Sample records for acid dca trichloroacetic

  1. IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

    EPA Pesticide Factsheets

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroacetic acid (TCA) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of trichloroacetic acid provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

  2. X-ray diffraction, vibrational and quantum chemical investigations of 2-methyl-4-nitroanilinium trichloroacetate trichloroacetic acid

    NASA Astrophysics Data System (ADS)

    Arjunan, V.; Marchewka, Mariusz K.; Pietraszko, A.; Kalaivani, M.

    2012-11-01

    The structural investigations of the molecular complex of 2-methyl-4-nitroaniline with trichloroacetic acid, namely 2-methyl-4-nitroanilinium trichloroacetate trichloroacetic acid (C11H10Cl6N2O6) have been performed by means of single crystal and powder X-ray diffraction method. The complex was formed with accompanying proton transfer from trichloroacetic acid molecule to 2-methyl-4-nitroaniline. The studied crystal is built up of singly protonated 2-methyl-4-nitroanilinium cations, trichloroacetate anions and neutral trichloroacetic acid molecules. The crystals are monoclinic, space group P21/c, with a = 14.947 Å, b = 6.432 Å, c = 19.609 Å and Z = 4. The vibrational assignments and analysis of 2-methyl-4-nitroanilinium trichloroacetate trichloroacetic acid have also been performed by FTIR, FT-Raman and far-infrared spectral studies. More support on the experimental findings were added from the quantum chemical studies performed with DFT (B3LYP) method using 6-31G**, cc-pVDZ, 6-31G and 6-31++G basis sets. The structural parameters, energies, thermodynamic parameters and the NBO charges of 2M4NATCA were also determined by the DFT methods.

  3. X-ray diffraction, vibrational and quantum chemical investigations of 2-methyl-4-nitroanilinium trichloroacetate trichloroacetic acid.

    PubMed

    Arjunan, V; Marchewka, Mariusz K; Pietraszko, A; Kalaivani, M

    2012-11-01

    The structural investigations of the molecular complex of 2-methyl-4-nitroaniline with trichloroacetic acid, namely 2-methyl-4-nitroanilinium trichloroacetate trichloroacetic acid (C(11)H(10)Cl(6)N(2)O(6)) have been performed by means of single crystal and powder X-ray diffraction method. The complex was formed with accompanying proton transfer from trichloroacetic acid molecule to 2-methyl-4-nitroaniline. The studied crystal is built up of singly protonated 2-methyl-4-nitroanilinium cations, trichloroacetate anions and neutral trichloroacetic acid molecules. The crystals are monoclinic, space group P2(1)/c, with a=14.947Å, b=6.432Å, c=19.609Å and Z=4. The vibrational assignments and analysis of 2-methyl-4-nitroanilinium trichloroacetate trichloroacetic acid have also been performed by FTIR, FT-Raman and far-infrared spectral studies. More support on the experimental findings were added from the quantum chemical studies performed with DFT (B3LYP) method using 6-31G, cc-pVDZ, 6-31G and 6-31++G basis sets. The structural parameters, energies, thermodynamic parameters and the NBO charges of 2M4NATCA were also determined by the DFT methods. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. GENOTOXICITY STUDIES OF SODIUM DICHLOROACETATE AND SODIUM TRICHLOROACETATE

    EPA Science Inventory

    The genotoxic properties of sodium dichloroacetate (DCA) and sodium trichloroacetate (TCA)were evaluated in several short-term in vitro and in vivo assays. Neither compound was mutagenic in tester strain TA102 in the Salmonella mutagenicity assay. Both DCA and TCA were weak induc...

  5. Trichloroacetic acid

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 09 / 003F www.epa.gov / iris TOXICOLOGICAL REVIEW OF TRICHLOROACETIC ACID ( CAS No . 76 - 03 - 9 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) September 2011 U.S . Environmental Protection Agency Washington , DC ii DISCLAIMER This document has

  6. IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

    EPA Pesticide Factsheets

    EPA is releasing the draft report, Toxicological Review of Trichloroacetic Acid (TCA), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies and White House Offices are provided below with external peer review panel comments. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

  7. IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

    EPA Pesticide Factsheets

    On September 24, 2009, the Toxicological Review of Trichloroacetic Acid (TCA) and the charge to external peer reviewers were released for external peer review and public comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. In the new IRIS process, introduced by the EPA Administrator, all written comments on IRIS assessments submitted by other federal agencies and White House Offices will be made publicly available. Accordingly, interagency comments and the interagency science consultation draft of the IRIS Toxicological Review of Trichloroacetic Acid and the charge to external peer reviewers are posted on this site. The draft Toxicological Review of Trichloroacetic Acid provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

  8. IRIS TOXICOLOGICAL REVIEW AND SUMMARY DOCUMENTS FOR TRICHLOROACETIC ACID

    EPA Science Inventory

    Trichloroacetic acid is a crystalline solid with sharp, pungent odor. It is used as a soil sterilizer; and as a laboratory intermediate or reagent in the synthesis of a variety of medicinal products and organic chemicals. Trichloroacetic acid is also used industrially as an etc...

  9. EFFECT OF PRETREATMENT WITH DICHLOROACETIC OR TRICHLOROACETIC ACID IN DRINKING WATER ON THE PHARMACOKINETICS OF A SUBSEQUENT CHALLENGE DOSE IN B6C3F1 MICE. (R825954)

    EPA Science Inventory

    h2>Abstract

    Dichloroacetate (DCA) and trichloroacetate (TCA) are prominent by-products of chlorination of drinking water. Both chemicals have been shown to be hepatic carcinogens in mice. Prior work has demonstrated that DCA inhibits its own metabolism in rats and humans. ...

  10. DICHLOROACETIC ACID (DCA) INHIBITS PROLIFERATION AND APOPTOSIS IN NORMAL HEPATOCYTES OF MALE F344 RATS

    EPA Science Inventory

    Dichloroacetic acid (DCA} inhibits proliferation and apoptosis in nonnal hepatocytes of
    male F344 rats.

    Large segments of the population are chronically exposed to dichloroacetic acid (DCA}: DCA is a by product of the chlorine disinfection of drinking water, a metab...

  11. Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

    PubMed

    Centuori, Sara M; Martinez, Jesse D

    2014-10-01

    A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

  12. Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer

    PubMed Central

    Centuori, Sara M.; Martinez, Jesse D.

    2014-01-01

    A high fat diet coincides with elevated levels of bile acids. This elevation of bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR) mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway. PMID:25027205

  13. Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice: Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Sungkyoon; Kim, David; Pollack, Gary M.

    2009-07-01

    Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE, such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to be hepatotoxic and carcinogenic in mice. The reactive products of glutathione conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats. Recently, we developed a new analytical method for simultaneous assessment of these TCE metabolites in small-volume biological samples. Since important gaps remain in our understanding of the pharmacokinetics of TCE and its metabolites, we studied a time-course of DCA, TCA,more » DCVG and DCVG formation and elimination after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. Based on systemic concentration-time data, we constructed multi-compartment models to explore the kinetic properties of the formation and disposition of TCE metabolites, as well as the source of DCA formation. We conclude that TCE-oxide is the most likely source of DCA. According to the best-fit model, bioavailability of oral TCE was {approx} 74%, and the half-life and clearance of each metabolite in the mouse were as follows: DCA: 0.6 h, 0.081 ml/h; TCA: 12 h, 3.80 ml/h; DCVG: 1.4 h, 16.8 ml/h; DCVC: 1.2 h, 176 ml/h. In B6C3F1 mice, oxidative metabolites are formed in much greater quantities ({approx} 3600 fold difference) than glutathione-conjugative metabolites. In addition, DCA is produced to a very limited extent relative to TCA, while most of DCVG is converted into DCVC. These pharmacokinetic studies provide insight into the kinetic properties of four key biomarkers of TCE toxicity in the mouse, representing novel information that can be used in risk assessment.« less

  14. Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice: Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine

    PubMed Central

    Kim, Sungkyoon; Kim, David; Pollack, Gary M.; Collins, Leonard B.; Rusyn, Ivan

    2009-01-01

    Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE, such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to be hepatotoxic and carcinogenic in mice. The reactive products of glutathione conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats. Recently, we developed a new analytical method for simultaneous assessment of these TCE metabolites in small-volume biological samples. Since important gaps remain in our understanding of the pharmacokinetics of TCE and its metabolites, we studied a time-course of DCA, TCA, DCVG and DCVG formation and elimination after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. Based on systemic concentration-time data, we constructed multi-compartment models to explore the kinetic properties of the formation and disposition of TCE metabolites, as well as the source of DCA formation. We conclude that TCE-oxide is the most likely source of DCA. According to the best-fit model, bioavailability of oral TCE was ~74%, and the half-life and clearance of each metabolite in the mouse were as follows: DCA: 0.6 hr, 0.081 ml/hr; TCA: 12 hr, 3.80 ml/hr; DCVG: 1.4 hr, 16.8 ml/hr; DCVC: 1.2 hr, 176 ml/hr. In B6C3F1 mice, oxidative metabolites are formed in much greater quantities (~3600 fold difference) than glutathione-conjugative metabolites. In addition, DCA is produced to a very limited extent relative to TCA, while most of DCVG is converted into DCVC. These pharmacokinetic studies provide insight into the kinetic properties of four key biomarkers of TCE toxicity in the mouse, representing novel information that can be used in risk assessment. PMID:19409406

  15. Glycation inhibits trichloroacetic acid (TCA)-induced whey protein precipitation

    USDA-ARS?s Scientific Manuscript database

    Four different WPI saccharide conjugates were successfully prepared to test whether glycation could inhibit WPI precipitation induced by trichloroacetic acid (TCA). Conjugates molecular weights after glycation were analyzed with SDS-PAGE. No significant secondary structure change due to glycation wa...

  16. IRIS Toxicological Review of Trichloroacetic Acid (Tca) (Final Report)

    EPA Science Inventory

    EPA has finalized the Toxicological Review of Trichloroacetic Acid: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health.

  17. Utilizing two detectors in the measurement of trichloroacetic acid in human urine by reaction headspace gas chromatography.

    PubMed

    Xie, Wei-Qi; Gong, Yi-Xian; Yu, Kong-Xian

    2018-05-16

    A reaction headspace gas chromatography (HS-GC) technique was investigated for quantitatively analyzing trichloroacetic acid in human urine. This method is based on the decomposition reaction of trichloroacetic acid under high-temperature conditions. The carbon dioxide and chloroform formed from the decomposition reaction can be respectively detected by the thermal conductivity detection HS-GC and flame ionization detection HS-GC. The reaction can be completed in 60 min at 90°C. This method was used to quantify 25 different human urine samples, which had a range of trichloroacetic acid from 0.52 to 3.47 mg/L. It also utilized two different detectors, the thermal conductivity detector and the flame ionization detector. The present reaction HS-GC method is accurate, reliable and well suitable for batch detection of trichloroacetic acid in human urine. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Effect of pre-treatment with dichloroacetic or trichloroacetic acid in drinking water on the pharmacokinetics of a subsequent challenge dose in B6C3F1 mice.

    PubMed

    Gonzalez-Leon, A; Merdink, J L; Bull, R J; Schultz, I R

    1999-12-15

    Dichloroacetate (DCA) and trichloroacetate (TCA) are prominent by-products of chlorination of drinking water. Both chemicals have been shown to be hepatic carcinogens in mice. Prior work has demonstrated that DCA inhibits its own metabolism in rats and humans. This study focuses on the effect of prior administration of DCA or TCA in drinking water on the pharmacokinetics of a subsequent challenge dose of DCA or TCA in male B6C3F1 mice. Mice were provided with DCA or TCA in their drinking water at 2 g/l for 14 days and then challenged with a 100 mg/kg i.v. (non-labeled) or gavage (14C-labeled) dose of DCA or TCA. The challenge dose was administered after 16 h fasting and removal of the haloacetate pre-treatment. The haloacetate blood concentration-time profile and the disposition of 14C were characterized and compared with controls. The effect of pre-treatment on the in vitro metabolism of DCA in hepatic S9 was also evaluated. Pre-treatment with DCA caused a significant increase in the blood concentration-time profiles of the challenge dose of DCA. No effect on the blood concentration-time profile of DCA was observed after pre-treatment with TCA. Pre-treatment with TCA had no effect on subsequent doses of DCA. Pre-treatment with DCA did not have a significant effect on the formation of 14CO2 from radiolabeled DCA. In vitro experiments with liver S9 from DCA-pre-treated mice demonstrated that DCA inhibits it own metabolism. These results indicate that DCA metabolism in mice is also susceptible to inhibition by prior treatment with DCA, however the impact on clearance is less marked in mice than in F344 rats. In contrast, the metabolism and pharmacokinetics of TCA is not affected by pre-treatment with either DCA or TCA.

  19. IRIS Toxicological Review of Trichloroacetic Acid (TCA) (External Review Draft)

    EPA Science Inventory

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroacetic acid (TCA) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

  20. Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

    PubMed

    Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

    2015-09-01

    Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Efficacy of Trichloro-Acetic Acid Peel Alone Versus Combined Topical Magnesium Ascorbyl Phosphate for Epidermal Melasma.

    PubMed

    Murtaza, Fatima; Bangash, Abdur Rahim; Khushdil, Arshad; Noor, Sahibzada Mahmood

    2016-07-01

    To compare the efficacy in terms of reduction in melasma area and severity index (MASI) score by more than 10 of a combination of 20% trichloro-acetic acid peel plus 5% topical magnesium ascorbyl phosphate versus 20% trichloroacetic acid peel alone in the treatment of epidermal melasma. Randomized controlled trial. Department of Dermatology, Lady Reading Hospital (LRH), Peshawar, from May 2012 to May 2013. Patients aged 18 - 65 years, with Fitzpatrick skin type III-V were divided into two equal groups having 74 patients each. Detailed history was taken and Wood's lamp examination done to rule out mixed and dermal melasma. Melasma area and severity index (MASI) score was calculated for every patient. Priming was done for all patients with tretinoin cream applied once daily at night for 2 weeks, and to use a broad spectrum sun block cream before sun exposure. Patients in group Awere subjected to combined treatment, i.e. trichloro-acetic acid peel 20% (weekly) plus magnesium ascorbyl phosphate cream (applied once daily), while patients in group B were subjected to trichloro-acetic acid peel 20% (weekly) alone. Treatment was continued for 6 weeks. After completion of treatment, MASI score was recalculated. Proportion of patients with significant MASI score reduction was compared using chi-square test with significance at p < 0.05. Male and female patients were 11 (14.9%) and 63 (85.1%), respectively in group A, whereas 13 (17.6%) and 61 (82.4%) in group B. The mean age in group Awas 30.28 ±8.08 years, and 29.36 ±6.84 years in group B. Significant MASI score reduction in group Awas seen in 60 (81.1%) patients and in group B 49 (66.2%, p= 0.040). Combination of trichloro-acetic acid peel and topical magnesium ascorbyl phosphate cream was significantly more effective than trichloro-acetic acid peel alone in treatment of melasma.

  2. Trichloroacetic Acid Versus Salicylic Acid in the Treatment of Acne Vulgaris in Dark-Skinned Patients.

    PubMed

    Abdel Meguid, Azza Mahfouz; Elaziz Ahmed Attallah, Dalia Abd; Omar, Howida

    2015-12-01

    Treatment options for acne include chemical peeling. Trichloroacetic acid (TCA) has been used for treating acne. The ability of TCA to diminish corneocyte cohesion and keratinocyte plugging addresses this mode of treatment. Salicylic acid is an excellent keratolytic agent. It is believed to function through solubilization of intercellular cement, thereby reducing corneocyte adhesion. Comparing the therapeutic efficacy of TCA 25% peels with those of salicylic acid 30% in patients with acne vulgaris. Twenty patients, Fitzpatrick skin Types III to V with facial acne, were enrolled. Twenty-five percent of TCA was applied to the right half of the face and 30% salicylic acid to the left half at 2-week interval for 2 months. Total improvement was more frequent with salicylic acid peeling (95%) versus (85%) with TCA. Total comedones improvement was more frequent with TCA peeling (80%) versus (70%) with salicylic acid. Improvement of inflammatory lesions was more frequent among the side treated with salicylic acid (85%) versus (80%) with TCA peeling. However, the results did not reach the statistical significance level. Trichloroacetic acid is more superior in treating comedonal lesions, whereas salicylic is more superior in treating inflammatory lesions, without significant different between their results.

  3. A STUDY COMPARING CHEMICAL PEELING USING MODIFIED JESSNER'S SOLUTION AND 15%TRICHLOROACETIC ACID VERSUS 15% TRICHLOROACETIC ACID IN THE TREATMENT OF MELASMA

    PubMed Central

    Safoury, Omar Soliman; Zaki, Nagla Mohamed; El Nabarawy, Eman Ahmad; Farag, Eman Abas

    2009-01-01

    Background: Melasma is a symmetric progressive hyperpigmentation of the facial skin that occurs in all races but has a predilection for darker skin phenotypes. Depigmenting agents, laser and chemical peeling as classic Jessner's solution, modified Jessner's solution and trichloroacetic acid have been used alone and in combination in the treatment of melasma. Objectives: The aim of the study was to compare the therapeutic effect of combined 15% Trichloroacetic acid (TCA) and modified Jessner's solution with 15% TCA on melasma. Materials and Methods: Twenty married females with melasma (epidermal type), with a mean age of 38.25 years, were included in this study. All were of skin type III or IV. Fifteen percent TCA was applied to the whole face, with the exception of the left malar area to which combined TCA 15% and modified Jessner's solution was applied. Results: Our results revealed statistically highly significant difference between MASI Score (Melasma Area and Severity Index) between the right malar area and the left malar area. Conclusion: Modified Jessner's solution proved to be useful as an adjuvant treatment with TCA in the treatment of melasma, improving the results and minimizing postinflammatory hyperpigmentation. PMID:20049268

  4. The efficacy of various degreasing agents used in trichloroacetic acid peels.

    PubMed

    Peikert, J M; Krywonis, N A; Rest, E B; Zachary, C B

    1994-11-01

    Adequate preparation of the skin is necessary for a successful chemical peel. Little detailed attention has been given to the effect of degreasing on the efficacy of the peel. To assess the influence of degreasers on the peel, compare their flammabilities, and discuss alternatives. Six patients with androgenetic alopecia and widespread actinic keratoses of the scalp were treated with 35% trichloroacetic acid. Scalps were divided into sections and degreased with acetone, rubbing alcohol, Freon Skin Degreaser, or Hibiclens. The influence of these degreasers on trichloroacetic acid peels was assessed by clinical and histologic examination. Acetone was not found to be superior to the other agents. Furthermore, the flashpoint of acetone is markedly lower than the others, making it more flammable and hazardous in the workplace. The use of alternative degreasers may lessen or eliminate this hazard.

  5. IRIS Toxicological Review of Trichloroacetic Acid (TCA) (Interagency Science Discussion Draft)

    EPA Science Inventory

    EPA is releasing the draft report, Toxicological Review of Trichloroacetic Acid (TCA), that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development ...

  6. Manual resurfacing and trichloroacetic acid for the treatment of patients with widespread actinic damage. Clinical and histologic observations.

    PubMed

    Cooley, J E; Casey, D L; Kauffman, C L

    1997-05-01

    A facial resurfacing regimen combining manual abrasion of the skin and 25% trichloroacetic acid has been reported to produce excellent results, but the histologic depth of injury produced by this technique has not been studied. To describe our experience with this technique treating patients with extensive actinic damage and to determine the histologic depth of injury produced. We treated 40 patients using manual resurfacing and trichloroacetic acid, primarily for widespread actinic keratoses. Resurfacing tools included silicone carbide sandpaper, drywall screen, electrocautery tip cleaners, abrasive pads, scalpel blades, and curettes. Four patients underwent sequential biopsies to evaluate the depth of wounding using this technique. Manual resurfacing combined with trichloroacetic acid consistently produced excellent cosmetic results and nearly complete eradication of actinic keratoses. Histologically, treated areas showed replacement of the dermal elastotic band by newly formed collagen, a significantly deeper level of wounding than the Jessner's/35% trichloroacetic acid peel. There was no evidence for foreign body granulomas clinically or histologically as a result of the abrasive materials. The deeper level of this peel explains the improved cosmetic outcome and greater eradication of actinic keratoses. This treatment is particularly well suited for patients with extensive photodamage and widespread actinic keratoses.

  7. A MULTISTAGE BIOLOGICALLY BASED MATHEMATICAL MODEL FOR MOUSE LIVER TUMORS INDUCED BY DICHLOROACETIC ACID (DCA) - EXPLORATION OF THE MODEL

    EPA Science Inventory

    A biologically based mathematical model for the induction of liver tumors in mice by dichloroacetic acid (DCA) has been developed from histopathologic analysis of the livers of exposed mice. This analysis suggests that following chronic exposure to DCA, carcinomas can arise dire...

  8. Reductive Dehalogenation of Trichloroacetic Acid by Trichlorobacter thiogenes gen. nov., sp. nov.

    PubMed Central

    De Wever, Helene; Cole, James R.; Fettig, Michael R.; Hogan, Deborah A.; Tiedje, James M.

    2000-01-01

    A bacterium able to grow via reductive dechlorination of trichloroacetate was isolated from anaerobic soil enrichments. The isolate, designated strain K1, is a member of the δ proteobacteria and is related to other known sulfur and ferric iron reducers. In anaerobic mineral media supplemented with acetate and trichloroacetate, its doubling time was 6 h. Alternative electron donor and acceptors were acetoin and sulfur or fumarate, respectively. Trichloroacetate dehalogenation activity was constitutively present, and the dechlorination product was dichloroacetate and chloride. Trichloroacetate conversion seemed to be coupled to a novel sulfur-sulfide redox cycle, which shuttled electrons from acetate oxidation to trichloroacetate reduction. In view of its unique physiological characteristics, the name Trichlorobacter thiogenes is suggested for strain K1. PMID:10831402

  9. Q-switched Nd: YAG laser versus trichloroacetic acid peeling in the treatment of melasma among Egyptian patients.

    PubMed

    Moubasher, Alaa E A; Youssef, Eman M K; Abou-Taleb, Doaa A E

    2014-08-01

    Melasma is a common disorder of facial hyperpigmentation that is often resistant to treatment. To evaluate the efficacy of trichloroacetic acid (TCA) peeling in comparison with double frequency Q-switched neodymium-doped:yttrium aluminum garnet (QS-Nd:YAG) laser in the treatment of melasma. Sixty-five adult Egyptian female patients with melasma were enrolled in this study. Wood light was used for determination of the histological type of melasma. The patients were divided into 4 groups according to treatment modalities: peeling with different concentrations of TCA and double frequency QS-Nd:YAG laser. Trichloroacetic acid peeling was performed every 2 weeks up to 8 sessions, whereas laser treatment was performed every month up to 6 sessions. Melasma area and severity index (MASI) score was used before and after treatment for evaluation. Improvement percentage of MASI score was significantly higher among patients treated with TCA 25% (p < .001). Epidermal type of melasma was significantly improved compared with the dermal type (p = .0029). Q-switched neodymium-doped:yttrium aluminum garnet laser showed the highest incidence of postinflammatory hyperpigmentation (53.3%). Trichloroacetic acid peeling is effective in the treatment of melasma, TCA 25% was the most effective concentration. Q-switched neodymium-doped:yttrium aluminum garnet laser is not recommended in the treatment of melasma because it was associated with the highest incidence of complications.

  10. Ethanol-Induced Changes in Trichloroethylene Toxicity

    DTIC Science & Technology

    1988-09-30

    DCA or TCA. METHODS Chei .Ls. [l-14C]palmitoyl-CoA was purchased from New England Nuclear Products (Boston, MA); clofibrate , dichloroacetic acid (DCA...CLASSIFICATION OF _*NIS PAGE All other 04itions are obsolete. UCASFE UNLSSFE 0 . ( 1(A0~, AYOS-Th ච-1 173 .6. Aid (D,’Al and Trichlo’u,:eti: Acid ...published in 1231gj1gg 94 A221i2d EhabgnSggg 21:45-54 1088. Copy of manuscript "Dichloroacetic acid (DCA) and Trichloroacetic Acid (TCA) induced DNA

  11. APOPTOSIS AND PROLIFERATION DURING DICHLOROACETIC ACID (DCA) INDUCED HEPTACELLULAR CARCINOGENESIS IN THE F344 MALE RAT

    EPA Science Inventory

    Apoptosis and Proliferation During DicWoroacetic Acid (DCA) Induced Hepatocellular
    Carcinogenesis in the F344 Male Rat

    Chlorine, introduced into public drinking \\\\'ater supplies for disinfection, can react with organic compounds in surface waters to form toxic by-prod...

  12. Dynamic controlled atmosphere (DCA): interaction between DCA methods and 1-methylcyclopropene on 'Fuji Suprema' apple quality.

    PubMed

    Weber, Anderson; Thewes, Fabio Rodrigo; Anese, Rogerio de Oliveira; Both, Vanderlei; Pavanello, Elizandra Pivotto; Brackmann, Auri

    2017-11-15

    The objective of the present work was to evaluate the appropriate respiratory quotient (RQ) value to achieve a safe lowest oxygen limit (LOL), during storage of 'Fuji Suprema' apples, in dynamic controlled atmosphere (DCA), treated with or without 1-methylcyclopropene (1-MCP). The apples were stored in DCA-RQ, a new technology for storing fruits, and were compared with the HarvestWatch™, a system based on chlorophyll fluorescence DCA (DCA-CF), and static controlled atmosphere. DCA-RQ1.5 is the most suited for the storage of 'Fuji Suprema' apples. In this condition fermentative products were induced, which reduced ethylene production and respiration rate; however, it did not increase physiological disorders, and the concentration of ethyl acetate was below the odour threshold. 1-MCP application maintained higher flesh firmness and reduced the anaerobic metabolism, although it decreased fruit quality due to the occurrence of cavities, therefore its application is not recommended for 'Fuji Suprema' apple stored in DCA conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Combined Jessner Solution and Trichloroacetic Acid Versus Trichloroacetic Acid Alone in the Treatment of Melasma in Dark-Skinned Patients.

    PubMed

    Abdel-Meguid, Azza M; Taha, Emad A; Ismail, Sahar A

    2017-05-01

    Melasma is a common challenging pigmentary skin disorder especially in dark-skinned females urging them to seek medical help. Many modalities of treatment are available, but none is satisfactory. To compare safety and efficacy of combined trichloroacetic acid (TCA) (20%-25%) and Jessner's solution versus TCA (20%-25%) alone in dark patients with melasma. The study design was a split face, right-left, assessor-blinded, randomized controlled study. Twenty-four adult female patients (skin phototypes IV-V) with bilateral melasma were treated for 6 sessions at 2 weeks intervals. Clinical assessment of the 2 sides of the face with Melasma Area and Severity Index (MASI) score was performed, and photographs were taken before and after the peeling course. Both therapeutic modalities showed significant decrease in MASI score, which was significantly lower on the side treated with both Jessner solution and TCA. There were significant negative correlations between the percentage of improvement of MASI score and both age of the patients and duration of the melasma. Dark skin melasma can be treated with both regimens safely and effectively; however, combined Jessner solution and TCA is more effective.

  14. Cardiovascular Ultrasound of Neonatal Long Evans Rats Exposed Prenatally to Trichloroacetic Acid: Effects on Heart Rate, Ejection Fraction, and Cardiac Output

    EPA Science Inventory

    This abstract describes the use of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development. The abstract describes the effects of two known cardiac teratogens, trichloroacetic acid and dimethadio...

  15. Determination of dichloroacetic acid and trichloroacetic acid in drinking water by acidic methanol esterification and headspace gas chromatography.

    PubMed

    Wang, Y H; Wong, P K

    2005-05-01

    A simple and rapid headspace method for gas chromatographic determination of dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in drinking water was developed. Acidic methanol esterification followed by a headspace technique using a capillary column gas chromatograph (GC) equipped with an electron capture detector (ECD) was applied to determine the levels of DCAA and TCAA in drinking water. The major advantages of this method are the use of acidic methanol as the derivatization agent instead of the hazardous diazomethane, and esterification is carried out in water instead of organic solvent. DCAA and TCAA methyl esters produced in the reaction were determined directly by a headspace GC/ECD method. The linear correlation coefficients at concentrations ranging from 0 to 60 microg/L were 0.992 and 0.996 for DCAA and TCAA, respectively. The relative standard deviations (RSD, %) for the determination of DCAA and TCAA in drinking water were 15 and 21.3%, respectively (n=3). The detection limits of this method were 3 and 0.5 microg/L for DCAA and TCAA, respectively, and the recovery was 68-103.2% for DCAA and TCAA.

  16. Electrochemical degradation of trichloroacetic acid in aqueous media: influence of the electrode material.

    PubMed

    Esclapez, M D; Díez-García, M I; Sàez, V; Bonete, P; González-García, José

    2013-01-01

    The electrochemical degradation of trichloroacetic acid (TCAA) in water has been analysed through voltammetric studies with a rotating disc electrode and controlled-potential bulk electrolyses. The influence of the mass-transport conditions and initial concentration of TCAA for titanium, stainless steel and carbon electrodes has been studied. It is shown that the electrochemical reduction of TCAA takes place prior to the massive hydrogen evolution in the potential window for all electrode materials studied. The current efficiency is high (> 18%) compared with those normally reported in the literature, and the fractional conversion is above 50% for all the electrodes studied. Only dichloroacetic acid (DCAA) and chloride anions were routinely detected as reduction products for any of the electrodes, and reasonable values of mass balance error were obtained. Of the three materials studied, the titanium cathode gave the best results.

  17. Open release of the DCA++ project

    NASA Astrophysics Data System (ADS)

    Haehner, Urs; Solca, Raffaele; Staar, Peter; Alvarez, Gonzalo; Maier, Thomas; Summers, Michael; Schulthess, Thomas

    We present the first open release of the DCA++ project, a highly scalable and efficient research code to solve quantum many-body problems with cutting edge quantum cluster algorithms. The implemented dynamical cluster approximation (DCA) and its DCA+ extension with a continuous self-energy capture nonlocal correlations in strongly correlated electron systems thereby allowing insight into high-Tc superconductivity. With the increasing heterogeneity of modern machines, DCA++ provides portable performance on conventional and emerging new architectures, such as hybrid CPU-GPU and Xeon Phi, sustaining multiple petaflops on ORNL's Titan and CSCS' Piz Daint. Moreover, we will describe how best practices in software engineering can be applied to make software development sustainable and scalable in a research group. Software testing and documentation not only prevent productivity collapse, but more importantly, they are necessary for correctness, credibility and reproducibility of scientific results. This research used resources of the Oak Ridge Leadership Computing Facility (OLCF) awarded by the INCITE program, and of the Swiss National Supercomputing Center. OLCF is a DOE Office of Science User Facility supported under Contract DE-AC05-00OR22725.

  18. SuperDCA for genome-wide epistasis analysis.

    PubMed

    Puranen, Santeri; Pesonen, Maiju; Pensar, Johan; Xu, Ying Ying; Lees, John A; Bentley, Stephen D; Croucher, Nicholas J; Corander, Jukka

    2018-05-29

    The potential for genome-wide modelling of epistasis has recently surfaced given the possibility of sequencing densely sampled populations and the emerging families of statistical interaction models. Direct coupling analysis (DCA) has previously been shown to yield valuable predictions for single protein structures, and has recently been extended to genome-wide analysis of bacteria, identifying novel interactions in the co-evolution between resistance, virulence and core genome elements. However, earlier computational DCA methods have not been scalable to enable model fitting simultaneously to 10 4 -10 5 polymorphisms, representing the amount of core genomic variation observed in analyses of many bacterial species. Here, we introduce a novel inference method (SuperDCA) that employs a new scoring principle, efficient parallelization, optimization and filtering on phylogenetic information to achieve scalability for up to 10 5 polymorphisms. Using two large population samples of Streptococcus pneumoniae, we demonstrate the ability of SuperDCA to make additional significant biological findings about this major human pathogen. We also show that our method can uncover signals of selection that are not detectable by genome-wide association analysis, even though our analysis does not require phenotypic measurements. SuperDCA, thus, holds considerable potential in building understanding about numerous organisms at a systems biological level.

  19. THE INDUCTION OF HEPATOCELLULAR NEOPLASIA BY TRICHLOROACETIC ACID ADMINISTERED IN THE DRINKING WATER OF THE MALE B6C3F1 MOUSE

    EPA Science Inventory

    Summary What is the study? The study is a chronic bioassay (2 years) of trichloroacetic acid, a drinking water disinfection by-product, in the male B6C3F1 mouse.
    What is the impact to the field and the Agency?
    The impact of this study will derive from the use of...

  20. Quantitative Assessment of Peroxisome Proliferation in B6C3F1 Mouse Liver after Subchronic Exposure to Trichloroethylene by Gavage.

    DTIC Science & Technology

    1997-07-01

    levels have been reported in association with a number of different peroxisome proliferators, such as clofibric acid (Bars, et al., 1993; Prough, et...exposure. Similar results have been reported for CYP4A1 mRNA after exposure to clofibric acid (Bars, et al., 1993). The present study also indicated...trichloroacetic acid (TCA), and dichloroacetic acid (DCA) (Herren-Freund, et al., 1987; Daniel, et al., 1992; DeAngelo, et al., 1991). Only CH has been found to

  1. Trichloroacetic acid in the environment.

    PubMed

    McCulloch, A

    2002-05-01

    Suppositions that the trichloroacetic acid (TCA, CCl3C(O)OH) found in nature was a consequence solely of the use of chlorinated hydrocarbon solvents prompted this critical review of the literature on its environmental fluxes and occurrences. TCA is widely distributed in forest soils (where it was rarely used as an herbicide) and measurements suggest a soil flux of 160 000 tonnes yr(-1) in European forests alone. TCA is also produced during oxidative water treatment and the global flux could amount to 55 000 tonnes yr(-1) (from pulp and paper manufacture, potable water and cooling water treatments). By contrast, the yields of TCA from chlorinated hydrocarbon solvents are small: from tetrachloroethene 13 600 tonnes yr(-1) and from 1,1,1-trichloroethane 4300 tonnes yr(-1) on a global basis, at the atmospheric burdens and removal rates typical of the late 1990s. TCA is ubiquitous in rainwater and snow. Its concentrations are highly variable and the variations cannot be connected with location or date. However, there is no significant difference between the concentrations found in Chile and in eastern Canada (by the same analysts), or between Malawi and western Canada, or between Antarctica and Switzerland, nor any significant difference globally between the concentrations in cloud, rain and snow (although local enhancement in fog water has been shown). TCA is present in old ice and firn. At the deepest levels, the firn was deposited early in the 19th century, well before the possibility of contamination by industrial production of reactive chlorine, implying a non-industrial background. This proposition is supported by plume measurements from pulp mills in Finland. TCA is ubiquitous in soils; concentrations are very variable but there are some indications that soils under coniferous trees contain higher amounts. The concentrations of TCA found in plant tissue are region-specific and may also be plant-specific, to the extent that conifers seem to contain more than other

  2. Application of Carbon-Microsphere-Modified Electrodes for Electrochemistry of Hemoglobin and Electrocatalytic Sensing of Trichloroacetic Acid

    PubMed Central

    Wang, Wen-Cheng; Yan, Li-Jun; Shi, Fan; Niu, Xue-Liang; Huang, Guo-Lei; Zheng, Cai-Juan; Sun, Wei

    2015-01-01

    By using the hydrothermal method, carbon microspheres (CMS) were fabricated and used for electrode modification. The characteristics of CMS were investigated using various techniques. The biocompatible sensing platform was built by immobilizing hemoglobin (Hb) on the micrometer-sized CMS-modified electrode with a layer of chitosan membrane. On the cyclic voltammogram, a couple of quasi-reversible cathodic and anodic peaks appeared, showing that direct electrochemistry of Hb with the working electrode was achieved. The catalytic reduction peak currents of the bioelectrode to trichloroacetic acid was established in the linear range of 2.0~70.0 mmol·L−1 accompanied by a detection limit of 0.30 mmol·L−1 (3σ). The modified electrode displayed favorable sensitivity, good reproducibility and stability, which suggests that CMS is promising for fabricating third-generation bioelectrochemical sensors. PMID:26703621

  3. Specific bile acids inhibit hepatic fatty acid uptake

    PubMed Central

    Nie, Biao; Park, Hyo Min; Kazantzis, Melissa; Lin, Min; Henkin, Amy; Ng, Stephanie; Song, Sujin; Chen, Yuli; Tran, Heather; Lai, Robin; Her, Chris; Maher, Jacquelyn J.; Forman, Barry M.; Stahl, Andreas

    2012-01-01

    Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. Here we tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%. In summary, the data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease. PMID:22531947

  4. Trichloroacetic acid (TCA) and trifluoroacetic acid (TFA) mixture toxicity to the macrophytes Myriophyllum spicatum and Myriophyllum sibiricum in aquatic microcosms.

    PubMed

    Hanson, Mark L; Sibley, Paul K; Mabury, Scott A; Solomon, Keith R; Muir, Derek C G

    2002-02-21

    Trichloroacetic acid (TCA) and trifluoroacetic acid (TFA) have been detected together in environmental water samples throughout the world. TCA may enter into aquatic systems via rainout as the degradation product of chlorinated solvents, herbicide use, as a by-product of water disinfection and from emissions of spent bleach liquor of kraft pulp mills. Sources of TFA include degradation of hydrofluorocarbons (HFCs) refrigerants and pesticides. These substances are phytotoxic and widely distributed in aquatic environments. A study to assess the risk of a binary mixture of TCA and TFA to macrophytes in aquatic microcosms was conducted as part of a larger study on haloacetic acids. M. spicatum and M. sibiricum were exposed to 0.1, 1, 3 and 10 mg/l of both TCA and TFA (neutralized with sodium hydroxide) in replicate (n = 3) 12000 l aquatic microcosms for 49 days in an one-way analysis of variance design. Each microcosm was stocked with 14 individual apical shoots per species. The plants were sampled at regular intervals and assessed for the somatic endpoints of plant length, root growth, number of nodes and wet and dry mass and the biochemical endpoints of chlorophyll-a, chlorophyll-b, carotenoid content and citric acid levels. Results indicate that there were statistically significant effects of the TCA/TFA mixture on certain pigment concentrations immediately after the start of exposure (2-7 days), but the plants showed no signs of stress thereafter. These data suggest that TCA/TFA mixtures at environmentally relevant concentrations do not pose a significant risk to these aquatic macrophytes.

  5. Improved Proteomic Analysis Following Trichloroacetic Acid Extraction of Bacillus anthracis Spore Proteins

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kaiser, Brooke LD; Wunschel, David S.; Sydor, Michael A.

    2015-08-07

    Proteomic analysis of bacterial samples provides valuable information about cellular responses and functions under different environmental pressures. Proteomic analysis is dependent upon efficient extraction of proteins from bacterial samples without introducing bias toward extraction of particular protein classes. While no single method can recover 100% of the bacterial proteins, selected protocols can improve overall protein isolation, peptide recovery, or enrich for certain classes of proteins. The method presented here is technically simple and does not require specialized equipment such as a mechanical disrupter. Our data reveal that for particularly challenging samples, such as B. anthracis Sterne spores, trichloroacetic acid extractionmore » improved the number of proteins identified within a sample compared to bead beating (714 vs 660, respectively). Further, TCA extraction enriched for 103 known spore specific proteins whereas bead beating resulted in 49 unique proteins. Analysis of C. botulinum samples grown to 5 days, composed of vegetative biomass and spores, showed a similar trend with improved protein yields and identification using our method compared to bead beating. Interestingly, easily lysed samples, such as B. anthracis vegetative cells, were equally as effectively processed via TCA and bead beating, but TCA extraction remains the easiest and most cost effective option. As with all assays, supplemental methods such as implementation of an alternative preparation method may provide additional insight to the protein biology of the bacteria being studied.« less

  6. DCA_Tools

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Summers, Michael S

    2017-11-08

    HPC software for ab-initio, condensed-matter physics, quantum mechanics calculations needs to be built on top of well tested libraries some of which address requirements unique to the programming domain. During the development of the DCA++ code, that we use in our research, we have developed a collection of libraries that may be of use to other computational scientists working in the same or similar domains. The libraries include: a) a pythonic input-language system, b) tensors whose shape is constructed from generalized dimension objects such at time domains. frequency domains, momentum domains, vertex domains et. al. and c) linear algebra operationsmore » that resolve to BLA/LAPACK operations when possible. This supports the implementation of Greens functions and operations on them such as are used in condensed matter physics.« less

  7. The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing.

    PubMed

    Mroz, Magdalena S; Lajczak, Natalia K; Goggins, Bridie J; Keely, Simon; Keely, Stephen J

    2018-03-01

    The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T 84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl - channels, whereas inhibition of CFTR activity with either CFTR- inh -172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes

  8. Membrane-aerated biofilm reactor for the removal of 1,2-dichloroethane by Pseudomonas sp. strain DCA1.

    PubMed

    Hage, J C; Van Houten, R T; Tramper, J; Hartmans, S

    2004-06-01

    A membrane-aerated biofilm reactor (MBR) with a biofilm of Pseudomonas sp. strain DCA1 was studied for the removal of 1,2-dichloroethane (DCA) from water. A hydrophobic membrane was used to create a barrier between the liquid and the gas phase. Inoculation of the MBR with cells of strain DCA1 grown in a continuous culture resulted in the formation of a stable and active DCA-degrading biofilm on the membrane. The maximum removal rate of the MBR was reached at a DCA concentration of approximately 80 micro M. Simulation of the DCA fluxes into the biofilm showed that the MBR performance at lower concentrations was limited by the DCA diffusion rate rather than by kinetic constraints of strain DCA1. Aerobic biodegradation of DCA present in anoxic water could be achieved by supplying oxygen solely from the gas phase to the biofilm grown on the liquid side of the membrane. As a result, direct aeration of the water, which leads to undesired coagulation of iron oxides, could be avoided.

  9. Comparison of efficacy of chemical peeling with 25% trichloroacetic acid and 0.1% retinoic acid for facial rejuvenation.

    PubMed

    Yildirim, Selda; Gurel, Mehmet Salih; Gungor, Sule; Tekeli, Omur; Canat, Dilek

    2016-06-01

    Skin aging is a problem which negatively affects the psyche of the person, social relations, as well as work life and health and which compels the patients to find appropriate treatment methods. Numerous treatment methods have been developed in order to delay aging and to reduce the aging effects in addition to having a younger, healthier and more beautiful facial appearance. To compare the efficiency, cosmetic results and possible adverse effects of the peeling treatment with 25% trichloroacetic acid (TCA) and 0.1% retinoic acid for facial rejuvenation in patients presenting with skin aging. Fifty female patients in total presenting with medium and advanced degree skin aging were subject to this study. Two separate treatment groups were formed; the first group underwent chemical skin treatment with 25% TCA while the other group was applied with 0.1% retinoic acid treatment. Following the 4 months' treatment the patients were controlled three times in total for post lesional hypopigmentation, hyperpigmentation, scars, skin irritation and other possible changes per month. The pretreatment and first follow-up visit, and final control images were comparatively evaluated by three observers via specific software. The healing rates of the group subject to retinoic acid were statistically higher (p < 0.05) compared to patients in the TCA group in the final follow-up visit following the treatment according to the first and second observers. On the other hand, according to the third observer, patients applied with retinoic acid presented with higher healing rates compared to those treated with TCA, however; this rate was not statistically significant (p > 0.05). The frequency of TCA- and retinoic acid-associated adverse effects was similar in both groups (p > 0.05). As a result of both treatments, a reduction in the quality of life scores as well as a pronounced recovery (p = 0.001) in the quality of life of those patients with skin aging was observed. The photo aging

  10. Comparison of efficacy of chemical peeling with 25% trichloroacetic acid and 0.1% retinoic acid for facial rejuvenation

    PubMed Central

    Gurel, Mehmet Salih; Gungor, Sule; Tekeli, Omur; Canat, Dilek

    2016-01-01

    Introduction Skin aging is a problem which negatively affects the psyche of the person, social relations, as well as work life and health and which compels the patients to find appropriate treatment methods. Numerous treatment methods have been developed in order to delay aging and to reduce the aging effects in addition to having a younger, healthier and more beautiful facial appearance. Aim To compare the efficiency, cosmetic results and possible adverse effects of the peeling treatment with 25% trichloroacetic acid (TCA) and 0.1% retinoic acid for facial rejuvenation in patients presenting with skin aging. Material and methods Fifty female patients in total presenting with medium and advanced degree skin aging were subject to this study. Two separate treatment groups were formed; the first group underwent chemical skin treatment with 25% TCA while the other group was applied with 0.1% retinoic acid treatment. Following the 4 months’ treatment the patients were controlled three times in total for post lesional hypopigmentation, hyperpigmentation, scars, skin irritation and other possible changes per month. The pretreatment and first follow-up visit, and final control images were comparatively evaluated by three observers via specific software. Results The healing rates of the group subject to retinoic acid were statistically higher (p < 0.05) compared to patients in the TCA group in the final follow-up visit following the treatment according to the first and second observers. On the other hand, according to the third observer, patients applied with retinoic acid presented with higher healing rates compared to those treated with TCA, however; this rate was not statistically significant (p > 0.05). The frequency of TCA- and retinoic acid-associated adverse effects was similar in both groups (p > 0.05). As a result of both treatments, a reduction in the quality of life scores as well as a pronounced recovery (p = 0.001) in the quality of life of those patients

  11. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells.

    PubMed

    Lajczak, Natalia K; Saint-Criq, Vinciane; O'Dwyer, Aoife M; Perino, Alessia; Adorini, Luciano; Schoonjans, Kristina; Keely, Stephen J

    2017-09-01

    Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release. Effects of DCA were mimicked by the Takeda GPCR 5 agonist, INT-777 (50 μM), but not by the farnesoid X receptor agonist, GW4064 (10 μM). INT-777 also stimulated colonic HβD1 and HβD2 release from wild-type, but not Takeda GPCR 5 -/- , mice. DCA stimulated phosphorylation of the p65 subunit of NF-κB, an effect that was attenuated by ursodeoxycholic acid, whereas an NF-κB inhibitor, BMS-345541 (25 μM), inhibited DCA-induced HβD2, but not HβD1, release. We conclude that bile acids can differentially regulate colonic epithelial HβD expression and secretion and discuss the implications of our findings for intestinal health and disease.-Lajczak, N. K., Saint-Criq, V., O'Dwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells. © FASEB.

  12. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression in Jurkat Cells.

    PubMed

    Pan, Yao; Wei, Xuetao; Hao, Weidong

    2015-08-28

    Trichloroethylene (TCE) is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells.

  13. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression inJurkat Cells

    PubMed Central

    Pan, Yao; Wei, Xuetao; Hao, Weidong

    2015-01-01

    Trichloroethylene (TCE) is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells. PMID:26343699

  14. THE ECOLOGICAL EFFECTS OF TRICHLORACETIC ACID (TCAA) IN THE ENVIRONMENT

    EPA Science Inventory

    Trichloroacetic acid (TCAA) is a member of the family of compounds known as chloroacetic acids, which includes mono-, di- and trichloroacetic acid. The significant property these compounds share is that they are all phytotoxic. TCAA once was widely used as a potent herbicide. ...

  15. Temporal variability in urinary levels of drinking water disinfection byproducts dichloroacetic acid and trichloroacetic acid among men

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Yi-Xin; Zeng, Qiang; Wang, Le

    Urinary haloacetic acids (HAAs), such as dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), have been suggested as potential biomarkers of exposure to drinking water disinfection byproducts (DBPs). However, variable exposure to and the short elimination half-lives of these biomarkers can result in considerable variability in urinary measurements, leading to exposure misclassification. Here we examined the variability of DCAA and TCAA levels in the urine among eleven men who provided urine samples on 8 days over 3 months. The urinary concentrations of DCAA and TCAA were measured by gas chromatography coupled with electron capture detection. We calculated the intraclass correlation coefficientsmore » (ICCs) to characterize the within-person and between-person variances and computed the sensitivity and specificity to assess how well single or multiple urine collections accurately determined personal 3-month average DCAA and TCAA levels. The within-person variance was much higher than the between-person variance for all three sample types (spot, first morning, and 24-h urine samples) for DCAA (ICC=0.08–0.37) and TCAA (ICC=0.09–0.23), regardless of the sampling interval. A single-spot urinary sample predicted high (top 33%) 3-month average DCAA and TCAA levels with high specificity (0.79 and 0.78, respectively) but relatively low sensitivity (0.47 and 0.50, respectively). Collecting two or three urine samples from each participant improved the classification. The poor reproducibility of the measured urinary DCAA and TCAA concentrations indicate that a single measurement may not accurately reflect individual long-term exposure. Collection of multiple urine samples from one person is an option for reducing exposure classification errors in studies exploring the effects of DBP exposure on reproductive health. - Highlights: • We evaluated the variability of DCAA and TCAA levels in the urine among men. • Urinary DCAA and TCAA levels varied greatly over a 3

  16. Influence of trichloroacetic acid peeling on the skin stress response system.

    PubMed

    Kimura, Ayako; Kanazawa, Nobuo; Li, Hong-Jin; Yonei, Nozomi; Yamamoto, Yuki; Furukawa, Fukumi

    2011-08-01

    Although trichloroacetic acid (TCA) peeling is widely applied for cosmetic treatment of photodamaged skin, the entire biological mechanisms have yet to be determined. The skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) products that are locally-generated in response to locally-provided stressors or pro-inflammatory cytokines. This system would restrict tissue damage and restore local homeostasis. To determine the influence of TCA peeling on the SSRS in vitro and in vivo, expressions of POMC, melanocortin receptor 1 (MC1R), CRH and CRH receptor 1 (CRHR1) mRNA were examined by reverse transcription polymerase chain reaction in Pam212 murine keratinocytes, murine plantar and healthy human abdominal skin specimens after TCA treatment. In addition, their protein expressions as well as those of POMC-derived peptides were examined immunohistochemically. After TCA treatment, transient upregulation of POMC and MC1R mRNA expressions was observed in both murine and human skin, as well as in Pam212. Enhanced POMC protein, recovery of once-impaired MC1R protein, and no enhancement of POMC-derived peptide productions were revealed immunohistochemically in both murine and human epidermis. In contrast, neither expression levels of CRH and CRHR1 mRNA nor epidermal protein were enhanced after TCA application in murine and human skin, except for induction of human CRH mRNA expression. These results suggest that TCA activates the SSRS by inducing POMC and MC1R productions of keratinocytes in the CRH-independent manner, and that the biological effects of POMC itself are responsible for the TCA-induced epidermal SSRS activation. © 2010 Japanese Dermatological Association.

  17. Synthesis of feather-like CeO2 microstructures and enzymatic electrochemical catalysis for trichloroacetic acid

    NASA Astrophysics Data System (ADS)

    Xiao, Xin; Zhang, Dong En; Zhang, Fan; Gong, Jun Yan; Zhang, Xiao Bo; Wang, Yi Hui; Ma, Juan Juan; Tong, Zhi Wei

    Novel feather-like CeO2 microstructures were achieved by a thermal decomposition approach of Ce(OH)CO3 precursor. The Ce(OH)CO3 was obtained from a solvothermal method employing Ce(NO3)3.6H2O with C6H12N4 and C16H33(CH3)3NBr (CTAB) at 190∘C in a water-PEG-200 mixed solution. The feather-like CeO2 dendrite was obtained by thermal conversion of the feather-like Ce(OH)CO3 at 650∘C in air. A reasonable growth mechanism was proposed with the soft-template effect of PEG-200. The electrochemical behavior and enzyme activity of myoglobin (Mb) immobilized on CeO2-Nafion modified glassy carbon electrode (GCE) are demonstrated by cyclic voltammetric measurements. The results indicate that CeO2 can obviously promote the direct electron transfer between the Mb redox centers and the electrode. The Mb on CeO2-Nafion behaves as an elegant performance on the electrochemical reduction of trichloroacetic acid (TCA) from 0.32μM to 2.28μM. The detection limit is estimated to be 0.08μM.

  18. Input of trichloroacetic acid into the vegetation of various climate zones--measurements on several continents.

    PubMed

    Weissflog, Ludwig; Krüger, Gert; Elansky, Nikolai; Putz, Erich; Pfennigsdorff, Andrea; Seyfarth, Klaus Ullrich; Nüchter, Matthias; Lange, Christian; Kotte, Karsten

    2003-07-01

    Trichloroacetic acid (TCA, CCl(3)COOH) is a phytotoxic chemical. Although TCA salts and derivates were once used as herbicides to combat perennial grasses and weeds, they have since been banned because of their indiscriminate herbicidal effects on woody plant species. However, TCA can also be formed in the atmosphere. For instance, the high-volatile C(2)-chlorohydrocarbons tetrachloroethene (TECE, C(2)Cl(4)) and 1,1,1-trichloroethane (TCE, CCl(3)CH(3)) can react under oxidative conditions in the atmosphere to form TCA and other substances. The ongoing industrialisation of Southeast Asia, South Africa and South America means that use of TECE as solvents in the metal and textile industries of these regions in the southern hemisphere can be expected to rise. The increasing emissions of this substance--together with the rise in the atmospheric oxidation potential caused by urban activities, slash and burn agriculture and forest fires in the southern hemisphere--could lead to a greater input/formation of TCA in the vegetation located in the lee of these emission sources. By means of biomonitoring studies, the input/formation of TCA in vegetation was detected at various locations in South America, North America, Africa, and Europe.

  19. Vapor intrusion risk of lead scavengers 1,2-dibromoethane (EDB) and 1,2-dichloroethane (DCA).

    PubMed

    Ma, Jie; Li, Haiyan; Spiese, Richard; Wilson, John; Yan, Guangxu; Guo, Shaohui

    2016-06-01

    Vapor intrusion of synthetic fuel additives represented a critical yet still neglected problem at sites impacted by petroleum fuel releases. This study used an advanced numerical model to simulate the vapor intrusion risk of lead scavengers 1,2-dibromoethane (ethylene dibromide, EDB) and 1,2-dichloroethane (DCA) under different site conditions. We found that simulated EDB and DCA indoor air concentrations can exceed USEPA screening level (4.7 × 10(-3) μg/m(3) for EDB and 1.1 × 10(-1) μg/m(3) for DCA) if the source concentration is high enough (is still within the concentration range found at leaking UST site). To evaluate the chance that vapor intrusion of EDB might exceed the USEPA screening levels for indoor air, the simulation results were compared to the distribution of EDB at leaking UST sites in the US. If there is no degradation of EDB or only abiotic degradation of EDB, from 15% to 37% of leaking UST sites might exceed the USEPA screening level. This study supports the statements made by USEPA in the Petroleum Vapor Intrusion (PVI) Guidance that the screening criteria for petroleum hydrocarbon may not provide sufficient protectiveness for fuel releases containing EDB and DCA. Based on a thorough literature review, we also compiled previous published data on the EDB and DCA groundwater source concentrations and their degradation rates. These data are valuable in evaluating EDB and DCA vapor intrusion risk. In addition, a set of refined attenuation factors based on site-specific information (e.g., soil types, source depths, and degradation rates) were provided for establishing site-specific screening criteria for EDB and DCA. Overall, this study points out that lead scavengers EDB and DCA may cause vapor intrusion problems. As more field data of EDB and DCA become available, we recommend that USEPA consider including these data in the existing PVI database and possibly revising the PVI Guidance as necessary. Copyright © 2016 Elsevier Ltd. All

  20. Tumorigenic effects of dichloroacetic acid in female F344 rats

    EPA Science Inventory

    Introduction: Dichloroacetic acid (DCA) is a halogenated organic acid produced during oxidant disinfection of drinking water. Prior studies indicate that DCA may increase liver tumors in mice. Here we evaluated the hepatic tumorigenicity of DCA in female rats when given alone ...

  1. Lack of formic acid production in rat hepatocytes and human renal proximal tubule cells exposed to chloral hydrate or trichloroacetic acid

    PubMed Central

    Lock, Edward A; Reed, Celia J; McMillan, JoEllyn M; Oatis, John R; Schnellmann, Rick G

    2007-01-01

    The industrial solvent trichloroethylene (TCE) and its major metabolites have been shown to cause formic aciduria in male rats. We have examined whether chloral hydrate (CH) and trichloroacetic acid (TCA), known metabolites of TCE, produce an increase in formic acid in vitro in cultures of rat hepatocytes or human renal proximal tubule cells (HRPTC). The metabolism and cytotoxicity of CH was also examined to establish that the cells were metabolically active and not compromised by toxicity. Rat hepatocytes and HRPTC were cultured in serum-free medium and then treated with 0.3–3mM CH for 3 days or 0.03–3mM CH for 10 days respectively and formic acid production, metabolism to trichloroethanol (TCE-OH) and TCA and cytotoxicity determined. No increase in formic acid production in rat hepatocytes or HRPTC exposed to CH was observed over and above that due to chemical degradation, neither was formic acid production observed in rat hepatocytes exposed to TCA. HRPTC metabolised CH to TCE-OH and TCA with a 12-fold greater capacity to form TCE-OH versus TCA. Rat hepatocytes exhibited a 1.6-fold and 3-fold greater capacity than HRPTC to form TCE-OH and TCA respectively. CH and TCA were not cytotoxic to rat hepatocytes at concentrations up to 3mM/day for 3 days. With HRPTC, one sample showed no cytotoxicity to CH at concentrations up to 3mM/day for 10 days, while in another cytotoxicity was seen at 1mM/day for 3 days. In summary, increased formic acid production was not observed in rat hepatocytes or HRPTC exposed to TCE metabolites, suggesting that the in vivo response cannot be modelled in vitro. CH was toxic to HRPTC at millimolar concentrations/day over 10 days, while glutathione derived metabolites of TCE were toxic at micromolar concentrations/day over 10 days (Lock et al., 2006) supporting the view that glutathione derived metabolites are likely to be responsible for nephrotoxicity. PMID:17161896

  2. Honokiol bis-dichloroacetate (Honokiol DCA) demonstrates activity in vemurafenib-resistant melanoma in vivo.

    PubMed

    Bonner, Michael Y; Karlsson, Isabella; Rodolfo, Monica; Arnold, Rebecca S; Vergani, Elisabetta; Arbiser, Jack L

    2016-03-15

    The majority of human melanomas bears BRAF mutations and thus is treated with inhibitors of BRAF, such as vemurafenib. While patients with BRAF mutations often demonstrate an initial dramatic response to vemurafenib, relapse is extremely common. Thus, novel agents are needed for the treatment of these aggressive melanomas. Honokiol is a small molecule compound derived from Magnolia grandiflora that has activity against solid tumors and hematopoietic neoplasms. In order to increase the lipophilicity of honokiol, we have synthesized honokiol DCA, the dichloroacetate ester of honokiol. In addition, we synthesized a novel fluorinated honokiol analog, bis-trifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro). Both compounds exhibited activity against A375 melanoma in vivo, but honokiol DCA was more active. Gene arrays comparing treated with vehicle control tumors demonstrated induction of the respiratory enzyme succinate dehydrogenase B (SDHB) by treatment, suggesting that our honokiol analogs induce respiration in vivo. We then examined its effect against a pair of melanomas, LM36 and LM36R, in which LM36R differs from LM36 in that LM36R has acquired vemurafenib resistance. Honokiol DCA demonstrated in vivo activity against LM36R (vemurafenib resistant) but not against parental LM36. Honokiol DCA and hexafluoro inhibited the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Honokiol DCA may act in vemurafenib resistant melanomas to increase both respiration and reactive oxygen generation, leading to activity against aggressive melanoma in vivo.

  3. Sparse Covariance Matrix Estimation by DCA-Based Algorithms.

    PubMed

    Phan, Duy Nhat; Le Thi, Hoai An; Dinh, Tao Pham

    2017-11-01

    This letter proposes a novel approach using the [Formula: see text]-norm regularization for the sparse covariance matrix estimation (SCME) problem. The objective function of SCME problem is composed of a nonconvex part and the [Formula: see text] term, which is discontinuous and difficult to tackle. Appropriate DC (difference of convex functions) approximations of [Formula: see text]-norm are used that result in approximation SCME problems that are still nonconvex. DC programming and DCA (DC algorithm), powerful tools in nonconvex programming framework, are investigated. Two DC formulations are proposed and corresponding DCA schemes developed. Two applications of the SCME problem that are considered are classification via sparse quadratic discriminant analysis and portfolio optimization. A careful empirical experiment is performed through simulated and real data sets to study the performance of the proposed algorithms. Numerical results showed their efficiency and their superiority compared with seven state-of-the-art methods.

  4. Removal of EDB and 1,2-DCA by Abiotic Reaction with Iron(II) Sulfide

    EPA Science Inventory

    Ethylene Dibromide (EDB) and 1,2-Dichloroethane (1,2-DCA) were used as lead scavengers in leaded motor gasoline in the USA until the late 1980s. Leaded gasoline in contact with ground water should produce concentrations of EDB near 1900 µg/L, and concentrations of 1,2-DCA near 3...

  5. Comparative Study of the Use of Trichloroacetic Acid and Phenolic Acid in the Treatment of Atrophic-Type Acne Scars.

    PubMed

    Dalpizzol, Mariana; Weber, Magda B; Mattiazzi, Anna Paula F; Manzoni, Ana Paula D

    2016-03-01

    Many therapies involving varying degrees of complexity have been used to treat acne scars, but none is considered the gold standard treatment. A comparative evaluation of 88% phenol and 90% trichloroacetic acid (TCA) applied using the chemical reconstruction of skin scars (CROSS) technique. A nonrandomized, single-blinded self-controlled clinical trial was conducted among patients with ice pick-type and boxcar-type atrophic acne scars. Using 88% phenol on the left hemiface and 90% TCA on the right hemiface was adopted as the standard practice of the CROSS technique. The dermatological quality of life index (DLQI) questionnaire, acne scar grading scale Échelle d´Evaluation Clinique des Cicatrices d'Acne (ECCA), and evaluation of improvement were performed pretreatment and post-treatment. Regarding ECCA, significant differences were found in pretreatment and post-treatment (p < .001). Regarding tolerance to pain, it was found that the discomfort felt with 90% TCA was significantly less than that felt with 88% phenol (p = .020). Regarding the quality of life measured with the DLQI, the results showed that the mean score in post-treatment assessment was significantly lower than that in the pretreatment assessment (p < .05). Hypochromia and enlargement scar were only seen after the use of 90% TCA. This study confirmed the efficacy of both TCA and phenol for treating such scars, with less severe complications from the use of phenol.

  6. Trichloroacetic acid fate and toxicity to the macrophytes Myriophyllum spicatum and Myriophyllum sibiricum under field conditions.

    PubMed

    Hanson, Mark L; Sibley, Paul K; Ellis, David A; Fineberg, Neil A; Mabury, Scott A; Solomon, Keith R; Muir, Derek C

    2002-03-01

    Trichloroacetic acid (TCA) has been detected in rain, snow, and river samples throughout the world. It may enter into natural water systems via herbicide use, as a by-product of water disinfection, from emissions of spent bleach liquor of kraft pulp mills, and as a natural fungal product. This compound is phytotoxic and likely to accumulate in aquatic environments. A study to assess the fate of TCA in semi-natural aquatic environments and the toxicity of TCA to rooted aquatic macrophytes was conducted. The experiment involved exposing three replicate 12000 l aquatic microcosms at the University of Guelph Microcosm Facility to 0.05, 0.5, 3, and 10 mg/l of TCA for 35 days in a one-way analysis of variance design. Each microcosm was stocked with 14 individual 5 cm apical shoots of Myriophyllum spicatum and M. sibiricum. The plants were sampled at regular intervals and assessed for the somatic endpoints of plant length, root growth, number of nodes and wet and dry mass and the biochemical endpoints of chlorophyll-a and chlorophyll-b, carotenoid content, and citric acid levels. TCA half-lives in the microcosms ranged from 190 to 296 h depending on the initial concentration of TCA. Myriophyllum spp. results indicate that while there were some statistically significant differences from controls, there were no biologically significant effects of TCA for any of the endpoints examined. These data suggest that TCA does not pose a significant risk to these macrophytes up to 10 mg/l, which typically exceeds environmentally relevant concentrations by several orders of magnitude.

  7. Opposing effects of bile acids deoxycholic acid and ursodeoxycholic acid on signal transduction pathways in oesophageal cancer cells.

    PubMed

    Abdel-Latif, Mohamed M; Inoue, Hiroyasu; Reynolds, John V

    2016-09-01

    Ursodeoxycholic acid (UDCA) was reported to reduce bile acid toxicity, but the mechanisms underlying its cytoprotective effects are not fully understood. The aim of the present study was to examine the effects of UDCA on the modulation of deoxycholic acid (DCA)-induced signal transduction in oesophageal cancer cells. Nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activity was assessed using a gel shift assay. NF-κB activation and translocation was performed using an ELISA-based assay and immunofluorescence analysis. COX-2 expression was analysed by western blotting and COX-2 promoter activity was assessed by luciferase assay. DCA induced NF-κB and AP-1 DNA-binding activities in SKGT-4 and OE33 cells. UDCA pretreatment inhibited DCA-induced NF-κB and AP-1 activation and NF-κB translocation. This inhibitory effect was coupled with a blockade of IκB-α degradation and inhibition of phosphorylation of IKK-α/β and ERK1/2. Moreover, UDCA pretreatment inhibited COX-2 upregulation. Using transient transfection of the COX-2 promoter, UDCA pretreatment abrogated DCA-induced COX-2 promoter activation. In addition, UDCA protected oesophageal cells from the apoptotic effects of deoxycholate. Our findings indicate that UDCA inhibits DCA-induced signalling pathways in oesophageal cancer cells. These data indicate a possible mechanistic role for the chemopreventive actions of UDCA in oesophageal carcinogenesis.

  8. Importance of Dichloroacetate and Trichloroacetate to the Hepatocarcinogenic Response to Trichloroeylene in B6C3F1 Mice

    DTIC Science & Technology

    1989-10-15

    Baker Co., polysorbate (Tween 80), beta- glucuronidase (Type VII), N-methyl-N’-nitro-N-nitrosoguanidine (MNNG), clofibrate , phenobllbital, DCA, TCA...TCOH conjugated wit’a glucuronic acid was determined in an aliquot of sample treated with beta-glucuronidase. A Varian Model 3700 gas chromatQgraph...diaminobenzoic acid fluorimetric assay. The fraction of DNA unwound during the two hour incubation at OC was calculated as: (Total DNA - DS DNA)t

  9. Identification and Characterization of Daurichromenic Acid Synthase Active in Anti-HIV Biosynthesis.

    PubMed

    Iijima, Miu; Munakata, Ryosuke; Takahashi, Hironobu; Kenmoku, Hiromichi; Nakagawa, Ryuichi; Kodama, Takeshi; Asakawa, Yoshinori; Abe, Ikuro; Yazaki, Kazufumi; Kurosaki, Fumiya; Taura, Futoshi

    2017-08-01

    Daurichromenic acid (DCA) synthase catalyzes the oxidative cyclization of grifolic acid to produce DCA, an anti-HIV meroterpenoid isolated from Rhododendron dauricum We identified a novel cDNA encoding DCA synthase by transcriptome-based screening from young leaves of R. dauricum The gene coded for a 533-amino acid polypeptide with moderate homologies to flavin adenine dinucleotide oxidases from other plants. The primary structure contained an amino-terminal signal peptide and conserved amino acid residues to form bicovalent linkage to the flavin adenine dinucleotide isoalloxazine ring at histidine-112 and cysteine-175. In addition, the recombinant DCA synthase, purified from the culture supernatant of transgenic Pichia pastoris , exhibited structural and functional properties as a flavoprotein. The reaction mechanism of DCA synthase characterized herein partly shares a similarity with those of cannabinoid synthases from Cannabis sativa , whereas DCA synthase catalyzes a novel cyclization reaction of the farnesyl moiety of a meroterpenoid natural product of plant origin. Moreover, in this study, we present evidence that DCA is biosynthesized and accumulated specifically in the glandular scales, on the surface of R. dauricum plants, based on various analytical studies at the chemical, biochemical, and molecular levels. The extracellular localization of DCA also was confirmed by a confocal microscopic analysis of its autofluorescence. These data highlight the unique feature of DCA: the final step of biosynthesis is completed in apoplastic space, and it is highly accumulated outside the scale cells. © 2017 American Society of Plant Biologists. All Rights Reserved.

  10. Physiologically Based Pharmacokinetic (PBPK) Modeling of ...

    EPA Pesticide Factsheets

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, inter-individual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data.Objectives: To evaluate the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and one hybrid mouse strains to calibrate and extend existing physiologically-based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). A Bayesian population analysis of inter-strain variability was used to quantify variability in TCE metabolism. Results: Concentration-time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation was less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production was less variable (2-fold range) than DCA production (5-fold range), although uncertainty bounds for DCA exceeded the predicted variability. Conclusions:

  11. Comparative cytotoxic and genotoxic potential of 13 drinking water disinfection by-products using a microplate-based cytotoxicity assay and a developed SOS/umu assay.

    PubMed

    Zhang, Shao-Hui; Miao, Dong-Yue; Tan, Li; Liu, Ai-Lin; Lu, Wen-Qing

    2016-01-01

    The implications of disinfection by-products (DBPs) present in drinking water are of public health concern because of their potential mutagenic, carcinogenic and other toxic effects on humans. In this study, we selected 13 main DBPs found in drinking water to quantitatively analyse their cytotoxicity and genotoxicity using a microplate-based cytotoxicity assay and a developed SOS/umu assay in Salmonella typhimurium TA1535/pSK1002. With the developed SOS/umu test, eight DBPs: 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-fura3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H]-furanone (MX), dibromoacetonitrile (DBN), iodoacetic acid (IA), bromochloroacetonitrile (BCN), bromoacetic acid (BA), trichloroacetonitrile (TCN), dibromoacetic acid (DBA) and dichloroacetic acid (DCA) were significantly genotoxic to S. typhimurium. Three DBPs: chloroacetic acid (CA), trichloroacetic acid (TCA) and dichloroacetonitrile (DCN) were weakly genotoxic, whereas the remaining DBPs: chloroacetonitrile (CN) and chloral hydrate (CH) were negative. The rank order in decreasing genotoxicity was as follows: MX > DBN > IA > BCN > BA > TCN > DBA > DCA > CA, TCA, DCN > CN, CH. MX was approximately 370 000 times more genotoxic than DCA. In the microplate-based cytotoxicity assay, cytotoxic potencies of the 13 DBPs were compared and ranked in decreasing order as follows: MX > IA > DBN > BCN > BA > TCN > DCN > CA > DCA > DBA > CN > TCA > CH. MX was approximately 19 200 times more cytotoxic than CH. A statistically significant correlation was found between cytotoxicity and genotoxicity of the 13 DBPs in S. typhimurium. Results suggest that microplate-based cytotoxicity assay and the developed SOS/umu assay are feasible tools for analysing the cytotoxicity and genotoxicity of DBPs, particularly for comparing their toxic intensities quantitatively. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e

  12. Evaluation of the Role of Peroxisome Proliferator-Activated Receptor α (PPARα) in Mouse Liver Tumor Induction by Trichloroethylene and Metabolites

    EPA Science Inventory

    Trichloroethylene (TCE) is an industrial solvent and a widespread environmental contaminant. Induction of liver cancer in mice by TCE is thought to be mediated by two metabolites, dichloroacetate (DCA) and trichloroacetate (TCA), both of which are themselves mouse liver carcinoge...

  13. ALTERED GENE EXPRESSION IN MOUSE LIVERS AFTER DICHLOROACETIC ACID EXPOSURE

    EPA Science Inventory

    Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated that DCA exhibits hepatocarcinogenic effects in rodents when administered in drinking water. The mechanism(s) involved in DCA induction of cancer are not clear...

  14. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids.

    PubMed

    Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H; Wang, David H; Chen, Minhu; Souza, Rhonda F; Spechler, Stuart Jon

    2014-07-15

    Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. Copyright © 2014 the American Physiological Society.

  15. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids

    PubMed Central

    Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H.; Wang, David H.; Chen, Minhu; Spechler, Stuart Jon

    2014-01-01

    Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. PMID:24852569

  16. Vibrational, calorimetric and nonlinear optical studies of melaminium-bis(trichloroacetate) monohydrate molecular ionic crystal

    NASA Astrophysics Data System (ADS)

    Debrus, S.; Marchewka, M. K.; Drozd, M.; Ratajczak, H.

    2007-04-01

    The efficiency of second harmonic generation for melaminium bis(trichloroacetate) was estimated relatively to KDP: deff = 3.09 deff (KDP). Room temperature FT IR and FT Raman spectra were recorded. Some spectral features of this new crystal are referred to corresponding one for melamine crystal as well as for other trichloroacetates. Differential scanning calorimetric measurements performed on powder sample indicate the phase transition point at approximately 276 and 239 K for heating and cooling, respectively.

  17. MICROARRAY ANALYSIS OF DICHLOROACETIC ACID-INDUCED CHANGES IN GENE EXPRESSION

    EPA Science Inventory


    MICROARRAY ANALYSIS OF DICHLOROACETIC ACID-INDUCED CHANGES IN GENE EXPRESSION

    Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated the hepatocarcinogenicity of DCA in rodents when administered in dri...

  18. Focal high-concentration trichloroacetic acid peeling for treatment of atrophic facial chickenpox scar: an open-label study.

    PubMed

    Barikbin, Behrooz; Saadat, Nelda; Akbari, Zahra; Yousefi, Maryam; Toossi, Parviz

    2012-10-01

    Despite their prevalence, there is a paucity of information in the medical literature on the treatment of atrophic chickenpox scars. To evaluate the efficacy and safety of using the chemical reconstruction of skin scar technique for the treatment of atrophic facial chickenpox scars. One hundred patients (mean age 23 years; Fitzpatrick skin types II-IV) were treated with focal chemical peeling with 70% trichloroacetic acid (TCA) for a maximum of six sessions. Improvement rate, frequency of adverse events and patient satisfaction were assessed. Five hundred thirty-three peeling sessions in 100 consecutive patients were performed. Final assessment at 12-week follow-up visit after the last treatment revealed improvement in 95% of patients: mild improvement in 12 cases, moderate improvement in 42 cases, and marked improvement in 41 cases. The appearance of scars did not change in five patients. Seventy-nine patients expressed moderate to high satisfaction with the results. Post-treatment side effects were mild and transient, resolving gradually within the study period. Focal peeling with high-concentration TCA appears to be a safe and effective alternative in the treatment of atrophic facial chickenpox scars. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  19. Evaluation of 99mtechnetium-radiopharmaceutical binding to blood elements using different trichloroacetic acid concentrations.

    PubMed

    Freitas, R S; Gutfilen, B; da Fonseca, L M; Bernardo-Filho, M

    1996-01-01

    Secure determination of the binding of 99mTc-radiopharmaceuticals to plasma (P) and blood cell (BC) constituents can help to understand the biodistribution of radiophamaceuticals. The reported precipitation studies of blood with radiopharmaceuticals have shown that the results can not be easily compared between studies. We decided to determine the "gold standard" concentration of trichloroacetic acid (TCA) to evaluate the binding to blood elements for several radiopharmaceuticals used in routine nuclear medicine. We have studied phytic (99mTc-PHY), diethylenetriaminepentaacetic (99mTc-DTPA), glucoheptonic (99mTc-GHA) and dimercaptosuccinic (99mTc-DMSA) acids. Blood was incubated with radiopharmaceuticals, centrifuged and P and BC separated. Samples of P and BC were also precipitated with TCA concentrations (20.0, 10.0, 5.0, 1.0, 0.5 and 0.1 percent) and soluble (SF) and insoluble fractions (IF) were isolated. The percent radioactivity (percent rad) in IF-P depends on TCA concentration. It varied from 36.4 to 65.0 (99mTc-PHY), from 17.9 to 32.0 (99mTc-DTPA), from 11.5 to 38.8 (99mTc-GHA) and from 52.8 to 66.2 (99mTc-DMSA). The results for the binding of 99mTc-PHY to IF-P show that there was no differences in the percent rad when TCA concentrations of 0.1 to 1.0 percent were used. For 99mTc-DTPA, 5.0 percent is the best TCA concentration. For 99mTc-GHA, low values of percent rad bound to IF-P is found with TCA concentrations of 0.1, 0.5 and 1.0. Interestingly, with 99mTc-DMSA, high values of bound radioactivity are not dependent on TCA concentrations (0.1 to 10.0). Radioactivity in IF-BC depends on TCA concentration and it varied for 99mTc-PHY (80.1 to 54.1) and for 99mTc-GHA (85.5 to 61.7). With 99mTc-DTPA and with 99mTc-DMSA the percent rad in IF-BC seems independent of TCA concentration. We suggest that the evaluation of the binding of the various 99mTc-radiopharmaceuticals to blood constituents, using only one TCA concentration, should be avoided.

