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Sample records for acid protects human

  1. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

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    Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  2. Potent protection of gallic acid against DNA oxidation: Results of human and animal experiments

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    Ferk, Franziska; Chakraborty, Asima [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Jaeger, Walter [Department of Clinical Pharmacy and Diagnostic, University of Vienna, Vienna (Austria); Kundi, Michael [Institute of Environmental Health, Center for Public Health, Medical University of Vienna, A-1090 Vienna (Austria); Bichler, Julia; Misik, Miroslav [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Wagner, Karl-Heinz [Department of Nutritional Sciences, University of Vienna, 1090 Vienna (Austria); Grasl-Kraupp, Bettina; Sagmeister, Sandra [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Haidinger, Gerald [Department of Epidemiology, Center for Public Health, Medical University of Vienna, A-1090 Vienna (Austria); Hoelzl, Christine; Nersesyan, Armen [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Dusinska, Maria [Health Effect Laboratory, Center for Ecological Economics, Norwegian Institute for Air Research, NO-2027 Kjeller (Norway); Simic, Tatjana [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria); Knasmueller, Siegfried, E-mail: siegfried.knasmueller@meduniwien.ac.at [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, A-1090 Vienna (Austria)

    2011-10-01

    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a constituent of plant derived foods, beverages and herbal remedies. We investigated its DNA protective properties in a placebo controlled human intervention trial in single cell gel electrophoresis experiments. Supplementation of drinking water with GA (12.8 mg/person/d) for three days led to a significant reduction of DNA migration attributable to oxidised pyrimidines (endonuclease III sensitive sites) and oxidised purines (formamidopyrimidine glycosylase sensitive sites) in lymphocytes of healthy individuals by 75% and 64% respectively. Also DNA damage caused by treatment of the cells with reactive oxygen species (ROS) was reduced after GA consumption (by 41%). These effects were paralleled by an increase of the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and glutathion-S-transferase-{pi}) and a decrease of intracellular ROS concentrations in lymphocytes, while no alterations of the total antioxidant capacity (TAC), of malondialdehyde levels in serum and of the urinary excretion of isoprostanes were found. Experiments with rats showed that GA reduces oxidatively damaged DNA in lymphocytes, liver, colon and lungs and protects these organs against {gamma}-irradiation-induced strand breaks and formation of oxidatively damaged DNA-bases. Furthermore, the number of radiation-induced preneoplastic hepatic foci was decreased by 43% after oral administration of the phenolic. Since we did not find alterations of the TAC in plasma and lipid peroxidation of cell membranes but intracellular effects it is likely that the antioxidant properties of GA seen in vivo are not due to direct scavenging of radicals but rather to indirect mechanisms (e.g. protection against ROS via activation of transcription factors). As the amount of GA used in the intervention trial is similar to the daily intake in Middle Europe (18 mg/person/day), our findings indicate that it may contribute to prevention of

  3. Pretreatment of Ferulic Acid Protects Human Dermal Fibroblasts against Ultraviolet A Irradiation

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    Hahn, Hyung Jin; Kim, Ki Bbeum; Bae, Seunghee; Choi, Byung Gon; An, Sungkwan

    2016-01-01

    Background Approximately 90%~99% of ultraviolet A (UVA) ray reaches the Earth's surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging. Objective Researchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages. Methods HDF proliferation was analyzed using the water-soluble tetrazolium salt assay. Cell cycle distribution and intracellular ROS levels were assessed by flow cytometric analysis. Senescence was evaluated using a senescence-associated β-galactosidase assay, while Gadd45α promoter activity was analyzed through a luciferase assay. The expression levels of superoxide dismutase 1 (SOD1), catalase (CAT), xeroderma pigmentosum complementation group A and C, matrix metalloproteinase 1 and 3, as well as p21 and p16 were measured using quantitative real-time polymerase chain reaction. Results Inhibition of proliferation and cell cycle arrest were detected in cells that were irradiated with UVA only. Pretreatment with ferulic acid significantly increased the proliferation and cell cycle progression in HDFs. Moreover, ferulic acid pretreatment produced antioxidant effects such as reduced DCF intensity, and affected SOD1 and CAT mRNA expression. These effects were also demonstrated in the analysis of cell senescence, promoter activity, expression of senescent markers, and DNA repair. Conclusion These results demonstrate that ferulic acid exerts protective effects on UVA-induced cell damages via anti-oxidant and stress-inducible cellular mechanisms in HDFs. PMID:27904274

  4. Protection of Salvianolic Acid B for Human Endothelial Cells Against Hydrogen Peroxide-Induced Oxidative Damage

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jungang; ZHAO Guangrong; LIU Jinling; JI Xiangwu

    2009-01-01

    Salvianolic acid B(Sal B) is an active component of traditional Chinese medicine Salvia miltiorrhiza and is used to treat vascular diseases. To better understand its mechanism, the antioxidant capacities of Sal B was evaluated with human endothelial cells under oxidative stress. Human endothelial cells were pretreated with Sal B for 12 h followed by hydrogen peroxide for another 12 h. Production of reactive oxygen species (ROS), activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and concentration of glu-tathione were measured: Protective effect of Sal B on the endothelial cells from hydrogen peroxide-induced damage ' was observed, and ROS production in the cells was found significantly inhibited. Sal B remarkably enhanced the activities of antioxidant enzymes SOD, CAT and GPX. Furthermore, Sal B up-regulated the intracellular glutathione concentration. The results indicate that Sal B protected endothelial cells from oxidative stress by improving the redox status of the cells through enhancing the antioxidant enzyme activities and increasing the reductive glutathione concentration after the oxidative challenge.

  5. Lactic acid bacteria protect human intestinal epithelial cells from Staphylococcus aureus and Pseudomonas aeruginosa infections.

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    Affhan, S; Dachang, W; Xin, Y; Shang, D

    2015-12-16

    Staphylococcus aureus and Pseudomonas aeruginosa are opportunistic pathogens that cause nosocomial and food-borne infections. They promote intestinal diseases. Gastrointestinal colonization by S. aureus and P. aeruginosa has rarely been researched. These organisms spread to extra gastrointestinal niches, resulting in increasingly progressive infections. Lactic acid bacteria are Gram-positive bacteria that produce lactic acid as the major end-product of carbohydrate fermentation. These bacteria inhibit pathogen colonization and modulate the host immune response. This study aimed to investigate the effects of Lactobacillus acidophilus and Lactobacillus rhamnosus on enteric infections caused by the paradigmatic human pathogens S. aureus ATCC25923 and P. aeruginosa ATCC27853. The effect of whole cells and neutralized cell-free supernatant (CFS) of the lactobacilli on LoVo human carcinoma enterocyte (ATCC CCL-229) infection was analyzed by co-exposure, pre-exposure, and post-exposure studies. Simultaneous application of whole cells and CFS of the lactobacilli significantly eradicated enterocyte infection (P cells and CFS were added after or prior to the infection (P > 0.05). This result could be attributed to interference by extracellular polymeric substances and cell surface hydrophobicity, which resulted in the development of a pathogen that did not form colonies. Furthermore, results of the plate count and LIVE/ DEAD BacLight bacterial viability staining attributed this inhibition to a non-bacteriocin-like substance, which acted independently of organic acid and H2O2 production. Based on these results, the cell-free supernatant derived from lactobacilli was concluded to restrain the development of S. aureus and P. aeruginosa enteric infections.

  6. Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol

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    Donejko, Magdalena; Rysiak, Edyta; Galicka, Elżbieta; Terlikowski, Robert; Głażewska, Edyta Katarzyna; Przylipiak, Andrzej

    2017-01-01

    Aim The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. Materials and methods Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Results Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. Conclusion This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol. PMID:28293103

  7. Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol

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    Donejko M

    2017-03-01

    Full Text Available Magdalena Donejko,1 Edyta Rysiak,2 Elżbieta Galicka,1 Robert Terlikowski,3 Edyta Katarzyna Głażewska,1 Andrzej Przylipiak1 1Department of Esthetic Medicine, 2Department of Medicinal Chemistry, Faculty of Pharmacy, 3Department of Health Restoration, Medical University of Białystok, Białystok, Poland Aim: The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK, and the influence of HA on those processes. Materials and methods: Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Results: Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. Conclusion: This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol. Keywords: apoptosis, skin fibroblast, focal adhesion kinase, hyaluronic acid, ethanol

  8. Mechanism of Human Influenza Virus RNA Persistence and Virion Survival in Feces: Mucus Protects Virions From Acid and Digestive Juices.

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    Hirose, Ryohei; Nakaya, Takaaki; Naito, Yuji; Daidoji, Tomo; Watanabe, Yohei; Yasuda, Hiroaki; Konishi, Hideyuki; Itoh, Yoshito

    2017-07-01

    Although viral RNA or infectious virions have been detected in the feces of individuals infected with human influenza A and B viruses (IAV/IBV), the mechanism of viral survival in the gastrointestinal tract remains unclear. We developed a model that attempts to recapitulate the conditions encountered by a swallowed virus. While IAV/IBV are vulnerable to simulated digestive juices (gastric acid and bile/pancreatic juice), highly viscous mucus protects viral RNA and virions, allowing the virus to retain its infectivity. Our results suggest that virions and RNA present in swallowed mucus are not inactivated or degraded by the gastrointestinal environment, allowing their detection in feces. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  9. Radio-protective effect of cinnamic acid, a phenolic phytochemical, on genomic instability induced by X-rays in human blood lymphocytes in vitro.

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    Cinkilic, Nilufer; Tüzün, Ece; Çetintaş, Sibel Kahraman; Vatan, Özgür; Yılmaz, Dilek; Çavaş, Tolga; Tunç, Sema; Özkan, Lütfi; Bilaloğlu, Rahmi

    2014-08-01

    The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.

  10. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

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    Didik Priyandoko

    Full Text Available The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera leaf extract on methoxyacetic acid (MAA induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

  11. Oleanolic Acid, a Compound Present in Grapes and Olives, Protects against Genotoxicity in Human Mammary Epithelial Cells

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    Cristina Sánchez-Quesada

    2015-07-01

    Full Text Available Oleanolic acid (AO and maslinic acid (MA are constituents of the skins of different fruits, including olives and white or red grapes. Although both compounds are known to have beneficial properties against different types of cancers, thus far, there are no studies about their chemopreventive effects in human breast cancer. Thus, we sought to elucidate whether both compounds possess chemopreventive activity. Two cell lines of human breast cancer cells and one noncancerous human mammary epithelial cells were used to determine the effects of OA and MA. The results showed that OA inhibited the proliferation and increased the oxidative stress of highly invasive cells. Additionally, OA decreased oxidative stress and oxidative damage to the DNA in human mammary epithelial cells. These results suggest that OA could act as a chemopreventive agent in human breast cancer and could inhibit the proliferation of highly invasive breast cancer cells.

  12. Protective effects of non-mitogenic human acidic fibroblast growth factor on hydrogen peroxide-induced damage to cardiomyocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    Zhuo-Feng Lin; Xiao-Kun Li; Yuan Lin; Fan Wu; Li-Min Liang; Xiao-Bing Fu

    2005-01-01

    AIM: To study the protective effect of non-mitogenic human acidic fibroblast growth factor (FGF) on cardiac oxidative injury in vivo.METHODS: Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco's minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37 ℃, as well as assessed by immunocytochemical assay. We constructed the cardiomyocyte injury model by exposure to a certain concentration of H2O2.Cellular viability, superoxide dismutase (SOD) activity,leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF.RESULTS: Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed b,y an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to the toxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate.CONCLUSION: Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.

  13. Protection of free radical-induced cytotoxicity by 2-O-α-D-glucopyranosyl-L-ascorbic acid in human dermal fibroblasts.

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    Hanada, Yukako; Iomori, Atsuko; Ishii, Rie; Gohda, Eiichi; Tai, Akihiro

    2014-01-01

    The stable ascorbic acid (AA) derivative, 2-O-α-D-glucopyranosyl-L-ascorbic acid (AA-2G), exhibits vitamin C activity after enzymatic hydrolysis to AA. The biological activity of AA-2G per se has not been studied in detail, although AA-2G has been noted as a stable source for AA supply. The protective effect of AA-2G against the oxidative cell death of human dermal fibroblasts induced by incubating with 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) for 24 h was investigated in this study. AA-2G showed a significant protective effect against the oxidative stress in a concentration-dependent manner. AA-2G did not exert a protective effect during the initial 12 h of incubation, but had a significant protective effect in the later part of the incubation period. Experiments using a α-glucosidase inhibitor and comparative experiments using a stereoisomer of AA-2G confirmed that AA-2G had a protective effect against AAPH-induced cytotoxicity without being converted to AA. Our results provide an insight into the efficacy of AA-2G as a biologically interesting antioxidant and suggest the practical use of AA-2G even before being converted into AA as a beneficial antioxidant.

  14. Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation.

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    Cordes, N; Plasswilm, L; Bamberg, M; Rodemann, H P

    2002-01-01

    Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 microg ml(-1) for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 microg ml(-1) Ukrain for 24h plus 2-8 Gy. Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without affecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical

  15. The role of enamel proteins in protecting mature human enamel against acidic environments: a double layer force spectroscopy study.

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    Lubarsky, Gennady V; D'Sa, Raechelle A; Deb, Sanjukta; Meenan, Brian J; Lemoine, Patrick

    2012-12-01

    Characterisation of the electrostatic properties of dental enamel is important for understanding the interfacial processes that occur on a tooth surface and how these relate to the natural ability of our teeth to withstand chemical attack from the acids in many soft drinks. Whereas, the role of the mineral component of the tooth enamel in providing this resistance to acid erosion has been studied extensively, the influence of proteins that are also present within the structure is not well understood. In this paper, we report for the first time the use of double-layer force spectroscopy to directly measure electrostatic forces on as received and hydrazine-treated (deproteinated) enamel surfaces in solutions with different pH to determine how the enamel proteins influence acid erosion surface potential and surface charge of human dental enamel. The deproteination of the treated samples was confirmed by the loss of the amide bands (~1,300-1,700 cm(-1)) in the FTIR spectrum of the sample. The force characteristics observed were found to agree with the theory of electrical double layer interaction under the assumption of constant potential and allowed the surface charge per unit area to be determined for the two enamel surfaces. The values and, importantly, the sign of these adsorbed surface charges indicates that the protein content of dental enamel contributes significantly to the electrostatic double layer formation near the tooth surface and in doing so can buffer the apatite crystals against acid attack. Moreover, the electrostatic interactions within this layer are a driving factor for the mineral transfer from the tooth surface and the initial salivary pellicle formation.

  16. Comparison of protective effect of ascorbic acid on redox and endocannabinoid systems interactions in in vitro cultured human skin fibroblasts exposed to UV radiation and hydrogen peroxide.

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    Gęgotek, Agnieszka; Bielawska, Katarzyna; Biernacki, Michał; Zaręba, Ilona; Surażyński, Arkadiusz; Skrzydlewska, Elżbieta

    2017-05-01

    The mechanisms of biological activity of commonly used natural compounds are constantly examined. Therefore, the aim of this study was to compare ascorbic acid efficacy in counteracting the consequences of UV and hydrogen peroxide treatment on lipid mediators and their regulative action on antioxidant abilities. Skin fibroblasts exposed to UVA and UVB irradiation, treated with hydrogen peroxide and ascorbic acid. The redox system was estimated through reactive oxygen species (ROS) generation (electron spin resonance spectrometer) and antioxidants level/activity (HPLC/spectrometry) which activity was evaluated by the level of phospholipid metabolites: 4-hydroxynonenal, malondialdehyde, 8-isoprostanes and endocannabinoids (GC/LC-MS) in the human skin fibroblasts. Protein and DNA oxidative modifications were also determined (LC). The expression of nuclear factor erythroid 2-related factor 2 (Nrf2), its activators and inhibitors as well as pro/anti-apoptotic proteins and endocannabinoid receptors was examined (Western blot) and collagen metabolism was evaluated by collagen biosynthesis and prolidase activity (spectrometry). UVA and UVB irradiation and hydrogen peroxide treatment enhanced activity of xanthine and NADPH oxidases resulting in ROS generation as well as diminution of antioxidant phospholipid protection (glutathione peroxidase-glutathione-vitamin E), what led to increased lipid peroxidation and decreased endocannabinoids level. Dysregulation of cannabinoid receptors expression and environment of transcription factor Nrf2 caused apoptosis induction. Ascorbic acid partially prevented ROS generation, antioxidant capacity diminution and endocannabinoid systems disturbances but only slightly protected macromolecules such as phospholipid, protein and DNA against oxidative modifications. However, ascorbic acid significantly prevented decrease in collagen type I biosynthesis. Ascorbic acid in similar degree prevents UV (UVA and UVB) and hydrogen peroxide

  17. Characterization of protective human CD4CD25 FOXP3 regulatory T cells generated with IL-2, TGF-β and retinoic acid.

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    Ling Lu

    Full Text Available BACKGROUND: Protective CD4+CD25+ regulatory T cells bearing the Forkhead Foxp3 transcription factor can now be divided into three subsets: Endogenous thymus-derived cells, those induced in the periphery, and another subset induced ex-vivo with pharmacological amounts of IL-2 and TGF-β. Unfortunately, endogenous CD4+CD25+ regulatory T cells are unstable and can be converted to effector cells by pro-inflammatory cytokines. Although protective Foxp3+CD4+CD25+ cells resistant to proinflammatory cytokines have been generated in mice, in humans this result has been elusive. Our objective, therefore, was to induce human naïve CD4+ cells to become stable, functional CD25+ Foxp3+ regulatory cells that were also resistant to the inhibitory effects of proinflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: The addition of the vitamin A metabolite, all-trans retinoic acid (atRA to human naïve CD4+ cells suboptimally activated with IL-2 and TGF-β enhanced and stabilized FOXP3 expression, and accelerated their maturation to protective regulatory T cells. AtRA, by itself, accelerated conversion of naïve to mature cells but did not induce FOXP3 or suppressive activity. The combination of atRA and TGF-β enabled CD4+CD45RA+ cells to express a phenotype and trafficking receptors similar to natural Tregs. AtRA/TGF-β-induced CD4+ regs were anergic and low producers of IL-2. They had potent in vitro suppressive activity and protected immunodeficient mice from a human-anti-mouse GVHD as well as expanded endogenous Tregs. However, treatment of endogenous Tregs with IL-1β and IL-6 decreased FOXP3 expression and diminished their protective effects in vivo while atRA-induced iTregs were resistant to these inhibitory effects. CONCLUSIONS/SIGNIFICANCE: We have developed a methodology that induces human CD4(+ cells to rapidly become stable, fully functional suppressor cells that are also resistant to proinflammatory cytokines. This methodology offers a practical

  18. The protective effect of ursodeoxycholic acid in an in vitro model of the human fetal heart occurs via targeting cardiac fibroblasts.

