low to form organic salt hydrate crystals and brine. The crystals are separated from the brine, rinsed, and melted to form an aqueous solution of organic salt. Some of the water is removed from the aqueous organic salt solution. The purified water is collected, and the remaining more concentrated aqueous organic salt solution is reused.

  20. Crushed Salt Constitutive Model

    SciTech Connect

    Callahan, G.D.

    1999-02-01

    The constitutive model used to describe the deformation of crushed salt is presented in this report. Two mechanisms -- dislocation creep and grain boundary diffusional pressure solution -- are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. Upon complete consolidation, the crushed-salt model reproduces the Multimechanism Deformation (M-D) model typically used for the Waste Isolation Pilot Plant (WIPP) host geological formation salt. New shear consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on WIPP and southeastern New Mexico salt. Nonlinear least-squares model fitting to the database produced two sets of material parameter values for the model -- one for the shear consolidation tests and one for a combination of the shear and hydrostatic consolidation tests. Using the parameter values determined from the fitted database, the constitutive model is validated against constant strain-rate tests. Shaft seal problems are analyzed to demonstrate model-predicted consolidation of the shaft seal crushed-salt component. Based on the fitting statistics, the ability of the model to predict the test data, and the ability of the model to predict load paths and test data outside of the fitted database, the model appears to capture the creep consolidation behavior of crushed salt reasonably well.

  1. Exposure to Zinc Sulfate Results in Differential Effects on Olfactory Sensory Neuron Subtypes in Adult Zebrafish

    PubMed Central

    Hentig, James T.; Byrd-Jacobs, Christine A.

    2016-01-01

    Zinc sulfate is a known olfactory toxicant, although its specific effects on the olfactory epithelium of zebrafish are unknown. Olfactory organs of adult zebrafish were exposed to zinc sulfate and, after 2, 3, 5, 7, 10 or 14 days, fish were processed for histological, immunohistochemical, ultrastructural, and behavioral analyses. Severe morphological disruption of the olfactory organ was observed two days following zinc sulfate exposure, including fusion of lamellae, epithelial inflammation, and significant loss of anti-calretinin labeling. Scanning electron microscopy revealed the apical surface of the sensory region was absent of ciliated structures, but microvilli were still present. Behavioral analysis showed significant loss of the ability to perceive bile salts and some fish also had no response to amino acids. Over the next several days, olfactory organ morphology, epithelial structure, and anti-calretinin labeling returned to control-like conditions, although the ability to perceive bile salts remained lost until day 14. Thus, exposure to zinc sulfate results in rapid degeneration of the olfactory organ, followed by restoration of morphology and function within two weeks. Zinc sulfate appears to have a greater effect on ciliated olfactory sensory neurons than on microvillous olfactory sensory neurons, suggesting differential effects on sensory neuron subtypes. PMID:27589738

  2. Exposure to Zinc Sulfate Results in Differential Effects on Olfactory Sensory Neuron Subtypes in Adult Zebrafish.

    PubMed

    Hentig, James T; Byrd-Jacobs, Christine A

    2016-01-01

    Zinc sulfate is a known olfactory toxicant, although its specific effects on the olfactory epithelium of zebrafish are unknown. Olfactory organs of adult zebrafish were exposed to zinc sulfate and, after 2, 3, 5, 7, 10 or 14 days, fish were processed for histological, immunohistochemical, ultrastructural, and behavioral analyses. Severe morphological disruption of the olfactory organ was observed two days following zinc sulfate exposure, including fusion of lamellae, epithelial inflammation, and significant loss of anti-calretinin labeling. Scanning electron microscopy revealed the apical surface of the sensory region was absent of ciliated structures, but microvilli were still present. Behavioral analysis showed significant loss of the ability to perceive bile salts and some fish also had no response to amino acids. Over the next several days, olfactory organ morphology, epithelial structure, and anti-calretinin labeling returned to control-like conditions, although the ability to perceive bile salts remained lost until day 14. Thus, exposure to zinc sulfate results in rapid degeneration of the olfactory organ, followed by restoration of morphology and function within two weeks. Zinc sulfate appears to have a greater effect on ciliated olfactory sensory neurons than on microvillous olfactory sensory neurons, suggesting differential effects on sensory neuron subtypes. PMID:27589738

  3. Microstructural Study Of Zinc Hot Dip Galvanized Coatings with Titanium Additions In The Zinc Melt

    NASA Astrophysics Data System (ADS)

    Konidaris, S.; Pistofidis, N.; Vourlias, G.; Pavlidou, E.; Stergiou, A.; Stergioudis, G.; Polychroniadis, E. K.