  20. Supercritical carbon dioxide treatment as a method for polymorph preparation of deoxycholic acid.

    PubMed

    Tozuka, Yuichi; Kawada, Dai; Oguchi, Toshio; Yamamoto, Keiji

    2003-09-16

    A new polymorph of deoxycholic acid (DCA) was formed by using a supercritical carbon dioxide treatment. Deoxycholic acid crystals were stored in a pressure vessel purged with carbon dioxide at 12MPa, 60 degrees C for definite intervals. After storage for 1h in supercritical carbon dioxide (SC-CO2), new X-ray diffraction (XRD) peaks, not found in the bulk DCA crystal, were observed at 2theta = 7.4 degrees, 9.7 degrees and 14.0 degrees. The intensities of the new diffraction peaks increased with an increase in storage time, whereas the intensities of the diffraction peaks due to bulk DCA crystal decreased. On the DSC curves, the crystals obtained showed an exothermic peak at around 155 degrees C followed by the melting peak of bulk DCA crystal at 175 degrees C. By the temperature-controlled powder XRD measurement, the crystals obtained were found to be a metastable form of DCA. The polymorphs of DCA have not been reported; therefore, the SC-CO2 treatment would be a peculiar method to obtain a DCA polymorph.

  1. The Role of Biotransformation and Oxidative Stress in 3,5-Dichloroaniline (3,5-DCA) Induced Nephrotoxicity in Isolated Renal Cortical Cells from Male Fischer 344 Rats

    PubMed Central

    Racine, Christopher R.; Ferguson, Travis; Preston, Debbie; Ward, Dakota; Ball, John; Anestis, Dianne; Valentovic, Monica; Rankin, Gary O.

    2016-01-01

    Among the mono- and dichloroanilines, 3,5-Dichloroaniline (3,5-DCA) is the most potent nephrotoxicant in vivo and in vitro. However, the role of renal biotransformation in 3,5-DCA induced nephrotoxicity is unknown. The current study was designed to determine the in vitro nephrotoxic potential of 3,5-DCA in isolated renal cortical cells (IRCC) obtained from male Fischer 344 rats, and the role of renal bioactivation and oxidative stress in 3,5-DCA nephrotoxicity. IRCC (~4 million cells/ml) from male rats were exposed to 3,5-DCA (0-1.0 mM) for up to 120 min. In IRCC, 3,5-DCA was cytotoxic at 1.0 mM by 60 min as evidenced by the increased release of lactate dehydrogenase (LDH), but 120 min was required for 3,5-DCA 0.5 mM to increase LDH release. In subsequent studies, IRCC were exposed to a pretreatment (antioxidant or enzyme inhibitor) prior to exposure to 3,5-DCA (1.0 mM) for 90 min. Cytotoxicity induced by 3,5-DCA was attenuated by pretreatment with inhibitors of flavin-containing monooxygenase (FMO; methimazole, N-octylamine), cytochrome P450 (CYP; piperonyl butoxide, metyrapone), or peroxidase (indomethacin, mercaptosuccinate) enzymes. Use of more selective CYP inhibitors suggested that the CYP 2C family contributed to 3,5-DCA bioactivation. Antioxidants (glutathione, N-acetyl-L-cysteine, α-tocopherol, ascorbate, pyruvate) also attenuated 3,5-DCA nephrotoxicity, but oxidized glutathione levels and the oxidized/reduced glutathione ratios were not increased. These results indicate that 3,5-DCA may be activated via several renal enzyme systems to toxic metabolites, and that free radicals, but not oxidative stress, contribute to 3,5-DCA induced nephrotoxicity in vitro. PMID:26808022

  2. Comparison of DNA damage in human-derived hepatoma line (HepG2) exposed to the fifteen drinking water disinfection byproducts using the single cell gel electrophoresis assay.

    PubMed

    Zhang, Li; Xu, Liang; Zeng, Qiang; Zhang, Shao-Hui; Xie, Hong; Liu, Ai-Lin; Lu, Wen-Qing

    2012-01-24

    Disinfection of drinking water reduces pathogenic infection, but generates disinfection by-products (DBPs) in drinking water. In this study, the effect of fifteen DBPs on DNA damage in human-derived hepatoma line (HepG2) was investigated by the single cell gel electrophoresis (SCGE) assay. These fifteen DBPs are: four trihalomethanes (THMs), six haloacetic acides (HAAs), three haloacetonitriles (HANs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), and chloral hydrate (CH). Based on the minimal effective concentration (MEC) at which DBPs induced significant increase in olive tail moment (OTM), the rank order of DNA-damaging potency is: bromodichloromethane (BDCM)>dibromochloromethane (DBCM)>tribromomethane (TBM)>trichloromethane (TCM) of the four THMs; iodoacetic acid (IA)>bromoacetic acid (BA)>dibromoacetic acid (DBA)>dichloracetic acid (DCA)>trichloroacetic acid (TCA) of the five HAAs; dibromoacetonitrile (DBN)approximately dichloroacetonitrile (DCN)>trichloroacetonitrile (TCN) of the three HANs. The DNA damaging potency of MX and CH is similar to TCA and DCA, respectively. IA is the most genotoxic DBP in the fifteen DBPs, followed by BA. Chloroacetic acid (CA) is not genotoxic in this assay. Our findings indicated that HepG2/SCGE is a sensitive tool to evaluate the genotoxicity of DBPs and iodinated DBPs are more genotoxic than brominated DBPs, but chlorinated DBPs are less genotoxic than brominated DBPs. © 2011 Elsevier B.V. All rights reserved.

  3. RENEB intercomparisons applying the conventional Dicentric Chromosome Assay (DCA).

    PubMed

    Oestreicher, Ursula; Samaga, Daniel; Ainsbury, Elizabeth; Antunes, Ana Catarina; Baeyens, Ans; Barrios, Leonardo; Beinke, Christina; Beukes, Philip; Blakely, William F; Cucu, Alexandra; De Amicis, Andrea; Depuydt, Julie; De Sanctis, Stefania; Di Giorgio, Marina; Dobos, Katalin; Dominguez, Inmaculada; Duy, Pham Ngoc; Espinoza, Marco E; Flegal, Farrah N; Figel, Markus; Garcia, Omar; Monteiro Gil, Octávia; Gregoire, Eric; Guerrero-Carbajal, C; Güçlü, İnci; Hadjidekova, Valeria; Hande, Prakash; Kulka, Ulrike; Lemon, Jennifer; Lindholm, Carita; Lista, Florigio; Lumniczky, Katalin; Martinez-Lopez, Wilner; Maznyk, Nataliya; Meschini, Roberta; M'kacher, Radia; Montoro, Alegria; Moquet, Jayne; Moreno, Mercedes; Noditi, Mihaela; Pajic, Jelena; Radl, Analía; Ricoul, Michelle; Romm, Horst; Roy, Laurence; Sabatier, Laure; Sebastià, Natividad; Slabbert, Jacobus; Sommer, Sylwester; Stuck Oliveira, Monica; Subramanian, Uma; Suto, Yumiko; Que, Tran; Testa, Antonella; Terzoudi, Georgia; Vral, Anne; Wilkins, Ruth; Yanti, LusiYanti; Zafiropoulos, Demetre; Wojcik, Andrzej

    2017-01-01

    Two quality controlled inter-laboratory exercises were organized within the EU project 'Realizing the European Network of Biodosimetry (RENEB)' to further optimize the dicentric chromosome assay (DCA) and to identify needs for training and harmonization activities within the RENEB network. The general study design included blood shipment, sample processing, analysis of chromosome aberrations and radiation dose assessment. After manual scoring of dicentric chromosomes in different cell numbers dose estimations and corresponding 95% confidence intervals were submitted by the participants. The shipment of blood samples to the partners in the European Community (EU) were performed successfully. Outside the EU unacceptable delays occurred. The results of the dose estimation demonstrate a very successful classification of the blood samples in medically relevant groups. In comparison to the 1st exercise the 2nd intercomparison showed an improvement in the accuracy of dose estimations especially for the high dose point. In case of a large-scale radiological incident, the pooling of ressources by networks can enhance the rapid classification of individuals in medically relevant treatment groups based on the DCA. The performance of the RENEB network as a whole has clearly benefited from harmonization processes and specific training activities for the network partners.

  4. Therapeutic value of trichloroacetic acid in the treatment of isolated genital warts on the external female genitalia.

    PubMed

    Taner, Zeki M; Taskiran, Cagatay; Onan, Anil M; Gursoy, Rifat; Himmetoglu, Ozdemir

    2007-06-01

    To evaluate the value of 85% trichloroacetic acid (TCA) in the treatment of human papillomavirus (HPV)-associated genital warts of the external genitalia and to detect the recurrence rate and side effects of this therapeutic regimen. All patients with a suspected HPV-related papillary vulvar lesion after initial examination underwent vulvoscopic evaluation with a magnification of 8-20x using acetic acid and toluidine blue. Under local anesthesia, biopsies were taken from acuminate or papillary warts for histopathologic confirmation and from suspicious areas to exclude preinvasive or invasive diseases. Following histopathologic diagnosis, patients were treated with 85% TCA. Overall, 51 patients with isolated vulvar and/or perianal genital warts were included. Of those patients, 11 (21.5%) had acuminate and 40 (78.5%) had papular genital warts. All the women had lesions of the labia minora. The other localizations were as follows: labia majora, 18 (35.3%); lateral vulva, 5 (9.8%); clitoris, 9 (17.6%); fourchette, 16 (31.3%); and perianal area, 7 (13.7%). All lesions were successfully treated by the end of the treatment period (median, 4; range 2-5). None of the patients had recurrence or new lesions during the 6-month follow-up period. In the second 6 months, 9 patients (17.6%) were diagnosed with recurrent lesions. Although all the patients experienced transient burning pain during therapy, none of them discontinued the therapy. Ulceration was observed in 8 patients (15.6%). Of those patients only 3 had permanent scarring (5.8%). We recommend the use of TCA in patients with external genital warts, especially for mild to moderate cases. It is associated with a high success rate and low morbidity if sufficient care is taken during application.

  5. Comparison between DCA - SSO - VDR and VMAT dose delivery techniques for 15 SRS/SRT patients

    NASA Astrophysics Data System (ADS)

    Tas, B.; Durmus, I. F.

    2018-02-01

    To evaluate dose delivery between Dynamic Conformal Arc (DCA) - Segment Shape Optimization (SSO) - Variation Dose Rate (VDR) and Volumetric Modulated Arc Therapy (VMAT) techniques for fifteen SRS patients using Versa HD® lineer accelerator. Fifteen SRS / SRT patient's optimum treatment planning were performed using Monaco5.11® treatment planning system (TPS) with 1 coplanar and 3 non-coplanar fields for VMAT technique, then the plans were reoptimized with the same optimization parameters for DCA - SSO - VDR technique. The advantage of DCA - SSO - VDR technique were determined less MUs and beam on time, also larger segments decrease dosimetric uncertainities of small fields quality assurance. The advantage of VMAT technique were determined a little better GI, CI, PCI, brain V12Gy and brain mean dose. The results show that the clinical objectives and plans for both techniques satisfied all organs at risks (OARs) dose constraints. Depends on the shape and localization of target, we could choose one of these techniques for linear accelerator based SRS / SRT treatment.

  6. [A case report: anomaly of the fourth branchial pouch with recurring cervical abscesses. Cauterization with trichloroacetic acid closed the fistula opening and cured the patient].

    PubMed

    Stenquist, Monika; Juhlin, Claes; Aström, Gunnar; Friberg, Ulla

    2003-04-24

    A fourth branchial pouch sinus is a rare congenital anomaly, which in a 13-year-old girl presented clinically as recurrent deep cervical abscesses. The location of the majority of these anomalies is the left side of the neck (90%). Radiological and endoscopic investigations verified the diagnosis. The internal orifice located at the apex of the pyriform sinus could facilitate contamination by infectious pharyngeal secretions and lead to abscess recurrence. Traditionally, the recommended treatment is radical surgery. It can, however, be technically difficult to excise the whole fistula tract. In this patient we used a non-invasive treatment modality; chemocauterization with 40% trichloroacetic acid (TCA). After three treatments the fistula was closed. To date (month no. 15) there has been no abscess recurrence. TCA chemocauterization seems to be a safe first-line treatment for patients with pyriform sinus fistulas.

  7. An Optimized Trichloroacetic Acid/Acetone Precipitation Method for Two-Dimensional Gel Electrophoresis Analysis of Qinchuan Cattle Longissimus Dorsi Muscle Containing High Proportion of Marbling.

    PubMed

    Hao, Ruijie; Adoligbe, Camus; Jiang, Bijie; Zhao, Xianlin; Gui, Linsheng; Qu, Kaixing; Wu, Sen; Zan, Linsen

    2015-01-01

    Longissimus dorsi muscle (LD) proteomics provides a novel opportunity to reveal the molecular mechanism behind intramuscular fat deposition. Unfortunately, the vast amounts of lipids and nucleic acids in this tissue hampered LD proteomics analysis. Trichloroacetic acid (TCA)/acetone precipitation is a widely used method to remove contaminants from protein samples. However, the high speed centrifugation employed in this method produces hard precipitates, which restrict contaminant elimination and protein re-dissolution. To address the problem, the centrifugation precipitates were first grinded with a glass tissue grinder and then washed with 90% acetone (TCA/acetone-G-W) in the present study. According to our result, the treatment for solid precipitate facilitated non-protein contaminant removal and protein re-dissolution, ultimately improving two-dimensional gel electrophoresis (2-DE) analysis. Additionally, we also evaluated the effect of sample drying on 2-DE profile as well as protein yield. It was found that 30 min air-drying did not result in significant protein loss, but reduced horizontal streaking and smearing on 2-DE gel compared to 10 min. In summary, we developed an optimized TCA/acetone precipitation method for protein extraction of LD, in which the modifications improved the effectiveness of TCA/acetone method.

  8. EARLY GENE EXPRESSION CHANGES IN THE LIVERS OF MICE EXPOSED TO DICHLOROACETIC ACID

    EPA Science Inventory

    EARLY GENE EXPRESSION CHANGES IN THE LIVERS OF MICE EXPOSED TO DICHLOROACETIC ACID

    Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have shown that DCA induces liver tumors in rodents when administered in drinking wate...

  9. Deep peeling using phenol versus percutaneous collagen induction combined with trichloroacetic acid 20% in atrophic post-acne scars; a randomized controlled trial.

    PubMed

    Leheta, Tahra Mohamed; Abdel Hay, Rania Mounir; El Garem, Yehia Farouk

    2014-04-01

    Deep peeling using phenol and percutaneous collagen induction (PCI) are used in treating acne scars. To compare deep peeling using phenol and PCI combined with trichloroacetic acid (TCA) 20% in treating atrophic acne scars. 24 patients with post-acne atrophic scars were randomly divided into two groups; group 1 was subjected to one session of deep peeling using phenol, and group 2 was subjected to four sessions of PCI combined with TCA 20%. As a secondary outcome measure, side effects were recorded and patients were asked to assess their % of improvement by a questionnaire completed 8 months after the procedure. Scar severity scores improved by a mean of 75.12% (p < 0.001) in group 1 and a mean of 69.43% (p < 0.001) in group 2. Comparing the degree of improvement in different types of scars, within the same group after treatment, revealed a significant highest degree of improvement in the rolling type (p = 0.005) in group 2. Deep peeling using phenol and PCI with TCA 20% were effective in treating post-acne atrophic scars.

  10. [Evaluation of DCA vantage for rapid in-clinic measurement of HbA1c on capillary blood in young type 1 diabetic patients].

    PubMed

    El Arabi, H; Willems, D; Mélot, C; Dorchy, H

    2013-01-01

    Rapid in clinic measurement of glycated hemoglogin (HbA1c) allows to determine the level of metabolic control within a few minutes on capillary blood. We have evaluated the new DCA Vantage (Siemens) based on an immunological technique, replacing the DCA 2000+ (Siemens). The study included 120 unselected young type 1 diabetic patients, with different degrees of metabolic control. The DCA Vantage was compared with the HPLC system (Menarini HA 8160) whose deviation from the DCCT was < 0.1% across the clinical range. The mean underestimation of the DCA Vantage was -0.40%. The agreement limits (+/- 1.96 SD) were between 0.14% and -0.93%; this means +/- 0.53% around -0.40%. In conclusion, the DCA Vantage underestimates HbA1c levels; however it met the acceptance criteria of having a coefficient of variation < 3%.

  11. DETECTION OF EARLY GENE EXPRESSION CHANGES BY DIFFERENTIAL DISPLAY IN THE LIVERS OF MICE EXPOSED TO DICHLOROACETIC ACID

    EPA Science Inventory

    Dichloroacetic acid (DCA) is a major by-product of water disinfection by chlorination. Several studies have demonstrated the hepatocarcinogenicity of DCA in mice when administered in drinking water. The mechanism of DCA carcinogenicity is not clear and we speculate that changes...

  12. Serum bile acid level and fatty acid composition in Chinese children with non-alcoholic fatty liver disease.

    PubMed

    Lu, Li Ping; Wan, Yan Ping; Xun, Peng Cheng; Zhou, Ke Jun; Chen, Cheng; Cheng, Si Yang; Zhang, Min Zhong; Wu, Chun Hua; Lin, Wei Wei; Jiang, Ying; Feng, Hai Xia; Wang, Jia Lu; He, Ka; Cai, Wei

    2017-08-01

    To determine serum bile acid (BA) and fatty acid (FA) profiles in Chinese children with non-alcoholic fatty liver disease (NAFLD). A total 76 children aged 4-17 years were categorized into three groups according to the presence and absence of as well as the severity of NAFLD, that is, non-NAFLD (control), mild and moderate to severe NAFLD groups, respectively, based on their liver ultrasonography findings. Serum BA and FA profiles were quantified separately by mass spectrometry and gas chromatography. General linear models were performed to assess the differences among the groups. After adjusted for potential confounders, children with NAFLD had higher levels of chenodeoxycholic acid (CDCA), unconjugated primary BAs (CDCA + cholic acid) but lower levels of deoxycholic acid (DCA), taurodeoxycholic acid (TDCA), glycodeoxycholic acid (GDCA), total DCA (DCA + TDCA + GDCA), glycolithocholic acid (GLCA) and total lithocholic acid (GLCA + taurolithocholic acid) than children without NAFLD. As for FAs, children with mild and moderate to severe NAFLD had higher levels of n-7 monounsaturated FA. Circulating BA and FA profiles may change in children with NAFLD. Further studies are needed to determine their associations and to understand the underlying mechanism of action. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  13. Carryover effects of dichloroacetic acid on hepatic tumorigenesis in mice.

    EPA Science Inventory

    Introduction: Dichloroacetic acid (DCA) is a major by-product of drinking water chlorination. Chronic DCA exposure has been shown to increase liver tumors in mice, although carryover effects and interactions with other promotional agents are not known. Here we evaluated effects...

  14. Individual bile acids have differential effects on bile acid signaling in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Song, Peizhen, E-mail: songacad@gmail.com; Rockwell, Cheryl E., E-mail: rockwelc@msu.edu; Cui, Julia Yue, E-mail: juliacui@uw.edu

    2015-02-15

    Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In themore » liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

  15. Trichloroacetic acid in the vegetation of polluted and remote areas of both hemispheres—Part I. Its formation, uptake and geographical distribution

    NASA Astrophysics Data System (ADS)

    Weissflog, Ludwig; Pfennigsdorff, Andrea; Martinez-Pastur, Guillermo; Puliafito, Enrique; Figueroa, Dante; Elansky, Nikolai; Nikonov, Vyasheslav; Putz, Erich; Krüger, Gert; Kellner, Klaus

    Trichloroacetic acid (TCA; CCl 3COOH) is a phytotoxic chemical. Although TCA salts and derivatives were once deployed as herbicides against perennial grasses and weeds, their use has since been banned because of their indiscriminate herbicidal effects on woody plant species. However, TCA can also be formed in the atmosphere. For instance, high-volatile C 2-chlorohydrocarbons tetrachloroethene (TECE, C 2Cl 4) and 1,1,1-trichloroethane (TCE, CCl 3CH 3) can react to TCA and other substances under oxidative conditions here. Owing to further industrialisation of Southeast Asia, South Africa and South America, a rise can be expected in the use of TECE as solvents in the metal and textile industries of these regions in the southern hemisphere (SH). The increasing emissions of this substance—together with the rise in the atmospheric oxidation potential caused by urban activities, slash and burn agriculture and forest fires in the SH—will result in the increased input/formation of TCA in the vegetation located on the lee side of these emission sources. By means of biomonitoring studies, inputs/formation of TCA related to the climatic conditions were detected at various locations in South America, Africa, and Europe.

  16. New fluorescent bile acids: synthesis, chemical characterization, and disastereoselective uptake by Caco-2 cells of 3-deoxy 3-NBD-amino deoxycholic and ursodeoxycholic acid.

    PubMed

    Májer, Ferenc; Salomon, Johanna J; Sharma, Ruchika; Etzbach, Simona V; Najib, Mohd Nadzri Mohd; Keaveny, Ray; Long, Aideen; Wang, Jun; Ehrhardt, Carsten; Gilmer, John F

    2012-03-01

    Deoxycholic acid (DCA), a secondary bile acid (BA), and ursodeoxycholic acid (UDCA), a tertiary BA, cause opposing effects in vivo and in cell suspensions. Fluorescent analogues of DCA and UDCA could help investigate important questions about their cellular interactions and distribution. We have prepared a set of isomeric 3α- and 3β-amino analogues of UDCA and DCA and derivatised these with the discrete fluorophore, 4-nitrobenzo-2-oxa-1,3-diazol (NBD), forming the corresponding four fluorescent adducts. These absorb in the range 465-470 nm and fluoresce at approx. 535 nm. In order to determine the ability of the new fluorescent bile acids to mimic the parents, their uptake was studied using monolayers of Caco-2 cells, which are known to express multiple proteins of the organic anion-transporting peptide (OATP) subfamily of transporters. Cellular uptake was monitored over time at 4 and 37°C to distinguish between passive and active transport. All four BA analogues were taken up but in a strikingly stereo- and structure-specific manner, suggesting highly discriminatory interactions with transporter protein(s). The α-analogues of DCA and to a lesser extent UDCA were actively transported, whereas the β-analogues were not. The active transport process was saturable, with Michaelis-Menten constants for 3α-NBD DCA (5) being K(m)=42.27±12.98 μM and V(max)=2.8 ± 0.4 nmol/(mg protein*min) and for 3α-NBD UDCA (3) K(m)=28.20 ± 7.45 μM and V(max)=1.8 ± 0.2 nmol/(mg protein*min). These fluorescent bile acids are promising agents for investigating questions of bile acid biology and for detection of bile acids and related organic anion transport processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Biliary Bile Acids in Primary Biliary Cirrhosis: Effect of Ursodeoxycholic Acid

    PubMed Central

    Combes, Burton; Carithers, Robert L.; Maddrey, Willis C.; Munoz, Santiago; Garcia-Tsao, Guadalupe; Bonner, Gregory F.; Boyer, James L.; Luketic, Velimir A.; Shiffman, Mitchell L.; Peters, Marion G.; White, Heather; Zetterman, Rowen K.; Risser, Richard; Rossi, Stephen S.; Hofmann, Alan F.

    2014-01-01

    Bile acid composition in fasting duodenal bile was assessed at entry and at 2 years in patients with primary biliary cirrhosis (PBC) enrolled in a randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) (10–12 mg/kg/d) taken as a single bedtime dose. Specimens were analyzed by a high-pressure liquid chromatography method that had been validated against gas chromatography. Percent composition in bile (mean ± SD) for 98 patients at entry for cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA), and ursodeoxycholic (UDCA) acids, respectively, were 57.4 ± 18.6, 31.5 ± 15.5, 8.0 ± 9.3, 0.3 ± 1.0, and 0.6 ± 0.9. Values for CA were increased, whereas those for CDCA, DCA, LCA, and UDCA were decreased when compared with values in normal persons. Bile acid composition of the major bile acids did not change after 2 years on placebo medication. By contrast, in patients receiving UDCA for 2 years, bile became enriched with UDCA on average to 40.1%, and significant decreases were noted for CA (to 32.2%) and CDCA (to 19.5%). No change in percent composition was observed for DCA and LCA. Percent composition at entry and changes in composition after 2 years on UDCA were similar in patients with varying severity of PBC. In patients whose bile was not enriched in UDCA (entry and placebo-treated specimens), CA, CDCA, DCA, and the small amount of UDCA found in some of these specimens were conjugated to a greater extent with glycine (52%–64%) than with taurine (36%–48%). Treatment with UDCA caused the proportion of all endogenous bile acids conjugated with glycine to increase to 69% to 78%, while the proportion conjugated with taurine (22%–31%) fell (P < .05). Administered UDCA was also conjugated predominantly with glycine (87%). PMID:10347103

  18. An Optimized Trichloroacetic Acid/Acetone Precipitation Method for Two-Dimensional Gel Electrophoresis Analysis of Qinchuan Cattle Longissimus Dorsi Muscle Containing High Proportion of Marbling

    PubMed Central

    Hao, Ruijie; Adoligbe, Camus; Jiang, Bijie; Zhao, Xianlin; Gui, Linsheng; Qu, Kaixing; Wu, Sen; Zan, Linsen

    2015-01-01

    Longissimus dorsi muscle (LD) proteomics provides a novel opportunity to reveal the molecular mechanism behind intramuscular fat deposition. Unfortunately, the vast amounts of lipids and nucleic acids in this tissue hampered LD proteomics analysis. Trichloroacetic acid (TCA)/acetone precipitation is a widely used method to remove contaminants from protein samples. However, the high speed centrifugation employed in this method produces hard precipitates, which restrict contaminant elimination and protein re-dissolution. To address the problem, the centrifugation precipitates were first grinded with a glass tissue grinder and then washed with 90% acetone (TCA/acetone-G-W) in the present study. According to our result, the treatment for solid precipitate facilitated non-protein contaminant removal and protein re-dissolution, ultimately improving two-dimensional gel electrophoresis (2-DE) analysis. Additionally, we also evaluated the effect of sample drying on 2-DE profile as well as protein yield. It was found that 30 min air-drying did not result in significant protein loss, but reduced horizontal streaking and smearing on 2-DE gel compared to 10 min. In summary, we developed an optimized TCA/acetone precipitation method for protein extraction of LD, in which the modifications improved the effectiveness of TCA/acetone method. PMID:25893432

  19. Biodegradation of six haloacetic acids in drinking water.

    PubMed

    Bayless, Walt; Andrews, Robert C

    2008-03-01

    Haloacetic acids (HAAs) are produced by the reaction of chlorine with natural organic matter and are regulated disinfection by-products of health concern. Biofilms in drinking water distribution systems and in filter beds have been associated with the removal of some HAAs, however the removal of all six routinely monitored species (HAA(6)) has not been previously reported. In this study, bench-scale glass bead columns were used to investigate the ability of a drinking water biofilm to degrade HAA(6). Monochloroacetic acid (MCAA) and monobromoacetic acid (MBAA) were the most readily degraded of the halogenated acetic acids. Trichloroacetic acid (TCAA) was not removed biologically when examined at a 90% confidence level. In general, di-halogenated species were removed to a lesser extent than the mono-halogenated compounds. The order of biodegradability by the biofilm was found to be monobromo > monochloro > bromochloro > dichloro > dibromo > trichloroacetic acid.

  20. Comparative Evaluation of Topical 10% Potassium Hydroxide and 30% Trichloroacetic Acid in the Treatment of Plane Warts

    PubMed Central

    Jayaprasad, Sandhaya; Subramaniyan, Radhakrishnan; Devgan, Shalini

    2016-01-01

    Background: Warts are benign proliferations of skin and mucosa caused by the human papillomavirus (HPV). Plane warts are caused by HPV types 3, 10, 28, and 41, occurring mostly in children and young adults. Among the treatment modalities, topical application of trichloroacetic acid (TCA) is age old. Potassium hydroxide (KOH) has a keratolytic effect on virus-infected cells. It is less irritating, less painful, less scar forming, and can be safely used in children too. Hence, it could be a better topical agent in the treatment of plane warts. Aims and Objectives: To compare the safety and efficacy of topical 10% KOH with 30% TCA in the treatment of plane warts. Materials and Methods: Sixty consecutive patients with plane warts were randomly assigned into two arms of thirty patients each; arm A received topical 10% KOH and arm B received topical 30% TCA as a once weekly application until the complete clearance of warts or a maximum period of 12 weeks. Results: Statistically no significant difference (P = 0.07) was found between the objective therapeutic response to 10% KOH and 30% TCA at the end of study (12 weeks). However, subjective response to 10% KOH was better and statistically significant (P = 0.03). There was no recurrence of warts seen on follow-up for 3 months of complete responders in both the arms. Conclusion: 10% KOH is found to be equally effective in the treatment of plane warts compared to 30% TCA with the advantage of faster onset of action and tendency of completely clearing warts with fewer side effects. PMID:27904181

  1. Comparative studies of the structure, morphology and electrical conductivity of polyaniline weakly doped with chlorocarboxylic acids

    NASA Astrophysics Data System (ADS)

    Gmati, Fethi; Fattoum, Arbi; Bohli, Nadra; Dhaoui, Wadia; Belhadj Mohamed, Abdellatif

    2007-08-01

    We report the results of studies on two series of polyaniline (PANI), doped with dichloroacetic (DCA) and trichloroacetic (TCA) acids, respectively, at various doping rates and obtained by the in situ polymerization method. Samples were characterized by x-ray diffraction, scanning electron microscopy and conductivity measurements. The direct current (dc) and alternating current (ac) electrical conductivities of PANI salts have been investigated in the temperature range 100-310 K and frequency range 7-106 Hz. The results of this study indicate better chain ordering and higher conductivity for PANI doped with TCA. The dc conductivity of all samples is suitably fitted to Mott's three-dimensional variable-range hopping (VRH) model. Different Mott parameters such as characteristic temperature T0, density of states at the Fermi level (N(EF)), average hopping energy (W) and the average hopping distance (R) have been evaluated. The dependence of such values on the dopant acid used is discussed. At high frequencies, the ac conductivity follows the power law σac(ω,T) = A(T)ωs(T,ω), which is characteristic for charge transport in disordered materials by hopping or tunnelling processes. The observed increase in the frequency exponent s with temperature suggests that the small-polaron tunnelling model best describes the dominant ac conduction mechanism. A direct correlation between conductivity, structure and morphology was obtained in our systems.

  2. The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-kappaB activation in oesophageal cells, with a mechanism of action involving ROS.

    PubMed

    Jenkins, G J S; Cronin, J; Alhamdani, A; Rawat, N; D'Souza, F; Thomas, T; Eltahir, Z; Griffiths, A P; Baxter, J N

    2008-09-01

    Deoxycholic acid (DCA) is a secondary bile acid implicated in various cancers of the gastrointestinal (GI) tract. In oesophageal adenocarcinoma, DCA is believed to contribute to carcinogenesis during reflux where stomach contents enter the lower oesophagus. It is imperative that we understand the mechanisms whereby oesophageal carcinogens function in order that therapeutic options may be developed. We have previously shown that DCA can damage chromosomes and does so through its generation of reactive oxygen species (ROS). We show here, after detailed experiments, that DCA appears to have a non-linear dose response for DNA damage. DCA induces DNA damage (as measured by the micronucleus assay) at doses of 100 microM and higher in oesophageal OE33 cells, but fails to induce such DNA damage below this cut-off dose. We also show that in terms of NF-kappaB activation (as measured by up-regulation of two NF-kappaB target genes) by DCA, a similar dose response is observed. This dose-response data may be important clinically as DCA exposure to the oesophagus may be used as a way to identify the 10% of Barrett's oesophagus patients currently progressing to cancer from the 90% of patients who do not progress. Only quantitative studies measuring DCA concentrations in refluxates correlated with histological progression will answer this question. We further show here that ROS are behind DCAs ability to activate NF-kappaB as antioxidants (epigallocatechin gallate, resveratrol and vitamin C) abrogate DCAs ability to up-regulate NF-kappaB-controlled genes. In conclusion, low doses of DCA appear to be less biologically significant in vitro. If this were to be confirmed in vivo, it might suggest that reflux patients with low DCA concentrations may be at a lower risk of cancer progression compared to patients with high levels of DCA in their refluxate. Either way, antioxidant supplementation may possibly help prevent the deleterious effects of DCA in the whole GI tract.

  3. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

    USDA-ARS?s Scientific Manuscript database

    Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of DCA and...

  4. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation.

    PubMed

    Zeng, Huawei; Claycombe, Kate J; Reindl, Katie M

    2015-10-01

    Consumption of a high-fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk, while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer-preventive effects. To distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen), we examined the effects of physiologically relevant doses of butyrate (0.5-2 mmol/l) and DCA (0.05-0.3 mmol/l) on colon cell proliferation. We hypothesize that butyrate and DCA each modulates the cell cycle and apoptosis via common and distinct cellular signaling targets. In this study, we demonstrated that both butyrate and DCA inhibited cell proliferation by up to 89% and 92% and increased cell apoptosis rate by up to 3.1- and 4.5-fold, respectively. Cell cycle analyses revealed that butyrate led to an increase in G1 and G2 fractions with a concomitant drop in the S-phase fraction, but DCA induced an increase in only G1 fraction with a concomitant drop in the S-phase fraction when compared with the untreated cells. The examination of early cellular signaling revealed that DCA but not butyrate increased intracellular reactive oxygen species, genomic DNA breakage, the activation of ERK1/2, caspase-3 and PARP. In contrast, DCA decreased activated Rb protein level, and butyrate but not DCA increased p21 expression. Collectively, although both butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases tumor suppressor activation in cell cycle and apoptosis pathways. Published by Elsevier Inc.

  5. Theoretical Investigation of the Reactivity of Sodium Dicyanamide with Nitric Acid.

    PubMed

    Vogelhuber, Kristen M; Booth, Ryan S; Annesley, Christopher J

    2018-03-01

    There is a need to replace current hydrazine fuels with safer propellants, and dicyanamide (DCA - )-based systems have emerged as promising alternatives because they autoignite when mixed with some oxidizers. Previous studies of the hypergolic reaction mechanism have focused on the reaction between DCA - and the oxidizer HNO 3 ; here, we compare the calculated pathway of DCA - + HNO 3 with the reaction coordinate of the ion pair sodium dicyanamide with nitric acid, Na[DCA] + HNO 3 . Enthalpies and free energies are calculated in the gas phase and in solution using a quantum mechanical continuum solvation model, SMD-GIL. The barriers to the Na[DCA] + HNO 3 reaction are dramatically lowered relative to those of the reaction with the bare anion, and an exothermic exit channel to produce NaNO 3 and the reactive intermediate HDCA appears. These results suggest that Na[DCA] may accelerate the ignition reaction.

  6. Functionalization of carbon nanotubes with water-insoluble porphyrin in ionic liquid: direct electrochemistry and highly sensitive amperometric biosensing for trichloroacetic acid.

    PubMed

    Tu, Wenwen; Lei, Jianping; Ju, Huangxian

    2009-01-01

    A functional composite of single-walled carbon nanotubes (SWNTs) with hematin, a water-insoluble porphyrin, was first prepared in 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF(6)]) ionic liquid. The novel composite in ionic liquid was characterized by scanning electron microscopy, ultraviolet absorption spectroscopy, and electrochemical impedance spectroscopy, and showed a pair of direct redox peaks of the Fe(III)/Fe(II) couple. The composite-[BMIM][PF(6)]-modified glassy carbon electrode showed excellent electrocatalytic activity toward the reduction of trichloroacetic acid (TCA) in neutral media due to the synergic effect among SWNTs, [BMIM][PF(6)], and porphyrin, which led to a highly sensitive and stable amperometric biosensor for TCA with a linear range from 9.0x10(-7) to 1.4x10(-4) M. The detection limit was 3.8x10(-7) M at a signal-to-noise ratio of 3. The TCA biosensor had good analytical performance, such as rapid response, good reproducibility, and acceptable accuracy, and could be successfully used for the detection of residual TCA in polluted water. The functional composite in ionic liquid provides a facile way to not only obtain the direct electrochemistry of water-insoluble porphyrin, but also construct novel biosensors for monitoring analytes in real environmental samples.

  7. Thermodynamic Equilibrium Solubility of Diethanolamine – N-Butyl-1-Methylpyrrolidinium Dicyanamide [DEABMPYRR DCA] Mixtures for Carbon Dioxide Capture

    NASA Astrophysics Data System (ADS)

    Salleh, R. M.; Jamaludin, S. N.

    2018-05-01

    Solubility data of carbon dioxide (CO2) in aqueous Diethanolamine (DEA) blended with pyrrolidinium-based ionic liquid: N-Butyl-1-Methylpyrrolidinium Dıcyanamıde [Bmpyrr][DCA] are presented at various temperatures (313.15K-333.15K) and pressure up to about 700 psi. The concentration of [Bmpyrr][DCA] ranges from 0-10wt% and 30-40wt% for DEA. The solubility of CO2 was evaluated by measuring the pressure drop in high pressure stirred absorption cell reactor. The CO2 loading in all studied mixtures increases with an increase in CO2 partial pressure and decreases with temperature. It was also found that the CO2 loading capacity decrease as the concentration of [Bmpyrr][DCA] increases. The experimental data were correlated as a function of temperature and CO2 partial pressure to predict the solubility of CO2 in the mixtures. It was found that the model predicted results in a good agreement with experimental value.

  8. Evaluation of the DCA Vantage analyzer for HbA 1c assay.

    PubMed

    Szymezak, Jean; Leroy, Nathalie; Lavalard, Emmanuelle; Gillery, Philippe

    2008-01-01

    Measurement of HbA 1c is key in monitoring diabetic patients in both laboratories and clinical units, where HbA 1c results are used as part of patient education. We have evaluated the DCA Vantage, a new device for immunological assay of HbA 1c. HbA 1c results obtained were evaluated in terms of precision, linearity, specificity and practicability, and were compared with results obtained by a Variant II HPLC method. The method exhibited intra- and inter-assay coefficients of variation lower than 2.6% and 4.0%, respectively, and good correlation with the comparison HPLC method (r2=0.9776). No interference was noted in the presence of labile HbA 1c or carbamylated hemoglobin. The new device exhibited improved practicability characteristics and allowed better sample identification, better management of quality control routines and greater connectivity possibilities compared to the previous DCA 2000 analyzer. This new analyzer exhibited analytical and practical characteristics very suitable for HbA 1c assay for laboratory or point-of-care use according to good laboratory practice.

  9. Key Issues in the Modes of Action and Effects of Trichloroethylene Metabolites for Liver and Kidney Tumorigenesis

    PubMed Central

    Caldwell, Jane C.; Keshava, Nagalakshmi

    2006-01-01

    Trichloroethylene (TCE) exposure has been associated with increased risk of liver and kidney cancer in both laboratory animal and epidemiologic studies. The U.S. Environmental Protection Agency 2001 draft TCE risk assessment concluded that it is difficult to determine which TCE metabolites may be responsible for these effects, the key events involved in their modes of action (MOAs), and the relevance of these MOAs to humans. In this article, which is part of a mini-monograph on key issues in the health risk assessment of TCE, we present a review of recently published scientific literature examining the effects of TCE metabolites in the context of the preceding questions. Studies of the TCE metabolites dichloroacetic acid (DCA), trichloroacetic acid (TCA), and chloral hydrate suggest that both DCA and TCA are involved in TCE-induced liver tumorigenesis and that many DCA effects are consistent with conditions that increase the risk of liver cancer in humans. Studies of S-(1,2-dichlorovinyl)-l-cysteine have revealed a number of different possible cell signaling effects that may be related to kidney tumorigenesis at lower concentrations than those leading to cytotoxicity. Recent studies of trichloroethanol exploring an alternative hypothesis for kidney tumorigenesis have failed to establish the formation of formate as a key event for TCE-induced kidney tumors. Overall, although MOAs and key events for TCE-induced liver and kidney tumors have yet to be definitively established, these results support the likelihood that toxicity is due to multiple metabolites through several MOAs, none of which appear to be irrelevant to humans. PMID:16966105

  10. Deoxycholic acid modulates cell death signaling through changes in mitochondrial membrane properties[S

    PubMed Central

    Sousa, Tânia; Castro, Rui E.; Pinto, Sandra N.; Coutinho, Ana; Lucas, Susana D.; Moreira, Rui; Rodrigues, Cecília M. P.; Prieto, Manuel; Fernandes, Fábio

    2015-01-01

    Cytotoxic bile acids, such as deoxycholic acid (DCA), are responsible for hepatocyte cell death during intrahepatic cholestasis. The mechanisms responsible for this effect are unclear, and recent studies conflict, pointing to either a modulation of plasma membrane structure or mitochondrial-mediated toxicity through perturbation of mitochondrial outer membrane (MOM) properties. We conducted a comprehensive comparative study of the impact of cytotoxic and cytoprotective bile acids on the membrane structure of different cellular compartments. We show that DCA increases the plasma membrane fluidity of hepatocytes to a minor extent, and that this effect is not correlated with the incidence of apoptosis. Additionally, plasma membrane fluidity recovers to normal values over time suggesting the presence of cellular compensatory mechanisms for this perturbation. Colocalization experiments in living cells confirmed the presence of bile acids within mitochondrial membranes. Experiments with active isolated mitochondria revealed that physiologically active concentrations of DCA change MOM order in a concentration- and time-dependent manner, and that these changes preceded the mitochondrial permeability transition. Importantly, these effects are not observed on liposomes mimicking MOM lipid composition, suggesting that DCA apoptotic activity depends on features of mitochondrial membranes that are absent in protein-free mimetic liposomes, such as the double-membrane structure, lipid asymmetry, or mitochondrial protein environment. In contrast, the mechanism of action of cytoprotective bile acids is likely not associated with changes in cellular membrane structure. PMID:26351365

  11. A Quantitative Description of Suicide Inhibition of Dichloroacetic Acid in Rats and Mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Keys, Deborah A.; Schultz, Irv R.; Mahle, Deirdre A.

    Dichloroacetic acid (DCA), a minor metabolite of trichloroethylene (TCE) and water disinfection byproduct, remains an important risk assessment issue because of its carcinogenic potency. DCA has been shown to inhibit its own metabolism by irreversibly inactivating glutathione transferase zeta (GSTzeta). To better predict internal dosimetry of DCA, a physiologically based pharmacokinetic (PBPK) model of DCA was developed. Suicide inhibition was described dynamically by varying the rate of maximal GSTzeta mediated metabolism of DCA (Vmax) over time. Resynthesis (zero-order) and degradation (first-order) of metabolic activity were described. Published iv pharmacokinetic studies in native rats were used to estimate an initial Vmaxmore » value, with Km set to an in vitro determined value. Degradation and resynthesis rates were set to estimated values from a published immunoreactive GSTzeta protein time course. The first-order inhibition rate, kd, was estimated to this same time course. A secondary, linear non-GSTzeta-mediated metabolic pathway is proposed to fit DCA time courses following treatment with DCA in drinking water. The PBPK model predictions were validated by comparing predicted DCA concentrations to measured concentrations in published studies of rats pretreated with DCA following iv exposure to 0.05 to 20 mg/kg DCA. The same model structure was parameterized to simulate DCA time courses following iv exposure in native and pretreated mice. Blood and liver concentrations during and postexposure to DCA in drinking water were predicted. Comparisons of PBPK model predicted to measured values were favorable, lending support for the further development of this model for application to DCA or TCE human health risk assessment.« less

  12. Removal of EDB and 1,2-DCA by Abiotic Reaction with Iron (II) Sulfide

    EPA Science Inventory

    To properly evaluate the risk associated with exposure to EDB and 1,2-DCA in ground water from old spills of leaded gasoline, it is necessary to understand the mechanisms that may attenuate concentrations of these compounds in ground water. TCE reacts rapidly with iron (II) sulf...

  13. TRAPPING AND IDENTIFICATION OF THE DICHLOROACETATE RADICAL FROM THE REDUCTIVE DEHALOGENATION OF TRICHLOROACETATE BY MOUSE AND RAT LIVER MICROSOMES. (R825954)

    EPA Science Inventory

    A key question in the risk assessment of trichloroethylene (TRI) is the extent to which its carcinogenic effects might depend on the formation of dichloroacetate (DCA) as a metabolite. One of the metabolic pathways proposed for the formation of DCA from TRI is by the reductive...

  14. High abundances of oxalic, azelaic, and glyoxylic acids and methylglyoxal in the open ocean with high biological activity: Implication for secondary OA formation from isoprene

    NASA Astrophysics Data System (ADS)

    Bikkina, Srinivas; Kawamura, Kimitaka; Miyazaki, Yuzo; Fu, Pingqing

    2014-05-01

    Atmospheric dicarboxylic acids (DCA) are a ubiquitous water-soluble component of secondary organic aerosols (SOA), which can act as cloud condensation nuclei (CCN), affecting the Earth's climate. Despite the high abundances of oxalic acid and related compounds in the marine aerosols, there is no consensus on what controls their distributions over the open ocean. Marine biological productivity could play a role in the production of DCA, but there is no substantial evidence to support this hypothesis. Here we present latitudinal distributions of DCA, oxoacids and α-dicarbonyls in the marine aerosols from the remote Pacific. Their concentrations were found several times higher in more biologically influenced aerosols (MBA) than less biologically influenced aerosols. We propose isoprene and unsaturated fatty acids as sources of DCA as inferred from significantly higher abundances of isoprene-SOA tracers and azelaic acid in MBA. These results have implications toward the reassessment of climate forcing feedbacks of marine-derived SOA.

  15. Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison.

    PubMed

    El-Domyati, Moetaz; Abdel-Wahab, Hossam; Hossam, Aliaa

    2018-02-01

    Minimally invasive procedures provide effective, safe, relatively long-lasting, and natural results without large damage to the skin. A combination treatment is considered an approach that includes at least 2 different and unrelated modalities. This study aims to evaluate the use and effectiveness of some combined minimally invasive procedures for management of acne scarring. Twenty-four volunteers with postacne atrophic scars were randomly divided into 3 equal groups according to performed procedure on each side of the face (microneedling by dermaroller alone or combined with platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and received 6 bi-weekly sessions of treatment. Photography and punch biopsies were taken before and after 3 months of treatment for clinical, histological, and histometrical evaluation. Combined treatment of dermaroller and PRP or dermaroller and TCA 15% showed significant improvement when compared with dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed statistically significant increase in studied groups, mainly after dermaroller and TCA 15%. Moreover, the 3 studied groups showed more organized collagen bundles and newly formed collagen formation and markedly decreased abnormal elastic fibers. Based on the clinical, histometrical, and histochemical assessment, inspite that most volunteers showed significant improvement after treatment, however, the combined use of dermaroller and TCA 15% was more effective in postacne atrophic scars than the use of dermaroller and PRP or dermaroller only. © 2017 Wiley Periodicals, Inc.

  16. Split-face comparative study of 1550 nm fractional photothermolysis and trichloroacetic acid 15% chemical peeling for facial melasma in Asian skin.

    PubMed

    Hong, Seung-Phil; Han, Seung-Seog; Choi, Seok-Joo; Kim, Myoung-Shin; Won, Chong-Hyun; Lee, Mi-Woo; Choi, Jee-Ho; Moon, Kee-Chan; Kim, Youn Jin; Chang, Sung-Eun

    2012-04-01

    Fractional photothermolysis (FP) therapy and chemical peels have been reported to be effective in patients with recalcitrant melasma. However, there is little information to compare the efficacy of single treatment session in Asian women. The aim of this study was to examine the efficacy, long-lasting outcomes and safety of a single session of 1550-nm erbium-doped FP in Asian patients, compared with trichloroacetic acid (TCA) peel with a medium depth. Eighteen Korean women (Fitzpatrick skin type III or IV) with moderate-to-severe bilateral melasma were randomly treated with a single session of 1550-nm FP on one cheek, and with a 15% TCA peel on the other cheek. Outcome measures included an objective melasma area severity index and subjective patient-rated overall improvement at 4 and 12 weeks after treatment. Melasma lesions were significantly improved 4 weeks after either treatment, but melasma recurred at 12 weeks. Post-inflammatory hyperpigmentation developed in 28% of patients at 4 weeks but resolved in all but one patient by 12 weeks. There was no difference between FP treatment and TCA peeling with respect to any outcome measure. FP laser and TCA peel treatments were equally effective and safe when used to treat moderate-to-severe melasma, but neither treatment was long-lasting. We suggest that multiple or periodic maintenance treatments and/or supplemental procedures may be required for the successful treatment of melasma in Asian women.

  17. Carboxymethyl Cellulose, Trichloroacetic Acid, and Unna Boot for Healing Venous Ulcers: A Comparative Study of Their Efficacy and Socioeconomic Impact.

    PubMed

    Carneiro, Sueli; Januário, Virginia; Oliveira, Maria Leide W; de Oliveira Teixeira, Maria Luiza; Maciel, Solange; Macedo, João Carlos; Ramos-E-Silva, Marcia

    2017-01-01

    Chronic ulcers are defined as a breakdown of the long-term cutaneous barrier or frequent recurrence of breakdowns. Dressings are a form of treatment and, in view of the variety and high cost of the products on the market, three agents were selected for this investigation, regarding their efficacy and cost/benefit ratio. The objective of the investigation was to evaluate and compare the efficacy, costs, and benefits of carboxymethylcellulose in paste at 20% (CMC 20%), trichloroacetic acid at 90% (TCA 90%), and Unna boot for treatment of chronic venous ulcers. Three groups of 30 patients each were chosen randomly for ambulatory treatment with TCA 90% (G1), CMC 20% (G2), and Unna boot (G3). The evolution of the cicatricial process of each group separately and between groups was analyzed with measurement of the lesion areas in square centimeters (cm2) and observation of the amount of exudate from observation of the photographic record, until their healing, in the maximum period of 20 weeks. A significant reduction of lesion areas in all groups was observed ( P =.0001), with a median reduction of 7.6 cm 2 (38.1%) for G1, 3.9 cm 2 (38.8%) for G2, and 16.2 cm 2 (77.8%) for G3. There was a significant difference in the absolute delta of the lesion areas ( P =.0001) of the groups. The three types of treatments promoted effective improvement, with acquisition and utilization of all three products in the public health services being recommended.

  18. Deoxycholic acid and selenium metabolite methylselenol exert common and distinct effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon cancer cells.

    PubMed

    Zeng, Huawei; Botnen, James H; Briske-Anderson, Mary

    2010-01-01

    The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause compensatory hyperproliferation of colonic epithelial cells and consequently increase colon cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as anticancer nutrients. Methylselenol has been hypothesized to be a critical Se metabolite for anticancer activity in vivo. In this study, we demonstrated that both DCA (75-300 micromol/l) and submicromolar methylselenol inhibited colon cancer cell proliferation by up to 64% and 63%, respectively. In addition, DCA and methylselenol each increased colon cancer cell apoptosis rate by up to twofold. Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis and inhibited cell growth, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the molecular basis for opposite effects of methylselenol and DCA on colon tumorigenesis.

  19. Microbial Transformation of Dicarboxylic Acids by Airborne Bacteria

    NASA Astrophysics Data System (ADS)

    Cote, V.; Ariya, P.

    2004-05-01

    Organic aerosols are assumed to be key players in driving climatic changes and can cause health problems for human. Dicarboxylic acids (DCA) include a large fraction of identified important class of organic aerosols. In addition to direct sources, DCA are partly formed as the result of ozonolysis of terpenes and cyclic alkenes. Previous works in our laboratory show that airborne fungi collected from urban and suburban air play an important role in the transformation of severals organic aerosols such as DCA. Our present study focuses on understanding the potential chemical transformation induced by airborne bacteria and on identification of the transformation products. Airborne bacteria have been collected using a biosampler and cultivated on a solid media. Each bacterial colony is being tested by HPLC for their ability to transform DCA in liquid cultures. Also, GC-MS, SPME and NMR are being used to identify the metabolites generated from the transformation. We will present our preliminary results and we will discuss the application of bacterial activities on the chemical transformation of organics in atmosphere.

  20. Spermatotoxicity of dichloroacetic acid

    EPA Science Inventory

    The testicular toxicity of dichloroacetic acid (DCA), a disinfection byproduct of drinking water, was evaluated in adult male rats given both single and multiple (up to 14 d) oral doses. Delayed spermiation and altered resorption of residual bodies were observed in rats given sin...

  1. Dicarboxylic acids and levoglucosan in aerosols from Indo-Gangetic Plain: Inferences from day night variability during wintertime.

    PubMed

    Sorathia, Fena; Rajput, Prashant; Gupta, Tarun

    2018-05-15

    This study assesses daytime and nighttime atmospheric abundance and molecular distribution of dicarboxylic acids (DCA: C 2 -C 10 ) and biomass burning tracers (levoglucosan and biomass burning derived potassium: K + BB ) in PM 10 (particulate matter with aerodynamic diameter≤10μm) from an urban location, Kanpur (in central Indo-Gangetic Plain: IGP) during wintertime (December 2015-February 2016). In this study, PM 10 varied from 130 to 242 and 175-388μgm -3 during daytime and nighttime, respectively. The average ratios of OC/EC (day: 12.3; night: 9.3) and WSOC/OC (day: 0.74; night: 0.48) were relatively high during daytime (OC: organic carbon; EC: elemental carbon; WSOC: water-soluble organic carbon). Strong linear correlations (R 2 ≥0.6; p<0.05) of OC with levoglucosan and K + BB suggest biomass burning emission as predominant source of organic aerosols over the IGP. The measured concentrations of total DCA (ΣC 2 -C 10 ) showed pronounced diurnal variability with a higher concentration during nighttime (2510±1025ngm -3 ) as compared to that in daytime (1499±562ngm -3 ). Concentrations of oxalic acid (C 2 ), succinic acid (C 4 ) and malonic acid (C 3 ) were predominantly high as compared to other congeners of DCA (C 2 -C 10 ) over central IGP. Relatively higher mass fraction (73.4%) of C 2 in total DCA during nighttime than that in daytime (61.5%) indicates role of secondary organic aerosols (SOAs) formation involving aqueous-phase chemistry. Strong linear correlations of C 2 with C 3 and C 4 plausibly suggest that C 2 can have predominant formation pathways via decomposition of higher congeners of DCA. Overall, strong linear correlations of C 2 with levoglucosan and sulphate suggest that biomass burning emission and secondary transformations are predominant sources of DCA over IGP during wintertime. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Decreasing cartilage damage in a rat model of osteoarthritis by intra-articular injection of deoxycholic acid

    PubMed Central

    Yan, Zhaowei; Xiong, Jianbin; Zhao, Chunyang; Qin, Chenhao; He, Chunyan

    2015-01-01

    Background: The aim of this experimental study was to evaluate the effect of intra-articular injection of Deoxycholic acid (DCA) on articular cartilage and subchondral bone following induction of knee Osteoarthritis (OA) in a rat model. Methods: Twenty-four Sprague Dawley rats were randomized divided into 4 groups (n = 6). Eighteen of the 24 rats underwent surgical destabilization of the medial meniscus on the right knee joints to induce OA, were divided into 3 groups: DCA 30 mg/kg group, DCA 120 mg/kg group and OA group. The rats in DCA-treated groups were given intra-articular injections of DCA (30 mg/kg or 120 mg/kg) in the operated knees once per 3 days for 42 days. The rats in OA group given intra-articular injections of vehicle alone in the operated knees under the same conditions. The remaining 6 rats (sham-operation group) received sham operations on the right knee joints. 45 days postoperatively, all of the animals were euthanized for macroscopic, histological and radiographic analysis to evaluate the effect of DCA on OA and to determine its potential mechanisms. Results: The results showed that DCA attenuated the severity of OA by reducing macroscopic observation sores for femoral condyles and histological sores for articular cartilage. DCA also significantly decreased bone destruction and erosion of joint evaluated by radiographic examination. Furthermore, DCA could markedly reduce the release of MMP-1, MMP-3 and IL-1β in serum. Conclusions: Intra-articular injection of DCA is beneficial for knee OA. It might repair and protect OA cartilage by delaying cartilage degeneration and impairing the function of inflammatory mediators. These findings highlight DCA might be a useful therapeutic agent for OA. PMID:26309557

  3. Physiologically Based Pharmacokinetic (PBPK) Modeling of Interstrain Variability in Trichloroethylene Metabolism in the Mouse

    PubMed Central

    Campbell, Jerry L.; Clewell, Harvey J.; Zhou, Yi-Hui; Wright, Fred A.; Guyton, Kathryn Z.

    2014-01-01

    Background: Quantitative estimation of toxicokinetic variability in the human population is a persistent challenge in risk assessment of environmental chemicals. Traditionally, interindividual differences in the population are accounted for by default assumptions or, in rare cases, are based on human toxicokinetic data. Objectives: We evaluated the utility of genetically diverse mouse strains for estimating toxicokinetic population variability for risk assessment, using trichloroethylene (TCE) metabolism as a case study. Methods: We used data on oxidative and glutathione conjugation metabolism of TCE in 16 inbred and 1 hybrid mouse strains to calibrate and extend existing physiologically based pharmacokinetic (PBPK) models. We added one-compartment models for glutathione metabolites and a two-compartment model for dichloroacetic acid (DCA). We used a Bayesian population analysis of interstrain variability to quantify variability in TCE metabolism. Results: Concentration–time profiles for TCE metabolism to oxidative and glutathione conjugation metabolites varied across strains. Median predictions for the metabolic flux through oxidation were less variable (5-fold range) than that through glutathione conjugation (10-fold range). For oxidative metabolites, median predictions of trichloroacetic acid production were less variable (2-fold range) than DCA production (5-fold range), although the uncertainty bounds for DCA exceeded the predicted variability. Conclusions: Population PBPK modeling of genetically diverse mouse strains can provide useful quantitative estimates of toxicokinetic population variability. When extrapolated to lower doses more relevant to environmental exposures, mouse population-derived variability estimates for TCE metabolism closely matched population variability estimates previously derived from human toxicokinetic studies with TCE, highlighting the utility of mouse interstrain metabolism studies for addressing toxicokinetic variability

  4. The Bile Acid Receptor TGR5 Does Not Interact with β-Arrestins or Traffic to Endosomes but Transmits Sustained Signals from Plasma Membrane Rafts*

    PubMed Central

    Jensen, Dane D.; Godfrey, Cody B.; Niklas, Christian; Canals, Meritxell; Kocan, Martina; Poole, Daniel P.; Murphy, Jane E.; Alemi, Farzad; Cottrell, Graeme S.; Korbmacher, Christoph; Lambert, Nevin A.; Bunnett, Nigel W.; Corvera, Carlos U.

    2013-01-01

    TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion, and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs (deoxycholic acid (DCA), taurolithocholic acid) and the selective agonists oleanolic acid and 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated cAMP formation but did not induce TGR5 endocytosis or recruitment of β-arrestins, as assessed by confocal microscopy. DCA, taurolithocholic acid, and oleanolic acid did not stimulate TGR5 association with β-arrestin 1/2 or G protein-coupled receptor kinase (GRK) 2/5/6, as determined by bioluminescence resonance energy transfer. 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N, 5-dimethylisoxazole-4-carboxamide stimulated a low level of TGR5 interaction with β-arrestin 2 and GRK2. DCA induced cAMP formation at the plasma membrane and cytosol, as determined using exchange factor directly regulated by cAMP (Epac2)-based reporters, but cAMP signals did not desensitize. AG1478, an inhibitor of epidermal growth factor receptor tyrosine kinase, the metalloprotease inhibitor batimastat, and methyl-β-cyclodextrin and filipin, which block lipid raft formation, prevented DCA stimulation of ERK1/2. Bioluminescence resonance energy transfer analysis revealed TGR5 and EGFR interactions that were blocked by disruption of lipid rafts. DCA stimulated TGR5 redistribution to plasma membrane microdomains, as localized by immunogold electron microscopy. Thus, TGR5 does not interact with β-arrestins, desensitize, or traffic to endosomes. TGR5 signals from plasma membrane rafts that facilitate EGFR interaction and transactivation. An understanding of the spatiotemporal control of TGR5 signaling provides insights into the actions of BAs and therapeutic TGR5 agonists

  5. Monochloroacetic acid lethality in the rat in relation to lactic acid accumulation in the cerebrospinal fluid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mitroka, J.G.

    1989-01-01

    Potential antidotes for human exposure to monochloroacetic acid (MCA) were evaluated using a rodent model. Dichloroacetic acid (DCA) and phenobarbital (PB) but not ethanol or phenytoin, were found to be effective antidotes to monochloroacetic acid (MCA) in rats. DCA (110 mg/kg, ip), administered to rats 15 minutes after a LD-80 of MCA (80 mg/kg, iv), consistently reduced mortality to 0%, while PB reduced mortality to less than 20%. Both DCA and PB were found to be similarly effective in mice. The hypothesis that PB reduces mortality in MCA treated rats by altering the metabolic disposition of MCA was evaluated andmore » rejected. Administration of PB to rats treated with a lethal dose of ({sup 14}C)MCA did not alter the concentrations of MCA or its metabolites in plasma or cerebrospinal fluid (CSF), or the extent of covalent binding between radioactivity equivalent to ({sup 14}C)MCA and brain proteins. The relationship between altered blood-brain barrier permeability and death in MCA treated rats was investigated. Treatment with MCA (80 mg/kg, iv) was associated with a significant (50%) increase in the permeability of the rat blood-brain barrier to ({sup 125}I)BSA. The effect was not altered by treatment with PB, however, suggesting that altered blood-brain barrier permeability does not have an important role in the lethal effect of MCA in rats. The effect of MCA on brain carbohydrate metabolism in vivo was investigated. CSF and blood lactic acid concentrations increased in MCA treated rats, and the increase in CSF levels was dose related. In individual MCA treated rats, CSF lactate concentrations paralleled the time course of ataxia and a discrete threshold for death (18 mmol/L) was observed. The relationship between excess brain lactate levels and death in MCA treated rats was investigated further.« less

  6. EARLY GENE EXPRESSION CHANGES IN THE LIVERS OF MICE EXPOSED TO DICHOLORACETC ACID

    EPA Science Inventory

    EARLY GENE EXPRESSION CHANGES IN THE LIVERS OF MICE EXPOSED TO DICHLOROACETIC ACID

    Dichloroacetic acid COCA) is a major by-product ofwater disinfection by cWorination. Several
    studies have shown that DCA induces liver tumors in rodents when administered in drinkmg wate...

  7. A TWO-YEAR DOSE-RESPONSE STUDY OF LESION SEQUENCES DURING HEPATOCELLULAR CARCINOGENESIS IN THE MALE B6C3F1 MOUSE GIVEN THE DRINKING WATER CHEMICAL DICHLOROACETIC ACID

    EPA Science Inventory

    ABSTRACT

    Dichloroacetic acid (DCA) is carcinogenic to the B6C3F 1 mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver, and the known concentrations of this compound in drinking water, reliable biologically-based models to reduce the uncertai...

  8. Deoxycholic Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Exacerbates DSS-Induced Colitis through Promoting Cathepsin B Release.

    PubMed

    Zhao, Shengnan; Gong, Zizhen; Du, Xixi; Tian, Chunyan; Wang, Lingyu; Zhou, Jiefei; Xu, Congfeng; Chen, Yingwei; Cai, Wei; Wu, Jin

    2018-01-01

    We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1 β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

  9. UPTAKE AND ELIMINATION OF DICHLOROACETIC ACID BY RAINBOW TROUT

    EPA Science Inventory

    Dichloroacetic acid (DCA) is a by-product of drinking water chlorination and is a hepatocarcinogen in rodents. Preliminary results of a chronic testing effort with Japanese medaka suggest the possibility of similar effects is fish. Adult rainbow trout were cannulated from the dor...

  10. Identification of trichloroethylene and its metabolites in human seminal fluid of workers exposed to trichloroethylene.

    PubMed

    Forkert, Poh-Gek; Lash, Lawrence; Tardif, Robert; Tanphaichitr, Nongnuj; Vandevoort, Catherine; Moussa, Madeleine

    2003-03-01

    We have investigated the potential of the male reproductive tract to accumulate trichloroethylene (TCE) and its metabolites, including chloral, trichloroethanol (TCOH), trichloroacetic acid (TCA), and dichloroacetic acid (DCA). Human seminal fluid and urine samples from eight mechanics diagnosed with clinical infertility and exposed to TCE occupationally were analyzed. In in vivo experimental studies, TCE and its metabolites were determined in epididymis and testis of mice exposed to TCE (1000 ppm) by inhalation for 1 to 4 weeks. In other studies, incubations of monkey epididymal microsomes were performed in the presence of TCE and NADPH. Our results showed that seminal fluid from all eight subjects contained TCE, chloral, and TCOH. DCA was present in samples from two subjects, and only one contained TCA. TCA and/or TCOH were also identified in urine samples from only two subjects. TCE, chloral, and TCOH were detected in murine epididymis after inhalation exposure with TCE for 1 to 4 weeks. Levels of TCE and chloral were similar throughout the entire exposure period. TCOH levels were similar at 1 and 2 weeks but increased significantly after 4 weeks of TCE exposure. Chloral was identified in microsomal incubations with TCE in monkey epididymis. CYP2E1, a P450 that metabolizes TCE, was localized in human and monkey epididymal epithelium and testicular Leydig cells. These results indicated that TCE is metabolized in the reproductive tract of the mouse and monkey. Furthermore, TCE and its metabolites accumulated in seminal fluid, and suggested associations between production of TCE metabolites, reproductive toxicity, and impaired fertility.

  11. A New Perspective on an Old Problem, Natural Attenuation of the Lead Scavengers EDB and DCA in Ground Water

    EPA Science Inventory

    Tetra-ethyl lead was widely used in leaded automobile gasoline from 1923 until 1987. To prevent lead deposits from fouling the engine, 1,2-dibromoethane (EDB) and 1,2-dichloroethane (1,2-DCA) were added to the gasoline to act as lead scavengers. If leaded gasoline is spilled to...

  12. A MULTISTAGE BIOLOGICALLY BASED MODEL FOR MOUSE LIVER TUMORS RESULTING FROM EXPOSURE TO DICHLOROACETIC ACID

    EPA Science Inventory

    Dichloroacetic Acid (DCA) is a major byproduct of the chlorine disinfection of humic acid containing drinking water sources. It is a hepatocarcinogen in mice and rats at exposure concentrations in drinking water that are at least 4 orders of magnitude above the concentrations in ...

  13. Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids.

    PubMed

    Bowen, Christopher H; Bonin, Jeff; Kogler, Anna; Barba-Ostria, Carlos; Zhang, Fuzhong

    2016-03-18

    In search of sustainable approaches to plastics production, many efforts have been made to engineer microbial conversions of renewable feedstock to short-chain (C2-C8) bifunctional polymer precursors (e.g., succinic acid, cadaverine, 1,4-butanediol). Less attention has been given to medium-chain (C12-C14) monomers such as ω-hydroxy fatty acids (ω-OHFAs) and α,ω-dicarboxylic acids (α,ω-DCAs), which are precursors to high performance polyesters and polyamides. Here we engineer a complete microbial conversion of glucose to C12 and C14 ω-OHFAs and α,ω-DCAs, with precise control of product chain length. Using an expanded bioinformatics approach, we screen a wide range of enzymes across phyla to identify combinations that yield complete conversion of intermediates to product α,ω-DCAs. Finally, through optimization of culture conditions, we enhance production titer of C12 α,ω-DCA to nearly 600 mg/L. Our results indicate potential for this microbial factory to enable commercially relevant, renewable production of C12 α,ω-DCA-a valuable precursor to the high-performance plastic, nylon-6,12.

  14. The nature of chlorine-inhibition of photocatalytic degradation of dichloroacetic acid in a TiO2-based microreactor.

    PubMed

    Krivec, M; Dillert, R; Bahnemann, D W; Mehle, A; Štrancar, J; Dražić, G

    2014-07-28

    Photocatalytic degradation of dichloroacetic acid (DCA) was studied in a continuous-flow set-up using a titanium microreactor with an immobilized double-layered TiO2 nanoparticle/nanotube film. Chloride ions, formed during the degradation process, negatively affect the photocatalytic efficiency and at a certain concentration (approximately 0.5 mM) completely stop the reaction in the microreactor. Two proposed mechanisms of inhibition with chloride ions, competitive adsorption and photogenerated-hole scavenging, have been proposed and investigated by adsorption isotherms and electron paramagnetic resonance (EPR) measurements. The results show that chloride ions block the DCA adsorption sites on the titania surface and reduce the amount of adsorbed DCA molecules. The scavenging effect of chloride ions during photocatalysis through the formation of chlorine radicals was not detected.

  15. Metabolism and Excretion of Trichloroethylene after Inhalation by Human Subjects

    PubMed Central

    Bartoníček, V.

    1962-01-01

    Eight volunteers were exposed to trichloroethylene vapour (1,042 μg./l.) for five hours; 51 to 64% of the inhaled trichloroethylene was retained. The concentration of trichloroethanol and trichloroacetic acid in the urine was studied daily for a three-week period; on the third day both metabolites were determined in faeces, sweat, and saliva. The concentration of trichloroacetic acid in plasma and red blood cells was studied on alternate days. Of the trichloroethylene retained, 38·0 to 49·7% was excreted in the urine as trichloroethanol and 27·4 to 35·7% as trichloroacetic acid. Of both metabolites 8·4% was excreted in the faeces. Sweat collected on the third day of the experiment contained 0·10 to 1·92 mg./100 ml. trichloroethanol and 0·15 to 0·35 mg./100 ml. trichloroacetic acid. In saliva the concentrations were 0·09 to 0·32 mg./100 ml. trichloroethanol and 0·10 to 0·15 mg./100 ml. trichloroacetic acid. The value of the expression trichloroethanol/trichloroacetic acid calculated in the urine within 22 days was within the range 1·15 to 1·81. PMID:13865497

  16. Effective protein extraction protocol for proteomics studies of Jerusalem artichoke leaves.

    PubMed

    Zhang, Meide; Shen, Shihua

    2013-07-01

    Protein extraction is a crucial step for proteomics studies. To establish an effective protein extraction protocol suitable for two-dimensional electrophoresis (2DE) analysis in Jerusalem artichoke (Helianthus tuberosus L.), three different protein extraction methods-trichloroacetic acid/acetone, Mg/NP-40, and phenol/ammonium acetate-were evaluated using Jerusalem artichoke leaves as source materials. Of the three methods, trichloroacetic acid/acetone yielded the best protein separation pattern and highest number of protein spots in 2DE analysis. Proteins highly abundant in leaves, such as Rubisco, are typically problematic during leaf 2DE analysis, however, and this disadvantage was evident using trichloroacetic acid/acetone. To reduce the influence of abundant proteins on the detection of low-abundance proteins, we optimized the trichloroacetic acid/acetone method by incorporating a PEG fractionation approach. After optimization, 363 additional (36.2%) protein spots were detected on the 2DE gel. Our results suggest that trichloroacetic acid/acetone method is a better protein extraction technique than Mg/NP-40 and phenol/ammonium acetate in Jerusalem artichoke leaf 2DE analysis, and that trichloroacetic acid/acetone method combined with PEG fractionation procedure is the most effective approach for leaf 2DE analysis of Jerusalem artichoke. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation

    USDA-ARS?s Scientific Manuscript database

    Consumption of a high fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer preventive effects. To distinguish these opposing effects of D...

  18. Latent carcinogenicity of early-life exposure to dichloroacetic acid in mice

    EPA Science Inventory

    AbstractEnvironmental exposures occurring early in life may have an important influence on cancer risk later in life. Here we investigated carryover effects of young-adult exposure to dichloroacetic acid (DCA), a small molecule analog of pyruvate and low-level environmental cont...

  19. Deoxycholic acid inhibits smooth muscle contraction via protein kinase C-dependent modulation of L-type Ca2+ channels in rat proximal colon.

    PubMed

    Hu, Liu-Dan; Yu, Bao-Ping; Yang, Bin

    2012-10-01

    The aim of this study was to investigate the effects of deoxycholic acid (DCA) on the contractions of rat proximal colonic smooth muscle (PCSM) in vitro. The contractile response of rat PCSM strips was tested using a polyphysio-graph. The whole cell patch-clamp technique was also used in rat colonic smooth muscle cells (SMCs) isolated by an enzymatic procedure to record the L-type calcium current (I(Ca-L)) prior to and following the application of various concentrations of DCA. The application of DCA (10(-6)-10(-4) M) decreased the amplitude of spontaneous contractions of the PCSM strips in a dose-dependent manner. The administration of DCA (10(-5) M) caused the relaxation of isolated smooth muscle strips pre-contracted by acetylcholine (Ach) or KCl (by 12.2±1.5 and 16.3±6.9%, respectively). The concentration-response curve of CaCl2 was shifted to the right. Pre-treatment of the strips with the protein kinase C (PKC) inhibitor chelerythrine (1 µM) significantly attenuated the effects of DCA on the strips pre-contracted by Ach. DCA reduced the peak I(Ca-L) by 6.02±0.87% at 10(-6) M, 15.02±1.73% at 10(-5) M and 47.14±3.79% at 10(-4) M. DCA shifted the current-voltage (I-V) curve of ICa-L upward, but the contour of the I-V curve was unchanged, and the peak current-induced voltage remained at 0 mV. Pre-treatment with chelerythrine (1 µM) blocked the actions of DCA on the I(Ca-L). Taken together, the actions of DCA on I(Ca-L) in rat colonic SMCs contributed to a negative inotropic effect. These actions appear to be mediated through protein kinase C. Furthermore, this study suggests another possible mechanism for the DCA-related modulation of gastrointestinal motility.

  20. Examination of age-related epigenetic changes following early-life exposure to dichloroacetic acid

    EPA Science Inventory

    Recent studies have shown that transient early-life exposure to dichloroacetic acid (DCA), a pyruvate analog and metabolic reprogramming agent, increases liver cancer incidence in older mice. This carcinogenic effect is not associated with direct mutagenicity, persistent cytotoxi...

  1. Developmental toxicity of mixtures: the water disinfection by-products dichloro-, dibromo- and bromochloro acetic acid in rat embryo culture

    EPA Science Inventory

    The chlorination of drinking water results in production of numerous disinfection by-products (DBPs). One of the important classes of DBPs is the haloacetic acids. We have previously shown that the haloacetic acids (HAs), dichloro (DCA), dibromo (DBA) and bromochloro (BCA) acetic...

  2. DNA Methylation Alterations Associated with Latent Carcinogenic Activity of Dichloroacetic Acid in Mice

    EPA Science Inventory

    Early-life environmental factors can influence later-life susceptibility to cancer. Epigenetic changes serve as promising biomarkers for these latent effects. Previously, we reported that short-term postnatal exposure to dichloroacetic acid (DCA), a byproduct of drinking water ch...

  3. IRIS TOXICOLOGICAL REVIEW AND SUMMARY ...

    EPA Pesticide Factsheets

    Trichloroacetic acid is a crystalline solid with sharp, pungent odor. It is used as a soil sterilizer; and as a laboratory intermediate or reagent in the synthesis of a variety of medicinal products and organic chemicals. Trichloroacetic acid is also used industrially as an etching and pickling agent for the surface treatment of metals and as a solvent in the plastics industry. Trichloroacetic acid can be formed as a combustion byproduct of organic compounds in the presence of chlorine. It is also formed as a disinfection byproduct during water chlorination. The existing IRIS entry was added to the IRIS data base between 1994 and 1996. No RfD was developed. The IRIS program is updating the IRIS assessment for Trichloroacetic Acid. This update will incorporate health effects information published since the last assessment was prepared as well as new risk assessment methods. The IRIS assessment for Trichloroacetic Acid will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physicochemical and toxicokinetic properties of the chemical and its toxicity in humans and experimental systems. The assessment will present reference value for noncancer effects of Trichloroacetic Acid (RfD) and a cancer assessment. The Toxicological Review and IRIS Summary will be subject to internal peer consultation, Agency review and external scientific peer review. The final products will constitute the Agency's opinion on the

  4. Inorganic salts interact with organic di-acids in sub-micron particles to form material with low hygroscopicity and volatility

    NASA Astrophysics Data System (ADS)

    Drozd, G.; Woo, J.; Häkkinen, S. A. K.; Nenes, A.; McNeill, V. F.