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    Schultz, Francisca; Hasan, Alveera; Alvarez-Laviada, Anita; Miragoli, Michele; Bhogal, Navneet; Wells, Sarah; Poulet, Claire; Chambers, Jenny; Williamson, Catherine; Gorelik, Julia

    2016-01-01

    Bile acids are elevated in the blood of women with intrahepatic cholestasis of pregnancy (ICP) and this may lead to fetal arrhythmia, fetal hypoxia and potentially fetal death in utero. The bile acid taurocholic acid (TC) causes abnormal calcium dynamics and contraction in neonatal rat cardiomyocytes. Ursodeoxycholic acid (UDCA), a drug clinically used to treat ICP, prevents adverse effects of TC. During development, the fetus is in a state of relative hypoxia. Although this is essential for the development of the heart and vasculature, resident fibroblasts can transiently differentiate into myofibroblasts and form gap junctions with cardiomyocytes in vitro, resulting in cardiomyocyte depolarization. We expanded on previously published work using an in vitro hypoxia model to investigate the differentiation of human fetal fibroblasts into myofibroblasts. Recent evidence shows that potassium channels are involved in maintaining the membrane potential of ventricular fibroblasts and that ATP-dependent potassium (KATP) channel subunits are expressed in cultured fibroblasts. KATP channels are a valuable target as they are thought to have a cardioprotective role during ischaemic and hypoxic conditions. We investigated whether UDCA could modulate fibroblast membrane potential. We established the isolation and culture of human fetal cardiomyocytes and fibroblasts to investigate the effect of hypoxia, TC and UDCA on human fetal cardiac cells. UDCA hyperpolarized myofibroblasts and prevented TC-induced depolarisation, possibly through the activation of KATP channels that are expressed in cultured fibroblasts. Also, similar to the rat model, UDCA can counteract TC-induced calcium abnormalities in human fetal cultures of cardiomyocytes and myofibroblasts. Under normoxic conditions, we found a higher number of myofibroblasts in cultures derived from human fetal hearts compared to cells isolated from neonatal rat hearts, indicating a possible increased number of myofibroblasts

  19. Protecting human subjects in research.

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    Orticio, Lily P

    2009-01-01

    The quest for advancing scientific knowledge through human experimentations using vulnerable groups is traced back to ancient history, when Herophilus performed vivisections on prisoners. The violation of the rights of human subjects through the 20th century led to the formulation of the Nuremberg Code in 1947 and the Declaration of Helsinki in 1964. In the United States, the most infamous was the Tuskegee public health study that resulted in the enactment of the National Research Act that authorized the creation of the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research in 1974. In spite of existing federal regulations, the system of protecting human subjects is still flawed. Transparency of conflict ofinterest, clarity, and strict adherence to institutional guidelines are critical in safeguarding the rights and safety of human subjects and the integrity of research. Education on ethics and emerging complex ethical issues, global awareness, and governmental cooperation and sanctions are important steps in addressing the inadequacies in protecting the most vulnerable populations in experimentations worldwide. Investigators must always remember that the primary safeguards of protecting human life rest in their hands.

  20. Protective Effects of Ferulic Acid on High Glucose-Induced Protein Glycation, Lipid Peroxidation, and Membrane Ion Pump Activity in Human Erythrocytes.

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    Weerachat Sompong

    Full Text Available Ferulic acid (FA is the ubiquitous phytochemical phenolic derivative of cinnamic acid. Experimental studies in diabetic models demonstrate that FA possesses multiple mechanisms of action associated with anti-hyperglycemic activity. The mechanism by which FA prevents diabetes-associated vascular damages remains unknown. The aim of study was to investigate the protective effects of FA on protein glycation, lipid peroxidation, membrane ion pump activity, and phosphatidylserine exposure in high glucose-exposed human erythrocytes. Our results demonstrated that FA (10-100 μM significantly reduced the levels of glycated hemoglobin (HbA1c whereas 0.1-100 μM concentrations inhibited lipid peroxidation in erythrocytes exposed to 45 mM glucose. This was associated with increased glucose consumption. High glucose treatment also caused a significant reduction in Na+/K+-ATPase activity in the erythrocyte plasma membrane which could be reversed by FA. Furthermore, we found that FA (0.1-100 μM prevented high glucose-induced phosphatidylserine exposure. These findings provide insights into a novel mechanism of FA for the prevention of vascular dysfunction associated with diabetes.

  1. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    OpenAIRE

    1983-01-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu ga...

  2. Evaluation of ascorbic acid in protecting labile folic acid derivatives.

    Science.gov (United States)

    Wilson, S D; Horne, D W

    1983-11-01

    The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives.

  3. China's Judicial Protection of Human Rights

    Institute of Scientific and Technical Information of China (English)

    SHEN LIANG

    2007-01-01

    @@ China has devoted great efforts to improving judicial protection of human rights in the past 30 years.It has ratified the International Covenant on Economic,Social and Cultural Rights,signed but yet to ratify the International Covenant on Civil and Political Rights and become a state party to the Convention against Torture and Other Cruel,Inhuman or Degrading Treatment or Punishment.In March 2004,the 10th National People's Congress adopted at its second plenary session the amendments to the Constitution,writing "the state respects and protects human rights" into the Constitution,declaring that China will use legal means to protect and safeguard human rights.

  4. Radical Cations and Acid Protection during Radiolysis

    Energy Technology Data Exchange (ETDEWEB)

    Bruce J. Mincher; Christopher A. Zarzana; Stephen P. Mezyk

    2016-09-01

    Ligand molecules for used nuclear fuel separation schemes are exposed to high radiation fields and high concentrations of acid. Thus, an understanding of the complex interactions between extraction ligands, diluent, and acid is critical to understanding the performance of a separation process. The diglycolamides are ligands with important structural similarities to CMPO; however, previous work has shown that their radiolytic degradation has important mechanistic differences from CMPO. The DGAs do not enjoy radioprotection by HNO3 and the kinetics of DGA radiolytic degradation are different. CMPO degrades with pseudo-zero-order kinetics in linear fashion with absorbed dose while the DGAs degrade in pseudo-first-order, exponential fashion. This suggests that the DGAs degrade by simple reaction with some product of direct diluent radiolysis, while CMPO degradation is probably multi-step, with a slow step that is not dependent on the CMPO concentration, and mitigated by HNO3. It is thus believed that radio-protection and the zero-order radiolytic degradation kinetics are related, and that these phenomena are a function of either the formation of strong acid complexes with CMPO and/or to the presence of the CMPO phenyl ring. Experiments to test both these hypotheses have been designed and partially conducted. This report summarizes findings related to these phenomena for FY16, in satisfaction of milestone M3FT-16IN030104053. It also reports continued kinetic measurements for the reactions of the dodecane radical cation with solvent extraction ligands.

  5. Human subjects protection in the African context

    Directory of Open Access Journals (Sweden)

    Embry Howell

    2016-06-01

    Full Text Available Research and evaluation are growing in Africa. All evaluators have an ethical responsibility to protect their research subjects from harm that could occur if sensitive data are revealed. In this article, we use a literature and document review to provide an overview of the protection of human subjects internationally and in Africa; we then use interviews with evaluators working in Africa to place human subjects protection principles and practice in an African context. We conclude that human subjects protection must be supported by improved guidelines tailored to the African context and local conditions; improved infrastructure for implementing and enforcing the guidelines; and increased training in awareness of human subjects principles and approaches. These efforts could stimulate increased research and evaluation and more confidence in results in the communities where research is conducted.

  6. Ectoine as a promising protective agent in humans and animals.

    Science.gov (United States)

    Bownik, Adam; Stępniewska, Zofia

    2016-12-01

    Ectoine is a compatible water molecule-binding solute (osmoprotectant) produced by several bacterial species in response to osmotic stress and unfavourable environmental conditions. This amino acid derivative can accumulate inside cells at high concentrations without interfering with natural processes and can protect the cell against radiation or osmotic stress. This brief review presents the current state of knowledge about the effects of ectoine on animals and focuses on its practical use for enzyme stabilisation, human skin protection, anti-inflammatory treatment, inhibitory effects in neurodegenerative diseases, and other therapeutic potential in human or veterinary medicine.

  7. How China's Procuratorial Organs Protect Human Rights

    Institute of Scientific and Technical Information of China (English)

    JING DALI

    2011-01-01

    @@ Question: The Twelfth Five-Year Program, which was approved by the 2011 session of the National People's Congress, calls for better protection of human rights and more work to promote China's human rights cause.Would you tell us about the role played by procuratorial organs in this endeavor?

  8. Alpha-linolenic acid protects against gentamicin induced toxicity

    Directory of Open Access Journals (Sweden)

    Priyadarshini M

    2012-11-01

    Full Text Available Medha Priyadarshini, Mohammad Aatif, Bilqees BanoDepartment of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, IndiaBackground: Recent studies indicate that reactive oxygen species are the major culprits behind the renal damage induced by gentamicin, an aminoglycoside antibiotic used to treat serious and life threatening Gram-negative infections. Experimental evidence suggests a protective role of alpha-linolenic acid supplementation against oxidative stress. The aim of the present study was to investigate the possible beneficial role of alpha-linolenic acid against gentamicin induced renal distress.Methods: Male Wistar rats were divided into three groups of eight rats each, with the first group serving as a control. The other groups were treated intraperitoneally with gentamicin 100 mg/kg body weight per day for 10 days ± alpha-linolenic acid and vitamin E (each given as 250 mg/kg body weight per day. Concentrations of creatinine, urea, cholesterol, inorganic phosphate in serum, malondialdehyde and total sulfhydryl levels, and glutathione-S-transferase, superoxide dismutase, and catalase activity in kidney tissues were determined.Results: Administration of gentamicin to rats induced marked renal failure, characterized by a profound increase in serum creatinine, urea, and cholesterol concentrations, accompanied by significant lowering of renal alkaline phosphatase and acid phosphatase activity, an increase in malondialdehyde, a decline in total sulfhydryl levels, and lowered superoxide dismutase, catalase, and glutathione-S-transferase activity. Cotreatment with alpha-linolenic acid produced amelioration in these biochemical indices of nephrotoxicity in serum as well as in tissue. Further histopathological and human studies are necessary to demonstrate the beneficial effects of alpha-linolenic acid in renal disease.Conclusion: Alpha-linolenic acid may represent a nontoxic and effective intervention strategy in

  9. Oleanolic acid modulates the immune-inflammatory response in mice with experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic implications for the human disease.

    Science.gov (United States)

    Martín, R; Cordova, C; San Román, J A; Gutierrez, B; Cachofeiro, V; Nieto, M L

    2014-07-01

    Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the

  10. Salvianolic Acid B Protects Normal Human Dermal Fibroblasts Against Ultraviolet B Irradiation-Induced Photoaging Through Mitogen-Activated Protein Kinase and Activator Protein-1 Pathways.

    Science.gov (United States)

    Sun, Zhengwang; Park, Sang-Yong; Hwang, Eunson; Zhang, Mengyang; Jin, Fengxie; Zhang, Baochun; Yi, Tae Hoo

    2015-01-01

    Exposure to ultraviolet (UV) light causes increased matrix metalloproteinase (MMP) activity and decreased collagen synthesis, leading to skin photoaging. Salvianolic acid B (SAB), a polyphenol, was extracted and purified from salvia miltiorrhiza. We assessed effects of SAB on UVB-induced photoaging and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts. Our results show that SAB significantly inhibited the UVB-induced expression of metalloproteinases-1 (MMP-1) and interleukin-6 (IL-6) while promoting the production of type I procollagen and transforming growth factor β1 (TGF-β1). Moreover, treatment with SAB in the range of 1-100 μg/mL significantly inhibited UVB-induced extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 phosphorylation, which resulted in decreasing UVB-induced phosphorylation of c-Fos and c-Jun. These results indicate that SAB downregulates UV-induced MMP-1 expression by inhibiting Mitogen-activated protein kinase (MAPK) signaling pathways and activator protein-1 (AP-1) activation. Our results suggest a potential use for SAB in skin photoprotection.

  11. G-CSF protects human brain vascular endothelial cells injury induced by high glucose, free fatty acids and hypoxia through MAPK and Akt signaling.

    Directory of Open Access Journals (Sweden)

    Jingjing Su

    Full Text Available Granulocyte-colony stimulating factor (G-CSF has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM-derived endothelial progenitor cells (EPCs, promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A, cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2 and Akt, and deactivation of c-Jun N terminal kinase (JNK and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK and Akt

  12. G-CSF Protects Human Brain Vascular Endothelial Cells Injury Induced by High Glucose, Free Fatty Acids and Hypoxia through MAPK and Akt Signaling

    Science.gov (United States)

    Tao, Yinghong; Guo, Jingchun; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Yanyan; Tang, Yuping; Dong, Qiang; Hu, Renming

    2015-01-01

    Granulocyte-colony stimulating factor (G-CSF) has been shown to play a neuroprotective role in ischemic stroke by mobilizing bone marrow (BM)-derived endothelial progenitor cells (EPCs), promoting angiogenesis, and inhibiting apoptosis. Impairments in mobilization and function of the BM-derived EPCs have previously been reported in animal and human studies of diabetes where there is both reduction in the levels of the BM-derived EPCs and its ability to promote angiogenesis. This is hypothesized to account for the pathogenesis of diabetic vascular complications such as stroke. Here, we sought to investigate the effects of G-CSF on diabetes-associated cerebral vascular defect. We observed that pretreatment of the cultured human brain vascular endothelial cells (HBVECs) with G-CSF largely prevented cell death induced by the combination stimulus with high glucose, free fatty acids (FFA) and hypoxia by increasing cell viability, decreasing apoptosis and caspase-3 activity. Cell ultrastructure measured by transmission electron microscope (TEM) revealed that G-CSF treatment nicely reduced combination stimulus-induced cell apoptosis. The results from fluorescent probe Fluo-3/AM showed that G-CSF greatly suppressed the levels of intracellular calcium ions under combination stimulus. We also found that G-CSF enhanced the expression of cell cycle proteins such as human cell division cycle protein 14A (hCdc14A), cyclinB and cyclinE, inhibited p53 activity, and facilitated cell cycle progression following combination stimulus. In addition, activation of extracellular signal-regulated kinase1/2 (ERK1/2) and Akt, and deactivation of c-Jun N terminal kinase (JNK) and p38 were proved to be required for the pro-survival effects of G-CSF on HBVECs exposed to combination stimulus. Overall, G-CSF is capable of alleviating HBVECs injury triggered by the combination administration with high glucose, FFA and hypoxia involving the mitogen-activated protein kinases (MAPK) and Akt signaling

  13. The corrosion protection of several aluminum alloys by chromic acid and sulfuric acid anodizing

    Science.gov (United States)

    Danford, M. D.

    1994-01-01

    The corrosion protection afforded 7075-T6, 7075-T3, 6061-T6, and 2024-T3 aluminum alloys by chromic acid and sulfuric acid anodizing was examined using electrochemical techniques. From these studies, it is concluded that sulfuric acid anodizing provides superior corrosion protection compared to chromic acid anodizing.

  14. Salvianolic acid B inhibits IL-1β-induced inflammatory cytokine production in human osteoarthritis chondrocytes and has a protective effect in a mouse osteoarthritis model.

    Science.gov (United States)

    Lou, Yiting; Wang, Chenggui; Zheng, Wenhao; Tang, Qian; Chen, Yu; Zhang, Xiaolei; Guo, Xiaoshan; Wang, Jianshun

    2017-02-27

    Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti-inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100μM) for 2h, then incubated with IL-1β (10ng/mL) for 24h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX-2, MMP-13, ADAMTS-5 and NF-κB-related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal-injection of either Sal B (25mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin-O-Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8weeks following the surgery. Sal B inhibited the over-production of NO and PGE2, while the elevated expression of INOS, COX-2, MMP-13 and ADAMTS-5 were reversed by Sal B in IL-1β-induced chondrocytes. In addition, IL-1β significantly induced phosphorylation of NF-κB signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL-1β-induced p65 nuclear translocation. In vivo, the cartilage in Sal B-treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment.

  15. Salicylic acid protects the skin from UV damage.

    Science.gov (United States)

    Mammone, Thomas; Gan, David; Goyarts, Earl; Maes, Daniel

    2006-01-01

    Aspirin(acetyl salicylate) has long been used as an analgesic. Salicylic acid has been reported to have anti-inflammatory properties. These activities include inhibiting activity of cox-1, cox-2, and NF-kb. In addition, salicylic acid has also been shown in some systems to induce Hsp70. We have demonstrated that salicylic acid inhibits UVB-induced sunburn cell formation, as well as increase the removal of UVB induced TT dimer formation in living skin equivalents. Given these protective properties of salicylic acid, we propose the use of salicylic acid as a topical therapeutic to protect the skin from sun damage.

  16. Human subjects research handbook: Protecting human research subjects. Second edition

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-30

    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  17. Chlorogenic acid and caffeic acid are absorbed in humans

    OpenAIRE

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the absorption of chlorogenic acid and caffeic acid in humans are lacking. We determined the absorption of chlorogenic acid and caffeic acid in a cross-over study with 4 female and 3 male healthy ileo...

  18. Human embryonic stem cells and patent protection

    Directory of Open Access Journals (Sweden)

    Radovanović Sanja M.

    2015-01-01

    Full Text Available Given the importance of biotechnological research in modern diagnostics and therapeutics, on the one hand, and stimulative function of a patent, on the other hand, this work deals with the question of the possibility of pa-tent protection of human embryonic stem cells. Taking into account that this is a biotechnological invention, the key question that this paper highlights is the interpretation of the provisions of their patentability. Namely, thanks to the advanced methods of isolation, purification and preparation for implementation, modern patent systems do not exclude a priori living organisms from patent protection. Therefore, the analysis of representative administrative decisions or court rulings sought to define the criteria that would be applied in order to give patent protection to a certain biotechnological invention (stem cells while others do not.

  19. The protection of individuals by means of diplomatic protection: diplomatic protection as a human rights instrument

    OpenAIRE

    2007-01-01

    Individuals whose international (human) rights are violated outside their state of nationality often have very limited means to address such violations. For instance, the foreign nationals detained by the United States in Guantanamo Bay have been unable to improve their situation themselves. Their state of nationality however can protect them through the exercise of diplomatic protection, thereby invoking the international responsibility of the host state for a violation of international law....

  20. The protection of glycyrrhetinic acid (GA) towards acetaminophen ...

    African Journals Online (AJOL)

    ... (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, ... Aims: To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced .... Liu A, Tanaka N, Sun L, Guo B, Kim JH, Krausz.

  1. Novel glycosylated mycosporine-like amino acid, 13-O-(β-galactosyl)-porphyra-334, from the edible cyanobacterium Nostoc sphaericum-protective activity on human keratinocytes from UV light.