    2007-04-01

    Zinc hot-dip galvanizing is a method for protecting iron and steel against corrosion. Galvanizing with pure Zn or Zn with additions like Ni, Al, Pb and Bi has been extensively studied, but there is a lack of scientific information about other additions. The present work examines the effect of a 0.5 wt% Ti addition in the Zn melt. The samples were exposed to accelerated corrosion in a salt spray chamber (SSC). The microstructure and chemical composition of the coatings were determined by Optical Microscopy, XRD and SEM associated with an EDS Analyzer. The results indicate that the coatings have a typical morphology, while Zn-Ti phases were also detected.

  4. 76 FR 51992 - Determination That PENTETATE ZINC TRISODIUM (Zinc Trisodium Diethylenetriaminepentaacetate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... HUMAN SERVICES Food and Drug Administration Determination That PENTETATE ZINC TRISODIUM (Zinc Trisodium... Administration (FDA) has determined that PENTETATE ZINC TRISODIUM (zinc trisodium diethylenetriaminepentaacetate... PENTETATE ZINC TRISODIUM (Zn-DTPA) solution for intravenous or inhalation administration (EQ 1 g base/5...

  5. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc...

  6. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc...

  7. 21 CFR 522.2690 - Zinc gluconate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc gluconate. 522.2690 Section 522.2690 Food and..., FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2690 Zinc gluconate. (a) Specifications. Each milliliter of solution contains 13.1 milligrams zinc as zinc...

  8. Regeneration of zinc chloride hydrocracking catalyst

    DOEpatents

    Zielke, Clyde W.

    1979-01-01

    Improved rate of recovery of zinc values from the solids which are carried over by the effluent vapors from the oxidative vapor phase regeneration of spent zinc chloride catalyst is achieved by treatment of the solids with both hydrogen chloride and calcium chloride to selectively and rapidly recover the zinc values as zinc chloride.

  9. Zinc Bells Rang in Jerusalem!

    PubMed Central

    Hershfinkel, Michal; Aizenman, Elias; Andrews, Glen; Sekler, Israel

    2010-01-01

    “Oh, Jerusalem of gold, and of light, and of bronze…” goes the popular song. But it was another metal that towered above the Jerusalem landscape during the meeting of the International Society for Zinc Biology (ISZB; http://www.iszb.org/), held at Mishkenot Sha’ananim, a whisper away from the Old City walls. More than 100 scientists gathered on 1 to 5 December 2009 to discuss their research on the biology of this metal. Zinc is a double-edged sword. Zinc supplementation accelerates wound healing and growth and promotes an effective immune response. On the other hand, zinc deficiency leads to growth retardation and impaired learning and memory function, and has been linked to mood disorders. At the cellular level, however, uncontrolled increases in zinc concentrations can lead to neuronal cell death and may be involved in neurodegenerative disorders. Through regulation of various intracellular signaling pathways, zinc can accelerate cell growth and possibly contribute to cancer. However, despite the physiological and clinical importance of this metal, research on the molecular basis of these effects is still in its infancy. The 2009 ISZB meeting provided a venue for investigators working on various zinc-related issues to share their thoughts and ideas and to promote the growth of this field. PMID:20606213

  10. Statins reverse renal inflammation and endothelial dysfunction induced by chronic high salt intake.

    PubMed

    Fiore, M C; Jimenez, P M; Cremonezzi, D; Juncos, L I; García, N H

    2011-08-01

    High salt intake (HS) is a risk factor for cardiovascular and kidney disease. Indeed, HS may promote blood-pressure-independent tissue injury via inflammatory factors. The lipid-lowering 3-hydroxy 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors exert beneficial lipid-independent effects, reducing the expression and synthesis of inflammatory factors. We hypothesized that HS impairs kidney structure and function in the absence of hypertension, and these changes are reversed by atorvastatin. Four groups of rats were treated for 6 wk in metabolic cages with their diets: normal salt (NS); HS, NS plus atorvastatin and HS plus atorvastatin. We measured basal and final body weight, urinary sodium and protein excretion (U(Prot)V), and systolic blood pressure (SBP). At the end of the experimental period, cholesterolemia, creatinine clearance, renal vascular reactivity, glomerular volume, cortical and glomerular endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-β1 expression were measured. We found no differences in SBP, body weight, and cholesterolemia. HS rats had increased creatinine clearence, U(Prot)V, and glomerular volume at the end of the study. Acetylcholine-induced vasodilatation decreased by 40.4% in HS rats (P < 0.05). HS decreased cortical and glomerular eNOS and caused mild glomerular sclerosis, interstitial mononuclear cell infiltration, and increased cortical expression of TGF-β1. All of these salt-induced changes were reversed by atorvastatin. We conclude that long-term HS induces inflammatory and hemodynamic changes in the kidney that are independent of SBP. Atorvastatin corrected all, suggesting that the nitric oxide-oxidative stress balance plays a significant role in the earlier stages of salt induced kidney damage.