    2013-11-01

    Volatility and hygroscopicity are two key properties of organic aerosol components, and both are strongly related to chemical identity. Here we show that inorganic-organic component interactions typically not considered in atmospheric models may strongly affect aerosol volatility and hygroscopicity. In particular, bi-dentate binding of di-carboxylic acids (DCA) to soluble inorganic ions can lead to very strongly bound metal-organic complexes with largely undetermined hygroscopicity and volatility. These reactions profoundly impact particle hygroscopicity, transforming hygroscopic components into irreversibly non-hygroscopic material. While the hygroscopicities of pure salts, DCA, and DCA salts are known, the hygroscopicity of internal mixtures of hygroscopic salts and DCA, as they are typically found in the atmosphere, has not been fully characterized. We have studied the volatility of pure, dry organic salt particles and the hygroscopicity of internal mixtures of oxalic acid (OxA, the dominant DCA in the atmosphere) and a number of salts, both mono- and di-valent. The formation of very low volatility organic salts was confirmed, with minimal evaporation of oxalate salt particles below 75 °C. Dramatic increases in the CCN activation diameter for particles with divalent salts (e.g. CaCl2) and relatively small particle mass fractions of OxA indicate that standard volume additivity rules for hygroscopicity do not apply. Thus small organic compounds with high O:C are capable of forming low volatility and very low hygroscopicity particles. Given current knowledge of the formation mechanisms of OxA and M-Ox salts, surface enrichment of insoluble M-Ox salts is expected. The resulting formation of an insoluble coating of metal-oxalate salts can explain low particle hygroscopicities. The formation of particles with a hard coating could offer an alternative explanation for observations of glass-like particles with very low viscosity.

  5. Growth and characterization of Melaminium bis (trichloroacetate) dihydrate

    NASA Astrophysics Data System (ADS)

    Kanagathara, N.; Renganathan, N. G.; Marchewka, M. K.; Sivakumar, N.; Gayathri, K.; Krishnan, P.; Gunasekaran, S.; Anbalagan, G.

    2013-01-01

    Single crystals of melaminium bis (trichloroacetate) dihydrate have been grown successfully by slow evaporation solution growth technique at room temperature. Single crystal X-ray diffraction analysis reveals that the compound crystallizes in monoclinic system with non -centrosymmetric space group C2 with lattice parameters a = 17.70 Å, b = 8.44 Å, c = 6.09 Å, α = 90°, β = 100.24°, γ = 90° and V = 900 (Å)3. The UV-Vis transmittance spectrum shows that the crystal has a good optical transmittance in the entire visible region with lower cutoff wavelength of 351 nm. The vibrational frequencies of various functional groups present in the crystal have been derived from FI-IR, FT-Raman and Confocal Raman analyses. The chemical structure of the compound was established by 1H and 13C NMR spectrum. TGA-DTA analysis reveals that the materials have good thermal stability and the melting point of the crystal is found to be 195 °C. The dielectric response of the crystals was studied in the frequency range 50 Hz to 5 MHz at different temperatures and the results are discussed. Etching studies show the growth pattern of the crystals. The second harmonic generation efficiency was measured in comparison with KDP by employing powder Kurtz method.

  6. Stromal COX-2 signaling activated by deoxycholic acid mediates proliferation and invasiveness of colorectal epithelial cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu, Yingting, E-mail: yitizhu@yahoo.com; Tissue Tech Inc., Miami, FL 33173; Zhu, Min

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Human colonic cancer associated fibroblasts are major sources of COX-2 and PGE{sub 2}. Black-Right-Pointing-Pointer The fibroblasts interact with human colonic epithelial cancer cells. Black-Right-Pointing-Pointer Activation of COX-2 signaling in the fibroblasts affects behavior of the epithelia. Black-Right-Pointing-Pointer Protein Kinase C controls the activation of COX-2 signaling. -- Abstract: COX-2 is a major regulator implicated in colonic cancer. However, how COX-2 signaling affects colonic carcinogenesis at cellular level is not clear. In this article, we investigated whether activation of COX-2 signaling by deoxycholic acid (DCA) in primary human normal and cancer associated fibroblasts play a significant role in regulationmore » of proliferation and invasiveness of colonic epithelial cancer cells. Our results demonstrated while COX-2 signaling can be activated by DCA in both normal and cancer associated fibroblasts, the level of activation of COX-2 signaling is significantly greater in cancer associated fibroblasts than that in normal fibroblasts. In addition, we discovered that the proliferative and invasive potential of colonic epithelial cancer cells were much greater when the cells were co-cultured with cancer associated fibroblasts pre-treated with DCA than with normal fibroblasts pre-treated with DCA. Moreover, COX-2 siRNA attenuated the proliferative and invasive effect of both normal and cancer associate fibroblasts pre-treated with DCA on the colonic cancer cells. Further studies indicated that the activation of COX-2 signaling by DCA is through protein kinase C signaling. We speculate that activation of COX-2 signaling especially in cancer associated fibroblasts promotes progression of colonic cancer.« less

  7. Transcription of exogenous and endogenous deoxyribonucleic acid templates in cold-shocked Bacillus subtilis.

    PubMed Central

    Kuhl, S J; Brown, L R

    1980-01-01

    Ribonucleic acid (RNA) synthesis was examined in cold-shocked Bacillus subtilis cells. The cells were grown to mid-log stage, harvested, and cold shocked. RNA synthesis was monitored by the incorporation of [3H]uridine triphosphate or [alpha 32P]adenosine triphosphate into trichloroacetic acid-precipitable material in the presence of all four nucleoside triphosphates. The inhibition of RNA synthesis in cold-shocked cells by lipiarmycin, ethidium bromide, rifampin. or streptolydigin was analyzed using mutant or wild-type cells. Also examined were the effects of temperature, salt concentration, and the addition of polyamines or highly phosphorylated nucleotides. In ultraviolet-irradiated and cold-shocked cells, RNA wynthesis decreased to low levels. The addition of exogenous phi 29 or TSP-1 template to these cells caused a 13- to 20-fold increase in RNA synthesis, as monitored by trichloroacetic acid-precipitable counts. RNA synthesized in the presence of phi 29 deoxyribonucleic acid (DNA) hybridizes mainly to EcoRI fragments A and C of phi 29 DBA, These two fragments direct transcription by purified RNA polymerase in vitro and hybridize to early phi 29 DNA produced in vivo. Our results with TSP-1 DNA in this system indicated that the RNA produced hybridizes to the same fragments as early RNA produced in vivo. Plasmic pUB110 DNA was not transcribed in this system. Images PMID:6157674

  8. Metabolic Disruption Early in Life is Associated With Latent Carcinogenic Activity of Dichloroacetic Acid in Mice

    EPA Science Inventory

    Early-life environmental factors can influence later-life susceptibility to cancer. Recent evidence suggests that metabolic pathways may mediate this type of latency effect. Previously, we reported that short-term exposure to dichloroacetic acid (DCA) increased liver cancer in mi...

  9. Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin-αv trafficking.

    PubMed

    Prichard, David O; Byrne, Anne Marie; Murphy, James O; Reynolds, John V; O'Sullivan, Jacintha; Feighery, Ronan; Doyle, Brendan; Eldin, Osama Sharaf; Finn, Stephen P; Maguire, Aoife; Duff, Deirdre; Kelleher, Dermot P; Long, Aideen

    2017-12-01

    The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus (BO) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium (HET-1A) and BO (QH) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α 3 , α 4, α 5 , α 6 and α ν ). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease (GORD) and in patient tissue microarrays. The bile acid deoxycholic acid (DCA) specifically reduced adhesion of HET-1A cells to vitronectin and reduced cell-surface expression of integrin-α ν via effects on endocytic recycling processes. Increased expression of integrin-α v was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin-α ν was observed in QH BO cells compared to HET-1A cells. QH cells were resistant to DCA-mediated loss of adhesion and reduction in cell-surface expression of integrin-α ν . We demonstrated that a specific component of the gastric refluxate, DCA, affects the epithelial barrier through modulation of integrin α ν expression, providing a novel mechanism for bile acid-mediated erosion of oesophageal squamous epithelium and promotion of BO. Strategies aimed at preventing bile acid-mediated erosion should be considered in the clinical management of patients with GORD. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Detection of genotoxic effects of drinking water disinfection by-products using Vicia faba bioassay.

    PubMed

    Hu, Yu; Tan, Li; Zhang, Shao-Hui; Zuo, Yu-Ting; Han, Xue; Liu, Na; Lu, Wen-Qing; Liu, Ai-Lin

    2017-01-01

    Plant-based bioassays have gained wide use among the toxicological and/or ecotoxicological assessment procedures because of their simplicity, sensitivity, low cost, and reliability. The present study describes the use of Vicia faba (V. faba) micronucleus (MN) test and V. faba comet assay in the evaluation of the genotoxic potential of disinfection by-products (DBPs) commonly found in chlorine-disinfected drinking water. Five haloacetic acids and three halogenated acetonitriles were chosen as representatives of DBPs in this study because they are of potentially great public health risk. Results of the MN test indicated that monochloroacetic acid (MCA), monobromoacetic acid (MBA), dichloroacetic acid (DCA), dibromoacetic acid (DBA), trichloroacetic acid (TCA), and trichloroacetonitrile (TCAN) caused a statistically significant increase in MN frequency in V. faba root tip cells. However, no genotoxic response was observed for dichloroacetonitrile (DCAN) and dibromoacetonitrile (DBAN). Results of the comet assay showed that all tested DBPs induced a statistically significant increase in genomic DNA damage to V. faba root tip cells. On considering the capacity to detect genomic damage of a different nature, we suggest that a combination of V. faba MN test and V. faba comet assay is a useful tool for the detection of genotoxic effects of DBPs. It is worthy of assessing the feasibility of using V. faba comet assay combined with V. faba MN test to screen for the genotoxic activity of chlorinated drinking water in future work.

  11. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Liver Effects

    PubMed Central

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Shymonyak, Svitlana; Uehara, Takeki; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a widely used organic solvent. Although TCE is classified as carcinogenic to humans, substantial gaps remain in our understanding of inter-individual variability in TCE metabolism and toxicity, especially in the liver. We tested a hypothesis that amounts of oxidative metabolites of TCE in mouse liver are associated with liver-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione] in serum and liver, and various liver toxicity phenotypes. In sub-acute study, inter-strain variability in TCE metabolite amounts was observed in serum and liver. No induction of Cyp2e1 protein levels in liver was detected. Serum and liver levels of TCA and DCA were correlated with increased transcription of peroxisome proliferator-marker genes Cyp4a10 and Acox1, but not with degree of induction in hepatocellular proliferation. In sub-chronic study, serum and liver levels of oxidative metabolites gradually decreased over time despite continuous dosing. Liver protein levels of Cyp2e1, Adh and Aldh2 were unaffected by treatment with TCE. While the magnitude of induction of peroxisome proliferator-marker genes also declined, hepatocellular proliferation increased. This study offers a unique opportunity to provide a scientific data-driven rationale for some of the major assumptions in human health assessment of TCE. PMID:25424544

  12. Selective removal of monoterpenes from bergamot oil by inclusion in deoxycholic acid.

    PubMed

    Fantin, Giancarlo; Fogagnolo, Marco; Maietti, Silvia; Rossetti, Stefano

    2010-05-12

    A new approach for removing monoterpenes (MTs) from bergamot oil by selective inclusion in deoxycholic acid (DCA) is proposed. The inclusion process is very efficient, the included fraction being composed mainly of limonene (71.7%) and gamma-terpinene (19.8%). On the other hand, the deterpenated bergamot oil fraction showed for the linalool and linalyl acetate derivatives significant increases from 16.6 and 21.4% to 18.3 and 42.2%, respectively. The major advantages of this methodology are its simplicity, the mild conditions employed, and the quantitative recovery of both host (DCA) and guest (monoterpenes) compounds. Differential scanning calorimetry (DSC), thermal gravimetry (TG), powder X-ray diffractometry (XRPD), infrared spectroscopy (IR), and proton magnetic resonance ((1)H NMR) analysis were used to investigate and characterize the inclusion compounds.

  13. Inorganic salts interact with oxalic acid in submicron particles to form material with low hygroscopicity and volatility

    NASA Astrophysics Data System (ADS)

    Drozd, G.; Woo, J.; Häkkinen, S. A. K.; Nenes, A.; McNeill, V. F.

    2014-05-01

    Volatility and hygroscopicity are two key properties of organic aerosol components, and both are strongly related to chemical identity. While the hygroscopicities of pure salts, di-carboxylic acids (DCA), and DCA salts are known, the hygroscopicity of internal mixtures of these components, as they are typically found in the atmosphere, has not been fully characterized. Here we show that inorganic-organic component interactions typically not considered in atmospheric models can lead to very strongly bound metal-organic complexes and greatly affect aerosol volatility and hygroscopicity; in particular, the bi-dentate binding of DCA to soluble inorganic ions. We have studied the volatility of pure, dry organic salt particles and the hygroscopicity of internal mixtures of oxalic acid (OxA, the dominant DCA in the atmosphere) and a number of salts, both mono- and di-valent. The formation of very low volatility organic salts was confirmed, with minimal evaporation of oxalate salt particles below 75 °C. Dramatic increases in the cloud condensation nuclei (CCN) activation diameter for particles with di-valent salts (e.g., CaCl2) and relatively small particle volume fractions of OxA indicate that standard volume additivity rules for hygroscopicity do not apply. Thus small organic compounds with high O : C ratios are capable of forming low-volatility and very low hygroscopicity particles. Given current knowledge of the formation mechanisms of OxA and M-Ox salts, surface enrichment of insoluble M-Ox salts is expected. The resulting formation of an insoluble coating of metal-oxalate salts can explain low-particle hygroscopicities. The formation of particles with a hard coating could offer an alternative explanation for observations of glass-like particles without the need for a phase transition.

  14. Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.

    PubMed

    Sheng, Lili; Jena, Prasant Kumar; Hu, Ying; Liu, Hui-Xin; Nagar, Nidhi; Kalanetra, Karen M; French, Samuel William; French, Samuel Wheeler; Mills, David A; Wan, Yu-Jui Yvonne

    2017-12-01

    Dysregulated bile acid (BA) synthesis or reduced farnesoid X receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis-induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild-type (WT) and FXR knockout (KO) male mice were placed on a control (CD) or western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15-month-old WD-fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7-month-old WD-fed FXR KO for 3 months. Hepatic phenotypes, microbiota profile, and BA composition were analyzed. Butyrate-generating bacteria and colonic butyrate concentration were reduced due to FXR inactivation and further reduced by WD intake. In addition, WD-fed FXR KO male mice had the highest concentration of hepatic β-muricholic acid (β-MCA) and bacteria-generated deoxycholic acid (DCA) accompanied by serious hepatitis. Moreover, dysregulated BA and reduced SCFA signaling co-existed in both human liver cancers and WD-fed FXR KO mice. Microbiota transplantation using butyrate-deficient feces derived from 15-month-old WD-fed FXR KO mice increased hepatic lymphocyte numbers as well as hepatic β-MCA and DCA concentrations. Furthermore, butyrate supplementation reduced hepatic β-MCA as well as DCA and eliminated hepatic lymphocyte infiltration. In conclusion, reduced butyrate contributes to the development of hepatitis in the FXR KO mouse model. In addition, butyrate reverses dysregulated BA synthesis and its associated hepatitis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  15. Urinary trichloroacetic acid levels and semen quality: A hospital-based cross-sectional study in Wuhan, China

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xie, Shao-Hua; The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Li, Yu-Feng

    Toxicological studies indicate an association between exposure to disinfection by-products (DBPs) and impaired male reproductive health in animals. However, epidemiological evidence in humans is still limited. We conducted a hospital-based cross-sectional study to investigate the effect of exposure to DBPs on semen quality in humans. Between May 2008 and July 2008, we recruited 418 male partners in sub-fertile couples seeking infertility medical instruction or assisted reproduction services from the Tongji Hospital in Wuhan, China. Major semen parameters analyzed included sperm concentration, motility, and morphology. Exposure to DBPs was estimated by their urinary creatinine-adjusted trichloroacetic (TCAA) concentrations that were measured withmore » the gas chromatography/electron capture detection method. We used linear regression to assess the relationship between exposure to DBPs and semen quality. According to the World Health Organization criteria (<20 million/mL for sperm concentration and <50% motile for sperm motility) and threshold value recommended by Guzick (<9% for sperm morphology), there were 265 men with all parameters at or above the reference values, 33 men below the reference sperm concentration, 151 men below the reference sperm motility, and 6 men below the reference sperm morphology. The mean (median) urinary creatinine-adjusted TCAA concentration was 9.2 (5.1) {mu}g/g creatinine. Linear regression analyses indicated no significant association of sperm concentration, sperm count, and sperm morphology with urinary TCAA levels. Compared with those in the lowest quartile of creatinine-adjusted urinary TCAA concentrations, subjects in the second and third quartiles had a decrease of 5.1% (95% CI: 0.6%, 9.7%) and 4.7% (95% CI: 0.2%, 9.2%) in percent motility, respectively. However, these associations were not significant after adjustment for age, abstinence time, and smoking status. The present study provides suggestive but inconclusive evidence

  16. Natural Attenuation of the Lead Scavengers 1,2-Dibromoethane (EDB) and 1.2-Dichloroethane (1,2-DCA) at Motor Fuel Release Sites and Implications for Risk Management

    EPA Science Inventory

    The lead scavengers 1,2-dibromoethane (EDB) and 1,2-dichloroethane (1,2-DCA) were included along with lead in conventional leaded gasoline used for automobiles in the US prior to 1988. Old spills of leaded gasoline from underground storage tank systems (USTs) at gasoline service...

  17. Deproteinizing methods evaluated for determination of uric acid in serum by reversed-phase liquid chromatography with ultraviolet detection.

    PubMed

    Sakuma, R; Nishina, T; Kitamura, M

    1987-08-01

    We evaluated six deproteinizing methods for determination of uric acid in serum by "high-performance" liquid chromatography with ultraviolet detection: those involving zinc hydroxide, sodium tungstate, trichloroacetic acid, perchloric acid, acetonitrile, and centrifugal ultrafiltration (with Amicon MPS-1 devices). We used a Toyosoda ODS-120A reversed-phase column. The mobile phase was sodium phosphate buffer (40 mmol/L, pH 2.2) containing 20 mL of methanol per liter. Absorbance of the eluate was monitored at 284 nm. The precipitation method with perchloric acid gave high recoveries of uric acid and good precision, and results agreed with those by the uricase-catalase method of Kageyama (Clin Chim Acta 1971;31:421-6).

  18. Taurocholic acid metabolism by gut microbes and colon cancer

    PubMed Central

    Ridlon, Jason M.; Wolf, Patricia G.; Gaskins, H. Rex

    2016-01-01

    ABSTRACT Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively. PMID:27003186

  19. Haloacetates in fog and rain.

    PubMed

    Römpp, A; Klemm, O; Fricke, W; Frank, H

    2001-04-01

    Atmospheric haloacetates can arise from photochemical degradation of halogenated hydrocarbons and from direct anthropogenic emissions. Furthermore, there is also evidence of natural sources although these are quantitatively uncertain. As haloacetates are highly soluble in water, hydrometeors are most significant for their deposition. Fogwater (96 samples) and rainwater samples (over 100 samples) were collected from July 1998 to March 1999 at an ecological research site in northeastern Bavaria, Germany. They were analyzed for monofluoroacetate (MFA), difluoroacetate (DFA), trifluoroacetate (TFA), monochloroacetate (MCA), dichloroacetate (DCA), trichloroacetate (TCA), monobromoacetate (MBA), and dibromoacetate (DBA). The major inorganic ions were also determined. High concentrations of up to 11 microg/L MCA, 5 microg/L DCA, 2 microg/L TCA, and 2 microg/L TFA were found in fogwater associated with westerly winds. Backward trajectories were calculated to determine the origin of the air masses. MBA and DBA have highest concentrations in fogwater advected with air originating from the Atlantic, suggesting the marine origin of these two compounds. All analyzed substances show higher average concentrations in fog than in rain. Estimates of the deposition of haloacetates suggest that the contribution of fog may be more important than rain for the total burden of a forest ecosystem.

  20. Quantitative analysis of glycerol in dicarboxylic acid-rich cutins provides insights into Arabidopsis cutin structure.

    PubMed

    Yang, Weili; Pollard, Mike; Li-Beisson, Yonghua; Ohlrogge, John

    2016-10-01

    Cutin is an extracellular lipid polymer that contributes to protective cuticle barrier functions against biotic and abiotic stresses in land plants. Glycerol has been reported as a component of cutin, contributing up to 14% by weight of total released monomers. Previous studies using partial hydrolysis of cuticle-enriched preparations established the presence of oligomers with glycerol-aliphatic ester links. Furthermore, glycerol-3-phosphate 2-O-acyltransferases (sn-2-GPATs) are essential for cutin biosynthesis. However, precise roles of glycerol in cutin assembly and structure remain uncertain. Here, a stable isotope-dilution assay was developed for the quantitative analysis of glycerol by GC/MS of triacetin with simultaneous determination of aliphatic monomers. To provide clues about the role of glycerol in dicarboxylic acid (DCA)-rich cutins, this methodology was applied to compare wild-type (WT) Arabidopsis cutin with a series of mutants that are defective in cutin synthesis. The molar ratio of glycerol to total DCAs in WT cutins was 2:1. Even when allowing for a small additional contribution from hydroxy fatty acids, this is a substantially higher glycerol to aliphatic monomer ratio than previously reported for any cutin. Glycerol content was strongly reduced in both stem and leaf cutin from all Arabidopsis mutants analyzed (gpat4/gpat8, att1-2 and lacs2-3). In addition, the molar reduction of glycerol was proportional to the molar reduction of total DCAs. These results suggest "glycerol-DCA-glycerol" may be the dominant motif in DCA-rich cutins. The ramifications and caveats for this hypothesis are presented. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Effect of chemical peeling on photocarcinogenesis.

    PubMed

    Abdel-Daim, Mohamed; Funasaka, Yoko; Kamo, Tsuneyoshi; Ooe, Masahiko; Matsunaka, Hiroshi; Yanagita, Emmy; Itoh, Tomoo; Nishigori, Chikako

    2010-10-01

    Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photo-aged skin. We assessed the photo-chemopreventive effect of several clinically used chemical peeling agents on the ultraviolet-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, and 10% or 35% trichloroacetic acid in distilled water at the right back of ultraviolet-irradiated hairless mice every 2 weeks for glycolic acid, salicylic acid and 10% trichloroacetic acid, and every 4 weeks for 35% trichloroacetic acid for a total of 18 weeks after the establishment of photo-aged mice by irradiation with ultraviolet B range light three times a week for 14 weeks at a total dose of 6.66 J/cm(2) . Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of p53 expression and mRNA expression of cyclooxygenase-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also in the non-treated area. Peeling suppressed retention of p53-positive abnormal cells and reduced mRNA expression of cyclooxygenase-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo-damaged cells. © 2010 Japanese Dermatological Association.

  2. Binding of bile acids by pastry products containing bioactive substances during in vitro digestion.

    PubMed

    Dziedzic, Krzysztof; Górecka, Danuta; Szwengiel, Artur; Smoczyńska, Paulina; Czaczyk, Katarzyna; Komolka, Patrycja

    2015-03-01

    The modern day consumer tends to choose products with health enhancing properties, enriched in bioactive substances. One such bioactive food component is dietary fibre, which shows a number of physiological properties including the binding of bile acids. Dietary fibre should be contained in everyday, easily accessible food products. Therefore, the aim of this study was to determine sorption capacities of primary bile acid (cholic acid - CA) and secondary bile acids (deoxycholic - DCA and lithocholic acids - LCA) by muffins (BM) and cookies (BC) with bioactive substances and control muffins (CM) and cookies (CC) in two sections of the in vitro gastrointestinal tract. Variations in gut flora were also analysed in the process of in vitro digestion of pastry products in a bioreactor. Enzymes: pepsin, pancreatin and bile salts: cholic acid, deoxycholic acid and lithocholic acid were added to the culture. Faecal bacteria, isolated from human large intestine, were added in the section of large intestine. The influence of dietary fibre content in cookies and concentration of bile acids in two stages of digestion were analysed. Generally, pastry goods with bioactive substances were characterized by a higher content of total fibre compared with the control samples. These products also differ in the profile of dietary fibre fractions. Principal Component Analysis (PCA) showed that the bile acid profile after two stages of digestion depends on the quality and quantity of fibre. The bile acid profile after digestion of BM and BC forms one cluster, and with the CM and CC forms a separate cluster. High concentration of H (hemicellulose) is positively correlated with LCA (low binding effect) and negatively correlated with CA and DCA contents. The relative content of bile acids in the second stage of digestion was in some cases above the content in the control sample, particularly LCA. This means that the bacteria introduced in the 2nd stage of digestion synthesize the LCA.

  3. Chemical Peeling: A Useful Tool in the Office.

    PubMed

    Truchuelo, M; Cerdá, P; Fernández, L F

    2017-05-01

    Chemical peeling is a common treatment in cosmetic dermatology. A peel that has been used for many years is trichloroacetic acid. Its adverse effects have for a long time been a major limitation. We present a practical review of the characteristics, mechanisms of action, indications, and complications of superficial chemical peels and of peeling with trichloroacetic acid. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Structural, optical, mechanical and dielectric studies of pure and doped L-Prolinium trichloroacetate single crystals.

    PubMed

    Renuka, N; Ramesh Babu, R; Vijayan, N; Vasanthakumar, Geetha; Krishna, Anuj; Ramamurthi, K

    2015-02-25

    In the present work, pure and metal substituted L-Prolinium trichloroacetate (LPTCA) single crystals were grown by slow evaporation method. The grown crystals were subjected to single crystal X-ray diffraction (XRD), powder X-ray diffraction, FTIR, UV-Visible-NIR, hardness, photoluminescence and dielectric studies. The dopant concentration in the crystals was measured by inductively coupled plasma (ICP) analysis. Single crystal X-ray diffraction studies of the pure and metal substituted LPTCA revealed that the grown crystals belong to the trigonal system. Ni(2+) and Co(2+) doping slightly altered the lattice parameters of LPTCA without affecting the basic structure of the crystal. FTIR spectral analysis confirms the presence of various functional groups in the grown crystals. The mechanical behavior of pure and doped crystals was analyzed by Vickers's microhardness test. The optical transmittance, dielectric and photoluminescence properties of the pure and doped crystals were analyzed. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Changes in the faecal bile acid profile in dogs fed dry food vs high content of beef: a pilot study.

    PubMed

    Herstad, Kristin Marie Valand; Rønning, Helene Thorsen; Bakke, Anne Marie; Moe, Lars; Skancke, Ellen

    2018-05-11

    Dogs are fed various diets, which also include components of animal origin. In humans, a high-fat/low-fibre diet is associated with higher faecal levels of bile acids, which can influence intestinal health. It is unknown how an animal-based diet high in fat and low in fibre influences the faecal bile acid levels and intestinal health in dogs. This study investigated the effects of high intake of minced beef on the faecal bile acid profile in healthy, adult, client-owned dogs (n = 8) in a 7-week trial. Dogs were initially adapted to the same commercial dry food. Thereafter, incremental substitution of the dry food by boiled minced beef over 3 weeks resulted in a diet in which 75% of each dog's total energy requirement was provided as minced beef during week 5. Dogs were subsequently reintroduced to the dry food for the last 2 weeks of the study. The total taurine and glycine-conjugated bile acids, the primary bile acids chenodeoxycholic acid and cholic acid, and the secondary bile acids lithocholic acid, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) were analysed, using liquid chromatography-tandem mass spectrometry. The faecal quantities of DCA were significantly higher in dogs fed the high minced beef diet. These levels reversed when dogs were reintroduced to the dry food diet. The faecal levels of UDCA and taurine-conjugated bile acids had also increased in response to the beef diet, but this was only significant when compared to the last dry food period. These results suggest that an animal-based diet with high-fat/low-fibre content can influence the faecal bile acids levels. The consequences of this for canine colonic health will require further investigation.

  6. A patient with scirrhous stomach cancer treated with combination of hyperthermotherapy and 5-aminolevulinic acid (ALA).

    PubMed

    Saito, Masashi; Yano, Kazuhito; Kamigaki, Takashi; Goto, Shigenori

    2013-07-01

    A 35-year-old female with scirrhous stomach cancer (stage IV) was treated with a combination of 5-aminolevulinic acid (ALA), sodium dichloroacetate (DCA), hyperthermotherapy, and immunotherapy as terminal care. The patient survived for one year and seven months, during which her quality of life was markedly improved and she returned to work. The patient was diagnosed with poorly-differentiated adenocarcinoma and progressive signet-ring cell carcinoma, accompanied by left ovarian metastasis, peritoneal dissemination, and right hydronephrosis stage IV, and treated with combination chemotherapy with tegafur-gimeracil-oteracil potassium (TS-1) and docetaxel. Oral ALA and DCA were concomitantly administered at 50 mg each three times a day (150 mg/day, respectively). In addition, hyperthermotherapy using thermotron was concomitantly performed at 2- to 3-week intervals. Cellular immunotherapy with αβ T- and immature dendritic cells was also performed. The disease did not progress for 11 months, her quality of life was markedly improved, and she was able to return to work. However, the signs of enlargement of the ovarian metastatic lesion were noted later, for which chemotherapy with four cycles of second-line paclitaxel and a half dose of irinotecan and cisplatin as third-line treatment were performed. Combination of ALA/DCA, hyperthermotherapy, and cellular immunotherapy may be a low-invasive palliative therapy superior in maintaining quality of life of tumor-bearing terminally ill individuals.

  7. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fang, Zhong-Ze; Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin; Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian

    Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showedmore » that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.« less

  8. Activation of Pyruvate Dehydrogenase by Sodium Dichloroacetate Shifts Metabolic Consumption from Amino Acids to Glucose in IPEC-J2 Cells and Intestinal Bacteria in Pigs.

    PubMed

    An, Rui; Tang, Zhiru; Li, Yunxia; Li, Tiejun; Xu, Qingqing; Zhen, Jifu; Huang, Feiru; Yang, Jing; Chen, Cheng; Wu, Zhaoliang; Li, Mao; Sun, Jiajing; Zhang, Xiangxin; Chen, Jinchao; Wu, Liuting; Zhao, Shengjun; Qingyan, Jiang; Zhu, Weiyun; Yin, Yulong; Sun, Zhihong

    2018-04-18

    The extensive metabolism of amino acids (AA) as fuel is an important reason for the low use efficiency of protein in pigs. In this study, we investigated whether regulation of the pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase alpha 1 (PDHA1) pathway affected AA consumption by porcine intestinal epithelial (IPEC-J2) cells and intestinal bacteria in pigs. The effects of knockdown of PDHA1 and PDK1 with small interfering RNA (siRNA) on nutrient consumption by IPEC-J2 cells were evaluated. IPEC-J2 cells were then cultured with sodium dichloroacetate (DCA) to quantify AA and glucose consumption and nutrient oxidative metabolism. The results showed that knockdown of PDHA1 using siRNA decreased glucose consumption but increased total AA (TAA) and glutamate (Glu) consumption by IPEC-J2 cells ( P < 0.05). Opposite effects were observed using siRNA targeting PDK1 ( P < 0.05). Additionally, culturing IPEC-J2 cells in the presence of 5 mM DCA markedly increased the phosphorylation of PDHA1 and PDH phosphatase 1, but inhibited PDK1 phosphorylation ( P < 0.05). DCA treatment also reduced TAA and Glu consumption and increased glucose depletion ( P < 0.05). These results indicated that PDH was the regulatory target for shifting from AA metabolism to glucose metabolism and that culturing cells with DCA decreased the consumption of AAs by increasing the depletion of glucose through PDH activation.

  9. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    PubMed

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Summary of Salient Findings of "Natural Attenuation of the Lead Scavengers 1,2-Dibromoethane (EDB) and 1,2-Dichloroethane (1,2-DCA) at Motor Fuel Release Sites and Implications for Risk Management"

    EPA Science Inventory

    Tetra-ethyl lead was widely used in leaded automobile gasoline from 1923 until 1987 (See Figure 1). To prevent lead deposits from fouling the engine, 1,2-dibromoethane (EDB) and 1,2-dichloroethane (1,2-DCA) were added to the gasoline to act as lead scavengers. These compounds r...

  11. Reductive dehalogenation of haloacetic acids by hemoglobin-loaded carbon nanotube electrode.

    PubMed

    Li, Yu-Ping; Cao, Hong-Bin; Zhang, Yi

    2007-01-01

    Hemoglobin (Hb) was immobilized on carbon nanotube (CNT) electrode to catalyze the dehalogenation of haloacetic acids (HAAs). FTIR and UV measurements were performed to investigate the activity-keep of Hb after immobilization on CNT. The electrocatalytic behaviors of the Hb-loaded electrode for the dehalogenation of HAAs were studied by cyclic voltammmetry and constant-potential electrolysis technique. An Hb-loaded packed-bed flow reactor was also constructed for bioelectrocatalytic dehalogenation of HAAs. The results showed that Hb retained its nature, the essential features of its native secondary structure, and its biocatalytic activity after immobilization on CNT. Chloroacetic acids and bromoacetic acids could be dehalogenated completely with Hb catalysis through a stepwise dehalogenation process at -0.400V (vs. saturated calomel electrode (SCE)) and -0.200V (vs. SCE), respectively. The removal of 10.5mM trichloroacetic acid and dichloroacetic acid is ca. 97% and 63%, respectively, with electrolysis for 300min at -0.400V (vs. SCE) using the Hb-loaded packed-bed flow reactor, and almost 100% of tribromoacetic acid and dibromoacetic acid was removed with electrolysis for 40min at -0.200V (vs. SCE). The average current efficiency of Hb-catalytic dehalogenation almost reaches 100%.

  12. Results of an Innovative Education, Training and Quality Assurance Program for Point-of-Care HbA1c Testing using the Bayer DCA 2000 in Australian Aboriginal Community Controlled Health Services

    PubMed Central

    Shephard, Mark D; Gill, Janice P

    2003-01-01

    This study describes the development, implementation and management of a multi-faceted quality assurance program called Quality Assurance for Aboriginal Medical Services (QAAMS) to support point-of-care HbA1c testing on the Bayer DCA 2000 in Aboriginal people with diabetes from 45 Australian Aboriginal Community Controlled Health Services. The quality assurance program comprised four elements: production of culturally appropriate education resources, formal training for Aboriginal Health Workers conducting HbA1c testing, an external quality assurance program and on-going quality management support services including a help hotline and an annual workshop. Aboriginal Health Workers were required to test two quality assurance (QAAMS) samples in a blind sense every month since July 1999. Samples were linearly related and comprised six paired levels of HbA1c. The short and long term performance of each service’s DCA 2000 was reviewed monthly and at the end of each six month testing cycle. The average participation rate over 7 six-monthly QAAMS testing cycles was 88%. 84% of 3100 quality assurance tests performed were within preset limits of acceptability. The median precision (CV%) for HbA1c testing has averaged 3.8% across the past 5 cycles (range 3.4 to 4.0%) and is continuing to improve. The introduction of a medical rebate for HbA1c testing has ensured the program’s sustainability. Through continuing education and training, Aboriginal Health Workers have achieved consistent analytical performance for HbA1c testing on the DCA 2000, equivalent to that of laboratory scientists using the same instrument. This unique quality assurance model can be readily adapted to other Indigenous health settings and other point-of-care tests and instruments. PMID:18568052

  13. 40 CFR 141.53 - Maximum contaminant level goals for disinfection byproducts.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... byproduct MCLG(mg/L) Bromodichloromethane zero Bromoform zero Bromate zero Chlorite 0.8 Chloroform 0.07 Dibromochloromethane 0.06 Dichloroacetic acid zero Monochloroacetic acid 0.07 Trichloroacetic acid 0.02 [63 FR 69465...

  14. 40 CFR 141.53 - Maximum contaminant level goals for disinfection byproducts.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... byproduct MCLG(mg/L) Bromodichloromethane zero Bromoform zero Bromate zero Chlorite 0.8 Chloroform 0.07 Dibromochloromethane 0.06 Dichloroacetic acid zero Monochloroacetic acid 0.07 Trichloroacetic acid 0.02 [63 FR 69465...

  15. 40 CFR 141.53 - Maximum contaminant level goals for disinfection byproducts.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... byproduct MCLG(mg/L) Bromodichloromethane zero Bromoform zero Bromate zero Chlorite 0.8 Chloroform 0.07 Dibromochloromethane 0.06 Dichloroacetic acid zero Monochloroacetic acid 0.07 Trichloroacetic acid 0.02 [63 FR 69465...

  16. 40 CFR 141.53 - Maximum contaminant level goals for disinfection byproducts.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... byproduct MCLG(mg/L) Bromodichloromethane zero Bromoform zero Bromate zero Chlorite 0.8 Chloroform 0.07 Dibromochloromethane 0.06 Dichloroacetic acid zero Monochloroacetic acid 0.07 Trichloroacetic acid 0.02 [63 FR 69465...

  17. Campylobacter jejuni type VI secretion system: roles in adaptation to deoxycholic acid, host cell adherence, invasion, and in vivo colonization.

    PubMed

    Lertpiriyapong, Kvin; Gamazon, Eric R; Feng, Yan; Park, Danny S; Pang, Jassia; Botka, Georgina; Graffam, Michelle E; Ge, Zhongming; Fox, James G

    2012-01-01

    The recently identified type VI secretion system (T6SS) of proteobacteria has been shown to promote pathogenicity, competitive advantage over competing microorganisms, and adaptation to environmental perturbation. By detailed phenotypic characterization of loss-of-function mutants, in silico, in vitro and in vivo analyses, we provide evidence that the enteric pathogen, Campylobacter jejuni, possesses a functional T6SS and that the secretion system exerts pleiotropic effects on two crucial processes--survival in a bile salt, deoxycholic acid (DCA), and host cell adherence and invasion. The expression of T6SS during initial exposure to the upper range of physiological levels of DCA (0.075%-0.2%) was detrimental to C. jejuni proliferation, whereas down-regulation or inactivation of T6SS enabled C. jejuni to resist this effect. The C. jejuni multidrug efflux transporter gene, cmeA, was significantly up-regulated during the initial exposure to DCA in the wild type C. jejuni relative to the T6SS-deficient strains, suggesting that inhibition of proliferation is the consequence of T6SS-mediated DCA influx. A sequential modulation of the efflux transporter activity and the T6SS represents, in part, an adaptive mechanism for C. jejuni to overcome this inhibitory effect, thereby ensuring its survival. C. jejuni T6SS plays important roles in host cell adhesion and invasion as T6SS inactivation resulted in a reduction of adherence to and invasion of in vitro cell lines, while over-expression of a hemolysin co-regulated protein, which encodes a secreted T6SS component, greatly enhanced these processes. When inoculated into B6.129P2-IL-10(tm1Cgn) mice, the T6SS-deficient C. jejuni strains did not effectively establish persistent colonization, indicating that T6SS contributes to colonization in vivo. Taken together, our data demonstrate the importance of bacterial T6SS in host cell adhesion, invasion, colonization and, for the first time to our knowledge, adaptation to DCA

  18. The use of trichloroacetic acid imprinted polymer coated quartz crystal microbalance as a screening method for determination of haloacetic acids in drinking water.

    PubMed

    Suedee, Roongnapa; Intakong, Wimon; Dickert, Franz L

    2006-08-15

    An alternative screening method for haloacetic acids (HAAs) disinfection by-products in drinking water is described. The method is based on the use of piezoelectric quartz crystal microbalance (QCM) transducing system, where the electrode is coated with a trichloacetic acid-molecularly imprinted polymer (TCAA-MIP). This MIP comprises a crosslinked poly(ethyleneglycoldimethacrylate-co-4-vinylpyridine). The coated QCM is able to specifically detect the analytes in water samples in terms of the mass change in relation to acid-base interactions of the analytes with the MIP. The TCAA-MIP coated QCM showed high specificity for the determination of TCAA in aqueous solutions containing inorganic anions, but its sensitivity reduced in water samples containing hydrochloric acid due to a mass loss at the sensor surface. Cross-reactivity studies with HAA analogs (dichloro-, monochloro-, tribromo-, dibromo-, and monobromo-acetic acids) and non-structurally related TCAA molecules (acetic acid and malonic acid) indicated that recognition of the structurally related TCAA compounds by the TCAA-MIP-based QCM is due to a carboxylic acid functional group, and probably involves a combination of both size and shape selectivity. The total response time of sensor is in the order of 10min. The achieved limits of detection for HAAs (20-50mugl(-1)) are at present higher than the actual concentrations found in real-life samples, but below the guidelines for the maximum permissible levels (60mugl(-1) for mixed HAAs). Recovery studies with drinking water samples spiked with TCAA or spiked with mixtures of HAAs revealed the reproducibility and precision of the method. The present work has demonstrated that the proposed assay can be a fast, reliable and inexpensive screening method for HAA contaminants in water samples, but further refinement is required to improve the limits of detection.

  19. Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo

    PubMed Central

    Feuerecker, Benedikt; Pirsig, Sabine; Seidl, Christof; Aichler, Michaela; Feuchtinger, Annette; Bruchelt, Gernot; Senekowitsch-Schmidtke, Reingard

    2012-01-01

    Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis–Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells. We investigated the effects of (R)-(+)-α-lipoic acid (LPA) and dichloroacetate (DCA), possible activators of pyruvate dehydrogenase, on suppression of aerobic glycolysis and induction of cell death. The neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations (0.1–30 mM) of LPA and DCA. The effects of both compounds on cell viability/proliferation (WST-1 assay), [18F]-FDG uptake, lactate production and induction of apoptosis (flow cytometric detection of caspase-3) were evaluated. Furthermore, NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA (i.p, 18.5 mg/kg) starting at day 7 p.i.. Tumor development was measured with a sliding calliper and monitored via [18F]-FDG-PET. Residual tumors after therapy were examined histopathologically. These data suggests that LPA can reduce (1) cell viability/proliferation, (2) uptake of [18F]-FDG and (3) lactate production and increase apoptosis in all investigated cell lines. In contrast, DCA was almost ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment with LPA retarded tumor progression. Therefore, LPA seems to be a promising compound for cancer treatment. PMID:22954700

  20. Growth and physicochemical properties of second-order nonlinear optical 2-amino-5-chloropyridinium trichloroacetate single crystals

    NASA Astrophysics Data System (ADS)

    Renugadevi, R.; Kesavasamy, R.

    2015-09-01

    The growth of organic nonlinear optical (NLO) crystal 2-amino-5-chloropyridinium trichloroacetate (2A5CPTCA) has been synthesized and single crystals have been grown from methanol solvent by slow evaporation technique. The grown crystals were subjected to various characterization analyses in order to find out the suitability for device fabrication. Single crystal X-ray diffraction analysis reveals that 2A5CPTCA crystallizes in monoclinic system with the space group Cc. The grown crystal was further characterized by Fourier transform infrared spectral analysis to find out the functional groups. The nuclear magnetic resonance spectroscopy is a research technique that exploits the magnetic properties of certain atomic nuclei. The optical transparency window in the visible and near-IR (200--1100 nm) regions was found to be good for NLO applications. Thermogravimetric analysis and differential thermal analysis were used to study its thermal properties. The powder second harmonic generation efficiency measurement with Nd:YAG laser (1064 nm) radiation shows that the highest value when compared with the standard potassium dihydrogen phosphate crystal.

  1. Optimization of Protein Extraction and Two-Dimensional Electrophoresis Protocols for Oil Palm Leaf.

    PubMed

    Daim, Leona Daniela Jeffery; Ooi, Tony Eng Keong; Yusof, Hirzun Mohd; Majid, Nazia Abdul; Karsani, Saiful Anuar Bin

    2015-08-01

    Oil palm (Elaeis guineensis) is an important economic crop cultivated for its nutritional palm oil. A significant amount of effort has been undertaken to understand oil palm growth and physiology at the molecular level, particularly in genomics and transcriptomics. Recently, proteomics studies have begun to garner interest. However, this effort is impeded by technical challenges. Plant sample preparation for proteomics analysis is plagued with technical challenges due to the presence of polysaccharides, secondary metabolites and other interfering compounds. Although protein extraction methods for plant tissues exist, none work universally on all sample types. Therefore, this study aims to compare and optimize different protein extraction protocols for use with two-dimensional gel electrophoresis of young and mature leaves from the oil palm. Four protein extraction methods were evaluated: phenol-guanidine isothiocyanate, trichloroacetic acid-acetone precipitation, sucrose and trichloroacetic acid-acetone-phenol. Of these four protocols, the trichloroacetic acid-acetone-phenol method was found to give the highest resolution and most reproducible gel. The results from this study can be used in sample preparations of oil palm tissue for proteomics work.

  2. MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

    EPA Science Inventory

    Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

  3. Effects of dynamic controlled atmosphere by respiratory quotient on some quality parameters and volatile profile of 'Royal Gala' apple after long-term storage.

    PubMed

    Both, Vanderlei; Thewes, Fabio Rodrigo; Brackmann, Auri; de Oliveira Anese, Rogerio; de Freitas Ferreira, Daniele; Wagner, Roger

    2017-01-15

    The effects of dynamic controlled atmosphere (DCA) storage based on chlorophyll fluorescence (DCA-CF) and respiratory quotient (DCA-RQ) on the quality and volatile profile of 'Royal Gala' apple were evaluated. DCA storage reduces ACC (1-aminocyclopropane-1-carboxylate) oxidase activity, ethylene production and respiration rate of apples stored for 9months at 1.0°C plus 7days at 20°C, resulting in higher flesh firmness, titratable acidity and lesser physiological disorders, and provided a higher proportion of healthy fruit. Storage in a regular controlled atmosphere gave higher levels of key volatiles (butyl acetate, 2-methylbutyl acetate and hexyl acetate), as compared to fruit stored under DCA-CF, but fruit stored under DCA-RQ 1.5 and RQ 2.0 also showed higher amounts of key volatile compounds, with increment in ethanol and ethyl acetate, but far below the odour threshold. Storage in DCA-CF reduces fruit ester production, especially 2-methylbutyl acetate, which is the most important component of 'Royal Gala' apple flavour. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Method of analysis at the U.S. Geological Survey California Water Science Center, Sacramento Laboratory - determination of haloacetic acid formation potential, method validation, and quality-control practices

    USGS Publications Warehouse

    Zazzi, Barbara C.; Crepeau, Kathryn L.; Fram, Miranda S.; Bergamaschi, Brian A.

    2005-01-01

    An analytical method for the determination of haloacetic acid formation potential of water samples has been developed by the U.S. Geological Survey California Water Science Center Sacramento Laboratory. The haloacetic acid formation potential is measured by dosing water samples with chlorine under specified conditions of pH, temperature, incubation time, darkness, and residual-free chlorine. The haloacetic acids formed are bromochloroacetic acid, bromodichloroacetic acid, dibromochloroacetic acid, dibromoacetic acid, dichloroacetic acid, monobromoacetic acid, monochloroacetic acid, tribromoacetic acid, and trichloroacetic acid. They are extracted, methylated, and then analyzed using a gas chromatograph equipped with an electron capture detector. Method validation experiments were performed to determine the method accuracy, precision, and detection limit for each of the compounds. Method detection limits for these nine haloacetic acids ranged from 0.11 to 0.45 microgram per liter. Quality-control practices include the use of blanks, quality-control samples, calibration verification standards, surrogate recovery, internal standard, matrix spikes, and duplicates.

  5. Lead-acid batteries in micro-hybrid applications. Part I. Selected key parameters

    NASA Astrophysics Data System (ADS)

    Schaeck, S.; Stoermer, A. O.; Kaiser, F.; Koehler, L.; Albers, J.; Kabza, H.

    Micro-hybrid electric vehicles were launched by BMW in March 2007. These are equipped with brake energy regeneration (BER) and the automatic start and stop function (ASSF) of the internal combustion engine. These functions are based on common 14 V series components and lead-acid (LA) batteries. The novelty is given by the intelligent onboard energy management, which upgrades the conventional electric system to the micro-hybrid power system (MHPS). In part I of this publication the key factors for the operation of LA batteries in the MHPS are discussed. Especially for BER one is high dynamic charge acceptance (DCA) for effective boost charging. Vehicle rest time is identified as a particular negative parameter for DCA. It can be refreshed by regular fully charging at elevated charge voltage. Thus, the batteries have to be outstandingly robust against overcharge and water loss. This can be accomplished for valve-regulated lead-acid (VRLA) batteries at least if they are mounted in the trunk. ASSF goes along with frequent high-rate loads for warm cranking. The internal resistance determines the drop of the power net voltage during cranking and is preferably low for reasons of power net stability even after years of operation. Investigations have to be done with aged 90 Ah VRLA-absorbent glass mat (AGM) batteries. Battery operation at partial state-of-charge gives a higher risk of deep discharging (overdischarging). Subsequent re-charging then is likely to lead to the formation of micro-short circuits in the absorbent glass mat separator.

  6. Sensitive assay, based on hydroxy fatty acids from lipopolysaccharide lipid A, for Gram-negative bacteria in sediments.

    PubMed Central

    Parker, J H; Smith, G A; Fredrickson, H L; Vestal, J R; White, D C

    1982-01-01

    Biochemical measures have provided insight into the biomass and community structure of sedimentary microbiota without the requirement of selection by growth or quantitative removal from the sediment grains. This study used the assay of the hydroxy fatty acids released from the lipid A of the lipopolysaccharide in sediments to provide an estimate of the gram-negative bacteria. The method was sensitive to picomolar amounts of hydroxy fatty acids. The recovery of lipopolysaccharide hydroxy fatty acids from organisms added to sediments was quantitative. The lipids were extracted from the sediments with single-phase chloroform-methanol extraction. The lipid-extraction residue was hydrolyzed in 1 N HCl, and the hydroxy fatty acids of the lipopolysaccharide were recovered in chloroform for analysis by gas-liquid chromatography. This method proved to be about fivefold more sensitive than the classical phenol-water or trichloroacetic acid methods when applied to marine sediments. By examination of the patterns of hydroxy fatty acids, it was also possible to help define the community structure of the sedimentary gram-negative bacteria. PMID:6817712

  7. Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.

    PubMed

    Fujita, Kyosuke; Iguchi, Yusuke; Une, Mizuho; Watanabe, Shiro

    2017-04-01

    The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.

  8. Mesoporous nitrogen-doped carbon microfibers derived from Mg-biquinoline-dicarboxy compound for efficient oxygen electroreduction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kong, Aiguo, E-mail: agkong@chem.ecnu.edu.cn; Fan, Xiaohong; Chen, Aoling

    An in-situ MgO-templating synthesis route was introduced to obtain the mesoporous nitrogen-doped carbon microfibers by thermal conversion of new Mg-2,2′-biquinoline 4,4-dicarboxy acid coordination compound (Mg-DCA) microfibers. The investigated crystal structure of Mg-DCA testified that the assembling of Mg{sup 2+} and DCA through Mg-O coordination bond and hydrogen bond contributed to the formation of one-dimensional (1D) crystalline Mg-DCA microfibers. The nitrogen-doped carbons derived from the pyrolysis of Mg-DCA showed the well-defined microfiber morphology with high mesopore-surface area. Such mesoporous microfibers exhibited the efficient catalytic activity for oxygen reduction reaction (ORR) in alkaline solutions with better stability and methanol-tolerance performance. - Graphicalmore » abstract: Mesoporous nitrogen-doped carbon microfibers with efficient oxygen electroreduction activity were prepared by thermal conversion of new Mg-biquinoline-based coordination compound microfibers.« less

  9. METHOD OF ELECTROPLATING ON URANIUM

    DOEpatents

    Rebol, E.W.; Wehrmann, R.F.

    1959-04-28

    This patent relates to a preparation of metallic uranium surfaces for receiving coatings, particularly in order to secure adherent electroplated coatings upon uranium metal. In accordance with the invention the uranium surface is pretreated by degreasing in trichloroethylene, followed by immersion in 25 to 50% nitric acid for several minutes, and then rinsed with running water, prior to pickling in trichloroacetic acid. The last treatment is best accomplished by making the uranium the anode in an aqueous solution of 50 per cent by weight trichloroacetic acid until work-distorted crystals or oxide present on the metal surface have been removed and the basic crystalline structure of the base metal has been exposed. Following these initial steps the metallic uranium is rinsed in dilute nitric acid and then electroplated with nickel. Adnerent firmly-bonded coatings of nickel are obtained.

  10. Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS.

    PubMed

    Mori, Masato; Yamagata, Takanori; Goto, Tamako; Saito, Shigeko; Momoi, Mariko Y

    2004-10-01

    The long-term effects of the sodium salt of dichloroacetic acid (DCA) were evaluated in four patients with mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes (MELAS) carrying A3243G mutation. Oral administration of DCA in MELAS patients was followed for an average of 5 years 4 months. Serum levels of lactate and pyruvate were maintained at around 10 and 0.6 mg/dl, respectively. Serum levels of DCA were 40-136 microg/ml. Symptoms responding to treatment included persistent headache, abdominal pain, muscle weakness, and stroke-like episodes. In contrast, no improvements in mental status, deafness, short stature, or neuroelectrophysiological findings were observed. Adverse effects included mild liver dysfunction in all patients, hypocalcemia in three and peripheral neuropathy in one. None of these adverse events was severe enough to require discontinuation of treatment. To determine suitable indications for DCA therapy, analysis of many more patients who have undergone DCA administration is required.

  11. Prenatal and Postnatal Expression of Glutathione Transferase ζ 1 in Human Liver and the Roles of Haplotype and Subject Age in Determining Activity with Dichloroacetate

    PubMed Central

    Li, Wenjun; Gu, Yuan; Hines, Ronald N.; Simpson, Pippa; Langaee, Taimour; Stacpoole, Peter W.

    2012-01-01

    Glutathione transferase ζ 1 (GSTZ1), also known as maleylacetoacetate isomerase, catalyzes the penultimate step of tyrosine catabolism and metabolizes several α-halocarboxylic acids, including dichloroacetic acid (DCA), an investigational drug used for lactic acidosis and, recently, solid tumors. Age-related differences have been suggested in DCA pharmacotoxicology, but no information is available on GSTZ1 ontogeny in humans. Here, we investigated the cytosolic GSTZ1 developmental expression pattern and the influence of haplotype on GSTZ1 activity with DCA by using human livers from donors between 10 weeks gestation and 74 years. GSTZ1 expression was very low in fetal livers (<2 pmol of GSTZ1/mg cytosol). The expression began to increase after birth in an age-dependent manner until age 7 years. GSTZ1 was then sustained at stable, yet variable, levels (median, 20.0 pmol/mg cytosol; range, 4.8–47.3 pmol/mg cytosol) until age 74 years. GSTZ1 activity with DCA was strongly associated with haplotype and expression level. Samples homozygous or heterozygous for GSTZ1A exhibited ∼3-fold higher DCA dechlorinating activity than samples carrying other alleles at a given level of expression. The correlations (r2) between activity and expression were 0.90 and 0.68, respectively, for GSTZ1A carriers (n = 11) and noncarriers (n = 61). GSTZ1 is expressed in mitochondria in addition to cytosol. The GSTZ1A allele exhibited similar effects in the mitochondrial fraction by conferring a higher activity with DCA. In summary, we report a neonatal onset and an age-related increase in GSTZ1 protein expression during human liver development. Haplotype influenced GSTZ1 activity with DCA but not protein expression. PMID:22028318

  12. Effect of Boron Clusters on the Ignition Reaction of HNO3 and Dicynanamide-Based Ionic Liquids.

    PubMed

    Schmidt, Michael W; Gordon, Mark S

    2017-10-19

    Many ionic liquids containing the dicynamide anion (DCA - , formula N(CN) 2 - ) exhibit hypergolic ignition when exposed to the common oxidizer nitric acid. However, the ignition delay is often about 10 times longer than the desired 5 ms for rocket applications, so that improvements are desired. Experiments in the past decade have suggested both a mechanism for the early reaction steps and also that additives such as decaborane can reduce the ignition delay. The mechanisms for reactions of nitric acid with both DCA - and protonated DCAH are considered here, using accurate wave function methods. Complexation of DCA - or DCAH with borane clusters B 10 H 14 or B 9 H 14 - is found to modify these mechanisms slightly by changing the nature of some of the intermediate saddle points and by small reductions in the reaction barriers.

  13. Bile acid changes after high-dose ursodeoxycholic acid treatment in primary sclerosing cholangitis: relation to disease progression

    PubMed Central

    Sinakos, Emmanouil; Marschall, Hanns-Ulrich; Kowdley, Kris V.; Befeler, Alex; Keach, Jill; Lindor, Keith

    2010-01-01

    High-dose (28-30mg/kg/day) ursodeoxycholic acid (UDCA) treatment improves serum liver tests in patients with primary sclerosing cholangitis (PSC) but does not improve survival and is associated with increased rates of serious adverse events. The mechanism for the latter undesired effect remains unclear. High-dose UDCA could result in the production of hepatotoxic bile acids, such as lithocholic acid (LCA), due to limited small bowel absorption of UDCA and conversion of UDCA by bacteria in the colon. We determined the serum bile acid composition in 56 patients with PSC previously enrolled in a randomized, double-blind controlled trial of high dose UDCA versus placebo. Samples for analysis were obtained at baseline and at the end of treatment. The mean changes in UDCA (16.86 vs 0.05 μmol/L) and total bile acid (17.21 vs −0.55 μmol/L) levels were significantly higher in the UDCA group (n=29) compared to placebo (n=27) when pretreatment levels were compared (p<0.0001). LCA was also markedly increased (0.22 vs 0.01 μmol/L) in the UDCA group compared to placebo (p=0.001). No significant changes were detected for cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). Patients (n=9) in the UDCA group who reached clinical endpoints of disease progression (development of cirrhosis, varices, liver transplantation or death) tend to have greater increase in their post-treatment total bile acid levels (34.99 vs 9.21 μmol/L) (p<0.08) compared to those who did not. Conclusion High-dose UDCA treatment in PSC patients results in marked UDCA enrichment and significant expansion of the total serum bile acid pool including lithocholic acid. PMID:20564380

  14. Tetramer model of leukoemeraldine-emeraldine electrochemistry in the presence of trihalogenoacetic acids. DFT approach.

    PubMed

    Barbosa, Nuno Almeida; Grzeszczuk, Maria; Wieczorek, Robert

    2015-01-15

    First results of the application of the DFT computational approach to the reversible electrochemistry of polyaniline are presented. A tetrameric chain was used as the simplest model of the polyaniline polymer species. The system under theoretical investigation involved six tetramer species, two electrons, and two protons, taking part in 14 elementary reactions. Moreover, the tetramer species were interacting with two trihalogenoacetic acid molecules. Trifluoroacetic, trichloroacetic, and tribromoacetic acids were found to impact the redox transformation of polyaniline as shown by cyclic voltammetry. The theoretical approach was considered as a powerful tool for investigating the main factors of importance for the experimental behavior. The DFT method provided molecular structures, interaction energies, and equilibrium energies of all of the tetramer-acid complexes. Differences between the energies of the isolated tetramer species and their complexes with acids are discussed in terms of the elementary reactions, that is, ionization potentials and electron affinities, equilibrium constants, electrode potentials, and reorganization energies. The DFT results indicate a high impact of the acid on the reorganization energy of a particular elementary electron-transfer reaction. The ECEC oxidation path was predicted by the calculations. The model of the reacting system must be extended to octamer species and/or dimeric oligomer species to better approximate the real polymer situation.

  15. Retinoic acid stimulation of human dermal fibroblast proliferation is dependent on suboptimal extracellular Ca2+ concentration.

    PubMed Central

    Varani, J.; Shayevitz, J.; Perry, D.; Mitra, R. S.; Nickoloff, B. J.; Voorhees, J. J.

    1990-01-01

    Human dermal fibroblasts failed to proliferate when cultured in medium containing 0.15 mmol/l (millimolar) Ca2+ (keratinocyte growth medium [KGM]) but did when the external Ca2+ concentration was raised to 1.4 mmol/l. All-trans retinoic acid (retinoic acid) stimulated proliferation in KGM but did not further stimulate growth in Ca2(+)-supplemented KGM. The ability of retinoic acid to stimulate proliferation was inhibited in KGM prepared without Ca2+ or prepared with 0.03 mmol/l Ca2+ and in KGM treated with 1 mmol/l ethylene-glycol-bis-(beta-aminoethyl ether)N,N'-tetra acetic acid. Using 45Ca2+ to measure Ca2+ influx and efflux, it was found that retinoic acid minimally increased Ca2+ uptake into fibroblasts. In contrast, retinoic acid treatment of fibroblasts that had been pre-equilibrated for 1 day with 45Ca2+ inhibited release of intracellular Ca2+ into the extracellular fluid. Retinoic acid also stimulated 35S-methionine incorporation into trichloroacetic acid-precipitable material but in contrast to its effect on proliferation, stimulation of 35S-methionine incorporation occurred in both high-Ca2+ and low-Ca2+ medium. These data indicate that retinoic acid stimulation of proliferation, but not protein synthesis, is dependent on the concentration of Ca2+ in the extracellular environment. PMID:2356860

  16. Regulation of Deoxycholate Induction of CXCL8 by the Adenomatous Polyposis Coli Gene in Colorectal Cancer

    PubMed Central

    Rial, Nathaniel S; Lazennec, Gwendal; Prasad, Anil R; Krouse, Robert S; Lance, Peter; Gerner, Eugene W

    2009-01-01

    Elevated deoxycholic acid (DCA), mutations in the adenomatous polyposis coli (APC) gene and chronic inflammation are associated with increased risk of colorectal cancer (CRC). APC status was manipulated to determine whether DCA mediates inflammatory molecules in normal or initiated colonic mucosa. DCA increased steady state mRNA and protein levels of CXCL8 in cells which do not express wild type APC. Steady state CXCL8 mRNA and protein were suppressed when cells with conditional expression of wild type APC were exposed to DCA. Immunostaining did not detect CXCL8 in normal human colonic mucosa. CXCL8 was expressed in adenomatous polyps and adenocarcinomas. CXCL8 expression correlated with nuclear β-catenin localization in epithelial cells of adenomas, but was associated with endothelial cells and neutrophils in the adenocarcinomas. DCA-mediated CXCL8 promoter-reporter activity was elevated in a mutant APC background. Wild type APC suppressed this effect. Mutation of activator protein-1 (AP-1) or nuclear factor kappa B (NF-κB) sites suppressed the activation of the CXCL8 promoter-reporter by DCA. Chromatin immunoprecipitation (ChIP) revealed that AP-1 and NF-κB binding to the 5′-promoter of CXCL8 was induced by DCA. The β-catenin transcription factor was bound to the 5′-promoter of CXCL8 in the absence or presence of DCA. Phenotypic assays determined that DCA-mediated invasion was blocked by antibody directed against CXCL8 or wild type-APC. CXCL8 exposure lead to matrix metalloproteinase-2 (MMP-2) production and increased invasion on laminin coated filters. These data suggest that DCA-mediated CXCL8 occurs in initiated colonic epithelium and neutralizing CXCL8 could reduce the invasive potential of tumors. PMID:19173296

  17. Aerosol characterisation at the FEBUKO upwind station Goldlauter (II): Detailed organic chemical characterisation

    NASA Astrophysics Data System (ADS)

    Müller, K.; van Pinxteren, D.; Plewka, A.; Svrcina, B.; Kramberger, H.; Hofmann, D.; Bächmann, K.; Herrmann, H.

    An extensive set of gaseous and particulate organic compounds was quantified before an orographic cloud passage at the upwind site of the research region in Thüringer Wald. Samples were collected with two different time resolutions, 2 h for gaseous species and spray absorber samples and the whole cloud event duration to determine the concentrations of ketones, aldehydes, monocarboxylic acids, dicarboxylic acids (DCA), hydrocarbons, biogenic sugars and alcohols in both the gas and particle phase. The measurement of different groups of organic compounds delivered size-segregated concentrations at the upwind site of a cloud experiment. The size distribution of DCA showed a peak in the mass-rich impactor stage 3 (0.42-1.2 μm). The concentrations of DCA from the filters, the impactor foils as well as the spray absorber samples decreased with increasing C-number. The time resolved measurements revealed an increasing mixing ratio from night time to midday for carboxylic and DCA, and related carbonyl compounds. The biogenic compounds xylitol (up to 103 ng m -3), levoglucosan (up to 62 ng m -3) and pinonaldehyde (up to 34 ng m -3) were the compounds found in highest concentrations in the particle phase beside the oxalate (up to 104 ng m -3). The organic trace gases with the highest mixing ratios identified were formaldehyde (up to 1.47 ppbv), acetaldehyde (up to 0.84 ppbv) and acetone (up to 0.65 ppbv), acetic acid (up to 0.43 ppbv) and formic acid (up to 0.41 ppbv).

  18. β-Klotho deficiency protects against obesity through a crosstalk between liver, microbiota, and brown adipose tissue

    PubMed Central

    Henry, Hugues; Bruce, Stephen J.; Aeby, Sébastien; Rosikiewicz, Marta; Sykiotis, Gerasimos P.; Asrih, Mohammed; Jornayvaz, François R.; Denechaud, Pierre Damien; Mohammadi, Moosa; Acierno, James S.; Schoonjans, Kristina; Pitteloud, Nelly

    2017-01-01

    β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb–/– mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb–/– mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb–/– mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity. Klb–/– mice exhibited not only an increase but also a shift in bile acid (BA) composition featured by activation of the classical (neutral) BA synthesis pathway at the expense of the alternative (acidic) pathway. High hepatic production of cholic acid (CA) results in a large excess of microbiota-derived deoxycholic acid (DCA). DCA is specifically responsible for activating the TGR5 receptor that stimulates BAT thermogenic activity. In fact, combined gene deletion of Klb and Tgr5 or antibiotic treatment abrogating bacterial conversion of CA into DCA both abolish DIO resistance in Klb–/– mice. These results suggested that DIO resistance in Klb–/– mice is caused by high levels of DCA, signaling through the TGR5 receptor. These data also demonstrated that gut microbiota can regulate host thermogenesis via conversion of primary into secondary BA. Pharmacologic or nutritional approaches to selectively modulate BA composition may be a promising target for treating metabolic disorders. PMID:28422755

  19. Engineering a Catabolic Pathway in Plants for the Degradation of 1,2-Dichloroethane1[OA

    PubMed Central

    Mena-Benitez, Gilda L.; Gandia-Herrero, Fernando; Graham, Stuart; Larson, Tony R.; McQueen-Mason, Simon J.; French, Christopher E.; Rylott, Elizabeth L.; Bruce, Neil C.

    2008-01-01

    Plants are increasingly being employed to clean up environmental pollutants such as heavy metals; however, a major limitation of phytoremediation is the inability of plants to mineralize most organic pollutants. A key component of organic pollutants is halogenated aliphatic compounds that include 1,2-dichloroethane (1,2-DCA). Although plants lack the enzymatic activity required to metabolize this compound, two bacterial enzymes, haloalkane dehalogenase (DhlA) and haloacid dehalogenase (DhlB) from the bacterium Xanthobacter autotrophicus GJ10, have the ability to dehalogenate a range of halogenated aliphatics, including 1,2-DCA. We have engineered the dhlA and dhlB genes into tobacco (Nicotiana tabacum ‘Xanthi’) plants and used 1,2-DCA as a model substrate to demonstrate the ability of the transgenic tobacco to remediate a range of halogenated, aliphatic hydrocarbons. DhlA converts 1,2-DCA to 2-chloroethanol, which is then metabolized to the phytotoxic 2-chloroacetaldehyde, then chloroacetic acid, by endogenous plant alcohol dehydrogenase and aldehyde dehydrogenase activities, respectively. Chloroacetic acid is dehalogenated by DhlB to produce the glyoxylate cycle intermediate glycolate. Plants expressing only DhlA produced phytotoxic levels of chlorinated intermediates and died, while plants expressing DhlA together with DhlB thrived at levels of 1,2-DCA that were toxic to DhlA-expressing plants. This represents a significant advance in the development of a low-cost phytoremediation approach toward the clean-up of halogenated organic pollutants from contaminated soil and groundwater. PMID:18467461

  20. In vivo effects of naproxen, salicylic acid, and valproic acid on the pharmacokinetics of trichloroethylene and metabolites in rats.

    PubMed

    Rouhou, Mouna Cheikh; Charest-Tardif, Ginette; Haddad, Sami

    2015-01-01

    It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.

  1. Atmospheric production of oxalic acid/oxalate and nitric acid/nitrate in the Tampa Bay airshed: Parallel pathways

    NASA Astrophysics Data System (ADS)

    Martinelango, P. Kalyani; Dasgupta, Purnendu K.; Al-Horr, Rida S.

    Oxalic acid is the dominant dicarboxylic acid (DCA), and it constitutes up to 50% of total atmospheric DCAs, especially in non-urban and marine atmospheres. A significant amount of particulate H 2Ox/oxalate (Ox) occurred in the coarse particle fraction of a dichotomous sampler, the ratio of oxalate concentrations in the PM 10 to PM 2.5 fractions ranged from 1 to 2, with mean±sd being 1.4±0.2. These results suggest that oxalate does not solely originate in the gas phase and condense into particles. Gaseous H 2Ox concentrations are much lower than particulate Ox concentrations and are well correlated with HNO 3, HCHO, and O 3, supporting a photochemical origin. Of special relevance to the Bay Region Atmospheric Chemistry Experiment (BRACE) is the extent of nitrogen deposition in the Tampa Bay estuary. Hydroxyl radical is primarily responsible for the conversion of NO 2 to HNO 3, the latter being much more easily deposited. Hydroxyl radical is also responsible for the aqueous phase formation of oxalic acid from alkenes. Hence, we propose that an estimate of rad OH can be obtained from H 2Ox/Ox production rate and we accordingly show that the product of total oxalate concentration and NO 2 concentration approximately predicts the total nitrate concentration during the same period.

  2. MECHANISMS INVOLVED IN TRICHLOROETHYLENE INDUCED LIVER CANCER: IMPORTANCE TO ENVIRONMENTAL CLEANUP

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bull, Richard J.; Thrall, Brain D.

    2001-12-31

    Trichloroethylene (TCE) is a common contaminant of groundwater as a result of poor disposal practices of the past. As a consequence, this solvent is the focus of many clean-up operations of uncontrolled hazardous waste sites. TCE is carcinogenic in both mice and rats, but at different sites, the liver and kidney, respectively (NCI 1976; NTP 1988; NTP 1990). Liver tumor induction in mice has been the tumor most critical from the standpoint of environmental regulation (Bull 2000). Under the proposed cancer risk guidelines of the Environmental Protection Agency (EPA 1996), identifying the dose-response behavior of key events involved in carcinogenicmore » responses can be used for developing alternative risk assessments. A major difficulty in developing alternative approaches for TCE is the fact that three of its metabolites are capable of inducing liver cancer in mice (Bull et al. 1990; Daniel et al. 1992; DeAngelo et al. 1999; Pereria 1996). Two of these metabolites have distinct modes of action, dichloroacetate (DCA) and trichloroacetate (TCA). The third metabolite, chloral hydrate, is probably active as a result of its conversion to one or both of these two metabolites. Ordinarily, the first approach to assigning causality to a metabolite in tumorigenesis would be an attempt to measure its concentration in the body and associate that with tumorigenic concentrations observed when the compound is itself administered. This can be done with relative ease with TCA. However, it has been more difficult with DCA since blood levels of this metabolite after exposure to carcinogenic doses of DCA fall rapidly below detection limits (Kato-Weinstein et al. 1998; Merdink et al. 1998). Mutations in the ras protooncogene have been used to determine if distinct patterns of DNAsequence alterations can provide indications of the type of DNA damage that might be produced by carcinogens. The presence of ras mutations in chemically-induced tumors was suggested as a means o f

  3. Identification and determination of disinfection byproducts in chlorine-containing household cleansing products.

    PubMed

    Shin, Ho-Sang; Lim, Hyun-Hee

    2017-05-01

    Seven halogenated volatile organic compounds (HVOCs) and two haloacetic acids were detected and quantified in 15 household products, including sodium hypochlorite, by gas chromatography-mass spectrometry (GC-MS). Chloroform was detected in a range of 0.2-30.2 mg kg -1 in all products, and carbon tetrachloride was observed in 13 samples in a range of 0.05-352 mg kg -1 . Dichloroacetic acid and trichloroacetic acid were also detected up to 94 and 146 mg kg -1 in household products. The estimated human exposures of chloroform, carbon tetrachloride, dichloroacetic acid and trichloroacetic acid were calculated to 0.041, 0.240, 0.913 and 2.39 mg/kg/day by the exposure algorithm from the Japan National Institute of Technology and Evaluation, respectively. According to the calculated result, the total estimated human exposure of chloroform were determined to exceed the tolerable concentration of inhalation exposure presented by the World Health Organization. The DBPs should be controlled to the lowest concentrations in the chlorine-containing household cleansing products. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Solid state parameters, structure elucidation, High Resolution X-Ray Diffraction (HRXRD), phase matching, thermal and impedance analysis on L-Proline trichloroacetate (L-PTCA) NLO single crystals.

    PubMed

    Kalaiselvi, P; Raj, S Alfred Cecil; Jagannathan, K; Vijayan, N; Bhagavannarayana, G; Kalainathan, S

    2014-11-11

    Nonlinear optical single crystal of L-Proline trichloroacetate (L-PTCA) was successfully grown by Slow Evaporation Solution Technique (SEST). The grown crystals were subjected to single crystal X-ray diffraction analysis to confirm the structure. From the single crystal XRD data, solid state parameters were determined for the grown crystal. The crystalline perfection has been evaluated using high resolution X-ray diffractometer. The frequencies of various functional groups were identified from FTIR spectral analysis. The percentage of transmittance was obtained from UV Visible spectral analysis. TGA-DSC measurements indicate the thermal stability of the crystal. The dielectric constant, dielectric loss and ac conductivity were measured by the impedance analyzer. The DC conductivity was calculated by the cole-cole plot method. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Structural, vibrational and theoretical studies of anilinium trichloroacetate: New hydrogen bonded molecular crystal with nonlinear optical properties

    NASA Astrophysics Data System (ADS)

    Tanak, H.; Pawlus, K.; Marchewka, M. K.; Pietraszko, A.

    2014-01-01

    In this work, we report a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of the potential nonlinear optical (NLO) material anilinium trichloroacetate. The FT-IR and FT-Raman spectra of the compound have been recorded together between 4000-80 cm-1 and 3600-80 cm-1 regions, respectively. The compound crystallizes in the noncentrosymmetric space group of monoclinic system. The optimized molecular structure, vibrational wavenumbers, IR intensities and Raman activities have been calculated by using density functional method (B3LYP) with 6-311++G(d,p) as higher basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. DSC measurements on powder samples do not indicate clearly on the occurrence of phase transitions in the temperature 113-293 K. The Kurtz and Perry powder reflection technique appeared to be very effective in studies of second-order nonlinear optical properties of the molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, frontier orbitals and thermodynamic properties were also performed at 6-311++G(d,p) level of theory. For title crystal the SHG efficiency was estimated by Kurtz-Perry method to be deff = 0.70 deff (KDP).

  6. Crystal structures of eight 3D molecular adducts derived from bis-imidazole, bis(benzimidazole), and organic acids

    NASA Astrophysics Data System (ADS)

    Ding, Aihua; Jin, Shouwen; Jin, Shide; Hu, KaiKai; Lin, Zhihao; Liu, Hui; Wang, Daqi

    2018-01-01

    Cocrystallization of the bis(imidazole)/bis(benzimidazole) with a series of organic acids gave a total of eight molecular adducts with the compositions: (3,6-bis(imidazole-1-yl)pyridazine): (trichloroacetic acid)2(1) [(H2L1)2+ · (tca-)2, L1 = 3,6-bis(imidazole-1-yl)pyridazine, tca- = trichloroacetate], (bis(N-imidazolyl)methane): (suberic acid) (2) [(L2) · (H2suba), L2 = bis(N-imidazolyl)methane, H2suba = suberic acid], bis(N-imidazolyl)methane: (3-nitrophthalic acid): 3H2O (3) [(H2L2)2+ · (3-Hnpa-)2 · 3H2O, 3-Hnpa- = 3-nitro hydrogenphthalate], (bis(N-imidazolyl)butane)0.5: (4-nitrophthalic acid): H2O (4) [(H2L3)0.5+ · (4-Hnpa-)- · H2O, L3 = bis(N-imidazolyl)butane, 4-Hnpa- = 4-nitro hydrogenphthalate], (1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole): (3,5-dinitrosalicylic acid) (5) [(HL4) · (3,5-dns-), L4 = 1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole, 3,5-dns- = 3,5-dinitrosalicylate], (1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole): (3-nitrophthalic acid) (6) [(H2L4) · (3-npa2-), L4 = 1-(3-(1H-benzimidazol-1-yl)propyl)-1H-benzimidazole, 3-npa2-=3-nitrogenphthalate], (bis(N-imidazolyl)butane): (pamoic acid) (7) [(H2L3) · (pam), pam = pamoate], and (3,6-bis(imidazole-1-yl)pyridazine): (1,5-naphthalenedisulfonic acid) [(H2L1)2+ · (npda)2- = 1,5-naphthalenedisulfonate] (8). The eight adducts have been characterized by X-ray diffraction technique, infrared spectrum, and elemental analysis, and the melting points of all adducts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the eight investigated crystals both the end ring N in the bis(imidazole) moieties are protonated when the organic acids are deprotonated except 2, and 5, and the crystal packing is interpreted in terms of the strong ionic Nsbnd H⋯O H-bond between the imidazolium and the deprotonated acidic groups. Except the Nsbnd H⋯O H-bond, the Osbnd H⋯O H-bonds were also found at the salts 3, 4

  7. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

    PubMed Central

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

  8. Structural, vibrational and theoretical studies of anilinium trichloroacetate: new hydrogen bonded molecular crystal with nonlinear optical properties.