    Science.gov (United States)

    Ishihara, Kenji; Watanabe, Ryuichi; Uchida, Hajime; Suzuki, Toshiyuki; Yamashita, Michiaki; Takenaka, Hiroyuki; Nazifi, Ehsan; Matsugo, Seiichi; Yamaba, Minami; Sakamoto, Toshio

    2017-07-01

    A UV-absorbing compound was purified and identified as a novel glycosylated mycosporine-like amino acid (MAA), 13-O-β-galactosyl-porphyra-334 (β-Gal-P334) from the edible cyanobacterium Nostoc sphaericum, known as "ge xian mi" in China and "cushuro" in Peru. Occurrence of the hexosylated derivative of shinorine (hexosyl-shinorine) was also supported by LC-MS/MS analysis. β-Gal-P334 accounted for about 86.5% of total MAA in N. sphaericum, followed by hexosyl-shinorine (13.2%) and porphyra-334 (0.2%). β-Gal-P334 had an absorption maximum at 334nm and molecular absorption coefficient was 46,700 at 334nm. Protection activity of β-Gal-P334 from UVB and UVA+8-methoxypsoralen induced cell damage on human keratinocytes (HaCaT) was assayed in comparison with other MAA (porphyra-334, shinorine, palythine and mycosporine-glycine). The UVB protection activity was highest in mycosporine-glycine, followed by palythine, β-Gal-P334, porphyra-334 and shinorine in order. β-Gal-P334 had highest protection activity from UVA+8-methoxypsoralen induced cell damage followed by porphyra-334, shinorine, mycosporine-glycine and palythine. We also found an antioxidant (radical-scavenging) activity of β-Gal-P334 by colorimetric and ESR methods. From these findings, β-Gal-P334 was suggested to play important roles in stress tolerant mechanisms such as UV and oxidative stress in N. sphaericum as a major MAA. We also consider that the newly identified MAA, β-Gal-P334 has a potential for use as an ingredient of cosmetics and toiletries. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Benzylidene Acetal Protecting Group as Carboxylic Acid Surrogate: Synthesis of Functionalized Uronic Acids and Sugar Amino Acids.

    Science.gov (United States)

    Banerjee, Amit; Senthilkumar, Soundararasu; Baskaran, Sundarababu

    2016-01-18

    Direct oxidation of the 4,6-O-benzylidene acetal protecting group to C-6 carboxylic acid has been developed that provides an easy access to a wide range of biologically important and synthetically challenging uronic acid and sugar amino acid derivatives in good yields. The RuCl3 -NaIO4 -mediated oxidative cleavage method eliminates protection and deprotection steps and the reaction takes place under mild conditions. The dual role of the benzylidene acetal, as a protecting group and source of carboxylic acid, was exploited in the efficient synthesis of six-carbon sialic acid analogues and disaccharides bearing uronic acids, including glycosaminoglycan analogues.

  3. Protected areas as frontiers for human migration.

    Science.gov (United States)

    Zommers, Zinta; MacDonald, David W

    2012-06-01

    Causes of human population growth near protected areas have been much debated. We conducted 821 interviews in 16 villages around Budongo Forest Reserve, Masindi district, Uganda, to explore the causes of human migration to protected areas and to identify differences in forest use between migrant and nonmigrant communities. We asked subjects for information about birthplace, migration, household assets, household activities, and forest use. Interview subjects were categorized as nonmigrants (born in one of the interview villages), socioeconomic migrants (chose to emigrate for economic or social reasons) from within Masindi district (i.e., local migrants) and from outside the Masindi district (i.e., regional migrants), or forced migrants (i.e., refugees or internally displaced individuals who emigrated as a result of conflict, human rights abuses, or natural disaster). Only 198 respondents were born in interview villages, indicating high rates of migration between 1998 and 2008. Migrants were drawn to Budongo Forest because they thought land was available (268 individuals) or had family in the area (161 individuals). A greater number of regional migrants settled in villages near Lake Albert than did forced and local migrants. Migration category was also associated with differences in sources of livelihood. Of forced migrants 40.5% earned wages through labor, whereas 25.5% of local and 14.5% of regional migrants engaged in wage labor. Migrant groups appeared to have different effects on the environment. Of respondents that hunted, 72.7% were regional migrants. Principal component analyses indicated households of regional migrants were more likely to be associated with deforestation. Our results revealed gaps in current models of human population growth around protected areas. By highlighting the importance of social networks and livelihood choices, our results contribute to a more nuanced understanding of causes of migration and of the environmental effects of

  4. Retinoic acid protects human breast cancer cells against etoposide-induced apoptosis by NF-kappaB-dependent but cIAP2-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Gronemeyer Hinrich

    2010-01-01

    Full Text Available Abstract Background Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. These ligands can determine the ultimate fate of target cells by stimulating or repressing gene expression directly, or indirectly through crosstalking with other signal transducers. Results Using different breast cancer cell models, we show here that depending on the cellular context retinoids can signal either towards cell death or cell survival. Indeed, retinoids can induce the expression of pro-apoptotic (i.e. TRAIL, TNF-Related Apoptosis-Inducing Ligand, Apo2L/TNFSF10 and anti-apoptotic (i.e. cIAP2, inhibitor of apoptosis protein-2 genes. Promoter mapping, gel retardation and chromatin immunoprecipitation assays revealed that retinoids induce the expression of this gene mainly through crosstalk with NF-kappaB. Supporting this crosstalk, the activation of NF-kappaB by retinoids in T47D cells antagonizes the apoptosis triggered by the chemotherapeutic drugs etoposide, camptothecin or doxorubicin. Notably apoptosis induced by death ligands (i.e. TRAIL or antiFAS is not antagonized by retinoids. That knockdown of cIAP2 expression by small interfering RNA does not alter the inhibition of etoposide-induced apoptosis by retinoids in T47D cells reveals that stimulation of cIAP2 expression is not the cause of their anti-apoptotic action. However, ectopic overexpression of a NF-kappaB repressor increases apoptosis by retinoids moderately and abrogates almost completely the retinoid-dependent inhibition of etoposide-induced apoptosis. Our data exclude cIAP2 and suggest that retinoids target other regulator(s of the NF-kappaB signaling pathway to induce resistance to etoposide on certain breast cancer cells. Conclusions This study shows an important role for the NF-kappaB pathway in retinoic acid signaling and retinoic acid-mediated resistance to

  5. Protections for Subjects in Human Research with Pesticides

    Science.gov (United States)

    All pesticide research using human subjects must meet our strict protective standards before we would consider using them in evaluating pesticides. EPA's regulation “Protections for Subjects in Human Research” was promulgated in 2006 and amended in 2013.

  6. Communist Party of China and Human Rights Protection for Criminals

    Institute of Scientific and Technical Information of China (English)

    YAN JIA; PEI JUNJIE

    2011-01-01

    Protection of criminals' human rights is an important issue that has received full attention at home and abroad.The Communlst Party of China (CPC) has always attached much importance to the protection of criminals' human rights.Since the founding of New China,the Party and the state have paid full attention to protecting the human rights of criminals.

  7. Radiation protection by ascorbic acid in sodium alginate solutions

    Energy Technology Data Exchange (ETDEWEB)

    Aliste, A.J.; Mastro, N.L. Del [Center of Radiation Technology, IPEN/CNEN/SP, University City, 05508-000 Sao Paulo (Brazil)]. E-mail: ajaliste@ipen.br

    2004-07-01

    Alginates are gelling hydrocolloids extracted from brown seaweed used widely in the nourishing and pharmaceutical industries. As alginic acid gellification retard food entrance in the stomach alginate is an additive used in diets. The objective of this work was to study the protective action of the ascorbic acid in alginate solutions against the action of {sup 60} Co gamma radiation. One % (w/v) solutions of alginate had been used and concentrations of ascorbic acid varied from 0 to 2.5% (w/v). The solutions were irradiated with doses up to 10 kGy. Viscosity/dose relationship and the p H of the solutions at 25 Centigrade were determined. Ascorbic acid behaved as an antioxidant against radiation oxidative shock in this model system of an irradiated viscous solution. Besides its radiation protective role on alginate solutions ascorbic acid promoted a viscosity increase in the range of concentrations employed. (Author)

  8. Enamel protection from acid challenge--benefits of marketed fluoride dentifrices.

    Science.gov (United States)

    Faller, R V; Eversole, S L

    2013-01-01

    To determine the ability of various marketed dentifrices containing stabilized stannous fluoride (SnF2), sodium fluoride (NaF), or sodium monofluorophosphate (SMFP) to protect enamel against the earliest stages of erosive dietary acid damage using an in vitro enamel protection model. Acid-challenged, extracted human teeth were treated with a 1:3 dilution of dentifrice, rinsed, and then challenged in a controlled series of tests using four dietary acids considered potentially erosive to teeth. Each acid was collected and analyzed to determine the level of mineral (phosphorous) removed from the teeth during the challenge. Post-treatment results were compared to baseline values for each acid. Results for the four acids were averaged and reported as an average percent protection value for each of the dentifrices tested, with higher values representing greater acid protection. The study included six dentifrices formulated with (A) sodium fluoride (NaF), (B) stabilized stannous fluoride (SnF2), (C,D) NaF plus 5% potassium nitrate (KNO3), (E) sodium monofluorophosphate (SMFP), or (F) SMFP plus 8% arginine bicarbonate. The stabilized SnF2 dentifrice demonstrated an average protection score of 39.3%, while products formulated with NaF resulted in protection scores between 11 and 13%. The SMFP dentifrice was rated at -3.5%, and the SMFP + arginine bicarbonate dentifrice resulted in a net average score of -5.0%. Results of this test were statistically significant (p A = C = D > E = F), in favor of the stabilized SnF2 dentifrice. These results suggest the stabilized SnF2 dentifrice has the potential to provide significantly better overall acid protection versus any of the other dentifrices included in the study.

  9. Kynurenic acid synthesis by human glioma

    DEFF Research Database (Denmark)

    Vezzani, A; Gramsbergen, J B; Versari, P;

    1990-01-01

    Biopsy material from human gliomas obtained during neurosurgery was used to investigate whether pathological human brain tissue is capable of producing kynurenic acid (KYNA), a natural brain metabolite which can act as an antagonist at excitatory amino acid receptors. Upon in vitro exposure to 40...

  10. Caffeine prevents protection in two human models of ischemic preconditioning.

    NARCIS (Netherlands)

    Riksen, N.P.; Zhou, Z.; Oyen, W.J.G.; Jaspers, R.A.; Ramakers, B.P.; Brouwer, R.M.H.J.; Boerman, O.C.; Steinmetz, N.; Smits, P.; Rongen, G.A.

    2006-01-01

    OBJECTIVES: We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans. BACKGROUND: Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP.

  11. Caffeine prevents protection in two human models of ischemic preconditioning.

    NARCIS (Netherlands)

    Riksen, N.P.; Zhou, Z.; Oyen, W.J.G.; Jaspers, R.A.; Ramakers, B.P.; Brouwer, R.M.H.J.; Boerman, O.C.; Steinmetz, N.; Smits, P.; Rongen, G.A.

    2006-01-01

    OBJECTIVES: We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans. BACKGROUND: Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP. ME

  12. The question of the system of protection of human rights

    OpenAIRE

    Revina S.; Pochuykina V.

    2016-01-01

    The Russian state is subject to the human rights activities through the system of state bodies, including the judiciary, as reflected in the Constitution of the Russian Federation. The authors consider the human rights function of the state, judicial protection as one of the ways of state protection of the rights and freedoms of man and citizen, study the elements of General system of protection of human rights in the Russian Federation and its Central element — the right to judicial protecti...

  13. United States Federal Guidance on Witness Protection in Human Trafficking

    Science.gov (United States)

    2015-06-12

    UNITED STATES FEDERAL GUIDANCE ON WITNESS PROTECTION IN HUMAN TRAFFICKING A thesis presented to the Faculty of the U.S. Army...JUN 2015 4. TITLE AND SUBTITLE United States Federal Guidance on Witness Protection in Human Trafficking 5a. CONTRACT NUMBER 5b. GRANT NUMBER...United States needs overarching federal guidance on witness protection for human trafficking victims/witnesses in order to enhance their safety and

  14. Stearic acid protects primary cultured cortical neurons against oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Ze-jian WANG; Cui-ling LIANG; Guang-mei LI; Cai-yi YU; Ming YIN

    2007-01-01

    Aim: To observe the effects of stearic acid against oxidative stress in primary cultured cortical neurons. Methods: Cortical neurons were exposed to glutamate,hydrogen peroxide (H202), or NaN3 insult in the presence or absence of stearic acid. Cell viability of cortical neurons was determined by MTT assay and LDH release. Endogenous antioxidant enzymes activity[superoxide dismutases (SOD),glutathione peroxidase (GSH-Px), and catalase (CAT)] and lipid peroxidation in cultured cortical neurons were evaluated using commercial kits. {3-[1(p-chloro-benzyl)-5-(isopropyl)-3-t-butylthiondol-2-yl]-2,2-dimethylpropanoic acid, Na}[MK886; 5 pmol/L; a noncompetitive inhibitor of proliferator-activated receptor(PPAR)α], bisphenol A diglycidyl ether (BADGE; 100 μmol/L; an antagonist of PPARγ), and cycloheximide (CHX; 30 μmol/L, an inhibitor of protein synthesis)were tested for their effects on the neuroprotection afforded by stearic acid.Western blotting was used to determine the PPARγ protein level in cortical neurons.Results: Stearic acid dose-dependently protected cortical neurons against glutamate or H202 injury and increased glutamate uptake in cultured neurons.This protection was concomitant to the inhibition of lipid peroxidation and to the promotion activity of Cu/Zn SOD and CAT in cultured cortical neurons. Its neuroprotective effects were completely blocked by BADGE and CHX. After incubation with H2O2 for 24 h, the expression of the PPARγ protein decreased significantly (P<0.05), and the inhibitory effect of H2O2 on the expression of PPARγ can be attenuated by stearic acid. Conclusion: Stearic acid can protect cortical neurons against oxidative stress by boosting the internal antioxidant enzymes.Its neuroprotective effect may be mainly mediated by the activation of PPARγ and new protein synthesis in cortical neurons.

  15. Human physiology as the determining factor in protective clothing design

    NARCIS (Netherlands)

    Daanen, Hein

    2014-01-01

    Protective clothing is designed to protect humans against risks like fire, chemicals or blunt impact. Although protect¡ve clothing diminishes the effects of external risks, it may hinder people in functioning and it may also introduce new (internal) risks. Manufacturers are often not aware of the se

  16. Eicosapentaenoic Acid Protects against Palmitic Acid-Induced Endothelial Dysfunction via Activation of the AMPK/eNOS Pathway

    Directory of Open Access Journals (Sweden)

    Che-Hsin Lee

    2014-06-01

    Full Text Available Recent studies have shown that free fatty acids are associated with chronic inflammation, which may be involved in vascular injury. The intake of eicosapentaenoic acid (EPA can decrease cardiovascular disease risks, but the protective mechanisms of EPA on endothelial cells remain unclear. In this study, primary human umbilical vein endothelial cells (HUVECs treated with palmitic acid (PA were used to explore the protective effects of EPA. The results revealed that EPA attenuated PA-induced cell death and activation of apoptosis-related proteins, such as caspase-3, p53 and Bax. Additionally, EPA reduced the PA-induced increase in the generation of reactive oxygen species, the activation of NADPH oxidase, and the upregulation of inducible nitric oxide synthase (iNOS. EPA also restored the PA-mediated reduction of endothelial nitric oxide synthase (eNOS and AMP-activated protein kinase (AMPK phosphorylation. Using AMPK siRNA and the specific inhibitor compound C, we found that EPA restored the PA-mediated inhibitions of eNOS and AKT activities via activation of AMPK. Furthermore, the NF-κB signals that are mediated by p38 mitogen-activated protein kinase (MAPK were involved in protective effects of EPA. In summary, these results provide new insight into the possible molecular mechanisms by which EPA protects against atherogenesis via the AMPK/eNOS-related pathway.

  17. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  18. Neutron effects in humans: protection considerations

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1985-01-01

    Committee I of the International Commission on Radiological Protection has recommended that the Quality Factor for neutrons should be changed from 10 to 20. This article is an interesting recount of the tale of Q from the viewpoint of an observer which illustrates many of the problems that the selection of protection standards pose. 32 refs., 5 tabs.

  19. Bile-acid-induced cell injury and protection

    Institute of Scientific and Technical Information of China (English)

    Maria J Perez; Oscar Briz

    2009-01-01

    Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-Nmethylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties.

  20. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Curt Einarsson; Ewa Ellis; Anna Abrahamsson; Bo-G6ran Ericzon; Ingemar Bj rkhem; Magnus Axelson

    2000-01-01

    AIM To evaluate a culture system for bile acid formation in primary human hepatocytes in comparison with HepG2 cells. METHODS Hepatocytes were isolated from normal human liver tissue and were cultured in serum-free William's E medium. The medium was collected and renewed every 24 h. Bile acids and their precursors in media were finally analysed by gas chromatography-mass spectrometry. RESULTS Cholic acid ( CA ) andchenodeoxycholic acid (CDCA) conjugated with glycine or taurine accounted for 70% and 25% of total steroids. A third of CDCA was also conjugated with sulphuric acid. Dexamathasone and thyroid hormorm alone or in combination did not significantly effect bile acid formation. The addition of cyclosporin A (10 μmol/L) inhibited the synthesis of CA and CDCA by about 13% and 30%, respectively. CONCLUSION Isolated human hepatocytes in primary culture behave as in the intact liver by converting cholesterol to conjugated CA and CDCA. This is in contrast to cultured HepG2 cells, which release large amounts of bile acid precursors and unconjugated bile acids into the medium.

  1. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Curt Einarsson; Ewa Ellis; Anna Abrahamsson; Bo-G ran Ericzon; Ingemar Bj rkhem; Magnus Axelson

    2000-01-01

    AIM To evaluate a system for bile acid formation in human hepatocytes in comparison with HepG2 cells.METHODS Hepatocytes were isolated from normal human liver tissue and were cultured in serum-freeWilliam's E medium. The medium was collected and renewed every 24 h. Bile acids and their precursors inmedia were finally analysed by gas chromatography-mass spectrometry.RESULTS Cholic acid (CA) and chenodeoxycholic acid (CDCA) conjugated with glycine or taurineaccounted for 70% and 25% of total steroids. One third of CDCA was also conjugated with sulphuric acid.Dexamethasone and thyroid hormone alone or in combination did not significantly affect bile acid formation.The addition of cyclosporin A (10 tm) inhibited the synthesis of CA and CDCA by about 13% and 30%,respectively.CONCLUSION Isolated human hepatocytes in primary culture behave as in the intact liver by convertingalmost quantitatively cholesterol to conjugated CA and CDCA. This is in contrast to cultured HepG2 cells,which release large amounts of bile acid precursors and unconjugated bile acids into the medium.

  2. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress.

    Science.gov (United States)

    Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena; Garelli, Andrés; Politi, Luis E; Agbaga, Martin-Paul; Anderson, Robert E; Rotstein, Nora P

    2016-03-01

    Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA.

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Cryptococcal 3-hydroxy fatty acids protect cells against amoebal phagocytosis

    Directory of Open Access Journals (Sweden)

    Uju Lynda Madu

    2015-12-01

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

  5. Promethazine protects against 3-nitropropionic acid-induced neurotoxicity.

    Science.gov (United States)

    Cleren, Carine; Calingasan, Noel Y; Starkov, Anatoly; Jacquard, Carine; Chen, Junya; Brouillet, Emmanuel; Beal, M Flint

    2010-01-01

    Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    OpenAIRE

    Han, Xiao; Liu, Jian-Xun; Xin-zhi LI

    2010-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes. Methods: Cardiac myocytes were incubated under starvation conditions (GD) for 0, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sal B (50 μmol/L) in the presence or absence of chloroquine (3 μmol/L) under GD 3 h, the amount of LC3-II, the abundance of LC3-positive fluoresce...