  11. Cooking without salt

    MedlinePlus

    ... flavor and nutrition. Plant-based foods -- carrots, spinach, apples, and peaches -- are naturally salt-free. Sun-dried ... types of pepper, including black, white, green, and red. Experiment with vinegars (white and red wine, rice ...

  12. Molten salt electrochemistry

    SciTech Connect

    Gallegos, U.F.; Williamson, M.A.

    1997-12-31

    The objective of this work is to develop preparation and clean-up processes for the fuel and carrier salt used in the Los Alamos Accelerator-Driven Transmutation Technology molten salt nuclear system. The front-end or fuel preparation process focuses on the removal of fission products, uranium, and zirconium from spent nuclear fuel by utilizing electrochemical methods. The same method provide the separation of the transition metal fission products at the back end of the fuel cycle. Molten salts provide a natural medium for the separation of actinides and fission products from one another because they are robust, radiation resistant solvents that can be recycled. The presentation will describe the design of the electrochemistry system, the method used for salt purification, and results of preliminary experiments.

  13. Shaking the Salt Habit

    MedlinePlus

    ... use the pepper shaker or mill. Add fresh lemon juice instead of salt to season fish and ... soups, salads, vegetables, tomatoes, potatoes Ginger: Chicken, fruits Lemon juice: Lean meats, fish, poultry, salads, vegetables Mace: ...

  14. Amine salts of nitroazoles

    DOEpatents

    Kienyin Lee; Stinecipher, M.M.

    1993-10-26

    Compositions of matter, a method of providing chemical energy by burning said compositions, and methods of making said compositions are described. These compositions are amine salts of nitroazoles. 1 figure.

  15. Electrodialysis technology for salt recovery from aluminum salt cake

    SciTech Connect

    Hryn, J. N.; Krumdick, G.; Graziano, D.; Sreenivasarao, K.

    2000-02-02

    Electrodialysis technology for recovering salt from aluminum salt cake is being developed at Argonne National Laboratory. Salt cake, a slag-like aluminum-industry waste stream, contains aluminum metal, salt (NaCl and KCl), and nonmetallics (primarily aluminum oxide). Salt cake can be recycled by digesting with water and filtering to recover the metal and oxide values. A major obstacle to widespread salt cake recycling is the cost of recovering salt from the process brine. Electrodialysis technology developed at Argonne appears to be a cost-effective approach to handling the salt brines, compared to evaporation or disposal. In Argonne's technology, the salt brine is concentrated until salt crystals are precipitated in the electrodialysis stack; the crystals are recovered downstream. The technology is being evaluated on the pilot scale using Eurodia's EUR 40-76-5 stack.

  16. Electrodeposited Zinc-Nickel as an Alternative to Cadmium Plating for Aerospace Application

    NASA Technical Reports Server (NTRS)

    Mcmillan, V. C.

    1991-01-01

    Corrosion evaluation studies were conducted on 4130 alloy steel samples coated with electrodeposited zinc-nickel and samples coated with electrodeposited cadmium. The zinc nickel was deposited by the selection electrochemical metallizing process. These coated samples were exposed to a 5-percent salt fog environment at 35 plus or minus 2 C for a period ranging from 96 to 240 hours. An evaluation of the effect of dichromate coatings on the performance of each plating was conducted. The protection afforded by platings with a dichromate seal was compared to platings without the seal. During the later stages of testing, deposit adhesion and the potential for hydrogen entrapment were also evaluated.

  17. Zinc - an indispensable micronutrient.

    PubMed

    Sharma, Ashish; Patni, Babita; Shankhdhar, Deepti; Shankhdhar, S C

    2013-01-01

    Availability of Zn to plant is hampered by its immobile nature and adverse soil conditions. Thus, Zn deficiency is observed even though high amount is available in soil. Root-shoot barrier, a major controller of zinc transport in plant is highly affected by changes in the anatomical structure of conducting tissue and adverse soil conditions like pH, clay content, calcium carbonate content, etc. Zn deficiency results in severe yield losses and in acute cases plant death. Zn deficiency in edible plant parts results in micronutrient malnutrition leading to stunted growth and improper sexual development in humans. To overcome this problem several strategies have been used to enrich Zn availability in edible plant parts, including nutrient management, biotechnological tools, and classical and molecular breeding approaches. PMID:24381434

  18. Removal of uranium from spent salt from the moltensalt oxidation process

    SciTech Connect

    Summers, L.; Hsu, P. C.; Holtz, E. V.; Hipple, D.; Wang, F.; Adamson, M.