    PubMed

    Tanak, H; Pawlus, K; Marchewka, M K; Pietraszko, A

    2014-01-24

    In this work, we report a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of the potential nonlinear optical (NLO) material anilinium trichloroacetate. The FT-IR and FT-Raman spectra of the compound have been recorded together between 4000-80 cm(-1) and 3600-80 cm(-1) regions, respectively. The compound crystallizes in the noncentrosymmetric space group of monoclinic system. The optimized molecular structure, vibrational wavenumbers, IR intensities and Raman activities have been calculated by using density functional method (B3LYP) with 6-311++G(d,p) as higher basis set. The obtained vibrational wavenumbers and optimized geometric parameters were seen to be in good agreement with the experimental data. DSC measurements on powder samples do not indicate clearly on the occurrence of phase transitions in the temperature 113-293 K. The Kurtz and Perry powder reflection technique appeared to be very effective in studies of second-order nonlinear optical properties of the molecule. The non-linear optical properties are also addressed theoretically. The predicted NLO properties of the title compound are much greater than ones of urea. In addition, DFT calculations of the title compound, molecular electrostatic potential, frontier orbitals and thermodynamic properties were also performed at 6-311++G(d,p) level of theory. For title crystal the SHG efficiency was estimated by Kurtz-Perry method to be d(eff)=0.70 d(eff) (KDP). Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Effects of food on a gastrically degraded drug: azithromycin fast-dissolving gelatin capsules and HPMC capsules.

    PubMed

    Curatolo, William; Liu, Ping; Johnson, Barbara A; Hausberger, Angela; Quan, Ernest; Vendola, Thomas; Vatsaraj, Neha; Foulds, George; Vincent, John; Chandra, Richa

    2011-07-01

    Commercial azithromycin gelatin capsules (Zithromax®) are known to be bioequivalent to commercial azithromycin tablets (Zithromax®) when dosed in the fasted state. These capsules exhibit a reduced bioavailability when dosed in the fed state, while tablets do not. This gelatin capsule negative food effect was previously proposed to be due to slow and/or delayed capsule disintegration in the fed stomach, resulting in extended exposure of the drug to gastric acid, leading to degradation to des-cladinose-azithromycin (DCA). Azithromycin gelatin capsules were formulated with "superdisintegrants" to provide fast-dissolving capsules, and HPMC capsule shells were substituted for gelatin capsule shells, in an effort to eliminate the food effect. Healthy volunteers were dosed with these dosage forms under fasted and fed conditions; pharmacokinetics were evaluated. DCA pharmacokinetics were also evaluated for the HPMC capsule subjects. In vitro disintegration of azithromycin HPMC capsules in media containing food was evaluated and compared with commercial tablets and commercial gelatin capsules. When the two fast-dissolving capsule formulations were dosed to fed subjects, the azithromycin AUC was 38.9% and 52.1% lower than after fasted-state dosing. When HPMC capsules were dosed to fed subjects, the azithromycin AUC was 65.5% lower than after fasted-state dosing. For HPMC capsules, the absolute fasting-state to fed-state decrease in azithromycin AUC (on a molar basis) was similar to the increase in DCA AUC. In vitro capsule disintegration studies revealed extended disintegration times for commercial azithromycin gelatin capsules and HPMC capsules in media containing the liquid foods milk and Ensure®. Interaction of azithromycin gelatin and HPMC capsules with food results in slowed disintegration in vitro and decreased bioavailability in vivo. Concurrent measurement of serum azithromycin and the acid-degradation product DCA demonstrates that the loss of azithromycin

  10. Lead-acid batteries in micro-hybrid applications. Part II. Test proposal

    NASA Astrophysics Data System (ADS)

    Schaeck, S.; Stoermer, A. O.; Albers, J.; Weirather-Koestner, D.; Kabza, H.

    In the first part of this work [1] selected key parameters for applying lead-acid (LA) batteries in micro-hybrid power systems (MHPS) were investigated. Main results are integrated in an accelerated, comprehensive test proposal presented here. The test proposal aims at a realistic representation of the pSoC operation regime, which is described in Refs. [1,6]. The test is designed to be sensitive with respect to dynamic charge acceptance (DCA) at partially discharged state (critical for regenerative braking) and the internal resistance at high-rate discharge (critical for idling stop applications). First results are presented for up-to-date valve-regulated LA batteries with absorbent glass mat (AGM) separators. The batteries are close to the limits of the first proposal of pass/fail-criteria. Also flooded batteries were tested; the first out of ten units failed already.

  11. Determination of trace-level haloacetic acids in drinking water by ion chromatography-inductively coupled plasma mass spectrometry.

    PubMed

    Liu, Yongjian; Mou, Shifen; Chen, Dengyun

    2004-06-11

    A new method for the determination of nine haloacetic acids (HAAs) with ion chromatography (IC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) was developed. With the very hydrophilic anion-exchange column and steep gradient of sodium hydroxide, the nine HAAs could be well separated in 15 min. After suppression with an ASRS suppressor that was introduced in between IC and ICP-MS, the background was much decreased, the interference caused by sodium ion present in eluent was removed, and the sensitivities of HAAs were greatly improved. The chlorinated and brominated HAAs could be detected as 35ClO and 79Br without interference of the matrix due to the elemental selective ICP-MS. The detection limits for mono-, di-, trichloroacetic acids were between 15.6 and 23.6 microg/l. For the other six bromine-containing HAAs, the detection limits were between 0.34 and 0.99 microg/l. With the pretreatment of OnGuard Ag cartridge to remove high concentration of chloride in sample, the developed method could be applied to the determination of HAAs in many drinking water matrices.

  12. Determination of haloacetic acids in water by ion chromatography--method development.

    PubMed

    Lopez-Avila, V; Liu, Y; Charan, C

    1999-01-01

    The microextraction/ion chromatographic (IC) method developed in this study involves extraction of 9 haloacetic acids (HAAs) from aqueous samples (acidified with sulfuric acid to a pH of < 0.5 and amended with copper sulfate pentahydrate and sodium sulfate) with methyl tert-butyl ether (MTBE), back extraction into reagent water, and analysis by IC with conductivity detection. The separation column consists of an Ion Pac AG-11 (2 mm id x 50 mm length) guard column and an Ion Pac AS-11 (2 mm id x 250 mm length) analytical column, and the concentration column is a 4 mm id x 35 mm length Dionex TAC-LP column. Use of the 2 mm id Dionex AS-11 column improved detection limits especially for trichloracetic acid (TCAA), bromodichloroacetic acid (BDCAA), dibromochloroacetic acid (DBCAA), and tribromoacetic acid (TBAA). The peak interfering with BCAA elutes at the same retention time as nitrate; however, we have not confirmed the presence of nitrate. Stability studies indicate that HAAs are stable in water for at least 8 days when preserved with ammonium chloride at 100 mg/L and stored at 4 degrees C in the dark. At day 30, recoveries were still high (e.g., 92.1-106%) for dichloroacetic acid (DCAA), BCAA, dibromoacetic acid (DBAA), trichloroacetic acid (TCAA), BDCAA, and DBCAA. However, recoveries of monochloroacetic acid (MCAA), monobromoacetic acid (MBAA), and TBAA were only 54.6, 56.8, and 66.8%, respectively. Stability studies of HAAs in H2SO4-saturated MTBE indicate that all compounds except TBAA are stable for 48 h when stored at 4 degrees C in the dark. TBAA recoveries dropped to 47.1% after 6 h of storage and no TBAA was detected after 48 h of storage. The method described here is only preliminary and was tested in only one laboratory. Additional research is needed to improve method performance.

  13. Molecular structure and spectral properties of ethyl 3-quinolinecarboxylate (E3Q) and [Ag(E3Q)2(TCA)] complex (TCA = Trichloroacetate)

    NASA Astrophysics Data System (ADS)

    Soliman, Saied M.; Kassem, Taher S.; Badr, Ahmed M. A.; Abou Youssef, Morsy A.; Assem, Rania

    2014-09-01

    A new [Ag(E3Q)2(TCA)] complex; (E3Q = Ethyl 3-quinolinecarboxylate and TCA = Trichloroacetate) has been synthesized and characterized using elemental analysis, FTIR, NMR and mass spectroscopy. The molecular geometry and spectroscopic properties of the complex as well as the free ligand have been calculated using the hybrid B3LYP method. The calculations predicted a distorted tetrahedral arrangement around Ag(I) ion. The vibrational spectra of the studied compounds have been assigned using potential energy distribution (PED). TD-DFT method was used to predict the electronic absorption spectra. The most intense absorption band showed a bathochromic shift and lowering of intensity in case of the complex (233.7 nm, f = 0.5604) compared to E3Q (λmax = 228.0 nm, f = 0.9072). The calculated 1H NMR chemical shifts using GIAO method showed good correlations with the experimental data. The computed dipole moment, polarizability and HOMO-LUMO energy gap were used to predict the nonlinear optical (NLO) properties. It is found that Ag(I) enhances the NLO activity. The natural bond orbital (NBO) analyses were used to elucidate the intramolecular charge transfer interactions causing stabilization for the investigated systems.

  14. Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats

    PubMed Central

    Matthews, Jessica L.; Schultz, Irvin R.; Easterling, Michael R.; Melnick, Ronald L.

    2010-01-01

    A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite α-halocarboxymethylglutathione (αH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical- and species-specific parameters. PMID:20045428

  15. Characterization of the newly isolated ω-oxidizing yeast Candida sorbophila DS02 and its potential applications in long-chain dicarboxylic acid production.

    PubMed

    Lee, Heeseok; Sugiharto, Yohanes Eko Chandra; Lee, Seunghoon; Park, Gyuyeon; Han, Changpyo; Jang, Hyeran; Jeon, Wooyoung; Park, Heejoon; Ahn, Jungoh; Kang, Kyungbo; Lee, Hongwoen

    2017-08-01

    α, ω-Dicarboxylic acids (DCAs) are multipurpose chemicals widely used in polymers, perfumes, plasticizers, lubricants, and adhesives. The biotransformation of DCAs from alkanes and fatty acids by microorganisms has attracted recent interest, since synthesis via chemical oxidation causes problems in terms of the environment and safety. We isolated an ω-oxidizing yeast from a wastewater disposal facility of a petrochemical factory by chemostat enrichment culture. The haploid strain identified as Candida sorbophila DS02 grew on glucose and dodecane, exhibiting greater cell shrinkage on the latter. In flask cultures with mixed alkanes (C10-16) and fatty acid methyl esters (C10-16), DS02 used mixed alkanes simultaneously unlike Candida tropicalis and Yarrowia lipolytica and showed high substrate resistance. In flask cultures with acrylic acid-a known inhibitor of β-oxidation-DS02 produced 0.28 g/l dodecanedioic acid (DDDA) from dodecane, similar to wild-type C. tropicalis ATCC 20336. In fed-batch fermentation, DS02 produced 9.87 g/l DDDA, which was 5.7-fold higher than wild-type C. tropicalis. These results suggest that C. sorbophila strain DS02 has potential applications for the large-scale production of DCA.

  16. Quantum chemical study, spectroscopic investigations, NBO and HOMO-LUMO analyses of 3-aminoquinoline (3AQ) and [Ag(3AQ)2(TCA)] complex (TCA = Trichloroacetate)

    NASA Astrophysics Data System (ADS)

    Soliman, Saied M.; Kassem, Taher S.; Badr, Ahmed M. A.; Abu Youssef, Morsy A.; Assem, Rania

    2014-09-01

    The new [Ag(3AQ)2(TCA)]; (3AQ = 3-aminoquinoline and TCA = Trichloroacetate) complex is synthesized and characterized using elemental analysis, FTIR, NMR and mass spectroscopy. The molecular geometry, vibrational frequencies, gauge-including atomic orbital (GIAO) 1H chemical shift values of the free and coordinated 3AQ in the ground state have been calculated by using DFT/B3LYP method. The TD-DFT results of the [Ag(3AQ)2(TCA)] complex showed a π-π* transition band at 240.3-242.6 nm (f = 0.1334-0.1348) which has longer wavelength and lower absorption intensity than that for the free 3AQ (233.2 nm, f = 0.3958). Dipole moment, polarizability and HOMO-LUMO gap values predicted better nonlinear optical properties (NLO) for the [Ag(3AQ)2(TCA)] than the 3AQ ligand. NBO analysis has been used to predict the most accurate Lewis structure of the studied molecules. The energies of the different intramolecular charge transfer (ICT) interactions within the studied molecules were estimated using second order perturbation theory.

  17. Avoiding pitfalls in the determination of halocarboxylic acids: the photochemistry of methylation.

    PubMed

    Rubio, F J; Urbansky, E T; Magnuson, M L

    2000-06-01

    Haloethanoic (haloacetic) acids are formed during chlorination of drinking water and are regulated by the Environmental Protection Agency (EPA). These compounds are normally quantified by gas chromatography with electron capture detection (GC-ECD) as the methyl esters. EPA Method 552 uses diazomethane (CH2N2) for this purpose, but has only been validated by EPA for HAA6: chloro-, dichloro-, bromo-, dibromo-, bromochloro- and trichloroacetic acids. EPA Method 552.2 was developed and validated for all nine analytes (HAA9 = HAA6 + dibromochloro-, bromodichloro- and tribromoethanoic acids). Since the promulgation of Method 552.2, which uses acidic methanol, a debate has ensued over discrepancies observed by various laboratories when using diazomethane instead. In an effort to identify and eliminate potential sources for these discrepancies, a comparative study was undertaken for HAA9. Better accuracy and precision were observed for all HAA9 species by Method 552.2; recoveries were satisfactory in de-ionized and tap water. Method 552 remains satisfactory for HAA6. Systematic differences in instrumental response are observed for the two methods, but these are precise and may be accounted for using similarly treated standards and analyte-fortified (spiked) samples. That notwithstanding, Method 552 (CH2N2) was shown to be unsuitable for dibromochloro-, bromodichloro- and tribromoethanoic acids (HAA9-6). The primary problem appears to be a photoactivated reaction between diazomethane and the HAA9-6 analytes; however, side reactions were found to occur even in the dark. Analyte loss is most pronounced under typical laboratory lighting (white F40 fluorescent lamps + sunlight), but it is also observed under Philips gold F40 lamps (lambda > or = 520 nm), and in the dark.

  18. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis

    PubMed Central

    Xie, Guoxiang; Wang, Xiaoning; Huang, Fengjie; Zhao, Aihua; Chen, Wenlian; Yan, Jingyu; Zhang, Yunjing; Lei, Sha; Ge, Kun; Zheng, Xiaojiao; Liu, Jiajian; Su, Mingming; Liu, Ping; Jia, Wei

    2017-01-01

    Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. PMID:27273788

  19. In vitro bioacessibility and transport across Caco-2 monolayers of haloacetic acids in drinking water.

    PubMed

    Melo, A; Faria, M A; Pinto, E; Mansilha, C; Ferreira, I M P L V O

    2016-10-01

    Water disinfection plays a crucial role in water safety but it is also a matter of concern as the use of disinfectants promotes the formation of disinfection by-products (DBPs). Haloacetic acids (HAAs) are one of the major classes of DBPs since they are frequently found in treated water, are ubiquitous, pervasive and have high water solubility, so a great concern emerged about their formation, occurrence and toxicity. Exposure to HAAs is influenced by consumption patterns and diet of individuals thus their bioavailability is an important parameter to the overall toxicity. In the current study the bioacessibility of the most representative HAAs (chloroacetic acid - MCAA, bromoacetic acid - MBAA, dichloroacetic acid - DCAA, dibromoacetic acid - DBAA, and trichloroacetic acid - TCAA) after simulated in vitro digestion (SIVD) in tap water and transport across Caco-2 monolayers was evaluated. Compounds were monitored in 8 points throughout the digestion phases by an optimized LC-MS/MS methodology. MCAA and MBAA were not bioaccessible after SIVD whereas DCAA, DBAA and TCAA are highly bioaccessible (85 ± 4%, 97 ± 4% and 106 ± 7% respectively). Concerning transport assays, DCAA and DBAA were highly permeable throughout the Caco-2 monolayer (apparent permeability and calculated fraction absorbed of 13.62 × 10(-6) cm/s and 90% for DCAA; and 8.82 × 10(-6) cm/s and 84% for DBAA), whereas TCAA showed no relevant permeability. The present results may contribute to efficient risk analysis studies concerning HAAs oral exposure from tap water taking into account the different biological behaviour of these chemically similar substances. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344 rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matthews, Jessica L., E-mail: Jessica_Matthews@sra.co; Schultz, Irvin R., E-mail: irv.schultz@pnl.go; Easterling, Michael R., E-mail: Michael_Easterling@sra.co

    A novel physiologically based pharmacokinetic (PBPK) model structure, which includes submodels for the common metabolites (glyoxylate (GXA) and oxalate (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic acid (DBA), has been developed. Particular attention is paid to the representation of hepatic metabolism, which is the primary elimination mechanism. DBA-induced suicide inhibition is modeled by irreversible covalent binding of the intermediate metabolite alpha-halocarboxymethylglutathione (alphaH1) to the glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA, but not dichloroacetic acid (DCA), that produces GXA. The model is calibratedmore » with plasma and urine concentration data from DBA exposures in female F344 rats through intravenous (IV), oral gavage, and drinking water routes. Sensitivity analysis is performed to confirm identifiability of estimated parameters. Finally, model validation is performed with data sets not used during calibration. Given the structural similarity of dihaloacetates (DHAs), we hypothesize that the PBPK model presented here has the capacity to describe the kinetics of any member or mixture of members of this class in any species with the alteration of chemical-and species-specific parameters.« less

  1. Biodegradation of haloacetic acids by bacterial isolates and enrichment cultures from drinking water systems.

    PubMed

    Zhang, Ping; Lapara, Timothy M; Goslan, Emma H; Xie, Yuefeng; Parsons, Simon A; Hozalski, Raymond M

    2009-05-01

    Biodegradation is a potentially important loss process for haloacetic acids (HAAs), a class of chlorination byproducts, in water treatment and distribution systems, but little is known about the organisms involved (i.e., identity, substrate range, biodegradation kinetics). In this research, 10 biomass samples (i.e., tap water, distribution system biofilms, and prechlorinated granular activated carbon filters) from nine drinking water systems were used to inoculate a total of thirty enrichment cultures fed monochloroacetic acid (MCAA), dichloroacetic acid (DCAA), or trichloroacetic (TCAA) as sole carbon and energy source. HAA degraders were successfully enriched from the biofilm samples (GAC and distribution system) but rarely from tap water. Half of the MCAA and DCAA enrichment cultures were positive, whereas only one TCAA culture was positive (two were inconclusive). Eight unique HAA-degrading isolates were obtained including several Afipia spp. and a Methylobacterium sp.; all isolates were members of the phylum Proteobacteria. MCAA, monobromoacetic acid (MBAA), and monoiodoacetic acid (MIAA) were rapidly degraded by all isolates, and DCAA and tribromoacetic (TBAA) were also relatively labile. TCAA and dibromoacetic acid (DBAA)were degraded by only three isolates and degradation lagged behind the other HAAs. Detailed DCAA biodegradation kinetics were obtained for two selected isolates and two enrichment cultures. The maximum biomass-normalized degradation rates (Vm) were 0.27 and 0.97 microg DCAA/ microg protein/h for Methylobacterium fujisawaense strain PAWDI and Afipia felis strain EMD2, respectively, which were comparable to the values obtained for the enrichment cultures from which those organisms were isolated (0.39 and 1.37 microg DCAN/microg protein/h, respectively). The half-saturation constant (Km) values ranged from 4.38 to 77.91 microg DCAA/L and the cell yields ranged from 14.4 to 36.1 mg protein/g DCAA.

  2. Association of SSR markers with contents of fatty acids in olive oil and genetic diversity analysis of an olive core collection.

    PubMed

    Ipek, M; Ipek, A; Seker, M; Gul, M K

    2015-03-27

    The purpose of this research was to characterize an olive core collection using some agronomic characters and simple sequence repeat (SSR) markers and to determine SSR markers associated with the content of fatty acids in olive oil. SSR marker analysis demonstrated the presence of a high amount of genetic variation between the olive cultivars analyzed. A UPGMA dendrogram demonstrated that olive cultivars did not cluster on the basis of their geographic origin. Fatty acid components of olive oil in these cultivars were determined. The results also showed that there was a great amount of variation between the olive cultivars in terms of fatty acid composition. For example, oleic acid content ranged from 57.76 to 76.9% with standard deviation of 5.10%. Significant correlations between fatty acids of olive oil were observed. For instance, a very high negative correlation (-0.812) between oleic and linoleic acids was detected. A structured association analysis between the content of fatty acids in olive oil and SSR markers was performed. STRUCTURE analysis assigned olive cultivars to two gene pools (K = 2). Assignment of olive cultivars to these gene pools was not based on geographical origin. Association between fatty acid traits and SSR markers was evaluated using the general linear model of TASSEL. Significant associations were determined between five SSR markers and stearic, oleic, linoleic, and linolenic acids of olive oil. Very high associations (P < 0.001) between ssrOeUA-DCA14 and stearic acid and between GAPU71B and oleic acid indicated that these markers could be used for marker-assisted selection in olive.

  3. Edible Oil Barriers for Treatment of Chlorinated Solvent Contaminated Groundwater

    DTIC Science & Technology

    2009-07-01

    CF Chloroform Cl# Chlorine Number CO Carbon Monoxide CT Carbon Tetrachloride CVOC Chlorinated Volatile Organic Compound 1,2-DCA 1,2...As Safe HCl Hydrochloric Acid HRC® Hydrogen Release Compound IDW Investigation-Derived Waste ISCO In Situ Chemical Oxidation LEL Lower...Total Organic Carbon VC Vinyl Chloride VFA Volatile Fatty Acid VOC Volatile Organic Compound ZVI Zero Valent Iron viii ACKNOWLEDGEMENTS

  4. In matrix derivatization of trichloroethylene metabolites in human plasma with methyl chloroformate and their determination by solid-phase microextraction-gas chromatography-electron capture detector.

    PubMed

    Mudiam, Mohana Krishna Reddy; Jain, Rajeev; Varshney, Meenu; Ch, Ratnasekhar; Chauhan, Abhishek; Goyal, Sudhir Kumar; Khan, Haider A; Murthy, R C

    2013-04-15

    Trichloroethylene (TCE) is a common industrial chemical that has been widely used as metal degreaser and for many industrial purposes. In humans, TCE is metabolized into dichloroacetic acid (DCA), trichloroacetic acid (TCA) and trichloroethanol (TCOH). A simple and rapid method has been developed for the quantitative determination of TCE metabolites. The procedure involves the in situ derivatization of TCE metabolites with methyl chloroformate (MCF) directly in diluted plasma samples followed by extraction and analysis with solid-phase microextraction (SPME) coupled to gas chromatography-electron capture detector (GC-ECD). Factors which can influence the efficiency of derivatization such as amount of MCF and pyridine (PYR), ratio of water/methanol were optimized. The factors which can affect the extraction efficiencies of SPME were screened using 2(7-4) Placket-Burman Design (PBD). A central composite design (CCD) was then applied to further optimize the most significant factors for optimum SPME extraction. The optimum factors for the SPME extraction were found to be 562.5mg of NaCl, pH at 1 and an extraction time of 22 min. Recoveries and detection limits of all three analytes in plasma were found to be in the range of 92.69-97.55% and 0.036-0.068 μg mL(-1) of plasma, respectively. The correlation coefficients were found to be in the range of 0.990-0.995. The intra- and inter-day precisions for TCE metabolites were found to be in the range of 2.37-4.81% and 5.13-7.61%, respectively. The major advantage of this method is that MCF derivatization allows conversion of TCE metabolites into their methyl esters in very short time (≤30 s) at room temperature directly in the plasma samples, thus makes it a solventless analysis. The method developed was successfully applied to the plasma samples of humans exposed to TCE. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Magnetic solid phase extraction with CoFe2O4/oleic acid nanoparticles coupled to gas chromatography-mass spectrometry for the determination of alkylphenols in baby foods.

    PubMed

    Pastor-Belda, Marta; Viñas, Pilar; Campillo, Natalia; Hernández-Córdoba, Manuel

    2017-04-15

    Magnetic solid phase extraction (MSPE) with cobalt ferrite nanoparticles coated with oleic acid is described for the determination of alkylphenols (APs), 4-tert-butylphenol (TBP), 4-pentylphenol (PP), 4-hexylphenol (HP), 4-tert-octylphenol (TOP), 4-n-octylphenol (OP) and 4-nonylphenol (NP) in baby foods using gas chromatography with mass spectrometry (GC-MS). Prior to MSPE, the sample was treated with trichloroacetic acid, and the APs derivatized with acetic anhydride. Parameters affecting the extraction efficiency: amount of magnetic nanoparticles, extraction time and desorption conditions, were optimized. The enriched phase obtained was evaporated to dryness and the residue reconstituted in 50μL of methanol, 1μL of which was injected into the GC-MS. Samples were quantified applying matrix-matched calibration and using 2-chloro-5-bromoanisole as surrogate standard. The analysis of 0.5g of sample provided detection limits in the 0.4-1.7ngg -1 range. Some samples contained APs at levels of between 3ngg -1 for HP and 122ngg -1 for TOP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Ionic Liquid as a Solvent and Catalyst for Acylation of Maltodextrin

    USDA-ARS?s Scientific Manuscript database

    Catalyst-free esterification of maltodextrin was carried out in ionic liquid. Stearate esters of maltodextrin were obtained in various degree of substitution (DS) when vinyl stearate or stearic acid was heated with maltodextrin in ionic liquid, 1-butyl-3-methylimidazolium cyanamide (bmim[dca]). Re...

  7. Study of disulfide reduction and alkyl chloroformate derivatization of plasma sulfur amino acids using gas chromatography-mass spectrometry.

    PubMed

    Svagera, Zdeněk; Hanzlíková, Dagmar; Simek, Petr; Hušek, Petr

    2012-03-01

    Four disulfide-reducing agents, dithiothreitol (DTT), 2,3-dimercaptopropanesulfonate (DMPS), and the newly tested 2-mercaptoethanesulfonate (MESNA) and Tris(hydroxypropyl)phosphine (THP), were investigated in detail for release of sulfur amino acids in human plasma. After protein precipitation with trichloroacetic acid (TCA), the plasma supernatant was treated with methyl, ethyl, or propyl chloroformate via the well-proven derivatization-extraction technique and the products were subjected to gas chromatographic-mass spectrometric (GC-MS) analysis. All the tested agents proved to be rapid and effective reducing agents for the assay of plasma thiols. When compared with DTT, the novel reducing agents DMPS, MESNA, and THP provided much cleaner extracts and improved analytical performance. Quantification of homocysteine, cysteine, and methionine was performed using their deuterated analogues, whereas other analytes were quantified by means of 4-chlorophenylalanine. Precise and reliable assay of all examined analytes was achieved, irrespective of the chloroformate reagent used. Average relative standard deviations at each analyte level were ≤6%, quantification limits were 0.1-0.2 μmol L(-1), recoveries were 94-121%, and linearity was over three orders of magnitude (r(2) equal to 0.997-0.998). Validation performed with the THP agent and propyl chloroformate derivatization demonstrated the robustness and reliability of this simple sample-preparation methodology.

  8. Proteomic Retrieval from Nucleic Acid Depleted Space-Flown Human Cells

    NASA Technical Reports Server (NTRS)

    Hammond, D. K.; Elliott, T. F.; Holubec, K.; Baker, T. L.; Allen, P. L.; Hammond, T. G.; Love, J. E.

    2006-01-01

    Compared to experiments utilizing humans in microgravity, cell-based approaches to questions about subsystems of the human system afford multiple advantages, such as crew safety and the ability to achieve statistical significance. To maximize the science return from flight samples, an optimized method was developed to recover protein from samples depleted of nucleic acid. This technique allows multiple analyses on a single cellular sample and when applied to future cellular investigations could accelerate solutions to significant biomedical barriers to human space exploration. Cell cultures grown in American Fluoroseal bags were treated with an RNA stabilizing agent (RNAlater - Ambion), which enabled both RNA and immunoreactive protein analyses. RNA was purified using an RNAqueous(registered TradeMark) kit (Ambion) and the remaining RNA free supernatant was precipitated with 5% trichloroacetic acid. The precipitate was dissolved in SDS running buffer and tested for protein content using a bicinchoninic acid assay (1) (Sigma). Equal loads of protein were placed on SDS-PAGE gels and either stained with CyproOrange (Amersham) or transferred using Western Blotting techniques (2,3,4). Protein recovered from RNAlater-treated cells and stained with protein stain, was measured using Imagequant volume measurements for rectangles of equal size. BSA treated in this way gave quantitative data over the protein range used (Fig 1). Human renal cortical epithelial (HRCE) cells (5,6,7) grown onboard the International Space Station (ISS) during Increment 3 and in ground control cultures exhibited similar immunoreactivity profiles for antibodies to the Vitamin D receptor (VDR) (Fig 2), the beta isoform of protein kinase C (PKC ) (Fig 3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (Fig 4). Parallel immunohistochemical studies on formalin-fixed flight and ground control cultures also showed positive immunostaining for VDR and other biomarkers (Fig 5). These results are

  9. Regional Air Quality Model Application of the Aqueous-Phase ...

    EPA Pesticide Factsheets

    In most ecosystems, atmospheric deposition is the primary input of mercury. The total wet deposition of mercury in atmospheric chemistry models is sensitive to parameterization of the aqueous-phase reduction of divalent oxidized mercury (Hg2+). However, most atmospheric chemistry models use a parameterization of the aqueous-phase reduction of Hg2+ that has been shown to be unlikely under normal ambient conditions or use a non mechanistic value derived to optimize wet deposition results. Recent laboratory experiments have shown that Hg2+ can be photochemically reduced to elemental mercury (Hg) in the aqueous-phase by dissolved organic matter and a mechanism and the rate for Hg2+ photochemical reduction by dicarboxylic acids (DCA) has been proposed. For the first time in a regional scale model, the DCA mechanism has been applied. The HO2-Hg2+ reduction mechanism, the proposed DCA reduction mechanism, and no aqueous-phase reduction (NAR) of Hg2+ are evaluated against weekly wet deposition totals, concentrations and precipitation observations from the Mercury Deposition Network (MDN) using the Community Multiscale Air Quality (CMAQ) model version 4.7.1. Regional scale simulations of mercury wet deposition using a DCA reduction mechanism evaluated well against observations, and reduced the bias in model evaluation by at least 13% over the other schemes evaluated, although summertime deposition estimates were still biased by −31.4% against observations. The use of t

  10. Assessment of biostimulation and bioaugmentation for removing chlorinated volatile organic compounds from groundwater at a former manufacture plant.

    PubMed

    Zhang, Shu; Hou, Zhen; Du, Xiao-Ming; Li, Dong-Ming; Lu, Xiao-Xia

    2016-11-01

    Site in a former chemical manufacture plant in China was found contaminated with high level of chlorinated volatile organic compounds (CVOCs). The major contaminants chloroform (CF), 1,2-dichloroethane (1,2-DCA) and vinyl chloride (VC) in groundwater were up to 4.49 × 10 4 , 2.76 × 10 6 and 4.35 × 10 4 μg/L, respectively. Ethene and methane were at concentrations up to 2219.80 and 165.85 μg/L, respectively. To test the hypothesis that the CVOCs in groundwater at this site could be removed via biodegradation, biomarker analyses and microcosm studies were conducted. Dehalococcoides 16S rRNA gene and VC-reductase gene vcrA at densities up to 1.5 × 10 4 and 3.2 × 10 4  copies/L were detected in some of the groundwater samples, providing strong evidence that dechlorinating bacteria were present in the aquifer. Results from the microcosm studies showed that at moderate concentrations (CF about 4000 μg/L and 1,2-DCA about 100 μg/L), CF was recalcitrant under natural condition but was degraded under biostimulation and bioaugmentation, while 1,2-DCA was degraded under all the three conditions. At high concentration (CF about 1,000,000 μg/L and 1,2-DCA about 20,000 μg/L), CF was recalcitrant under all the three treatments and 1,2-DCA was only degraded under bioaugmentation, indicating that high concentrations of contaminants were inhibitory to the bacteria. Electron donors had influence on the degradation of contaminants. Of the four fatty acids (pyruvate, acetate, propionate and lactate) examined, all could stimulate the degradation of 1,2-DCA at both moderate and high concentrations, whereas only pyruvate and acetate could stimulate the degradation of CF at moderate concentration. In the microcosms, the observed first-order degradation rates of CF and 1,2-DCA were up to 0.12 and 0.11/day, respectively. Results from the present study provided scientific basis for remediating CVOCs contaminated groundwater at the site.

  11. UDCA and CDCA alleviate 17α-ethinylestradiol-induced cholestasis through PKA-AMPK pathways in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Xiaojiaoyang; Yuan, Zihang

    Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model. Our results showed that, both CDCA and UDCA significantly inducedmore » time- and concentration-dependent reduction in AMPK phosphorylation in SCRHs. Despite having different effects on FXR activation, CDCA and UDCA both inhibited EE-induced AMPK activation, accompanied with the up-regulation of FXR and its downstream bile acid transporters. However, although DCA activates FXR and induces SHP, it was unable to alleviate EE-induced FXR suppression and further aggravated EE-induced cholestasis. We further demonstrated that both CDCA and UDCA, but not DCA, activated cyclic AMP dependent protein kinase (PKA) in SCRHs and the livers of male rats (8 weeks old) liver. Furthermore, PKA antagonist, H89, blocked the AMPK inhibition by CDCA and UDCA, and pharmacological and genetic activation of PKA suppressed EE-induced AMPK activation and its downstream effects. Collectively, these results suggest that CDCA and UDCA protect against estrogen-induced cholestatic injury via PKA signaling pathway and up-regulation of EE-suppressed FXR, which suggests a potential therapeutic target for ICP. - Highlights: • AMPK is involved in cholestatic liver injury with bile acid dysregulation. • CDCA and UDCA inhibit the phosphorylation of AMPK and alleviate estrogen-induced cholestasis. • PKA activation

  12. Evaluation of the combined solar TiO2/photo-Fenton process using multivariate analysis.

    PubMed

    Nogueira, R F P; Trovó, A G; Paterlini, W C

    2004-01-01

    The effect of combining the photocatalytic processes using TiO2 and the photo-Fenton reaction with Fe3+ or ferrioxalate as a source of Fe2+ was investigated in the degradation of 4-chlorophenol (4CP) and dichloroacetic acid (DCA) using solar irradiation. Multivariate analysis was used to evaluate the role of three variables: iron, H2O2 and TiO2 concentrations. The results show that TiO2 plays a minor role when compared to iron and H2O2 in the solar degradation of 4CP and DCA in the studied conditions. However, its presence can improve TOC removal when H2O2 is totally consumed. Iron and peroxide play major roles, especially when Fe(NO3)3 is used in the degradation of 4CP. No significant synergistic effect was observed by the addition of TiO2 in this process. On the other hand, synergistic effects were observed between FeOx and TiO2 and between H2O2 and TiO2 in the degradation of DCA.

  13. Thermophysical properties of energetic ionic liquids/nitric acid mixtures: Insights from molecular dynamics simulationsa)

    NASA Astrophysics Data System (ADS)

    Hooper, Justin B.; Smith, Grant D.; Bedrov, Dmitry

    2013-09-01

    Molecular dynamics (MD) simulations of mixtures of the room temperature ionic liquids (ILs) 1-butyl-4-methyl imidazolium [BMIM]/dicyanoamide [DCA] and [BMIM][NO3-] with HNO3 have been performed utilizing the polarizable, quantum chemistry based APPLE&P® potential. Experimentally it has been observed that [BMIM][DCA] exhibits hypergolic behavior when mixed with HNO3 while [BMIM][NO3-] does not. The structural, thermodynamic, and transport properties of the IL/HNO3 mixtures have been determined from equilibrium MD simulations over the entire composition range (pure IL to pure HNO3) based on bulk simulations. Additional (non-equilibrium) simulations of the composition profile for IL/HNO3 interfaces as a function of time have been utilized to estimate the composition dependent mutual diffusion coefficients for the mixtures. The latter have been employed in continuum-level simulations in order to examine the nature (composition and width) of the IL/HNO3 interfaces on the millisecond time scale.

  14. In situ crosslinked smart polypeptide nanoparticles for multistage responsive tumor-targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Yi, Huqiang; Liu, Peng; Sheng, Nan; Gong, Ping; Ma, Yifan; Cai, Lintao

    2016-03-01

    Smart tumor-targeted drug delivery is crucial for improving the effect of chemotherapy and reducing the adverse effects. Here, we synthesized a smart polypeptide copolymer based on n-butylamine-poly(l-lysine)-b-poly(l-cysteine) (PLL-PLC) with functionalization of folic acid (FA) and 1,2-dicarboxylic-cyclohexene anhydride (DCA) for multistage responsive tumor-targeted drug delivery. The copolymers (FA-PLL(DCA)-PLC) spontaneously crosslinked in situ to form redox and pH dual responsive FA-PLL(DCA)-PLC nanoparticles (FD-NPs), which had a reversible zeta potential around -30 mV at pH 7.4, but switched to +15 mV at pH 5.0. Moreover, FD-NPs effectively loaded DOX with a loading capacity at 15.7 wt%. At pH 7.4, only 24.5% DOX was released within 60 h. However, at pH 5.0, the presence of 10 mM DTT dramatically accelerated DOX release with over 90% of DOX released within 10 h. Although the FD-NPs only enhanced DOX uptake in FA receptor positive (FR+) cancer cells at pH 7.4, a weak acidic condition promoted FD-NP-facilitated DOX uptake in both FR+ HeLa and FR- A549 cells, as well as significantly improving cellular binding and end/lysosomal escape. In vivo studies in a HeLa cancer model demonstrated that the charge-reversible FD-NPs delivered DOX into tumors more effectively than charge-irreversible nanoparticles. Hence, these multistage responsive FD-NPs would serve as highly efficient drug vectors for targeted cancer chemotherapy.Smart tumor-targeted drug delivery is crucial for improving the effect of chemotherapy and reducing the adverse effects. Here, we synthesized a smart polypeptide copolymer based on n-butylamine-poly(l-lysine)-b-poly(l-cysteine) (PLL-PLC) with functionalization of folic acid (FA) and 1,2-dicarboxylic-cyclohexene anhydride (DCA) for multistage responsive tumor-targeted drug delivery. The copolymers (FA-PLL(DCA)-PLC) spontaneously crosslinked in situ to form redox and pH dual responsive FA-PLL(DCA)-PLC nanoparticles (FD-NPs), which had a reversible

  15. Cardiovascular Ultrasound of Neonatal Long Evans Rats ...

    EPA Pesticide Factsheets

    This abstract describes the use of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development. The abstract describes the effects of two known cardiac teratogens, trichloroacetic acid and dimethadione, and their effects as determined by echocardiography. This abstract describes the use and development of a relatively new technology, cardiovascular ultrasound (echocardiography) for evaluating developmental toxicity affecting heart development.

  16. Incorporation of DNA and Protein Precursors into Macromolecules by Bacteria at −15oC

    PubMed Central

    Christner, Brent C.

    2002-01-01

    DNA and protein precursors were incorporated into trichloroacetic acid-precipitated material by bacterial cell suspensions during incubation for 50 to 100 days at −15oC. Incorporation did not occur at −70oC and was inhibited by antibiotics. The results demonstrate that bacteria can perform macromolecular synthesis under conditions that mimic entrapment in glacial ice. PMID:12450874

  17. Effect of dissolved oxygen concentration on iron efficiency: Removal of three chloroacetic acids.

    PubMed

    Tang, Shun; Wang, Xiao-mao; Mao, Yu-qin; Zhao, Yu; Yang, Hong-wei; Xie, Yuefeng F

    2015-04-15

    The monochloroacetic, dichloroacetic and trichloroacetic acid (MCAA, DCAA and TCAA) removed by metallic iron under controlled dissolved oxygen conditions (0, 0.75, 1.52, 2.59, 3.47 or 7.09 mg/L DO) was investigated in well-mixed batch systems. The removal of CAAs increased first and then decreased with increasing DO concentration. Compared with anoxic condition, the reduction of MCAA and DCAA was substantially enhanced in the presence of O2, while TCAA reduction was significantly inhibited above 2.59 mg/L. The 1.52 mg/L DO was optimum for the formation of final product, acetic acid. Chlorine mass balances were 69-102%, and carbon mass balances were 92-105%. With sufficient mass transfer from bulk to the particle surface, the degradation of CAAs was limited by their reduction or migration rate within iron particles, which were dependent on the change of reducing agents and corrosion coatings. Under anoxic conditions, the reduction of CAAs was mainly inhibited by the available reducing agents in the conductive layer. Under low oxic conditions, the increasing reducing agents and thin lepidocrocite layer were favorable for CAA dechlorination. Under high oxic conditions, the redundant oxygen competing for reducing agents and significant lepidocrocite growth became the major restricting factors. Various CAA removal mechanisms could be potentially applied to explaining the effect of DO concentration on iron efficiency for contaminant reduction in water and wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. A multiple-cathode, high-power, rectangular ion thruster discharge chamber of increasing thruster lifetime

    NASA Astrophysics Data System (ADS)

    Rovey, Joshua Lucas

    Ion thrusters are high-efficiency, high-specific impulse space propulsion systems proposed for deep space missions requiring thruster operational lifetimes of 7--14 years. One of the primary ion thruster components is the discharge cathode assembly (DCA). The DCA initiates and sustains ion thruster operation. Contemporary ion thrusters utilize one molybdenum keeper DCA that lasts only ˜30,000 hours (˜3 years), so single-DCA ion thrusters are incapable of satisfying the mission requirements. The aim of this work is to develop an ion thruster that sequentially operates multiple DCAs to increase thruster lifetime. If a single-DCA ion thruster can operate 3 years, then perhaps a triple-DCA thruster can operate 9 years. Initially, a multiple-cathode discharge chamber (MCDC) is designed and fabricated. Performance curves and grid-plane current uniformity indicate operation similar to other thrusters. Specifically, the configuration that balances both performance and uniformity provides a production cost of 194 W/A at 89% propellant efficiency with a flatness parameter of 0.55. One of the primary MCDC concerns is the effect an operating DCA has on the two dormant cathodes. Multiple experiments are conducted to determine plasma properties throughout the MCDC and near the dormant cathodes, including using "dummy" cathodes outfitted with plasma diagnostics and internal plasma property mapping. Results are utilized in an erosion analysis that suggests dormant cathodes suffer a maximum pre-operation erosion rate of 5--15 mum/khr (active DCA maximum erosion is 70 mum/khr). Lifetime predictions indicate that triple-DCA MCDC lifetime is approximately 2.5 times longer than a single-DCA thruster. Also, utilization of new keeper materials, such as carbon graphite, may significantly decrease both active and dormant cathode erosion, leading to a further increase in thruster lifetime. Finally, a theory based on the near-DCA plasma potential structure and propellant flow rate effects

  19. Formation of disinfection byproducts in typical Chinese drinking water.

    PubMed

    Liu, Wenbo; Zhao, Yanmei; Chow, Christopher W K; Wang, Dongsheng

    2011-01-01

    Eight typical drinking water supplies in China were selected in this study. Both source and tap water were used to investigate the occurrence of chlorinated disinfection byproducts (DBPs), and seasonal variation in the concentrations of trihalomethanes (THMs) of seven water sources was compared. The results showed that the pollution level for source water in China, as shown by DBP formation potential, was low. The most encountered DBPs were chloroform, dichloroacetic acid, trichloroacetic acid, and chlorodibromoacetic acid. The concentration of every THMs and haloacetic acid (HAA) compound was under the limit of standards for drinking water quality. The highest total THMs concentrations were detected in spring.

  20. Extraction of Cell-Wall Polysaccharide Antigen from Streptococci

    PubMed Central

    Slade, Hutton D.

    1965-01-01

    Slade, Hutton D. (Northwestern University Medical School, Chicago, Ill., and Max-Planck Institut für Immunbiologie, Freiburg, Germany). Extraction of cell-wall polysaccharide antigen from streptococci. J. Bacteriol. 90:667–672. 1965.—The carbohydrate grouping antigens in the cell walls of streptococci belonging to groups A, E, G, L, and T were extracted with 5% trichloroacetic acid at 90 C. The antigens were removed also from dry whole cells by extraction with trichloroacetic acid followed by treatment with phenol-water. Details of the methods are presented. The antigens obtained by use of either of these procedures were suitable for studies on immunological specificity and chemical structure. Quantitative enzymatic and chemical analyses of two group E antigens and one group T preparation showed the presence of l-rhamnose (22 to 44%), d-glucose (7 to 22%), d-galactose (T antigen only, 26%), glucosamine (2 to 16%), and galactosamine (T antigen only, 3%). In addition, analyses of A and G antigen preparations are presented. The protein and phosphate content of the A and E antigens were about 1% each. Quantitative precipitin curves of these antigens are presented. PMID:16562065

  1. HPLC/ELSD analysis of amidated bile acids: an effective and rapid way to assist continuous flow chemistry processes.

    PubMed

    Sardella, Roccaldo; Gioiello, Antimo; Ianni, Federica; Venturoni, Francesco; Natalini, Benedetto

    2012-10-15

    The employment of the flow N-acyl amidation of natural bile acids (BAs) required the in-line connection with suitable analytical tools enabling the determination of reaction yields as well as of the purity grade of the synthesized glyco- and tauro-conjugated derivatives. In this framework, a unique HPLC method was successfully established and validated for ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), deoxycholic (DCA) and cholic (CA) acids, as well as the corresponding glyco- and tauro-conjugated forms. Because of the shared absence of relevant chromophoric moieties in the sample structure, an evaporative light scattering detector (ELSD) was profitably utilized for the analysis of such steroidal species. For each of the investigated compounds, all the runs were contemporarily carried out on the acidic free and the two relative conjugated variants. The different ELSD response of the free and the corresponding conjugated BAs, imposed to build-up separate calibration curves. In all the cases, very good precision (RSD% values ranging from 1.04 to 6.40% in the long-period) and accuracy (Recovery% values ranging from 96.03 to 111.14% in the long-period) values along with appreciably low LOD and LOQ values (the former being within the range 1-27 ng mL(-1) and the latter within the range 2-44 ng mL(-1)) turned out. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats

    PubMed Central

    Chai, Jin; Du, Xiaohuang; Chen, Sheng; Feng, XinChan; Cheng, Ying; Zhang, Liangjun; Gao, Yu; Li, Shaoxue; He, Xiaochong; Wang, Rongquan; Zhou, Xiangdong; Yang, Yong; Luo, Weizao; Chen, Wensheng

    2015-01-01

    Background & aims: Oleanolic acid is abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb for the treatment of jaundice. However, the hepatoprotective role of oleanolic acid in obstructive cholestasis and its underlying molecular mechanism are unclear. Methods: Normal rats and bile duct-ligated (BDL) rats were given oleanolic acid and serum biochemistry, bile salts, and pro-inflammatory factors were measured, as well as the expression levels of liver bile acid synthesis and detoxification enzymes, membrane transporters, nuclear receptors, and transcriptional factors. Results: Oral administration of oleanolic acid at 100 mg/kg did not cause rat liver injury. However, it significantly reduced the serum levels of alanine aminotransferase (ALT) on days 7 and 14, aspartate aminotransferase (AST) and TNF-α on day 14, and alkaline phosphatase (ALP) and IL-1β on days 3, 7, and 14 in the BDL rats. Furthermore, the serum levels of total bile acid (TBA) and bile acids, including CDCA, CA, DCA, and Tα/βMCA were significantly reduced by oleanolic acid on day 3 in the BDL rats. In addition, the expression levels of detoxification enzymes Cyp3a, Ugt2b, Sult2a1, Gsta1-2, and Gstm1-3, membrane transporters Mrp3, Mrp4, Ostβ, Mdr1, Mdr2, and Bsep, nuclear receptors Pxr, Vdr, Hnf4α, Rxrα, Rarα, Lxr, and Lrh-1, and transcriptional factors Nrf2, Hnf3β, and Ahr were significantly increased in oleanolic acid-treated rats. Conclusion: We demonstrated that the oral administration of oleanolic acid attenuates liver injury, inflammation, and cholestasis in BDL rats. The anti-cholestatic effect may be associated with the induction of hepatic detoxification enzymes and efflux transporters mediated by nuclear receptors and transcriptional factors. PMID:25932098

  3. Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart.

    PubMed

    Matsuhashi, Tomohiro; Hishiki, Takako; Zhou, Heping; Ono, Tomohiko; Kaneda, Ruri; Iso, Tatsuya; Yamaguchi, Aiko; Endo, Jin; Katsumata, Yoshinori; Atsushi, Anzai; Yamamoto, Tsunehisa; Shirakawa, Kohsuke; Yan, Xiaoxiang; Shinmura, Ken; Suematsu, Makoto; Fukuda, Keiichi; Sano, Motoaki

    2015-05-01

    Dichloroacetate (DCA) promotes pyruvate entry into the Krebs cycle by inhibiting pyruvate dehydrogenase (PDH) kinase and thereby maintaining PDH in the active dephosphorylated state. DCA has recently gained attention as a potential metabolic-targeting therapy for heart failure but the molecular basis of the therapeutic effect of DCA in the heart remains a mystery. Once-daily oral administration of DCA alleviates pressure overload-induced left ventricular remodeling. We examined changes in the metabolic fate of pyruvate carbon (derived from glucose) entering the Krebs cycle by metabolic interventions of DCA. (13)C6-glucose pathway tracing analysis revealed that instead of being completely oxidized in the mitochondria for ATP production, DCA-mediated PDH dephosphorylation results in an increased acetyl-CoA pool both in control and pressure-overloaded hearts. DCA induces hyperacetylation of histone H3K9 and H4 in a dose-dependent manner in parallel to the dephosphorylation of PDH in cultured cardiomyocytes. DCA administration increases histone H3K9 acetylation in in vivo mouse heart. Interestingly, DCA-dependent histone acetylation was associated with an up-regulation of 2.3% of genes (545 out of 23,474 examined). Gene ontology analysis revealed that these genes are highly enriched in transcription-related categories. This evidence suggests that sustained activation of PDH by DCA results in an overproduction of acetyl-CoA, which exceeds oxidation in the Krebs cycle and results in histone acetylation. We propose that DCA-mediated PDH activation has the potential to induce epigenetic remodeling in the heart, which, at least in part, forms the molecular basis for the therapeutic effect of DCA in the heart. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Potentiation of mitochondrial dysfunction in tumor cells by conjugates of metabolic modulator dichloroacetate with a Pt(IV) derivative of oxaliplatin.

    PubMed

    Zajac, Juraj; Kostrhunova, Hana; Novohradsky, Vojtech; Vrana, Oldrich; Raveendran, Raji; Gibson, Dan; Kasparkova, Jana; Brabec, Viktor

    2016-03-01

    The molecular and cellular mechanisms of enhanced toxic effects in tumor cells of the Pt(IV) derivatives of antitumor oxaliplatin containing axial dichloroacetate (DCA) ligands were investigated. DCA ligands were chosen because DCA has shown great potential as an apoptosis sensitizer and anticancer agent reverting the Wartburg effect. In addition, DCA reverses mitochondrial changes in a wide range of cancers, promoting tumor cell apoptosis in a mitochondrial-dependent pathway. We demonstrate that (i) the transformation of oxaliplatin to its Pt(IV) derivatives containing axial DCA ligands markedly enhances toxicity in cancer cells and helps overcome inherent and acquired resistance to cisplatin and oxaliplatin; (ii) a significant fraction of the intact molecules of DCA conjugates with Pt(IV) derivative of oxaliplatin accumulates in cancer cells where it releases free DCA; (iii) mechanism of biological action of the Pt(IV) derivatives of oxaliplatin containing DCA ligands is connected with the effects of DCA released in cancer cells from the Pt(IV) prodrugs on mitochondria and metabolism of glucose; (iv) treatments with the Pt(IV) derivatives of oxaliplatin containing DCA ligands activate an autophagic response in human colorectal cancer cells; (v) the toxic effects in cancer cells of the Pt(IV) derivatives of oxaliplatin containing DCA ligands can be potentiated if cells are treated with these prodrugs in combination with 5-fluorouracil. These properties of the Pt(IV) derivatives of oxaliplatin containing DCA ligands provide opportunities for further development of new platinum-based agents with the capability of killing cancer cells resistant to conventional antitumor platinum drugs used in the clinic. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. ASSESSING THE EFFECTS OF DICHLOROACETIC ACID (DCA) USING A MULTI-ENDPOINT MEDAKA ASSAY

    EPA Science Inventory

    In regulating the safety of water, EPA makes decisions on what chemical contaminants to regulate and at what levels. To make these decisions, the EPA needs hazard identification and dose-response information. Current rodent methods for generating required information have limita...

  6. Changes in extrathymic T cells in the liver and intestinal intraepithelium in mice with obstructive jaundice.

    PubMed

    Ueno, Kimihiko; Ajiki, Tetsuo; Watanabe, Hisami; Abo, Toru; Takeyama, Yoshifumi; Onoyama, Hirohiko; Kuroda, Yoshikazu

    2004-03-01

    Recently, T cells were classified into two categories: intrathymic T cells (ITCs; thymus-derived T cells) and extrathymic T cells (ETCs). ETC, localized in the liver and intestinal intraepithelium (IE), play an important immunologic role in the suppressed condition of T-cell development in the thymus. Given the fact that complications of surgery in patients with obstructive jaundice are often related to immunosuppression in the gut-liver circulation, we attempted to investigate the changes in the proportion of ETCs in mice with obstructive jaundice. Three mice models were prepared ( n = 10 per group): sham group with simple laparotomy; ligation group with common bile duct ligation; deoxycholic acid (DCA) group with an oral intake of DCA as a model of the presence of bile salts in the gut lumen. In each model, total mononuclear cells (MNCs), ITCs in the thymus, and ETCs in the liver and IE were counted using monoclonal antibodies in conjunction with a two-color immunofluorescence test by flow cytometry. In the ligation group the number of MNCs was reduced in the thymus and IE, and only those in the IE recovered after oral intake of DCA. A decrease of ITCs in the thymus and the increase in ETCs in the liver and IE occurred simultaneously during the early phase of biliary obstruction. At day 7 after biliary obstruction, ETCs in the livers of the DCA and ligation groups decreased to nearly the level in the sham group. However, on day 7 the ETCs in the IE remained significantly higher in the DCA group than in the ligation group. These results suggested that ETCs can act in place of ITCs at an early phase of obstructive jaundice, and the presence of bile in the gut lumen may be associated with the consumption of ETCs in the IE, a reaction that may bring about improved immunoreactivity.

  7. Monte Carlo decision curve analysis using aggregate data.

    PubMed

    Hozo, Iztok; Tsalatsanis, Athanasios; Djulbegovic, Benjamin

    2017-02-01

    Decision curve analysis (DCA) is an increasingly used method for evaluating diagnostic tests and predictive models, but its application requires individual patient data. The Monte Carlo (MC) method can be used to simulate probabilities and outcomes of individual patients and offers an attractive option for application of DCA. We constructed a MC decision model to simulate individual probabilities of outcomes of interest. These probabilities were contrasted against the threshold probability at which a decision-maker is indifferent between key management strategies: treat all, treat none or use predictive model to guide treatment. We compared the results of DCA with MC simulated data against the results of DCA based on actual individual patient data for three decision models published in the literature: (i) statins for primary prevention of cardiovascular disease, (ii) hospice referral for terminally ill patients and (iii) prostate cancer surgery. The results of MC DCA and patient data DCA were identical. To the extent that patient data DCA were used to inform decisions about statin use, referral to hospice or prostate surgery, the results indicate that MC DCA could have also been used. As long as the aggregate parameters on distribution of the probability of outcomes and treatment effects are accurately described in the published reports, the MC DCA will generate indistinguishable results from individual patient data DCA. We provide a simple, easy-to-use model, which can facilitate wider use of DCA and better evaluation of diagnostic tests and predictive models that rely only on aggregate data reported in the literature. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumar, Ajay; Kant, Shiva; Singh, Sukh Mahendra, E-mail: sukhmahendrasingh@yahoo.com

    Targeting of tumor metabolism is emerging as a novel therapeutic strategy against cancer. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been shown to exert a potent tumoricidal action against a variety of tumor cells. The main mode of its antineoplastic action implicates a shift of glycolysis to oxidative metabolism of glucose, leading to generation of cytotoxic reactive oxygen intermediates. However, the effect of DCA on tumor microenvironment, which in turn regulates tumor cell survival; remains speculative to a large extent. It is also unclear if DCA can exert any modulatory effect on the process of hematopoiesis, whichmore » is in a compromised state in tumor-bearing hosts undergoing chemotherapy. In view of these lacunas, the present study was undertaken to investigate the so far unexplored aspects with respect to the molecular mechanisms of DCA-dependent tumor growth retardation and chemosensitization. BALB/c mice were transplanted with Dalton's lymphoma (DL) cells, a T cell lymphoma of spontaneous origin, followed by administration of DCA with or without cisplatin. DCA-dependent tumor regression and chemosensitization to cisplatin was found to be associated with altered repertoire of key cell survival regulatory molecules, modulated glucose metabolism, accompanying reconstituted tumor microenvironment with respect to pH homeostasis, cytokine balance and alternatively activated TAM. Moreover, DCA administration also led to an alteration in the MDR phenotype of tumor cells and myelopoietic differentiation of macrophages. The findings of this study shed a new light with respect to some of the novel mechanisms underlying the antitumor action of DCA and thus may have immense clinical applications. - Highlights: • DCA modulates tumor progression and chemoresistance. • DCA alters molecules regulating cell survival, glucose metabolism and MDR. • DCA reconstitutes biophysical and cellular composition of tumor microenvironment

  9. Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

    PubMed

    Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

    2006-12-01

    Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

  10. Stimulation of 3,4-dichloroaniline mineralization by aniline.

    PubMed Central

    You, I S; Bartha, R

    1982-01-01

    Mineralization of free and of humus-bound 3,4-dichloroaniline (DCA) by a Pseudomonas putida strain isolated by analog enrichment was greatly enhanced in the presence of aniline. The addition of aniline to soil that contained 0.2 to 100 micrograms of DCA per g in free or in humus-bound form increased the mineralization rates of DCA severalfold. Within the concentration ranges tested, absolute mineralization of DCA per unit time was positively correlated with both increasing DCA and increasing aniline concentrations. The specific enrichment of microbial populations and the induction of pathways that can co-metabolize DCA are the most plausible explanations for the effect of aniline. The observed phenomenon points to a potential approach for eliminating xenobiotic pollutants from contaminated soils. PMID:7138005

  11. A liquid chromatography with tandem mass spectrometry method for simultaneous determination of UTL-5g and its metabolites in human plasma.

    PubMed

    Shaw, Jiajiu; Wiegand, Richard; Wu, Jianmei; Bao, Xun; Valeriote, Frederick; Li, Jing

    2015-06-01

    UTL-5g is a novel small-molecule TNF-α inhibitor under investigation as both a chemoprotective and radioprotective agent. Animal studies showed that pretreatment of UTL-5g protected kidney, liver, and platelets from cisplatin-induced toxicity. In addition, UTL-5g reduced liver and lung injuries induced by radiation in vivo. Although a number of preclinical studies have been conducted, a validated bioanalytical method for UTL-5g in human plasma has not been published. In this work, a sensitive and reproducible reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the determination of UTL-5g and its metabolites, 5-methylisoxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA), in human plasma. The method involves a simple methanol precipitation step followed by injection of the supernatant onto a Waters 2695 HPLC system coupled with a Waters Quattro Micro™ triple quadrupole mass spectrometer. Chromatographic separation was accomplished using a Waters Nova-Pak C18 column maintained at 30°C, running at gradient mode with mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in methanol at a flow rate of 0.2mL/min. The analytes were monitored under positive electrospray ionization (ESI). Quantitation of these compounds in plasma was linear from 0.05 to 10μM. The lower limit of quantitation (LLOQ) was 0.05, 0.1, and 0.2μM for UTL-5g, ISOX and DCA, respectively. The accuracy and intra-and inter-day precisions were within the generally accepted criteria for bioanalytical method (<15%). This method provides a practical tool to measure and characterize the plasma concentration-time profiles for UTL-5g and its metabolites, ISOX and DCA. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Chlorination of humic materials: Byproduct formation and chemical interpretations

    USGS Publications Warehouse

    Reckhow, D.A.; Singer, P.C.; Malcolm, R.L.

    1990-01-01

    Ten aquatic humic and fulvic acids were isolated and studied with respect to their reaction with chlorine. Yields of TOX, chloroform, trichloroacetic acid, dichloroacetic acid, dichloroacetonitrile, and 1,1,1-trichloropropanone were measured at pH 7 and 12. Humic acids produced higher concentrations than their corresponding fulvic acids of all byproducts except 1,1,1-trichloropropanone. Chlorine consumption and byproduct formation were related to fundamental chemical characteristics of the humic materials. A statistical model was proposed for activated aromatic content based on 13C NMR and base titration data. The values estimated from this model were found to be well correlated with chlorine consumption. Specific byproduct formation was related to UV absorbance, nitrogen content, or the activated aromatic content. ?? 1990 American Chemical Society.

  13. Viscosity, conductivity, and electrochemical property of dicyanamide ionic liquids

    NASA Astrophysics Data System (ADS)

    Yuan, Wen-Li; Yang, Xiao; He, Ling; Xue, Ying; Qin, Song; Tao, Guo-Hong

    2018-03-01

    The instructive structure-property relationships of ionic liquids (ILs) can be put to task-specific design of new functionalized ILs. The dicyanamide (DCA) ILs are typical CHN type ILs which are halogen free, chemical stable, low-viscous and fuel-rich. The transport properties of DCA ionic liquids are significant for their applications as solvents, electrolytes and hypergolic propellants. This work systematically investigates several important transport properties of four DCA ILs ([C4mim][N(CN)2], [C4m2im][N(CN)2], N4442[N(CN)2], and N8444[N(CN)2]) including viscosity, conductivity, and electrochemical property at different temperatures. The melting points, temperature-dependent viscosities and conductivities reveal the structure-activity relationship of four DCA ILs. From the Walden plots, the imidazolium cations exhibit stronger cation–anion attraction than the ammonium cations. DCA ILs have relatively high values of electrochemical windows (EWs), which indicates that the DCA ILs are potential candidates for electrolytes in electrochemical applications. The cyclic voltammograms of Eu(III) in these DCA ILs at GC working electrode at various temperatures 303–333 K consists of quasi-reversible waves. The electrochemical properties of the DCA ILs are also dominated by the cationic structures. The current intensity (ip), the diffusion coefficients (Do), the charge transfer rate constants (ks) of Eu(III) in DCA ILs all increased with the molar conductivities increased. The cationic structure-transport property relationships of DCA ILs were constructed for designing novel functionalized ILs to fulfill specific demands.

  14. Viscosity, Conductivity, and Electrochemical Property of Dicyanamide Ionic Liquids

    PubMed Central

    Yuan, Wen-Li; Yang, Xiao; He, Ling; Xue, Ying; Qin, Song; Tao, Guo-Hong

    2018-01-01

    The instructive structure-property relationships of ionic liquids (ILs) can be put to task-specific design of new functionalized ILs. The dicyanamide (DCA) ILs are typical CHN type ILs which are halogen free, chemical stable, low-viscous, and fuel-rich. The transport properties of DCA ionic liquids are significant for their applications as solvents, electrolytes, and hypergolic propellants. This work systematically investigates several important transport properties of four DCA ILs ([C4mim][N(CN)2], [C4m2im][N(CN)2], N4442[N(CN)2], and N8444[N(CN)2]) including viscosity, conductivity, and electrochemical property at different temperatures. The melting points, temperature-dependent viscosities and conductivities reveal the structure-activity relationship of four DCA ILs. From the Walden plots, the imidazolium cations exhibit stronger cation–anion attraction than the ammonium cations. DCA ILs have relatively high values of electrochemical windows (EWs), which indicates that the DCA ILs are potential candidates for electrolytes in electrochemical applications. The cyclic voltammograms of Eu(III) in these DCA ILs at GC working electrode at various temperatures 303–333 K consists of quasi-reversible waves. The electrochemical properties of the DCA ILs are also dominated by the cationic structures. The current intensity (ip), the diffusion coefficients (Do), the charge transfer rate constants (ks) of Eu(III) in DCA ILs all increased with the molar conductivities increased. The cationic structure-transport property relationships of DCA ILs were constructed for designing novel functionalized ILs to fulfill specific demands. PMID:29600245

  15. Acid- and base-catalysis in the mononuclear rearrangement of some (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole in toluene: effect of substituents on the course of reaction.

    PubMed

    D'Anna, Francesca; Frenna, Vincenzo; Ghelfi, Franco; Marullo, Salvatore; Spinelli, Domenico

    2011-04-15

    The reaction rates for the rearrangement of eleven (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole 3a-k into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas 4a-k in the presence of trichloroacetic acid or of piperidine have been determined in toluene at 313.1 K. The results have been related to the effect of the aryl substituent by using Hammett and/or Ingold-Yukawa-Tsuno correlations and have been compared with those previously collected in a protic polar solvent (dioxane/water) as well as with those on the analogous rearrangement of the corresponding (Z)-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole 1a-k in benzene. Some light can thus be shed on the general differences of chemical reactivity between protic polar (or dipolar aprotic) and apolar solvents.

  16. Dichloroacetate toxicokinetics and disruption of tyrosine catabolism in B6C3F1 mice: dose-response relationships and age as a modifying factor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schultz, Irv R.; Merdink, James L.; Gonzalez-Leon, Alberto

    Dichloroacetate (DCA) is a well established rodent carcinogen commonly found in municipal drinking water supplies. Previous toxicokinetic studies have established that elimination of DCA is controlled by liver metabolism. DCA metabolism occurs by the cytosolic enzyme glutathione-S-transferase-zeta (GSTz). An important feature of the GSTz pathway is the autoinhibition of metabolism due to suicide inactivation of GSTz by DCA resulting in a direct reduction in GSTz activity. GSTz is identical to a key tyrosine catabolism enzyme known as maleylacetoacetate isomerase (MAAI; EC 5.3.1.2). In the tyrosine metabolism pathway, GSTz plays a critical role in catalyzing the isomerization of maleylacetoacetate to fumarylacetoacetate.more » Disruption of tyrosine catabolism has been linked to increased cancer risk in humans. We studied the elimination of i.v. doses of DCA to juvenile (8 week) and senescent (60 week) mice previously treated with DCA in their drinking water for 2 or 54 weeks. The diurnal change in blood concentrations of DCA was also monitored in mice exposed to three different drinking water concentrations of DCA (2.0, 0.5 and 0.05 g/L). Additional experiments measured the in-vitro metabolism of DCA in liver homogenates prepared from treated mice given various recovery times following treatment. The MAAI activity was also measured in liver cytosol obtained from treated mice. Results indicate juvenile mice were the most sensitive to changes in DCA elimination after drinking water treatment. MAAI activity was reduced up to 80% in liver cytosol from treated mice. These results indicate that inactivation and re-synthesis of GSTz is a highly dynamic process and is supportive of the hypothesis that decreased MAAI activity is a contributing factor in the carcinogenesis of DCA.« less

  17. Directional coronary atherectomy (DCA)

    MedlinePlus Videos and Cool Tools

    ... catheter called a nosecone, and removed after the intervention is complete. Together with rotation of the catheter, ... artery to keep the vessel open. After the intervention is completed the doctor injects contrast media and ...

  18. An enzyme-linked immunosorbent assay-based system for determining the physiological level of poly(ADP-ribose) in cultured cells.

    PubMed

    Ida, Chieri; Yamashita, Sachiko; Tsukada, Masaki; Sato, Teruaki; Eguchi, Takayuki; Tanaka, Masakazu; Ogata, Shin; Fujii, Takahiro; Nishi, Yoshisuke; Ikegami, Susumu; Moss, Joel; Miwa, Masanao

    2016-02-01

    PolyADP-ribosylation is mediated by poly(ADP-ribose) (PAR) polymerases (PARPs) and may be involved in various cellular events, including chromosomal stability, DNA repair, transcription, cell death, and differentiation. The physiological level of PAR is difficult to determine in intact cells because of the rapid synthesis of PAR by PARPs and the breakdown of PAR by PAR-degrading enzymes, including poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3. Artifactual synthesis and/or degradation of PAR likely occurs during lysis of cells in culture. We developed a sensitive enzyme-linked immunosorbent assay (ELISA) to measure the physiological levels of PAR in cultured cells. We immediately inactivated enzymes that catalyze the synthesis and degradation of PAR. We validated that trichloroacetic acid is suitable for inactivating PARPs, PARG, and other enzymes involved in metabolizing PAR in cultured cells during cell lysis. The PAR level in cells harvested with the standard radioimmunoprecipitation assay buffer was increased by 450-fold compared with trichloroacetic acid for lysis, presumably because of activation of PARPs by DNA damage that occurred during cell lysis. This ELISA can be used to analyze the biological functions of polyADP-ribosylation under various physiological conditions in cultured cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Metabolic Engineering of Raoultella ornithinolytica BF60 for Production of 2,5-Furandicarboxylic Acid from 5-Hydroxymethylfurfural

    PubMed Central

    Hossain, Gazi Sakir; Yuan, Haibo; Li, Jianghua; Shin, Hyun-dong; Wang, Miao; Du, Guocheng; Chen, Jian

    2016-01-01

    ABSTRACT 2,5-Furandicarboxylic acid (FDCA) is an important renewable biotechnological building block because it serves as an environmentally friendly substitute for terephthalic acid in the production of polyesters. Currently, FDCA is produced mainly via chemical oxidation, which can cause severe environmental pollution. In this study, we developed an environmentally friendly process for the production of FDCA from 5-hydroxymethyl furfural (5-HMF) using a newly isolated strain, Raoultella ornithinolytica BF60. First, R. ornithinolytica BF60 was identified by screening and was isolated. Its maximal FDCA titer was 7.9 g/liter, and the maximal molar conversion ratio of 5-HMF to FDCA was 51.0% (mol/mol) under optimal conditions (100 mM 5-HMF, 45 g/liter whole-cell biocatalyst, 30°C, and 50 mM phosphate buffer [pH 8.0]). Next, dcaD, encoding dicarboxylic acid decarboxylase, was mutated to block FDCA degradation to furoic acid, thus increasing FDCA production to 9.2 g/liter. Subsequently, aldR, encoding aldehyde reductase, was mutated to prevent the catabolism of 5-HMF to HMF alcohol, further increasing the FDCA titer, to 11.3 g/liter. Finally, the gene encoding aldehyde dehydrogenase 1 was overexpressed. The FDCA titer increased to 13.9 g/liter, 1.7 times that of the wild-type strain, and the molar conversion ratio increased to 89.0%. IMPORTANCE In this work, we developed an ecofriendly bioprocess for green production of FDCA in engineered R. ornithinolytica. This report provides a starting point for further metabolic engineering aimed at a process for industrial production of FDCA using R. ornithinolytica. PMID:27795308

  20. [Diagnosis and treatment guidelines for difficult-to-control asthma in children].

    PubMed

    Navarro Merino, M; Andrés Martín, A; Asensio de la Cruz, O; García García, M L; Liñán Cortes, S; Villa Asensi, J R

    2009-12-01

    Children suffering from difficult-to-control asthma (DCA) require frequent appointments with their physician, complex treatment regimes and often admissions to hospital. Less than 5% of the asthmatic population suffer this condition. DCA must be correctly characterised to rule out false causes of DCA and requires making a differential diagnosis from pathologies that mimic asthma, comorbidity, environmental and psychological factors, and analysing the factors to determine poor treatment compliance. In true DCA cases, inflammation studies (exhaled nitric oxide, induced sputum, broncho-alveolar lavage and bronchial biopsy), pulmonary function and other clinical aspects can classify DCA into different phenotypes which could make therapeutic decision-making easier.

  1. TCA precipitation.

    PubMed

    Koontz, Laura

    2014-01-01

    Trichloroacetic acid (TCA) precipitation of proteins is commonly used to concentrate protein samples or remove contaminants, including salts and detergents, prior to downstream applications such as SDS-PAGE or 2D-gels. TCA precipitation denatures the protein, so it should not be used if the protein must remain in its folded state (e.g., if you want to measure a biochemical activity of the protein). © 2014 Elsevier Inc. All rights reserved.

  2. Induction of anti-melanoma CTL response using DC transfected with mutated mRNA encoding full-length Melan-A/MART-1 antigen with an A27L amino acid substitution.

    PubMed

    Abdel-Wahab, Zeinab; Kalady, Matthew F; Emani, Sirisha; Onaitis, Mark W; Abdel-Wahab, Omar I; Cisco, Robin; Wheless, Lee; Cheng, Tsung-Yen; Tyler, Douglas S; Pruitt, Scott K

    2003-08-01

    Modification of the parental immunodominant Melan-A/MART-1 peptide (MART-1(26-35)) by replacing the alanine with leucine (A27L) enhances its immunogenicity. Because of the reported advantages of RNA over peptides in DC vaccines, we sought to mutate the MART-1 gene to encode a full-length MART-1 antigen with an A27L amino acid substitution. Human DC were transfected with A27L-mutated MART-1 RNA (A27L RNA) or native MART-1 RNA, and then used to stimulate autologous T cells from a series of 8 HLA-A2+ volunteers. After three stimulations, all CTL induced with DC/A27L RNA exhibited more tetramer+ cells, and demonstrated stronger antigen-specific IFNgamma-secreting activity compared to CTL induced with DC/native RNA. A potent MART-1-specific, and predominantly class-I-restricted lysis was detected in most CTL induced with DC/A27L RNA, while native RNA-induced CTL showed minimal and non-specific lysis. HLA-A2+ DC and MART-1 negative/A2+ melanoma cells transfected with the A27L RNA were recognized and killed by MART-1-specific CTL, suggesting that these APC efficiently processed the A27L RNA and presented correct MART-1-specific epitope(s). In summary, introducing an A27L mutation into the MART-1 full-length mRNA sequence enhanced the immunogenicity of the encoded MART-1 Ag. The ease with which such a mutation can be made in RNA presents another potential advantage of using RNA for immunotherapy. Our results support considering this strategy for enhancing the immunogenicity of DC-based RNA vaccines.

  3. Functional Intestinal Bile Acid 7α-Dehydroxylation by Clostridium scindens Associated with Protection from Clostridium difficile Infection in a Gnotobiotic Mouse Model.