  7. Evaluation of salicylic acid fatty ester prodrugs for UV protection.

    Science.gov (United States)

    Im, Jong Seob; Balakrishnan, Prabagar; Oh, Dong Hoon; Kim, Jung Sun; Jeon, Eun-Mi; Kim, Dae-Duk; Yong, Chul Soon; Choi, Han-Gon

    2011-07-01

    The purpose of this study was to investigate the physicochemical properties and in vitro evaluation of fatty ester prodrugs of salicylic acid for ultraviolet (UV) protection. The physicochemical properties such as lipophilicity, chemical stability and enzymatic hydrolysis were investigated with the following fatty ester prodrugs of salicylic acid: octanoyl (C8SA), nonanoyl (C9SA), decanoyl (C10SA), lauroyl (C12SA), myristoyl (C14SA) and palmitoyl oxysalicylate (C16SA). Furthermore, their skin permeation and accumulation were evaluated using a combination of common permeation enhancing techniques such as the use of a lipophilic receptor solution, removal of stratum corneum and delipidization of skin. Their k' values were proportional to the degree of carbon-carbon saturation in the side chain. All these fatty esters were highly stable in 2-propanol, acetonitrile and glycerin, but unstable in methanol and ethanol. They were relatively unstable in liver and skin homogenates. In particular, C16SA was mostly hydrolyzed to its parent compound in hairless mouse liver and skin homogenates, suggesting that it might be converted to salicylic acid after its topical administration. In the skin permeation and accumulation study, C16SA showed the poorest permeation in all skins, suggesting that it could not be permeated in the skin. Furthermore, C14SA and C16SA were less accumulated in delipidized skin compared with normal skin or stripped skin, suggesting that these esters had relatively strong affinities for lipids compared with the other prodrugs in the skin. C16SA showed significantly higher dermal accumulation in all skins compared with its parent salicylic acid. Thus, the palmitoyl oxysalicylate (C16SA) might be a potential candidate for UV protection due to its absence of skin permeation, smaller uptake in the lipid phase and relatively lower skin accumulation.

  8. Role of hepatocyte S6K1 in palmitic acid-induced endoplasmic reticulum stress, lipotoxicity, insulin resistance and in oleic acid-induced protection.

    Science.gov (United States)

    Pardo, Virginia; González-Rodríguez, Águeda; Muntané, Jordi; Kozma, Sara C; Valverde, Ángela M

    2015-06-01

    The excess of saturated free fatty acids, such as palmitic acid, that induces lipotoxicity in hepatocytes, has been implicated in the development of non-alcoholic fatty liver disease also associated with insulin resistance. By contrast, oleic acid, a monounsaturated fatty acid, attenuates the effects of palmitic acid. We evaluated whether palmitic acid is directly associated with both insulin resistance and lipoapoptosis in mouse and human hepatocytes and the impact of oleic acid in the molecular mechanisms that mediate both processes. In human and mouse hepatocytes palmitic acid at a lipotoxic concentration triggered early activation of endoplasmic reticulum (ER) stress-related kinases, induced the apoptotic transcription factor CHOP, activated caspase 3 and increased the percentage of apoptotic cells. These effects concurred with decreased IR/IRS1/Akt insulin pathway. Oleic acid suppressed the toxic effects of palmitic acid on ER stress activation, lipoapoptosis and insulin resistance. Besides, oleic acid suppressed palmitic acid-induced activation of S6K1. This protection was mimicked by pharmacological or genetic inhibition of S6K1 in hepatocytes. In conclusion, this is the first study highlighting the activation of S6K1 by palmitic acid as a common and novel mechanism by which its inhibition by oleic acid prevents ER stress, lipoapoptosis and insulin resistance in hepatocytes.

  9. [Lysophosphatidic acid and human erythrocyte aggregation].

    Science.gov (United States)

    Sheremet'ev, Iu A; Popovicheva, A N; Levin, G Ia

    2014-01-01

    The effects of lysophosphatidic acid on the morphology and aggregation of human erythrocytes has been studied. Morphology of erythrocytes and their aggregates were studied by light microscopy. It has been shown that lysophosphatidic acid changes the shape of red blood cells: diskocyte become echinocytes. Aggregation of red blood cells (rouleaux) was significantly reduced in autoplasma. At the same time there is a strong aggregation of echinocytes. This was accompanied by the formation of microvesicles. Adding normal plasma to echinocytes restores shape and aggregation of red blood cells consisting of "rouleaux". A possible mechanism of action of lysophosphatidic acid on erythrocytes is discussed.

  10. institutional mechanisms for human rights protection in nigeria

    African Journals Online (AJOL)

    Mofasony

    legal and institutional mechanisms for protecting the human rights guaranteed in .... by the Constitution of the Federal Republic of Nigeria, African Charter, the .... special care administrative acts which are or appear to be contrary to any law or.

  11. Planetary Protection Considerations for Human And Robotic Missions to Mars

    Science.gov (United States)

    Mogul, R.; Stabekis, P. D.; Race, M. S.; Conley, C. A.

    2012-06-01

    Incorporating planetary protection into human missions, as supported by NASA Policy Directive NPD 8020.7G, is essential to preventing the forward contamination of Mars, ensuring astronaut health, and preventing backward contamination of Earth.

  12. Physico-chemical modifications of conjugated linoleic acid for ruminal protection and oxidative stability

    Directory of Open Access Journals (Sweden)

    Choi Yun-Jaie

    2008-06-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA, 18:2n-6]. Although ruminant milk and meat products represent the largest natural source of CLA and therefore, their concentration in ruminant lipids are of interest to human health, chemical or physical modifications of CLA should be needed as a means to enhance oxidative stability, to improve post-ruminal bioavailability, and to increase the clinical application. In fact, CLA are rapidly decomposed to form furan fatty acids when its are oxidized in air, and the effectiveness of dietary supplements of CLA may be related to the extent that their metabolisms by rumen bacteria are avoided. For these reasons, many scientists have examined the effect of manufacturing and protection on the stability of CLA in ruminants and food products. In this review, physico-chemical modifications of CLA for ruminal protection such as calcium salt (Ca, formaldehyde protection (FP, lipid encapsulation (LE, and amide linkage (AL, and for oxidative stability such as green tea catechin (GTC, cyclodextrin (CD, arginine (Arg, amylase, and PEGylation are proposed.

  13. Physico-chemical modifications of conjugated linoleic acid for ruminal protection and oxidative stability.

    Science.gov (United States)

    Moon, Hyun-Seuk; Lee, Hong-Gu; Chung, Chung-Soo; Choi, Yun-Jaie; Cho, Chong-Su

    2008-06-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6]. Although ruminant milk and meat products represent the largest natural source of CLA and therefore, their concentration in ruminant lipids are of interest to human health, chemical or physical modifications of CLA should be needed as a means to enhance oxidative stability, to improve post-ruminal bioavailability, and to increase the clinical application. In fact, CLA are rapidly decomposed to form furan fatty acids when its are oxidized in air, and the effectiveness of dietary supplements of CLA may be related to the extent that their metabolisms by rumen bacteria are avoided. For these reasons, many scientists have examined the effect of manufacturing and protection on the stability of CLA in ruminants and food products. In this review, physico-chemical modifications of CLA for ruminal protection such as calcium salt (Ca), formaldehyde protection (FP), lipid encapsulation (LE), and amide linkage (AL), and for oxidative stability such as green tea catechin (GTC), cyclodextrin (CD), arginine (Arg), amylase, and PEGylation are proposed.

  14. Child protection from trafficking in humans

    Directory of Open Access Journals (Sweden)

    Žegarac Nevenka

    2005-01-01

    Full Text Available Trafficking in children is particularly severe form of exploitation and breach of the children rights, while security and welfare of children that are exposed to trafficking are obligations of state authorities, services and organizations of civil society. System of protection and support to children victims of trafficking should contain following: criteria for proper identification of child-victim of trafficking, mechanisms for immediate referring of a child to specialized services, procedures for appointing a guardian who will secure that procedures and decisions are in accordance with the best interest of child, measures for regulating of residential status, assistance with reparation and reintegration as well as measures for protection of children witnesses and victims of trafficking. Finally, it should include a proper access to justice. In the article, recommendations are proposed for improvement of identification system, proper evaluation of needs and planning services and protection measures as well as measures and activities which should secure long term solutions in accordance with rights of the child and her/his best interests.

  15. Synergistic protective effects of ceftriaxone and ascorbic acid against subacute deltamethrin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Abdel-Daim, Mohamed M; El-Ghoneimy, Ashraf

    2015-03-01

    Deltamethrin (DLM) is a synthetic class II pyrethroid acaricide and insecticide widely used for veterinary and agricultural purposes. However, its animal and human exposure leads to nephrotoxicity. Our experimental objective was to evaluate protective effects of ceftriaxone and/or ascorbic acid against DLM-induced renal injury in male Wistar albino rats. DLM-treated animals revealed significant alterations in serum biochemical parameters related to renal injury; urea, uric acid and creatinine. There was a significant increase in renal lipid peroxidation and a significant inhibition in antioxidant biomarkers. Moreover, DLM significantly reduced serum acetylcholinesterase (AChE) activity. In addition, It induced serum and kidney tumor necrosis factor-α (TNF-α). Both ceftriaxone and ascorbic acid protect against DLM-induced biochemical alterations in serum and renal tissue when used alone or in combination along with DLM-intoxication. Furthermore, both ceftriaxone and ascorbic acid produced synergetic nephroprotective and antioxidant effects. Therefore, it could be concluded that ceftriaxone and/or ascorbic acid administration able to minimize the toxic effects of DLM through their free radical-scavenging and potent antioxidant activity.

  16. Does biodiversity protect humans against infectious disease?

    Science.gov (United States)

    Wood, Chelsea L; Lafferty, Kevin D; DeLeo, Giulio; Young, Hillary S; Hudson, Peter J; Kuris, Armand M

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  17. Progress in the international protection of human rights.

    Science.gov (United States)

    Suter, Keith

    2002-01-01

    Great progress has been made in the international protection of human rights since 10 December 1948 (when the United Nations General Assembly adopted the Universal Declaration of Human Rights). Amidst the doom and gloom of the media's reporting of current affairs, it is easy to overlook this progress. This article provides a definition of 'human rights' and examines early human rights campaigns. It then considers the areas of progress: human rights are now part of the international political vocabulary, there is a recognition that respect for human rights can assist a country's economic and social development, there has been a growth of human rights treaties and techniques and non-governmental organizations (NGOs) see protecting human rights as a major activity. State sovereignty has been eroded as national governments are being held accountable to the international community for their human rights policies. A new challenge is to ensure respect for human rights by non-state entities, such as transnational corporations. The growing culture of international protection of human rights is here to stay. This is not a reason for complacency, but it is a sign of hope.

  18. Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.METHODS: Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d.UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment.RESULTS: At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 ±77.5 U/L vs 333.6 ± 50.4 U/L and 254.3 ± 35.5 U/L, respectively, P < 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.CONCLUSION: The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.

  19. Optical Properties of Linoleic Acid Protected Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ratan Das

    2011-01-01

    Full Text Available Linoleic acid-protected gold nanoparticles have been synthesized through the chemical reduction of tetrachloroaurate ions by ethanol in presence of sodium linoleate. The structure of these nanoparticles is investigated using transmission electron microscopy, which shows that the Au nanoparticles are spherical in shape with a narrow size distribution which ranges from 8 to 15 nm. Colloidal dispersion of gold nanoparticles in cyclohexane exhibits absorption bands in the ultraviolet-visible range due to surface plasmon resonance, with absorption maximum at 530 nm. Fluorescence spectra of gold nanoparticles also show an emission peak at 610 nm when illuminated at 450 nm. UV-Vis spectroscopy reveals that these nanoparticles remain stable for 10 days.

  20. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    Science.gov (United States)

    Han, Xiao; Liu, Jian-xun; Li, Xin-zhi

    2011-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes. Methods: Cardiac myocytes were incubated under starvation conditions (GD) for 0, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sal B (50 μmol/L) in the presence or absence of chloroquine (3 μmol/L) under GD 3 h, the amount of LC3-II, the abundance of LC3-positive fluorescent dots in cells, cell viability and cellular ATP levels were determined using immunoblotting, immunofluorescence microscopy, MTT assay and luminometer, respectively. Moreover, electron microscopy (EM) and immunofluorescent duel labeling of LC3 and Caspase-8 were used to examine the characteristics of autophagy and apoptosis. Results: Immunoblot analysis showed that the amount of LC3-II in starving cells increased in a time-dependent manner accompanied by increased LC3-positive fluorescence and decreased cell viability and ATP content. Sal B (50 μmol/L) inhibited the increase in LC3-II, reduced the abundance of LC3 immunofluorescence and intensity of Caspase-8 fluorescence, and enhanced cellular viability and ATP levels in myocytes under GD 3 h, regardless of whether chloroquine was present. Conclusion: Autophagy induced by starvation for 3 h led to cell injury. Sal B protected starving cells by blocking the early stage of autophagic flux and inhibiting apoptosis that occurred during autophagy. PMID:21113177

  1. Unsaturated fatty acids, desaturases, and human health.

    Science.gov (United States)

    Lee, Hyungjae; Park, Woo Jung

    2014-02-01

    With the increasing concern for health and nutrition, dietary fat has attracted considerable attention. The composition of fatty acids in a diet is important since they are associated with major diseases, such as cancers, diabetes, and cardiovascular disease. The biosynthesis of unsaturated fatty acids (UFA) requires the expression of dietary fat-associated genes, such as SCD, FADS1, FADS2, and FADS3, which encode a variety of desaturases, to catalyze the addition of a double bond in a fatty acid chain. Recent studies using new molecular techniques and genomics, as well as clinical trials have shown that these genes and UFA are closely related to physiological conditions and chronic diseases; it was found that the existence of alternative transcripts of the desaturase genes and desaturase isoforms might affect human health and lipid metabolism in different ways. In this review, we provide an overview of UFA and desaturases associated with human health and nutrition. Moreover, recent findings of UFA, desaturases, and their associated genes in human systems are discussed. Consequently, this review may help elucidate the complicated physiology of UFA in human health and diseases.

  2. Erosion protection conferred by whole human saliva, dialysed saliva, and artificial saliva

    Science.gov (United States)

    Baumann, T.; Kozik, J.; Lussi, A.; Carvalho, T. S.

    2016-01-01

    During dental erosion, tooth minerals are dissolved, leading to a softening of the surface and consequently to irreversible surface loss. Components from human saliva form a pellicle on the tooth surface, providing some protection against erosion. To assess the effect of different components and compositions of saliva on the protective potential of the pellicle against enamel erosion, we prepared four different kinds of saliva: human whole stimulated saliva (HS), artificial saliva containing only ions (AS), human saliva dialysed against artificial saliva, containing salivary proteins and ions (HS/AS), and human saliva dialysed against deionised water, containing only salivary proteins but no ions (HS/DW). Enamel specimens underwent four cycles of immersion in either HS, AS, HS/AS, HS/DW, or a humid chamber (Ctrl), followed by erosion with citric acid. During the cycling process, the surface hardness and the calcium released from the surface of the specimens were measured. The different kinds of saliva provided different levels of protection, HS/DW exhibiting significantly better protection than all the other groups (p < 0.0001). Different components of saliva, therefore, have different effects on the protective properties of the pellicle and the right proportions of these components in saliva are critical for the ability to form a protective pellicle. PMID:27703230

  3. Erosion protection conferred by whole human saliva, dialysed saliva, and artificial saliva

    Science.gov (United States)

    Baumann, T.; Kozik, J.; Lussi, A.; Carvalho, T. S.

    2016-10-01

    During dental erosion, tooth minerals are dissolved, leading to a softening of the surface and consequently to irreversible surface loss. Components from human saliva form a pellicle on the tooth surface, providing some protection against erosion. To assess the effect of different components and compositions of saliva on the protective potential of the pellicle against enamel erosion, we prepared four different kinds of saliva: human whole stimulated saliva (HS), artificial saliva containing only ions (AS), human saliva dialysed against artificial saliva, containing salivary proteins and ions (HS/AS), and human saliva dialysed against deionised water, containing only salivary proteins but no ions (HS/DW). Enamel specimens underwent four cycles of immersion in either HS, AS, HS/AS, HS/DW, or a humid chamber (Ctrl), followed by erosion with citric acid. During the cycling process, the surface hardness and the calcium released from the surface of the specimens were measured. The different kinds of saliva provided different levels of protection, HS/DW exhibiting significantly better protection than all the other groups (p saliva, therefore, have different effects on the protective properties of the pellicle and the right proportions of these components in saliva are critical for the ability to form a protective pellicle.

  4. Nucleic acid association to human prostasomes.

    Science.gov (United States)

    Olsson, I; Ronquist, G

    1990-01-01

    Human prostasomes isolated from seminal plasma were subjected to phenol extraction and then to absorbance (A) measurements at 260 nm (A260) and 280 nm (A280). The A260/A280 ratio was about 2 for prostasome extract and lower for seminal plasma extract, indicative of the presence of nucleic acid. The ratio of nucleic acid to protein in prostasomes was about 1:100, and the ratio in seminal plasma was 1:1,000. Hence nucleic acid is enriched in prostasomes (compared to seminal plasma of 10). Treatment of prostasome samples with 2% sodium dodecyl sulfate resulted in an efficient dissociation of nucleic acid from prostasomes as demonstrated by electrophoresis. The association of nucleic acids of various sizes (range; 200 to 20,000 base pairs) to prostasome membranes was most probably genuine and not the result of contamination from spermatozoa, erythrocytes, leukocytes, or bacteria. The results of experiments employing nucleic acid-degrading enzymes favored the concept that double-stranded DNA but not RNA is present at the prostasome membrane surface.

  5. Reaction of 5-aminosalicylic acid with peroxyl radicals: protection and recovery by ascorbic acid and amino acids.

    Science.gov (United States)

    López-Alarcón, Camilo; Rocco, Claudia; Lissi, Eduardo; Carrasco, Catalina; Squella, J Arturo; Nuñez-Vergara, Luis; Speisky, Hernan

    2005-10-01

    The aims of the study are to analyze the interaction between 5-aminosalicylic acid (5-ASA) and peroxyl radicals and to evaluate the effect of some endogenous compounds such as ascorbic acid and amino acids on the oxidation of 5-ASA induced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride. The consumption and/or the recovery of 5-ASA (7.6 microM) exposed to a peroxyl radical source [2,2'-azo-bis(2-amidinopropane)] was followed by techniques such as spectrofluorescence, high-performance liquid chromatography, and differential pulse voltammetry. 5-Aminosalicylic acid was found to readily react with peroxyl radicals at micromolar concentrations and to protect c-Phycocyanin in a very similar fashion to that shown by Trolox. Exposure of 5-ASA to peroxyl radicals led to its oxidation into the corresponding quinone-imine. Disappearance of 5-ASA was prevented by tryptophan, cysteine, glutathione, and ascorbic acid. Furthermore, some of these compounds induced the partial (cysteine and glutathione) or total (ascorbic acid) recovery of 5-ASA when added after its almost total consumption. 5-Aminosalicylic acid is a very efficient peroxyl radical scavenger. The 5-ASA oxidation by peroxyl radicals was prevented by ascorbic acid, cysteine, and glutathione. In addition, 5-ASA can be regenerated by these endogenous compounds, which would be a valuable mechanism to preserve 5-ASA in tissues undergoing oxidative stress conditions.