    1997-03-01

    Molten salt oxidation (MSO) is a thermal process that has the capability of destroying organic constituents of mixed wastes, hazardous wastes, and energetic materials. In this process, combustible waste and air are introduced into the molten sodium carbonate salt. The organic constituents of the waste materials are oxidized to carbon dioxide and water, while most of the inorganic constituents, including toxic metals, minerals, and radioisotopes, are retained in the molten salt bath. As these impurities accumulate in the salt, the process efficiency drops and the salt must be replaced. An efficient process is needed to separate these toxic metals, minerals, and radioisotopes from the spent carbonate to avoid generating a large volume of secondary waste. Toxic metals such as cadmium, chromium, lead, and zinc etc. are removed by a method described elsewhere. This paper describes a separation strategy developed for radioisotope removal from the mixed spent salt, as well as experimental results, as part of the spent salt cleanup. As the MSO system operates, inorganic products resulting from the reaction of halides, sulfides, phosphates, metals and radionuclides with carbonate accumulate in the salt bath. These must be removed to prevent complete conversion of the sodium carbonate, which would result in eventual losses of destruction efficiency and acid scrubbing capability. There are two operational modes for salt removal: (1) during reactor operation a slip-stream of molten salt is continuously withdrawn with continuous replacement by carbonate, or (2) the spent salt melt is discharged completely and the reactor then refilled with carbonate in batch mode. Because many of the metals and/or radionuclides captured in the salt are hazardous and/or radioactive, spent salt removed from the reactor would create a large secondary waste stream without further treatment. A spent salt clean up/recovery system is necessary to segregate these materials and minimize the amount of

  19. Mass transport in bedded salt and salt interbeds

    SciTech Connect

    Hwang, Y.; Pigford, T.H.; Chambre, P.L.; Lee, W.W.L.

    1989-08-01

    Salt is the proposed host rock for geologic repositories of nuclear waste in several nations because it is nearly dry and probably impermeable. Although experiments and experience at potential salt sites indicate that salt may contain brine, the low porosity, creep, and permeability of salt make it still a good choice for geologic isolation. In this paper we summarize several mass-transfer and transport analyses of salt repositories. The mathematical details are given in our technical reports.

  20. Salt Lake City, Utah

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Salt Lake City, Utah, will host the 2002 Winter Olympic Games. The city is located on the southeastern shore of the Great Salt Lake and sits to the west of the Wasatch Mountains, which rise more than 3,500 meters (10,000 feet) above sea level. The city was first settled in 1847 by pioneers seeking relief from religious persecution. Today Salt Lake City, the capital of Utah, is home to more than 170,000 residents. This true-color image of Salt Lake City was acquired by the Enhanced Thematic Mapper Plus (ETM+), flying aboard Landsat 7, on May 26, 2000. The southeastern tip of the Great Salt Lake is visible in the upper left of the image. The furrowed green and brown landscape running north-south is a portion of the Wasatch Mountains, some of which are snow-capped (white pixels). The greyish pixels in the center of the image show the developed areas of the city. A number of water reservoirs can be seen east of the mountain range. Salt Lake City International Airport is visible on the northwestern edge of the city. About 20 miles south of the airport is the Bingham Canyon Copper Mine (tan pixels), the world's largest open pit excavation. See also this MODIS image of Utah. Image courtesy NASA Landsat7 Science Team and USGS Eros Data Center

  1. Mineral resource of the month: zinc

    USGS Publications Warehouse

    Tolcin, Amy C.

    2009-01-01

    The article provides information on zinc, the fourth most-widely consumed metal. It traces the first use of zinc with the Romans' production of brass. It describes the presence of zinc in Earth's crust and the importance of sphalerite as a source of zinc and other some minor metal production. The production and consumption of zinc as well as the commercial and industrial uses of this metal are also discussed.

  2. Zinc tolerance and zinc removal ability of living and dried biomass of Desmodesmus communis.

    PubMed

    Novák, Zoltán; Jánószky, Mihály; B-Béres, Viktória; Nagy, Sándor Alex; Bácsi, István

    2014-12-01

    Effects of zinc on growth, cell morphology, oxidative stress, and zinc removal ability of the common phytoplankton species Desmodesmus communis were investigated at a concentration range of 0.25-160 mg L(-1) zinc. Cell densities and chlorophyll content decreased in treated cultures, changes in coenobia morphology and elevated lipid peroxidation levels appeared above 2.5 mg L(-1) zinc. The most effective zinc removal was observed at 5 mg L(-1) zinc concentration, while maximal amount of removed zinc appeared in 15 mg L(-1) zinc treated culture. Removed zinc is mainly bound on the cell surface. Dead biomass adsorbed more zinc than living biomass relative to unit of dry mass, but living biomass was more effective, relative to initial zinc content. This study comprehensively examines the zinc tolerance and removal ability of D. communis and demonstrates, in comparison with published literature, that these characteristics of different isolates of the same species can vary within a wide range. PMID:25193446

  3. Zinc toxicology following particulate inhalation.

    PubMed

    Cooper, Ross G

    2008-04-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl(2) inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection.