    PubMed

    Studer, Nicolas; Desharnais, Lyne; Beutler, Markus; Brugiroux, Sandrine; Terrazos, Miguel A; Menin, Laure; Schürch, Christian M; McCoy, Kathy D; Kuehne, Sarah A; Minton, Nigel P; Stecher, Bärbel; Bernier-Latmani, Rizlan; Hapfelmeier, Siegfried

    2016-01-01

    Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms are well-adapted to normal concentrations of bile acids in the gut. In contrast, physiological concentrations of the various intestinal bile acid species play an important role in the resistance to intestinal colonization by pathogens such as Clostridium difficile . Antibiotic therapy can perturb the gut microbiota and thereby impair the production of protective secondary bile acids. The most important bile acid transformation is 7α-dehydroxylation, producing deoxycholic acid (DCA) and lithocholic acid (LCA). The enzymatic pathway carrying out 7α-dehydroxylation is restricted to a narrow phylogenetic group of commensal bacteria, the best-characterized of which is Clostridium scindens . Like many other intestinal commensal species, 7-dehydroxylating bacteria are understudied in vivo . Conventional animals contain variable and uncharacterized indigenous 7α-dehydroxylating organisms that cannot be selectively removed, making controlled colonization with a specific strain in the context of an undisturbed microbiota unfeasible. In the present study, we used a recently established, standardized gnotobiotic mouse model that is stably associated with a simplified murine 12-species "oligo-mouse microbiota" (Oligo-MM 12 ). It is representative of the major murine intestinal bacterial phyla, but is deficient for 7α-dehydroxylation. We find that the Oligo-MM 12 consortium carries out bile acid deconjugation, a prerequisite for 7α-dehydroxylation, and confers no resistance to C. difficile infection (CDI). Amendment of Oligo-MM 12 with C. scindens normalized the large intestinal bile acid composition by reconstituting 7

  4. Modifying influence of swine-serum-induced liver fibrosis on development of preneoplastic lesions in rat liver.

    PubMed

    Wada, S; Kato, T; Mutai, M; Ozaki, K; Yamaguchi, S; Kim, D J; Baba-Toriyama, H; Asamoto, M; Ito, N; Tsuda, H

    1996-03-01

    Modifying effects of fibrosis or a cirrhotic state, caused by treatment with swine serum (SS), on the induction of preneoplastic focal lesions were assessed in a rat medium-term liver bioassay model for the detection of environmental carcinogens, in which the test compound is administered during the promotion phase after initiation with diethylnitrosamine. In experiment I, repeated intraperitoneal administration of SS concomitantly with the hepatopromoting agent deoxycholic acid (DCA) or phenobarbital (PB) resulted in a cirrhotic state and a significant increase in the number or size of preneoplastic glutathione S-transferase placental form (GST-P)-positive liver cell foci as compared to the corresponding DCA or PB alone groups. In experiment II, SS was given prior to commencement of the same medium-term bioassay system, in which a known hepatopromoting agent, DCA, 17-alpha-ethynylestradiol, or 2-acetylaminofluorene, was applied. In this case, the liver did not show obvious cirrhotic change and, rather than any enhancement, slight inhibition of promotion occurred. The results indicate that a coexisting, but not a pre-existing, cirrhotic condition acts to increase growth pressure on GST-P+ preneoplastic foci, and suggest that concomitant administration of SS with the promoting agent could be applied to improve the sensitivity of the assay protocol.

  5. Metformin combined with sodium dichloroacetate promotes B leukemic cell death by suppressing anti-apoptotic protein Mcl-1

    PubMed Central

    Melloni, Elisabetta; Gilli, Paola; Bertolasi, Valerio; Casciano, Fabio; Rigolin, Gian Matteo; Zauli, Giorgio; Secchiero, Paola

    2016-01-01

    Metformin and the mitochondrial targeting dichloroacetate (DCA) have recently received attention due to their ability to inhibit anaerobic glycolysis, which renders most cancer cells resistant to apoptosis induction. We observed that Metformin alone exhibited a dose-dependent anti-leukemic activity in both B leukemic cell lines and primary B-chronic lymphocytic leukemia (B-CLL) patients' cells and its anti-leukemic activity was enhanced when used in combination with DCA. In order to overcome the problems of poor bioavailability and cellular uptake, which limit DCA efficacy, we have designed and synthetized cocrystals consisting of Metformin and DCA (Met-DCA) at different stoichiometric ratios. Of note, the MetH2++•2DCA− cocrystal exhibited enhanced in vitro anti-leukemic activity, with respect to the treatment with the mix consisting of Metformin plus DCA. In particular, the treatment with the cocrystal MetH2++•2DCA− induced a synergistic apoptotic cell death coupled to a marked down-modulation of the anti-apoptotic Mcl-1 protein. Taken together, our data emphasize that innovative compounds based on Metformin-DCA combination merit to be further evaluated as chemotherapeutic agents for the treatment of B-CLL. PMID:26959881

  6. Interference of psychological factors in difficult-to-control asthma.

    PubMed

    Halimi, Laurence; Vachier, Isabelle; Varrin, Muriel; Godard, Philippe; Pithon, Gérard; Chanez, Pascal

    2007-01-01

    Most patients with asthma can be controlled with suitable medication, but 5-10% of them remain difficult to control despite optimal management. We investigated whether patients with difficult-to-control asthma (DCA) or controlled asthma (CA) differ with respect to psychological factors, such as general control beliefs on life events. DCA was defined as an absence of control despite optimal management. Recent control was measured using the Asthma Control Questionnaire. General control beliefs were investigated using a Locus of Control scale (LOC). Patients with DCA had a significantly higher external LOC as compared to patients with CA (P=0.01). In the DCA group, the hospital admission rate was highly significant in association with the external LOC (P=0.004) as compared to the internal LOC trend. This study showed that patients with DCA had different general control beliefs which might have hampered their management and interfered with their therapeutic adherence. The present findings could enhance management of DCA in a clinical setting.

  7. Dynamic controlled atmosphere and ultralow oxygen storage on 'Gala' mutants quality maintenance.

    PubMed

    Thewes, Fabio Rodrigo; Both, Vanderlei; Brackmann, Auri; Weber, Anderson; de Oliveira Anese, Rogerio

    2015-12-01

    The aim of the present work was to compare the effect of ultralow oxygen (ULO) with dynamic controlled atmosphere (DCA) and controlled atmosphere (CA) on the post storage quality of 'Royal Gala' and 'Galaxy' apples after long-term storage. Two experiments were carried out with 'Royal Gala' and 'Galaxy' apples, in the years 2012 and 2013, respectively. A higher internal ethylene concentration was observed in fruits stored under CA; intermediate concentration in fruits under ULO; and the lowest by fruits stored under DCA-CF (DCA based on chlorophyll fluorescence). Flesh firmness was higher in fruits stored under DCA-CF and ULO differing from CA, in the year 2012, but in 2013 fruits stored under ULO showed the highest flesh firmness, differing from CA fruits. DCA-CF is efficient in quality maintenance of 'Royal Gala' and 'Galaxy' apples. Both 'Gala' mutants stored under ULO show a similar quality maintenance to those stored under DCA-CF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Monocarboxylic and dicarboxylic acids over oceans from the East China Sea to the Arctic Ocean: Roles of ocean emissions, continental input and secondary formation.

    PubMed

    Hu, Qihou; Xie, Zhouqing; Wang, Xinming; Kang, Hui; Zhang, Yuqing; Ding, Xiang; Zhang, Pengfei

    2018-05-30

    Organic acids are major components in marine organic aerosols. Many studies on the occurrence, sources and sinks of organic acids over oceans in the low and middle latitudes have been conducted. However, the understanding of relative contributions of specific sources to organic acids over oceans, especially in the high latitudes, is still inadequate. This study measured organic acids, including C 14:0 - C 32:0 saturated monocarboxylic acids (MCAs), C 16:1 , C 18:1 and C 18:2 unsaturated MCAs, and di-C 4 - di-C 10 dicarboxylic acids (DCAs), in the marine boundary layer from the East China Sea to the Arctic Ocean during the 3rd Chinese Arctic Research Expedition (CHINARE 08). The average concentrations were 18 ± 16 ng/m 3 and 11 ± 5.4 ng/m 3 for ΣMCA and ΣDCA, respectively. The levels of saturated MCAs were much higher than those of unsaturated DCAs, with peaks at C 16:0 , C 18:0 and C 14:0 . DCAs peaked at di-C 4 , followed by di-C 9 and di-C 8 . Concentrations of MCAs and DCAs generally decreased with increasing latitudes. Sources of MCAs and DCAs were further investigated using principal component analysis with a multiple linear regression (PCA-MLR) model. Overall, carboxylic acids originated from ocean emissions, continental input (including biomass burning, anthropogenic emissions and terrestrial plant emissions), and secondary formation. All the five sources contributed to MCAs with ocean emissions as the predominant source (48%), followed by biomass burning (20%). In contrast, only 3 sources (i.e., secondary formation (50%), anthropogenic emissions (41%) and biomass burning (9%)) contributed to DCAs. Furthermore, the sources varied with regions. Over the Arctic Ocean, only secondary formation and anthropogenic emissions contributed to MCAs and DCAs. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Co-occurrence of genes for aerobic and anaerobic biodegradation of dichloroethane in organochlorine-contaminated groundwater.

    PubMed

    Munro, Jacob E; Kimyon, Önder; Rich, Deborah J; Koenig, Joanna; Tang, Sihui; Low, Adrian; Lee, Matthew; Manefield, Mike; Coleman, Nicholas V

    2017-11-01

    1,2-Dichloroethane (DCA) is a problematic groundwater pollutant. Factors influencing the distribution and activities of DCA-degrading bacteria are not well understood, which has hampered their application for bioremediation. Here, we used quantitative PCR to investigate the distribution of putative DCA-dehalogenating bacteria at a DCA-impacted site in Sydney (Australia). The dehalogenase genes dhlA, tceA and bvcA were detected in all groundwater samples (n = 15), while vcrA was found in 11/15 samples. The 16S rRNA gene sequences specific to the dehalogenating genera Dehalobacter, Desulfitobacterium and Dehalogenimonas were detected in 15/15, 13/15 and 13/15 samples, respectively, while Dehalococcoides sequences were found in 9/15 samples. The tceA, bvcA and vcrA genes occurred in the same samples as Dehalococcoides and Dehalobacter. Microcosm experiments confirmed the presence of bacteria capable of dechlorination under anoxic conditions. The abundance of the dhlA gene, which is found in hydrolytic DCA degraders, was positively correlated to the DCA concentration, and was unexpectedly most abundant in samples with low oxygen conditions. A dhlA-containing bacterium isolated from the site (Xanthobacter EL8) was capable of anaerobic growth on DCA under denitrifying conditions. The presence of diverse DCA-dehalogenating bacteria at this site indicates that natural attenuation or biostimulation could be valid approaches for site cleanup. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Formation of 2,4-D bound residues in soils: New insights into microbial metabolism.

    PubMed

    Botero, Liliana Rocío; Mougin, Chistian; Peñuela, Gustavo; Barriuso, Enrique

    2017-04-15

    The microbial contribution to the formation of bound residues in soils is studied by characterizing the metabolic activity of three microorganisms (Trametes versicolor, Fusarium solani and Ralstonia eutropha) on 14 C-2,4-dichlorophenoxyacetic acid (2,4-D) during incubation in synthetic liquid media and soil. A fractionation protocol was applied to quantify the 14 C-2,4-D that was incorporated into the biomass among biomolecular-like fractions. Successive fractionation of microbial biomass was implemented to break up and quantify the methanol/dichloromethane fraction (corresponding to the 14 C-lipid-like fraction), the trichloroacetic acid fraction (or hydrolysed 14 C-polysaccharide-like fraction) and the acid hydrolysable fraction (or the hydrolysed 14 C-protein-like fraction). Relevant differences in the 2,4-D degradation and biomass radioactivity distribution among the three microorganisms were found. The 14 C-protein-like fraction was the most consistent biomass fraction for reflecting the pesticide use capacity of the microorganisms under liquid and soil conditions. 2,4-D and its metabolite 4-chlorophenol were detected in methanol/dichloromethane and trichloroacetic acid fractions of the biomass of microorganisms exhibiting a low capacity to mineralize 2,4-D, thus proving that the microbial participation in the formation of bound residues while conserving the initial pesticide structure under natural soil conditions may be intimately associated with the lipid- and polysaccharide-like constituents. The fractionation protocol differentiates between 14 C that is incorporated into biomass as a biomolecular constituent and the pesticide or its metabolites that accumulate in the biomass and thus correspond to the stricto sensu definition of bound residues. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Use of diagnostic coronary angiography in women and men presenting with acute myocardial infarction: a matched cohort study.

    PubMed

    Bjerking, Louise Hougesen; Hansen, Kim Wadt; Madsen, Mette; Jensen, Jan Skov; Madsen, Jan Kyst; Sørensen, Rikke; Galatius, Søren

    2016-06-01

    Based on evident sex-related differences in the invasive management of patients presenting with acute myocardial infarction (AMI), we sought to identify predictors of diagnostic coronary angiography (DCA) and to investigate reasons for opting out an invasive strategy in women and men. The study was designed as a matched cohort study. We randomly selected 250 female cases from a source population of 4000 patients hospitalized with a first AMI in a geographically confined region of Denmark from January 2010 to November 2011. Each case was matched to a male control on age and availability of cardiac invasive facilities at the index hospital. We systematically reviewed medical records for risk factors, comorbid conditions, clinical presentation, and receipt of DCA. Clinical justifications, as stated by the treating physician, were noted for the subset of patients who did not receive a DCA. Overall, 187 women and 198 men received DCA within 60 days (75 % vs. 79 %, hazard ratio: 0.82 [0.67-1.00], p = 0.047).In the subset of patients who did not receive a DCA (n = 114), clinical justifications for opting out an invasive strategy was not documented for 21 patients (18.4 %). Type 2 myocardial infarction was noted in 11 patients (women versus men; 14.5 % vs. 3.8 %, p = 0.06) and identified as a potential confounder of the sex-DCA relationship. Receipt of DCA was predicted by traditional risk factors for ischaemic heart disease (family history of cardiovascular disease, hypercholesterolemia, and smoking) and clinical presentation (chest pain, ST-segment elevations). Although prevalent in both women and men, the presence of relative contraindications did not prohibit the use of DCA. In this matched cohort of patients with a first AMI, women and men had different clinical presentations despite similar age. However, no differences in the distribution of relative contraindications for DCA were found between the sexes. Type 2 MI posed a potentiel confounder for

  12. Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma

    PubMed Central

    Wicks, Robert T.; Azadi, Javad; Mangraviti, Antonella; Zhang, Irma; Hwang, Lee; Joshi, Avadhut; Bow, Hansen; Hutt-Cabezas, Marianne; Martin, Kristin L.; Rudek, Michelle A.; Zhao, Ming; Brem, Henry; Tyler, Betty M.

    2015-01-01

    Background 3-bromopyruvate (3-BrPA) and dichloroacetate (DCA) are inhibitors of cancer-cell specific aerobic glycolysis. Their application in glioma is limited by 3-BrPA's inability to cross the blood-brain-barrier and DCA's dose-limiting toxicity. The safety and efficacy of intracranial delivery of these compounds were assessed. Methods Cytotoxicity of 3-BrPA and DCA were analyzed in U87, 9L, and F98 glioma cell lines. 3-BrPA and DCA were incorporated into biodegradable pCPP:SA wafers, and the maximally tolerated dose was determined in F344 rats. Efficacies of the intracranial 3-BrPA wafer and DCA wafer were assessed in a rodent allograft model of high-grade glioma, both as a monotherapy and in combination with temozolomide (TMZ) and radiation therapy (XRT). Results 3-BrPA and DCA were found to have similar IC50 values across the 3 glioma cell lines. 5% 3-BrPA wafer-treated animals had significantly increased survival compared with controls (P = .0027). The median survival of rats with the 50% DCA wafer increased significantly compared with both the oral DCA group (P = .050) and the controls (P = .02). Rats implanted on day 0 with a 5% 3-BrPA wafer in combination with TMZ had significantly increased survival over either therapy alone. No statistical difference in survival was noted when the wafers were added to the combination therapy of TMZ and XRT, but the 5% 3-BrPA wafer given on day 0 in combination with TMZ and XRT resulted in long-term survivorship of 30%. Conclusion Intracranial delivery of 3-BrPA and DCA polymer was safe and significantly increased survival in an animal model of glioma, a potential novel therapeutic approach. The combination of intracranial 3-BrPA and TMZ provided a synergistic effect. PMID:25053853

  13. Sand consolidation method

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, B.M.

    1965-10-05

    This is a new and improved sand consolidation method wherein an in-situ curing of a resinous fluid is undertaken. This method does not require that the resinous fluids be catalyzed at the surface of the well or well bore as is the case in previous methods. This method consists of, first, pumping an acid-curable consolidating fluid into the unconsolidated sand or earth formation and, secondly, pumping an oil overflush solution containing a halogenated organic or other organic acid or delayed acid-producing chemical. A small quantity of diesel oilspacer may be used between the plastic catalyst solution. The overflush functions tomore » remove permeability, and its acid or acid producing component promotes subsequent hardening of the remaining film of consolidating fluid. Trichloroacetic acid and benzotrichloride are satisfactory to add to the overflush solution for curing the resins. (17 claims)« less

  14. Chemical peels in active acne and acne scars.

    PubMed

    Kontochristopoulos, Georgios; Platsidaki, Eftychia

    Chemical peeling is a widely used procedure in the management of acne and acne scars. It causes controlled destruction of a part of or the entire epidermis, with or without the dermis, leading to exfoliation and removal of superficial lesions, followed by regeneration of new epidermal and dermal tissues. The most frequently used peeling agents are salicylic acid, glycolic acid, pyruvic acid, lactic acid, mandelic acid, Jessner solution, trichloroacetic acid, and phenol. The appropriate peel is chosen based on the patient's skin type, acne activity, and type of acne scars. Combination peels minimize side effects. In acne scars, chemical peels may be combined with other procedures to achieve better clinical results. A series of chemical peels can lead to significant improvement over a short period, leading to patient satisfaction and maintenance of clinical results. © 2016 Elsevier Inc. All rights reserved. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A New Catabolic Plasmid in Xanthobacter and Starkeya spp. from a 1,2-Dichloroethane-Contaminated Site

    PubMed Central

    Munro, Jacob E.; Liew, Elissa F.; Ly, Mai-Anh

    2016-01-01

    ABSTRACT 1,2-Dichloroethane (DCA) is a problematic xenobiotic groundwater pollutant. Bacteria are capable of biodegrading DCA, but the evolution of such bacteria is not well understood. In particular, the mechanisms by which bacteria acquire the key dehalogenase genes dhlA and dhlB have not been well defined. In this study, the genomic context of dhlA and dhlB was determined in three aerobic DCA-degrading bacteria (Starkeya novella strain EL1, Xanthobacter autotrophicus strain EL4, and Xanthobacter flavus strain EL8) isolated from a groundwater treatment plant (GTP). A haloalkane dehalogenase gene (dhlA) identical to the canonical dhlA gene from Xanthobacter sp. strain GJ10 was present in all three isolates, and, in each case, the dhlA gene was carried on a variant of a 37-kb circular plasmid, which was named pDCA. Sequence analysis of the repA replication initiator gene indicated that pDCA was a member of the pTAR plasmid family, related to catabolic plasmids from the Alphaproteobacteria, which enable growth on aromatics, dimethylformamide, and tartrate. Genes for plasmid replication, mobilization, and stabilization were identified, along with two insertion sequences (ISXa1 and ISPme1) which were likely to have mobilized dhlA and dhlB and played a role in the evolution of aerobic DCA-degrading bacteria. Two haloacid dehalogenase genes (dhlB1 and dhlB2) were detected in the GTP isolates; dhlB1 was most likely chromosomal and was similar to the canonical dhlB gene from strain GJ10, while dhlB2 was carried on pDCA and was not closely related to dhlB1. Heterologous expression of the DhlB2 protein confirmed that this plasmid-borne dehalogenase was capable of chloroacetate dechlorination. IMPORTANCE Earlier studies on the DCA-degrading Xanthobacter sp. strain GJ10 indicated that the key dehalogenases dhlA and dhlB were carried on a 225-kb linear plasmid and on the chromosome, respectively. The present study has found a dramatically different gene organization in more

  16. Genetic Diversity Among Historical Olive (Olea europaea L.) Genotypes from Southern Anatolia Based on SSR Markers.

    PubMed

    Sakar, Ebru; Unver, Hulya; Ercisli, Sezai

    2016-12-01

    Olive (Olea europaea) is an ancient and important crop in both olive oil production and table use. It is important to identify the genetic diversity of olive genetic resources for cultivar development and evaluation of olive germplasm. In the study, 14 microsatellite markers (UDO4, UDO8, UDO9, UDO11, UDO12, UDO22, UDO24, UDO26, UDO28, DCA9, DCA11, DCA13, DCA15, and DCA18) were used to assess the genetic variation on 76 olive (Olea europaea L.) genotypes from Mardin province together with 6 well-known Turkish and 4 well-known foreign reference cultivars. All microsatellite markers showed polymorphism and the number of alleles varied between 9 and 22, with an average of 14.57. The most informative loci were DCA 11 (22 alleles) and DCA 9 (21 alleles). Dendrogram based on genetic distances was constructed for the 86 olive genotypes/cultivars, which revealed the existence of different clusters. The high genetic similarity was evident between Bakırkire2 and Zinnar5 (0.74) genotypes, while the most genetically divergent genotypes were Gürmeşe5 and Yedikardeşler2 (0.19). It was concluded that there was abundant SSR polymorphism in olive germplasm in southern Anatolia in Turkey and could be important for future breeding activities.

  17. Sustaining 1,2-Dichloroethane Degradation in Nanoscale Zero-Valent Iron induced Fenton system by using Sequential H2O2 Addition at Natural pH

    NASA Astrophysics Data System (ADS)

    Phenrat, T.; Le, T. S. T.

    2017-12-01

    1,2-Dichloroethane (1,2-DCA) is a prevalent subsurface contaminant found in groundwater and soil around the world. Nanoscale zero-valent iron (NZVI) is a promising in situ remediation agent for chlorinated organics. Nevertheless, 1,2-DCA is recalcitrant to reductive dechlorination using NZVI. Chemical oxidation using Fenton's reaction with conventional Fe2+ is a valid option for 1,2-DCA remediation with a major technical challenge, i.e. aquifer acidification is needed to maintain Fe2+ for catalytic reaction. In this work, NZVI Fenton's process at neutral pH was applied to degrade 1,2-DCA at high concentration (2,000 mg/L) representing dissolved 1,2-DCA concentration close to non-aqueous phase liquid source zone. Instead of using acidification to maintain dissolved Fe2+ concentration, NZVI Fenton's process is self-catalytic based on oxidative dissolution of NZVI in the present of H2O2. Interfacial H+ is produced at NZVI surface to provide appropriate local pH which continuously releases Fe2+ for Fenton's reaction. Approximately, 87% of 1,2-DCA was degraded at neutral pH with the pseudo first-order rate constant of 0.98 hour-1 using 10 g/L of NZVI and 200 mM of H2O2. However, the reaction was prohibited quickly within 3 hours presumably due to the rapid depletion of H2O2. The application of sequential H2O2 addition provided a better approach to prevent rapid inhibition via controlling the H2O2 concentration in the system to be sufficient but not excess, thus resulting in the higher degradation efficiency (the pseudo first-order rate constant of 0.49 hour-1 and 99 % degradation in 8 hours). Using NZVI with sequential H2O2 addition was also successful in degrading 1,2-DCA sorbed on to soil, yielding 99% removal of 1,2-DCA within 16 hours at the rate constant of 0.23 hour-1, around two times slower than in the system without soil presumably due to rate-limited 1,2-DCA desorption from soil. Mechanistic understanding of how sequential addition of H2O2, in comparison to

  18. PdNi- and Pd-coated electrodes prepared by electrodeposition from ionic liquid for nonenzymatic electrochemical determination of ethanol and glucose in alkaline media.

    PubMed

    Huang, Hsin-Yi; Chen, Po-Yu

    2010-12-15

    Nonenzymatic electrochemical determination of ethanol and glucose was respectively achieved using PdNi- and Pd-coated electrodes prepared by electrodeposition from the novel metal-free ionic liquid (IL); N-butyl-N-methylpyrrolidinium dicyanamide (BMP-DCA). BMP-DCA provided an excellent environment and wide cathodic limit for electrodeposition of metals and alloys because many metal chlorides could dissolve in this IL where the reduction potentials of Pd(II) and Ni(II) indeed overlapped, leading to the convenience of potentiostatic codeposition. In aqueous solutions, the reduction potentials of Pd(II) and Ni(II) are considerably separated. The bimetallic PdNi coatings with atomic ratios of ∼ 80/20 showed the highest current for ethanol oxidation reaction (EOR). Ethanol was detected by either cyclic voltammetry (CV) or hydrodynamic amperometry (HA). Using CV, the dependence of EOR peak current on concentration was linear from 4.92 to 962 μM with a detection limit of 2.26 μM (σ=3), and a linearity was observed from 4.92 to 988 μM using HA (detection limit 0.83 μM (σ=3)). The Pd-coated electrodes prepared by electrodeposition from BMP-DCA showed electrocatalytic activity to glucose oxidation and CV, HA, and square-wave voltammetry (SWV) were employed to determine glucose. SWV showed the best sensitivity and linearity was observed from 2.86 μM to 107 μM, and from 2.99 mM to 10.88 mM with detection limits of 0.78 μM and 25.9 μM (σ=3), respectively. For glucose detection, the interference produced from ascorbic acid, uric acid, and acetaminophen was significantly suppressed, compared with a regular Pt disk electrode. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. SU-F-J-189: A Method to Improve the Spatial Resolution of Prompt Gamma Based Compton Imaging for Proton Range Verification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Draeger, E; Chen, H; Polf, J

    Purpose: To test two new techniques, the distance-of-closest approach (DCA) and Compton line (CL) filters, developed as a means of improving the spatial resolution of Compton camera (CC) imaging. Methods: Gammas emitted from {sup 22}Na, {sup 137}Cs, and {sup 60}Co point sources were measured with a prototype 3-stage CC. The energy deposited and position of each interaction in each stage were recorded and used to calculate a “cone-of-origin” for each gamma that scattered twice in the CC. A DCA filter was developed which finds the shortest distance from the gamma’s cone-of-origin surface to the location of the gamma source. Themore » DCA filter was applied to the data to determine the initial energy of the gamma and to remove “bad” interactions that only contribute noise to the image. Additionally, a CL filter, which removes gamma events that do not follow the theoretical predictions of the Compton scatter equation, was used to further remove “bad” interactions from the measured data. Then images were reconstructed with raw, unfiltered data, DCA filtered data, and DCA+CL filtered data and the achievable image resolution of each dataset was compared. Results: Spatial resolutions of ∼2 mm, and better than 2 mm, were achievable with the DCA and DCA+CL filtered data, respectively, compared to > 5 mm for the raw, unfiltered data. Conclusion: In many special cases in medical imaging where information about the source position may be known, such as proton radiotherapy range verification, the application of the DCA and CL filters can result in considerable improvements in the achievable spatial resolutions of Compton imaging.« less

  20. Dihydroconiferyl alcohol - A cell division factor from Acer species.

    PubMed

    Lee, T S; Purse, J G; Pryce, R J; Horgan, R; Wareing, P F

    1981-10-01

    A compound that stimulated growth of soybean callus was isolated from spring sap of sycamore (Acer pseudoplatanus L.). Insufficient compound was isolated to permit it to be characterised. A compound with identical properties was isolated from commercial maple syrup, the concentrated spring sap of Acer saccharum L. The compound was identified as 3-(3-methoxy-4-hydroxyphenyl)-propan-1-ol (dihydroconiferyl alcohol, DCA). DCA was also active in the tobacco callus and radish leaf senescence assays, but was inactive in four other tests for cytokinin activity. DCA acted synergistically with kinetin to promote soybean callus growth. It is concluded that DCA has properties distinct from those of purine cytokinins.

  1. Isomerization of α-pinene in the terpentin oil with TCA/Natural Zeolite using microwave irradiation

    NASA Astrophysics Data System (ADS)

    Wijayati, N.; Supartono; Kusumastuti, E.

    2018-04-01

    The catalytic potensial of trichloroacetic acid (TCA)//Natural Zeolite in the isomerization of α-pinene in the terpentin oil was investigated. The purpose of this study is to investigate the influence of the power of microvawe on activity and selectivity of catalyst. The main product were champhene, terpinene, limonene, p-cymene, and terpinolene. The highest selectivity was 28.26% with a conversion of 23.25%, whereas the higher conversion was 98.99% with selectivity of 16.90% at room temperature using power of microwave 640 W.

  2. Quantitative Evaluation of Dichloroacetic Acid Kinetics in Human -- A Physiologically-Based Pharmacokinetic Modeling Investigation

    DTIC Science & Technology

    2008-01-01

    weight) Plasma VPLAC 4.4 (Merrill et al., 2005) Liver VLC 2.6 (Brown et al., 1997) Kidney VKC 0.44 (Brown et al., 1997) Rapidly perfused VRC 9.86...entire data set with the exception of individual subject optimized kinetic data reported by Schultz and Shangraw (2006). Perhaps the most challenging ...GSTzeta as well as the 0.02 mg/kg DCA administered daily in drinking water between the 2 challenges . If a person is administered 50 mg/kg/day by IV

  3. A novel, simple and inexpensive procedure for the simultaneous determination of iopamidol and p-aminohippuric acid for renal function assessment from plasma samples in awake rats.

    PubMed

    Rodríguez-Romero, Violeta; González-Villalva, Karla I; Reyes, José L; Franco-Bourland, Rebecca E; Guízar-Sahagún, Gabriel; Castañeda-Hernández, Gilberto; Cruz-Antonio, Leticia

    2015-03-25

    The purpose of the current study was to design, validate and implement a novel analytical method for the simultaneous plasma measurement of iopamidol and p-aminohippuric acid (PAH) to estimate renal function in awake rats. A reverse-phase high performance liquid chromatographic (RP-HPLC) method for the simultaneous measurement of iopamidol (for glomerular filtration rate estimation, GFR) and PAH (for tubular secretion determination, TS) was designed and validated using a C-18 column, 0.1M acetic acid-10% acetonitrile (90:10, v/v) as mobile phase, at a flow rate of 0.3 ml/min, and UV detection at 270 nm. Iopamidol (244.8 mg/kg) was administered intravenously followed immediately by sodium PAH (100 mg/kg) to healthy female Sprague-Dawley rats. Plasma samples obtained at 2.5, 5, 10, 15, 20, 30, 45, 60, 90, and 120 min after drug administration were deproteinized with 2.5% trichloroacetic acid containing p-aminobenzoic acid as internal standard, and separated by the validated RP-HPLC method described above. The iopamidol and PAH chromatographic data were analyzed using a non-compartmental model. The results demonstrated that the RP-HPLC method was linear in ranges between 15-120 μg/ml and 2.5-120 μg/ml for iopamidol and PAH, respectively. Precision and accuracy were within 15% for both drugs. Recovery of iopamidol and PAH was 92% and 100%, respectively. Plasma iopamidol and PAH clearances in awake rats, estimates for GFR and TS, respectively, were 1.49±0.20 ml/min and 3.73±0.38 ml/min. In conclusion, the method here described is a simple and reliable procedure, for the simultaneous and time-saving determination of GFR and TS from plasma samples in the conscious rat. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Building toy models of proteins using coevolutionary information

    NASA Astrophysics Data System (ADS)

    Cheng, Ryan; Raghunathan, Mohit; Onuchic, Jose

    2015-03-01

    Recent developments in global statistical methodologies have advanced the analysis of large collections of protein sequences for coevolutionary information. Coevolution between amino acids in a protein arises from compensatory mutations that are needed to maintain the stability or function of a protein over the course of evolution. This gives rise to quantifiable correlations between amino acid positions within the multiple sequence alignment of a protein family. Here, we use Direct Coupling Analysis (DCA) to infer a Potts model Hamiltonian governing the correlated mutations in a protein family to obtain the sequence-dependent interaction energies of a toy protein model. We demonstrate that this methodology predicts residue-residue interaction energies that are consistent with experimental mutational changes in protein stabilities as well as other computational methodologies. Furthermore, we demonstrate with several examples that DCA could be used to construct a structure-based model that quantitatively agrees with experimental data on folding mechanisms. This work serves as a potential framework for generating models of proteins that are enriched by evolutionary data that can potentially be used to engineer key functional motions and interactions in protein systems. This research has been supported by the NSF INSPIRE award MCB-1241332 and by the CTBP sponsored by the NSF (Grant PHY-1427654).

  5. Metabolism of halogenated ethylenes.

    PubMed Central

    Leibman, K C; Ortiz, E

    1977-01-01

    The metabolism of the chlorinated ethylenes may be explained by the formation of chloroethylene epoxides as the first intermediate products. The evidence indicates that these epoxides rearrange with migration of chlorine to form chloroacetaldehydes and chloroacetyl chlorides. Thus, monochloroacetic acid, chloral hydrate, and trichloroacetic acid have been found in reaction mixtures of 1,1-dichloroethylene, trichloroethylene, and tetrachloroethylene, respectively, with rat liver microsomal systems. Rearrangements of the chloroethylene, and glycols formed from the epoxides by hydration may also take place, but would appear, at least in the case of 1,1-dichloroethylene, to be quantitatively less important. The literature on the metabolism of chlorinated ethylenes and its relationship to their toxicity is reviewed. PMID:612463

  6. Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV

    PubMed Central

    Kollipara, Ramya; Ekhlassi, Erfon; Downing, Christopher; Guidry, Jacqueline; Lee, Michael; Tyring, Stephen K.

    2015-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid), virucidal (cidofovir, interferon-α), antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil), immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod) or miscellaneous (trichloroacetic acid, polyphenon E). The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed. PMID:26239450

  7. Self-penetration--a structural compromise between single networks and interpenetration: magnetic properties and crystal structures of

    PubMed

    Jensen; Price; Batten; Moubaraki; Murray

    2000-09-01

    The three-dimensional coordination polymers [Mn(dca)2(H2O)] (1) and [M(dca)(tcm)], M =Co (2), Ni (3), Cu (4), dca =dicyanamide, N(CN)2-, tcm = tricyanomethanide, C(CN)3-, have isomorphous structures. In 1 half the dca ligands coordinate directly (through all three nitrogen atoms) to three Mn atoms (all metal atoms are six-coordinate), while the other half coordinate to two Mn atoms (through the nitrile nitrogens) and hydrogen bond to water molecules coordinated to a third Mn atom (through the amide nitrogen). This dca. H2O structural moiety is disordered over a mirror plane, and is replaced by the structurally equivalent tcm ligand in compounds 2-4. The resulting structures display a new self-penetrating 3,6-connected (2:1) network topology that can be related to, but is different from, the rutile net. The self-penetrating [M(dca)(tcm)] network can be viewed as a structural compromise between the two interpenetrating rutile-like networks of [M(tcm)2] and the single rutile-like network of alpha-[M(dca)2]. The temperature and field dependence of the DC and AC magnetic susceptibilities and magnetisations has been measured for complexes 1-4. Compounds 1-3 exhibit long-range magnetic order with critical temperatures of 6.3 K for 1, 3.5 K for 2 and 8.0 K for 3. The Cu11 compound 4 does not order and is essentially a paramagnet. Hysteresis measurements of coercive field and remnant magnetisation show that 1, 2 and 3 are soft magnets, 1 being a canted-spin antiferromagnet (weak ferromagnet), while 2 and 3 are ferromagnets that display some unusual features in their high-field magnetisation isotherms in comparison to their related alpha-[M(dca)2] phases.

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fu, Zidong Donna; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and smallmore » intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.« less

  9. Evaluation of media for simultaneous enumeration of total coliform and Escherichia coli in drinking water supplies by membrane filtration techniques.

    PubMed

    Wang, Dunling; Fiessel, Wanda

    2008-01-01

    This study evaluated three different dehydrated media for simultaneous detection and enumeration of total coliform (TC) and Escherichia coli in drinking water samples with a standard membrane filtration procedure. The experiment indicated that the differential coliform agar (DCA) medium was the most effective among the tested media in enumerating TC and E. coli, without the need for extensive accompanying confirmation tests. The results for DCA medium were highly reproducible for both TC and E. coli with standard deviation of 6.0 and 6.1, respectively. A high agreement (82%) was found between DCA and m-Endo media on 152 drinking water samples in terms of TC positive. The DCA medium also reduced concealment of background bacteria.

  10. FreeContact: fast and free software for protein contact prediction from residue co-evolution.

    PubMed

    Kaján, László; Hopf, Thomas A; Kalaš, Matúš; Marks, Debora S; Rost, Burkhard

    2014-03-26

    20 years of improved technology and growing sequences now renders residue-residue contact constraints in large protein families through correlated mutations accurate enough to drive de novo predictions of protein three-dimensional structure. The method EVfold broke new ground using mean-field Direct Coupling Analysis (EVfold-mfDCA); the method PSICOV applied a related concept by estimating a sparse inverse covariance matrix. Both methods (EVfold-mfDCA and PSICOV) are publicly available, but both require too much CPU time for interactive applications. On top, EVfold-mfDCA depends on proprietary software. Here, we present FreeContact, a fast, open source implementation of EVfold-mfDCA and PSICOV. On a test set of 140 proteins, FreeContact was almost eight times faster than PSICOV without decreasing prediction performance. The EVfold-mfDCA implementation of FreeContact was over 220 times faster than PSICOV with negligible performance decrease. EVfold-mfDCA was unavailable for testing due to its dependency on proprietary software. FreeContact is implemented as the free C++ library "libfreecontact", complete with command line tool "freecontact", as well as Perl and Python modules. All components are available as Debian packages. FreeContact supports the BioXSD format for interoperability. FreeContact provides the opportunity to compute reliable contact predictions in any environment (desktop or cloud).

  11. Impaired Cerebral Autoregulation Is Associated with Brain Atrophy and Worse Functional Status in Chronic Ischemic Stroke

    PubMed Central

    Aoi, Mikio C.; Hu, Kun; Lo, Men-Tzung; Selim, Magdy; Olufsen, Mette S.; Novak, Vera

    2012-01-01

    Dynamic cerebral autoregulation (dCA) is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients. We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL), modified Rankin Scale, and NIH Stroke Score. Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ( = 0.029), faster gait speed ( = 0.018) and lower IADL score (0.002). Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions. PMID:23071639

  12. Dietary calcium intake, serum copper concentration and bone density in postmenopausal women

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Strause, L.; Andon, M.B.; Howard, G.

    1991-03-11

    Data from experimental animal nutrition and animal husbandry indicate that several trace minerals, including copper (Cu) are involved in bone metabolism. In addition, a large body of data suggests that low dietary calcium (Ca) intake is a risk factor for age related bone loss. The authors measured the serum (Cu), dietary Ca intake (dCa) and bone mineral density (BMD) in the spine of 225 postmenopausal women. The median dCa and serum (Cu) were 562 mg/d and 9.73 umoles/L, respectively. Serum (Cu) but, not dCa, was greater in subjects with a history of estrogen therapy (ERT). BMD was higher in subjectsmore » with above median dCa and serum (Cu) (group 1) compared to those with below median values (group 2). BMD was intermediate for subjects with either Low serum (Cu):High dCa or High serum (Cu):Low dCa. This relationship was observed in the subject group as a whole, as well as in subgroups partitioned according to history of ERT. Groups 1 and 2 did not differ in basic demographic characteristics such as age, age at menopause, body weight and height. These data support the hypothesis that Ca and Cu nutriture are determinants of skeletal health in postmenopausal women.« less

  13. Genetic Relationships Among Olive (Olea europaea L.) Cultivars Native to Turkey.

    PubMed

    Sakar, Ebru; Unver, Hulya; Bakir, Melike; Ulas, Mehmet; Sakar, Zeynep Mujde

    2016-08-01

    Olive is a widely cultivated, mainly in the Mediterranean region, and economically important fruit species used as both olive oil and table olive consumption. In Turkey, more than 50 olive cultivars have been authorized for commercial plantations, representing the developmental base for the olive industry. The aim of the present study was to identify genetic relationships among the most widely grown 27 olive cultivars in Turkey, using microsatellite or simple sequence repeat markers. Nine well-known foreign olive cultivars from different countries are also included in the study to compare the Turkish cultivars. To determine genetic relationship and diversity, 10 SSR loci (DCA3, DCA9, DCA15, DCA18, UDO4, UDO9, UDO11, UDO12, UDO24, UDO28) were used. Jaccard's similarity coefficient and the UPGMA method for cluster analysis were performed using the software NTSYSpc. The results showed that the number of alleles per locus ranging from 4 (UDO4, UDO9, UDO11, UDO12, DCA15) to 12 (DCA9) presenting high polymorphism. There were no identical cultivars. High similarity was shown by cultivars Maviand Adana topağı (0.754). The most genetically divergent cultivars, Domat-Meski (0.240) and Domat-NizipYağlık (0.245), were also identified.

  14. Department of Defense, Department of the Navy FY 1995 Budget Estimates Submission Report on Information Technology Systems

    DTIC Science & Technology

    1994-02-01

    awarded in 1984 to Martin Marietta Data System. A one-year extension to this contract has been approved, with the option of an additional year, if needed...remaining enhancements currently available with the Increment I software. B. Contracts: Martin Marietta , Information Systems Group is the systems...0016-Boeing Information Services Inc. DCA100-94-D-0017-Electronic Data Systems Corporation DCA100-94-D-0018- Martin Marietta Technical Svcs, Inc. DCA100

  15. The CCTC Quick-Reacting General War Gaming System (QUICK) Program Maintenance Manual. Volume I. Data Management Subsystem. Change 3.

    DTIC Science & Technology

    1980-05-22

    cross -referenced with the number of the data transaction listed in the data module quality con- trol list NVB Integer variable used to...Organization of the Joint Chiefs of Staff. Technical support was provided by System Sciences, Incorporated under Contract Number DCA100-75-C-0019. Change set... Contract Number DCA 100-75-C-0019. Change set two was prepared u nder Contract Number DCA 100-78-C-0035. Computer Sciences Corporation prepared change

  16. Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets.

    PubMed

    Sun, Lue; Moritake, Takashi; Ito, Kazuya; Matsumoto, Yoshitaka; Yasui, Hironobu; Nakagawa, Hidehiko; Hirayama, Aki; Inanami, Osamu; Tsuboi, Koji

    2017-01-01

    Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76. Here, we assessed reactive oxygen species (ROS) production, mitochondria function, oxygen consumption rate (OCR), energy state, and metabolites of glycolysis and tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher lactate production and lower oxygen consumption rate than parental cells. Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production, and existed in a low-energy state. Treatment with the metabolic modifier dichloroacetate (DCA) resulted in mitochondria dysfunction, glycolysis inhibition, elongated mitochondria morphology, and increased ROS production. DCA also increased radiosensitivity by suppression of the DNA repair capacity through nuclear oxidization and accelerated the generation of acetyl CoA to compensate for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like characters (e.g., CD133 positivity and sphere-forming ability) in rMSLCs. Together, our findings provide insights into the specific metabolism of rMSLCs and illuminate potential metabolic targets that might be exploited for therapeutic benefit in medulloblastoma.

  17. Analysis of 3,5-dichloroaniline as a biomarker of vinclozolin and iprodione in human urine using liquid chromatography/triple quadrupole mass spectrometry.

    PubMed

    Lindh, Christian H; Littorin, Margareta; Amilon, Asa; Jönsson, Bo A G

    2007-01-01

    The fungicides vinclozolin and iprodione are widely used in agriculture. These pesticides are dicarboximide fungicides containing the common moiety 3,5-dichloroaniline (3,5-DCA). It has been suggested that low-level exposures to such compounds may be associated with adverse health effects such as endocrine disruption. In this study a method using liquid chromatography/triple quadrupole mass spectrometry (LC/MS/MS) was developed for the analysis of 3,5-DCA as a biomarker of exposure to these fungicides in human urine. The urine samples were treated by basic hydrolysis to degrade the fungicides, their metabolites and conjugates to 3,5-DCA. The 3,5-DCA was then extracted using toluene and derivatized using pentafluoropropionic anhydride (PFPA). Analysis of the derivative was carried out using selected reaction monitoring (SRM) in the negative ion mode. Quantification of the derivative was performed using [(13)C(6)]-labeled 3,4-DCA as an internal standard with good precision and linearity in the range 0.1-200 ng/mL urine. The limit of detection was determined to be 0.1 ng/mL. The metabolites in urine were found to be stable during storage at -20 degrees C. To validate 3,5-DCA as a biomarker the method was applied in a human experimental exposure to iprodione and vinclozolin. Two healthy volunteers received 200 microg single oral doses of each pesticide followed by urine sampling during 72-120 h post-exposure. Between 78-107% of the dose was recovered as 3,5-DCA in the urine after exposure. Copyright (c) 2007 John Wiley & Sons, Ltd.

  18. Expected utility versus expected regret theory versions of decision curve analysis do generate different results when treatment effects are taken into account.

    PubMed

    Hozo, Iztok; Tsalatsanis, Athanasios; Djulbegovic, Benjamin

    2018-02-01

    Decision curve analysis (DCA) is a widely used method for evaluating diagnostic tests and predictive models. It was developed based on expected utility theory (EUT) and has been reformulated using expected regret theory (ERG). Under certain circumstances, these 2 formulations yield different results. Here we describe these situations and explain the variation. We compare the derivations of the EUT- and ERG-based formulations of DCA for a typical medical decision problem: "treat none," "treat all," or "use model" to guide treatment. We illustrate the differences between the 2 formulations when applied to the following clinical question: at which probability of death we should refer a terminally ill patient to hospice? Both DCA formulations yielded identical but mirrored results when treatment effects are ignored; they generated significantly different results otherwise. Treatment effect has a significant effect on the results derived by EUT DCA and less so on ERG DCA. The elicitation of specific values for disutilities affected the results even more significantly in the context of EUT DCA, whereas no such elicitation was required within the ERG framework. EUT and ERG DCA generate different results when treatment effects are taken into account. The magnitude of the difference depends on the effect of treatment and the disutilities associated with disease and treatment effects. This is important to realize as the current practice guidelines are uniformly based on EUT; the same recommendations can significantly differ if they are derived based on ERG framework. © 2016 The Authors. Journal of Evaluation in Clinical Practice Published by John Wiley & Sons Ltd.

  19. Expected utility versus expected regret theory versions of decision curve analysis do generate different results when treatment effects are taken into account

    PubMed Central

    Hozo, Iztok; Tsalatsanis, Athanasios

    2016-01-01

    Abstract Rationale, aims, and objectives Decision curve analysis (DCA) is a widely used method for evaluating diagnostic tests and predictive models. It was developed based on expected utility theory (EUT) and has been reformulated using expected regret theory (ERG). Under certain circumstances, these 2 formulations yield different results. Here we describe these situations and explain the variation. Methods We compare the derivations of the EUT‐ and ERG‐based formulations of DCA for a typical medical decision problem: “treat none,” “treat all,” or “use model” to guide treatment. We illustrate the differences between the 2 formulations when applied to the following clinical question: at which probability of death we should refer a terminally ill patient to hospice? Results Both DCA formulations yielded identical but mirrored results when treatment effects are ignored; they generated significantly different results otherwise. Treatment effect has a significant effect on the results derived by EUT DCA and less so on ERG DCA. The elicitation of specific values for disutilities affected the results even more significantly in the context of EUT DCA, whereas no such elicitation was required within the ERG framework. Conclusion EUT and ERG DCA generate different results when treatment effects are taken into account. The magnitude of the difference depends on the effect of treatment and the disutilities associated with disease and treatment effects. This is important to realize as the current practice guidelines are uniformly based on EUT; the same recommendations can significantly differ if they are derived based on ERG framework. PMID:27981695

  20. Carbon catabolite repression and cell dispersal affect degradation of the xenobiotic compound 3,4-dichloroaniline in Comamonas testosteroni WDL7 biofilms.

    PubMed

    Horemans, Benjamin; Breugelmans, Philip; Hofkens, Johan; Springael, Dirk

    2017-03-01

    Organic pollutant degrading biofilms in natural ecosystems and water treatment systems are often exposed to other carbon sources in addition to the pollutant. The availability of auxiliary carbon sources can lead to surplus biomass growth, changes in biofilm structure and carbon catabolite repression (CCR) which together will affect pollutant degradation rate and efficiency of the system. To understand the interplay between these processes, continuous biofilms of the 3,4-dichloroaniline (3,4-DCA) degrading Comamonas testosteroni WDL7-RFP were grown in single- and dual-substrate conditions with 3,4-DCA and/or citrate and reciprocal effects on 3,4-DCA/citrate degradation, biofilm biomass and biofilm structure were examined. The main mechanism affecting 3,4-DCA degradation in biofilms in dual-substrate conditions was citrate-mediated CCR as reflected by a decrease in specific 3,4-DCA degrading activity. Growth on citrate partially compensated for the lowered specific 3,4-DCA degradation activity under dual substrate conditions but not to the extent expected from growth observed under single-substrate conditions with citrate. This was explained by higher residual 3,4-DCA concentrations in the presence of citrate that increased cell dispersal in the biofilms. Our results show hampered pollutant removal in biofilms due to a complex interplay of auxiliary organic C source utilization for growth affecting the specific pollutant degradation rate and changes in cell physiology due to increased exposure to the pollutant as a result of lowered pollutant degradation rates. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Functionalised carboxylic acids in atmospheric particles: An annual cycle revealing seasonal trends and possible sources

    NASA Astrophysics Data System (ADS)

    Teich, Monique; van Pinxteren, Dominik; Herrmann, Hartmut

    2013-04-01

    Carboxylic acids represent a major fraction of the water soluble organic carbon (WSOC) in atmospheric particles. Among the particle phase carboxylic acids, straight-chain monocarboxylic acids (MCA) and dicarboxylic acids (DCA) with 2-10 carbon atoms have extensively been studied in the past. However, only a few studies exist dealing with functionalised carboxylic acids, i.e. having additional hydroxyl-, oxo- or nitro-groups. Regarding atmospheric chemistry, these functionalised carboxylic acids are of particular interest as they are supposed to be formed during atmospheric oxidation processes, e.g. through radical reactions. Therefore they can provide insights into the tropospheric multiphase chemistry. During this work 28 carboxylic acids (4 functionalised aliphatic MCAs, 5 aromatic MCAs, 3 nitroaromatic MCAs, 6 aliphatic DCAs, 6 functionalised aliphatic DCAs, 4 aromatic DCAs) were quantitatively determined in 256 filter samples taken at the rural research station Melpitz (Saxony, Germany) with a PM10 Digitel DHA-80 filter sampler. All samples were taken in 2010 covering a whole annual cycle. The resulting dataset was examined for a possible seasonal dependency of the acid concentrations. Furthermore the influence of the air mass origin on the acid concentrations was studied based on a simple two-sector classification (western or eastern sector) using a back trajectory analysis. Regarding the annual average, adipic acid was found to be the most abundant compound with a mean concentration of 7.8 ng m-3 followed by 4-oxopimelic acid with 6.1 ng m-3. The sum of all acid concentrations showed two maxima during the seasonal cycle; one in summer and one in winter, whereas the highest overall acid concentrations were found in summer. In general the target acids could be divided into two different groups, where one group has its maximum concentration in summer and the other group during winter. The first group contains all investigated aliphatic mono- and dicarboxylic

  2. Pulse Radiolysis and Computational Studies on a Pyrrolidinium Dicyanamide Ionic Liquid: Detection of the Dimer Radical Anion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Das, Laboni; Kumar, Rahul; Maity, Dilip K.

    A pulse radiolysis study on pyrrolidinium cation based ionic liquids is presented here in this paper. Time-resolved absorption spectra for 1-methyl-1-propylpyrrolidinium dicyanamide (DCA) at 500 ns after the electron pulse show broad absorption bands at wavelengths below 440 nm and at 640 nm. In pyrrolidinium bis(trifluoromethylsulfonyl)imide (NTf 2) and tris(perfluoroethyl)trifluorophosphate (FAP) ILs, the transient absorption below 440 nm is much weaker. The absorption at 500 ns, which increases with wavelength from 500 nm to beyond 800 nm, was assigned to the tail of the solvated electron NIR absorption spectrum, since it disappears in the presence of N 2O. In themore » DCA IL, the presence of a reducing species was confirmed by the formation of pyrene radical anion. The difference in the transient species in the case of the DCA IL compared to other two ILs should be due to the anion, with cations being similar. In pseudohalide ILs such as DCA, radicals are formed by direct hole trapping by the anion (X – + h + → X•), followed by addition to the parent anion. Prediction of the UV/vis absorption spectra of the dimer radical anion by computational calculation supports the experimental results. The oxidizing efficiency of (DCA) 2•– and its reduction potential (E(DCA)2•–/(2DCA–)) have been determined.« less

  3. Predictive Value of Dynamic Cerebral Autoregulation Assessment in Surgical Management of Patients with High-Grade Carotid Artery Stenosis

    PubMed Central

    Semenyutin, Vladimir B.; Asaturyan, Gregory A.; Nikiforova, Anna A.; Aliev, Vugar A.; Panuntsev, Grigory K.; Iblyaminov, Vadim B.; Savello, Alexander V.; Patzak, Andreas

    2017-01-01

    Dynamic cerebral autoregulation (DCA) capacity along with the degree of internal carotid artery (ICA) stenosis and characteristics of the plaque can also play an important role in selection of appropriate treatment strategy. This study aims to classify the patients with severe ICA stenosis according to preoperative state of DCA and to assess its dynamics after surgery. Thirty-five patients with severe ICA stenosis having different clinical type of disease underwent reconstructive surgery. DCA was assessed with transfer function analysis (TFA) by calculating phase shift (PS) between Mayer waves of blood flow velocity (BFV) and blood pressure (BP) before and after operation. In 18 cases, regardless of clinical type, preoperative PS on ipsilateral side was within the normal range and did not change considerably after surgery. In other 17 cases preoperative PS was reliably lower both in patients with symptomatic and asymptomatic stenosis. Surgical reconstruction led to restoration of impaired DCA evidenced by significant increase of PS in postoperative period. Our data suggest that regardless clinical type of disease various state of DCA may be present in patients with severe ICA stenosis. This finding can contribute to establishing the optimal treatment strategy, and first of all for asymptomatic patients. Patients with compromised DCA should be considered as ones with higher risk of stroke and first candidates for reconstructive surgery. PMID:29163214

  4. Pulse Radiolysis and Computational Studies on a Pyrrolidinium Dicyanamide Ionic Liquid: Detection of the Dimer Radical Anion

    DOE PAGES

    Das, Laboni; Kumar, Rahul; Maity, Dilip K.; ...

    2018-03-06

    A pulse radiolysis study on pyrrolidinium cation based ionic liquids is presented here in this paper. Time-resolved absorption spectra for 1-methyl-1-propylpyrrolidinium dicyanamide (DCA) at 500 ns after the electron pulse show broad absorption bands at wavelengths below 440 nm and at 640 nm. In pyrrolidinium bis(trifluoromethylsulfonyl)imide (NTf 2) and tris(perfluoroethyl)trifluorophosphate (FAP) ILs, the transient absorption below 440 nm is much weaker. The absorption at 500 ns, which increases with wavelength from 500 nm to beyond 800 nm, was assigned to the tail of the solvated electron NIR absorption spectrum, since it disappears in the presence of N 2O. In themore » DCA IL, the presence of a reducing species was confirmed by the formation of pyrene radical anion. The difference in the transient species in the case of the DCA IL compared to other two ILs should be due to the anion, with cations being similar. In pseudohalide ILs such as DCA, radicals are formed by direct hole trapping by the anion (X – + h + → X•), followed by addition to the parent anion. Prediction of the UV/vis absorption spectra of the dimer radical anion by computational calculation supports the experimental results. The oxidizing efficiency of (DCA) 2•– and its reduction potential (E(DCA)2•–/(2DCA–)) have been determined.« less

  5. The spectroscopic (FTIR, FT-IR gas phase and FT-Raman), first order hyperpolarizabilities, NMR analysis of 2,4-dichloroaniline by ab initio HF and density functional methods.

    PubMed

    Sundaraganesan, N; Karpagam, J; Sebastian, S; Cornard, J P

    2009-07-01

    In this work, the experimental and theoretical study on molecular structure and vibrational spectra of 2,4-dichloroaniline (2,4-DCA) were studied. The Fourier transform infrared (gas phase) and Fourier transform Raman spectra of 2,4-DCA were recorded. The molecular geometry and vibrational frequencies of 2,4-DCA in the ground state were calculated by using the Hartree-Fock (HF) and density functional (DF) methods (BLYP, B3LYP and SVWN) with 6-31G(d,p) as basis set. Comparison of the observed fundamental vibrational frequencies of 2,4-DCA with calculated results by HF and density functional methods indicates that BLYP is superior to other methods for molecular vibrational problems. The difference between the observed and scaled wave number values of most of the fundamentals is very small. The electric dipole moment (micro) and the first hyperpolarizability (beta) values of the investigated molecule were computed using ab initio quantum mechanical calculations. The calculated results also show that the 2,4-DCA molecule might have microscopic nonlinear optical (NLO) behavior with non-zero values. Natural atomic charges of 2,4-DCA and 4-chloroaniline was calculated and compared. The isotropic chemical shift computed by (13)C NMR analyses also shows good agreement with experimental observations. The theoretically predicted FTIR and FT-Raman spectra of the title molecule have been constructed.

  6. Effects of short-term mechanical hyperventilation on cerebral blood flow and dynamic cerebral autoregulation in critically ill patients with sepsis.

    PubMed

    Berg, Ronan M G; Plovsing, Ronni R

    2016-01-01

    In sepsis, higher PaCO2 levels are associated with impaired dynamic cerebral autoregulation (dCA), which may expose the brain to hypo- and hyperperfusion during acute fluctuations in blood pressure. We hypothesised that short-term mechanical hyperventilation would dCA in critically ill patients with sepsis. Seven mechanically ventilated septic patients were included. We assessed dCA before and after 30 min of mechanical hyperventilation. Transfer function analysis of spontaneous oscillations in transcranial Doppler-based middle cerebral artery blood flow velocity (MCAv) and invasive mean arterial blood pressure was used to assess dCA. Mechanical enhance hyperventilation reduced the median PaCO2 from 5.3 (IQR, 5.0-6.5) to 4.7 (IQR, 4.2-5.1) kPa (p < 0.05). This was associated with a reduction in the median MCAv from 57 (IQR, 33-68) to 32 (IQR, 21-40) cm sec(-1) (p < 0.05). Apart from a small increase in gain in the low frequency range (2.32 [IQR 1.80-2.41] vs. 2.59 (2.40-4.64) cm mmHg(-1) sec(-1); p < 0.05), this was not associated with any enhancement in dCA. In conclusion, cerebral CO2 vasoreactivity was found to be preserved in septic patients; nevertheless, and in contrast to our working hypothesis, short-term mechanical hyperventilation did not enhance dCA.

  7. Toxicologic Evaluation of Trichloroacetic Acid: Effects on Rat Liver Peroxisomes and Enzyme Altered Foci.

    DTIC Science & Technology

    1986-05-01

    studies with the hypolipid- emic agent gemfibrozil . J Natl Cancer Inst. 67:1105- 1120 (1981). 88. De La Iglesia, F.A., Pinns, S.M., Luca, J., and McGuire...E.J. Quantitative sterology of peroxisomes in hepatocytes from hyperlipoproteinemic patients receiv- ing gemfibrozil . Micron. 12:97-98 (1981). 89

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeong, K; Basavatia, A; Mynampati, D

    Purpose: To compare VMAT SRS plans, dynamic conformal arc (DCA) plans, and Brainlab iPlan’s capability of planning and delivering brain SRS plans by employing HybridArc. HybridArc utilizes both DCA and IMRT. Using HybridArc, the amount of DCA versus IMRT needs to be optimized. Methods: Four SRS patients with the aim of reducing brainstem dose were selected for this study. All patients were contoured in iPlan and transferred to Eclipse for VMAT planning. In iPlan, DCA plans were created for each case. Moreover, nine HybridArc plans with DCA-IMRT ratios between 9:1 through 1:9 were created with a single ring structure generatedmore » by subtracting 3 mm expansion of target from a 10 mm expansion of the target. Two static IMRT beams were used in each of the five DCA arcs for HybridArc. The dose was prescribed to DCA only and HybridArc plans and normalized so that the target volume (TV) receives 100% dose to 99.5% of the TV to achieve 120% ∼ 130% max dose within targets. Following metrics were compared: PITV, V12Gy, CGIc, CGIg, CGI, brainstem max dose, and total monitor units (MUs). Results: A brainstem max dose comparable with VMAT from 30% IMRT and less with 50% or more IMRT could be achieved. PITV decreased with increasing IMRT portion and begins to saturate past an IMRT portion of 30%. The CGIg index, which represents how fast the dose falls off, was better with HybridArc in all HybridArc plans. Total MUs increased with increasing IMRT but less than VMAT in all cases. Conclusion: Overall, a lower brainstem max dose and a lower V12Gy with fewer MUs can be achieved with HybridArc. Considering all factors, it would be best to use a DCA-IMRT ratio of either 7:3 or 6:4.« less

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maurer, J; Sintay, B; Manning, M

    Purpose: This study evaluates a novel algorithm that can be used with any treatment planning system for simple and rapid generation of stereotactic radiosurgery (SRS) plans for treating multiple brain metastases using a single isocenter dynamic conformal arc (DCA) approach. This technique is compared with a single isocenter volumetric modulated arc therapy (VMAT) technique in terms of delivery time, conformity, low dose spread and delivery accuracy. Methods: Five patients, with a total of 37 (5 – 11) targets were planned using a previously published method for generating optimal VMAT plans and using the proposed DCA algorithm. All planning target volumesmore » (PTVs) were planned to 20 Gy, meeting a minimum 99% coverage and maximum 135 % hot spot for both techniques. Quality assurance was performed using radiochromic film, with films placed in the high dose regions of each PTV. Normal tissue volumes receiving 12 Gy and 6 Gy (V12 and V6) were computed for each plan. Conformity index (CI) and gamma evaluations (95% of points passing 4%/0.5mm) were computed for each PTV. Results: Delivery times, including beam on and table rotation times, were comparable: 17 – 22 minutes for all deliveries. V12s for DCA plans were (18.5±15.2 cc) vs. VMAT (19.7±14.4 cc). V6s were significantly lower for DCA (69.0±52.0 cc) compared with VMAT (154.0±91.0 cc) (p <<0.05). CIs for VMAT targets were (1.38±0.50) vs. DCA (1.61±0.41). 36 of 37 DCA planned targets passed gamma tests, while 29 of 37 VMAT planned targets passed. Conclusion: Single isocenter DCA plans were easily achieved. The evaluation suggests that DCA may represent a favorable technique compared with VMAT for multiple target SRS by reducing dose to normal tissue and more accurately depicting deliverable dose.« less

  10. Internalization and degradation of human chorionic gonadotropin in ovine luteal cells: Kinetic studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmed, C.E.; Sawyer, H.R.; Niswender, G.D.

    1981-11-01

    Ovine luteal cells grown in suspensions and/or monolayer culture were used to study the rates of internalization and degradation of (/sup 125/I)hCG. At specified times after a 5- to 7-min exposure to (/sup 125/I)hCG, cells were treated with acidic buffer (pH 3.9) to elute membrane-bound hormone, which left the internalized radioactivity associated with the cell pellet. Radioactivity released into the medium during the incubation periods was subjected to 20% trichloroacetic acid and/or thin layer chromatography to monitor the extent of degradation of the radioactive hormone. Secretion of progesterone into the medium and exclusion of trypan blue were used to monitormore » the viability of the cells in each experiment. Radioactivity was lost from the plasma membrane with a tsub1/2 of 9.6 h, with approximately 85% of the radioactivity being lost within 24 h. Cell-associated radioactivity increased linearly with time to a plateau at 4 h, remained stable until 12 h, and then decreased between 12-24 h. The plateau between 4-12 h reflected an equilibrium between the (/sup 125/I)hCG which was internalized and degraded and the (/sup 125/I)hCG which was released into the medium. The degraded (/sup 125/I)hCG increased essentially linearly up to 24 h. These data suggest that the majority of (/sup 125/I)hCG bound to receptors in luteal cells is internalized and degraded. Less than 20% of the radioactivity bound initially to cells dissociated into the incubation medium and was trichloroacetic acid precipitable within 24 h. The internalization and degradation of (/sup 125/I)hCG was temperature dependent, with essentially no hCG internalized and/or degraded at 4C.« less

  11. A new nonhuman primate model of severe dry eye.

    PubMed

    Qin, Yi; Tan, Xiaobo; Zhang, Yingnan; Jie, Ying; Labbe, Antoine; Pan, Zhiqiang

    2014-05-01

    The aim of this study was to establish a new rhesus monkey model of severe dry eye. A total of 8 rhesus monkeys were used for the study. Four monkeys had their main lacrimal gland and nictitating membrane surgically removed (group 1). Another 4 monkeys had a similar surgery with further application of 50% trichloroacetic acid on the bulbar conjunctiva (group 2). The ocular surface was evaluated before and after the surgery (1, 4, 8, 12, and 24 weeks) using Schirmer-1 test, corneal fluorescein staining, and the lissamine green test. Conjunctival impression cytology was also performed before and 24 weeks after the surgery. Finally, the cornea and the conjunctiva were evaluated using light microscopy. A significant decrease in tear secretion was observed in all operated eyes. Schirmer test data measured were ≤4 mm in all the operated eyes. Slit-lamp examination also revealed abnormal staining in all the operated eyes that remained stable until the end of the experiment. In group 2, corneal fluorescein staining and lissamine green test values were always ≥5 (max 12) and ≥4 (max 9), respectively. Impression cytology specimens of both the treated groups showed conjunctival squamous metaplasia and a decreased number of goblet cells. Under light microscopy, the corneal epithelium appeared irregular with edematous basal epithelial cells. The conjunctiva showed a decreased goblet cell density with infiltration of inflammatory cells. Complete removal of the principal lacrimal gland and nictitating membrane associated with the application of 50% trichloroacetic acid on the conjunctiva could induce severe dry eye in rhesus monkeys.

  12. Undetected Groundwater Contamination at Underground Storage Tank Sites by the Gasoline Lead Scavengers Ethylene Dibromide and 1,2-Dichloroethane

    NASA Astrophysics Data System (ADS)

    Falta, R. W.

    2004-05-01

    Ethylene dibromide (EDB) is a synthetic organic chemical that was produced in large amounts for use as a leaded gasoline additive and pesticide. The chlorinated solvent 1,2-dichlorethane (1,2-DCA) is widely used in the chemical industry, and was also added to leaded gasoline. EDB and 1,2-DCA are classified as probable human carcinogens by the United States Environmental Protection Agency (EPA), and EDB's use as a pesticide was suspended in 1984. The current EPA maximum contaminant level (MCL) for EDB in drinking water is 0.05 ug/l, and the MCL for 1,2-DCA is 5 ug/l. EDB has proven to be both mobile and persistent in groundwater, and contamination of groundwater by EDB was documented in several states beginning in the early 1980s. The majority of this contamination is attributed to agricultural uses of EDB, however approximately 90 percent of the EDB produced was used as a leaded gasoline additive, and it was present in virtually all leaded gasoline sold in the US. 1,2-DCA is commonly found as a groundwater contaminant, and it is both mobile and persistent. Past site investigations and remediation efforts at underground storage tank sites contaminated by leaded gasoline have rarely addressed the potential for EDB or 1,2-DCA contamination. However, the concentrations of EDB and 1,2-DCA in leaded gasoline were high enough to produce groundwater concentrations of thousands of ug/l. For this reason, there is a substantial likelihood that undetected EDB and 1,2-DCA plumes above the MCL may exist at many sites where leaded gasoline leaked or spilled. An initial review of field data from underground storage tank sites in two states suggests that this problem is widespread.

  13. Kinetics of heavy metal inhibition of 1,2-dichloroethane biodegradation in co-contaminated water.

    PubMed

    Arjoon, Ashmita; Olaniran, Ademola Olufolahan; Pillay, Balakrishna

    2015-03-01

    Sites co-contaminated with heavy metals and 1,2-DCA may pose a greater challenge for bioremediation, as the heavy metals could inhibit the activities of microbes involved in biodegradation. Therefore, this study was undertaken to quantitatively assess the effects of heavy metals (arsenic, cadmium, mercury, and lead) on 1,2-DCA biodegradation in co-contaminated water. The minimum inhibitory concentrations (MICs) and concentrations of the heavy metals that caused half-life doubling (HLDs) of 1,2-DCA as well as the degradation rate coefficient (k(1)) and half-life (t(½)) of 1,2-DCA were measured and used to predict the toxicity of the heavy metals in the water microcosms. An increase in heavy metal concentration resulted in a progressive increase in the t(½) and relative t(½) and a decrease in k(1). The MICs and HLDs of the heavy metals were found to vary, depending on the heavy metals type. In addition, the presence of heavy metals was shown to inhibit 1,2-DCA biodegradation in a dose-dependent manner, with the following order of decreasing inhibitory effect: Hg(2+)  > As(3+)  > Cd(2+)  > Pb(2+). Findings from this study have significant implications for the development of bioremediation strategies for effective degradation of 1,2-DCA and other related compounds in wastewater co-contaminated with heavy metals. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Mechanistic study of the azithromycin dosage-form-dependent food effect.

    PubMed

    Curatolo, William; Foulds, George; Labadie, Robert

    2010-07-01

    Azithromycin capsules are known to exhibit a negative food effect, manifest as a decrease in azithromycin bioavailability in the fed state. Azithromycin tablets are known to be bioequivalent to capsules in the fasted state, but do not exhibit a food effect. In the present study, the involvement of gastric degradation of azithromycin to des-cladinose azithromycin (DCA) has been investigated as a possible mechanism for the observed capsule food effect. Healthy volunteers were dosed with azithromycin tablets and capsules, fasted and fed, in a four-way randomized crossover study. Serum levels of DCA were measured as a function of time post-dose. Natural log-transformed PK parameters were statistically analyzed using an ANOVA model appropriate for the study design. When capsules were dosed to fed subjects, the systemic AUC for DCA was 243% of the value observed after fasted-state dosing, and the DCA C(max) was 270% of the value observed after fasted-state dosing. When azithromycin tablets were dosed in the fasted and fed states, there was no significant difference in systemic DCA. Gastric degradation of azithromycin to DCA is the likely mechanism for the observed negative food effect observed for azithromycin capsules. This effect is not observed for tablets. These observations suggest that azithromycin capsules exhibit slow and/or delayed disintegration in the fed stomach, resulting in extended gastric residence and degradation of a portion of the gastrically retained azithromycin.

  15. Long-term Safety of Dichloroacetate in Congenital Lactic Acidosis

    PubMed Central

    Abdelmalak, Monica; Lew, Alicia; Ramezani, Ryan; Shroads, Albert L.; Coats, Bonnie S.; Langaee, Taimour; Shankar, Meena N.; Neiberger, Richard E.; Subramony, S.H.; Stacpoole, Peter W.

    2013-01-01

    We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the E1α subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (1 patient), IV (3 patients) or I+IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 hours) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean ± SD: 23.5 ± 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets. PMID:23611579

  16. Subcarrier intensity modulation for MIMO visible light communications

    NASA Astrophysics Data System (ADS)

    Celik, Yasin; Akan, Aydin

    2018-04-01

    In this paper, subcarrier intensity modulation (SIM) is investigated for multiple-input multiple-output (MIMO) visible light communication (VLC) systems. A new modulation scheme called DC-aid SIM (DCA-SIM) is proposed for the spatial modulation (SM) transmission plan. Then, DCA-SIM is extended for multiple subcarrier case which is called DC-aid Multiple Subcarrier Modulation (DCA-MSM). Bit error rate (BER) performances of the considered system are analyzed for different MIMO schemes. The power efficiencies of DCA-SIM and DCA-MSM are shown in correlated MIMO VLC channels. The upper bound BER performances of the proposed models are obtained analytically for PSK and QAM modulation types in order to validate the simulation results. Additionally, the effect of power imbalance method on the performance of SIM is studied and remarkable power gains are obtained compared to the non-power imbalanced cases. In this work, Pulse amplitude modulation (PAM) and MSM-Index are used as benchmarks for single carrier and multiple carrier cases, respectively. And the results show that the proposed schemes outperform PAM and MSM-Index for considered single carrier and multiple carrier communication scenarios.

  17. Ant Colony Optimization Algorithm for Centralized Dynamic Channel Allocation in Multi-Cell OFDMA Systems

    NASA Astrophysics Data System (ADS)

    Kim, Hyo-Su; Kim, Dong-Hoi

    The dynamic channel allocation (DCA) scheme in multi-cell systems causes serious inter-cell interference (ICI) problem to some existing calls when channels for new calls are allocated. Such a problem can be addressed by advanced centralized DCA design that is able to minimize ICI. Thus, in this paper, a centralized DCA is developed for the downlink of multi-cell orthogonal frequency division multiple access (OFDMA) systems with full spectral reuse. However, in practice, as the search space of channel assignment for centralized DCA scheme in multi-cell systems grows exponentially with the increase of the number of required calls, channels, and cells, it becomes an NP-hard problem and is currently too complicated to find an optimum channel allocation. In this paper, we propose an ant colony optimization (ACO) based DCA scheme using a low-complexity ACO algorithm which is a kind of heuristic algorithm in order to solve the aforementioned problem. Simulation results demonstrate significant performance improvements compared to the existing schemes in terms of the grade of service (GoS) performance and the forced termination probability of existing calls without degrading the system performance of the average throughput.

  18. Electrochemical preparation of nanostructured lanthanum using lanthanum chloride as a precursor in 1-butyl-3-methylimidazolium dicyanamide ionic liquid.

    PubMed

    Zhang, Q B; Yang, C; Hua, Y X; Li, Y; Dong, P

    2015-02-14

    Nanostructured lanthanum was electrochemically prepared on a platinum (Pt) substrate in the room temperature ionic liquid 1-butyl-3-methylimidazolium dicyanamide (BMI-DCA) containing anhydrous LaCl3 at 333 K. The electrochemical reduction behavior of La(iii) was investigated using cyclic voltammetry and chronoamperometry techniques. Cyclic voltammogram revealed that the reduction of La(iii) in BMI-DCA involved an irreversible process controlled by diffusion. Chronoamperometric transient analysis confirmed the diffusion controlled electrodeposition process with the diffusion coefficient of La(iii) species in the range of 10(-10) cm(2) s(-1). The strong complexing capability of DCA(-) anions facilitated the displacement of chloride ligands and induced the solubility of LaCl3. The subsequent coordination of La(iii) and DCA(-) anions forming [La(DCA)4](-) complex anions was monitored by designing amperometric titration experiments. Potentiostatically deposited La-deposits with different nanostructures were characterized by SEM, XRD and XPS analyses. The electrodeposition potential was found to play an important role in controlling the nucleation and growth kinetics of the nanocrystal during the electrodeposition process. Depending on the deposition potential, metallic lanthanum with either nanoparticles or nanoporous structures was obtained.

  19. Screen for soil fungi highly resistant to dichloroaniline uncovers mostly Fusarium species.

    PubMed

    Chan Ho Tong, Laetitia; Dairou, Julien; Bui, Linh-Chi; Bouillon, Julien; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Silar, Philippe

    2015-08-01

    Arylamines are frequent pollutants in soils. Fungi have proven to be efficient in detoxifying these chemicals by acetylating them using arylamine N-acetyl transferase enzymes. Here, we selected from natural soils fungi highly resistant to 3,4-dichloroaniline (DCA). Fusarium species were the most frequently isolated species, especially Fusarium solani. The sequenced strain of F. solani contains five NAT genes, as did all the DCA-resistant isolates. RT-PCR analysis showed that the five genes were expressed in F. solani. Expression of the F. solani genes in Podospora anserina and analysis of acetylation directly in F. solani showed that only the NhNAT2B gene conferred significant resistance to DCA and that F. solani likely uses pathways different from acetylation to resist high doses of DCA, as observed previously for Trichoderma. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Metabolic analysis of radioresistant medulloblastoma stem-like clones and potential therapeutic targets

    PubMed Central

    Sun, Lue; Moritake, Takashi; Ito, Kazuya; Matsumoto, Yoshitaka; Yasui, Hironobu; Nakagawa, Hidehiko; Hirayama, Aki; Inanami, Osamu; Tsuboi, Koji

    2017-01-01

    Medulloblastoma is a fatal brain tumor in children, primarily due to the presence of treatment-resistant medulloblastoma stem cells. The energy metabolic pathway is a potential target of cancer therapy because it is often different between cancer cells and normal cells. However, the metabolic properties of medulloblastoma stem cells, and whether specific metabolic pathways are essential for sustaining their stem cell-like phenotype and radioresistance, remain unclear. We have established radioresistant medulloblastoma stem-like clones (rMSLCs) by irradiation of the human medulloblastoma cell line ONS-76. Here, we assessed reactive oxygen species (ROS) production, mitochondria function, oxygen consumption rate (OCR), energy state, and metabolites of glycolysis and tricarboxylic acid cycle in rMSLCs and parental cells. rMSLCs showed higher lactate production and lower oxygen consumption rate than parental cells. Additionally, rMSLCs had low mitochondria mass, low endogenous ROS production, and existed in a low-energy state. Treatment with the metabolic modifier dichloroacetate (DCA) resulted in mitochondria dysfunction, glycolysis inhibition, elongated mitochondria morphology, and increased ROS production. DCA also increased radiosensitivity by suppression of the DNA repair capacity through nuclear oxidization and accelerated the generation of acetyl CoA to compensate for the lack of ATP. Moreover, treatment with DCA decreased cancer stem cell-like characters (e.g., CD133 positivity and sphere-forming ability) in rMSLCs. Together, our findings provide insights into the specific metabolism of rMSLCs and illuminate potential metabolic targets that might be exploited for therapeutic benefit in medulloblastoma. PMID:28426747

  1. Rapid in vitro production of cloned plants of Uraria picta (Jacq.) DC-A rare medicinal herb in long-term culture.

    PubMed

    Rai, Santosh Kumar; Sharma, Meena; Jain, Madhu; Awasthi, Abhishek; Purshottam, Dharmendra Kumar; Nair, Narayanan Kuttanpillai; Sharma, Ashok Kumar

    2010-11-01

    An efficient in vitro process for rapid production of cloned plants of Uraria picta has been developed employing nodal stem segments taken from field-grown plants. Explants showed bud-break followed by regeneration of shoots with restricted growth within 12 days on modified Murashige and Skoog's medium supplemented with 0.25 mg l(-1) each of 6-benzylaminopurine and indole-3-acetic acid and 25 mg l(-1) adenine sulfate. Normal growth of shoots with good proliferation rate was achieved by reducing the concentrations of 6-benzylaminopurine and indole-3-acetic acid to 0.1 mg l(-1) each and incorporating 0.5 mg l(-1) gibberellic acid in the medium in which, on an average, 19.6 shoots per explant were produced. Further, during successive subcultures, increased concentrations of adenine sulfate (50 mg l(-l)) and gibberellic acid (2 mg l(-l)) along with the addition of 20 mg l(-l)  DL: -tryptophan were found conducive to control the problem of necrosis of shoots. In this treatment, several "crops" of shoots were obtained from single culture by repeated subculturing of basal portion of stalk in long-term. Isolated shoots rooted 100% in 0.25 mg l(-1) indole-3-butyric acid. In vitro-raised plants after hardening in inorganic salt solution grew normally in soil and came to flowering. Genetic fidelity of in vitro-raised plants was ascertained by rapid amplified polymorphic DNA (RAPD) markers. Also, quantitative estimation of two isoflavonones in their root extracts further confirmed true-to-type nature of plantlets.