  6. Reimagining Human Research Protections for 21st Century Science

    Science.gov (United States)

    Bietz, Matthew; Bae, Deborah; Bigby, Barbara; Devereaux, Mary; Fowler, James; Waldo, Ann; Weibel, Nadir; Patrick, Kevin; Klemmer, Scott; Melichar, Lori

    2016-01-01

    Background Evolving research practices and new forms of research enabled by technological advances require a redesigned research oversight system that respects and protects human research participants. Objective Our objective was to generate creative ideas for redesigning our current human research oversight system. Methods A total of 11 researchers and institutional review board (IRB) professionals participated in a January 2015 design thinking workshop to develop ideas for redesigning the IRB system. Results Ideas in 5 major domains were generated. The areas of focus were (1) improving the consent form and process, (2) empowering researchers to protect their participants, (3) creating a system to learn from mistakes, (4) improving IRB efficiency, and (5) facilitating review of research that leverages technological advances. Conclusions We describe the impetus for and results of a design thinking workshop to reimagine a human research protections system that is responsive to 21st century science. PMID:28007687

  7. Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Liin, Sara I; Karlsson, Urban; Bentzen, Bo Hjorth

    2016-01-01

    , by shifting the conductance-versus-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μM). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel. CONCLUSIONS: These findings suggest that circulating...... acids reduce neuronal excitability. This article is protected by copyright. All rights reserved....

  8. Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions: Workshop Report

    Science.gov (United States)

    Race, Margaret S. (Editor); Johnson, James E. (Editor); Spry, James A. (Editor); Siegel, Bette; Conley, Catharine A.

    2015-01-01

    This report on Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions summarizes the presentations, deliberations and findings of a workshop at NASA Ames Research Center, March 24-26, 2015, which was attended by more than 100 participants representing a diverse mix of science, engineering, technology, and policy areas. The main objective of the three-day workshop was to identify specific knowledge gaps that need to be addressed to make incremental progress towards the development of NASA Procedural Requirements (NPRs) for Planetary Protection during human missions to Mars.

  9. Semicarbazone EGA Inhibits Uptake of Diphtheria Toxin into Human Cells and Protects Cells from Intoxication

    Directory of Open Access Journals (Sweden)

    Leonie Schnell

    2016-07-01

    Full Text Available Diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. In acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (DTA from endosomal lumen into the host cell cytosol. Here, DTA ADP-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. The compound 4-bromobenzaldehyde N-(2,6-dimethylphenylsemicarbazone (EGA has been previously shown to protect cells from various bacterial protein toxins which deliver their enzymatic subunits from acidic endosomes to the cytosol, including Bacillus anthracis lethal toxin and the binary clostridial actin ADP-ribosylating toxins C2, iota and Clostridium difficile binary toxin (CDT. Here, we demonstrate that EGA also protects human cells from diphtheria toxin by inhibiting the pH-dependent translocation of DTA across cell membranes. The results suggest that EGA might serve for treatment and/or prevention of the severe disease diphtheria.

  10. Salvianolic acid B inhibits autophagy and protects starving cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Xiao HAN; Jian-xun LIU; Xin-zhi LI

    2011-01-01

    Aim: To investigate the protective or lethal role of autophagy and the effects of Salvianolic acid B (Sal B) on autophagy in starving myocytes.Methods: Cardiac myocytes were incubated under starvation conditions (GD) for O, 1, 2, 3, and 6 h. Autophagic flux in starving cells was measured via chloroquine (3 μmol/L). After myocytes were treated with Sat B (50 μmol/L) in the presence or absence of chloro-quine (3 μmol/L) under GD 3 h, the amount of LC3-11, the abundance of LC3-positive fluorescent dots in cells, cell viability and cellular ATP levels were determined using immunoblotting, immunofluorescence microscopy, MTT assay and luminometer, respectively. More-over, electron microscopy (EM) and immunofluorescent duel labeling of LC3 and Caspase-8 were used to examine the characteristics of autophagy and apoptosis.Results: Immunoblot analysis showed that the amount of LC3-11 in starving cells increased in a time-dependent manner accompanied by increased LC3-positive fluorescence and decreased cell viability and ATP content. Sal B (50 μmol/L) inhibited the increase in LC3-11, reduced the abundance of LC3 immunofluorescence and intensity of Caspase-8 fluorescence, and enhanced cellular viability and ATP levels in myocytes under GD 3 h, regardless of whether chloroquine was present.Conclusion: Autophagy induced by starvation for 3 h led to cell injury. Sal B protected starving cells by blocking the early stage of autophagic flux and inhibiting apoptosis that occurred during autophagy.

  11. Fatty acid transport protein expression in human brain and potential role in fatty acid transport across human brain microvessel endothelial cells.

    Science.gov (United States)

    Mitchell, Ryan W; On, Ngoc H; Del Bigio, Marc R; Miller, Donald W; Hatch, Grant M

    2011-05-01

    The blood-brain barrier (BBB), formed by the brain capillary endothelial cells, provides a protective barrier between the systemic blood and the extracellular environment of the CNS. Passage of fatty acids from the blood to the brain may occur either by diffusion or by proteins that facilitate their transport. Currently several protein families have been implicated in fatty acid transport. The focus of the present study was to identify the fatty acid transport proteins (FATPs) expressed in the brain microvessel endothelial cells and characterize their involvement in fatty acid transport across an in vitro BBB model. The major fatty acid transport proteins expressed in human brain microvessel endothelial cells (HBMEC), mouse capillaries and human grey matter were FATP-1, -4 and fatty acid binding protein 5 and fatty acid translocase/CD36. The passage of various radiolabeled fatty acids across confluent HBMEC monolayers was examined over a 30-min period in the presence of fatty acid free albumin in a 1 : 1 molar ratio. The apical to basolateral permeability of radiolabeled fatty acids was dependent upon both saturation and chain length of the fatty acid. Knockdown of various fatty acid transport proteins using siRNA significantly decreased radiolabeled fatty acid transport across the HBMEC monolayer. Our findings indicate that FATP-1 and FATP-4 are the predominant fatty acid transport proteins expressed in the BBB based on human and mouse expression studies. While transport studies in HBMEC monolayers support their involvement in fatty acid permeability, fatty acid translocase/CD36 also appears to play a prominent role in transport of fatty acids across HBMEC.

  12. Protective benefits of a stabilised stannous-containing fluoride dentifrice against erosive acid damage.

    Science.gov (United States)

    Faller, Robert V; Eversole, Sandra L; Saunders-Burkhardt, Kymberly

    2014-03-01

    To assess the potential of a stabilised stannous (Sn)-containing NaF dentifrice (Oral B/blend-a-Med(®) Pro-Expert), in addition to a number of other marketed European dentifrices formulated with various fluoride actives and two control dentifrices, to protect enamel against erosive acid damage. Cores of human enamel (four per group) were soaked in pooled human saliva, and then treated with a 1:3 slurry (dentifrice:saliva) using a standardised in vitro erosion model (5-day cycling) that includes 10-minute challenges with 1% citric acid applied 60 minutes after each dentifrice treatment. Enamel surface loss was measured using transverse microradiography (TMR). Specimens treated with the Sn-containing NaF dentifrice showed 6.5 μm of surface loss ± 1.2 (SEM), which was not significantly different (P Sensodyne(®) ProNamel(™) : (1,450 ppm F as NaF + KNO3 ) 20.5 μm (1.26); Crest Cavity Protection (1,100 ppm F as NaF, reference control) 22.00 μm (2.04); and Mentadent(®) : (1,450 ppm F as NaF + Zn citrate) 22.3 μm (0.63). These results support the potential for the stabilised, Sn-containing NaF dentifrice to provide erosion protection benefits that are not significantly different from the positive control benchmark for erosion protection (stabilised SnF2 ), and are significantly better than a broad range of dentifrice formulations available on the European market. © 2014 FDI World Dental Federation.

  13. Ultraviolet-B Protective Effect of Flavonoids from Eugenia caryophylata on Human Dermal Fibroblast Cells

    OpenAIRE

    Patwardhan, Juilee; Bhatt, Purvi

    2015-01-01

    Background: The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects. Objective: To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast c...

  14. Protective effects of Emblica officinalis (Amla) on metal-induced lipid peroxidation in human erythrocytes.

    Science.gov (United States)

    Krishnamoorthy, Vijay Kumar; Rather, Irfan Ahmad

    2016-05-01

    The protective potential of Emblica officinalis (amla) was investigated on metal-induced lipid per oxidation in human erythrocytes. Increases in the levels of MDA and catalase activity were assessed as lipid per oxidation. In addition, glutathione peroxidase (GPX), glutathione (GSH), and ascorbic acid levels were assessed as antioxidant indices. Preliminary investigation of the extract exhibited a significant reduction in lipid per oxidation and an increase in antioxidant abilities, such as a decrease in MDA, GPx and GSH (Pamla extract (Pamla extract has significant protective potential against lipid per oxidation.

  15. Catalytic protection of stannous ion by ascorbic acid in diphosphonic acids solutions

    Institute of Scientific and Technical Information of China (English)

    LiuGuo-Zheng; LiuFei; 等

    1998-01-01

    The protective ability of ascorbic acid(Vc) on stannous ion and the influence of light irradiation on the stability of stannous ion in diphosphonate medium at pH=5 have been examined in order to attain minimal loss of stannous ion during the production of lyophilized radiopharmaceutical kits.The sum of stanous ion and Vc was determined with iodometric method.It was shown that the protective ability of Vc was still strong at Vc concentration much lower than that of stannous ion and the illumination by fluorescent lamp was unfavorable to the stability of stannous ion.The change of pH in the range 3-9 did not affect the action of Vc significantly.

  16. Pyridoxamine protects proteins from damage by hypohalous acids in vitro and in vivo.

    Science.gov (United States)

    Madu, Hartman; Avance, Josh; Chetyrkin, Sergei; Darris, Carl; Rose, Kristie Lindsey; Sanchez, Otto A; Hudson, Billy; Voziyan, Paul

    2015-12-01

    Diabetes is characterized, in part, by activation of toxic oxidative and glycoxidative pathways that are triggered by persistent hyperglycemia and contribute to diabetic complications. Inhibition of these pathways may benefit diabetic patients by delaying the onset of complications. One such inhibitor, pyridoxamine (PM), had shown promise in clinical trials. However, the mechanism of PM action in vivo is not well understood. We have previously reported that hypohalous acids can cause disruption of the structure and function of renal collagen IV in experimental diabetes (K.L. Brown et al., Diabetes 64:2242-2253, 2015). In the present study, we demonstrate that PM can protect protein functionality from hypochlorous and hypobromous acid-derived damage via a rapid direct reaction with and detoxification of these hypohalous acids. We further demonstrate that PM treatment can ameliorate specific hypohalous acid-derived structural and functional damage to the renal collagen IV network in a diabetic animal model. These findings suggest a new mechanism of PM action in diabetes, namely sequestration of hypohalous acids, which may contribute to known therapeutic effects of PM in human diabetic nephropathy.

  17. Protective Effects of Lycopene and Ellagic Acid on Gonadal Tissue, Maternal Newborn Rats Induced by Cadmiumchloride

    Directory of Open Access Journals (Sweden)

    K Hoshmand Motlagh

    2015-08-01

    Full Text Available Background & aim: Cadmium is a toxin which reduces the ability of the reproduction in humans .Different antioxidants damaging effects of toxins are eliminated .The purpose of this study was to investigate the protective effects of lycopene and Ellagic acid induced by cadmium chloride on the gonadal tissue of newborn rats during pregnancy. Methods: In the present experimental study, 30 adult female Wistar rats (180-200 gr were prepared and maintained in standard conditions. The female rats were used for mating with the male. After observation of vaginal plaque, pregnant rats were randomly divided into 5 groups of 6 rats. Group I (normal: They were given normal saline in 13 days during pregnancy. Group II (Control: Cadmium chloride (1.5 mg / kg/ IP was injected and normal saline was given to them in 13 days of during pregnancy. Group III: Cadmium chloride (1.5 mg / kg/ IP was injected and ellagic acid (10 mg/kg/orally in 13 days were injected during pregnancy. Group IV: Cadmium chloride (1.5 mg / kg/ IP was injected and copene acid (20 mg/kg/orally was injected in 13 days of during pregnancy. Group V: Cadmium chloride (1.5 mg / kg/ IP was injected and ellagic acid (10 mg/kg/orally and lycopene acid (20 mg/kg/orally were injected in 13 days during pregnancy. After postpartum, Neonatal rats were anesthetized with ether. Animals were dissected, then the testes and Ovaries were removed and transferred to 10% formalin solution. After tissue processing, tissue sections were prepared and H&E stained. Data were analyzed by SPSS software and ANOVA test. Results: Average number of Sertoli cells ,spermatogonia ,Leydig, and the number of seminiferous tube in control group were compared to other groups that were treated with lycopene - ellagic acid and ellagic acid had been reduced-proves to be significant(P <0.05. Average diameter of seminiferous tube in control group compared to other groups that are treated with lycopene - ellagic acid and ellagic acid had

  18. Palmitic Acid in Early Human Development.

    Science.gov (United States)

    Innis, Sheila M

    2016-09-09

    Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental.

  19. Essential fatty acids and human brain.

    Science.gov (United States)

    Chang, Chia-Yu; Ke, Der-Shin; Chen, Jen-Yin

    2009-12-01

    The human brain is nearly 60 percent fat. We've learned in recent years that fatty acids are among the most crucial molecules that determine your brain's integrity and ability to perform. Essential fatty acids (EFAs) are required for maintenance of optimal health but they can not synthesized by the body and must be obtained from dietary sources. Clinical observation studies has related imbalance dietary intake of fatty acids to impaired brain performance and diseases. Most of the brain growth is completed by 5-6 years of age. The EFAs, particularly the omega-3 fatty acids, are important for brain development during both the fetal and postnatal period. Dietary decosahexaenoic acid (DHA) is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Beyond their important role in building the brain structure, EFAs, as messengers, are involved in the synthesis and functions of brain neurotransmitters, and in the molecules of the immune system. Neuronal membranes contain phospholipid pools that are the reservoirs for the synthesis of specific lipid messengers on neuronal stimulation or injury. These messengers in turn participate in signaling cascades that can either promote neuronal injury or neuroprotection. The goal of this review is to give a new understanding of how EFAs determine our brain's integrity and performance, and to recall the neuropsychiatric disorders that may be influenced by them. As we further unlock the mystery of how fatty acids affect the brain and better understand the brain's critical dependence on specific EFAs, correct intake of the appropriate diet or supplements becomes one of the tasks we undertake in pursuit of optimal wellness.

  20. Acidic chitinase primes the protective immune response to gastrointestinal nematodes.

    Science.gov (United States)

    Vannella, Kevin M; Ramalingam, Thirumalai R; Hart, Kevin M; de Queiroz Prado, Rafael; Sciurba, Joshua; Barron, Luke; Borthwick, Lee A; Smith, Allen D; Mentink-Kane, Margaret; White, Sandra; Thompson, Robert W; Cheever, Allen W; Bock, Kevin; Moore, Ian; Fitz, Lori J; Urban, Joseph F; Wynn, Thomas A

    2016-05-01

    Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung.

  1. Ursolic Acid provides kidney protection in diabetic rats.

    Science.gov (United States)

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-12-01

    Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy.

  2. Ursolic Acid Provides Kidney Protection in Diabetic Rats☆

    Science.gov (United States)

    Ling, Chen; Jinping, Lu; Xia, Li; Renyong, Yang

    2013-01-01

    Background Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes and the leading cause of end-stage renal failure. However, the treatment of DN is still a problem in the world. Inflammatory process plays a critical role in the development of DN. Therefore, anti-inflammatory treatment of DN is worth exploring now and in the future. Objective The study aimed to evaluate the impact of ursolic acid (UA) on renal function in streptozotocin-induced diabetes. Methods Rats with streptozotocin-induced diabetes were treated with UA for 16 weeks. After 16 weeks, urine albumin excretion, serum creatinine, and blood urea nitrogen were measured. In addition, renal oxidative stress level, nuclear factor kappa-B (NF-κB) activity, P-selectin expression, and kidney histopathologic changes were evaluated. Results Sixteen weeks following streptozotocin injection, the rats produced significant alteration in renal function and increased oxidative stress, NF-κB activity, and P-selectin expression in the kidneys. Interestingly, UA significantly prevented biochemical and histopathologic changes in the kidneys associated with diabetes. Compared with untreated diabetic rats, UA treatment lowered urine albumin excretion, renal oxidative stress level, NF-κB activity, and P-selectin expression. Moreover, UA treatment also improved renal histopathologic changes in rats with diabetes. Conclusions UA treatment exhibited a protective effect on kidneys in diabetic rats, implying that UA could be a potential treatment for diabetic nephropathy. PMID:24465045

  3. 77 FR 37408 - Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2012-06-21

    ... Protections (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP; U.S. Department of Health and Human...; email address: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the authority of 42 U.S.C. 217a... as sign language interpretation or other reasonable accommodations, should notify the...

  4. 75 FR 37813 - Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2010-06-30

    ..., Office for Human Research Protections (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP; U.S...-8141; fax: 240-453-6909; e-mail address: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the... as sign language interpretation or other reasonable accommodations, should notify the...

  5. Protection from cyanide-induced brain injury by the Nrf2 transcriptional activator carnosic acid.

    Science.gov (United States)

    Zhang, Dongxian; Lee, Brian; Nutter, Anthony; Song, Paul; Dolatabadi, Nima; Parker, James; Sanz-Blasco, Sara; Newmeyer, Traci; Ambasudhan, Rajesh; McKercher, Scott R; Masliah, Eliezer; Lipton, Stuart A

    2015-06-01

    Cyanide is a life-threatening, bioterrorist agent, preventing cellular respiration by inhibiting cytochrome c oxidase, resulting in cardiopulmonary failure, hypoxic brain injury, and death within minutes. However, even after treatment with various antidotes to protect cytochrome oxidase, cyanide intoxication in humans can induce a delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Additional mechanisms are thought to underlie cyanide-induced neuronal damage, including generation of reactive oxygen species. This may account for the fact that antioxidants prevent some aspects of cyanide-induced neuronal damage. Here, as a potential preemptive countermeasure against a bioterrorist attack with cyanide, we tested the CNS protective effect of carnosic acid (CA), a pro-electrophilic compound found in the herb rosemary. CA crosses the blood-brain barrier to up-regulate endogenous antioxidant enzymes via activation of the Nrf2 transcriptional pathway. We demonstrate that CA exerts neuroprotective effects on cyanide-induced brain damage in cultured rodent and human-induced pluripotent stem cell-derived neurons in vitro, and in vivo in various brain areas of a non-Swiss albino mouse model of cyanide poisoning that simulates damage observed in the human brain. Cyanide, a potential bioterrorist agent, can produce a chronic delayed-onset neurological syndrome that includes symptoms of Parkinsonism. Here, cyanide poisoning treated with the proelectrophillic compound carnosic acid, results in reduced neuronal cell death in both in vitro and in vivo models through activation of the Nrf2/ARE transcriptional pathway. Carnosic acid is therefore a potential treatment for the toxic central nervous system (CNS) effects of cyanide poisoning. ARE, antioxidant responsive element; Nrf2 (NFE2L2, Nuclear factor (erythroid-derived 2)-like 2). © 2015 International Society for Neurochemistry.