  4. Zinc toxicology following particulate inhalation

    PubMed Central

    Cooper, Ross G.

    2008-01-01

    The current mini-review describes the toxic effects of zinc inhalation principally in the workplace and associated complications with breathing and respiration. The International Classification of Functioning, Disability and Health Criteria were used to specifically select articles. Most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever associated with inhalation of fumes of ZnO is characterized by fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and salivation. ZnCl2 inhalation results in edema in the alveolar surface and the protein therein the lavage fluid is elevated. Particular pathological changes associated with zinc intoxication include: pale mucous membranes; jaundice; numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for permissible exposure limits, excellent ventilation and extraction systems, and approved respirators are all important in providing adequate protection. PMID:20040991

  5. Preparation of highly reactive metal powders. A new procedure for the preparation of highly reactive zinc and magnesium metal powders

    SciTech Connect

    Rieke, R.D.; Li, P.T.J.; Burns, T.P.; Uhm, S.T.

    1981-10-09

    Highly reactive zinc and magnesium metal powders can be prepared by the lithium reduction of the corresponding metal salt with a catalytic amount of naphthalene as an electron carrier. Applications to the Reformatsky reaction, the Grignard reaction, and cyclopropanation (with dibromomethane) are described.

  6. Involvement of plant C(2)H(2)-type zinc finger transcription factors in stress responses.

    PubMed

    Kiełbowicz-Matuk, Agnieszka

    2012-04-01

    Abiotic and biotic stresses frequently impose constraints on plant distribution and affect agricultural productivity. Various aspects of the multiplicity and the complexity of stress responsive gene networks have been previously studied. Many of individual transcription factors in plants and their family classes that regulate the expression of several genes in responses to environmental stresses have been identified. One such class of transcription regulators is the C(2)H(2) class of zinc finger proteins. Numerous members of the C(2)H(2)-type zinc finger family have been shown to play diverse roles in the plant stress response and the hormone signal transduction. Transcription profiling analyses have demonstrated that the transcript level of many C(2)H(2)-type zinc finger proteins is elevated under different abiotic stress conditions such as low temperature, salt, drought, osmotic stress and oxidative stress. Some C(2)H(2)-type proteins are additionally involved in the biotic stress signaling pathway. Moreover, it has been reported that overexpression of some C(2)H(2)-type zinc finger protein genes resulted in both the activation of some stress-related genes and enhanced tolerance to various stresses. Current genetic studies have focused on possible interactions between different zinc finger transcription factors during stresses to regulate transcription. This review highlights the role of the C(2)H(2) class of the zinc finger proteins in regulating abiotic and biotic stress tolerance in the plants.

  7. On texture, corrosion resistance and morphology of hot-dip galvanized zinc coatings

    NASA Astrophysics Data System (ADS)

    Asgari, H.; Toroghinejad, M. R.; Golozar, M. A.

    2007-06-01

    Texture is an important factor which affects the coating properties. Chemical composition of the zinc bath can strongly influence the texture of hot-dip galvanized coatings. In this study, lead content of the zinc bath was changed from 0.01 wt.% to 0.11 wt.%. Specimens were prepared from zinc baths of different lead content and its texture was evaluated using X-ray diffraction. Corrosion behaviour was analyzed by Tafel extrapolation and linear polarization tests. To study the corrosion products of the specimens, salt spray test was employed. Also, the spangle size of the specimens was determined using line intercept method. From the experimental results it was found that (00.2) basal plane texture component would be weakened by increasing the lead content of the zinc and conversely, (20.1) high angle pyramidal texture components strengthened. Besides, coatings with strong (00.2) texture component and weaker (20.1) component have better corrosion resistance than the coatings with weak (00.2) and strong (20.1) texture components. In addition, surface morphology would be changed and presence of basal planes decreases at the coating surface due to the increase of lead in the zinc bath. Furthermore, spangle size would be increased by increasing the lead content of the zinc bath. Investigation on the effects of skin pass rolling showed that in this case, (00.2) basal texture component and corrosion resistance of the skin passed specimens, in comparison with non-skin passed specimens, have been decreased.