  2. Dichloroacetate treatment in Leigh syndrome caused by mitochondrial DNA mutation.

    PubMed

    Takanashi, J; Sugita, K; Tanabe, Y; Maemoto, T; Niimi, H

    1997-01-01

    Sodium dichloroacetate (DCA) was administered to a 1-year-old female case of Leigh syndrome, who had a T > G point mutation at nt 8993 of mitochondrial DNA. Her biochemical and clinical symptoms improved gradually, but proton magnetic resonance spectroscopy revealed reduction of the N-acetylaspartate/creatine ratio, and magnetic resonance imaging showed progressive cerebral atrophy despite the DCA therapy. These results suggest that DCA therapy may not retard the progress of the primary disease in Leigh syndrome, but produced clinical improvement most likely by reducing toxic accumulation of lactate.

  3. Acquisition Planning at the Defense Communications Agency.

    DTIC Science & Technology

    1984-04-01

    guidelines for interaction are developed under the leadership of DCA agencywide integrators with the participation of personnel from DCA, the Services...Communications System DCSO - Defense Communications System Organizatin . DDN - Defense Data Network DEC - Decision Making DG - Defense Guidance DIA - Defense

  4. DICHLOROACETATE TOXICOKINETICS AND DISRUPTION OF TYROSINE CATABOLISM IN B6C3F1 MICE: DOSE RESPONSE RELATIONSHIPS AND AGE AS A MODIFYING FACTOR. (R825954)

    EPA Science Inventory

    Dichloroacetate (DCA) is a rodent carcinogen commonly found in municipal drinking water supplies. Toxicokinetic studies have established that elimination of DCA is controlled by liver metabolism, which occurs by the cytosolic enzyme glutathione-S-transferase-zeta (GST-z...

  5. Is high–dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Bo; Yang, Yong, E-mail: yangy2@upmc.edu; Li, Xiang

    In linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT), circular cone(s) or conformal arc(s) are conventionally used to treat intracranial lesions. However, when the target is in close proximity to critical structures, it is frequently quite challenging to generate a quality plan using these techniques. In this study, we investigated the dosimetric characteristics of using high–dose rate RapidArc (RA) technique for radiosurgical treatment of intracranial lesions. A total of 10 intracranial SRS/SRT cases previously planned using dynamic conformal arc (DCA) or cone-based techniques have been included in this study. For each case, 3 treatment plans were generated: (1) a DCA planmore » with multiple noncoplanar arcs, (2) a high–dose rate RA plan with arcs oriented the same as DCA (multiple-arc RA), and 3) a high–dose rate RA plan with a single coplanar arc (single-arc RA). All treatment plans were generated under the same prescription and similar critical structure dose limits. Plan quality for different plans was evaluated by comparing various dosimetric parameters such as target coverage, conformity index (CI), homogeneity index (HI), critical structures, and normal brain tissue doses as well as beam delivery time. With similar critical structure sparing, high–dose rate RA plans can achieve much better target coverage, dose conformity, and dose homogeneity than the DCA plans can. Plan quality indices CI and HI, for the DCA, multiple-arc RA, and single-arc RA techniques, were measured as 1.67 ± 0.39, 1.32 ± 0.28, and 1.38 ± 0.30 and 1.24 ± 0.11, 1.10 ± 0.04, and 1.12 ± 0.07, respectively. Normal brain tissue dose (V{sub 12} {sub Gy}) was found to be similar for DCA and multiple-arc RA plans but much larger for the single-arc RA plans. Beam delivery was similar for DCA and multiple-arc RA plans but shorter with single-arc RA plans. Multiple-arc RA SRS/SRT can provide better treatment plans than conventional DCA plans, especially for

  6. 77 FR 49057 - Categorical Exclusion From Further Environmental Review for Standard Terminal Arrival Route...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... Environmental Review for Standard Terminal Arrival Route Procedures for Ronald Reagan Washington National... Ronald Reagan Washington National Airport (DCA). As required by the National Environmental Policy Act, an...), TRUPS1 (RNAV), and NUMMY. Location: Ronald Reagan Washington National Airport (DCA). This project...

  7. 49 CFR 1562.21 - Scope, general requirements, and definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for... to aircraft operations into or out of Ronald Reagan Washington National Airport (DCA), fixed base... not include an armed security officer. DCA means Ronald Reagan Washington National Airport. DASSP...

  8. 49 CFR 1562.21 - Scope, general requirements, and definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for... to aircraft operations into or out of Ronald Reagan Washington National Airport (DCA), fixed base... not include an armed security officer. DCA means Ronald Reagan Washington National Airport. DASSP...

  9. 49 CFR 1562.21 - Scope, general requirements, and definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for... operators located at DCA or gateway airports; individuals designated as a security coordinator by aircraft... not include an armed security officer. DCA means Ronald Reagan Washington National Airport. DASSP...

  10. 49 CFR 1562.21 - Scope, general requirements, and definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for... operators located at DCA or gateway airports; individuals designated as a security coordinator by aircraft... not include an armed security officer. DCA means Ronald Reagan Washington National Airport. DASSP...

  11. 49 CFR 1562.21 - Scope, general requirements, and definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... WASHINGTON, DC, METROPOLITAN AREA Ronald Reagan Washington National Airport: Enhanced Security Procedures for... operators located at DCA or gateway airports; individuals designated as a security coordinator by aircraft... not include an armed security officer. DCA means Ronald Reagan Washington National Airport. DASSP...

  12. Effects of Lowering Dialysate Calcium Concentration on Mineral and Bone Disorders in Chronic Hemodialysis Patients: Conversion from 3.0 mEq/L to 2.75 mEq/L.

    PubMed

    Yamada, Shunsuke; Ueki, Kenji; Tokumoto, Masanori; Suehiro, Takaichi; Kimura, Hiroshi; Taniguchi, Masatomo; Fujimi, Satoru; Kitazono, Takanari; Tsuruya, Kazuhiko

    2016-02-01

    Selection of a lower dialysate calcium concentration (DCa) can reduce calcium burden and prevent vascular calcification in hemodialysis patients. However, decreased DCa can worsen mineral and bone disorders. This 1-year retrospective observational study evaluated 121 hemodialysis patients at Fukuoka Renal Clinic who underwent conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. The primary outcomes were changes in serum levels of calcium, phosphate, and parathyroid hormone (PTH). The effects of baseline serum calcium and PTH levels on changes in biochemical parameters were also determined. One year after DCa conversion, mean serum calcium level decreased, while serum phosphate, alkaline phosphatase, and PTH concentrations increased. The rate of achievement of target PTH was higher in patients with lower serum PTH level at baseline, while patients with higher baseline serum PTH level tended to exceed the upper limit of the PTH target range. Patients with higher baseline serum calcium concentration showed a greater decrease in serum calcium level and a greater increase in serum PTH level at 1 year. Patients with a lower baseline serum PTH level can benefit from optimal PTH control following conversion of DCa from 3.0 mEq/L to 2.75 mEq/L. However, secondary hyperparathyroidism may be exacerbated in some patients with higher baseline serum calcium (Ca) and PTH levels. These results indicate that an individualized approach can maximize the benefits of Ca unloading after conversion to lower DCa. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  13. Toxicokinetics and oral bioavailability of halogenated acetic acids mixtures in naïve and GSTzeta-depleted rats.

    PubMed

    Saghir, Shakil A; Schultz, Irvin R

    2005-04-01

    Disinfection of drinking water typically produces a mixture of mono-, di-, and tri-halogenated acetic acids (HAAs). In this study, we investigated the toxicokinetics of HAA mixtures in naive and glutathione transferase zeta 1 (GSTzeta)-depleted male F344 rats administered orally or iv to Mixture-1 (monobromo [MBAA]- dichloro- [DCAA], chlorodibromo- [CDBAA], tribromo- [TBAA] acetic acids) or Mixture-2 (bromochloro- [BCAA], dibromo- [DBAA], trichloro- [TCAA] bromodichloro- [BDCAA] acetic acids) at a dose of 25 micromol/kg HAA. Serial blood samples were collected at various times up to 36 h, and the plasma concentrations of each HAA quantified by GC-ECD. Rats were pretreated for 7 d with drinking water containing 0.2 g/l DCAA to deplete the GSTzeta (GSTZ1-1) activity in the liver. An additional group of GSTzeta-depleted rats were orally dosed with each mixture and euthanized at 0.25, 0.5, 1, 2, and 4 h to determine tissue distribution of mixture components. In both mixtures, GSTzeta depletion primarily affected the toxicokinetics of di-HAAs (DCAA, BCAA, and DBAA), with the total body clearance (Cl b) decreasing 3- to 10-fold. Interestingly, DCAA pretreatment appeared to increase the elimination of Mixture-2 tri-HAAs (TCAA and BDCAA). After oral administration, DCAA exhibited a complex time-course plasma profile with secondary peaks appearing long after completion of the initial absorption phase. This phenomenon coincided with elevated DCA levels in the lower portion of the GI tract compared to CDBAA and TBAA. Comparison of the results with previous studies employing similar or higher doses of individual HAAs indicated the primary difference in HAA toxicokinetics when administered as mixture was a reduction in Cl b. These results suggest competitive interactions between tri- and di-HAAs beyond what would be predicted from individual HAA studies. For di-HAAs, the total dose is important, as clearance is dose dependent due to competition for GSTzeta. When considering HAA

  14. Determination of 17-oxosteroid glucuronides and sulfates in urine and serum by fluorescence high-performance liquid chromatography using dansyl hydrazine as a prelabeling reagent.

    PubMed

    Kawasaki, T; Maeda, M; Tsuji, A

    1982-12-10

    A fluorescence high-performance liquid chromatographic method is described for the direct determination of conjugated 17-oxosteroids in biological fluids without hydrolysis. Conjugated 17-oxosteroids are extracted with Sep-Pak C18 cartridge, labeled with dansyl hydrazine in trichloroacetic acid--benzene solution and then separated by high-performance liquid chromatography on reversed-phase muBondapak C18 column using 0.01 M sodium acetate in methanol-water-acetic acid (65:35:1, v/v) as the mobile phase. The eluate is monitored by a fluorophotometer at 365 nm (excitation) and 520 nm (emission). Linearities of fluorescence intensities (peak heights) with the amounts of various conjugated 17-oxosteroids were obtained between 10 pmol and 100 pmol. This method is sensitive, reliable and useful for the simultaneous determination of conjugated 17-oxosteroids in urine and serum.

  15. Application of decline curve analysis to estimate recovery factors for carbon dioxide enhanced oil recovery

    USGS Publications Warehouse

    Jahediesfanjani, Hossein

    2017-07-17

    IntroductionIn the decline curve analysis (DCA) method of estimating recoverable hydrocarbon volumes, the analyst uses historical production data from a well, lease, group of wells (or pattern), or reservoir and plots production rates against time or cumu­lative production for the analysis. The DCA of an individual well is founded on the same basis as the fluid-flow principles that are used for pressure-transient analysis of a single well in a reservoir domain and therefore can provide scientifically reasonable and accurate results. However, when used for a group of wells, a lease, or a reservoir, the DCA becomes more of an empirical method. Plots from the DCA reflect the reservoir response to the oil withdrawal (or production) under the prevailing operating and reservoir conditions, and they continue to be good tools for estimating recoverable hydrocarbon volumes and future production rates. For predicting the total recov­erable hydrocarbon volume, the DCA results can help the analyst to evaluate the reservoir performance under any of the three phases of reservoir productive life—primary, secondary (waterflood), or tertiary (enhanced oil recovery) phases—so long as the historical production data are sufficient to establish decline trends at the end of the three phases.

  16. Enhancing MRI of liver metastases with a zwitterionized biodegradable dendritic contrast agent.

    PubMed

    Zhou, Xiaoxuan; Ye, Mingzhou; Han, Yuxin; Tang, Jianbin; Qian, Yue; Hu, Hongjie; Shen, Youqing

    2017-07-25

    Metastasis is the main reason for cancer-associated mortality, and accurate diagnostic imaging of metastases is critical for the clinical administration and tailoring personalized treatments for metastatic tumors. However, magnetic resonance imaging of metastases in the liver is impeded by its low sensitivity because the currently used contrast agents accumulate in hepatocytes and Kupffer cells instead of cancer cells. Herein, a 4 th generation zwitterionized biodegradable dendritic contrast agent (DCA) with a size of ca. 9 nm and a longitudinal relaxivity of 15.7 mM -1 s -1 in terms of Gd was synthesized and used to enhance the MRI of liver metastasis. The DCA could remarkably enhance the MRI of metastasized tumors in the liver, because it could simultaneously reduce the background signal in the liver by avoiding uptake by hepatocytes and Kupffer cells through the zwitterionization and increase the signal in tumors through the enhanced permeability and retention effect. Moreover, in contrast to non-biodegradable DCA, this DCA showed minimal long-term Gd 3+ retention in all organs and tissues because it could be degraded into small fragments. The significant capability of enhancing the MRI of metastases in the liver plus its excellent biodegradability made this DCA a promising CA for metastatic tumor imaging.

  17. Washington, D.C. - Local Information | NREL

    Science.gov Websites

    International Airport (IAD), and Baltimore/Washington International Thurgood Marshall Airport (BWI). DCA is the additional information. Reagan National Airport - DCA Dulles International Airport - IAD Baltimore/Washington International Thurgood Marshall Airport - BWI Public Transportation The Washington Metropolitan Area Transit

  18. Temporal genetic structure of a drone congregation area of the giant Asian honeybee ( Apis dorsata)

    NASA Astrophysics Data System (ADS)

    Kraus, F. B.; Koeniger, N.; Tingek, S.; Moritz, R. F. A.

    2005-12-01

    The giant Asian honeybee ( Apis dorsata), like all other members of the genus Apis, has a complex mating system in which the queens and males (drones) mate at spatially defined drone congregation areas (DCAs). Here, we studied the temporal genetic structure of a DCA of A. dorsata over an 8-day time window by the genotyping of sampled drones with microsatellite markers. Analysis of the genotypic data revealed a significant genetic differentiation between 3 sampling days and indicated that the DCA was used by at least two subpopulations at all days in varying proportions. The estimation of the number of colonies which used the DCA ranged between 20 and 40 colonies per subpopulation, depending on the estimation procedure and population. The overall effective population size was estimated as high as N e=140. The DCA seems to counteract known tendencies of A. dorsata for inbreeding within colony aggregations by facilitating gene flow among subpopulations and increasing the effective population size.

  19. A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock.

    PubMed

    Boyd, Joseph S; Cheng, Ryan R; Paddock, Mark L; Sancar, Cigdem; Morcos, Faruck; Golden, Susan S

    2016-09-15

    Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium Synechococcus elongatus PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct-coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (cikB) in a sasA cikA null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems. Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently

  20. Volumetric Modulated Arc Radiotherapy for Vestibular Schwannomas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lagerwaard, Frank J.; Meijer, Otto W.M.; Hoorn, Elles A.P. van der

    2009-06-01

    Purpose: To evaluate volumetric modulated arc radiotherapy (RapidArc [RA]), a novel approach allowing for rapid treatment delivery, for the treatment of vestibular schwannoma (VS). Methods and Materials: The RA plans were generated for a small (0.5 cm{sup 3}), intermediate (2.8 cm{sup 3}), and large (14.8 cm{sup 3}) VS. The prescription dose was 12.5 Gy to the encompassing 80% isodose. The RA plans were compared with conventional radiosurgery plans using both a single dynamic conformal arc (1DCA) and five noncoplanar dynamic conformal arcs (5DCA). Conformity indices (CI) and dose-volume histograms of critical organs were compared. The RA plan for the medium-sizedmore » VS was measured in a phantom using Gafchromic EBT films and compared with calculated dose distributions. Results: The RA planning was completed within 30 min in all cases, and calculated treatment delivery time (after patient setup) was 5 min vs. 20 min for 5DCA. A superior CI was achieved with RA, with a substantial decrease in low-dose irradiation of the normal brain achieved relative to 5DCA plans. Maximum doses to critical organs were similar for RA and 5DCA but were higher for 1DCA. Film measurements showed the differences between calculated and measured doses to be smaller than 1.5% in the high-dose area and smaller than 3% in the low-dose area. Conclusion: The RA plans consistently achieved a higher CI and decrease in areas of low-dose irradiation. This, together with shorter treatment delivery times, has led to RA replacing our conventional five-arc radiosurgery technique for VS.« less

  1. High-throughput sample processing and sample management; the functional evolution of classical cytogenetic assay towards automation.

    PubMed

    Ramakumar, Adarsh; Subramanian, Uma; Prasanna, Pataje G S

    2015-11-01

    High-throughput individual diagnostic dose assessment is essential for medical management of radiation-exposed subjects after a mass casualty. Cytogenetic assays such as the Dicentric Chromosome Assay (DCA) are recognized as the gold standard by international regulatory authorities. DCA is a multi-step and multi-day bioassay. DCA, as described in the IAEA manual, can be used to assess dose up to 4-6 weeks post-exposure quite accurately but throughput is still a major issue and automation is very essential. The throughput is limited, both in terms of sample preparation as well as analysis of chromosome aberrations. Thus, there is a need to design and develop novel solutions that could utilize extensive laboratory automation for sample preparation, and bioinformatics approaches for chromosome-aberration analysis to overcome throughput issues. We have transitioned the bench-based cytogenetic DCA to a coherent process performing high-throughput automated biodosimetry for individual dose assessment ensuring quality control (QC) and quality assurance (QA) aspects in accordance with international harmonized protocols. A Laboratory Information Management System (LIMS) is designed, implemented and adapted to manage increased sample processing capacity, develop and maintain standard operating procedures (SOP) for robotic instruments, avoid data transcription errors during processing, and automate analysis of chromosome-aberrations using an image analysis platform. Our efforts described in this paper intend to bridge the current technological gaps and enhance the potential application of DCA for a dose-based stratification of subjects following a mass casualty. This paper describes one such potential integrated automated laboratory system and functional evolution of the classical DCA towards increasing critically needed throughput. Published by Elsevier B.V.

  2. Electron Microscopy of Staphylococcus aureus Cell Wall Lysis

    PubMed Central

    Virgilio, R.; González, C.; Muñoz, Nubia; Mendoza, Silvia

    1966-01-01

    Virgilio, Rafael (Escuela de Química y Farmacia, Universidad de Chile, Santiago, Chile), C. González, Nubia Muñoz, and Silvia Mendoza. Electron microscopy of Staphylococcus aureus cell wall lysis. J. Bacteriol. 91:2018–2024. 1966.—A crude suspension of Staphylococcus aureus cell walls (strain Cowan III) in buffer solution was shown by electron microscopy to lyse slightly after 16 hr, probably owing to the action of autolysin. The lysis was considerably faster and more intense after the addition of lysozyme. A remarkable reduction in thickness and rigidity of the cell walls, together with the appearance of many irregular protrusions in their outlines, was observed after 2 hr; after 16 hr, there remained only a few recognizable cell wall fragments but many residual particulate remnants. When autolysin was previously inactivated by trypsin, there was a complete inhibition of the lytic action of lysozyme; on the other hand, when autolysin was inactivated by heat and lysozyme was added, a distinct decrease in the thickness of the cell walls was observed, but there was no destruction of the walls. The lytic action of lysozyme, after treatment with hot 5% trichloroacetic acid, gave rise to a marked dissolution of the structure of the cell walls, which became lost against the background, without, however, showing ostensible alteration of wall outlines. From a morphological point of view, the lytic action of autolysin plus lysozyme was quite different from that of trichloroacetic acid plus lysozyme, as shown by electron micrographs, but in both cases it was very intense. This would suggest different mechanisms of action for these agents. Images PMID:5939482

  3. Electron microscopy of Staphylococcus aureus cell wall lysis.

    PubMed

    Virgilio, R; González, C; Muñoz, N; Mendoza, S

    1966-05-01

    Virgilio, Rafael (Escuela de Química y Farmacia, Universidad de Chile, Santiago, Chile), C. González, Nubia Muñoz, and Silvia Mendoza. Electron microscopy of Staphylococcus aureus cell wall lysis. J. Bacteriol. 91:2018-2024. 1966.-A crude suspension of Staphylococcus aureus cell walls (strain Cowan III) in buffer solution was shown by electron microscopy to lyse slightly after 16 hr, probably owing to the action of autolysin. The lysis was considerably faster and more intense after the addition of lysozyme. A remarkable reduction in thickness and rigidity of the cell walls, together with the appearance of many irregular protrusions in their outlines, was observed after 2 hr; after 16 hr, there remained only a few recognizable cell wall fragments but many residual particulate remnants. When autolysin was previously inactivated by trypsin, there was a complete inhibition of the lytic action of lysozyme; on the other hand, when autolysin was inactivated by heat and lysozyme was added, a distinct decrease in the thickness of the cell walls was observed, but there was no destruction of the walls. The lytic action of lysozyme, after treatment with hot 5% trichloroacetic acid, gave rise to a marked dissolution of the structure of the cell walls, which became lost against the background, without, however, showing ostensible alteration of wall outlines. From a morphological point of view, the lytic action of autolysin plus lysozyme was quite different from that of trichloroacetic acid plus lysozyme, as shown by electron micrographs, but in both cases it was very intense. This would suggest different mechanisms of action for these agents.

  4. Glutaric aciduria type I and methylmalonic aciduria: simulation of cerebral import and export of accumulating neurotoxic dicarboxylic acids in in vitro models of the blood-brain barrier and the choroid plexus.

    PubMed

    Sauer, Sven W; Opp, Silvana; Mahringer, Anne; Kamiński, Marcin M; Thiel, Christian; Okun, Jürgen G; Fricker, Gert; Morath, Marina A; Kölker, Stefan

    2010-06-01

    Intracerebral accumulation of neurotoxic dicarboxylic acids (DCAs) plays an important pathophysiological role in glutaric aciduria type I and methylmalonic aciduria. Therefore, we investigated the transport characteristics of accumulating DCAs - glutaric (GA), 3-hydroxyglutaric (3-OH-GA) and methylmalonic acid (MMA) - across porcine brain capillary endothelial cells (pBCEC) and human choroid plexus epithelial cells (hCPEC) representing in vitro models of the blood-brain barrier (BBB) and the choroid plexus respectively. We identified expression of organic acid transporters 1 (OAT1) and 3 (OAT3) in pBCEC on mRNA and protein level. For DCAs tested, transport from the basolateral to the apical site (i.e. efflux) was higher than influx. Efflux transport of GA, 3-OH-GA, and MMA across pBCEC was Na(+)-dependent, ATP-independent, and was inhibited by the OAT substrates para-aminohippuric acid (PAH), estrone sulfate, and taurocholate, and the OAT inhibitor probenecid. Members of the ATP-binding cassette transporter family or the organic anion transporting polypeptide family, namely MRP2, P-gp, BCRP, and OATP1B3, did not mediate transport of GA, 3-OH-GA or MMA confirming the specificity of efflux transport via OATs. In hCPEC, cellular import of GA was dependent on Na(+)-gradient, inhibited by NaCN, and unaffected by probenecid suggesting a Na(+)-dependent DCA transporter. Specific transport of GA across hCPEC, however, was not found. In conclusion, our results indicate a low but specific efflux transport for GA, 3-OH-GA, and MMA across pBCEC, an in vitro model of the BBB, via OAT1 and OAT3 but not across hCPEC, an in vitro model of the choroid plexus. Copyright 2010 Elsevier B.V. All rights reserved.

  5. Transcriptional Profile during Deoxycholate-Induced Sporulation in a Clostridium perfringens Isolate Causing Foodborne Illness.

    PubMed

    Yasugi, Mayo; Okuzaki, Daisuke; Kuwana, Ritsuko; Takamatsu, Hiromu; Fujita, Masaya; Sarker, Mahfuzur R; Miyake, Masami

    2016-05-15

    Clostridium perfringens type A is a common source of foodborne illness (FBI) in humans. Vegetative cells sporulate in the small intestinal tract and produce the major pathogenic factor C. perfringens enterotoxin. Although sporulation plays a critical role in the pathogenesis of FBI, the mechanisms inducing sporulation remain unclear. Bile salts were shown previously to induce sporulation, and we confirmed deoxycholate (DCA)-induced sporulation in C. perfringens strain NCTC8239 cocultured with human intestinal epithelial Caco-2 cells. In the present study, we performed transcriptome analyses of strain NCTC8239 in order to elucidate the mechanism underlying DCA-induced sporulation. Of the 2,761 genes analyzed, 333 were up- or downregulated during DCA-induced sporulation and included genes for cell division, nutrient metabolism, signal transduction, and defense mechanisms. In contrast, the virulence-associated transcriptional regulators (the VirR/VirS system, the agr system, codY, and abrB) were not activated by DCA. DCA markedly increased the expression of signaling molecules controlled by Spo0A, the master regulator of the sporulation process, whereas the expression of spo0A itself was not altered in the presence or absence of DCA. The phosphorylation of Spo0A was enhanced in the presence of DCA. Collectively, these results demonstrated that DCA induced sporulation, at least partially, by facilitating the phosphorylation of Spo0A and activating Spo0A-regulated genes in strain NCTC8239 while altering the expression of various genes. Disease caused by Clostridium perfringens type A consistently ranks among the most common bacterial foodborne illnesses in humans in developed countries. The sporulation of C. perfringens in the small intestinal tract is a key event for its pathogenesis, but the factors and underlying mechanisms by which C. perfringens sporulates in vivo currently remain unclear. Bile salts, major components of bile, which is secreted from the liver for

  6. Transcriptional Profile during Deoxycholate-Induced Sporulation in a Clostridium perfringens Isolate Causing Foodborne Illness

    PubMed Central

    Okuzaki, Daisuke; Kuwana, Ritsuko; Takamatsu, Hiromu; Fujita, Masaya; Sarker, Mahfuzur R.; Miyake, Masami

    2016-01-01

    ABSTRACT Clostridium perfringens type A is a common source of foodborne illness (FBI) in humans. Vegetative cells sporulate in the small intestinal tract and produce the major pathogenic factor C. perfringens enterotoxin. Although sporulation plays a critical role in the pathogenesis of FBI, the mechanisms inducing sporulation remain unclear. Bile salts were shown previously to induce sporulation, and we confirmed deoxycholate (DCA)-induced sporulation in C. perfringens strain NCTC8239 cocultured with human intestinal epithelial Caco-2 cells. In the present study, we performed transcriptome analyses of strain NCTC8239 in order to elucidate the mechanism underlying DCA-induced sporulation. Of the 2,761 genes analyzed, 333 were up- or downregulated during DCA-induced sporulation and included genes for cell division, nutrient metabolism, signal transduction, and defense mechanisms. In contrast, the virulence-associated transcriptional regulators (the VirR/VirS system, the agr system, codY, and abrB) were not activated by DCA. DCA markedly increased the expression of signaling molecules controlled by Spo0A, the master regulator of the sporulation process, whereas the expression of spo0A itself was not altered in the presence or absence of DCA. The phosphorylation of Spo0A was enhanced in the presence of DCA. Collectively, these results demonstrated that DCA induced sporulation, at least partially, by facilitating the phosphorylation of Spo0A and activating Spo0A-regulated genes in strain NCTC8239 while altering the expression of various genes. IMPORTANCE Disease caused by Clostridium perfringens type A consistently ranks among the most common bacterial foodborne illnesses in humans in developed countries. The sporulation of C. perfringens in the small intestinal tract is a key event for its pathogenesis, but the factors and underlying mechanisms by which C. perfringens sporulates in vivo currently remain unclear. Bile salts, major components of bile, which is secreted

  7. Associations Between Disinfection By-Product Exposures and Craniofacial Birth Defects.

    PubMed

    Kaufman, John A; Wright, J Michael; Evans, Amanda; Rivera-Núñez, Zorimar; Meyer, Amy; Narotsky, Michael G

    2018-02-01

    The aim of this study was to examine associations between craniofacial birth defects (CFDs) and disinfection by-product (DBP) exposures, including the sum of four trihalomethanes (THM4) and five haloacetic acids (HAA5) (ie, DBP9). We calculated first trimester adjusted odds ratios (aORs) for different DBPs in a matched case-control study of 366 CFD cases in Massachusetts towns with complete 1999 to 2004 THM and HAA data. We detected elevated aORs for cleft palate with DBP9 (highest quintile aOR = 3.52; 95% CI: 1.07, 11.60), HAA5, trichloroacetic acid (TCAA), and dichloroacetic acid. We detected elevated aORs for eye defects with TCAA and chloroform. This is the first epidemiological study of DBPs to examine eye and ear defects, as well as HAAs and CFDs. The associations for cleft palate and eye defects highlight the importance of examining specific defects and DBPs beyond THM4.

  8. Trichloroethylene Biotransformation and its Role in Mutagenicity, Carcinogenicity and Target Organ Toxicity

    PubMed Central

    Lash, Lawrence H.; Chiu, Weihsueh A.; Guyton, Kathryn Z.; Rusyn, Ivan

    2014-01-01

    Metabolism is critical for the mutagenicity, carcinogenicity, and other adverse health effects of trichloroethylene (TCE). Despite the relatively small size and simple chemical structure of TCE, its metabolism is quite complex, yielding multiple intermediates and end-products. Experimental animal and human data indicate that TCE metabolism occurs through two major pathways: cytochrome P450 (CYP)-dependent oxidation and glutathione (GSH) conjugation catalyzed by GSH S-transferases (GSTs). Herein we review recent data characterizing TCE processing and flux through these pathways. We describe the catalytic enzymes, their regulation and tissue localization, as well as the evidence for transport and inter-organ processing of metabolites. We address the chemical reactivity of TCE metabolites, highlighting data on mutagenicity of these end-products. Identification in urine of key metabolites, particularly trichloroacetate (TCA), dichloroacetate (DCA), trichloroethanol and its glucuronide (TCOH and TCOG), and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAcDCVC), in exposed humans and other species (mostly rats and mice) demonstrates function of the two metabolic pathways in vivo. The CYP pathway primarily yields chemically stable end-products. However, the GST pathway conjugate S-(1,2-dichlorovinyl)glutathione (DCVG) is further processed to multiple highly reactive species that are known to be mutagenic, especially in kidney where in situ metabolism occurs. TCE metabolism is highly variable across sexes, species, tissues and individuals. Genetic polymorphisms in several of the key enzymes metabolizing TCE and its intermediates contribute to variability in metabolic profiles and rates. In all, the evidence characterizing the complex metabolism of TCE can inform predictions of adverse responses including mutagenesis, carcinogenesis, and acute and chronic organ-specific toxicity. PMID:25484616

  9. Culturing and extraction of Coprococcus comes, absorption of serumagglutinins by soluble fractions and relation between agglutinins and antibodies in sera of patients with Crohn's disease.

    PubMed

    Hazenberg, M P; Pennock-Schröder, A M; van de Merwe, J P

    1986-01-01

    Agglutinating antibodies to Coprococcus comes and three other obligately anaerobic coccoid rods from the intestinal flora are used in the diagnosis of Crohn's disease. Further studies on the pathogenetic role as well as the development of more sensitive and specific methods for detecting antibodies require extraction of the antigen fractions. Culturing methods to obtain C. comes with optimal antigen presentation and isolation of soluble antigen fractions were therefore developed. Hot water extraction of whole cells and subsequent removal of proteins with trichloroacetic acid provided a fraction that absorbed serum agglutinins, was useful for an enzyme-linked immunosorbent assay and induced agglutinating antibodies in rats.

  10. Management of external genital warts.

    PubMed

    Karnes, Jonathan B; Usatine, Richard P

    2014-09-01

    Genital warts affect 1% of the sexually active U.S. population and are commonly seen in primary care. Human papillomavirus types 6 and 11 are responsible for most genital warts. Warts vary from small, flat-topped papules to large, cauliflower-like lesions on the anogenital mucosa and surrounding skin. Diagnosis is clinical, but atypical lesions should be confirmed by histology. Treatments may be applied by patients, or by a clinician in the office. Patient-applied treatments include topical imiquimod, podofilox, and sinecatechins, whereas clinician-applied treatments include podophyllin, bichloroacetic acid, and trichloroacetic acid. Surgical treatments include excision, cryotherapy, and electrosurgery. The quadrivalent human papillomavirus vaccine is active against virus subtypes that cause genital warts in men and women. Additionally, male circumcision may be effective in decreasing the transmission of human immunodeficiency virus, human papillomavirus, and herpes simplex virus.

  11. Comparison of three versions of Partin tables to predict final pathologic stage in a Chinese cohort: a decision curve analysis.

    PubMed

    Xiao, Wen-Jun; Ye, Ding-Wei; Yao, Xu-Dong; Zhang, Shi-Lin; Dai, Bo

    2013-01-01

    To compare Partin tables (PTs) 1997, 2001, and 2007 for their clinical applicability in a Chinese cohort based upon a decision curve analysis (DCA). Clinical and pathologic data of 264 consecutive Chinese patients with clinically localized prostate cancer were used. These patients underwent open radical prostatectomy between 2005 and 2011. DCA quantified the net benefit of different PT versions relating to specific threshold probabilities of established capsular penetration (ECP), seminal vesicle involvement (SVI), and lymph node involvement (LNI). Overall, ECP, SVI, and LNI were recorded in 23.1, 10.2, and 6.1%, respectively. When the threshold probability was below the prevalence for LNI and ECP predictions, the DCA favored the 2007 version versus the 1997 version for SVI. DCA indicates that for low threshold probability, decision models are useful to discriminate the performance differences of three PT versions, although net benefit differences were not apparent. For high threshold probability, there may not be an important benefit from the use of PTs and the current analysis cannot translate into meaningful net gains differences. Copyright © 2013 S. Karger AG, Basel.

  12. Didehydro-Cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and prevents potentiation of cocaine reward in Tat transgenic mice

    PubMed Central

    Mediouni, Sonia; Jablonski, Joseph; Paris, Jason J.; Clementz, Mark A.; Thenin-Houssier, Suzie; McLaughlin, Jay P.; Valente, Susana T.

    2015-01-01

    HIV-1 Tat protein has been shown to have a crucial role in HIV-1-associated neurocognitive disorders (HAND), which includes a group of syndromes ranging from undetectable neurocognitive impairment to dementia. The abuse of psychostimulants, such as cocaine, by HIV infected individuals, may accelerate and intensify neurological damage. On the other hand, exposure to Tat potentiates cocaine-mediated reward mechanisms, which further promotes HAND. Here, we show that didehydro-Cortistatin A (dCA), an analog of a natural steroidal alkaloid, crosses the blood-brain barrier, cross-neutralizes Tat activity from several HIV-1 clades and decreases Tat uptake by glial cell lines. In addition, dCA potently inhibits Tat mediated dysregulation of IL-1β, TNF-α and MCP-1, key neuroinflammatory signaling proteins. Importantly, using a mouse model where doxycycline induces Tat expression, we demonstrate that dCA reverses the potentiation of cocaine-mediated reward. Our results suggest that adding a Tat inhibitor, such as dCA, to current antiretroviral therapy may reduce HIV-1-related neuropathogenesis. PMID:25613133

  13. Effect of dynamic controlled atmosphere monitored by respiratory quotient and 1-methylcyclopropene on the metabolism and quality of 'Galaxy' apple harvested at three maturity stages.

    PubMed

    Thewes, Fabio Rodrigo; Brackmann, Auri; Anese, Rogerio de Oliveira; Ludwig, Vagner; Schultz, Erani Eliseu; Dos Santos, Luana Ferreira; Wendt, Lucas Mallmann

    2017-05-01

    The objective of this study was to evaluate the interaction between controlled atmosphere (CA), CA+1-methylcyclopropene (1-MCP) and dynamic controlled atmosphere monitored by respiratory quotient (DCA-RQ) with three fruit maturity stages at harvest (early harvest date, optimal harvest date and late harvest date) on 'Galaxy' apple metabolism and quality after harvest and 9months storage plus 7days of shelf life at 20°C. Fruit stored under dynamic controlled atmosphere monitored by respiratory quotient 1.3 (DCA-RQ 1.3) showed lower ethylene production, respiration rate, mealiness and higher flesh firmness in comparison to CA stored fruit, but did not differ from those treated with 1-MCP. The dynamic controlled atmosphere monitored by respiratory quotient 1.5 (DCA-RQ 1.5) increased the acetaldehyde, ethanol and ethyl acetate concentration, regardless of the fruit maturity at harvest. The storage of 'Galaxy' apple under DCA-RQ 1.3 is efficient in keeping quality regardless of the maturity stage at harvest. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Robust demarcation of basal cell carcinoma by dependent component analysis-based segmentation of multi-spectral fluorescence images.

    PubMed

    Kopriva, Ivica; Persin, Antun; Puizina-Ivić, Neira; Mirić, Lina

    2010-07-02

    This study was designed to demonstrate robust performance of the novel dependent component analysis (DCA)-based approach to demarcation of the basal cell carcinoma (BCC) through unsupervised decomposition of the red-green-blue (RGB) fluorescent image of the BCC. Robustness to intensity fluctuation is due to the scale invariance property of DCA algorithms, which exploit spectral and spatial diversities between the BCC and the surrounding tissue. Used filtering-based DCA approach represents an extension of the independent component analysis (ICA) and is necessary in order to account for statistical dependence that is induced by spectral similarity between the BCC and surrounding tissue. This generates weak edges what represents a challenge for other segmentation methods as well. By comparative performance analysis with state-of-the-art image segmentation methods such as active contours (level set), K-means clustering, non-negative matrix factorization, ICA and ratio imaging we experimentally demonstrate good performance of DCA-based BCC demarcation in two demanding scenarios where intensity of the fluorescent image has been varied almost two orders of magnitude. Copyright 2010 Elsevier B.V. All rights reserved.

  15. A distinct entorhinal cortex to hippocampal CA1 direct circuit for olfactory associative learning.

    PubMed

    Li, Yiding; Xu, Jiamin; Liu, Yafeng; Zhu, Jia; Liu, Nan; Zeng, Wenbo; Huang, Ning; Rasch, Malte J; Jiang, Haifei; Gu, Xiang; Li, Xiang; Luo, Minhua; Li, Chengyu; Teng, Junlin; Chen, Jianguo; Zeng, Shaoqun; Lin, Longnian; Zhang, Xiaohui

    2017-04-01

    Lateral and medial parts of entorhinal cortex (EC) convey nonspatial 'what' and spatial 'where' information, respectively, into hippocampal CA1, via both the indirect EC layer 2→ hippocampal dentate gyrus→CA3→CA1 and the direct EC layer 3→CA1 paths. However, it remains elusive how the direct path transfers distinct information and contributes to hippocampal learning functions. Here we report that lateral EC projection neurons selectively form direct excitatory synapses onto a subpopulation of morphologically complex, calbindin-expressing pyramidal cells (PCs) in the dorsal CA1 (dCA1), while medial EC neurons uniformly innervate all dCA1 PCs. Optogenetically inactivating the distinct lateral EC-dCA1 connections or the postsynaptic dCA1 calbindin-expressing PC activity slows olfactory associative learning. Moreover, optetrode recordings reveal that dCA1 calbindin-expressing PCs develop more selective spiking responses to odor cues during learning. Thus, our results identify a direct lateral EC→dCA1 circuit that is required for olfactory associative learning.

  16. Design and performance of controlled-diffusion stator compared with original double-circular-arc stator

    NASA Technical Reports Server (NTRS)

    Gelder, Thomas F.; Schmidt, James F.; Suder, Kenneth L.; Hathaway, Michael D.

    1987-01-01

    The capabilities of two stators, one with controlled-diffusion (CD) blade sections and one with double-circular-arc (DCA) blade sections, were compared. A CD stator was designed and tested that had the same chord length but half the blades of the DCA stator. The same fan rotor (tip speed, 429 m/sec; pressure ratio, 1.65) was used with each stator row. The design and analysis system is briefly described. The overall stage and rotor performances with each stator are compared, as are selected blade element data. The minimum overall efficiency decrement across the stator was approximately 1 percentage point greater with the CD balde sections than with the DCA blade sections.

  17. Design and performance of controlled-diffusion stator compared with original double-circular-arc stator

    NASA Technical Reports Server (NTRS)

    Gelder, Thomas F.; Schmidt, James F.; Suder, Kenneth L.; Hathaway, Michael D.

    1987-01-01

    The capabilities of two stators, one with controlled-diffusion (CD) blade sections and one with double-circular-arc (DCA) blade sections, were compared. A CD stator was designed and tested that had the same chord length but half the blades of the DCA stator. The same fan rotor (tip speed, 429 m/sec; pressure ratio, 1.65) was used with each stator row. The design and analysis system is briefly described. The overall stage and rotor performances with each stator are compared, as are selected blade element data. The minimum overall efficiency decrement across the stator was approximately 1 percentage point greater with the CD blade sections than with the DCA blade sections.

  18. Derivative component analysis for mass spectral serum proteomic profiles.

    PubMed

    Han, Henry

    2014-01-01

    As a promising way to transform medicine, mass spectrometry based proteomics technologies have seen a great progress in identifying disease biomarkers for clinical diagnosis and prognosis. However, there is a lack of effective feature selection methods that are able to capture essential data behaviors to achieve clinical level disease diagnosis. Moreover, it faces a challenge from data reproducibility, which means that no two independent studies have been found to produce same proteomic patterns. Such reproducibility issue causes the identified biomarker patterns to lose repeatability and prevents it from real clinical usage. In this work, we propose a novel machine-learning algorithm: derivative component analysis (DCA) for high-dimensional mass spectral proteomic profiles. As an implicit feature selection algorithm, derivative component analysis examines input proteomics data in a multi-resolution approach by seeking its derivatives to capture latent data characteristics and conduct de-noising. We further demonstrate DCA's advantages in disease diagnosis by viewing input proteomics data as a profile biomarker via integrating it with support vector machines to tackle the reproducibility issue, besides comparing it with state-of-the-art peers. Our results show that high-dimensional proteomics data are actually linearly separable under proposed derivative component analysis (DCA). As a novel multi-resolution feature selection algorithm, DCA not only overcomes the weakness of the traditional methods in subtle data behavior discovery, but also suggests an effective resolution to overcoming proteomics data's reproducibility problem and provides new techniques and insights in translational bioinformatics and machine learning. The DCA-based profile biomarker diagnosis makes clinical level diagnostic performances reproducible across different proteomic data, which is more robust and systematic than the existing biomarker discovery based diagnosis. Our findings demonstrate

  19. Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Perez, Maria J.; Castano, Beatriz; Jimenez, Silvia

    Maternal cholestasis causes oxidative damage to the placental-fetal unit that may challenge the outcome of pregnancy. This has been associated with the accumulation of biliary compounds able to induce oxidative stress. However, other cholephilic compounds such as ursodeoxycholic acid (UDCA) and bilirubin have direct anti-oxidant properties. In the present study we investigated whether these compounds exert a protective effect on cholestasis-induced oxidative stress in placenta as compared to maternal and fetal livers, and whether this is due in part to the activation of anti-oxidant mechanisms involving vitamin C uptake and biliverdin/bilirubin recycling. In human placenta (JAr) and liver (HepG2) cells,more » deoxycholic acid (DCA) similar rates of free radical generation. In JAr (not HepG2), the mitochondrial membrane potential and cell viability were impaired by low DCA concentrations; this was partly prevented by bilirubin and UDCA. In HepG2, taurocholic acid (TCA) and UDCA up-regulated biliverdin-IX{alpha} reductase (BVR{alpha}) and the vitamin C transporter SVCT2 (not SVCT1), whereas bilirubin up-regulated both SVCT1 and SVCT2. In JAr, TCA and UDCA up-regulated BVR{alpha}, SVCT1 and SVCT2, whereas bilirubin up-regulated only SVCT2. A differential response to these compounds of nuclear receptor expression (SXR, CAR, FXR and SHP) was found in both cell types. When cholestasis was induced in pregnant rats, BVR{alpha}, SVCT1 and SVCT2 expression in maternal and fetal livers was stimulated, and this was further enhanced by UDCA treatment. In placenta, only BVR{alpha} was up-regulated. In conclusion, bilirubin accumulation and UDCA administration may directly and indirectly protect the placental-fetal unit from maternal cholestasis-induced oxidative stress.« less

  20. Pharmacokinetic study of isocorynoxeine metabolites mediated by cytochrome P450 enzymes in rat and human liver microsomes.

    PubMed

    Zhao, Lizhu; Zang, Bin; Qi, Wen; Chen, Fangfang; Wang, Haibo; Kano, Yoshihiro; Yuan, Dan

    2016-06-01

    Isocorynoxeine (ICN) is one of the major bioactive tetracyclic oxindole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks. that is widely used for the treatment of hypertension, vascular dementia, and stroke. The present study was undertaken to assess the plasma pharmacokinetic characteristics of major ICN metabolites, and the role of simulated gastric and intestinal fluid (SGF and SIF), human and rat liver microsomes (HLMs and RLMs), and seven recombinant human CYP enzymes in the major metabolic pathway of ICN. A rapid, sensitive and accurate UHPLC/Q-TOF MS method was validated for the simultaneous determination of ICN and its seven metabolites in rat plasma after oral administration of ICN at 40mg/kg. It was found that 18.19-dehydrocorynoxinic acid (DCA) and 5-oxoisocorynoxeinic acid (5-O-ICA) were both key and predominant metabolites, rather than ICN itself, due to the rapid and extensive metabolism of ICN in vivo. The further study indicated that ICN was mainly metabolized in human or rat liver, and CYPs 2C19, 3A4 and 2D6 were the major enzymes responsible for the biotransformation of ICN to DCA and 5-O-ICA in human. These findings are of significance in understanding of the pharmacokinetic nature of tetracyclic oxindole alkaloids, and provide helpful information for the clinical co-administration of the herbal preparations containing U. rhynchophylla with antihypertensive drugs that are mainly metabolized by CYP3A4 and CYP2C19. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Proposal for Development of EBM-CDSS (Evidence-Based Clinical Decision Support System) to Aid Prognostication in Terminally Ill Patients

    DTIC Science & Technology

    2010-10-01

    Mathematics , Indiana University Northwest, Gary, IN 3Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, NY 4H...however, is mathematically more parsimonious. The original DCA formulation required several mathematical manipulations making the simplicity of regret...into treatment administration examples; IH developed the mathematical formulation of the model; AV is the author of DCA; BD proposed the regret theory

  2. THE OCCURRENCE OF APIOSE IN LEMNA (DUCKWEED) AND OTHER ANGIOSPERMS.

    PubMed

    DUFF, R B

    1965-03-01

    1. The branched-chain pentose apiose reacts with the benzidine-trichloroacetic acid reagent on paper chromatograms to give a yellow spot with.an intense white fluorescence in ultraviolet light; on chromatograms developed with butanol-acetic acid-water this spot lies between fucose and rhamnose. 2. Examination of paper chromatograms of hydrolysates of whole plant material has shown the presence of a substance with these properties in a wide variety of species. 3. Among the plants examined two members of the Lemnaceae (Lemna minor and Wolffia arrhiza) were found to be especially rich sources, comparable with Posidonia australis (Bell, Hardwick, Isherwood & Cahn, 1954). 4. Measurements of the apiose content of fractions derived from Lemna have shown that the sugar is present at a concentration of about 4% in the holocellulose, and part of this is retained in the alpha-cellulose left by extraction with 24% (w/v) potassium hydroxide containing borate.

  3. Substrate interactions in dehalogenation of 1,2-dichloroethane, 1,2-dichloropropane, and 1,1,2-trichloroethane mixtures by Dehalogenimonas spp.

    PubMed

    Dillehay, Jacob L; Bowman, Kimberly S; Yan, Jun; Rainey, Fred A; Moe, William M

    2014-04-01

    When chlorinated alkanes are present as soil or groundwater pollutants, they often occur in mixtures. This study evaluated substrate interactions during the anaerobic reductive dehalogenation of chlorinated alkanes by the type strains of two Dehalogenimonas species, D. lykanthroporepellens and D. alkenigignens. Four contaminant mixtures comprised of combinations of the chlorinated solvents 1,2-dichloroethane (1,2-DCA), 1,2-dichloropropane (1,2-DCP), and 1,1,2-trichloroethane (1,1,2-TCA) were assessed for each species. Chlorinated solvent depletion and daughter product formation determined as a function of time following inoculation into anaerobic media revealed preferential dechlorination of 1,1,2-TCA over both 1,2-DCA and 1,2-DCP for both species. 1,2-DCA in particular was not dechlorinated until 1,1,2-TCA reached low concentrations. In contrast, both species concurrently dechlorinated 1,2-DCA and 1,2-DCP over a comparably large concentration range. This is the first report of substrate interactions during chlorinated alkane dehalogenation by pure cultures, and the results provide insights into the chlorinated alkane transformation processes that may be expected for contaminant mixtures in environments where Dehalogenimonas spp. are present.

  4. The hypocholesterolemic and antiatherogenic effects of Cholazol H, a chemically functionalized insoluble fiber with bile acid sequestrant properties in hamsters.

    PubMed

    Wilson, T A; Romano, C; Liang, J; Nicolosi, R J

    1998-08-01

    bile acids (39%, P < .001, and 28%, P < .002, respectively) relative to HCD. Also, there was a 48% (P < .002) and 65% (P < .001) greater fecal concentration of cholic acid (CA) for Cholazol H-treated hamsters compared with HCD- and CSTY-treated hamsters, respectively. Cholazol H also significantly increased fecal concentration of deoxycholic acid (DCA; 56%, P < .02) compared with HCD. In summary, Cholazol H is as effective as CSTY for prevention of diet-induced hypercholesterolemia and early atherosclerosis in hamsters.

  5. Aeolian dunes as ground truth for atmospheric modeling on Mars

    USGS Publications Warehouse

    Hayward, R.K.; Titus, T.N.; Michaels, T.I.; Fenton, L.K.; Colaprete, A.; Christensen, P.R.

    2009-01-01

    Martian aeolian dunes preserve a record of atmosphere/surface interaction on a variety of scales, serving as ground truth for both Global Climate Models (GCMs) and mesoscale climate models, such as the Mars Regional Atmospheric Modeling System (MRAMS). We hypothesize that the location of dune fields, expressed globally by geographic distribution and locally by dune centroid azimuth (DCA), may record the long-term integration of atmospheric activity across a broad area, preserving GCM-scale atmospheric trends. In contrast, individual dune morphology, as expressed in slipface orientation (SF), may be more sensitive to localized variations in circulation, preserving topographically controlled mesoscale trends. We test this hypothesis by comparing the geographic distribution, DCA, and SF of dunes with output from the Ames Mars GCM and, at a local study site, with output from MRAMS. When compared to the GCM: 1) dunes generally lie adjacent to areas with strongest winds, 2) DCA agrees fairly well with GCM modeled wind directions in smooth-floored craters, and 3) SF does not agree well with GCM modeled wind directions. When compared to MRAMS modeled winds at our study site: 1) DCA generally coincides with the part of the crater where modeled mean winds are weak, and 2) SFs are consistent with some weak, topographically influenced modeled winds. We conclude that: 1) geographic distribution may be valuable as ground truth for GCMs, 2) DCA may be useful as ground truth for both GCM and mesoscale models, and 3) SF may be useful as ground truth for mesoscale models. Copyright 2009 by the American Geophysical Union.

  6. Evaluation of the performance of urine albumin, creatinine and albumin-creatinine ratio assay on two POCT analyzers relative to a central laboratory method.

    PubMed

    Omoruyi, Felix O; Mustafa, Gul M; Okorodudu, Anthony O; Petersen, John R

    2012-03-22

    The evaluation of microalbumin, creatinine and albumin-creatinine ratio is very important in patients with diabetes for the early detection of kidney disease and the identification of patients at risk for complications from diabetes or hypertension. A total of 88 spot urine samples previously analyzed using the Vitros 5,1 FS (creatinine) and Beckman Coulter Immage (microalbumin) located in the central laboratory and having microalbumin and creatinine values within the Afinion and DCA Vantage reportable ranges were run on 2 point of care (POC) instruments (Siemens DCA Vantage and Axis-Shield Afinion). The mean values for the DCA Vantage were: 42.6 mg/l for albumin, 10.3 mol/l for creatinine, and 5.4 mg/mol for ACR. For the Afinion AS100, the mean values were: 48.5mg/l for albumin, 9.5 mol/l for creatinine, and 6.7 mg/mol for ACR. The mean values obtained for CL were: 40.8 mg/l for albumin, 10.0 mol/l for creatinine, and 5.4 mg/mol for ACR. All POC analyzers showed good correlation to the central laboratory tests for microalbumin, creatinine and albumin creatinine ratio (ACR) for Afinion (R(2)=0.954, 0.974, and 0.964, respectively) and DCA Vantage (R(2)=0.989, 0.987, and 0.991, respectively). With the exception of the DCA Vantage ACR (p=0.53), the levels of microalbumin, creatinine and ACR obtained for the Afinion and DCA Vantage instruments as compared to the CL were statistically different (p<0.05). The inter and intraday imprecision for both POC instruments was <2.9% and total imprecision <8.7%. The 2 instruments evaluated in this study were in good agreement with the quantitative laboratory results and thus can be used for microalbumin, creatinine and ACR assays at the POC. However, facilities using Afinion will have to use different normal range for ACR. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Benthic algae of benchmark streams in agricultural areas of eastern Wisconsin

    USGS Publications Warehouse

    Scudder, Barbara C.; Stewart, Jana S.

    2001-01-01

    Multivariate analyses indicated multiple scales of environmental factors affect algae. Although two-way indicator species analysis (TWINSPAN), detrended correspondence analysis (DCA), and canonical correspondence analysis (CCA) generally separated sites according to RHU, only DCA ordination indicated a separation of sites according to ecoregion. Environmental variables con-elated with DCA axes 1 and 2 and therefore indicated as important explanatory factors for algal distribution and abundance were factors related to stream size, basin land use/cover, geomorphology, hydrogeology, and riparian disturbance. CCA analyses with a more limited set of environmental variables indicated that pH, average width of natural riparian vegetation (segment scale), basin land use/cover and Q/Q2 were the most important variables affecting the distribution and relative abundance of benthic algae at the 20 benchmark streams,

  8. Lack of linear correlation between dynamic and steady-state cerebral autoregulation.

    PubMed

    de Jong, Daan L K; Tarumi, Takashi; Liu, Jie; Zhang, Rong; Claassen, Jurgen A H R

    2017-08-15

    For correct application and interpretation of cerebral autoregulation (CA) measurements in research and in clinical care, it is essential to understand differences and similarities between dynamic and steady-state CA. The present study found no correlation between dynamic and steady-state CA indices in healthy older adults. There was variability between individuals in all (steady-state and dynamic) autoregulatory indices, ranging from low (almost absent) to highly efficient CA in this healthy population. These findings challenge the assumption that assessment of a single CA parameter or a single set of parameters can be generalized to overall CA functioning. Therefore, depending on specific research purposes, the choice for either steady-state or dynamic measures or both should be weighed carefully. The present study aimed to investigate the relationship between dynamic (dCA) and steady-state cerebral autoregulation (sCA). In 28 healthy older adults, sCA was quantified by a linear regression slope of proportionate (%) changes in cerebrovascular resistance (CVR) in response to proportionate (%) changes in mean blood pressure (BP) induced by stepwise sodium nitroprusside (SNP) and phenylephrine (PhE) infusion. Cerebral blood flow (CBF) was measured at the internal carotid artery (ICA) and vertebral artery (VA) and CBF velocity at the middle cerebral artery (MCA). With CVR = BP/CBF, Slope-CVR ICA , Slope-CVR VA and Slope-CVRi MCA were derived. dCA was assessed (i) in supine rest, analysed with transfer function analysis (gain and phase) and autoregulatory index (ARI) fit from spontaneous oscillations (ARI Baseline ), and (ii) with transient changes in BP using a bolus injection of SNP (ARI SNP ) and PhE (ARI PhE ). Comparison of sCA and dCA parameters (using Pearson's r for continuous and Spearman's ρ for ordinal parameters) demonstrated a lack of linear correlations between sCA and dCA measures. However, comparisons of parameters within dCA and within sCA were

  9. Regression models evaluating THMs, HAAs and HANs formation upon chloramination of source water collected from Yangtze River Delta Region, China.

    PubMed

    Lin, Jiajia; Chen, Xi; Ansheng, Zhu; Hong, Huachang; Liang, Yan; Sun, Hongjie; Lin, Hongjun; Chen, Jianrong

    2018-09-30

    Present study aimed to generate multiple regression models to estimate the formation of trihalomethanes (THMs), haloacetonitriles (HANs) and haloacetic acids (HAAs) during chloramination of source water obtained from Yangtze River Delta Region, China. The results showed that the regression models for trichloromethane (TCM), dichloroacetonitrile (DCAN), dichloroacetic acid (DCAA), dihaloacetic acids (DHAAs), 5 HAAs species regulated by U.S. EPA (HAA 5 ) and total haloacetic acids (HAA 9 ) have good evaluation ability (prediction accuracy reached 81-94%), while the models for total haloacetonitriles (HAN 4 ), trichloroacetic acid (TCAA), trihaloacetic acids (THAAs) and total trihalomethanes (THM 4 ), they appeared relative low prediction accuracy (58-72%). For THMs, dissolved organic nitrogen (DON) was their key organic precursor, yet for HAN, DHAAs and THAAs, UVA 254 played the dominant role. The other key factors influencing DBP formation included the bromide (THM 4 , DHAAs and HAA 9 ), reaction time (DCAN, HAN 4 ), chloramine dose (TCM, DCAA, TCAA, HAA 5 and THAAs). These results provided important information for water works to optimize the water treatment process to control DBPs, and give an evaluating method for DBPs levels when estimating the health risks related with DBP exposure during chloramination. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Dichloroacetate and cancer: new home for an orphan drug?

    PubMed

    Kankotia, Shyam; Stacpoole, Peter W

    2014-12-01

    We reviewed the anti-cancer effects of DCA, an orphan drug long used as an investigational treatment for various acquired and congenital disorders of mitochondrial intermediary metabolism. Inhibition by DCA of mitochondrial pyruvate dehydrogenase kinases and subsequent reactivation of the pyruvate dehydrogenase complex and oxidative phosphorylation is the common mechanism accounting for the drug's anti-neoplastic effects. At least two fundamental changes in tumor metabolism are induced by DCA that antagonize tumor growth, metastases and survival: the first is the redirection of glucose metabolism from glycolysis to oxidation (reversal of the Warburg effect), leading to inhibition of proliferation and induction of caspase-mediated apoptosis. These effects have been replicated in both human cancer cell lines and in tumor implants of diverse germ line origin. The second fundamental change is the oxidative removal of lactate, via pyruvate, and the co-incident buffering of hydrogen ions by dehydrogenases located in the mitochondrial matrix. Preclinical studies demonstrate that DCA has additive or synergistic effects when used in combination with standard agents designed to modify tumor oxidative stress, vascular remodeling, DNA integrity or immunity. These findings and limited clinical results suggest that potentially fruitful areas for additional clinical trials include 1) adult and pediatric high grade astrocytomas; 2) BRAF-mutant cancers, such as melanoma, perhaps combined with other pro-oxidants; 3) tumors in which resistance to standard platinum-class drugs alone may be overcome with combination therapy; and 4) tumors of endodermal origin, in which extensive experimental research has demonstrated significant anti-proliferative, pro-apoptotic effects of DCA, leading to improved host survival. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Distinct Dual C-Cl Isotope Fractionation Patterns during Anaerobic Biodegradation of 1,2-Dichloroethane: Potential To Characterize Microbial Degradation in the Field.

    PubMed

    Palau, J; Yu, R; Hatijah Mortan, S; Shouakar-Stash, O; Rosell, M; Freedman, D L; Sbarbati, C; Fiorenza, S; Aravena, R; Marco-Urrea, E; Elsner, M; Soler, A; Hunkeler, D

    2017-03-07

    This study investigates, for the first time, dual C-Cl isotope fractionation during anaerobic biodegradation of 1,2-dichloroethane (1,2-DCA) via dihaloelimination by Dehalococcoides and Dehalogenimonas-containing enrichment cultures. Isotopic fractionation of 1,2-DCA (ε bulk C and ε bulk Cl ) for Dehalococcoides (-33.0 ± 0.4‰ and -5.1 ± 0.1‰) and Dehalogenimonas-containing microcosms (-23 ± 2‰ and -12.0 ± 0.8‰) resulted in distinctly different dual element C-Cl isotope correlations (Λ = Δδ 13 C/Δδ 37 Cl ≈ ε bulk C /ε bulk Cl ), 6.8 ± 0.2 and 1.89 ± 0.02, respectively. Determined isotope effects and detected products suggest that the difference on the obtained Λ values for biodihaloelimination could be associated with a different mode of concerted bond cleavage rather than two different reaction pathways (i.e., stepwise vs concerted). Λ values of 1,2-DCA were, for the first time, determined in two field sites under reducing conditions (2.1 ± 0.1 and 2.2 ± 2.9). They were similar to the one obtained for the Dehalogenimonas-containing microcosms (1.89 ± 0.02) and very different from those reported for aerobic degradation pathways in a previous laboratory study (7.6 ± 0.1 and 0.78 ± 0.03). Thus, this study illustrates the potential of a dual isotope analysis to differentiate between aerobic and anaerobic biodegradation pathways of 1,2-DCA in the field and suggests that this approach might also be used to characterize dihaloelimination of 1,2-DCA by different bacteria, which needs to be confirmed in future studies.

  12. Simplified Acute Physiology Score II as Predictor of Mortality in Intensive Care Units: A Decision Curve Analysis.

    PubMed

    Allyn, Jérôme; Ferdynus, Cyril; Bohrer, Michel; Dalban, Cécile; Valance, Dorothée; Allou, Nicolas

    2016-01-01

    End-of-life decision-making in Intensive care Units (ICUs) is difficult. The main problems encountered are the lack of a reliable prediction score for death and the fact that the opinion of patients is rarely taken into consideration. The Decision Curve Analysis (DCA) is a recent method developed to evaluate the prediction models and which takes into account the wishes of patients (or surrogates) to expose themselves to the risk of obtaining a false result. Our objective was to evaluate the clinical usefulness, with DCA, of the Simplified Acute Physiology Score II (SAPS II) to predict ICU mortality. We conducted a retrospective cohort study from January 2011 to September 2015, in a medical-surgical 23-bed ICU at University Hospital. Performances of the SAPS II, a modified SAPS II (without AGE), and age to predict ICU mortality, were measured by a Receiver Operating Characteristic (ROC) analysis and DCA. Among the 4.370 patients admitted, 23.3% died in the ICU. Mean (standard deviation) age was 56.8 (16.7) years, and median (first-third quartile) SAPS II was 48 (34-65). Areas under ROC curves were 0.828 (0.813-0.843) for SAPS II, 0.814 (0.798-0.829) for modified SAPS II and of 0.627 (0.608-0.646) for age. DCA showed a net benefit whatever the probability threshold, especially under 0.5. DCA shows the benefits of the SAPS II to predict ICU mortality, especially when the probability threshold is low. Complementary studies are needed to define the exact role that the SAPS II can play in end-of-life decision-making in ICUs.

  13. Decision curve analysis to compare 3 versions of Partin Tables to predict final pathologic stage.

    PubMed

    Augustin, Herbert; Sun, Maxine; Isbarn, Hendrik; Pummer, Karl; Karakiewicz, Pierre

    2012-01-01

    To perform a decision curve analysis (DCA) to compare the Partin Tables 1997, 2001, and 2007 for their clinical applicability. Clinical and pathologic data of 687 consecutive patients treated with open radical prostatectomy for clinically localized prostate cancer between 2003 and 2008 at a single institution were used. DCA quantified the net benefit relating to specific threshold probabilities of extraprostatic extension (EPE), seminal vesicle involvement (SVI), and lymph node involvement (LNI). Overall, EPE, SVI, and LNI were recorded in 17.8, 6.0, and 1.2%, respectively. For EPE predictions, the DCA favored the 2007 version vs. 1997 for SVI vs. none of the versions for LNI. DCA indicate that for very low prevalence conditions such as LNI (1.2%), decision models are not useful. For low prevalence rates such as SVI, the use of different versions of the Partin Tables does not translate into meaningful net gains differences. Finally, for intermediate prevalence conditions such as EPE (18%), despite apparent performance differences, the net benefit differences were also marginal. In consequence, the current analysis could not confirm an important benefit from the use of the Partin Tables and it could not identify a clearly better version of any of the 3 available iterations. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fu, L.J.; Johnson, E.M.; Newman, L.M.

    A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity teratology tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the embryonic developmental portion of the assay than it was to the adults.more » Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.« less

  15. Evaluation of different methods of protein extraction and identification of differentially expressed proteins upon ethylene-induced early-ripening in banana peels.

    PubMed

    Zhang, Li-Li; Feng, Ren-Jun; Zhang, Yin-Dong

    2012-08-15

    Banana peels (Musa spp.) are a good example of a plant tissue where protein extraction is challenging due to the abundance of interfering metabolites. Sample preparation is a critical step in proteomic research and is critical for good results. We sought to evaluate three methods of protein extraction: trichloroacetic acid (TCA)-acetone precipitation, phenol extraction, and TCA precipitation. We found that a modified phenol extraction protocol was the most optimal method. SDS-PAGE and two-dimensional gel electrophoresis (2-DE) demonstrated good protein separation and distinct spots of high quality protein. Approximately 300 and 550 protein spots were detected on 2-DE gels at pH values of 3-10 and 4-7, respectively. Several spots were excised from the 2-DE gels and identified by mass spectrometry. The protein spots identified were found to be involved in glycolysis, the tricarboxylic acid cycle, and the biosynthesis of ethylene. Several of the identified proteins may play important roles in banana ripening. Copyright © 2012 Society of Chemical Industry.

  16. Comparison of Degrees of Potential-Energy-Surface Anharmonicity for Complexes and Clusters with Hydrogen Bonds

    NASA Astrophysics Data System (ADS)

    Kozlovskaya, E. N.; Doroshenko, I. Yu.; Pogorelov, V. E.; Vaskivskyi, Ye. V.; Pitsevich, G. A.

    2018-01-01

    Previously calculated multidimensional potential-energy surfaces of the MeOH monomer and dimer, water dimer, malonaldehyde, formic acid dimer, free pyridine-N-oxide/trichloroacetic acid complex, and protonated water dimer were analyzed. The corresponding harmonic potential-energy surfaces near the global minima were constructed for series of clusters and complexes with hydrogen bonds of different strengths based on the behavior of the calculated multidimensional potential-energy surfaces. This enabled the introduction of an obvious anharmonicity parameter for the calculated potential-energy surfaces. The anharmonicity parameter was analyzed as functions of the size of the analyzed area near the energy minimum, the number of points over which energies were compared, and the dimensionality of the solved vibrational problem. Anharmonicity parameters for potential-energy surfaces in complexes with strong, medium, and weak H-bonds were calculated under identical conditions. The obtained anharmonicity parameters were compared with the corresponding diagonal anharmonicity constants for stretching vibrations of the bridging protons and the lengths of the hydrogen bridges.

  17. Detection of malondialdehyde in processed meat products without interference from the ingredients.

    PubMed

    Jung, Samooel; Nam, Ki Chang; Jo, Cheorun

    2016-10-15

    Our aim was to develop a method for accurate quantification of malondialdehyde (MDA) in meat products. MDA content of uncured ground pork (Control); ground pork cured with sodium nitrite (Nitrite); and ground pork cured with sodium nitrite, sodium chloride, sodium pyrophosphate, maltodextrin, and a sausage seasoning (Mix) was measured by the 2-thiobarbituric acid (TBA) assay with MDA extraction by trichloroacetic acid (method A) and two high-performance liquid chromatography (HPLC) methods: i) HPLC separation of the MDA-dinitrophenyl hydrazine adduct (method B) and ii) HPLC separation of MDA (method C) after MDA extraction with acetonitrile. Methods A and B could not quantify MDA accurately in groups Nitrite and Mix. Nevertheless, MDA in groups Control, Nitrite, and Mix was accurately quantified by method C with good recovery. Therefore, direct MDA quantification by HPLC after MDA extraction with acetonitrile (method C) is useful for accurate measurement of MDA content in processed meat products. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Self-assembled PEG monolayer based SPR immunosensor for label-free detection of insulin.

    PubMed

    Gobi, K Vengatajalabathy; Iwasaka, Hiroyuki; Miura, Norio

    2007-02-15

    A simple and rapid continuous-flow immunosensor based on surface plasmon resonance (SPR) has been developed for detection of insulin as low as 1 ng ml-1 (ppb) with a response time of less than 5 min. At first, a heterobifunctional oligo(ethyleneglycol)-dithiocarboxylic acid derivative (OEG-DCA) containing dithiol and carboxyl end groups was used to functionalize the thin Au-film of SPR chip. Insulin was covalently bound to the Au-thiolate monolayer of OEG-DCA for activating the sensor surface to immunoaffinity interactions. An on-line competitive immunosensing principle is examined for detection of insulin, in which the direct affinity binding of anti-insulin antibody to the insulin on sensor surface is examined in the presence and absence of various concentrations of insulin. Immunoreaction of anti-insulin antibody with the sensor surface was optimized with reference to antibody concentration, sample analysis time and flow-rate to provide the desired detection limit and determination range. With the immunosensor developed, the lowest detectable concentration of insulin is 1 ng ml-1 and the determination range covers a wide concentration of 1-300 ng ml-1. The developed OEG-monolayer based sensor chip exhibited high resistance to non-specific adsorption of proteins, and an uninterrupted highly sensitive detection of insulin from insulin-impregnated serum samples has been demonstrated. After an immunoreaction cycle, active sensor surface was regenerated simply by a brief flow of an acidic buffer (glycine.HCl; pH 2.0) for less than 1 min. A same sensor chip was found reusable for more than 25 cycles without an appreciable change in the original sensor activity.

  19. Defense Communications Agency Cost and Planning Factors Manual. Change 1.

    DTIC Science & Technology

    1984-06-11

    shows the total costs for placing payloads in orbit. This includes reimbursement to NASA for Shuttle services, purchase of the upper stage, and upper...23-6 DCAC 600-60-1 SECTION D Change I ’" = TABLE 23-2. DCA MILITARY LABOR RATES : ANNLAL RATES : HCURLY RATES : REIMBURS -: :PTS FRCP:REIPEURS...DCAC 600-60-1 23-7 SECTION D Change I # : - TABLE 23-3. DCA MILITARY LABOR RATES - MAJOR : ANNLAL RATES : HCURLY RATES : REIMBURS -: : : : : : TS

  20. Evaluation of an alternative extraction procedure for enterotoxin determination in dairy products.

    PubMed

    Meyrand, A; Atrache, V; Bavai, C; Montet, M P; Vernozy-Rozand, C

    1999-06-01

    A concentration protocol based on trichloroacetic acid precipitation was evaluated and compared with the reference method using dialysis concentration. Different quantities of purified staphylococcal enterotoxins were added to pasteurized Camembert-type cheeses. Detection of enterotoxins in these cheeses was performed using an automated detection system. Raw goat milk Camembert-type cheeses involved in a staphylococcal food poisoning were also tested. Both enterotoxin extraction methods allowed detection of the lowest enterotoxin concentration level used in this study (0.5 ng g-1). Compared with the dialysis concentration method, TCA precipitation of staphylococcal enterotoxins was 'user-friendly' and less time-consuming. These results suggest that TCA precipitation is a rapid (1 h), simple and reliable method of extracting enterotoxin from food which gives excellent recovery from dairy products.

  1. Evaluation of disinfection by-product formation during chlor(am)ination from algal organic matter after UV irradiation.

    PubMed

    Chen, Shi; Deng, Jing; Li, Lei; Gao, Naiyun

    2018-02-01

    This study evaluated the effect of low-pressure ultraviolet (UV) irradiation on the formation of disinfection by-products (DBPs) from algal organic matter of Microcystis aeruginosa during subsequent chlorination and chloramination. The algal organic matter includes extracellular organic matter (EOM) and intracellular organic matter (IOM). The fluorescence excitation-emission matrix spectra indicated that the humic/fulvic acid-like organics of EOM and the protein-like organics of IOM may be preferentially degraded by UV treatment. UV irradiation with low specific UV absorbance values was effective in reducing the formation of trihalomethanes and dichloroacetic acid from EOM and IOM during the subsequent chlorination. During the UV-chloramine process, higher UV dose (1000 mJ/cm 2 ) led to the decrease of the formation of dichloroacetic acid, trichloroacetic acid, and haloketones from IOM by an average of 24%. Furthermore, UV irradiation can slightly increase the bromine substitution factors (BSFs) of haloacetic acids from EOM during chlorination, including dihaloacetic acids and trihaloacetic acids in the presence of bromide (50 μg/L). However, UV irradiation did not shift the formation of DBPs from IOM to more brominated species, since the BSFs of trihalomethanes, dihaloacetic acids, trihaloacetic acids, and dihaloacetonitriles almost kept unchanged during UV-chlorine process. As for UV-chloramine process, UV irradiation decreased the BSFs of trihalomethanes, while increased the BSFs of dihaloacetic acid for both EOM and IOM. Overall, the UV pretreatment process is a potential technology in treating algae-rich water.

  2. Sister Dehalobacter Genomes Reveal Specialization in Organohalide Respiration and Recent Strain Differentiation Likely Driven by Chlorinated Substrates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tang, Shuiquan; Wang, Po Hsiang; Higgins, Steven A.

    Here we report that the genomes of two closely related Dehalobacter strains (strain CF and strain DCA) were assembled from the metagenome of an anaerobic enrichment culture that reductively dechlorinates chloroform (CF), 1,1,1-trichloroethane (1,1,1-TCA) and 1,1-dichloroethane (1,1-DCA). The 3.1 Mbp genomes of strain CF (that dechlorinates CF and 1,1,1-TCA) and strain DCA (that dechlorinates 1,1-DCA) each contain 17 putative reductive dehalogenase homologous (rdh) genes. These two genomes were systematically compared to three other available organohalide-respiring Dehalobacter genomes (Dehalobacter restrictus strain PER-K23, Dehalobacter sp. strain E1 and Dehalobacter sp. strain UNSWDHB), and to the genomes of Dehalococcoides mccartyi strain 195 andmore » Desulfitobacterium hafniense strain Y51. This analysis compared 42 different metabolic and physiological categories. The genomes of strains CF and DCA share 90% overall average nucleotide identity and >99.8% identity over a 2.9 Mbp alignment that excludes large insertions, indicating that these genomes differentiated from a close common ancestor. This differentiation was likely driven by selection pressures around two orthologous reductive dehalogenase genes, cfrA and dcrA, that code for the enzymes that reduce CF or 1,1,1-TCA and 1,1-DCA. The many reductive dehalogenase genes found in the five Dehalobacter genomes cluster into two small conserved regions and were often associated with Crp/Fnr transcriptional regulators. Specialization is on-going on a strain-specific basis, as some strains but not others have lost essential genes in the Wood-Ljungdahl (strain E1) and corrinoid biosynthesis pathways (strains E1 and PER-K23). The gene encoding phosphoserine phosphatase, which catalyzes the last step of serine biosynthesis, is missing from all five Dehalobacter genomes, yet D. restrictus can grow without serine, suggesting an alternative or unrecognized biosynthesis route exists. In contrast to D. mccartyi, a

  3. Sister Dehalobacter Genomes Reveal Specialization in Organohalide Respiration and Recent Strain Differentiation Likely Driven by Chlorinated Substrates

    DOE PAGES

    Tang, Shuiquan; Wang, Po Hsiang; Higgins, Steven A.; ...