  6. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, M.R.; Hollman, P.C.H.; Katan, M.B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  7. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, M.R.; Hollman, P.C.H.; Katan, M.B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  8. Salvianolic acid B protects endothelial cells from oxidant-mediated damage

    Institute of Scientific and Technical Information of China (English)

    LI Xue-jun

    2008-01-01

    Objective To investigate the protective effects of Salvianolic acid B(Sal B) on hydrogen peroxide (H2O2)-induced injury in human umbilical vein endothelial cells (HUVECs). Sal B is considered as one of the most active anti-oxidant and the major pharmacological component of the herb, Salvia miltiorrhiza. Its beneficial effects include hepatoprotection, elicitation of endothelium-dependent vasodilation, lowering blood pressure in hypertension, inhibition of HIV-1 replication and suppressing inflammatory cytokine- stimulated endothelial adhesiveness to human monocytie cells by its strong antioxidant activities. Methods Treatment with H2O2 significantly decreased the cell viability and increased the lactate dehydrogenase (LDH) leakage that is an apoptotic feature. Pretreatment with Sal B prevented significantly from H2O2-induced cell apoptosis and other damages in a concentration-dependent manner. The mechanism of Sal B protection was studied with two-dimensional gel electrophoresis (2-DE) coupled to hybrid quadrupole time-of-flight mass spectrometry (Q-TOF) mass spectrometer. Results Data base searching implicated glucose-regulated protein 78 (GRP78), a central regulator for ER stress, was up-regulated in Sal B-exposed HUVECs. After exposure to Sal B, the level of activating transcription factor 4 (ATF4) was raised, with a transient phosphorylation of the α subunit of eukaryotic translation initiation factor (eIF2α). Knock-down of GRP78 by siRNA significantly reduced protective effects of Sal B. Conclusions These results suggest that Sal B-induced GRP78 upregulation via phosphorylation of eIF2α and resultant translation of ATF4. And up-regulation of ER chaperones induced by Sal B may play an important role in protecting human endothelial cells from oxidative stress-induced cellular damage.

  9. The protection of individuals by means of diplomatic protection : diplomatic protection as a human rights instrument

    NARCIS (Netherlands)

    Vermeer-Künzli, Anna Maria Helena

    2007-01-01

    Individuals whose international (human) rights are violated outside their state of nationality often have very limited means to address such violations. For instance, the foreign nationals detained by the United States in Guantanamo Bay have been unable to improve their situation themselves. Their

  10. To what extent can human and non-human radiation protection frameworks be integrated?

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, C.; Stark, Karolina [Stockholm University (Sweden); Beaugelin-Seiller, Karine; Hinton, Thomas [Institut de radioprotection et de surete nucleaire - IRSN (France); Beresford, Nicholas A. [Centre for Ecology and Hydrology - CEH (United Kingdom); Brown, Justin; Dowdall, Mark; Hosseini, Ali; Liland, Astrid [Norwegian Radiation Protection Authority - NRPA (Norway); Mora, Juan Carlos; Real, Almudena; Robles, Beatriz [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas - CIEMAT (Spain); Oughton, Deborah [Norwegian University of Life Sciences - UMB (Norway); Steiner, Martin [Federal Office for Radiation Protection - BfS (Germany); Sweeck, Lieve; Vives I Batlle, Jordi [Belgian Nuclear Research Centre SCK-CEN (Belgium)

    2014-07-01

    The first radiation protection frameworks were initiated in the early 20. century and focused on the protection of humans. Protection frameworks for non-human species were developed later, based on the human protection system as well as that used to protect the environment from adverse effects of chemicals. These two radiation protection frameworks have to some degree developed quite separately from each other over the last few decades, and it is a source of debate as to what extent the integration of the two is possible. This presentation critically reviews some of the key aspects of integrating human and non-human assessment frameworks, including both conceptual and practical issues, and focuses on five main topics: 1) the conceptual consideration of humans as part of ecosystems, rather than a separate entity; 2) the consistency and potential harmonisation of underlying data and transfer model parameters; 3) consideration of different life stages and life histories in radiation protection and the implications for exposure, dose and effects; 4) calculation of doses, including modelling approaches, spatial and temporal variability and biokinetic modelling; and 5) benchmarks and screening values. Similarities and differences between the two existing frameworks are highlighted and the feasibility of integrating the two discussed. Our recommendations on how to further integrate, where achievable and warranted, are given. Document available in abstract form only. (authors)

  11. On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

    Directory of Open Access Journals (Sweden)

    El-Gezeery Amina R

    2011-08-01

    Full Text Available Abstract Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA, serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA, serotonin (5HT and dopamine (DA as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6, tumor necrosis factor-α (TNF-α as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE, phosphatidylserine (PS and phosphatidylcholine (PC. Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as

  12. Fatty acid-based formulations for wood protection against mold and sapstain

    Science.gov (United States)

    Carol A. Clausen; Robert D. Coleman; Vina W. Yang

    2010-01-01

    Safer, highly effective biocides providing long-term protection of mold growth on wood-based materials is of interest to the wood protection industry. Moldicide formulations containing synergistic combinations of ingredients derived from natural sources are commonly recognized as a promising approach for the next generation of wood protectants. Although fatty acid (FA...

  13. Analysis of the effect of dietary protected organic acid blend on lactating sows and their piglets

    Directory of Open Access Journals (Sweden)

    Subramaniam Mohana Devi

    2016-02-01

    Full Text Available ABSTRACT The objective of the present study was to evaluate the effects of blends of dietary protected organic acid supplementation on growth performance, nutrient digestibility, blood profiles, faecal microflora, and gas emission on sows and piglets with emphasis on their modes of action to improve pig performance. A total of 12 sows with an average initial body weight (BW of 252.40±11.7 kg were used in this trial. Growth performance, blood profiles, and nutrient digestibility of sows and piglets fed protected organic acid were evaluated. The dietary treatments included a basal diet (CON; CON + 0.1% protected organic acid; and CON + 0.2% protected organic acid. The BW and back fat of sows was checked four days prior to farrowing and at the weaning day to calculate BW loss and back fat loss during that period. Inclusion of 0.2% protected organic acid provided a greater digestibility than CON diets throughout the experimental period in lactating sows. Dietary supplementation with 0.2% protected organic acid led to a higher white blood cell and lymphocyte concentration than CON treatment in sucking piglets. Immunoglobulin G concentration observed was greater in protected organic acid groups in lactating sow and sucking piglets. Increased faecal Lactobacillus counts with decreased E. coli concentrations were observed with the diets of protected organic acid fed to lactating sows. The E. coli counts were decreased in weaning piglets. The faecal H2S contents were decreased in 0.2% protected organic acid diets during farrowing on day 1. Dietary supplementation with protected organic acid blends beneficially affects the nutrient digestibility, ileal noxious gas (NH3 and H2S emission, as well as intestinal microbial balance in lactating sows.

  14. Planetary protection issues linked to human missions to Mars

    Science.gov (United States)

    Debus, A.

    According to United Nations Treaties and handled presently by the Committee of Space Research COSPAR the exploration of the Solar System has to comply with planetary protection requirements The goal of planetary protection is to protect celestial bodies from terrestrial contamination and also to protect the Earth environment from an eventual biocontamination carried by return samples or by space systems returning to the Earth Mars is presently one of the main target at exobiology point of view and a lot of missions are operating on travel or scheduled for its exploration Some of them include payload dedicated to the search of life or traces of life and one of the goals of these missions is also to prepare sample return missions with the ultimate objective to walk on Mars Robotic missions to Mars have to comply with planetary protection specifications well known presently and planetary protection programs are implemented with a very good reliability taking into account an experience of 40 years now For sample return missions a set of stringent requirements have been approved by the COSPAR and technical challenges have now to be won in order to preserve Earth biosphere from an eventual contamination risk Sending astronauts on Mars will gather all these constraints added with the human dimension of the mission The fact that the astronauts are huge contamination sources for Mars and that they are also potential carrier of a contamination risk back to Earth add also ethical considerations to be considered For the preparation of a such

  15. Planetary protection issues related to human missions to Mars

    Science.gov (United States)

    Debus, A.; Arnould, J.

    2008-09-01

    In accordance with the United Nations Outer Space Treaties [United Nations, Agreement Governing the Activities of States on the Moon and Other Celestial Bodies, UN doc A/RES/34/68, resolution 38/68 of December 1979], currently maintained and promulgated by the Committee on Space Research [COSPAR Planetary Protection Panel, Planetary Protection Policy accepted by the COSPAR Council and Bureau, 20 October 2002, amended 24 March 2005, http://www.cosparhq.org/scistr/PPPolicy.htm], missions exploring the Solar system must meet planetary protection requirements. Planetary protection aims to protect celestial bodies from terrestrial contamination and to protect the Earth environment from potential biological contamination carried by returned samples or space systems that have been in contact with an extraterrestrial environment. From an exobiology perspective, Mars is one of the major targets, and several missions are currently in operation, in transit, or scheduled for its exploration. Some of them include payloads dedicated to the detection of life or traces of life. The next step, over the coming years, will be to return samples from Mars to Earth, with a view to increasing our knowledge in preparation for the first manned mission that is likely to take place within the next few decades. Robotic missions to Mars shall meet planetary protection specifications, currently well documented, and planetary protection programs are implemented in a very reliable manner given that experience in the field spans some 40 years. With regards to sample return missions, a set of stringent requirements has been approved by COSPAR [COSPAR Planetary Protection Panel, Planetary Protection Policy accepted by the COSPAR Council and Bureau, 20 October 2002, amended 24 March 2005, http://www.cosparhq.org/scistr/PPPolicy.htm], and technical challenges must now be overcome in order to preserve the Earth’s biosphere from any eventual contamination risk. In addition to the human dimension of

  16. Mentha longifolia protects against acetic-acid induced colitis in rats.

    Science.gov (United States)

    Murad, Hussam A S; Abdallah, Hossam M; Ali, Soad S

    2016-08-22

    Mentha longifolia L (Wild Mint or Habak) (ML) is used in traditional medicine in treatment of many gastrointestinal disorders. This study aimed to evaluate potential protecting effect of ML and its major constituent, eucalyptol, against acetic acid-induced colitis in rats, a model of human inflammatory bowel disease (IBD). Rats were divided into ten groups (n=8) given orally for three days (mg/kg/day) the following: normal control, acetic acid-induced colitis (un-treated, positive control), vehicle (DMSO), sulfasalazine (500), ML extract (100, 500, 1000), and eucalyptol (100, 200, 400). After 24h-fasting, two ML of acetic acid (3%) was administered intrarectally. On the fifth day, serum and colonic biochemical markers, and histopathological changes were evaluated. Colitis significantly increased colonic myeloperoxidase activity and malonaldehyde level, and serum tumor necrosis factor-α, interleukin-6, and malonaldehyde levels while significantly decreased colonic and serum glutathione levels. All treatments (except ML 100, ML 1000, and eucalyptol 100) significantly reversed these changes where eucalyptol (400) showed the highest activity in a dose-dependent manner. The colitis-induced histopathological changes were mild in sulfasalazine and eucalyptol 400 groups, moderate in ML 500 and eucalyptol 200 groups, and severe in ML 100, ML 1000, and eucalyptol 100 groups nearly similar to colitis-untreated rats. ML (in moderate doses) and eucalyptol (dose-dependently) exerted protective effects against acetic acid-induced colitis in rats possibly through antioxidant and antiinflammatory properties suggesting a potential benefit in treatments of IBD. To our knowledge this is the first report addressing this point. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. [Human genetic data from a data protection law perspective].

    Science.gov (United States)

    Schulte In den Bäumen, Tobias

    2007-02-01

    The collection and use of genetic data have caused much concern in the German population. Data protection is widely seen as the tool to address these fears. The term genetic data is not self-explanatory, as it depends on the different types of genetic diseases. The protection of genetic data as defined with regard to the different sets of diseases needs to fit into the preexisting data protection legislation. Still, the particularities of genetic data such as the multipersonal impact need to be considered. A balance between the information needs of society and the right to privacy requires a medically driven criteria. The medical term of indication which corresponds with the data protection term of purpose should serve as a tool in order to balance the rights of the patients and their relatives or between clients and third persons involved. Some countries have set up new legislative acts to address the challenges of human genetics. The current state of German data protection law leaves citizen rather unprotected as long as the data are used for medical purposes in a wider sense. A special law on the collection of genetic data has been discussed for several years, but it should be questioned whether the scope of a sector-specific law would serve citizens better. It seems to be preferable to adjust the existing Data Protection Act rather than drafting a specific law which covers the field of human genetics. This adaptation should reflect upon the different technical ways in which genetic data are collected and used.

  18. People-oriented Development and Human Rights Protection for Criminals

    Institute of Scientific and Technical Information of China (English)

    LI YUQIAN

    2011-01-01

    @@ People-oriented development refers to the economic and social integrative development that regards human beings as the orientation and subject of economic and social development and considers the development of human beings the essence, objective, momentum and symbol of development.One of its important connotations is to protect human beings' rights and interests in all links and works of economic and social development.On December 10,2008, Hu Jintao, secretary general of the CPC Central Committee, clarified that "We will, as always, adhere to people-oriented principles in building a well-off society in an all-round way and accelerating the process of socialist modernization" in his letter to the China Society for Human Rights Studies.

  19. Does lycopene offer human LDL any protection against myeloperoxidase activity?

    Science.gov (United States)

    Chew, Poh Yeong; Riley, Lucy; Graham, Daniel L; Rahman, Khalid; Lowe, Gordon M

    2012-02-01

    Lycopene is a lipophilic antioxidant that is largely transported in human blood by Low Density Lipoproteins (LDL). One of the early events in the aetiology of atherosclerosis is thought to be the oxidation of LDL. Myeloperoxidase an enzyme secreted by neutrophils and macrophages is thought to oxidise human LDL particles. In this study, isolated human LDL was challenged with myeloperoxidase or copper, and the LDL was screened for lipoperoxidation and oxidation of apolipoprotein B100, depletion of lycopene and oxidation of cholesterol. Myeloperoxidase induced oxidation of LDL through direct interaction with apolipoprotein B100. No lipoperoxidation was observed following myeloperoxidase treatment; however, 7-ketocholesterol was detected indicating the products of myeloperoxidase interact with the surface of the LDL particles. Lycopene does react with the products of myeloperoxidase in solvent, but played no role in protecting against enzyme derived oxidation of human LDL.

  20. Discussion on Human Dignity and Human Rights Protection from the Perspective of Peacekeeping

    Institute of Scientific and Technical Information of China (English)

    GAO XINMAN

    2012-01-01

    From an academic point of view,human dignity is the source of human fights,and has a orofound academic history.Since the end of World War Ⅱ,the issue of human fights has received great attention from the international community.So,human right theories,for which human dignity is the basic consideration,have developed continuously.In this era of advocating rights,human dignity and human fights protection are universal values and concepts,which were emphasized once again after World War Ⅱ.Moreover,human dignity was clearly identified as the basis of human rights at the system level.This paper begins by describing the relationship between human dignity and human rights.

  1. Vitamin C fails to protect amino acids and lipids from oxidation during acute inflammation.

    Science.gov (United States)

    Gaut, Joseph P; Belaaouaj, Abderrazzaq; Byun, Jaeman; Roberts, L Jackson; Maeda, Nobuyo; Frei, Balz; Heinecke, Jay W

    2006-05-01

    The observation that antioxidant vitamins fail to confer protective benefits in large, well-designed randomized clinical trials has led many to question the role of oxidative stress in the pathogenesis of disease. However, there is little evidence that proposed antioxidants actually scavenge reactive intermediates in vivo. Ascorbate reacts rapidly with oxidants produced by activated neutrophils in vitro, and neutrophils markedly increase their oxidant production when mice are infected intraperitoneally with the gram-negative bacterium Klebsiella pneumoniae. To explore the antioxidant properties of ascorbate in vivo, we therefore used K. pneumoniae infection as a model of oxidative stress. When mice deficient in L-gulono-gamma-lactone oxidase (Gulo(-/-)), the rate-limiting enzyme in ascorbate synthesis, were depleted of ascorbate and infected with K. pneumoniae, they were three times as likely as ascorbate-replete Gulo(-/-)mice to die from infection. Mass spectrometric analysis of peritoneal lavage fluid revealed a marked increase in the levels of oxidized amino acids and of F2-isoprostanes (sensitive and specific markers of lipid oxidation) in infected animals. Surprisingly, there were no significant differences in the levels of the oxidation products in the ascorbate-deficient and -replete Gulo(-/-)mice. Our observations suggest that ascorbate plays a previously unappreciated role in host defense mechanisms against invading pathogens but that the vitamin does not protect amino acids and lipids from oxidative damage during acute inflammation. To examine the oxidation hypothesis of disease, optimal antioxidant regimens that block oxidative reactions in animals and humans need to be identified.

  2. Synergistic protective role of ceftriaxone and ascorbic acid against subacute diazinon-induced nephrotoxicity in rats.

    Science.gov (United States)

    Abdel-Daim, Mohamed M

    2016-03-01

    Diazinon (DZN) is a synthetic organophosphrus acaricide and insecticide widely used for veterinary and agricultural purposes. However, its animal and human exposure leads to nephrotoxicity. Our experimental objective was to evaluate protective effects of ceftriaxone and/or ascorbic acid-vitamin C against DZN-induced renal injury in male Wistar albino rats. DZN-treated animals revealed significant elevation in serum biochemical parameters related to renal injury: urea, uric acid and creatinine. DZN intoxication significantly increased renal lipid peroxidation, and significant inhibition in antioxidant biomarkers including, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase and total antioxidant capacity. In addition, DZN significantly reduced serum acetylcholinestrase level. Moreover, It induced serum and kidney tumor necrosis factor-α level. Both ceftriaxone and vitamin C protect against DZN-induced serum as well as renal tissue biochemical parameters when used alone or in combination along with DZN-intoxication. Furthermore, both ceftriaxone and vitamin C produced synergetic nephroprotective and antioxidant effects. Therefore, it could be concluded that ceftriaxone and/or vitamin C administration are able to minimize the toxic effects of DZN by its free radical-scavenging and potent antioxidant activity.

  3. Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy.

    Science.gov (United States)

    Shi, Min; Ma, Liang; Zhou, Li; Fu, Ping

    2016-10-18

    Aristolochic acid nephropathy (AAN) is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs) characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs)/angiotensin-converting enzyme inhibitors (ACEIs). It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2) was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr) and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells), E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15), p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.