  8. Development of a Highly Biocompatible Antituberculosis Nanodelivery Formulation Based on Para-Aminosalicylic Acid—Zinc Layered Hydroxide Nanocomposites

    PubMed Central

    Arulselvan, Palanisamy; El Zowalaty, Mohamed Ezzat; Fakurazi, Sharida; Webster, Thomas J.; Geilich, Benjamin; Hussein, Mohd Zobir

    2014-01-01

    Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 μg/mL compared to the free drug PAS with a MIC of 5.0 μg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies. PMID:25050392

  9. Alterations in zinc binding capacity, free zinc levels and total serum zinc in a porcine model of sepsis.

    PubMed

    Hoeger, Janine; Simon, Tim-Philipp; Doemming, Sabine; Thiele, Christoph; Marx, Gernot; Schuerholz, Tobias; Haase, Hajo

    2015-08-01

    Zinc is crucial for immune function. In addition, the redistribution of zinc and other nutrients due to infection is an integral part of the host immune response to limit availability to pathogens. However, the major zinc binding protein albumin is down regulated during the acute phase response, implicating a decrease in zinc binding capacity. A prospective animal study with eight female German landrace pigs was conducted to investigate alterations in zinc binding capacity, total serum zinc and free zinc levels in the initial phase of sepsis. Sepsis was induced by instillation of autologous feces via midline laparotomy. Total serum zinc declined significantly after 1 h (10.89 ± 0.42 µM vs. 7.67 ± 0.41 µM, p < 0.001), total serum copper and iron reached a significant reduction at 4 h. Urinary excretion of zinc declined in line with total serum zinc. In comparison to total serum zinc, free zinc levels declined to a lesser, though significant, extent. Zinc binding capacity of serum decreased over time, whereby free zinc levels after addition of zinc correlated negatively with total serum protein and albumin levels. In addition IL-6 and TNF-α concentrations were measured and increased significantly 2 h after induction of sepsis. Hence, total serum zinc was the first marker of inflammation in our experiment, and might therefore be a promising biomarker for the early diagnosis of sepsis. Furthermore the observation of a substantially different serum free zinc homeostasis during sepsis provides valuable information for a potential therapeutic zinc supplementation, which has to take buffering capacity by serum proteins into account.

  10. Nutritional zinc increases platelet reactivity.

    PubMed

    Marx, G; Krugliak, J; Shaklai, M

    1991-11-01

    After ingestion of 220 mg zinc sulfate, platelet aggregation was evaluated at various time intervals (i.e., T = 0, 1, and 3 hr) and the autologous plasma analyzed by atomic absorption analysis. The zinc levels increased maximally some 0.4 +/- 0.2 microgram/ml within 3 hr after ingestion, which for the entire blood pool corresponds to only 5% of the ingested zinc. Aggregation responses of platelet rich plasma (PRP), instigated with suboptimal levels of thrombin (less than 0.2 U/ml), ADP (less than 2 microM), epinephrine (less than 2 microM), collagen (less than 2 micrograms/ml), or PAF (less than 50 ng/ml), show significant improvement to at least one aggregant. Mean +/- SEM values for delta % aggregation increase are as follows: thrombin, 51 +/- 10%; epinephrine, 21 +/- 6%; ADP, 31 +/- 6%; collagen 23 +/- 6%; and platelet aggregating factor (PAF), 56 +/- 6%. For controls, the platelets from one individual with Glanzmann thrombasthenia as well as four undosed volunteers exhibited no significant changes in platelet responsiveness. Increased platelet responsiveness to agonists after zinc sulfate ingestion was observed in PRP from blood collected in either citrate or heparin. We demonstrate that within a relatively short time period, single bolus of nutritional zinc intake can significantly increase platelet reactivity. These findings show that nutritional zinc availability is relevant to hemostasis and may pertain to the viability of platelet concentrates in blood banks.

  11. Zinc and copper: proposed fortification levels and recommended zinc compounds.

    PubMed

    Rosado, Jorge L

    2003-09-01

    Micronutrient fortification of foods is now a highly relevant tool worldwide for overcoming micronutrient deficiency. Recent data show that subclinical zinc deficiency is widespread; in Mexico a national survey showed that 25% of children less than age 11 y had plasma zinc concentrations below 10.0 micromol/L (65 microg/dL). Copper deficiency in populations is unknown but copper supplementation is recommended to accompany zinc supplementation. Of the foods available for fortification, staple cereals are very good candidates for reducing micronutrient deficiencies. Because of its higher stability and lower cost, we recommend fortification of cereal flours with zinc oxide, which is absorbed as well as the less stable and more expensive forms of zinc. Depending on the amount of the food that is expected to be eaten, zinc fortification of staple foods could be 20-50 mg/kg of flour. For copper fortification the safer compound is copper gluconate. Copper sulfate is significantly less expensive, but an evaluation of potential physicochemical reactions that affect the final food product is recommended. The suggested amount of copper added to staple foods is 1.2-3.0 mg/kg of flour. For food supplements designed as part of supplementation programs to reduce micronutrient deficiency in children less than age 3 y, a dose of the final product (usually approximately 40-50 g) should contain approximately 4-5 mg of zinc and approximately 0.2-0.4 mg of copper depending on the habitual diet, magnitude of deficiencies and period of supplementation. PMID:12949397