    2016-02-12

    Here we report that the genomes of two closely related Dehalobacter strains (strain CF and strain DCA) were assembled from the metagenome of an anaerobic enrichment culture that reductively dechlorinates chloroform (CF), 1,1,1-trichloroethane (1,1,1-TCA) and 1,1-dichloroethane (1,1-DCA). The 3.1 Mbp genomes of strain CF (that dechlorinates CF and 1,1,1-TCA) and strain DCA (that dechlorinates 1,1-DCA) each contain 17 putative reductive dehalogenase homologous (rdh) genes. These two genomes were systematically compared to three other available organohalide-respiring Dehalobacter genomes (Dehalobacter restrictus strain PER-K23, Dehalobacter sp. strain E1 and Dehalobacter sp. strain UNSWDHB), and to the genomes of Dehalococcoides mccartyi strain 195 andmore » Desulfitobacterium hafniense strain Y51. This analysis compared 42 different metabolic and physiological categories. The genomes of strains CF and DCA share 90% overall average nucleotide identity and >99.8% identity over a 2.9 Mbp alignment that excludes large insertions, indicating that these genomes differentiated from a close common ancestor. This differentiation was likely driven by selection pressures around two orthologous reductive dehalogenase genes, cfrA and dcrA, that code for the enzymes that reduce CF or 1,1,1-TCA and 1,1-DCA. The many reductive dehalogenase genes found in the five Dehalobacter genomes cluster into two small conserved regions and were often associated with Crp/Fnr transcriptional regulators. Specialization is on-going on a strain-specific basis, as some strains but not others have lost essential genes in the Wood-Ljungdahl (strain E1) and corrinoid biosynthesis pathways (strains E1 and PER-K23). The gene encoding phosphoserine phosphatase, which catalyzes the last step of serine biosynthesis, is missing from all five Dehalobacter genomes, yet D. restrictus can grow without serine, suggesting an alternative or unrecognized biosynthesis route exists. In contrast to D. mccartyi, a

  4. Simplified Acute Physiology Score II as Predictor of Mortality in Intensive Care Units: A Decision Curve Analysis

    PubMed Central

    Allyn, Jérôme; Ferdynus, Cyril; Bohrer, Michel; Dalban, Cécile; Valance, Dorothée; Allou, Nicolas

    2016-01-01

    Background End-of-life decision-making in Intensive care Units (ICUs) is difficult. The main problems encountered are the lack of a reliable prediction score for death and the fact that the opinion of patients is rarely taken into consideration. The Decision Curve Analysis (DCA) is a recent method developed to evaluate the prediction models and which takes into account the wishes of patients (or surrogates) to expose themselves to the risk of obtaining a false result. Our objective was to evaluate the clinical usefulness, with DCA, of the Simplified Acute Physiology Score II (SAPS II) to predict ICU mortality. Methods We conducted a retrospective cohort study from January 2011 to September 2015, in a medical-surgical 23-bed ICU at University Hospital. Performances of the SAPS II, a modified SAPS II (without AGE), and age to predict ICU mortality, were measured by a Receiver Operating Characteristic (ROC) analysis and DCA. Results Among the 4.370 patients admitted, 23.3% died in the ICU. Mean (standard deviation) age was 56.8 (16.7) years, and median (first-third quartile) SAPS II was 48 (34–65). Areas under ROC curves were 0.828 (0.813–0.843) for SAPS II, 0.814 (0.798–0.829) for modified SAPS II and of 0.627 (0.608–0.646) for age. DCA showed a net benefit whatever the probability threshold, especially under 0.5. Conclusion DCA shows the benefits of the SAPS II to predict ICU mortality, especially when the probability threshold is low. Complementary studies are needed to define the exact role that the SAPS II can play in end-of-life decision-making in ICUs. PMID:27741304

  5. Defining when to offer operative treatment for intrahepatic cholangiocarcinoma: A regret-based decision curves analysis.

    PubMed

    Bagante, Fabio; Spolverato, Gaya; Cucchetti, Alessandro; Gani, Faiz; Popescu, Irinel; Ruzzenente, Andrea; Marques, Hugo P; Aldrighetti, Luca; Gamblin, T Clark; Maithel, Shishir K; Sandroussi, Charbel; Bauer, Todd W; Shen, Feng; Poultsides, George A; Marsh, James Wallis; Guglielmi, Alfredo; Pawlik, Timothy M

    2016-07-01

    Regret-based decision curve analysis (DCA) is a framework that assesses the medical decision process according to physician attitudes (expected regret) relative to disease-based factors. We sought to apply this methodology to decisions around the operative management of intrahepatic cholangiocarcinoma (ICC). Utilizing a multicentric database of 799 patients who underwent liver resection for ICC, we developed a prognostic nomogram. DCA tested 3 strategies: (1) perform an operation on all patients, (2) never perform an operation, and (3) use the nomogram to select patients for an operation. Four preoperative variables were included in the nomogram: major vascular invasion (HR = 1.36), tumor number (multifocal, HR = 1.18), tumor size (>5 cm, HR = 1.45), and suspicious lymph nodes on imaging (HR = 1.47; all P < .05). The regret-DCA was assessed using an online survey of 50 physicians, expert in the treatment of ICC. For a patient with a multifocal ICC, largest lesion measuring >5 cm, one suspicious malignant lymph node, and vascular invasion on imaging, the 1-year predicted survival was 52% according to the nomogram. Based on the therapeutic decision of the regret-DCA, 60% of physicians would advise against an operation for this scenario. Conversely, all physicians recommended an operation to a patient with an early ICC (single nodule measuring 3 cm, no suspicious lymph nodes, and no vascular invasion at imaging). By integrating a nomogram based on preoperative variables and a regret-based DCA, we were able to define the elements of how decisions rely on medical knowledge (postoperative survival predicted by a nomogram, severity disease assessment) and physician attitudes (regret of commission and omission). Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Oxidative stress: a key regulator of leiomyoma cell survival.

    PubMed

    Fletcher, Nicole M; Abusamaan, Mohammed S; Memaj, Ira; Saed, Mohammed G; Al-Hendy, Ayman; Diamond, Michael P; Saed, Ghassan M

    2017-06-01

    To determine the effects of attenuating oxidative stress with the use of dichloroacetate (DCA) on the expression of key redox enzymes myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) as well as on apoptosis. Prospective experimental study. University medical center. Cells established from myometrium and uterine fibroid from the same patients. Cells were exposed to normal (20% O 2 ) or hypoxic (2% O 2 ) conditions for 24 hours with or without DCA (20 μg/mL), a metabolic modulator that shifts anaerobic to aerobic metabolism. Nitrate/nitrite (iNOS activity indicator), iNOS, Bcl-2/Bax ratio, MPO, and caspase-3 activities and levels were determined by means of Greiss assay, real-time reverse-transcription polymerase chain reaction, and ELISA. Data were analyzed with the use of SPSS by means of one-way analysis of variance with Tukey post hoc analysis and independent t tests. MPO, iNOS, and nitrate/nitrite expression were higher in leiomyoma than in myometrial cells, and they were further enhanced by hypoxia in myometrial cells. Treatment with the use of DCA decreased MPO, iNOS, and nitrate/nitrite levels and negated the effect of hypoxia in both types of cells. Leiomyoma cells showed less apoptosis, as indicated by both caspase-3 activity and the Bcl-2/Bax ratio, than myometrial cells. Hypoxia further decreased apoptosis in myometrial cells with no further effect on leiomyoma cells. Treatment with DCA resulted in increased apoptosis in both types of cells, even in the presence of hypoxia. Shifting anaerobic to aerobic metabolism with the use of DCA resulted in an increase in apoptosis in leiomyoma cells and protected myometrial cells from the acquisition of the leiomyoma-like phenotype. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Identification and Characterization of the MADS-Box Genes and Their Contribution to Flower Organ in Carnation (Dianthus caryophyllus L.)

    PubMed Central

    Zhang, Xiaoni; Wang, Qijian; Yang, Shaozong; Lin, Shengnan; Bao, Manzhu; Wu, Quanshu; Wang, Caiyun; Fu, Xiaopeng

    2018-01-01

    Dianthus is a large genus containing many species with high ornamental economic value. Extensive breeding strategies permitted an exploration of an improvement in the quality of cultivated carnation, particularly in flowers. However, little is known on the molecular mechanisms of flower development in carnation. Here, we report the identification and description of MADS-box genes in carnation (DcaMADS) with a focus on those involved in flower development and organ identity determination. In this study, 39 MADS-box genes were identified from the carnation genome and transcriptome by the phylogenetic analysis. These genes were categorized into four subgroups (30 MIKCc, two MIKC*, two Mα, and five Mγ). The MADS-box domain, gene structure, and conserved motif compositions of the carnation MADS genes were analysed. Meanwhile, the expression of DcaMADS genes were significantly different in stems, leaves, and flower buds. Further studies were carried out for exploring the expression of DcaMADS genes in individual flower organs, and some crucial DcaMADS genes correlated with their putative function were validated. Finally, a new expression pattern of DcaMADS genes in flower organs of carnation was provided: sepal (three class E genes and two class A genes), petal (two class B genes, two class E genes, and one SHORT VEGETATIVE PHASE (SVP)), stamen (two class B genes, two class E genes, and two class C), styles (two class E genes and two class C), and ovary (two class E genes, two class C, one AGAMOUS-LIKE 6 (AGL6), one SEEDSTICK (STK), one B sister, one SVP, and one Mα). This result proposes a model in floral organ identity of carnation and it may be helpful to further explore the molecular mechanism of flower organ identity in carnation. PMID:29617274

  8. Identification and Characterization of the MADS-Box Genes and Their Contribution to Flower Organ in Carnation (Dianthus caryophyllus L.).

    PubMed

    Zhang, Xiaoni; Wang, Qijian; Yang, Shaozong; Lin, Shengnan; Bao, Manzhu; Bendahmane, Mohammed; Wu, Quanshu; Wang, Caiyun; Fu, Xiaopeng

    2018-04-04

    Dianthus is a large genus containing many species with high ornamental economic value. Extensive breeding strategies permitted an exploration of an improvement in the quality of cultivated carnation, particularly in flowers. However, little is known on the molecular mechanisms of flower development in carnation. Here, we report the identification and description of MADS-box genes in carnation ( DcaMADS ) with a focus on those involved in flower development and organ identity determination. In this study, 39 MADS-box genes were identified from the carnation genome and transcriptome by the phylogenetic analysis. These genes were categorized into four subgroups (30 MIKC c , two MIKC*, two Mα, and five Mγ). The MADS-box domain, gene structure, and conserved motif compositions of the carnation MADS genes were analysed. Meanwhile, the expression of DcaMADS genes were significantly different in stems, leaves, and flower buds. Further studies were carried out for exploring the expression of DcaMADS genes in individual flower organs, and some crucial DcaMADS genes correlated with their putative function were validated. Finally, a new expression pattern of DcaMADS genes in flower organs of carnation was provided: sepal (three class E genes and two class A genes), petal (two class B genes, two class E genes, and one SHORT VEGETATIVE PHASE ( SVP )), stamen (two class B genes, two class E genes, and two class C), styles (two class E genes and two class C), and ovary (two class E genes, two class C, one AGAMOUS-LIKE 6 ( AGL6 ), one SEEDSTICK ( STK ), one B sister , one SVP , and one Mα ). This result proposes a model in floral organ identity of carnation and it may be helpful to further explore the molecular mechanism of flower organ identity in carnation.

  9. Kinetics and mechanisms of formation of earthy and musty odor compounds: Chloroanisoles during water chlorination.

    PubMed

    Zhang, Kejia; Zhou, Xinyan; Zhang, Tuqiao; Mao, Minmin; Li, Lei; Liao, Wenchao

    2016-11-01

    Chloroanisoles are often reported as off-flavor compounds which produce an earthy and musty flavors and odors in drinking water. To improve understanding and ultimately minimize the formation of 2,4-dichloroanisole (2,4-DCA), 2,6-dichloroanisole (2,6-DCA) and 2,4,6-trichloroanisole (2,4,6-TCA), which have low odor threshold concentrations (OTC: 0.03-4 ng L(-1)), a kinetic database for the chlorination of anisole was established by kinetic measurements. The results showed that HOCl reacted with anisole in acidic solution, with the hydrogen ion as an important catalyst. Quantification of product distribution of the produced chloroanisoles demonstrated that a chlorine attack in the para-position was favored over the ortho-position. A kinetic model was formulated, which permitted investigation of the relative importance of the chlorine dose and other water quality parameters including the concentrations of anisole and several metal ions, as well as temperature, on the product distribution of chloroanisoles. In general, high chlorine doses led to low concentrations of intermediates. The presence of ions such as Fe(3+) and Al(3+) facilitated the formation of chloroanisoles, but Zn(2+) and Mn(2+) did not. The kinetic model can be applied to optimize water chlorination and minimize earthy and musty odors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. ACVR1 p.Q207E causes classic fibrodysplasia ossificans progressiva and is functionally distinct from the engineered constitutively active ACVR1 p.Q207D variant

    PubMed Central

    Haupt, Julia; Deichsel, Alexandra; Stange, Katja; Ast, Cindy; Bocciardi, Renata; Ravazzolo, Roberto; Di Rocco, Maja; Ferrari, Paola; Landi, Antonio; Kaplan, Frederick S.; Shore, Eileen M.; Reissner, Carsten; Seemann, Petra

    2014-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic disorder of progressive heterotopic ossification (HO). Here, we report a patient with an ultra-rare point mutation [c.619C>G, p.Q207E] located in a codon adjacent to the most common FOP mutation [c.617G>A, p.R206H] of Activin A Receptor, type 1 (ACVR1) and that affects the same intracellular amino acid position in the GS activation domain as the engineered constitutively active (c.a.) variant p.Q207D. It was predicted that both mutations at residue 207 have similar functional effects by introducing a negative charge. Transgenic p.Q207D-c.a. mice have served as a model for FOP HO in several in vivo studies. However, we found that the engineered ACVR1Q207D−c.a. is significantly more active than the classic FOP mutation ACVR1R206H when overexpressed in chicken limbs and in differentiation assays of chondrogenesis, osteogenesis and myogenesis. Importantly, our studies reveal that the ACVR1Q207E resembles the classic FOP receptor in these assays, not the engineered ACVR1Q207D−c.a.. Notably, reporter gene assays revealed that both naturally occurring FOP receptors (ACVR1R206H and ACVR1Q207E) were activated by BMP7 and were sensitive to deletion of the ligand binding domain, whereas the engineered ACVR1Q207D−c.a. exhibited ligand independent activity. We performed an in silico analysis and propose a structural model for p.Q207D-c.a. that irreversibly relocates the GS domain into an activating position, where it becomes ligand independent. We conclude that the engineered p.Q207D-c.a. mutation has severe limitations as a model for FOP, whereas the naturally occurring mutations p.R206H and p.Q207E facilitate receptor activation, albeit in a reversible manner. PMID:24852373

  11. Using a simple HPLC approach to identify the enzymatic products of UTL-5g, a small molecule TNF-α inhibitor, from porcine esterase and from rabbit esterase

    PubMed Central

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

    2013-01-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. As a prelude to investigating the metabolites of UTL-5g, we set out to identify the enzymatic products of UTL-5g under the treatment of both porcine liver esterase (PLE) and rabbit liver esterase (RLE). First, a number of mixtures made by UTL-5g and PLE were incubated at 25 °C. At predetermined time points, individual samples were quenched by acetonitrile, vortexed, and centrifuged. The supernatants were then analyzed by reversed-phase HPLC (using a C18 column). The retention times and UV/Vis spectra of individual peaks were compared to those of UTL-5g and its two postulated enzymatic products; thus the enzymatic products of UTL-5g were tentatively identified. Secondly, a different HPLC method (providing different retentions times) was used to cross-check and to confirm the identities of the two enzymatic products. Based on the observations, it was concluded that under the treatment of PLE, the major enzymatic products of UTL-5g were 5-methyliosxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA). Treatment of UTL-5g by RLE also provided the same enzymatic products of UTL-5g from esterase. These results indicate that the peptide bond in UTL-5g was cleaved by PLE/RLE. Michaelis–Menten kinetics showed that the Km values of UTL-5g were 2.07 mM with PLE and 0.37 mM with RLE indicating that UTL-5g had a higher affinity with RLE. In summary, by a simple HPLC approach, we have concluded that the peptide bond in UTL-5g was cleaved by esterase from either porcine liver or rabbit liver in vitro and afforded DCA (at a mole ratio of 1:1) and ISOX. However, further studies are needed in order to determine whether UTL-5g is metabolized by microsomal enzymes to produce ISOX and DCA. PMID:24126042

  12. Biotransformation of Trichoderma spp. and their tolerance to aromatic amines, a major class of pollutants.

    PubMed

    Cocaign, Angélique; Bui, Linh-Chi; Silar, Philippe; Chan Ho Tong, Laetitia; Busi, Florent; Lamouri, Aazdine; Mougin, Christian; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Dairou, Julien

    2013-08-01

    Trichoderma spp. are cosmopolitan soil fungi that are highly resistant to many toxic compounds. Here, we show that Trichoderma virens and T. reesei are tolerant to aromatic amines (AA), a major class of pollutants including the highly toxic pesticide residue 3,4-dichloroaniline (3,4-DCA). In a previous study, we provided proof-of-concept remediation experiments in which another soil fungus, Podospora anserina, detoxifies 3,4-DCA through its arylamine N-acetyltransferase (NAT), a xenobiotic-metabolizing enzyme that enables acetyl coenzyme A-dependent detoxification of AA. To assess whether the N-acetylation pathway enables AA tolerance in Trichoderma spp., we cloned and characterized NATs from T. virens and T. reesei. We characterized recombinant enzymes by determining their catalytic efficiencies toward several toxic AA. Through a complementary approach, we also demonstrate that both Trichoderma species efficiently metabolize 3,4-DCA. Finally, we provide evidence that NAT-independent transformation is solely (in T. virens) or mainly (in T. reesei) responsible for the observed removal of 3,4-DCA. We conclude that T. virens and, to a lesser extent, T. reesei likely utilize another, unidentified, metabolic pathway for the detoxification of AA aside from acetylation. This is the first molecular and functional characterization of AA biotransformation in Trichoderma spp. Given the potential of Trichoderma for cleanup of contaminated soils, these results reveal new possibilities in the fungal remediation of AA-contaminated soil.

  13. Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid

    PubMed Central

    Dutta, Moumita; Pollard, Dominic J.; Goldstone, David C.; Ramos, Andres; Müllers, Erik; Stirnnagel, Kristin; Stanke, Nicole; Lindemann, Dirk; Taylor, William R.; Rosenthal, Peter B.

    2016-01-01

    The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN—CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold. PMID:27829070

  14. Surtsey and Mount St. Helens: a comparison of early succession rates

    NASA Astrophysics Data System (ADS)

    del Moral, R.; Magnússon, B.

    2014-04-01

    Surtsey and Mount St. Helens are celebrated but very different volcanoes. Permanent plots allow for comparisons that reveal mechanisms that control succession and its rate and suggest general principles. We estimated rates from structure development, species composition using detrended correspondence analysis (DCA), changes in Euclidean distance (ED) of DCA vectors, and by principal components analysis (PCA) of DCA. On Surtsey, rates determined from DCA trajectory analyses decreased as follows: gull colony on lava with sand > gull colony on lava, no sand ≫ lava with sand > sand spit > block lava > tephra. On Mount St. Helens, plots on lahar deposits near woodlands were best developed. The succession rates of open meadows declined as follows: Lupinus-dominated pumice > protected ridge with Lupinus > other pumice and blasted sites > isolated lahar meadows > barren plain. Despite the prominent contrasts between the volcanoes, we found several common themes. Isolation restricted the number of colonists on Surtsey and to a lesser degree on Mount St. Helens. Nutrient input from outside the system was crucial. On Surtsey, seabirds fashioned very fertile substrates, while on Mount St. Helens wind brought a sparse nutrient rain, then Lupinus enhanced fertility to promote succession. Environmental stress limits succession in both cases. On Surtsey, bare lava, compacted tephra and infertile sands restrict development. On Mount St. Helens, exposure to wind and infertility slow succession.

  15. Surtsey and Mount St. Helens: a comparison of early succession rates

    NASA Astrophysics Data System (ADS)

    del Moral, R.; Magnússon, B.

    2013-12-01

    Surtsey and Mount St. Helens are celebrated, but very different volcanoes. Permanent plots allow comparisons that reveal mechanisms that control succession and its rate and suggest general principles. We estimated rates from structure development, species composition using detrended correspondence analysis (DCA), changes in Euclidean distance (ED) of DCA vectors and by principal components analysis (PCA) of DCA. On Surtsey, rates determined from DCA trajectory analyses decreased as follows: gull colony on lava with sand > gull colony on lava, no sand ≫ lava with sand > sand spit > block lava > tephra. On Mount St. Helens, plots on lahar deposits near woodlands were best developed. The succession rates of open meadows declined as follows: Lupinus-dominated pumice > protected ridge with Lupinus > other pumice and blasted sites > isolated lahar meadows > barren plain. Despite the prominent contrasts between the volcanoes, common themes were revealed. Isolation restricted the number of colonists on Surtsey and to a lesser degree on Mount St. Helens. Nutrient input from outside the system was crucial. On Surtsey, seabirds fashioned very fertile substrates, while on Mount St. Helens wind brought a sparse nutrient rain, then Lupinus enhanced fertility to promote succession. Environmental stress limits succession in both cases. On Surtsey, bare lava, compacted tephra and infertile sands restrict development. On Mount St. Helens, exposure to wind and infertility slow succession.

  16. Biodegradation of 3,4 dichloroaniline by fungal isolated from the preconditioning phase of winery wastes subjected to vermicomposting.

    PubMed

    Castillo, Jean Manuel; Nogales, Rogelio; Romero, Esperanza

    2014-02-28

    A hazardous contaminant, 3,4-dichloroaniline (DCA) is widespread in the environment due to its extensive use in the manufacture of chemicals and its application in different sectors. The ability of fungi grow on in winery wastes in the preconditioning period of vermicomposting to degrade DCA was investigated. Three filamentous fungi (F1, F2, and F3) were isolated and one identified as Aspergillus niger and two as Fusarium sp. strains. The culture media with the fungus alone or in consortium (Fmix) with DCA as the nitrogen source were analyzed by solid-phase microextraction and gas chromatography-mass spectrometry (SPME-GC/MS). The fastest degradation rate was measured in Fmix with a DT50 of 0.85day(-1). Fusarium sp. and A. niger differed in the metabolism of DCA. Five metabolites were identified as a result of oxidation, co-denitrification, N-acetylation, and polymerization reactions. The major metabolites were 3,4-dichloroacetanilide and dichloroquinolines. The azo-metabolites tetrachloroazobenzene and tetracloroazoxybenzene and 3,4-dichloronitrobenzene were found in minor amounts but appeared to be the most persistent in the Fusarium cultures (half-lives ranging from 8.3 to 30.9 days). This study highlights the metabolic potential of microorganisms in the preconditioning period of the vermicomposting process and its possible application for in situ bioremediation strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Near Discharge Cathode Assembly Plasma Potential Measurements in a 30-cm NSTAR Type Ion Engine During Beam Extraction

    NASA Technical Reports Server (NTRS)

    Herman, Daniel A.; Gallimore, Alec D.

    2006-01-01

    Floating emissive probe plasma potential data are presented over a two-dimensional array of locations in the near Discharge Cathode Assembly (DCA) region of a 30-cm diameter ring-cusp ion thruster. Discharge plasma data are presented with beam extraction at throttling conditions comparable to the NASA TH Levels 8, 12, and 15. The operating conditions of the Extended Life Test (ELT) of the Deep Space One (DS1) flight spare ion engine, where anomalous discharge keeper erosion occurred, were TH 8 and TH 12 consequently they are of specific interest in investigating discharge keeper erosion phenomena. The data do not validate the presence of a potential hill plasma structure downstream of the DCA, which has been proposed as a possible erosion mechanism. The data are comparable in magnitude to data taken by other researchers in ring-cusp electron-bombardment ion thrusters. The plasma potential structures are insensitive to thruster throttling level with a minimum as low as 14 V measured at the DCA exit plane and increasing gradually in the axial direction. A sharp increase in plasma potential to the bulk discharge value of 26 to 28 volts, roughly 10 mm radially from DCA centerline, was observed. Plasma potential measurements indicate a low-potential plume structure that is roughly 20 mm in diameter emanating from the discharge cathode that may be attributed to a free-standing plasma double layer.

  18. TiO2 structures doped with noble metals and/or graphene oxide to improve the photocatalytic degradation of dichloroacetic acid.

    PubMed

    Ribao, Paula; Rivero, Maria J; Ortiz, Inmaculada

    2017-05-01

    Noble metals have been used to improve the photocatalytic activity of TiO 2 . Noble metal nanoparticles prevent charge recombination, facilitating electron transport due to the equilibration of the Fermi levels. Furthermore, noble metal nanoparticles show an absorption band in the visible region due to a high localized surface plasmon resonance (LSPR) effect, which contributes to additional electron movements. Moreover, systems based on graphene, titanium dioxide, and noble metals have been used, considering that graphene sheets can carry charges, thereby reducing electron-hole recombination, and can be used as substrates of atomic thickness. In this work, TiO 2 -based nanocomposites were prepared by blending TiO 2 with noble metals (Pt and Ag) and/or graphene oxide (GO). The nanocomposites were mainly characterized via transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transformed infrared (FTIR), Raman spectroscopy, and photocurrent analysis. Here, the photocatalytic performance of the composites was analyzed via oxidizing dichloroacetic acid (DCA) model solutions. The influence of the noble metal load on the composite and the ability of the graphene sheets to improve the photocatalytic activity were studied, and the composites doped with different noble metals were compared. The results indicated that the platinum structures show the best photocatalytic degradation, and, although the presence of graphene oxide in the composites is supposed to enhance their photocatalytic performance, graphene oxide does not always improve the photocatalytic process. Graphical abstract It is a schematic diagram. Where NM is Noble Metal and LSPR means Localized Surface Plasmon Resonance.

  19. Aircraft Energy Conservation during Airport Ground Operations

    DTIC Science & Technology

    1982-03-01

    minimized. The model can be run in a non -optimizing mode to simulate movements along pre-assigned taxi paths. 8-6 The model is also designed ...5.5 5.6 5.7 Engine Designation by Airline and Aircraft Type IAD 2-6 Engine Designation by Airline and Aircraft Type DCA 2-7 Fuel Flow Rates...B.2 CY 1979 Aircraft Operations at IAD and DCA Airports . . 3-5 B.3 1979 Scheduled and Non -Scheduled Departures from IAD by Aircraft Type and

  20. STUDIES ON RENAL JUXTAGLOMERULAR CELLS

    PubMed Central

    Hartroft, Phyllis Merritt; Hartroft, W. Stanley

    1953-01-01

    Accumulation of granules in the juxtaglomerular cells occurred in rats which were maintained for 5 to 6 weeks on a diet low in sodium, chloride. Cytological evidence suggests that this was probably a storage phase of secretion following a decrease in the rate of liberation of the granules. Administration of DCA (desoxycorticosterone acetate) to salt-deficient rats did not alter this appearance of the juxtaglomerular cells. Two per cent sodium chloride taken in the drinking water consumed for 4 weeks by similar animals caused degranulation of the juxtaglomerular cells. This effect was enhanced by DCA. DCA administered to animals on a normal salt intake produced a lesser degree of degranulation. Cytological changes in degranulated cells suggested that these represent a stage of hyperactivity in the secretory cycle produced by an increase in the rate of liberation of granules. A hypothesis is suggested that the juxtaglomerular cells are involved in the hormonal regulation of sodium metabolism and/or blood pressure. PMID:13052809

  1. Contamination of mercury in tongkat Ali hitam herbal preparations.

    PubMed

    Ang, H H; Lee, K L

    2006-08-01

    The DCA (Drug Control Authority), Malaysia has implemented the phase three registration of traditional medicines on 1 January 1992. As such, a total of 100 products in various pharmaceutical dosage forms of a herbal preparation found in Malaysia, containing tongkat Ali hitam, either single or combined preparations, were analyzed for the presence of a heavy toxic metal, mercury, using atomic absorption spectrophotometer, after performing a simple random sampling to enable each sample an equal chance of being selected in an unbiased manner. Results showed that 26% of these products possessed 0.53-2.35 ppm of mercury, and therefore, do not comply with the quality requirement for traditional medicines in Malaysia. The quality requirement for traditional medicines in Malaysia is not exceeding 0.5 ppm for mercury. Out of these 26 products, four products have already registered with the DCA, Malaysia whilst the rest, however, have not registered with the DCA, Malaysia.

  2. Study of the mechanism for electrodeposition of dendrite-free zinc in an alkaline electrolyte modified with 1-ethyl-3-methylimidazolium dicyanamide

    NASA Astrophysics Data System (ADS)

    Xu, M.; Ivey, D. G.; Qu, W.; Xie, Z.

    2015-01-01

    Electrodeposition of Zn was conducted in a new electrolyte system composed of an alkaline solution (9 M KOH + 5 wt% ZnO) modified with a small amount (0.5 wt%) of room temperature ionic liquid 1-ethyl-3-methylimidazolium dicyanamide (EMI-DCA). At a high deposition current density of 80 mA cm-2, a porous, dendrite-free Zn film characterized by clusters of small Zn particles was obtained. The mechanism for the modified Zn morphology in the EMI-DCA containing electrolyte was studied by cyclic voltammetry, chronoamperometry, electrochemical impedance spectroscopy (EIS) and scanning electron microscopy. It was found that the addition of EMI-DCA changed the Zn nucleation process and reduced the potential variation during electrodeposition, which suppressed the uneven growth of Zn deposits and the formation of Zn dendrites. EIS results indicated that there was adsorption of EMI+ cations at the Zn film/electrolyte interface, which may have contributed to suppressed dendritic Zn growth.

  3. Characterization of dissolved organic matter from surface waters with low to high dissolved organic carbon and the related disinfection byproduct formation potential.

    PubMed

    Li, Angzhen; Zhao, Xu; Mao, Ran; Liu, Huijuan; Qu, Jiuhui

    2014-04-30

    In this study, the disinfection byproduct formation potential (DBPFP) of three surface waters with the dissolved organic carbon (DOC) content of 2.5, 5.2, and 7.9mg/L was investigated. The formation and distribution of trihalomethanes and haloacetic acids were evaluated. Samples collected from three surface waters in China were fractionated based on molecular weight and hydrophobicity. The raw water containing more hydrophobic (Ho) fraction exhibited higher formation potentials of haloacetic acid and trihalomethane. The DBPFP of the surface waters did not correlate with the DOC value. The values of DBPFP per DOC were correlated with the specific ultraviolet absorbance (SUVA) for Ho and Hi fractions. The obtained results suggested that SUVA cannot reveal the ability of reactive sites to form disinfection byproducts for waters with few aromatic structures. Combined with the analysis of FTIR and nuclear magnetic resonance spectra of the raw waters and the corresponding fractions, it was concluded that the Ho fraction with phenolic hydroxyl and conjugated double bonds was responsible for the production of trichloromethanes and trichloroacetic acids. The Hi fraction with amino and carboxyl groups had the potential to form dichloroacetic acids and chlorinated trihalomethanes. Copyright © 2014. Published by Elsevier B.V.

  4. Non-Hodgkin's Lymphoma Reversal with Dichloroacetate.

    PubMed

    Flavin, Dana F

    2010-01-01

    In June 2007, a 48-year-old male patient, diagnosed with Stage 4 Non-Hodgkin's Follicular Lymphoma (NHL), was treated for 3 months with conventional chemotherapy resulting in a complete remission. Almost one year later tumors returned in the nasopharynx and neck lymph glands. Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later. Since his last PET scan, May, 2009, he remains tumor-free from continuous DCA usage.

  5. Non-Hodgkin's Lymphoma Reversal with Dichloroacetate

    PubMed Central

    Flavin, Dana F.

    2010-01-01

    In June 2007, a 48-year-old male patient, diagnosed with Stage 4 Non-Hodgkin's Follicular Lymphoma (NHL), was treated for 3 months with conventional chemotherapy resulting in a complete remission. Almost one year later tumors returned in the nasopharynx and neck lymph glands. Refusing all suggested chemotherapies, the patient began self-administering dichloroacetate (DCA) 900 mg daily with a PET scan showing complete remission four months later. Since his last PET scan, May, 2009, he remains tumor-free from continuous DCA usage. PMID:20886020

  6. Methanol Metabolism in Pseudomonad C

    PubMed Central

    Stieglitz, B.; Mateles, R. I.

    1973-01-01

    Cell suspensions of pseudomonad C, a bacterium capable of growth on methanol as sole carbon source, were able to oxidize methanol, formaldehyde, and formate, although the rates of oxidation for the latter two compounds were much slower. The latter compounds also could not serve as sole carbon sources. Through the use of labeled compounds, it was shown that in the presence of methanol, formaldehyde, formate, and bicarbonate were incorporated into trichloroacetic acid-precipitable material. Hexose phosphate synthetase activity was found, indicating the assimilation of methanol via an allulose pathway. No hydroxypyruvate reductase activity was found, nor was any complex membrane structure observed. Such a combination of characteristics has been observed in an obligate methylotroph (Pseudomonas W1), but pseudomonad C can utilize a variety of non-methyl substrates. Images PMID:4349032

  7. Determination of Lead in Blood by Atomic Absorption Spectrophotometry1

    PubMed Central

    Selander, Stig; Cramér, Kim

    1968-01-01

    Lead in blood was determined by atomic absorption spectrophotometry, using a wet ashing procedure and a procedure in which the proteins were precipitated with trichloroacetic acid. In both methods the lead was extracted into isobutylmethylketone before measurement, using ammonium pyrrolidine dithiocarbamate as chelator. The simpler precipitation procedure was shown to give results identical with those obtained with the ashing technique. In addition, blood specimens were examined by the precipitation method and by spectral analysis, which method includes wet ashing of the samples, with good agreement. All analyses were done on blood samples from `normal' persons or from lead-exposed workers, and no additions of inorganic lead were made. The relatively simple protein precipitation technique gave accurate results and is suitable for the large-scale control of lead-exposed workers. PMID:5663425

  8. PURIFICATION OF THE SOLUBLE HEMOLYSINS OF LISTERIA MONOCYTOGENES

    PubMed Central

    Jenkins, E. M.; Njoku-Obi, A. N.; Adams, E. W.

    1964-01-01

    Jenkins, E. M. (Tuskegee Institute, Tuskegee, Ala.), A. N. Njoku-Obi, and E. W. Adams. Purification of the soluble hemolysins of Listeria monocytogenes. J. Bacteriol. 88:418–424. 1964.—A method is described for obtaining relatively purified hemolysin preparations from both virulent and avirulent strains of Listeria monocytogenes. These hemolysins are protein in nature as shown by heat lability, nondialyzable properties, precipitation with trichloroacetic acid, and electrophoretic mobility. The hemolysins are antigenic in rabbits as shown by serum neutralization tests. The potency of the purified hemolysin was markedly increased by cysteine, sodium hydrosulfite, and a number of reducing agents. Many of the actions of the purified hemolysin seemed to parallel that of streptolysin O, and certain of these activities could be explained by the “thioldisulfide hypothesis.” PMID:14203359

  9. Application of N-doped graphene modified carbon ionic liquid electrode for direct electrochemistry of hemoglobin.

    PubMed

    Sun, Wei; Dong, Lifeng; Deng, Ying; Yu, Jianhua; Wang, Wencheng; Zhu, Qianqian

    2014-06-01

    Nitrogen-doped graphene (NG) was synthesized and used for the investigation on direct electrochemistry of hemoglobin (Hb) with a carbon ionic liquid electrode as the substrate electrode. Due to specific characteristics of NG such as excellent electrocatalytic property and large surface area, direct electron transfer of Hb was realized with enhanced electrochemical responses appearing. Electrochemical behaviors of Hb on the NG modified electrode were carefully investigated with the electrochemical parameters calculated. The Hb modified electrode exhibited excellent electrocatalytic reduction activity toward different substrates, such as trichloroacetic acid and H2O2, with wider dynamic range and lower detection limit. These findings show that NG can be used for the preparation of chemically modified electrodes with improved performance and has potential applications in electrochemical sensing. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Halloysite Nanotubes as a New Adsorbent for Solid Phase Extraction and Spectrophotometric Determination of Iron in Water and Food Samples

    NASA Astrophysics Data System (ADS)

    Samadi, A.; Amjadi, M.

    2016-07-01

    Halloysite nanotubes (HNTs) have been introduced as a new solid phase extraction adsorbent for preconcentration of iron(II) as a complex with 2,2-bipyridine. The cationic complex is effectively adsorbed on the sorbent in the pH range of 3.5-6.0 and efficiently desorbed by trichloroacetic acid. The eluted complex has a strong absorption around 520 nm, which was used for determination of Fe(II). After optimizing extraction conditions, the linear range of the calibration graph was 5.0-500 μg/L with a detection limit of 1.3 μg/L. The proposed method was successfully applied for the determination of trace iron in various water and food samples, and the accuracy was assessed through the recovery experiments and analysis of a certified reference material (NIST 1643e).

  11. Dynamical cluster approximation plus semiclassical approximation study for a Mott insulator and d-wave pairing

    NASA Astrophysics Data System (ADS)

    Kim, SungKun; Lee, Hunpyo

    2017-06-01

    Via a dynamical cluster approximation with N c = 4 in combination with a semiclassical approximation (DCA+SCA), we study the doped two-dimensional Hubbard model. We obtain a plaquette antiferromagnetic (AF) Mott insulator, a plaquette AF ordered metal, a pseudogap (or d-wave superconductor) and a paramagnetic metal by tuning the doping concentration. These features are similar to the behaviors observed in copper-oxide superconductors and are in qualitative agreement with the results calculated by the cluster dynamical mean field theory with the continuous-time quantum Monte Carlo (CDMFT+CTQMC) approach. The results of our DCA+SCA differ from those of the CDMFT+CTQMC approach in that the d-wave superconducting order parameters are shown even in the high doped region, unlike the results of the CDMFT+CTQMC approach. We think that the strong plaquette AF orderings in the dynamical cluster approximation (DCA) with N c = 4 suppress superconducting states with increasing doping up to strongly doped region, because frozen dynamical fluctuations in a semiclassical approximation (SCA) approach are unable to destroy those orderings. Our calculation with short-range spatial fluctuations is initial research, because the SCA can manage long-range spatial fluctuations in feasible computational times beyond the CDMFT+CTQMC tool. We believe that our future DCA+SCA calculations should supply information on the fully momentum-resolved physical properties, which could be compared with the results measured by angle-resolved photoemission spectroscopy experiments.

  12. Biotransformation of Trichoderma spp. and Their Tolerance to Aromatic Amines, a Major Class of Pollutants

    PubMed Central

    Cocaign, Angélique; Bui, Linh-Chi; Silar, Philippe; Chan Ho Tong, Laetitia; Busi, Florent; Lamouri, Aazdine; Mougin, Christian; Rodrigues-Lima, Fernando

    2013-01-01

    Trichoderma spp. are cosmopolitan soil fungi that are highly resistant to many toxic compounds. Here, we show that Trichoderma virens and T. reesei are tolerant to aromatic amines (AA), a major class of pollutants including the highly toxic pesticide residue 3,4-dichloroaniline (3,4-DCA). In a previous study, we provided proof-of-concept remediation experiments in which another soil fungus, Podospora anserina, detoxifies 3,4-DCA through its arylamine N-acetyltransferase (NAT), a xenobiotic-metabolizing enzyme that enables acetyl coenzyme A-dependent detoxification of AA. To assess whether the N-acetylation pathway enables AA tolerance in Trichoderma spp., we cloned and characterized NATs from T. virens and T. reesei. We characterized recombinant enzymes by determining their catalytic efficiencies toward several toxic AA. Through a complementary approach, we also demonstrate that both Trichoderma species efficiently metabolize 3,4-DCA. Finally, we provide evidence that NAT-independent transformation is solely (in T. virens) or mainly (in T. reesei) responsible for the observed removal of 3,4-DCA. We conclude that T. virens and, to a lesser extent, T. reesei likely utilize another, unidentified, metabolic pathway for the detoxification of AA aside from acetylation. This is the first molecular and functional characterization of AA biotransformation in Trichoderma spp. Given the potential of Trichoderma for cleanup of contaminated soils, these results reveal new possibilities in the fungal remediation of AA-contaminated soil. PMID:23728813

  13. MtDNA COI-COII marker and drone congregation area: an efficient method to establish and monitor honeybee (Apis mellifera L.) conservation centres.

    PubMed

    Bertrand, Bénédicte; Alburaki, Mohamed; Legout, Hélène; Moulin, Sibyle; Mougel, Florence; Garnery, Lionel

    2015-05-01

    Honeybee subspecies have been affected by human activities in Europe over the past few decades. One such example is the importation of nonlocal subspecies of bees which has had an adverse impact on the geographical repartition and subsequently on the genetic diversity of the black honeybee Apis mellifera mellifera. To restore the original diversity of this local honeybee subspecies, different conservation centres were set up in Europe. In this study, we established a black honeybee conservation centre Conservatoire de l'Abeille Noire d'Ile de France (CANIF) in the region of Ile-de-France, France. CANIF's honeybee colonies were intensively studied over a 3-year period. This study included a drone congregation area (DCA) located in the conservation centre. MtDNA COI-COII marker was used to evaluate the genetic diversity of CANIF's honeybee populations and the drones found and collected from the DCA. The same marker (mtDNA) was used to estimate the interactions and the haplotype frequency between CANIF's honeybee populations and 10 surrounding honeybee apiaries located outside of the CANIF. Our results indicate that the colonies of the conservation centre and the drones of the DCA show similar stable profiles compared to the surrounding populations with lower level of introgression. The mtDNA marker used on both DCA and colonies of the conservation centre seems to be an efficient approach to monitor and maintain the genetic diversity of the protected honeybee populations. © 2014 John Wiley & Sons Ltd.

  14. Photolytic dehalogenation of disinfection byproducts in water by natural sunlight irradiation.

    PubMed

    Abusallout, Ibrahim; Hua, Guanghui

    2016-09-01

    The aqueous photolysis of halogenated disinfection byproducts (DBPs) by natural sunlight irradiation was studied to determine their photolytic dehalogenation kinetics. Total organic halogen analysis was used to quantify the dehalogenation extents of DBPs during outdoor photolysis experiments. Dichloroacetamide, chloral hydrate, chloroform, dichloroacetonitrile, monochloro-, monobromo-, dichloro-, dibromo-, and trichloroacetic acids were generally resistant to photolytic dehalogenation and showed less than 10% reduction after 6 h sunlight irradiation. Monoiodoacetic acid, tribromoacetic acid, bromoform, dibromoacetonitrile, and trichloronitromethane showed moderate to high dehalogenation degrees with half-lives of 4.0-19.3 h. Diiodoacetic acid, triiodoacetic acid, and iodoform degraded rapidly under the sunlight irradiation and exhibited half-lives of 5.3-10.2 min. In general, the photosensitive cleavage of carbon-halogen bonds of DBPs increased with increasing number of halogens (tri- > di- > mono-halogenated) and size of the substituted halogens (I > Br > Cl). Nitrate, nitrite, and pH had little impact on the photodehalogenation of DBPs under typical levels in surface waters. The presence of natural organic matter (NOM) inhibited the photodehalogenation of DBPs by light screening. The NOM inhibiting effects were more pronounced for the fast degrading iodinated DBPs. The results of this study improve our understanding about the photolytic dehalogenation of wastewater-derived DBPs in surface waters during water reuse. Published by Elsevier Ltd.

  15. A regret theory approach to decision curve analysis: a novel method for eliciting decision makers' preferences and decision-making.

    PubMed

    Tsalatsanis, Athanasios; Hozo, Iztok; Vickers, Andrew; Djulbegovic, Benjamin

    2010-09-16

    Decision curve analysis (DCA) has been proposed as an alternative method for evaluation of diagnostic tests, prediction models, and molecular markers. However, DCA is based on expected utility theory, which has been routinely violated by decision makers. Decision-making is governed by intuition (system 1), and analytical, deliberative process (system 2), thus, rational decision-making should reflect both formal principles of rationality and intuition about good decisions. We use the cognitive emotion of regret to serve as a link between systems 1 and 2 and to reformulate DCA. First, we analysed a classic decision tree describing three decision alternatives: treat, do not treat, and treat or no treat based on a predictive model. We then computed the expected regret for each of these alternatives as the difference between the utility of the action taken and the utility of the action that, in retrospect, should have been taken. For any pair of strategies, we measure the difference in net expected regret. Finally, we employ the concept of acceptable regret to identify the circumstances under which a potentially wrong strategy is tolerable to a decision-maker. We developed a novel dual visual analog scale to describe the relationship between regret associated with "omissions" (e.g. failure to treat) vs. "commissions" (e.g. treating unnecessary) and decision maker's preferences as expressed in terms of threshold probability. We then proved that the Net Expected Regret Difference, first presented in this paper, is equivalent to net benefits as described in the original DCA. Based on the concept of acceptable regret we identified the circumstances under which a decision maker tolerates a potentially wrong decision and expressed it in terms of probability of disease. We present a novel method for eliciting decision maker's preferences and an alternative derivation of DCA based on regret theory. Our approach may be intuitively more appealing to a decision-maker, particularly

  16. Classification and ordination of understory vegetation using multivariate techniques in the Pinus wallichiana forests of Swat Valley, northern Pakistan

    NASA Astrophysics Data System (ADS)

    Rahman, Inayat Ur; Khan, Nasrullah; Ali, Kishwar

    2017-04-01

    An understory vegetation survey of the Pinus wallichiana-dominated temperate forests of Swat District was carried out to inspect the structure, composition and ecological associations of the forest vegetation. A quadrat method of sampling was used to record the floristic and phytosociological data necessary for the analysis using 300 quadrats of 10 × 10 m each. Some vegetation parameters viz. frequency and density for trees (overstory vegetation) as well as for the understory vegetation were recorded. The results revealed that in total, 92 species belonging to 77 different genera and 45 families existed in the area. The largest families were Asteraceae, Rosaceae and Lamiaceae with 12, ten and nine species, respectively. Ward's agglomerative cluster analysis for tree species resulted in three floristically and ecologically distinct community types along different topographic and soil variables. Importance value indices (IVI) were also calculated for understory vegetation and were subjected to ordination techniques, i.e. canonical correspondence analysis (CCA) and detrended correspondence analysis (DCA). DCA bi-plots for stands show that most of the stands were scattered around the centre of the DCA bi-plot, identified by two slightly scattered clusters. DCA for species bi-plot clearly identified three clusters of species revealing three types of understory communities in the study area. Results of the CCA were somewhat different from the DCA showing the impact of environmental variables on the understory species. CCA results reveal that three environmental variables, i.e. altitude, slope and P (mg/kg), have a strong influence on distribution of stands and species. Impact of tree species on the understory vegetation was also tested by CCA which showed that four tree species, i.e. P. wallichiana A.B. Jackson, Juglans regia Linn., Quercus dilatata Lindl. ex Royle and Cedrus deodara (Roxb. ex Lamb.) G. Don, have strong influences on associated understory vegetation. It

  17. Intracranial dermoid cyst rupture-related brain ischemia: Case report and hemodynamic study.

    PubMed

    Jin, Hang; Guo, Zhen-Ni; Luo, Yun; Zhao, Ren; Sun, Ming-Shuo; Yang, Yi

    2017-01-01

    Spontaneous rupture of intracranial dermoid cyst is a rare but serious clinical event that can result in cerebral ischemia. Cerebral vasospasm and vasculitis are considered as potential mechanisms of dermoid cyst rupture-related cerebral ischemia. However, the hemodynamic mechanisms between cerebral ischemia and dermoid cyst rupture are not well known. A 55-year-old, right-handed man was admitted to our hospital with sudden receptive aphasia and right-sided hypoalgesia. Brain magnetic resonance imaging (MRI) revealed a ruptured dermoid cyst and watershed infarcts in the left hemisphere. Then brain magnetic resonance angiography disclosed mild stenosis in the left middle cerebral artery (MCA), and further high-resolution MRI demonstrated it was caused by an unstable atherosclerosis plaque. Transcranial Doppler of the patient showed a decreasing tendency of peak systolic velocity (PSV) of the left MCA at different time points after the stroke (from 290cm/s at day 6 to 120cm/s at day 30), indicating a transient vasospasm. However, the time course of dynamic cerebral autoregulation (dCA) seemed different from the PSV. The patient's dCA reached its lowest point at day 8 and was restored at day 10. The time course of dCA indicated a "called procedure" of a cerebrovascular regulating function to deal with the stimulation in subarachnoid space. A dermoid cyst rupture-related cerebral infarction was diagnosed in this patient. Aspirin (100 mg/d) and atorvastatin (20 mg/d) were given to the patient. A neurosurgical operation was strongly recommended to minimize the risk of further injury of the ruptured dermoid cyst; however, the patient refused the recommended treatment. The neurological deficit of the patient was significantly improved on 30 days follow-up. We found that the spread of cyst contents through the subarachnoid and/or ventricular system can induce a vasospasm. Then, dCA was "called" to deal with the stimulation in the subarachnoid space. Compromised dCA seems to

  18. Metabolic Modulation of Clear-cell Renal Cell Carcinoma with Dichloroacetate, an Inhibitor of Pyruvate Dehydrogenase Kinase.

    PubMed

    Kinnaird, Adam; Dromparis, Peter; Saleme, Bruno; Gurtu, Vikram; Watson, Kristalee; Paulin, Roxane; Zervopoulos, Sotirios; Stenson, Trevor; Sutendra, Gopinath; Pink, Desmond B; Carmine-Simmen, Katia; Moore, Ronald; Lewis, John D; Michelakis, Evangelos D

    2016-04-01

    Clear-cell renal cell carcinoma (ccRCC) exhibits suppressed mitochondrial function and preferential use of glycolysis even in normoxia, promoting proliferation and suppressing apoptosis. ccRCC resistance to therapy is driven by constitutive hypoxia-inducible factor (HIF) expression due to genetic loss of von Hippel-Lindau factor. In addition to promoting angiogenesis, HIF suppresses mitochondrial function by inducing pyruvate dehydrogenase kinase (PDK), a gatekeeping enzyme for mitochondrial glucose oxidation. To reverse mitochondrial suppression of ccRCC using the PDK inhibitor dichloroacetate (DCA). Radical nephrectomy specimens from patients with ccRCC were assessed for PDK expression. The 786-O ccRCC line and two animal models (chicken in ovo and murine xenografts) were used for mechanistic studies. Mitochondrial function, proliferation, apoptosis, HIF transcriptional activity, angiogenesis, and tumor size were measured in vitro and in vivo. Independent-sample t-tests and analysis of variance were used for statistical analyses. PDK was elevated in 786-O cells and in ccRCC compared to normal kidney tissue from the same patient. DCA reactivated mitochondrial function (increased respiration, Krebs cycle metabolites such as α-ketoglutarate [cofactor of factor inhibiting HIF], and mitochondrial reactive oxygen species), increased p53 activity and apoptosis, and decreased proliferation in 786-O cells. DCA reduced HIF transcriptional activity in an FIH-dependent manner, inhibiting angiogenesis in vitro. DCA reduced tumor size and angiogenesis in vivo in both animal models. DCA can reverse the mitochondrial suppression of ccRCC and decrease HIF transcriptional activity, bypassing its constitutive expression. Its previous clinical use in humans makes it an attractive candidate for translation to ccRCC patients. We show that an energy-boosting drug decreases tumor growth and tumor blood vessels in animals carrying human kidney cancer cells. This generic drug has been

  19. High-performance liquid chromatographic analysis of vigabatrin enantiomers in human serum by precolumn derivatization with o-phthaldialdehyde-N-acetyl-L-cysteine and fluorescence detection.

    PubMed

    Vermeij, T A; Edelbroek, P M

    1998-09-25

    A rapid and simple method is presented for the determination of vigabatrin enantiomers in human serum by high-performance liquid chromatography. Serum is deproteinized with trichloroacetic acid and aliquots of the supernatant are precolumn derivatized with o-phthaldialdehyde and N-acetyl-L-cysteine, resulting in the formation of diastereomeric isoindoles. Separation was achieved on a Spherisorb 3ODS2 column using a gradient solvent program and the column eluent is monitored using fluorescence detection. L-Homoarginine was used as an internal standard. Within-day precisions (C.V.; n=8) were 2.8 and 1.1%, respectively, for the (R)-(-)- and (S)-(+)-enantiomer in serum containing 15.4 mg/l (RS)-vigabatrin. The method was linear in the 0-45 mg/l range for both enantiomers and the minimum quantitation limit was 0.20 mg/l for (R)-(-)-vigabatrin and 0.14 mg/l for (S)-(+)-vigabatrin. No interferences were found from commonly co-administered antiepileptic drugs and from endogenous amino acids. The method is suitable for routine therapeutic drug monitoring and for pharmacokinetic studies.

  20. An effective protein extraction method for two-dimensional electrophoresis in the anticancer herb Andrographis paniculata Nees.

    PubMed

    Talei, Daryush; Valdiani, Alireza; Puad, Mohd Abdullah

    2013-01-01

    Proteomic analysis of plants relies on high yields of pure protein. In plants, protein extraction and purification present a great challenge due to accumulation of a large amount of interfering substances, including polysaccharides, polyphenols, and secondary metabolites. Therefore, it is necessary to modify the extraction protocols. A study was conducted to compare four protein extraction and precipitation methods for proteomic analysis. The results showed significant differences in protein content among the four methods. The chloroform-trichloroacetic acid-acetone method using 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer provided the best results in terms of protein content, pellets, spot resolution, and intensity of unique spots detected. An overall of 83 qualitative or quantitative significant differential spots were found among the four methods. Based on the 2-DE gel map, the method is expected to benefit the development of high-level proteomic and biochemical studies of Andrographis paniculata, which may also be applied to other recalcitrant medicinal plant tissues. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  1. Effect of chymosin and salt reduction on the quality of ultrafiltrated white-salted cheese.

    PubMed

    Al-Otaibi, Mutlag M; Wilbey, R Andrew

    2005-05-01

    This study demonstrated that both chymosin and salt-in-moisture (SM) were important factors for proteolysis in the manufacture of ultrafiltrated white-salted cheese, with significant effects on water-soluble nitrogen and nitrogen soluble in trichloroacetic acid. In contrast, the levels of free amino acids were not significantly affected by chymosin and salt treatments. The cheeses made, using high levels of chymosin with low SM had lower levels of residual alpha(S1)- and beta-casein at the end of ripening. On texture profile analysis, the hardness and fracturability of the cheeses significantly increased with SM and decreased during ripening. Increases in chymosin significantly contributed to the overall weakening of the structure throughout ripening. Bitter flavour was detected after 12 weeks in the cheese made with the higher chymosin level and lower SM, which could be the result of accumulation of gamma-casein fractions. The sensory data indicated that the hedonic responses for low chymosin with low SM cheeses were good and acceptable in flavour, which may be due to the moderate levels of proteolysis products.

  2. Potential of the TCE-degrading endophyte Pseudomonas putida W619-TCE to improve plant growth and reduce TCE phytotoxicity and evapotranspiration in poplar cuttings.

    PubMed

    Weyens, Nele; Truyens, Sascha; Dupae, Joke; Newman, Lee; Taghavi, Safiyh; van der Lelie, Daniel; Carleer, Robert; Vangronsveld, Jaco

    2010-09-01

    The TCE-degrading poplar endophyte Pseudomonas putida W619-TCE was inoculated in poplar cuttings, exposed to 0, 200 and 400 mg l(-1) TCE, that were grown in two different experimental setups. During a short-term experiment, plants were grown hydroponically in half strength Hoagland nutrient solution and exposed to TCE for 3 days. Inoculation with P. putida W619-TCE promoted plant growth, reduced TCE phytotoxicity and reduced the amount of TCE present in the leaves. During a mid-term experiment, plants were grown in potting soil and exposed to TCE for 3 weeks. Here, inoculation with P. putida W619-TCE had a less pronounced positive effect on plant growth and TCE phytotoxicity, but resulted in strongly reduced amounts of TCE in leaves and roots of plants exposed to 400 mg l(-1) TCE, accompanied by a lowered evapotranspiration of TCE. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), which are known intermediates of TCE degradation, were not detected. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. Rapid determination of trace copper in animal feed based on micro-plate colorimetric reaction and statistical partitioning correction.

    PubMed

    Niu, Yiming; Wang, Jiayi; Zhang, Chi; Chen, Yiqiang

    2017-04-15

    The objective of this study was to develop a micro-plate based colorimetric assay for rapid and high-throughput detection of copper in animal feed. Copper ion in animal feed was extracted by trichloroacetic acid solution and reduced to cuprous ion by hydroxylamine. The cuprous ion can chelate with 2,2'-bicinchoninic acid to form a Cu-BCA complex which was detected with high sensitivity by micro-plate reader at 354nm. The whole assay procedure can be completed within 20min. To eliminate matrix interference, a statistical partitioning correction approach was proposed, which makes the detection of copper in complex samples possible. The limit of detection was 0.035μg/mL and the detection range was 0.1-10μg/mL of copper in buffer solution. Actual sample analysis indicated that this colorimetric assay produced results consistent with atomic absorption spectrometry analysis. These results demonstrated that the developed assay can be used for rapid determination of copper in animal feed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. An improved method for the rapid determination of 90Sr in cow's milk.

    PubMed

    Guérin, Nicolas; Riopel, Remi; Rao, Ray; Kramer-Tremblay, Sheila; Dai, Xiongxin

    2017-09-01

    An improved method was developed to rapidly determine strontium-90 ( 90 Sr) in cow's milk samples in the event of a nuclear emergency. To perform this method, no heating or ashing steps were needed and all of the material used was disposable. Stable Sr tracer was added to each 40 mL milk sample. Hydrochloric acid (HCl) and trichloroacetic acid (TCA) were added to the sample to flocculate the suspended fat and proteins in the milk. The sample was centrifuged and the strontium in the supernatant was precipitated with carbonate. The resulting precipitate was dissolved in 8 M HNO 3 and the solution was passed through a Sr resin to remove potential interferents. Strontium was eluted from the resin using a small volume of water. Strontium-90 was measured by liquid-scintillation counting (LSC) and the tracer by inductively coupled plasma mass spectrometry (ICP-MS). The figures of merit of the method were determined and the method was validated using spiked samples. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  5. [Studies on interaction of acid-treated nanotube titanic acid and amino acids].

    PubMed

    Zhang, Huqin; Chen, Xuemei; Jin, Zhensheng; Liao, Guangxi; Wu, Xiaoming; Du, Jianqiang; Cao, Xiang

    2010-06-01

    Nanotube titanic acid (NTA) has distinct optical and electrical character, and has photocatalysis character. In accordance with these qualities, NTA was treated with acid so as to enhance its surface activity. Surface structures and surface groups of acid-treated NTA were characterized and analyzed by Transmission Electron Microscope (TEM) and Fourier Transform Infrared Spectrometry (FT-IR). The interaction between acid-treated NTA and amino acids was investigated. Analysis results showed that the lengths of acid-treated NTA became obviously shorter. The diameters of nanotube bundles did not change obviously with acid-treating. Meanwhile, the surface of acid-treated NTA was cross-linked with carboxyl or esterfunction. In addition, acid-treated NTA can catch amino acid residues easily, and then form close combination.

  6. Calcium balance in pediatric online hemodiafiltration: Beware of sodium and bicarbonate in the dialysate.

    PubMed

    Bacchetta, Justine; Sellier-Leclerc, Anne-Laure; Bertholet-Thomas, Aurélia; Carlier, Marie-Christine; Cartier, Régine; Cochat, Pierre; Ranchin, Bruno

    2015-11-01

    Online hemodiafiltration (oHDF) is increasingly used in children; we treated 28 children since 2009, adapting this technique to pediatric patients. In this service evaluation audit, we assessed plasma electrolytes to evaluate the evolution of total (tCa) and ionized (iCa) during a session, as well as dialysate calcium (dCa) concentrations. Using a 1.25 mmol Ca/L-dialysate, both tCa and iCa decreased during the session, with iCa falling below 1.1 mmol/L in 4/5 patients. In contrast, using a 1.5 mmol Ca/L-dialysate, iCa remained normal in all patients. Major discrepancies were observed between the expected and the measured dCa: 1.25 vs. 1.01 (0.83-1.04), and 1.5 vs. 1.47 (0.85-1.75) mmol/L, respectively (results presented as median [range]). These differences were explained by the modality of reconstituting dialysate: increasing bicarbonates and/or decreasing sodium requested in the dialysate decreases calcium extraction from the acid preparation. Proof of concept was given when requesting in an "ex-vivo" setting modifications in the requested sodium and bicarbonate in dialysate directly on the Fresenius machine. Nephrologists should be aware that "high bicarbonate and/or low sodium" requirements in oHDF decrease calcium in the dialysate. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  7. The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency

    PubMed Central

    Mousseau, Guillaume; Kessing, Cari F.; Fromentin, Rémi; Trautmann, Lydie; Chomont, Nicolas

    2015-01-01

    ABSTRACT Antiretroviral therapy (ART) inhibits HIV-1 replication, but the virus persists in latently infected resting memory CD4+ T cells susceptible to viral reactivation. The virus-encoded early gene product Tat activates transcription of the viral genome and promotes exponential viral production. Here we show that the Tat inhibitor didehydro-cortistatin A (dCA), unlike other antiretrovirals, reduces residual levels of viral transcription in several models of HIV latency, breaks the Tat-mediated transcriptional feedback loop, and establishes a nearly permanent state of latency, which greatly diminishes the capacity for virus reactivation. Importantly, treatment with dCA induces inactivation of viral transcription even after its removal, suggesting that the HIV promoter is epigenetically repressed. Critically, dCA inhibits viral reactivation upon CD3/CD28 or prostratin stimulation of latently infected CD4+ T cells from HIV-infected subjects receiving suppressive ART. Our results suggest that inclusion of a Tat inhibitor in current ART regimens may contribute to a functional HIV-1 cure by reducing low-level viremia and preventing viral reactivation from latent reservoirs. PMID:26152583

  8. Diverse Reductive Dehalogenases Are Associated with Clostridiales-Enriched Microcosms Dechlorinating 1,2-Dichloroethane

    PubMed Central

    Merlino, Giuseppe; Marzorati, Massimo; Rizzi, Aurora; Lavazza, Davide; de Ferra, Francesca; Carpani, Giovanna

    2015-01-01

    The achievement of successful biostimulation of active microbiomes for the cleanup of a polluted site is strictly dependent on the knowledge of the key microorganisms equipped with the relevant catabolic genes responsible for the degradation process. In this work, we present the characterization of the bacterial community developed in anaerobic microcosms after biostimulation with the electron donor lactate of groundwater polluted with 1,2-dichloroethane (1,2-DCA). Through a multilevel analysis, we have assessed (i) the structural analysis of the bacterial community; (ii) the identification of putative dehalorespiring bacteria; (iii) the characterization of functional genes encoding for putative 1,2-DCA reductive dehalogenases (RDs). Following the biostimulation treatment, the structure of the bacterial community underwent a notable change of the main phylotypes, with the enrichment of representatives of the order Clostridiales. Through PCR targeting conserved regions within known RD genes, four novel variants of RDs previously associated with the reductive dechlorination of 1,2-DCA were identified in the metagenome of the Clostridiales-dominated bacterial community. PMID:26273600

  9. The cognitive nuances of surprising events: exposure to unexpected stimuli elicits firing variations in neurons of the dorsal CA1 hippocampus.

    PubMed

    Valenti, Ornella; Mikus, Nace; Klausberger, Thomas

    2018-05-22

    The ability to recognize novel situations is among the most fascinating and vital of the brain functions. A hypothesis posits that encoding of novelty is prompted by failures in expectancy, according to computation matching incoming information with stored events. Thus, unexpected changes in context are detected within the hippocampus and transferred to downstream structures, eliciting the arousal of the dopamine system. Nevertheless, the precise locus of detection is a matter of debate. The dorsal CA1 hippocampus (dCA1) appears as an ideal candidate for operating a mismatch computation and discriminating the occurrence of diverse stimuli within the same environment. In this study, we sought to determine dCA1 neuronal firing during the experience of novel stimuli embedded in familiar contexts. We performed population recordings while head-fixed mice navigated virtual environments. Three stimuli were employed, namely a novel pattern of visual cues, an odor, and a reward with enhanced valence. The encounter of unexpected events elicited profound variations in dCA1 that were assessed both as opposite rate directions and altered network connectivity. When experienced in sequence, novel stimuli elicited specific responses that often exhibited cross-sensitization. Short-latency, event-triggered responses were in accordance with the detection of novelty being computed within dCA1. We postulate that firing variations trigger neuronal disinhibition, and constitute a fundamental mechanism in the processing of unexpected events and in learning. Elucidating the mechanisms underlying detection and computation of novelty might help in understanding hippocampal-dependent cognitive dysfunctions associated with neuropathologies and psychiatric conditions.

  10. Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes.

    PubMed

    Karacan, C Özgen; Olea, Ricardo A

    2013-04-01

    Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area. In addition, methane flowrates monitored from 10 GGVs were analyzed using decline curve analyses (DCA) techniques to determine parameters of decline rates. Surface elevation showed the most influence on methane production from GGVs and thus was used to investigate its relation with DCA parameters using correlation techniques on normal-scored data. Geostatistical analysis was pursued using sequential Gaussian co-simulation with surface elevation as the secondary variable and with DCA parameters as the primary variables. The primary DCA variables were effective percentage decline rate, rate at production start, rate at the beginning of forecast period, and production end duration. Co-simulation results were presented to visualize decline parameters at an area-wide scale. Wells located at lower elevations, i.e., at the bottom of valleys, tend to perform better in terms of their rate declines compared to those at higher elevations. These results were used to calculate drainage radii of GGVs using GIP realizations. The calculated drainage radii are close to ones predicted by pressure transient tests.

  11. Triple-element compound-specific stable isotope analysis of 1,2-dichloroethane for characterization of the underlying dehalogenation reaction in two Dehalococcoides mccartyi strains.

    PubMed

    Franke, Steffi; Lihl, Christina; Renpenning, Julian; Elsner, Martin; Nijenhuis, Ivonne

    2017-12-01

    Chlorinated ethanes belong to the most common groundwater and soil contaminants. Of these, 1,2-dichloroethane (1,2-DCA) is a man-made, persistent and toxic contaminant, released due to improper waste treatment at versatile production sites. This study investigated the anaerobic transformation of 1,2-DCA by Dehalococcoides mccartyi strain 195 and strain BTF08 using triple-element compound-specific stable isotope analysis of carbon, chlorine and hydrogen for the first time. Isotope fractionation patterns for carbon (εCBTF08 = -28.4 ± 3.7‰; εC195 = -30.9 ± 3.6‰) and chlorine (εClBTF08 = -4.6 ± 0.7‰; εCl195 = -4.2 ± 0.5‰) within both investigated D. mccartyi strains, as well as the dual-element analysis (ΛBTF08 = 6.9 ± 1.2; Λ195 = 7.1 ± 0.2), supported identical reaction mechanisms for dehalogenation of 1,2-DCA. Hydrogen isotope fractionation analysis revealed dihaloelimination as prevalent reaction mechanism. Vinyl chloride as major intermediate could be excluded by performing the experiment in deuterated aqueous media. Furthermore, evaluation of the derived apparent kinetic isotope effects (AKIECBTF08 = 1.029/AKIEC195 = 1.031; AKIEClBTF08 = 1.005/AKIECl195 = 1.004) pointed towards simultaneous abstraction of both involved chlorine-substituents in a concerted matter. It was shown that D. mccartyi strain BTF08 and strain 195 are capable of complete, direct dihaloelimination of 1,2-DCA to ethene. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes

    USGS Publications Warehouse

    Karacan, C. Özgen; Olea, Ricardo A.

    2013-01-01

    Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area. In addition, methane flowrates monitored from 10 GGVs were analyzed using decline curve analyses (DCA) techniques to determine parameters of decline rates. Surface elevation showed the most influence on methane production from GGVs and thus was used to investigate its relation with DCA parameters using correlation techniques on normal-scored data. Geostatistical analysis was pursued using sequential Gaussian co-simulation with surface elevation as the secondary variable and with DCA parameters as the primary variables. The primary DCA variables were effective percentage decline rate, rate at production start, rate at the beginning of forecast period, and production end duration. Co-simulation results were presented to visualize decline parameters at an area-wide scale. Wells located at lower elevations, i.e., at the bottom of valleys, tend to perform better in terms of their rate declines compared to those at higher elevations. These results were used to calculate drainage radii of GGVs using GIP realizations. The calculated drainage radii are close to ones predicted by pressure transient tests.

  13. Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes

    PubMed Central

    Karacan, C.Özgen; Olea, Ricardo A.

    2015-01-01

    Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area. In addition, methane flowrates monitored from 10 GGVs were analyzed using decline curve analyses (DCA) techniques to determine parameters of decline rates. Surface elevation showed the most influence on methane production from GGVs and thus was used to investigate its relation with DCA parameters using correlation techniques on normal-scored data. Geostatistical analysis was pursued using sequential Gaussian co-simulation with surface elevation as the secondary variable and with DCA parameters as the primary variables. The primary DCA variables were effective percentage decline rate, rate at production start, rate at the beginning of forecast period, and production end duration. Co-simulation results were presented to visualize decline parameters at an area-wide scale. Wells located at lower elevations, i.e., at the bottom of valleys, tend to perform better in terms of their rate declines compared to those at higher elevations. These results were used to calculate drainage radii of GGVs using GIP realizations. The calculated drainage radii are close to ones predicted by pressure transient tests. PMID:26190930

  14. Inhibition of protein synthesis in maize and wheat by trichothecene mycotoxins and hybridoma-based enzyme immunoassay for deoxynivalenol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Casale, W.L.

    1987-01-01

    The 12,13-epoxytrichothecene mycotoxins deoxynivalenol (DON, vomitoxin) and T-2 toxin inhibited protein synthesis in vivo and in cell-free systems from wheat and maize, host plants of trichothecene-producing Fusarium spp.Protein synthesis in tissue (leaf discs and kernel sections) was measured by incorporation of /sup 3/H-leucine into acetone:ethanol insoluble material, and in cell-free translation systems from wheat embryos and maize seedling plumules by incorporation of /sup 3/H-leucine into trichloroacetic acid-insoluble material. The toxin concentration inhibiting 50% of /sup 3/H-leucine incorporation (ID/sub 50/) by several maize varieties were 0.9 ..mu..M (T-2 toxin) and 9-22 ..mu..M (DON). ID/sub 50/ values for wheat were 0.25 ..mu..Mmore » (T-2 toxin) and 4.5 ..mu..M (DON).« less

  15. The compromise of dynamic disulfide/thiol homeostasis as a biomarker of oxidative stress in trichloroethylene exposure.

    PubMed

    Bal, C; Büyükşekerci, M; Koca, C; Ağış, E R; Erdoğan, S; Baran, P; Gündüzöz, M; Yilmaz, Öh

    2016-09-01

    In this study, we aimed to investigate disulfide/thiol homeostasis in trichloroethylene (TCE) exposure. The study was carried out in 30 nonsmoker TCE-exposed workers with a variety of occupations. Additionally, 30 healthy nonsmoker volunteers were recruited as the control group. TCE exposure was determined by measuring urinary trichloroacetic acid (TCA) concentration. Median urinary TCA levels of exposed workers (20.5 mg/L) were significantly higher than control subjects (5 mg/L). Thiol and disulfide concentrations were determined using a novel automated method. Disulfide/thiol ratio was significantly higher in the exposed group (p < 0.001). Thiol/disulfide homeostasis was found to be disturbed in TCE-exposed workers. We predict that in TCE-exposed workers this disturbance can be a therapeutic target, and the efficiency of the treatment can easily be monitored by the novel method we used. © The Author(s) 2015.

  16. Investigation on direct electrochemical and electrocatalytic behavior of hemoglobin on palladium-graphene modified electrode.

    PubMed

    Chen, Wei; Niu, Xueliang; Li, Xiaoyan; Li, Xiaobao; Li, Guangjiu; He, Bolin; Li, Qiutong; Sun, Wei

    2017-11-01

    Palladium-graphene (Pd-GR) nanocomposite was acted as modifier for construction of the modified electrode with direct electrochemistry of hemoglobin (Hb) realized. By using Nafion as the immobilization film, Hb was fixed tightly on Pd-GR nanocomposite modified carbon ionic liquid electrode. Electrochemical behaviors of Hb modified electrode were checked by cyclic voltammetry and a pair of redox peaks originated from direct electron transfer of Hb was appeared. The Hb modified electrode had excellent electrocatalytic activity to the reduction of trichloroacetic acid and sodium nitrite in the concentration range from 0.6 to 13.0mmol·L -1 and from 0.04 to 0.5 mmol·L -1 . Therefore Pd-GR nanocomposite was proven to be a good candidate for the fabrication of third-generation electrochemical biosensor. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Block clustering based on difference of convex functions (DC) programming and DC algorithms.

    PubMed

    Le, Hoai Minh; Le Thi, Hoai An; Dinh, Tao Pham; Huynh, Van Ngai

    2013-10-01

    We investigate difference of convex functions (DC) programming and the DC algorithm (DCA) to solve the block clustering problem in the continuous framework, which traditionally requires solving a hard combinatorial optimization problem. DC reformulation techniques and exact penalty in DC programming are developed to build an appropriate equivalent DC program of the block clustering problem. They lead to an elegant and explicit DCA scheme for the resulting DC program. Computational experiments show the robustness and efficiency of the proposed algorithm and its superiority over standard algorithms such as two-mode K-means, two-mode fuzzy clustering, and block classification EM.

  18. [Ecological relationships among artificial vegetations during their restoration in Antaibao mining area].

    PubMed

    Zhang, Guilian; Zhang, Jintun; Guo, Xiaoyu

    2005-01-01

    By the methods of TWINSPAN, DCA and DCCA, and from the aspects of the relations between plant species, communities and environmental factors, this paper studied the ecological relationships among artificial vegetations during their restoration in Antaibao mining area. 63 collected quadrates were classified into 12 community types by TWINSPAN, and the distribution of the communities could comprehensively reflect the influence of environmental factors. DCA ordination indicated that soil water content, which was increased with restoration time, was the main factor restricting the distribution of the communities. DCCA ordination showed that soil organic matter content was the decisive factor to the development of communities.

  19. Microbial degradation of poly(amino acid)s.

    PubMed

    Obst, Martin; Steinbüchel, Alexander

    2004-01-01

    Natural poly(amino acid)s are a group of poly(ionic) molecules (ionomers) with various biological functions and putative technical applications and play, therefore, an important role both in nature and in human life. Because of their biocompatibility and their synthesis from renewable resources, poly(amino acid)s may be employed for many different purposes covering a broad spectrum of medical, pharmaceutical, and personal care applications as well as the domains of agriculture and of environmental applications. Biodegradability is one important advantage of naturally occurring poly(amino acid)s over many synthetic polymers. The intention of this review is to give an overview about the enzyme systems catalyzing the initial steps in poly(amino acid) degradation. The focus is on the naturally occurring poly(amino acid)s cyanophycin, poly(epsilon-L-lysine) and poly(gamma-glutamic acid); but biodegradation of structurally related synthetic polyamides such as poly(aspartic acid) and nylons, which are known from various technical applications, is also included.

  20. Maternal-embryonic metabolic and antioxidant response of Chapalichthys pardalis (Teleostei: Goodeidae) induced by exposure to 3,4-dichloroaniline.