  4. Renal Protective Effects of 17β-Estradiol on Mice with Acute Aristolochic Acid Nephropathy

    Directory of Open Access Journals (Sweden)

    Min Shi

    2016-10-01

    Full Text Available Aristolochic acid nephropathy (AAN is a progressive kidney disease caused by a Chinese herb containing aristolochic acid. Excessive death of renal tubular epithelial cells (RTECs characterized the acute phase of AAN. Therapies for acute AAN were limited, such as steroids and angiotensin-receptor blockers (ARBs/angiotensin-converting enzyme inhibitors (ACEIs. It was interesting that, in acute AAN, female patients showed relative slower progression to renal failure than males. In a previous study, female hormone 17β-estradiol (E2 was found to attenuate renal ischemia-reperfusion injury. Thus, the aim of this study was to investigate the potential protective role of E2 in acute AAN. Compared with male C57BL/6 mice of acute AAN, lower serum creatinine (SCr and less renal injury, together with RTEC apoptosis in females, were found. Treatment with E2 in male AAN mice reduced SCr levels and attenuated renal tubular injury and RTEC apoptosis. In the mice kidney tissue and human renal proximal tubule cells (HK-2 cells, E2 both attenuated AA-induced cell apoptosis and downregulated the expression of phosphor-p53 (Ser15, p53, and cleaved-caspase-3. This study highlights that E2 exhibited protective effects on the renal injury of acute AAN in male mice by reducing RTEC apoptosis, which might be related to inhibiting the p53 signaling pathway.

  5. Basic Science Research and the Protection of Human Research Participants

    Science.gov (United States)

    Eiseman, Elisa

    2001-03-01

    Technological advances in basic biological research have been instrumental in recent biomedical discoveries, such as in the understanding and treatment of cancer, HIV/AIDS, and heart disease. However, many of these advances also raise several new ethical challenges. For example, genetic research may pose no physical risk beyond that of obtaining the initial blood sample, yet it can pose significant psychological and economic risks to research participants, such as stigmatization, discrimination in insurance and employment, invasion of privacy, or breach of confidentiality. These harms may occur even when investigators do not directly interact with the person whose DNA they are studying. Moreover, this type of basic research also raises broader questions, such as what is the definition of a human subject, and what kinds of expertise do Institutional Review Boards (IRBs) need to review the increasingly diverse types of research made possible by these advances in technology. The National Bioethics Advisory Commission (NBAC), a presidentially appointed federal advisory committee, has addressed these and other ethical, scientific and policy issues that arise in basic science research involving human participants. Two of its six reports, in particular, have proposed recommendations in this regard. "Research Involving Human Biological Materials: Ethical and Policy Guidance" addresses the basic research use of human tissues, cells and DNA and the protection of human participants in this type of research. In "Ethical and Policy Issues in the Oversight of Human Research" NBAC proposes a definition of research involving human participants that would apply to all scientific disciplines, including physical, biological, and social sciences, as well as the humanities and related professions, such as business and law. Both of these reports make it clear that the protection of research participants is key to conducting ethically sound research. By ensuring that all participants in

  6. Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review.

    Science.gov (United States)

    Heinze, Verónica M; Actis, Adriana B

    2012-02-01

    The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000-2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.

  7. Chemopreventive effect of corosolic acid in human hepatocellular ...

    African Journals Online (AJOL)

    Chemopreventive effect of corosolic acid in human hepatocellular carcinoma cells. ... The anticancer activity of corosolic acid through cell growth inhibition by 3-(4 ... and apoptotic fragmentations by fluorescence microscope was evaluated.

  8. Acetylsalicylic acid and acetaminophen protect against oxidative neurotoxicity.

    Science.gov (United States)

    Maharaj, H; Maharaj, D S; Daya, S

    2006-09-01

    Due to the implication of oxidative stress in neurodegenerative disorders we decided to investigate the antioxidant properties of acetylsalicylic acid and acetaminophen either alone or in combination. The thiobarbituric acid assay (TBA) and the nitroblue tetrazolium (NBT) assay were used to investigate quinolinic acid (QA)-induced: lipid peroxidation and superoxide anion generation in the rat hippocampus, in vivo. The study also shows, using cresyl violet staining, the preservation of structural integrity of neuronal cells following treatment with acetylsalicylic acid and acetaminophen in QA-lesioned rat hippocampus. Furthermore the study sought to determine whether these agents have any effect on endogenous (QA) formation. This study shows that acetylsalicylic acid and acetaminophen inhibit QA-induced superoxide anion generation, lipid peroxidation and cell damage, in vivo, in the rat hippocampus. In addition these agents inhibit the enzyme, 3-hydroxyanthranilic acid oxygenase (3-HAO), responsible for the synthesis of endogenous QA.

  9. Conjugated linoleic acid protects against gliadin-induced depletion of intestinal defenses.

    Science.gov (United States)

    Bergamo, Paolo; Gogliettino, Marta; Palmieri, Gianna; Cocca, Ennio; Maurano, Francesco; Stefanile, Rosita; Balestrieri, Marco; Mazzarella, Giuseppe; David, Chella; Rossi, Mauro

    2011-09-01

    The involvement of oxidative stress in gluten-induced toxicity has been evidenced in vitro and in clinical studies but has never been examined in vivo. We recently demonstrated the protective activity of conjugated linoleic acid (CLA), which functions by the activation of nuclear factor erythroid 2-related factor2 (Nrf2), a key transcription factor for the synthesis of antioxidant and detoxifying enzymes (phase 2). Here, we evaluate the involvement of nuclear factor erythroid 2-related factor2 in gliadin-mediated toxicity in human Caco-2 intestinal cells and in gliadin-sensitive human leukocyte antigen-DQ8 transgenic mice (DQ8) and the protective activity of CLA. Gliadin effects in differentiated Caco-2 cells and in DQ8 mice, fed with a gliadin-containing diet with or without CLA supplementation, were evaluated by combining enzymatic, immunochemical, immunohistochemical, and quantitative real-time PCR (qRT-PCR) assays. Gliadin toxicity was accompanied by downregulation of phase 2 and elevates proteasome-acylpeptide hydrolase activities in vitro and in vivo. Notably, gliadin was unable to generate severe oxidative stress extent or pathological consequences in DQ8 mice intestine comparable to those found in celiac patients and the alterations produced were hampered by CLA. The beneficial effects of CLA against the depletion of crucial intestinal cytoprotective defenses indicates a novel nutritional approach for the treatment of intestinal disease associated with altered redox homeostasis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. alpha-Linolenic acid protects renal cells against palmitic acid lipotoxicity via inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Katsoulieris, Elias; Mabley, Jon G; Samai, Mohamed; Green, Irene C; Chatterjee, Prabal K

    2009-11-25

    Unsaturated fatty acids may counteract the lipotoxicity associated with saturated fatty acids. Palmitic acid induced endoplasmic reticulum (ER) stress and caused apoptotic and necrotic cell death in the renal proximal tubular cell line, NRK-52E. We investigated whether alpha-linolenic acid, an unsaturated fatty acid, protected against ER stress and cell death induced by palmitic acid or by other non-nutrient ER stress generators. Incubation of NRK-52E cells for 24h with palmitic acid produced a significant increase in apoptosis and necrosis. Palmitic acid also increased levels of three indicators of ER stress - the phosphorylated form of the eukaryotic initiation factor 2alpha (eIF2alpha), C/EBP homologous protein (CHOP), and glucose regulated protein 78 (GRP78). alpha-Linolenic acid dramatically reduced cell death and levels of all three indicators of ER stress brought about by palmitic acid. Tunicamycin, which induces ER stress by glycosylation of proteins, produced similar effects to those obtained using palmitic acid; its effects were partially reversed by alpha-linolenic acid. Salubrinal (a phosphatase inhibitor) causes increased levels of the phosphorylated form of eIF2alpha - this effect was partially reversed by alpha-linolenic acid. Palmitoleate, a monosaturated fatty acid, had similar effects to those of alpha-linolenic acid. These results suggest that part of the mechanism of protection of the kidney by unsaturated fatty acids is through inhibition of ER stress, eIF2alpha phosphorylation and consequential reduction of CHOP protein expression and apoptotic renal cell death.

  11. On the Principle of Presumption of Innocence from the Perspective of Human Rights Protection

    Institute of Scientific and Technical Information of China (English)

    ZHU ZONGJIE

    2011-01-01

    @@ People pay more and more attention to human rights protection today.The human rights protection in the system of criminal procedure distinctly emphasizes the principle of presumptionof innocence (hereafter in this article referred to as the PPI).

  12. Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine in human immune system mice.

    Science.gov (United States)

    Li, Xiangming; Huang, Jing; Zhang, Min; Funakoshi, Ryota; Sheetij, Dutta; Spaccapelo, Roberta; Crisanti, Andrea; Nussenzweig, Victor; Nussenzweig, Ruth S; Tsuji, Moriya

    2016-08-31

    A number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic Plasmodium berghei sporozoites expressing full-length PfCSP and found that AdPfCSP-immunized (but not naïve) mice were protected against subsequent malaria challenge. The level of the HLA-A∗0201-restricted, PfCSP-specific human CD8+ T-cell response was closely correlated with the level of malaria protection. Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice almost completely abolished the anti-malaria immune response. Taken together, our data show that human CD8+ T cells mediate protective anti-malaria immunity in vivo.

  13. More Folic Acid in Pregnancy May Protect Kids from High Blood Pressure

    Science.gov (United States)

    ... Folic Acid in Pregnancy May Protect Kids From High Blood Pressure If mothers have heart disease risk factors, nutrient ... levels during pregnancy may reduce the risk of high blood pressure in children if their mothers have heart disease ...

  14. Effects of Phenolic Acids on Growth and Activities of Membrane Protective Enzymes of Cucumber Seedlings

    Institute of Scientific and Technical Information of China (English)

    WU Feng-zhi; HUANG Cai-hong; ZHAO Feng-yan

    2002-01-01

    Two phenolic acids P-hydroxy benzoic acid and cinnamic acid were designated as four concentrations (0, 50μmol/L, 100μmol/L, 150μmol/L) to investigate the effects of phenoic acids on the growth and the activities of membrane protective enzymes of cucumber seedlings. The results showed that both phenolic acids inhibited the seedlings growth. The inhibitory effects were increased with the concentration of phenolic acids increasing and the time of treatment prolonging. Seedlings treated with A150 (P-hydroxy benzoic acid, 150μmol/L), B50 (cinnamic acid, 50 μmol/L), B100 (cinnamic acid,100μmol/L), B150 (cinnamic acid, 150μmol/L) showed significantly shorter in plant height , smaller in leaf area. and lighter in fresh weight. The inhibitory effect of cinnamic acid was comparatively stronger than that of P-hydroxy benzoic acid. For protective enzymes system, compared to control, the POD activity increased at all concentrations of P-hydroxy benzoic acid during the treatment but increased at first then decreased before increased again at last at all concentrations of cinnamic acid . In the case of CAT, its activity increased at first, then decreased, and increased again at lower concentrations of phenolic acids. However, at higher concentrations the activities decreased at first, then increased a little, decreased continuously at last. In addition, the treatments of phenolic acids led to an increase then a decreaseof SOD activity and an increase of MDA content in the seedlings. All above indicated the accumulating of free radicalsand destruction of protective enzymes at higher concentrations of phenolic acids.

  15. Protective effects of arachidonic acid against palmitic acid-mediated lipotoxicity in HIT-T15 cells.

    Science.gov (United States)

    Cho, Young Sik; Kim, Chi Hyun; Kim, Ki Young; Cheon, Hyae Gyeong

    2012-05-01

    Saturated fatty acids have been considered major contributing factors in type 2 diabetes, whereas unsaturated fatty acids have beneficial effects for preventing the development of diabetes. However, the effects of polyunsaturated fatty acids in pancreatic β cells have not been reported. Here, we examined the effects of arachidonic acid (AA) on palmitic acid (PA)-mediated lipotoxicity in clonal HIT-T15 pancreatic β cells. AA prevented the PA-induced lipotoxicity as indicated by cell viability, DNA fragmentation and mitochondrial membrane potential, whereas eicosatetraynoic acid (ETYA), a non-metabolizable AA, had little effect on PA-induced lipotoxicity. In parallel with its protective effects against PA-induced lipotoxicity, AA restored impaired insulin expression and secretion induced by PA. AA but not ETYA increased intracellular triglyceride (TG) in the presence of PA compared with PA alone, and xanthohumol, a diacylglycerol acyltransferase (DGAT) inhibitor, reversed AA-induced protection from PA. Taken together, our results suggest that AA protects against PA-induced lipotoxicity in clonal HIT-T15 pancreatic β cells, and the protective effects may be associated with TG accumulation, possibly through sequestration of lipotoxic PA into TG.

  16. Monitoring Homovanillic Acid and Vanillylmandelic Acid in Human Urine by Capillary Electrophoresis with Electrochemical Detection

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A simple, rapid and low-cost method of separation and determination of homovanillic acid and vanillylmandelic acid in human urine was developed based on capillary zone electrophoresis / amperometric detection with high sensitivity and good resolution.

  17. Does foliar application of salicylic acid protects nitrate reductase and ...

    African Journals Online (AJOL)

    SAM

    2014-06-04

    Jun 4, 2014 ... spray could ameliorate the adverse effects of virus infection in two maize cultivars (maize cv. sabaini ... Salicylic acid (SA) is a component of the signal trans- ..... signal transduction pathway leading to the induction of SAR and.

  18. Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

    Institute of Scientific and Technical Information of China (English)

    Mirjana Gavella; Vaskresenija Lipovac

    2013-01-01

    This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage.The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa.Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety.The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration.The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects.In our study,we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation.The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation,thus protecting the DNA from cryopreservation-induced damage.Further actions of ganglioside micelles,which were documented by biochemical and biophysical studies,included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane.

  19. Docosahexaenoic acid, an omega-3 polyunsaturated acid protects against indomethacin-induced gastric injury.

    Science.gov (United States)

    Pineda-Peña, Elizabeth Arlen; Jiménez-Andrade, Juan Miguel; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2012-12-15

    Previous studies have shown gastroprotective effect of fish oil in several experimental models. However, the mechanisms and active compounds underlying this effect are not fully understood. Fish oil has several components; among them, one of the most studied is docosahexaenoic acid (DHA), which is an omega-3 long-chain polyunsaturated fatty acid. The aim of this study was to examine the gastroprotective effect of DHA as a pure compound in a rat model of indomethacin-induced gastric injury as well as elucidate some of the mechanism(s) behind DHA's gastroprotective effect. Indomethacin was orally administered to induce an acute gastric injury (3, 10 and 30mg/kg). Omeprazol (a proton pump inhibitor, 30mg/kg, p.o.) and DHA (3, 10, 30mg/kg, p.o.) were gavaged 30 and 120min, respectively, before indomethacin insult (30mg/kg p.o.). Three hours after indomethacin administration, rats were sacrificed, gastric injury was evaluated by determining the total damaged area. A sample of gastric tissue was harvested and processed to quantify prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) levels by enzyme-linked immunosorbent assay. Indomethacin produced gastric injury in dose-dependent manner. DHA protected against indomethacin-induced gastric damage, and this effect was comparable with omeprazol's gastroprotective effect. DHA did not reverse the indomethacin-induced reduction of PGE(2) gastric levels. In contrast, DHA partially prevented the indomethacin-induced increase in LTB(4) gastric levels. This is the first report demonstrating DHA's gastroprotective effect as a pure compound. Furthermore, the results reveal that the gastroprotective effect is mediated by a decrease in gastric LTB(4) levels in indomethacin-induced gastric damage.

  20. Avian influenza biosecurity: a key for animal and human protection

    Directory of Open Access Journals (Sweden)

    Nikolas Charisis

    2008-12-01

    Full Text Available Modern biosecurity methods have provided the best way of preventing the spread of a communicable disease since people realised that human and animal contact can transmit exotic diseases. The avian influenza virus is readily transmitted through animal vectors and inanimate matter and incurs heavy losses to the poultry industry. Biosecurity measures include the prevention of vaccination of flocks in an endemic area and the isolation of farms from the surrounding world (villages, other farms, fields, etc.. Veterinary services work in liaison with owners to implement national quarantine and vaccination measures for the benefit of farmers and the industry and for protection of public health.

  1. Multifaceted pathways protect human skin from UV radiation.

    Science.gov (United States)

    Natarajan, Vivek T; Ganju, Parul; Ramkumar, Amrita; Grover, Ritika; Gokhale, Rajesh S

    2014-07-01

    The recurrent interaction of skin with sunlight is an intrinsic constituent of human life, and exhibits both beneficial and detrimental effects. The apparent robust architectural framework of skin conceals remarkable mechanisms that operate at the interface between the surface and environment. In this Review, we discuss three distinct protective mechanisms and response pathways that safeguard skin from deleterious effects of ultraviolet (UV) radiation. The unique stratified epithelial architecture of human skin along with the antioxidant-response pathways constitutes the important defense mechanisms against UV radiation. The intricate pigmentary system and its intersection with the immune-system cytokine axis delicately balance tissue homeostasis. We discuss the relationship among these networks in the context of an unusual depigmenting disorder, vitiligo. The elaborate tunable mechanisms, elegant multilayered architecture and evolutionary selection pressures involved in skin and sunlight interaction makes this a compelling model to understand biological complexity.

  2. The gut microbiome, probiotics, bile acids axis, and human health.

    Science.gov (United States)

    Jones, Mitchell Lawrence; Tomaro-Duchesneau, Catherine; Prakash, Satya

    2014-06-01

    The human gut microbiome produces potent ligands to bile acid receptors, and probiotics could act as therapeutics of bile acid dysmetabolism. A recent study in Cell Reports demonstrates that probiotic VSL#3 affects bile acid deconjugation and excretion, as well as the gut-liver FXR-FGF15 axis.

  3. Stability of sublethal acid stress adaptaion and induced cross protection against lauric arginate in Listeria monocytogenes

    Science.gov (United States)

    The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced...

  4. A direct method for the synthesis of orthogonally protected furyl- and thienyl- amino acids.

    Science.gov (United States)

    Hudson, Alex S; Caron, Laurent; Colgin, Neil; Cobb, Steven L

    2015-04-01

    The synthesis of unnatural amino acids plays a key part in expanding the potential application of peptide-based drugs and in the total synthesis of peptide natural products. Herein, we report a direct method for the synthesis of orthogonally protected 5-membered heteroaromatic amino acids.

  5. The protective effect of salicylic acid on lysozyme against riboflavin-mediated photooxidation

    Science.gov (United States)

    Li, Kun; Wang, Hongbao; Cheng, Lingli; Zhu, Hui; Wang, Mei; Wang, Shi-Long

    2011-06-01

    As a metabolite of aspirin in vivo, salicylic acid was proved to protect lysozyme from riboflavin-mediated photooxidation in this study. The antioxidative properties of salicylic acid were further studied by using time-resolved laser flash photolysis of 355 nm. It can quench the triplet state of riboflavin via electron transfer from salicylic acid to the triplet state of riboflavin with a reaction constant of 2.25 × 10 9 M -1 s -1. Mechanism of antioxidant activities of salicylic acid on lysozyme oxidation was discussed. Salicylic acid can serve as a potential antioxidant to quench the triplet state of riboflavin and reduce oxidative pressure.