  12. Fundamental Properties of Salts

    SciTech Connect

    Toni Y Gutknecht; Guy L Fredrickson

    2012-11-01

    Thermal properties of molten salt systems are of interest to electrorefining operations, pertaining to both the Fuel Cycle Research & Development Program (FCR&D) and Spent Fuel Treatment Mission, currently being pursued by the Department of Energy (DOE). The phase stability of molten salts in an electrorefiner may be adversely impacted by the build-up of fission products in the electrolyte. Potential situations that need to be avoided, during electrorefining operations, include (i) fissile elements build up in the salt that might approach the criticality limits specified for the vessel, (ii) electrolyte freezing at the operating temperature of the electrorefiner due to changes in the liquidus temperature, and (iii) phase separation (non-homogenous solution). The stability (and homogeneity) of the phases can be monitored by studying the thermal characteristics of the molten salts as a function of impurity concentration. Simulated salt compositions consisting of the selected rare earth and alkaline earth chlorides, with a eutectic mixture of LiCl-KCl as the carrier electrolyte, were studied to determine the melting points (thermal characteristics) using a Differential Scanning Calorimeter (DSC). The experimental data were used to model the liquidus temperature. On the basis of the this data, it became possible to predict a spent fuel treatment processing scenario under which electrorefining could no longer be performed as a result of increasing liquidus temperatures of the electrolyte.

  13. Great Salt Lake, Utah

    USGS Publications Warehouse

    Stephens, Doyle W.; Gardner, Joe F.

    1999-01-01

    This document is intended as a source of general information and facts about Great Salt Lake, Utah. This U.S. Geological Survey information sheet answers frequently asked questions about Great Salt Lake. Topics include: History, salinity, brine shrimp, brine flies, migratory birds, and recreation. Great Salt Lake, the shrunken remnant of prehistoric Lake Bonneville, has no outlet. Dissolved salts accumulate in the lake by evaporation. Salinity south of the causeway has ranged from 6 percent to 27 percent over a period of 22 years (2 to 7 times saltier than the ocean). The high salinity supports a mineral industry that extracts about 2 million tons of salt from the lake each year. The aquatic ecosystem consists of more than 30 species of organisms. Harvest of its best-known species, the brine shrimp, annually supplies millions of pounds of food for the aquaculture industry worldwide. The lake is used extensively by millions of migratory and nesting birds and is a place of solitude for people. All this occurs in a lake that is located at the bottom of a 35,000-square-mile drainage basin that has a human population of more than 1.5 million.

  14. Effect of folic acid on zinc absorption

    SciTech Connect

    Wada, L.; Keating, S.; King, J.C.; Stokstad, E.L.R.

    1986-03-05

    The effect of folic acid on zinc uptake was studied in the human and in the rat. The serum zinc response to a 25 mg oral dose or zinc was measured with and without a 10 mg dose of folic acid. Serum zinc levels were measured prior to the oral dose of zinc and at hourly intervals up to 4 hours after the dose. When zinc was given along, the increases in serum zinc from baseline at hours 1, 2, 3 and 4 were 92, 118, 92 and 66 ..mu..g/dl, respectively. When both zinc and folic acid were given, the increases in serum zinc at hours 1, 2, 3 and 4 were 100, 140, 110 and 75 ..mu..g/dl, respectively. When the increases in serum zinc were plotted against time, there was no significant difference between the areas under the two curves. The everted jejunal sac from the rat was used to study the effect of folate on zinc transport using 100 ..mu..M zinc in the mucosal buffer. The addition of folic acid at levels up to 10/sup -3/M had no significant effect on zinc transport to the serosal side solution or on uptake by the intestinal mucosa. This in vivo study with humans and in vitro study with rat intestine does not support a direct adverse effect of folic acid on zinc absorption.