    PubMed

    Carbajal-Hernández, Ana Laura; Valerio-García, Roberto Carlos; Martínez-Ruíz, Erika Berenice; Jarquín-Díaz, Víctor Hugo; Martínez-Jerónimo, Fernando

    2017-07-01

    Chapalichthys pardalis is a viviparous fish, microendemic to the Tocumbo Region in the state of Michoacán, Mexico. Despite the peculiar type of reproduction of goodeid fish and their mother-embryo interaction, the effects on embryos induced by maternal exposure to aquatic xenobiotics are still unknown. The objective of the present work was to determine the maternal-embryonic metabolic and antioxidant response of C. pardalis exposed to 3,4-dichloroaniline (3,4-DCA), a compound considered highly noxious to the environment because of its high toxicity and persistence, which has been used as reference toxicant in toxicological bioassays. We determined the median lethal concentration (LC 50 , 96 h) and then exposed pregnant females to 3.3, 2.5, and 0.5 mg L -1 of 3,4-DCA (equivalent to LC 1 , LC 0.01 , and LC 50/10 , respectively) during 21 days. We assessed the activity of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), macromolecules content (proteins, lipids, carbohydrates), glucose, and lactate concentration, as well as the oxidative damage, by measuring thiobarbituric acid reactive substances, and protein oxidation. To interpret results, we used the integrated biomarker response (IBRv2). The average LC 50 was of 5.18 mg L -1 (4.8-5.5 mg L -1 ; p = 0.05). All females exposed to concentrations of 3.3 and 2.5 mg L -1 lost 100% of the embryos during the bioassay, whereas those exposed to 0.5 mg L -1 showed alterations in the antioxidant activity and oxidative damage, being the embryos and the maternal liver the most affected, with IBRv2 values of 10.09 and 9.21, respectively. Damage to macromolecules was greater in embryos and the maternal liver, with IBRv2 of 16.14 and 8.40, respectively. We conclude that exposure to xenobiotics, like 3,4-DCA, in species with a marked maternal-embryonic interaction represents a potential risk for the development and survival of the descendants, thereby, potentially affecting

  1. Using a simple HPLC approach to identify the enzymatic products of UTL-5g, a small molecule TNF-α inhibitor, from porcine esterase and from rabbit esterase.

    PubMed

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

    2013-12-01

    UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. As a prelude to investigating the metabolites of UTL-5g, we set out to identify the enzymatic products of UTL-5g under the treatment of both porcine liver esterase (PLE) and rabbit liver esterase (RLE). First, a number of mixtures made by UTL-5g and PLE were incubated at 25°C. At predetermined time points, individual samples were quenched by acetonitrile, vortexed, and centrifuged. The supernatants were then analyzed by reversed-phase HPLC (using a C18 column). The retention times and UV/vis spectra of individual peaks were compared to those of UTL-5g and its two postulated enzymatic products; thus the enzymatic products of UTL-5g were tentatively identified. Secondly, a different HPLC method (providing different retentions times) was used to cross-check and to confirm the identities of the two enzymatic products. Based on the observations, it was concluded that under the treatment of PLE, the major enzymatic products of UTL-5g were 5-methyliosxazole-3-carboxylic acid (ISOX) and 2,4-dichloroaniline (DCA). Treatment of UTL-5g by RLE also provided the same enzymatic products of UTL-5g from esterase. These results indicate that the peptide bond in UTL-5g was cleaved by PLE/RLE. Michaelis-Menten kinetics showed that the Km values of UTL-5g were 2.07mM with PLE and 0.37mM with RLE indicating that UTL-5g had a higher affinity with RLE. In summary, by a simple HPLC approach, we have concluded that the peptide bond in UTL-5g was cleaved by esterase from either porcine liver or rabbit liver in vitro and afforded DCA (at a mole ratio of 1:1) and ISOX. However, further studies are needed in order to determine whether UTL-5g is metabolized by microsomal enzymes to produce ISOX and DCA. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. In vitro metabolism and drug-drug interaction potential of UTL-5g, a novel chemo- and radioprotective agent.

    PubMed

    Wu, Jianmei; Shaw, Jiajiu; Dubaisi, Sarah; Valeriote, Frederick; Li, Jing

    2014-12-01

    N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 µM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited ∼30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 µM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute(-1)·mM(-1), respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  3. In Vitro Metabolism and Drug-Drug Interaction Potential of UTL-5g, a Novel Chemo- and Radioprotective Agent

    PubMed Central

    Wu, Jianmei; Shaw, Jiajiu; Dubaisi, Sarah; Valeriote, Frederick

    2014-01-01

    N-(2,4-dichlorophenyl)-5-methyl-1,2-oxazole-3-carboxamide (UTL-5g), a potential chemo- and radioprotective agent, acts as a prodrug requiring bioactivation to the active metabolite 5-methylisoxazole-3-carboxylic acid (ISOX). UTL-5g hydrolysis to ISOX and 2,4-dichloroaniline (DCA) has been identified in porcine and rabbit liver esterases. The purpose of this study was to provide insights on the metabolism and drug interaction potential of UTL-5g in humans. The kinetics of UTL-5g hydrolysis was determined in human liver microsomes (HLM) and recombinant human carboxylesterases (hCE1b and hCE2). The potential of UTL-5g and its metabolites for competitive inhibition and time-dependent inhibition of microsomal cytochrome P450 (P450) was examined in HLM. UTL-5g hydrolysis to ISOX and DCA in HLM were NADPH-independent, with a maximum rate of reaction (Vmax) of 11.1 nmol/min per mg and substrate affinity (Km) of 41.6 µM. Both hCE1b and hCE2 effectively catalyzed UTL-5g hydrolysis, but hCE2 exhibited ∼30-fold higher catalytic efficiency (Vmax/Km) than hCE1b. UTL-5g and DCA competitively inhibited microsomal CYP1A2, CYP2B6, and CYP2C19 (IC50 values <50 µM), and exhibited time-dependent inhibition of microsomal CYP1A2 with the inactivation efficiency (kinact/KI) of 0.68 and 0.51 minute−1·mM−1, respectively. ISOX did not inhibit or inactivate any tested microsomal P450. In conclusion, hCE1b and hCE2 play a key role in the bioactivation of UTL-5g. Factors influencing carboxylesterase activities may have a significant impact on the pharmacological and therapeutic effects of UTL-5g. UTL-5g has the potential to inhibit P450-mediated metabolism through competitive inhibition or time-dependent inhibition. Caution is particularly needed for potential drug interactions involving competitive inhibition or time-dependent inhibition of CYP1A2 in the future clinical development of UTL-5g. PMID:25249693

  4. Simultaneous high-performance liquid chromatographic analysis of pregabalin, gabapentin and vigabatrin in human serum by precolumn derivatization with o-phtaldialdehyde and fluorescence detection.

    PubMed

    Vermeij, T A C; Edelbroek, P M

    2004-10-25

    A rapid, simple and robust method is presented for the simultaneous determination of the gamma-amino-n-butyric acid (GABA) derivatives pregabalin (PGB), gabapentin (GBP) and vigabatrin (VGB) in human serum by high-performance liquid chromatography (HPLC). Serum is deproteinized with trichloroacetic acid and aliquots of the supernatant are precolumn derivatized with o-phtaldialdehyde (OPA) and 3-mercaptopropionic acid. Separation is achieved on a Alltima 3C18 column using isocratic elution; the drugs are monitored using fluorescence detection. Norvaline is used as an internal standard. Within-day precision (COV; n = 10) is 1.2% for PGB (serum concentration 10.0 mg/l), 1.1% for GBP (serum concentration 15.8 mg/l) and 0.3% for VGB (serum concentration 15.5 mg/l). The method is linear up to at least 63 mg/l for PGB, 40 mg/l for GBP and 62 mg/l for VGB. Lower limits of quantitation (LOQ) are 0.13 mg/l for PGB, 0.53 mg/l for GBP and 0.06 mg/l for VGB. No interferences were found from commonly coadministered antiepileptic drugs (AEDs) and from endogenous amino acids. Experimental design in combination with statistical evaluation (ANOVA) was used to study the robustness of chromatography and sample preparation. The method is very suitable for routine therapeutic drug monitoring and for pharmacokinetic studies.

  5. A homogeneous method to measure aminoacyl-tRNA synthetase aminoacylation activity using scintillation proximity assay technology.

    PubMed

    Macarrón, R; Mensah, L; Cid, C; Carranza, C; Benson, N; Pope, A J; Díez, E

    2000-09-10

    A new method to measure the aminoacylation of tRNA based upon the use of the scintillation proximity assay (SPA) technology has been developed. The assay detects incorporation of radiolabeled amino acids into cognate tRNA, catalyzed by a specific aminoacyl-tRNA synthetase (aaRS). Under acidic conditions, uncoated yttrium silicate SPA beads were found to bind tRNA aggregates, while the radiolabeled amino acid substrate remains in solution, resulting in good signal discrimination of these two species in the absence of any separation steps. The usefulness of this approach was demonstrated by measurement of steady-state kinetic constants and inhibitor binding constants for a range of aaRS enzymes in comparison with data from standard, trichloroacetic acid-precipitation-based assays. In all cases, the data were quantitatively comparable. Although the radioisotopic counting efficiency of the SPA method was less than that of standard liquid scintillation counting, the statistical performance (i.e., signal to background, variability, stability) of the SPA assays was at least equivalent to the separation-based methods. The assay was also shown to work well in miniaturized 384-well microtiter plate formats, resulting in considerable reagent savings. In summary, a new method to characterize aaRS activity is described that is faster and more amenable to high-throughput screening than traditional methods. Copyright 2000 Academic Press.

  6. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    ERIC Educational Resources Information Center

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  7. Omega-3 fatty acids: new insights into the pharmacology and biology of docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid.

    PubMed

    Davidson, Michael H

    2013-12-01

    Fish oil contains a complex mixture of omega-3 fatty acids, which are predominantly eicosapentaenoic acid (EPA), docosapentaenoic acid, and docosahexaenoic acid (DHA). Each of these omega-3 fatty acids has distinct biological effects that may have variable clinical effects. In addition, plasma levels of omega-3 fatty acids are affected not only by dietary intake, but also by the polymorphisms of coding genes fatty acid desaturase 1-3 for the desaturase enzymes that convert short-chain polyunsaturated fatty acids to long-chain polyunsaturated fatty acids. The clinical significance of this new understanding regarding the complexity of omega-3 fatty acid biology is the purpose of this review. FADS polymorphisms that result in either lower levels of long-chain omega-3 fatty acids or higher levels of long-chain omega-6 polyunsaturated fatty acids, such as arachidonic acid, are associated with dyslipidemia and other cardiovascular risk factors. EPA and DHA have differences in their effects on lipoprotein metabolism, in which EPA, with a more potent peroxisome proliferator-activated receptor-alpha effect, decreases hepatic lipogenesis, whereas DHA not only enhances VLDL lipolysis, resulting in greater conversion to LDL, but also increases HDL cholesterol and larger, more buoyant LDL particles. Overall, these results emphasize that blood concentrations of individual long-chain polyunsaturated fatty acids, which reflect both dietary intake and metabolic influences, may have independent, but also complementary- biological effects and reinforce the need to potentially provide a complex mixture of omega-3 fatty acids to maximize cardiovascular risk reduction.

  8. Monte-Carlo and multi-exposure assessment for the derivation of criteria for disinfection byproducts and volatile organic compounds in drinking water: Allocation factors and liter-equivalents per day.

    PubMed

    Akiyama, Megumi; Matsui, Yoshihiko; Kido, Junki; Matsushita, Taku; Shirasaki, Nobutaka

    2018-06-01

    The probability distributions of total potential doses of disinfection byproducts and volatile organic compounds via ingestion, inhalation, and dermal exposure were estimated with Monte Carlo simulations, after conducting physiologically based pharmacokinetic model simulations to takes into account the differences in availability between the three exposures. If the criterion that the 95th percentile estimate equals the TDI (tolerable daily intake) is regarded as protecting the majority of a population, the drinking water criteria would be 140 (trichloromethane), 66 (bromodichloromethane), 157 (dibromochloromethane), 203 (tribromomethane), 140 (dichloroacetic acid), 78 (trichloroacetic acid), 6.55 (trichloroethylene, TCE), and 22 μg/L (perchloroethylene). The TCE criterion was lower than the Japanese Drinking Water Quality Standard (10 μg/L). The latter would allow the intake of 20% of the population to exceed the TDI. Indirect inhalation via evaporation from water, especially in bathrooms, was the major route of exposure to compounds other than haloacetic acids (HAAs) and accounted for 1.2-9 liter-equivalents/day for the median-exposure subpopulation. The ingestion of food was a major indirect route of exposure to HAAs. Contributions of direct water intake were not very different for trihalomethanes (30-45% of TDIs) and HAAs (45-52% of TDIs). Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Disinfection byproduct formation in drinking water sources: A case study of Yuqiao reservoir.

    PubMed

    Zhai, Hongyan; He, Xizhen; Zhang, Yan; Du, Tingting; Adeleye, Adeyemi S; Li, Yao

    2017-08-01

    This study investigated the potential formation of disinfection byproducts (DBPs) during chlorination and chloramination of 20 water samples collected from different points of Yuqiao reservoir in Tianjin, China. The concentrations of dissolved organic matter and ammonia decreased downstream the reservoir, while the specific UV absorbance (SUVA: the ratio of UV 254 to dissolved organic carbon) increased [from 0.67 L/(mg*m) upstream to 3.58 L/(mg*m) downstream]. The raw water quality played an important role in the formation of DBPs. During chlorination, haloacetic acids (HAAs) were the major DBPs formed in most of the water samples, followed by trihalomethanes (THMs). CHCl 3 and CHCl 2 Br were the major THM species, while trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) were the major HAA species. Chloramination, on the other hand, generally resulted in lower concentrations of THMs (CHCl 3 ), HAAs (TCAA and DCAA), and haloacetonitriles (HANs). All the species of DBPs formed had positive correlations with the SUVA values, and HANs had the highest one (R 2  = 0.8). The correlation coefficients between the analogous DBP yields and the SUVA values in chlorinated samples were close to those in chloraminated samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. UNCERTAINTY ANALYSIS OF TCE USING THE DOSE EXPOSURE ESTIMATING MODEL (DEEM) IN ACSL

    EPA Science Inventory

    The ACSL-based Dose Exposure Estimating Model(DEEM) under development by EPA is used to perform art uncertainty analysis of a physiologically based pharmacokinetic (PSPK) model of trichloroethylene (TCE). This model involves several circulating metabolites such as trichloroacet...

  11. Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett's esophagus (BE).

    PubMed

    Cronin, James; McAdam, Elizabeth; Danikas, Antonios; Tselepis, Chris; Griffiths, Paul; Baxter, John; Thomas, Linzi; Manson, James; Jenkins, Gareth

    2011-01-01

    bile acid deoxycholic acid (DCA) (at neutral and acidic pH) and acid alone was capable of upregulating EGFR mRNA in vitro, and in the case of neutral pH DCA, this was NF-κB dependent. EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. Furthermore, as EGFR is a membranous protein expressed on the luminal surface of the esophageal mucosa, it may also be a useful target for biopsy guidance during endoscopy.

  12. A regret theory approach to decision curve analysis: A novel method for eliciting decision makers' preferences and decision-making

    PubMed Central

    2010-01-01

    Background Decision curve analysis (DCA) has been proposed as an alternative method for evaluation of diagnostic tests, prediction models, and molecular markers. However, DCA is based on expected utility theory, which has been routinely violated by decision makers. Decision-making is governed by intuition (system 1), and analytical, deliberative process (system 2), thus, rational decision-making should reflect both formal principles of rationality and intuition about good decisions. We use the cognitive emotion of regret to serve as a link between systems 1 and 2 and to reformulate DCA. Methods First, we analysed a classic decision tree describing three decision alternatives: treat, do not treat, and treat or no treat based on a predictive model. We then computed the expected regret for each of these alternatives as the difference between the utility of the action taken and the utility of the action that, in retrospect, should have been taken. For any pair of strategies, we measure the difference in net expected regret. Finally, we employ the concept of acceptable regret to identify the circumstances under which a potentially wrong strategy is tolerable to a decision-maker. Results We developed a novel dual visual analog scale to describe the relationship between regret associated with "omissions" (e.g. failure to treat) vs. "commissions" (e.g. treating unnecessary) and decision maker's preferences as expressed in terms of threshold probability. We then proved that the Net Expected Regret Difference, first presented in this paper, is equivalent to net benefits as described in the original DCA. Based on the concept of acceptable regret we identified the circumstances under which a decision maker tolerates a potentially wrong decision and expressed it in terms of probability of disease. Conclusions We present a novel method for eliciting decision maker's preferences and an alternative derivation of DCA based on regret theory. Our approach may be intuitively more

  13. Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure.

    PubMed

    Dominguez, G; Dagnas, M; Decorte, L; Vandesquille, M; Belzung, C; Béracochéa, D; Mons, N

    2016-03-01

    Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.

  14. Common modulation of limbic network activation underlies musical emotions as they unfold.

    PubMed

    Singer, Neomi; Jacoby, Nori; Lin, Tamar; Raz, Gal; Shpigelman, Lavi; Gilam, Gadi; Granot, Roni Y; Hendler, Talma

    2016-11-01

    Music is a powerful means for communicating emotions among individuals. Here we reveal that this continuous stream of affective information is commonly represented in the brains of different listeners and that particular musical attributes mediate this link. We examined participants' brain responses to two naturalistic musical pieces using functional Magnetic Resonance imaging (fMRI). Following scanning, as participants listened to the musical pieces for a second time, they continuously indicated their emotional experience on scales of valence and arousal. These continuous reports were used along with a detailed annotation of the musical features, to predict a novel index of Dynamic Common Activation (DCA) derived from ten large-scale data-driven functional networks. We found an association between the unfolding music-induced emotionality and the DCA modulation within a vast network of limbic regions. The limbic-DCA modulation further corresponded with continuous changes in two temporal musical features: beat-strength and tempo. Remarkably, this "collective limbic sensitivity" to temporal features was found to mediate the link between limbic-DCA and the reported emotionality. An additional association with the emotional experience was found in a left fronto-parietal network, but only among a sub-group of participants with a high level of musical experience (>5years). These findings may indicate two processing-levels underlying the unfolding of common music emotionality; (1) a widely shared core-affective process that is confined to a limbic network and mediated by temporal regularities in music and (2) an experience based process that is rooted in a left fronto-parietal network that may involve functioning of the 'mirror-neuron system'. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Mars Global Digital Dune Database (MGD3): Global dune distribution and wind pattern observations

    USGS Publications Warehouse

    Hayward, Rosalyn K.; Fenton, Lori; Titus, Timothy N.

    2014-01-01

    The Mars Global Digital Dune Database (MGD3) is complete and now extends from 90°N to 90°S latitude. The recently released south pole (SP) portion (MC-30) of MGD3 adds ∼60,000 km2 of medium to large-size dark dune fields and ∼15,000 km2 of sand deposits and smaller dune fields to the previously released equatorial (EQ, ∼70,000 km2), and north pole (NP, ∼845,000 km2) portions of the database, bringing the global total to ∼975,000 km2. Nearly all NP dunes are part of large sand seas, while the majority of EQ and SP dune fields are individual dune fields located in craters. Despite the differences between Mars and Earth, their dune and dune field morphologies are strikingly similar. Bullseye dune fields, named for their concentric ring pattern, are the exception, possibly owing their distinctive appearance to winds that are unique to the crater environment. Ground-based wind directions are derived from slipface (SF) orientation and dune centroid azimuth (DCA), a measure of the relative location of a dune field inside a crater. SF and DCA often preserve evidence of different wind directions, suggesting the importance of local, topographically influenced winds. In general however, ground-based wind directions are broadly consistent with expected global patterns, such as polar easterlies. Intriguingly, between 40°S and 80°S latitude both SF and DCA preserve their strongest, though different, dominant wind direction, with transport toward the west and east for SF-derived winds and toward the north and west for DCA-derived winds.

  16. Effects of a high O2 dynamic-controlled atmosphere technology on the browning of postharvest white mushroom ( Agaricus bisporus) in relation to energy metabolism.

    PubMed

    Li, Ling; Sun, Han; Kitazawa, Hiroaki; Wang, Xiangyou

    2017-07-01

    Browning is one of the main problems in senescence of mushrooms, and it is also one of the most important attributes accounting for the loss of the quality and reduction in market value. In order to study the relationship between the energy metabolism and the browning of white mushroom under high O 2 dynamic-controlled atmosphere (HO-DCA), mushrooms were stored in 100% O 2 (SCA1), 80% O 2  + 20% CO 2 (SCA2), 100% O 2 for three days and then transferred into the treatment of 80% O 2  + 20% CO 2 (HO-DCA) at 2 ± 1 ℃ and air as control. In this study, adenosine triphosphate (ATP) content, energy charge level, sensory evaluation, browning of surface and flesh, cell membrane integrity, exogenous ATP, polyphenol oxidase (PPO) and peroxidase (POD) activity and genes encoding PPO of the white mushroom were investigated. These were all closely related to the browning of products. The optimal storage condition of the HO-DCA treatment could delay the browning of pericarp and flesh tissues of the mushrooms, inhibit PPO activity and reduce the relative expression levels of the three genes encoding PPO. Meanwhile, it maintained moderate POD activity, good sensory properties and cell membrane integrity in a certain extent and thus slowed down the senescence of mushrooms. Results indicated that there was a positive correlation between the ATP content and whitening index ( r = 0.901). In addition, HO-DCA maintained a higher ATP level, prolonged the storage time to 28 days and it might be an ideal strategy for preserving the quality of mushroom during storage.

  17. Is Dynamic Cerebral Autoregulation Bilaterally Impaired after Unilateral Acute Ischemic Stroke?

    PubMed

    Xiong, Li; Tian, Ge; Lin, Wenhua; Wang, Wei; Wang, Lijuan; Leung, Thomas; Mok, Vincent; Liu, Jia; Chen, Xiangyan; Wong, Ka Sing

    2017-05-01

    Whether dynamic cerebral autoregulation (dCA) is impaired focally in the affected hemisphere or bilaterally in both the affected and nonaffected hemispheres after ischemic stroke remains controversial. We therefore investigated the pattern of dCA in acute ischemic stroke patients with different subtypes. Sixty acute ischemic stroke patients with unilateral anterior circulation infarct [30 with large artery atherosclerosis (LAA), 13 with small vessel disease (SVD), and 17 with coexisting LAA and SVD] and 16 healthy controls were enrolled. Spontaneous arterial blood pressure and cerebral blood flow velocity fluctuations in both bilateral middle cerebral arteries using transcranial Doppler were recorded over 10 minutes. Transfer function analysis was applied to obtain autoregulatory parameters, autoregulation index (ARI), phase difference (PD), and gain. PD was significantly lower on both the ipsilateral and contralateral sides in the LAA group (ipsilateral, 30.74 degrees; contralateral, 29.17 degrees) and the coexisting LAA and SVD group (20.23 degrees; 13.10 degrees) than that in healthy controls (left side, 51.66 degrees; right side, 58.48 degrees) (all P < .05), but there were no significant differences between the 2 sides when compared with each other in all groups. However, in the coexisting LAA and SVD group, phase on both sides was significantly lower when compared with that in the LAA and SVD groups, respectively. The results of ARI were consistent with the findings in PD. The results indicate that dCA is bilaterally impaired in acute ischemic patients with LAA, and the coexisting SVD may aggravate the bilateral impairment of dCA. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. Comparable dynamics of linuron catabolic genes and IncP-1 plasmids in biopurification systems (BPSs) as a response to linuron spiking.

    PubMed

    Nour, Eman H; Elsayed, Tarek R; Springael, Dirk; Smalla, Kornelia

    2017-06-01

    On-farm biopurification systems (BPSs) represent an efficient technology for treating pesticide-contaminated wastewater. Biodegradation by genetically adapted bacteria has been suggested to perform a major contribution to the removal of pesticides in BPSs. Recently, several studies pointed to the role of IncP-1 plasmids in the degradation of pesticides in BPSs but this was never linked with catabolic markers. Therefore, a microcosm experiment was conducted in order to examine whether changes in mobile genetic element (MGE) abundances in response to the application of phenylurea herbicide linuron are linked with changes in catabolic genes. Denaturing gradient gel electrophoresis (DGGE) fingerprints of 16S ribosomal RNA gene fragments amplified from total community (TC)-DNA suggested significant shifts in the bacterial community composition. PCR-Southern blot-based detection of genes involved in linuron hydrolysis (libA and hylA) or degradation of its metabolite 3,4-dichloroaniline (dcaQ I , dcaQ II , and ccdC) in TC-DNA showed that the abundance of the hylA gene was increased faster and stronger in response to linuron application than that of the libA gene, and that the dcaQ II gene was more abundant than the isofunctional gene dcaQ I 20 and 60 days after linuron addition. Furthermore, a significant increase in the relative abundance of the IncP-1-specific korB gene in response to linuron was recorded. Our data suggest that different bacterial populations bearing isofunctional genes coding for enzymes degrading linuron seemed to be enriched in BPSs in response to linuron and that IncP-1 plasmids might be involved in their dissemination.

  19. Boric acid and boronic acids inhibition of pigeonpea urease.

    PubMed

    Reddy, K Ravi Charan; Kayastha, Arvind M

    2006-08-01

    Urease from the seeds of pigeonpea was competitively inhibited by boric acid, butylboronic acid, phenylboronic acid, and 4-bromophenylboronic acid; 4-bromophenylboronic acid being the strongest inhibitor, followed by boric acid > butylboronic acid > phenylboronic acid, respectively. Urease inhibition by boric acid is maximal at acidic pH (5.0) and minimal at alkaline pH (10.0), i.e., the trigonal planar B(OH)3 form is a more effective inhibitor than the tetrahedral B(OH)4 -anionic form. Similarly, the anionic form of phenylboronic acid was least inhibiting in nature.

  20. Music exposure improves spatial cognition by enhancing the BDNF level of dorsal hippocampal subregions in the developing rats.

    PubMed

    Xing, Yingshou; Chen, Wenxi; Wang, Yanran; Jing, Wei; Gao, Shan; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-03-01

    Previous research has shown that dorsal hippocampus plays an important role in spatial memory process. Music exposure can enhance brain-derived neurotrophic factor (BDNF) expression level in dorsal hippocampus (DH) and thus enhance spatial cognition ability. But whether music experience may affect different subregions of DH in the same degree remains unclear. Here, we studied the effects of exposure to Mozart K.448 on learning behavior in developing rats using the classical Morris water maze task. The results showed that early music exposure could enhance significantly learning performance of the rats in the water maze test. Meanwhile, the BDNF/TrkB level of dorsal hippocampus CA3 (dCA3) and dentate gyrus (dDG) was significantly enhanced in rats exposed to Mozart music as compared to those without music exposure. In contrast, the BDNF/TrkB level of dorsal hippocampus CA1 (dCA1) was not affected. The results suggest that the spatial memory improvement by music exposure in rats may be associated with the enhanced BDNF/TrkB level of dCA3 and dDG. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation.

    PubMed

    De Preter, Géraldine; Neveu, Marie-Aline; Danhier, Pierre; Brisson, Lucie; Payen, Valéry L; Porporato, Paolo E; Jordan, Bénédicte F; Sonveaux, Pierre; Gallez, Bernard

    2016-01-19

    Glucose fermentation through glycolysis even in the presence of oxygen (Warburg effect) is a common feature of cancer cells increasingly considered as an enticing target in clinical development. This study aimed to analyze the link between metabolism, energy stores and proliferation rates in cancer cells. We found that cell proliferation, evaluated by DNA synthesis quantification, is correlated to glycolytic efficiency in six cancer cell lines as well as in isogenic cancer cell lines. To further investigate the link between glycolysis and proliferation, a pharmacological inhibitor of the pentose phosphate pathway (PPP) was used. We demonstrated that reduction of PPP activity decreases cancer cells proliferation, with a profound effect in Warburg-phenotype cancer cells. The crucial role of the PPP in sustaining cancer cells proliferation was confirmed using siRNAs against glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the PPP. In addition, we found that dichloroacetate (DCA), a new clinically tested compound, induced a switch of glycolytic cancer cells to a more oxidative phenotype and decreased proliferation. By demonstrating that DCA decreased the activity of the PPP, we provide a new mechanism by which DCA controls cancer cells proliferation.

  2. Numerical Simulation of Dynamic Contact Angles and Contact Lines in Multiphase Flows using Level Set Method

    NASA Astrophysics Data System (ADS)

    Pendota, Premchand

    Many physical phenomena and industrial applications involve multiphase fluid flows and hence it is of high importance to be able to simulate various aspects of these flows accurately. The Dynamic Contact Angles (DCA) and the contact lines at the wall boundaries are a couple of such important aspects. In the past few decades, many mathematical models were developed for predicting the contact angles of the inter-face with the wall boundary under various flow conditions. These models are used to incorporate the physics of DCA and contact line motion in numerical simulations using various interface capturing/tracking techniques. In the current thesis, a simple approach to incorporate the static and dynamic contact angle boundary conditions using the level set method is developed and implemented in multiphase CFD codes, LIT (Level set Interface Tracking) (Herrmann (2008)) and NGA (flow solver) (Desjardins et al (2008)). Various DCA models and associated boundary conditions are reviewed. In addition, numerical aspects such as the occurrence of a stress singularity at the contact lines and grid convergence of macroscopic interface shape are dealt with in the context of the level set approach.

  3. Determination of mercury by cold vapor atomic absorption spectrophotometer in Tongkat Ali preparations obtained in Malaysia.

    PubMed

    Ang, Hooi-Hoon; Lee, Ee-Lin; Cheang, Hui-Seong

    2004-01-01

    The DCA (Drug Control Authority), Malaysia, has implemented the phase 3 registration of traditional medicines on 1 January 1992, with special emphasis on the quality, efficacy, and safety (including the presence of heavy metals) in all pharmaceutical dosage forms of traditional medicine preparations. As such, a total of 100 products in various pharmaceutical dosage forms of a herbal preparation, containing Tongkat Ali, were analyzed for mercury content using cold vapor atomic absorption spectrophotometer. Results showed that 36% of the above products possessed 0.52 to 5.30 ppm of mercury and, therefore, do not comply with the quality requirement for traditional medicines in Malaysia. Out of these 36 products, 5 products that possessed 1.05 to 4.41 ppm of mercury were in fact have already registered with the DCA, Malaysia. However, the rest of the products that contain 0.52 to 5.30 ppm of mercury still have not registered with the DCA, Malaysia. Although this study showed that only 64% of the products complied with the quality requirement for traditional medicines in Malaysia pertaining to mercury, they cannot be assumed safe from mercury contamination because of batch-to-batch inconsistency.

  4. Comparing Models of Spontaneous Variations, Maneuvers and Indexes to Assess Dynamic Cerebral Autoregulation.

    PubMed

    Chacón, Max; Noh, Sun-Ho; Landerretche, Jean; Jara, José L

    2018-01-01

    We analyzed the performance of linear and nonlinear models to assess dynamic cerebral autoregulation (dCA) from spontaneous variations in healthy subjects and compared it with the use of two known maneuvers to abruptly change arterial blood pressure (BP): thigh cuffs and sit-to-stand. Cerebral blood flow velocity and BP were measured simultaneously at rest and while the maneuvers were performed in 20 healthy subjects. To analyze the spontaneous variations, we implemented two types of models using support vector machine (SVM): linear and nonlinear finite impulse response models. The classic autoregulation index (ARI) and the more recently proposed model-free ARI (mfARI) were used as measures of dCA. An ANOVA analysis was applied to compare the different methods and the coefficient of variation was calculated to evaluate their variability. There are differences between indexes, but not between models and maneuvers. The mfARI index with the sit-to-stand maneuver shows the least variability. Support vector machine modeling of spontaneous variation with the mfARI index could be used for the assessment of dCA as an alternative to maneuvers to introduce large BP fluctuations.

  5. In vivo voltammetry: from wire to wireless measurements.

    PubMed

    Crespi, Francesco; Dalessandro, Davide; Annovazzi-Lodi, Valerio; Heidbreder, Christian; Norgia, Michele

    2004-12-30

    A novel telemetric system based on either differential pulse voltammetry (DPV) or direct current amperometry (DCA) by using a diffused infrared transmission channel is presented. Unlike similar pre-existing instruments based on infrared transmission, the present system works on a single-way communication, thus avoiding problems related to cross-talking between two-way channels. The infrared channel is also immune from electromagnetic interferences from the surrounding environment. Further advancement is the development of an original miniaturised system (dimension 1cm x 1.2 cm x 0.5 cm) with reduced weight (5-6 g), suitable for affixing to the rat head and allowing real time telemetric monitoring using DCA sampling of neurotransmitters such as dopamine or serotonin every 100 ms. The set-up is based on a transmitter (TX) circuit mounted on the animal's head and connected to the electrodes inserted into its brain. The TX circuit generates the proper electrical signals for DPV or DCA, collects the electrical response of the brain and transmits it, via an infrared channel, to a receiving station (RX) interfaced with a personal computer. The PC performs the sampling and elaboration of polarographic traces in a flexible and programmable way.

  6. MISTIC2: comprehensive server to study coevolution in protein families.

    PubMed

    Colell, Eloy A; Iserte, Javier A; Simonetti, Franco L; Marino-Buslje, Cristina

    2018-06-14

    Correlated mutations between residue pairs in evolutionarily related proteins arise from constraints needed to maintain a functional and stable protein. Identifying these inter-related positions narrows down the search for structurally or functionally important sites. MISTIC is a server designed to assist users to calculate covariation in protein families and provide them with an interactive tool to visualize the results. Here, we present MISTIC2, an update to the previous server, that allows to calculate four covariation methods (MIp, mfDCA, plmDCA and gaussianDCA). The results visualization framework has been reworked for improved performance, compatibility and user experience. It includes a circos representation of the information contained in the alignment, an interactive covariation network, a 3D structure viewer and a sequence logo. Others components provide additional information such as residue annotations, a roc curve for assessing contact prediction, data tables and different ways of filtering the data and exporting figures. Comparison of different methods is easily done and scores combination is also possible. A newly implemented web service allows users to access MISTIC2 programmatically using an API to calculate covariation and retrieve results. MISTIC2 is available at: https://mistic2.leloir.org.ar.

  7. Acid Rain

    USGS Publications Warehouse

    Bricker, Owen P.; Rice, Karen C.

    1995-01-01

    Although acid rain is fading as a political issue in the United States and funds for research in this area have largely disappeared, the acidity of rain in the Eastern United States has not changed significantly over the last decade, and it continues to be a serious environmental problem. Acid deposition (commonly called acid rain) is a term applied to all forms of atmospheric deposition of acidic substances - rain, snow, fog, acidic dry particulates, aerosols, and acid-forming gases. Water in the atmosphere reacts with certain atmospheric gases to become acidic. For example, water reacts with carbon dioxide in the atmosphere to produce a solution with a pH of about 5.6. Gases that produce acids in the presence of water in the atmosphere include carbon dioxide (which converts to carbonic acid), oxides of sulfur and nitrogen (which convert to sulfuric and nitric acids}, and hydrogen chloride (which converts to hydrochloric acid). These acid-producing gases are released to the atmosphere through natural processes, such as volcanic emissions, lightning, forest fires, and decay of organic matter. Accordingly, precipitation is slightly acidic, with a pH of 5.0 to 5.7 even in undeveloped areas. In industrialized areas, most of the acid-producing gases are released to the atmosphere from burning fossil fuels. Major emitters of acid-producing gases include power plants, industrial operations, and motor vehicles. Acid-producing gases can be transported through the atmosphere for hundreds of miles before being converted to acids and deposited as acid rain. Because acids tend to build up in the atmosphere between storms, the most acidic rain falls at the beginning of a storm, and as the rain continues, the acids "wash out" of the atmosphere.

  8. Urinary excretion half life of trichloroacetic acid as a biomarker of exposure to chlorinated drinking water disinfection by-products

    PubMed Central

    Bader, E; Hrudey, S; Froese, K

    2004-01-01

    Methods: A longitudinal pilot exposure/intervention study measured the elimination half life of TCAA in urine. Beverage consumption was limited to a public water supply and bottled water of known TCAA concentration, and ingestion volume was managed. The five participants limited fluid consumption to only the water provided. Consumption journals were kept by each participant and their daily first morning urine (FMU) samples were analysed for TCAA and creatinine. TCAA elimination half life curves were generated from a two week washout period using TCAA-free bottled water. Results: Individual elimination half lives ranged from 2.1 to 6.3 days, for single compartment exponential decay, the model which fit the data. Conclusion: Urinary TCAA is persistent enough to be viable as a biomarker of medium term (days) exposure to drinking water TCAA ingestion within a range of realistic concentrations. PMID:15258281

  9. PHAGE FORMATION IN STAPHYLOCOCCUS MUSCAE CULTURES

    PubMed Central

    Price, Winston H.

    1952-01-01

    1. The synthesis of ribonucleic acid, desoxyribomicleic acid, and protein in S. muscae has been studied: (a) during the lag phase, (b) during the early log phase, and (c) while the cells are forming an adaptive enzyme for lactose utilization. 2. During the lag phase there may be a 60 per cent increase in ribonucleic acid and protein and a 50 per cent increase in dry weight without a change in cell count, as determined microscopically, or an increase in turbidity. 3. During this period, the increase in protein closely parallels the increase in ribonucleic acid, in contrast to desoxyribonucleic acid, which begins to be synthesized about 45 minutes after the protein and ribonucleic acid have begun to increase. 4. The RNA N/protein N ratio is proportional to the growth rate of all S. muscae strains studied. 5. While the RNA content per cell during the early log phase depends upon the growth rate, the DNA content per cell is fairly constant irrespective of the growth rate of the cell. 6. Resting cells of S. muscae have approximately the same RNA content per cell irrespective of their prospective growth rate. 7. While the cells are adapting to lactose, during which time there is little or no cellular division, there is never an increase of protein without a simultaneous increase in ribonucleic acid, the RNA N/protein N ratio during these intervals being approximately 0.15. 8. Lactose-adapting cells show a loss of ribonucleic acid. The purines-pyrimidines of the ribonucleic acid can be recovered in the cold 5 per cent trichloroacetic acid fraction, but the ribose component is completely lost from the system. 9. The significance of these results is discussed in relation to the importance of ribonucleic acid for protein synthesis. PMID:14955617

  10. Transformation efficiency and formation of transformation products during photochemical degradation of TCE and PCE at micromolar concentrations

    PubMed Central

    2014-01-01

    Background Trichloroethene and tetrachloroethene are the most common pollutants in groundwater and two of the priority pollutants listed by the U.S. Environmental Protection Agency. In previous studies on TCE and PCE photolysis and photochemical degradation, concentration ranges exceeding environmental levels by far with millimolar concentrations of TCE and PCE have been used, and it is not clear if the obtained results can be used to explain the degradation of these contaminants at more realistic environmental concentration levels. Methods Experiments with micromolar concentrations of TCE and PCE in aqueous solution using direct photolysis and UV/H2O2 have been conducted and product formation as well as transformation efficiency have been investigated. SPME/GC/MS, HPLC/UV and ion chromatography with conductivity detection have been used to determine intermediates of degradation. Results The results showed that chloride was a major end product in both TCE and PCE photodegradation. Several intermediates such as formic acid, dichloroacetic acid, dichloroacetaldehyede, chloroform, formaldehyde and glyoxylic acid were formed during both, UV and UV/H2O2 treatment of TCE. However chloroacetaldehyde and chloroacetic acid were only detected during direct UV photolysis of TCE and oxalic acid was only formed during the UV/H2O2 process. For PCE photodegradation, formic acid, di- and trichloroacetic acids were detected in both UV and UV/H2O2 systems, but formaldehyde and glyoxylic acid were only detected during direct UV photolysis. Conclusions For water treatment UV/H2O2 seems to be favorable over direct UV photolysis because of its higher degradation efficiency and lower risk for the formation of harmful intermediates. PMID:24401763

  11. Transformation efficiency and formation of transformation products during photochemical degradation of TCE and PCE at micromolar concentrations.

    PubMed

    Dobaradaran, Sina; Lutze, Holger; Mahvi, Amir Hossein; Schmidt, Torsten C

    2014-01-08

    Trichloroethene and tetrachloroethene are the most common pollutants in groundwater and two of the priority pollutants listed by the U.S. Environmental Protection Agency. In previous studies on TCE and PCE photolysis and photochemical degradation, concentration ranges exceeding environmental levels by far with millimolar concentrations of TCE and PCE have been used, and it is not clear if the obtained results can be used to explain the degradation of these contaminants at more realistic environmental concentration levels. Experiments with micromolar concentrations of TCE and PCE in aqueous solution using direct photolysis and UV/H2O2 have been conducted and product formation as well as transformation efficiency have been investigated. SPME/GC/MS, HPLC/UV and ion chromatography with conductivity detection have been used to determine intermediates of degradation. The results showed that chloride was a major end product in both TCE and PCE photodegradation. Several intermediates such as formic acid, dichloroacetic acid, dichloroacetaldehyede, chloroform, formaldehyde and glyoxylic acid were formed during both, UV and UV/H2O2 treatment of TCE. However chloroacetaldehyde and chloroacetic acid were only detected during direct UV photolysis of TCE and oxalic acid was only formed during the UV/H2O2 process. For PCE photodegradation, formic acid, di- and trichloroacetic acids were detected in both UV and UV/H2O2 systems, but formaldehyde and glyoxylic acid were only detected during direct UV photolysis. For water treatment UV/H2O2 seems to be favorable over direct UV photolysis because of its higher degradation efficiency and lower risk for the formation of harmful intermediates.

  12. Sequential injection redox or acid-base titration for determination of ascorbic acid or acetic acid.

    PubMed

    Lenghor, Narong; Jakmunee, Jaroon; Vilen, Michael; Sara, Rolf; Christian, Gary D; Grudpan, Kate

    2002-12-06

    Two sequential injection titration systems with spectrophotometric detection have been developed. The first system for determination of ascorbic acid was based on redox reaction between ascorbic acid and permanganate in an acidic medium and lead to a decrease in color intensity of permanganate, monitored at 525 nm. A linear dependence of peak area obtained with ascorbic acid concentration up to 1200 mg l(-1) was achieved. The relative standard deviation for 11 replicate determinations of 400 mg l(-1) ascorbic acid was 2.9%. The second system, for acetic acid determination, was based on acid-base titration of acetic acid with sodium hydroxide using phenolphthalein as an indicator. The decrease in color intensity of the indicator was proportional to the acid content. A linear calibration graph in the range of 2-8% w v(-1) of acetic acid with a relative standard deviation of 4.8% (5.0% w v(-1) acetic acid, n=11) was obtained. Sample throughputs of 60 h(-1) were achieved for both systems. The systems were successfully applied for the assays of ascorbic acid in vitamin C tablets and acetic acid content in vinegars, respectively.

  13. Synthesis, interaction with DNA and bovine serum albumin of the transition metal complexes of demethylcantharate and 2-aminobenzothiazole

    NASA Astrophysics Data System (ADS)

    Zhang, Fan; Lin, Qiu-Yue; Li, Shi-Kun; Zhao, Yu-Ling; Wang, Peng-Peng; Chen, Miao-Miao

    2012-12-01

    Four new transition metal complexes (Habtz)2[M(DCA)2]·6H2O (M = Co(II) (1), Ni(II) (2), Cu(II) (3), Zn(II) (4); DCA = demethylcantharate, 7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, C8H8O5; Habtz = 2-aminobenzothiazole acid, C7H7N2S) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and thermogravimetric analysis. The coordination number of complex was six. The X-ray diffraction analysis indicated that complex 3 crystallized in the triclinic crystal system with P1¯ space group. The DNA-binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra, viscosity measurements. Title complexes could bind to DNA via partial intercalative mode. The Kb of the complexes were 5.33 × 104 (1), 7.04 × 104 (2), 9.91 × 104 (3) and 5.03 × 104 L mol-1 (4). The results of agarose gel electrophoresis showed that Cu(II) complex could cleave pBR322 plasmid DNA via radical-based mechanism. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) through a static quenching with the binding constants Ka of 1.11 × 104 (1), 1.24 × 106 (2), 8.42 × 105 (3) and 1.75 × 104 L mol-1 (4). The complexes had intense antiproliferative activities against human hepatoma cell lines (SMMC7721) and human gastric cancer cells (MGC80-3) lines in vitro. Cu(II) complex had the strongest activity against human gastric cancer cells.

  14. Enantioselective oxidation of racemic lactic acid to D-lactic acid and pyruvic acid by Pseudomonas stutzeri SDM.

    PubMed

    Gao, Chao; Qiu, Jianhua; Li, Jingchen; Ma, Cuiqing; Tang, Hongzhi; Xu, Ping

    2009-03-01

    D-lactic acid and pyruvic acid are two important building block intermediates. Production of D-lactic acid and pyruvic acid from racemic lactic acid by biotransformation is economically interesting. Biocatalyst prepared from 9 g dry cell wt l(-1) of Pseudomonas stutzeri SDM could catalyze 45.00 g l(-1)DL-lactic acid into 25.23 g l(-1)D-lactic acid and 19.70 g l(-1) pyruvic acid in 10h. Using a simple ion exchange process, D-lactic acid and pyruvic acid were effectively separated from the biotransformation system. Co-production of d-lactic acid and pyruvic acid by enantioselective oxidation of racemic lactic acid is technically feasible.

  15. Effect of propionic acid on citric acid fermentation in an integrated citric acid-methane fermentation process.

    PubMed

    Xu, Jian; Bao, Jia-Wei; Su, Xian-Feng; Zhang, Hong-Jian; Zeng, Xin; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

    2016-03-01

    In this study, an integrated citric acid-methane fermentation process was established to solve the problem of wastewater treatment in citric acid production. Citric acid wastewater was treated through anaerobic digestion and then the anaerobic digestion effluent (ADE) was further treated and recycled for the next batch citric acid fermentation. This process could eliminate wastewater discharge and reduce water resource consumption. Propionic acid was found in the ADE and its concentration continually increased in recycling. Effect of propionic acid on citric acid fermentation was investigated, and results indicated that influence of propionic acid on citric acid fermentation was contributed to the undissociated form. Citric acid fermentation was inhibited when the concentration of propionic acid was above 2, 4, and 6 mM in initial pH 4.0, 4.5 and, 5.0, respectively. However, low concentration of propionic acid could promote isomaltase activity which converted more isomaltose to available sugar, thereby increasing citric acid production. High concentration of propionic acid could influence the vitality of cell and prolong the lag phase, causing large amount of glucose still remaining in medium at the end of fermentation and decreasing citric acid production.

  16. Effect of baseline plasma fatty acids on eicosapentaenoic acid levels in individuals supplemented with alpha-linolenic acid.

    PubMed

    DeFilippis, Andrew P; Harper, Charles R; Cotsonis, George A; Jacobson, Terry A

    2009-01-01

    We previously reported a >50% increase in mean plasma eicosapentaenoic acid levels in a general medicine clinic population after supplementation with alpha-linolenic acid. In the current analysis, we evaluate the variability of changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid and evaluated the impact of baseline plasma fatty acids levels on changes in eicosapentaenoic acid levels in these individuals. Changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid ranged from a 55% decrease to a 967% increase. Baseline plasma fatty acids had no statistically significant effect on changes in eicosapentaenoic levels acid after alpha-linolenic acid supplementation. Changes in eicosapentaenoic acid levels varied considerably in a general internal medicine clinic population supplemented with alpha-linolenic acid. Factors that may impact changes in plasma eicosapentaenoic acid levels after alpha-linolenic acid supplementation warrant further study.

  17. A novel method to analyze betaine in chicken liver: effect of dietary betaine and choline supplementation on the hepatic betaine concentration in broiler chicks.

    PubMed

    Saarinen, M T; Kettunen, H; Pulliainen, K; Peuranen, S; Tiihonen, K; Remus, J

    2001-02-01

    Betaine was measured from liver tissue by a high-performance liquid chromatographic (HPLC) method developed for this study. The method involves homogenization of liver in acetate buffer at pH 6 and precipitation of protein with trichloroacetic acid, which was removed by diethyl ether extraction. Betaine was separated using a cation exchange column in Ca(2+) form and detected with a refractive index detector. This method also allows the determination of S-adenosylmethionine (S-AM) from the same liver extract but with different HPLC conditions. Broiler chicks were fed with experimental diets supplemented with four different doses of betaine or choline ranging from 0 to 5 mol equiv. After a 3 week feeding period, the livers were analyzed for betaine and S-AM. Dietary betaine was twice as efficient in increasing the hepatic betaine concentration as dietary choline. The hepatic S-AM concentrations were similar in all dietary treatments.

  18. Rapid determination of ampicillin in bovine milk by liquid chromatography with fluorescence detection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ang, C.Y.W.; Luo, Wenhong

    1997-01-01

    A rapid and sensitive liquid chromatographic (LC) method was developed for the determination of ampicillin residues in raw bovine milk, processed skim milk, and pasteurized, homogenized whole milk with vitamin D. Milk samples were deproteinized with trichloroacetic acid (TCA) and acetonictrile. After centrifugation, the clear supernatant was reacted with formaldehyde and TCA under heat. The major fluorescent derivative of ampicillin was then determined by reversed-phase LC with fluorescence detection. Average recoveries of ampicillin fortified at 5, 10, and 20 ppb (ng/mL) were all >85% with coefficients of variation <10%. Limits of detection ranged from 0.31 to 0.51 ppb and limitsmore » of quantitation, from 0.66 to 1.2 ppb. After appropriate validation, this method should be suitable for rapid analysis of milk for ampicillin residues at the tolerance level of 10 ppb. 16 refs., 4 figs., 3 tabs.« less

  19. Sclerotherapy for congenital lesions in the head and neck.

    PubMed

    Kim, Kwang Hyun; Sung, Myung-Whun; Roh, Jong-Lyel; Han, Moon Hee

    2004-09-01

    This study retrospectively reviews the results of sclerotherapy using several sclerosants for congenital lesions of the head and neck. Between May 1990 and May 2002, patients with lymphatic malformations were treated by sclerotherapy; 10 with bleomycin, and 25 with OK-432. OK-432 sclerotherapy was also applied in 9 patients with plunging ranula and in 1 patient with branchial anomaly. Percutaneous sclerotherapy with ethanolamine oleate was used in 29 patients with venous malformations, and 28 patients with pyriform sinus fistula were treated by trichloroacetic acid chemocauterization. Overall, two thirds of patients with these lesions showed marked to complete response. One case of mortality occurred in the bleomycin sclerotherapy group. However, no major complications by other sclerosants were found. In lymphatic malformations, history of excision before sclerotherapy was a poor prognostic factor. Sclerotherapy using these sclerosants is a safe and effective primary treatment for congenital lesions in the head and neck.

  20. Studies on the extraction of nitrogenous and phosphorus-containing materials from the seeds of kidney beans (Phaseolus vulgaris)

    PubMed Central

    Pusztai, A.

    1965-01-01

    1. The conditions of extracting nitrogenous, phosphorus-containing and glucosamine-containing components of the seeds of kidney bean have been studied. 2. The dispersing of proteins was incomplete below pH 7, and the exact amount of protein extracted depended on the pH and the ionic strength of the solvent. 3. The extraction of proteins was practically complete in the range pH 7–9, but the relative amounts of the individual proteins obtained still depended on the pH of the extracting media, indicating a pH-dependent association–dissociation reaction between the protein molecules present. 4. The extraction of phosphorus-containing material showed an optimum at pH 6–7, and only a part of this was removed on dialysis. The precipitates obtained with trichloroacetic acid, on the other hand, retained very little phosphorus-containing material. 5. The significance of these findings is discussed. PMID:14340051

  1. EFFECT OF DICHLOROACETIC ACID AND TRICHLOROACETIC ACID ON DNA METHYLATION IN LIVER AND TUMORS OF FEMALE B6C3F1 MICE. (R825384)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. A simple, fast and sensitive screening LC-ESI-MS/MS method for antibiotics in fish.

    PubMed

    Guidi, Letícia Rocha; Santos, Flávio Alves; Ribeiro, Ana Cláudia S R; Fernandes, Christian; Silva, Luiza H M; Gloria, Maria Beatriz A

    2017-01-15

    The objective of this study was to develop and validate a fast, sensitive and simple liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the screening of six classes of antibiotics (aminoglycosides, beta-lactams, macrolides, quinolones, sulfonamides and tetracyclines) in fish. Samples were extracted with trichloroacetic acid. LC separation was achieved on a Zorbax Eclipse XDB C18 column and gradient elution using 0.1% heptafluorobutyric acid in water and acetonitrile as mobile phase. Analysis was carried out in multiple reaction monitoring mode via electrospray interface operated in the positive ionization mode, with sulfaphenazole as internal standard. The method was suitable for routine screening purposes of 40 antibiotics, according to EC Guidelines for the Validation of Screening Methods for Residues of Veterinary Medicines, taking into consideration threshold value, cut-off factor, detection capability, limit of detection, sensitivity and specificity. Real fish samples (n=193) from aquaculture were analyzed and 15% were positive for enrofloxacin (quinolone), one of them at a higher concentration than the level of interest (50µgkg -1 ), suggesting possible contamination or illegal use of that antibiotic. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Synthesis of protein in host-free reticulate bodies of Chlamydia psittaci and Chlamydia trachomatis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hatch, T.P.; Miceli, M.; Silverman, J.A.

    1985-06-01

    Synthesis of protein by the obligate intracellular parasitic bacteria Chlamydia psittaci (6BC) and Chlamydia trachomatis (serovar L2) isolated from host cells (host-free chlamydiae) was demonstrated for the first time. Incorporation of (/sup 35/S)methionine and (/sup 35/S)cysteine into trichloroacetic acid-precipitable material by reticulate bodies of chlamydiae persisted for 2 h and was dependent upon a exogenous source of ATP, an ATP-regenerating system, and potassium or sodium ions. Magnesium ions and amino acids stimulated synthesis; chloramphenicol, rifampin, oligomycin, and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (a proton ionophore) inhibited incorporation. Ribonucleoside triphosphates (other than ATP) had little stimulatory effect. The optimum pH for host-free synthesismore » was between 7.0 and 7.5. The molecular weights of proteins synthesized by host-free reticulate bodies closely resembled the molecular weights of proteins synthesized by reticulate bodies in an intracellular environment, and included outer membrane proteins. Elementary bodies of chlamydiae were unable to synthesize protein even when incubated in the presence of 10 mM dithiothreitol, a reducing agent which converted the highly disulfide bond cross-linked major outer membrane protein to monomeric form.« less

  4. Determination of piracetam in rat plasma by LC-MS/MS and its application to pharmacokinetics.

    PubMed

    Wang, Xianqin; Zhu, Jiayin; Xu, Renai; Yang, Xuezhi; Wu, Haiya; Lin, Dan; Ye, Faqing; Hu, Lufeng

    2010-10-01

    A sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of piracetam in rat plasma was developed and validated over the concentration range of 0.1-20 µg/mL. After addition of oxiracetam as internal standard, a simplified protein precipitation with trichloroacetic acid (5%) was employed for the sample preparation. Chromatographic separation was performed by a Zorbax SB-Aq column (150 × 2.1 mm, 3.5 µm). The mobile phase was acetonitrile-1% formic acid in water (10:90 v/v) delivered at a flow rate of 0.3 mL/min. The MS data acquisition was accomplished in multiple reaction monitoring mode with a positive electrospray ionization interface. The lower limit of quantification was 0.1 µg/mL. For inter-day and intra-day tests, the precision (RSD) for the entire validation was less than 9%, and the accuracy was within the 94.6-103.2% range. The developed method was successfully applied to pharmacokinetic studies of piracetam in rats following single oral administration dose of 50 mg/kg. Copyright © 2010 John Wiley & Sons, Ltd.

  5. [Lipid synthesis by an acidic acid tolerant Rhodotorula glutinis].

    PubMed

    Lin, Zhangnan; Liu, Hongjuan; Zhang, Jian'an; Wang, Gehua

    2016-03-01

    Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis.

  6. Determination of polyfluoroalkyl phosphoric acid diesters, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, perfluoroalkyl carboxylic acids, and perfluoroalkane sulfonic acids in lake trout from the Great Lakes region.

    PubMed

    Guo, Rui; Reiner, Eric J; Bhavsar, Satyendra P; Helm, Paul A; Mabury, Scott A; Braekevelt, Eric; Tittlemier, Sheryl A

    2012-11-01

    A comprehensive method to extract perfluoroalkyl carboxylic acids, perfluoroalkane sulfonic acids, perfluoroalkyl phosphonic acids, perfluoroalkyl phosphinic acids, and polyfluoroalkyl phosphoric acid diesters simultaneously from fish samples has been developed. The recoveries of target compounds ranged from 78 % to 121 %. The new method was used to analyze lake trout (Salvelinus namaycush) from the Great Lakes region. The results showed that the total perfluoroalkane sulfonate concentrations ranged from 0.1 to 145 ng/g (wet weight) with perfluorooctane sulfonate (PFOS) as the dominant contaminant. Concentrations in fish between lakes were in the order of Lakes Ontario ≈ Erie > Huron > Superior ≈ Nipigon. The total perfluoroalkyl carboxylic acid concentrations ranged from 0.2 to 18.2 ng/g wet weight. The aggregate mean perfluorooctanoic acid (PFOA) concentration in fish across all lakes was 0.045 ± 0.023 ng/g. Mean concentrations of PFOA were not significantly different (p > 0.1) among the five lakes. Perfluoroalkyl phosphinic acids were detected in lake trout from Lake Ontario, Lake Erie, and Lake Huron with concentration ranging from non-detect (ND) to 0.032 ng/g. Polyfluoroalkyl phosphoric acid diesters were detected only in lake trout from Lake Huron, at levels similar to perfluorooctanoic acid.

  7. Production of Succinic Acid from Citric Acid and Related Acids by Lactobacillus Strains

    PubMed Central

    Kaneuchi, Choji; Seki, Masako; Komagata, Kazuo

    1988-01-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, α-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli. PMID:16347795

  8. Production of succinic Acid from citric Acid and related acids by lactobacillus strains.

    PubMed

    Kaneuchi, C; Seki, M; Komagata, K

    1988-12-01

    A number of Lactobacillus strains produced succinic acid in de Man-Rogosa-Sharpe broth to various extents. Among 86 fresh isolates from fermented cane molasses in Thailand, 30 strains (35%) produced succinic acid; namely, 23 of 39 Lactobacillus reuteri strains, 6 of 18 L. cellobiosus strains, and 1 of 6 unidentified strains. All of 10 L. casei subsp. casei strains, 5 L. casei subsp. rhamnosus strains, 6 L. mali strains, and 2 L. buchneri strains did not produce succinic acid. Among 58 known strains including 48 type strains of different Lactobacillus species, the strains of L. acidophilus, L. crispatus, L. jensenii, and L. parvus produced succinic acid to the same extent as the most active fresh isolates, and those of L. alimentarius, L. collinoides, L. farciminis, L. fructivorans (1 of 2 strains tested), L. malefermentans, and L. reuteri were also positive, to lesser extents. Diammonium citrate in de Man-Rogosa-Sharpe broth was determined as a precursor of the succinic acid produced. Production rates were about 70% on a molar basis with two fresh strains tested. Succinic acid was also produced from fumaric and malic acids but not from dl-isocitric, alpha-ketoglutaric, and pyruvic acids. The present study is considered to provide the first evidence on the production of succinic acid, an important flavoring substance in dairy products and fermented beverages, from citrate by lactobacilli.

  9. Hemoglobin A1c Point-of-Care Assays; a New World with a Lot of Consequences!

    PubMed Central

    Lenters-Westra, Erna; Slingerland, Robbert J.

    2009-01-01

    Background Point-of-care instruments for the measurement of hemoglobin A1c (HbA1c) may improve the glycemic control of people with diabetes by providing a rapid result if the performance of the instruments used is acceptable. A 0.5% HbA1c difference between successive results is considered a clinically relevant change. With this in mind, the In2it from Bio-Rad and the DCA Vantage from Siemens were evaluated according to Clinical and Laboratory Standards Institute (CLSI) protocols. Methods The CLSI protocols EP-5 and EP-9 were applied to investigate precision, accuracy, and bias. The bias was compared with three certified secondary reference measurement procedures. Differences between capillary and venous blood were investigated by an end-user group consisting of nurse practitioners at a diabetes care center. Results At HbA1c levels of 5.1 and 11.2%, total coefficients of variation (CV) for the In2it were 4.9 and 3.3%, respectively, and for the DCA Vantage were 1.7 to 1.8% and 3.7 to 5.5% depending on the lot number of the cartridges. Method comparisons showed significant lot number-dependent results for the In2it and the DCA Vantage compared with the three reference methods. No overall difference was observed between capillary and venous blood for both methods. Conclusion Performance results of the In2it and the DCA Vantage showed variable and lot number-dependent results. To maintain the interlaboratory CV of 5% for HbA1c, the Clinical Laboratory Improvement Amendments rules for waived point-of-care instruments should be revised. An obligation for participating in external quality schemes and taking adequate action should be considered for POC instruments that perform poorly. PMID:20144277

  10. Comparison of Established and Emerging Biodosimetry Assays

    PubMed Central

    Rothkamm, K.; Beinke, C.; Romm, H.; Badie, C.; Balagurunathan, Y.; Barnard, S.; Bernard, N.; Boulay-Greene, H.; Brengues, M.; De Amicis, A.; De Sanctis, S.; Greither, R.; Herodin, F.; Jones, A.; Kabacik, S.; Knie, T.; Kulka, U.; Lista, F.; Martigne, P.; Missel, A.; Moquet, J.; Oestreicher, U.; Peinnequin, A.; Poyot, T.; Roessler, U.; Scherthan, H.; Terbrueggen, B.; Thierens, H.; Valente, M.; Vral, A.; Zenhausern, F.; Meineke, V.; Braselmann, H.; Abend, M.

    2014-01-01

    Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3–0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5–4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools. PMID:23862692

  11. Role of IncP-1β Plasmids pWDL7::rfp and pNB8c in Chloroaniline Catabolism as Determined by Genomic and Functional Analyses

    PubMed Central

    Król, J. E.; Penrod, J. T.; McCaslin, H.; Rogers, L. M.; Yano, H.; Stancik, A. D.; Dejonghe, W.; Brown, C. J.; Parales, R. E.; Wuertz, S.

    2012-01-01

    Broad-host-range catabolic plasmids play an important role in bacterial degradation of man-made compounds. To gain insight into the role of these plasmids in chloroaniline degradation, we determined the first complete nucleotide sequences of an IncP-1 chloroaniline degradation plasmid, pWDL7::rfp and its close relative pNB8c, as well as the expression pattern, function, and bioaugmentation potential of the putative 3-chloroaniline (3-CA) oxidation genes. Based on phylogenetic analysis of backbone proteins, both plasmids are members of a distinct clade within the IncP-1β subgroup. The plasmids are almost identical, but whereas pWDL7::rfp carries a duplicate inverted catabolic transposon, Tn6063, containing a putative 3-CA oxidation gene cluster, dcaQTA1A2BR, pNB8c contains only a single copy of the transposon. No genes for an aromatic ring cleavage pathway were detected on either plasmid, suggesting that only the upper 3-CA degradation pathway was present. The dcaA1A2B gene products expressed from a high-copy-number vector were shown to convert 3-CA to 4-chlorocatechol in Escherichia coli. Slight differences in the dca promoter region between the plasmids and lack of induction of transcription of the pNB8c dca genes by 3-CA may explain previous findings that pNB8C does not confer 3-CA transformation. Bioaugmentation of activated sludge with pWDL7::rfp accelerated removal of 3-CA, but only in the presence of an additional carbon source. Successful bioaugmentation requires complementation of the upper pathway genes with chlorocatechol cleavage genes in indigenous bacteria. The genome sequences of these plasmids thus help explain the molecular basis of their catabolic activities. PMID:22101050

  12. The fate of the herbicide propanil in plants of the littoral zone of the Three Gorges Reservoir (TGR), China.

    PubMed

    Chen, Zhongli; Schäffer, Andreas

    2016-10-01

    The anti-seasonal hydrology with 30m water fluctuations in the Three Gorges Reservoir (TGR) of China attracts growing environmental and ecological concerns. We investigated the biotransformation of the herbicide propanil in plants dominating in the littoral zone of the TGR by applying the 14 C-ring-labeled herbicide into non-aseptic hydroponic plant systems (Cynodon dactylon, Nelumbo nucifera and Bidens pilosa), aseptic plants (Lemna minor and Lemna gibba) and cell suspension cultures (C. dactylon and L. minor). (1) Propanil absorbed in plants of the hydroponic systems was (12.46±1.63)% of applied radioactivity (AR) (C. dactylon), (52.36±6.38)% (N. nucifera) and (76.55±6.07)% (B. pilosa), respectively. The 14 C-residues in the plant extractable fractions and the corresponding media were confirmed by radio-Thin Layer Chromatography (TLC), radio-High Performance Liquid Chromatography (HPLC) and Gas Chromatography-Electron Ionization Mass Spectrometry (GC-EIMS) as propanil, 3,4-dichloroaniline (DCA) and N-(3,4-dichlorophenyl)-β-d-glucopyranosylamine (Glu-DCA). (2) About 8% of AR was taken up by both aseptic plants, from which 7.0% of AR was extracted and identified also as propanil, DCA and Glu-DCA. (3) Concerning cell suspension cultures, (39.22±9.39)% of AR was absorbed by C. dactylon after 72hr, whereas the accumulated 14 C-propanil by L. minor cell suspension culture amounted to (65.04±1.72)% after 7days. The identified compounds in cell cultures are consistent with those in the tested plants. Most of the pesticide residues in the intact plants were un-extractable, which are recognized as the end of the detoxification process. We therefore consider these plants as suitable for the phytoremediation of the herbicide propanil in the TGR region. Copyright © 2016. Published by Elsevier B.V.

  13. SU-D-BRB-01: A Predictive Planning Tool for Stereotactic Radiosurgery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Palefsky, S; Roper, J; Elder, E

    Purpose: To demonstrate the feasibility of a predictive planning tool which provides SRS planning guidance based on simple patient anatomical properties: PTV size, PTV shape and distance from critical structures. Methods: Ten framed SRS cases treated at Winship Cancer Institute of Emory University were analyzed to extract data on PTV size, sphericity (shape), and distance from critical structures such as the brainstem and optic chiasm. The cases consisted of five pairs. Each pair consisted of two cases with a similar diagnosis (such as pituitary adenoma or arteriovenous malformation) that were treated with different techniques: DCA, or IMRS. A Naive Bayesmore » Classifier was trained on this data to establish the conditions under which each treatment modality was used. This model was validated by classifying ten other randomly-selected cases into DCA or IMRS classes, calculating the probability of each technique, and comparing results to the treated technique. Results: Of the ten cases used to validate the model, nine had their technique predicted correctly. The three cases treated with IMRS were all identified as such. Their probabilities of being treated with IMRS ranged between 59% and 100%. Six of the seven cases treated with DCA were correctly classified. These probabilities ranged between 51% and 95%. One case treated with DCA was incorrectly predicted to be an IMRS plan. The model’s confidence in this case was 91%. Conclusion: These findings indicate that a predictive planning tool based on simple patient anatomical properties can predict the SRS technique used for treatment. The algorithm operated with 90% accuracy. With further validation on larger patient populations, this tool may be used clinically to guide planners in choosing an appropriate treatment technique. The prediction algorithm could also be adapted to guide selection of treatment parameters such as treatment modality and number of fields for radiotherapy across anatomical sites.« less

  14. Interaction with biomacromolecules and antiproliferative activities of Mn(II), Ni(II), Zn(II) complexes of demethylcantharate and 2,2'-bipyridine

    NASA Astrophysics Data System (ADS)

    Zhang, Fan; Lin, Qiu-Yue; Hu, Wan-Li; Song, Wen-Ji; Shen, Shu-Ting; Gui, Pan

    2013-06-01

    Three new transition metal complexes [Mn2(DCA)2(bipy)2]·5H2O (1), [M2(DCA)2(bipy)2(H2O)]·10H2O(M = Ni(II)(2);Zn(II)(3)), (DCA = demethylcantharate, 7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C8H8O5) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and X-ray diffraction techniques. Each metal ion was six-coordinated in complexes. Complex 1 has a Mn2O2 center. Complexes 2 and 3 have asymmetric binuclear structure. Great amount of intermolecular hydrogen-bonding and π-π* stacking interactions were formed in these complex structures. The DNA-binding properties of complexes were investigated by electronic absorption spectra and viscosity measurements. The DNA binding constants Kb/(L mol-1) were 1.71 × 104 (1), 2.62 × 104 (2) and 1.59 × 104 (3) at 298 K. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) strongly through static quenching. The protein binding constants Ka/(L mol-1) were 7.27 × 104 (1), 4.55 × 104 (2) and 7.87 × 104 L mol-1 (3) and binding site was one. The complexes bind more tightly with DNA and BSA than with ligands. Complexes 1 and 3 had stronger inhibition ratios than Na2(DCA) against human hepatoma cells (SMMC-7721) lines and human gastric cancer cells (MGC80-3) lines in vitro. Complex 3 showed the strongest antiproliferative activity against SMMC-7721 (IC50 = 29.46 ± 2.12 μmol L-1) and MGC80-3 (IC50 = 27.02 ± 2.38 μmol L-1), which shows potential in anti-cancer drug development.

  15. Beneficial effect of pyruvate therapy on Leigh syndrome due to a novel mutation in PDH E1α gene.

    PubMed

    Koga, Yasutoshi; Povalko, Nataliya; Katayama, Koujyu; Kakimoto, Noriko; Matsuishi, Toyojiro; Naito, Etsuo; Tanaka, Masashi

    2012-02-01

    Leigh syndrome (LS) is a progressive untreatable degenerating mitochondrial disorder caused by either mitochondrial or nuclear DNA mutations. A patient was a second child of unconsanguineous parents. On the third day of birth, he was transferred to neonatal intensive care units because of severe lactic acidosis. Since he was showing continuous lactic acidosis, the oral supplementation of dichloroacetate (DCA) was introduced on 31st day of birth at initial dose of 50 mg/kg, followed by maintenance dose of 25 mg/kg/every 12 h. The patient was diagnosed with LS due to a point mutation of an A-C at nucleotide 599 in exon 6 in the pyruvate dehydrogenase E1α gene, resulting in the substitution of aspartate for threonine at position 200 (N200T). Although the concentrations of lactate and pyruvate in blood were slightly decreased, his clinical conditions were deteriorating progressively. In order to overcome the mitochondrial or cytosolic energy crisis indicated by lactic acidosis as well as clinical symptoms, we terminated the DCA and administered 0.5 g/kg/day TID of sodium pyruvate orally. We analyzed the therapeutic effects of DCA or sodium pyruvate in the patient, and found that pyruvate therapy significantly decreased lactate, pyruvate and alanine levels, showed no adverse effects such as severe neuropathy seen in DCA, and had better clinical response on development and epilepsy. Though the efficacy of pyruvate on LS will be evaluated by randomized double-blind placebo-controlled study design in future, pyruvate therapy is a possible candidate for therapeutic choice for currently incurable mitochondrial disorders such as LS. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. Preparation and characterization Al3+-bentonite Turen Malang for esterification fatty acid (palmitic acid, oleic acid and linoleic acid)

    NASA Astrophysics Data System (ADS)

    Abdulloh, Abdulloh; Aminah, Nanik Siti; Triyono, Mudasir, Trisunaryanti, Wega

    2016-03-01

    Catalyst preparation and characterization of Al3+-bentonite for esterification of palmitic acid, oleic acid and linoleic acid has been done. Al3+-bentonite catalyst was prepared from natural bentonite of Turen Malang through cation exchange reaction using AlCl3 solution. The catalysts obtained were characterized by XRD, XRF, pyridine-FTIR and surface area analyser using the BET method. Catalyst activity test of Al3+-bentonite for esterification reaction was done at 65°C using molar ratio of metanol-fatty acid of 30:1 and 0.25 g of Al3+-bentonite catalyst for the period of ½, 1, 2, 3, 4 and 5 hours. Based on the characterization results, the Al3+-bentonite Turen Malang catalyst has a d-spacing of 15.63 Ǻ, acid sites of Brönsted and Lewis respectively of 230.79 µmol/g and 99.39 µmol/g, surface area of 507.3 m2/g and the average of radius pore of 20.09 Å. GC-MS analysis results of the oil phase after esterification reaction showed the formation of biodiesel (FAME: Fatty acid methyl ester), namely methyl palmitate, methyl oleate and methyl linoleate. The number of conversions resulted in esterification reaction using Al3+-bentonite Turen Malang catalyst was 74.61%, 37.75%, and 20, 93% for the esterification of palmitic acid, oleic acid and linoleic acid respectively.

  17. Preventive effect of chemical peeling on ultraviolet induced skin tumor formation.

    PubMed

    Abdel-Daim, Mohamed; Funasaka, Yoko; Kamo, Tsuneyoshi; Ooe, Masahiko; Matsunaka, Hiroshi; Yanagita, Emmy; Itoh, Tomoo; Nishigori, Chikako

    2010-10-01

    Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Efficacy of Lactic Acid, Lactic Acid-Acetic Acid Blends, and Peracetic Acid To Reduce Salmonella on Chicken Parts under Simulated Commercial Processing Conditions.

    PubMed

    Ramirez-Hernandez, Alejandra; Brashears, Mindy M; Sanchez-Plata, Marcos X

    2018-01-01

    The poultry processing industry has been undergoing a series of changes as it modifies processing practices to comply with new performance standards for chicken parts and comminuted poultry products. The regulatory approach encourages the use of intervention strategies to prevent and control foodborne pathogens in poultry products and thus improve food safety and protect human health. The present studies were conducted to evaluate the efficacy of antimicrobial interventions for reducing Salmonella on inoculated chicken parts under simulated commercial processing conditions. Chicken pieces were inoculated by immersion in a five-strain Salmonella cocktail at 6 log CFU/mL and then treated with organic acids and oxidizing agents on a commercial rinsing conveyor belt. The efficacy of spraying with six different treatments (sterile water, lactic acid, acetic acid, buffered lactic acid, acetic acid in combination with lactic acid, and peracetic acid) at two concentrations was evaluated on skin-on and skin-off chicken thighs at three application temperatures. Skinless chicken breasts were used to evaluate the antimicrobial efficacy of lactic acid and peracetic acid. The color stability of treated and untreated chicken parts was assessed after the acid interventions. The lactic acid and buffered lactic acid treatments produced the greatest reductions in Salmonella counts. Significant differences between the control and water treatments were identified for 5.11% lactic acid and 5.85% buffered lactic acid in both skin-on and skin-off chicken thighs. No significant effect of treatment temperature for skin-on chicken thighs was found. Lactic acid and peracetic acid were effective agents for eluting Salmonella cells attached to chicken breasts.

  19. Preparation of the 3-monosulphates of cholic acid, chenodeoxycholic acid and deoxycholic acid.

    PubMed Central

    Haslewood, E S; Haslewood, G A

    1976-01-01

    1. The 3-sulphates of cholic, chenodeoxycholic and deoxycholic acids were prepared as crystalline disodium salts. 2. The method described shows that it is possible to prepare specific sulphate esters of polyhydroxy bile acids and to remove protecting acyl groups without removing the sulphate. 3. A study of bile acid sulphate solvolysis showed that none of the usual methods give the original bile acid in major yield in a single step. 4. An understanding of the preparation, properties and methods of solvolysis of bile acid sulphates is basic for investigations of cholestasis and liver disease. PMID:938488

  20. Effect of acetic acid on citric acid fermentation in an integrated citric acid-methane fermentation process.

    PubMed

    Xu, Jian; Chen, Yang-Qiu; Zhang, Hong-Jian; Tang, Lei; Wang, Ke; Zhang, Jian-Hua; Chen, Xu-Sheng; Mao, Zhong-Gui

    2014-09-01

    An integrated citric acid-methane fermentation process was proposed to solve the problem of extraction wastewater in citric acid fermentation process. Extraction wastewater was treated by anaerobic digestion and then recycled for the next batch of citric acid fermentation to eliminate wastewater discharge and reduce water resource consumption. Acetic acid as an intermediate product of methane fermentation was present in anaerobic digestion effluent. In this study, the effect of acetic acid on citric acid fermentation was investigated and results showed that lower concentration of acetic acid could promote Aspergillus niger growth and citric acid production. 5-Cyano-2,3-ditolyl tetrazolium chloride (CTC) staining was used to quantify the activity of A. niger cells, and the results suggested that when acetic acid concentration was above 8 mM at initial pH 4.5, the morphology of A. niger became uneven and the part of the cells' activity was significantly reduced, thereby resulting in deceasing of citric acid production. Effects of acetic acid on citric acid fermentation, as influenced by initial pH and cell number in inocula, were also examined. The result indicated that inhibition by acetic acid increased as initial pH declined and was rarely influenced by cell number in inocula.