  15. Zinc and Diabetic Retinopathy

    PubMed Central

    Miao, Xiao; Sun, Weixia; Miao, Lining; Fu, Yaowen; Wang, Yonggang; Su, Guanfang; Liu, Quan

    2013-01-01

    Zinc (Zn) is an important nutrient that is involved in various physiological metabolisms. Zn dyshomeostasis is often associated with various pathogeneses of chronic diseases, such as metabolic syndrome, diabetes, and related complications. Zn is present in ocular tissue in high concentrations, particularly in the retina and choroid. Zn deficiencies have been shown to affect ocular development, cataracts, age-related macular degeneration, and even diabetic retinopathy. However, the mechanism by which Zn deficiency increases the prevalence of diabetic retinopathy remains unclear. In addition, due to the negative effect of Zn deficiency on the eye, Zn supplementation should prevent diabetic retinopathy; however, limited available data do not always support this notion. Therefore, the goal of this paper was to summarize these pieces of available information regarding Zn prevention of diabetic retinopathy. Current theories and possible mechanisms underlying the role of Zn in the eye-related diseases are discussed. The possible factors that affect the preventive effect of Zn supplementation on diabetic retinopathy were also discussed. PMID:23671870

  16. Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

    SciTech Connect

    Boeckner, L.S.; Kies, C.

    1986-03-05

    The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10/sup -6/ was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study.

  17. Mineral resource of the month: salt

    USGS Publications Warehouse

    Kostick, Dennis S.

    2010-01-01

    The article presents information on various types of salt. Rock salt is either found from underground halite deposits or near the surface. Other types of salt include solar salt, salt brine, and vacuum pan salt. The different uses of salt are also given including its use as a flavor enhancer, as a road deicing agent, and to manufacture sodium hydroxide.

  18. Development of Al-containing zinc-rich paints for corrosion resistance

    NASA Astrophysics Data System (ADS)

    Chen, Wen-Ben; Chen, Peter; Chen, H. Y.; Wu, Jack; Tsai, Wen-Ta

    2002-02-01

    The effect of Al addition on the corrosion performance of zinc-rich paints (ZRP) was investigated. Both electrochemical measurement and salt spray test were employed to evaluate the corrosion performance of ZRP with or without Al addition. The Al content as percentage of the total metallic components in the ZRP, investigated in this study, varied from 0 to 75 wt.%. The experimental results showed that protective nature of ZRP altered from cathodic protection to barrier former as the Al content was increased beyond 20 wt.%. The results from salt spray tests also revealed that the corrosion products were modified with the presence of aluminum oxide in the Al-containing ZRP. The amount of zinc white on the painted steel decreased as the Al content in the ZRP increased. The protectiveness, in terms of the time of red rust formation and cathodic protection, was reduced as the Al content was higher than 20 wt.%.

  19. Sorbitol dehydrogenase is a zinc enzyme.

    PubMed Central

    Jeffery, J; Chesters, J; Mills, C; Sadler, P J; Jörnvall, H

    1984-01-01

    Evidence is given that tetrameric sorbitol dehydrogenase from sheep liver contains one zinc atom per subunit, most probably located at the active site, and no other specifically bound zinc or iron atom. In alcohol dehydrogenases that are structurally related to sorbitol dehydrogenase, more than one zinc atom per subunit can complicate investigations of zinc atom function. Therefore, sorbitol dehydrogenase will be particularly valuable for defining the precise roles of zinc in alcohol and polyol dehydrogenases, and for establishing correlations of structure and function with other important zinc-containing proteins. PMID:6370679

  20. Gas releases from salt

    SciTech Connect

    Ehgartner, B.; Neal, J.; Hinkebein, T.

    1998-06-01

    The occurrence of gas in salt mines and caverns has presented some serious problems to facility operators. Salt mines have long experienced sudden, usually unexpected expulsions of gas and salt from a production face, commonly known as outbursts. Outbursts can release over one million cubic feet of methane and fractured salt, and are responsible for the lives of numerous miners and explosions. Equipment, production time, and even entire mines have been lost due to outbursts. An outburst creates a cornucopian shaped hole that can reach heights of several hundred feet. The potential occurrence of outbursts must be factored into mine design and mining methods. In caverns, the occurrence of outbursts and steady infiltration of gas into stored product can effect the quality of the product, particularly over the long-term, and in some cases renders the product unusable as is or difficult to transport. Gas has also been known to collect in the roof traps of caverns resulting in safety and operational concerns. The intent of this paper is to summarize the existing knowledge on gas releases from salt. The compiled information can provide a better understanding of the phenomena and gain insight into the causative mechanisms that, once established, can help mitigate the variety of problems associated with gas releases from salt. Outbursts, as documented in mines, are discussed first. This is followed by a discussion of the relatively slow gas infiltration into stored crude oil, as observed and modeled in the caverns of the US Strategic Petroleum Reserve. A model that predicts outburst pressure kicks in caverns is also discussed.