  6. Chromium-induced membrane damage: protective role of ascorbic acid

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80 - 100gbody weight). It has been observed that the intoxication with chromium ( i. p. ) at the dose of 0.8 mg/100g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospbolipid of both liver and kidney. The alkaline pbosphatase, total ATPase and Na + -K + -ATPase activities were significantly decreased in both liver and kidney after chromium treatment,except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid ( i.p. at the dose of 0.5 mg,/100g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

  7. Folic Acid Protected Neural Cells Against Aluminum-Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation.

    Science.gov (United States)

    Zhu, Mingming; Li, Bingfei; Ma, Xiao; Huang, Cong; Wu, Rui; Zhu, Weiwei; Li, Xiaoting; Liang, Zhaofeng; Deng, Feifei; Zhu, Jianyun; Xie, Wei; Yang, Xue; Jiang, Ye; Wang, Shijia; Wu, Jieshu; Geng, Shanshan; Xie, Chunfeng; Zhong, Caiyun; Liu, Haiyan

    2016-08-01

    Aluminum (Al)-induced apoptosis is considered as the major cause of its neurotoxicity. Folic acid possesses neuroprotective function by preventing neural cell apoptosis. microRNAs (miRNAs) are important regulators of gene expression participating in cellular processes. As a key component of the miR-17-92 cluster, miR-19 is implicated in regulating apoptotic process, while its role in the neuroprotective effect of folic acid has not been investigated. The present study aimed to investigate the potential involvement and function of miR-19 in the protective action of folic acid against Al-induced neural cell apoptosis. Human SH-SY5Y cells were treated with Al-maltolate (Al-malt) in the presence or absence of folic acid. Results showed that Al-malt-induced apoptosis of SH-SY5Y cells was effectively prevented by folic acid. Al-malt suppressed the expression of miR-19a/19b, along with alterations of miR-19 related apoptotic proteins including PTEN, p-AKT, p53, Bax, Bcl-2, caspase 9 and caspase 3; and these effects were ameliorated by folic acid. miR-19 inhibitor alone induced apoptosis of SH-SY5Y cells. Combination treatment of folic acid and miR-19 inhibitor diminished the neuroprotective effect of folic acid. These findings demonstrated that folic acid protected neuronal cells against Al-malt-induced apoptosis by preventing the downregulation of miR-19 and modulation of miR-19 related downstream PTEN/AKT/p53 pathway.

  8. Salvianolic acid B protects the myelin sheath around injured spinal cord axons

    OpenAIRE

    Zhe Zhu; Lu Ding; Wen-feng Qiu; Hong-fu Wu; Rui Li

    2016-01-01

    Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose w...

  9. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells.

    Science.gov (United States)

    Huff, Ryan D; Hsu, Alan C-Y; Nichol, Kristy S; Jones, Bernadette; Knight, Darryl A; Wark, Peter A B; Hansbro, Philip M; Hirota, Jeremy A

    2017-01-01

    The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines.

  10. Caffeine prevents protection in two human models of ischemic preconditioning.

    Science.gov (United States)

    Riksen, Niels P; Zhou, Zhigang; Oyen, Wim J G; Jaspers, Rogier; Ramakers, Bart P; Brouwer, Rene M H J; Boerman, Otto C; Steinmetz, Neil; Smits, Paul; Rongen, Gerard A

    2006-08-15

    We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans. Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP. In vivo ischemia-reperfusion injury was assessed in the thenar muscle by 99mTc-annexin A5 scintigraphy. Forty-two healthy volunteers performed forearm ischemic exercise. In 24 subjects, this was preceded by a stimulus for IP. In a randomized double-blinded design, the subjects received caffeine (4 mg/kg) or saline intravenously before the experiment. At reperfusion, 99mTc-annexin A5 was administered intravenously. Targeting of annexin was quantified by region-of-interest analysis, and expressed as percentage difference between experimental and contralateral hand. In vitro, we assessed recovery of contractile function of human atrial trabeculae, harvested during heart surgery, as functional end point of ischemia-reperfusion injury. Field-stimulated contraction was quantified at baseline and after simulated ischemia-reperfusion, in a paired approach with and without 5 min of IP, in the presence (n=13) or absence (n = 17) of caffeine (10 mg/l). Ischemic preconditioning reduced annexin targeting in the absence of caffeine (from 13 +/- 3% to 7 +/- 1% at 1 h, and from 19 +/- 2% to 9 +/- 3% at 4 h after reperfusion, p = 0.006), but not after caffeine administration (targeting 11 +/- 2% and 16 +/- 3% at 1 and 4 h). In vitro, IP improved post-ischemic functional recovery in the control group, but not in the caffeine group (8 +/- 3% vs. -8 +/- 5%, p=0.003). Caffeine abolishes IP in 2 human models at a dose equivalent to the drinking of 2 to 4 cups of coffee. (The Effect of Caffeine on Ischemic Preconditioning; http://clinicaltrials.gov/ct/show/NCT00184912?order=1; NCT00184912).

  11. Protective effect of boric acid on lead- and cadmium-induced genotoxicity in V79 cells.

    Science.gov (United States)

    Ustündağ, Aylin; Behm, Claudia; Föllmann, Wolfram; Duydu, Yalçin; Degen, Gisela H

    2014-06-01

    The toxic heavy metals cadmium (Cd) and lead (Pb) are important environmental pollutants which can cause serious damage to human health. As the metal ions (Cd(2+) and Pb(2+)) accumulate in the organism, there is special concern regarding chronic toxicity and damage to the genetic material. Metal-induced genotoxicity has been attributed to indirect mechanisms, such as induction of oxidative stress and interference with DNA repair. Boron is a naturally occurring element and considered to be an essential micronutrient, although the cellular activities of boron compounds remain largely unexplored. The present study has been conducted to evaluate potential protective effects of boric acid (BA) against genotoxicity induced by cadmium chloride (CdCl2) and lead chloride (PbCl2) in V79 cell cultures. Cytotoxicity assays (neutral red uptake and cell titer blue assay) served to determine suitable concentrations for subsequent genotoxicity assays. Chromosomal damage and DNA strand breaks were assessed by micronucleus tests and comet assays. Both PbCl2 and CdCl2 (at 3, 5 and 10 µM) were shown to induce concentration-dependent increases in micronucleus frequencies and DNA strand breaks in V79 cells. BA itself was not cytotoxic (up to 300 µM) and showed no genotoxic effects. Pretreatment of cells with low levels of BA (2.5 and 10 µM) was found to strongly reduce the genotoxic effects of the tested metals. Based on the findings of this in vitro study, it can be suggested that boron provides an efficient protection against the induction of DNA strand breaks and micronuclei by lead and cadmium. Further studies on the underlying mechanisms for the protective effect of boron are needed.

  12. Fatal Folic Acid Toxicity in Humans.

    Science.gov (United States)

    Devnath, Gerard Pradeep; Kumaran, Senthil; Rajiv, R; Shaha, Kusa Kumar; Nagaraj, Ashok

    2017-03-06

    Folic acid is B-9 vitamin. Folic acid is prescribed commonly for pregnant women to prevent neural tube defects in the fetus, patients under chemotherapy, pernicious anemia and to reduce the risk of stroke and cardiovascular disease. Acute or chronic ingestion of a large dose of folic acid generally manifests as neurological complications, which are reversible. In this present case, a 23-year-old pregnant woman committed suicide by consuming folic acid tablets and succumbed to death within 36 h. Postmortem toxicological analysis detected folic acid in viscera. Death following acute consumption of folic acid is rare and has been not reported in the literature, to the best of our knowledge. © 2017 American Academy of Forensic Sciences.

  13. Stability of sublethal acid stress adaptation and induced cross protection against lauric arginate in Listeria monocytogenes.

    Science.gov (United States)

    Shen, Qian; Soni, Kamlesh A; Nannapaneni, Ramakrishna

    2015-06-16

    The stability of acid stress adaptation in Listeria monocytogenes and its induced cross protection effect against GRAS (generally recognized as safe) antimicrobial compounds has never been investigated before. In the present study, the acid stress adaptation in L. monocytogenes was initially induced in pH 5.0 tryptic soy broth supplemented with 0.6% yeast extract (TSB-YE) at 37 °C. Subsequently, the stability of acid stress adaptation, which was defined as the capacity to maintain its acquired acid adaptation after induction in the absence of sublethal acid stress, was determined at 37 °C, 22 °C or 4 °C in broth and in different food substrates. Then, the acid stress adaptation induced cross protection against lauric arginate (LAE) and its stability was investigated in TSB-YE, milk and carrot juice. Our findings show that the acid stress adaptation was stable at 4 °C up to 24h but was reversed at 37 °C or 22 °C within 2h. In the cross protection assay with LAE, the acid stress adapted cells had approximately 2 log CFU/ml greater survival than non-adapted cells in broth at 22 °C or in milk and carrot juice at 4 °C. The acid adaptation induced cross protection against LAE in L. monocytogenes was reversible within 1h at 4 °C in the absence of sublethal acid stress. Our findings suggest that the stability of acid adaptation in L. monocytogenes under cold conditions should be taken into account when the risk analysis is performed during food processing.

  14. Protective effect of folic acid and vitamin B12 on human neuroblastoma cell line SH-SY5Y cells%叶酸和维生素B12对人神经母细胞瘤株SH-SY5Y细胞的保护作用

    Institute of Scientific and Technical Information of China (English)

    张景燕; 陈娟; 王蓉; 赵静姝; 吴燕川

    2012-01-01

    Objective To observe the protective effect of folic acid and vitamin B12 on human nenroblastoma cell line SH-SY5Y cell growth in vitro. Methods SH-SY5Y cells cultured in vitro, divided into control group, the folic acid( 1. 875 mg/L) group, vitamin B12 (800 μg/L) group, folic acid ( 1. 875 mg/L) + vitamin B12(800 μg/L) group. Cell morphology, cell count analysis, thiazolyl blue (MTT) metabolic rate, and lactate dehydrogenase(LDH) leakage rate of each group were detected. Results Compared with the control group, cell count and MTT metabolic rate of folic acid group, vitamin B12 group, folic acid+vitamin B12 group increased(P<0. 05) , and LDH leakage rate decreased(P<0. 05). Compared with the control group, cell morphology were much better in those groups, cell body more plump, the number of surviving cells increased, adherence was good and neurite extension could be found. Conclusion Folic acid and vitamin B12 can promote nerve cell growth, reduce nerve cell death, in order to achieve the protection of neurons.%目的 通过观察叶酸和维生素B12对人神经母细胞瘤株SH-SY5Y细胞生长的影响,探讨叶酸和维生素B12对神经细胞的保护作用.方法 体外培养SH-SY5Y细胞,分为对照组、叶酸组(1.875 mg/L)、维生素B12组(800 μg/L)、叶酸(1.875 mg/L)+维生素B12(800 μg/L)组,进行细胞形态观察、细胞计数分析以及测定各组细胞的噻唑蓝(thiazolyl blue,MTT)代谢率、乳酸脱氢酶(lactate dehydrogenase,LDH)漏出率.结果 与对照组相比,叶酸组、维生素B12组、叶酸+维生素B12组的细胞计数和MTT代谢率升高(P<0.05),LDH漏出率降低(P<0.05),在细胞形态上,叶酸组、维生素B12组、叶酸+维生素B12组明显好于对照组,表现为细胞胞体饱满、存活细胞数目增多、贴壁良好、突起延长.结论 叶酸、维生素B12能促进神经细胞生长,降低神经细胞死亡率,从而达到保护神经元的作用.

  15. Human subjects protection issues in QUERI implementation research: QUERI Series

    Directory of Open Access Journals (Sweden)

    Ritchie Mona

    2008-02-01

    Full Text Available Abstract Background Human Subjects protections approaches, specifically those relating to research review board oversight, vary throughout the world. While all are designed to protect participants involved in research, the structure and specifics of these institutional review boards (IRBs can and do differ. This variation affects all types of research, particularly implementation research. Methods In 2001, we began a series of inter-related studies on implementing evidence-based collaborative care for depression in Veterans Health Administration primary care. We have submitted more than 100 IRB applications, amendments, and renewals, and in doing so, we have interacted with 13 VA and University IRBs across the United States (U.S.. We present four overarching IRB-related themes encountered throughout the implementation of our projects, and within each theme, identify key challenges and suggest approaches that have proved useful. Where applicable, we showcase process aids developed to assist in resolving a particular IRB challenge. Results There are issues unique to implementation research, as this type of research may not fit within the traditional Human Subjects paradigm used to assess clinical trials. Risks in implementation research are generally related to breaches of confidentiality, rather than health risks associated with traditional clinical trials. The implementation-specific challenges discussed are: external validity considerations, Plan-Do-Study-Act cycles, risk-benefit issues, the multiple roles of researchers and subjects, and system-level unit of analysis. Discussion Specific aspects of implementation research interact with variations in knowledge, procedures, and regulatory interpretations across IRBs to affect the implementation and study of best methods to increase evidence-based practice. Through lack of unambiguous guidelines and local liability concerns, IRBs are often at risk of applying both variable and inappropriate or

  16. [Human habitats and the protection of health in Islam].

    Science.gov (United States)

    Hadrović, A

    1997-01-01

    Architecture is an expression so wide in its dimensions and meanings, that it can be compared to expression "life". Architecture is a synthesis and an expression of all rational and irrational that attributes a man, family, community in general, or mankind at all-im one hand; and rational expression of physical structure given by architects, in other hand. Thus, architecture comes down from the highest spheres of philosophy, sociology, discussions on ethics etc., to life. That is the way how architecture becomes defining frame of human life. Human habitude and health protection in islam could be elaborated through theoretical concept of architecturally defined space (ADS), that considers (treats) architecture as a complex system, consisting of four fundamental elements: man, environment, limits and perspectives. Each of these elements, when looking from the perspective of islam, has its specific characteristics, that author discusses in this paper. No doubt, in islamic sphere of life there is a wide spectrum of architectural programmes, that follows natural environment, and has a goal to confirm human and general social values.

  17. Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

    Directory of Open Access Journals (Sweden)

    José J. Gaforio

    2011-10-01

    Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  18. Hydroxytyrosol protects against oxidative DNA damage in human breast cells.

    Science.gov (United States)

    Warleta, Fernando; Quesada, Cristina Sánchez; Campos, María; Allouche, Yosra; Beltrán, Gabriel; Gaforio, José J

    2011-10-01

    Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol's effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A) or breast cancer cells (MDA-MB-231 and MCF7). We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS) level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

  19. 2-Pyridinyl-N-(2,4-difluorobenzyl)aminoethyl Group As Thermocontrolled Implement for Protection of Carboxylic Acids.

    Science.gov (United States)

    Brzezinska, Jolanta; Witkowska, Agnieszka; Bałabańska, Sandra; Chmielewski, Marcin K

    2016-07-01

    A thermolabile protecting group strategy for carboxylic acids is expanded. Thermosensitive esters are readily prepared using a known procedure, and their stability under neutral condition is investigated. Effective thermolytic deprotection initiated only by temperature for different carboxylic acids is demonstrated, and the compatibility of a thermolytic protecting group with acidic and basic protecting groups in an orthogonal protection strategy is also presented. This study showed interesting correlations between the pKa of acids and the deprotection rate of their well-protected moieties.

  20. Scutellaria radix Extract as a Natural UV Protectant for Human Skin.

    Science.gov (United States)

    Seok, Jin Kyung; Kwak, Jun Yup; Choi, Go Woon; An, Sang Mi; Kwak, Jae-Hoon; Seo, Hyeong-Ho; Suh, Hwa-Jin; Boo, Yong Chool

    2016-03-01

    Ultraviolet (UV) radiation induces oxidative injury and inflammation in human skin. Scutellaria radix (SR, the root of Scutellaria baicalensis Georgi) contains flavonoids with high UV absorptivity and antioxidant properties. The purpose of this study was to examine the potential use of SR extract as an additive in cosmetic products for UV protection. SR extract and its butanol (BuOH) fraction strongly absorbed UV radiation and displayed free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radials and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals. They also attenuated the UV-induced death of HaCaT cells. Sunscreen creams, with or without supplementation of SR extract BuOH fraction, were tested in vivo in human trials to evaluate potential skin irritation and determine the sun protection factor (SPF). Both sunscreen creams induced no skin irritation. A sunscreen cream containing 24% ZnO showed an SPF value of 17.8, and it increased to 22.7 when supplemented with 5% SR extract BuOH fraction. This study suggests that SR-derived materials are useful as safe cosmetic additives that provide UV protection.

  1. Protection of 2024-T3 aluminium alloy by corrosion resistant phytic acid conversion coating

    Science.gov (United States)

    Shi, Hongwei; Han, En-Hou; Liu, Fuchun; Kallip, Silvar

    2013-09-01

    The corrosion protection properties of environmentally friendly phytic acid conversion coatings were studied on 2024-T3 aluminium alloy. The films were prepared under acidic conditions with various pH values and characterised by SEM, EDS, ATR-FTIR and electrochemical techniques. The results indicate that the conversion coatings obtained by immersing the alloy in phytic acid solutions at pH from 3 to 5.5 provide excellent corrosion resistance. ATR-FTIR confirms that the film is formed by deposition of reaction products between Al3+ and phosphate groups in phytic acid molecules. The conformation models of the deposition film are proposed.

  2. Does biodiversity protect humans against infectious disease? Reply

    Science.gov (United States)

    Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

    2016-01-01

    The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

  3. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

    Science.gov (United States)

    Turamanlar, Ozan; Özen, Oğuz Aslan; Songur, Ahmet; Yağmurca, Murat; Akçer, Sezer; Mollaoğlu, Hakan; Aktaş, Cevat

    2015-01-01

    Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250–300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were

  4. Protective effect of hyaluronic acid on cryopreserved boar sperm.

    Science.gov (United States)

    Qian, Li; Yu, Sijiu; Zhou, Yan

    2016-06-01

    This study aimed to evaluate the effects of supplementing freezing and thawing media with hyaluronic acid (HA) on the quality parameters of frozen-thawed boar spermatozoa. Boar semen samples were collected from seven mature Yorkshire boars once a week using the gloved hand technique; these samples were frozen-thawed in the extender with added HA. Boar sperm was cryopreserved in the extender with HA added at concentrations of 0 (used as control), 4, 6, 8, 8 and 12mg/L, and their effects on the quality of frozen-thawed boar sperm were evaluated. HA addition to the extender significantly improved sperm motility, sperm membrane integrity, mitochondrial activity, acrosomal integrity, superoxide dismutase and catalase activity, but decreased sperm malondialdehyde level (pboar sperm.

  5. Multiple changes in sialic acid biology during human evolution.

    Science.gov (United States)

    Varki, Ajit

    2009-04-01

    Humans are genetically very similar to "great apes", (chimpanzees, bonobos, gorillas and orangutans), our closest evolutionary relatives. We have discovered multiple genetic and biochemical differences between humans and these other hominids, in relation to sialic acids and in Siglecs (Sia-recognizing Ig superfamily lectins). An inactivating mutation in the CMAH gene eliminated human expression of N-glycolylneuraminic acid (Neu5Gc) a major sialic acid in "great apes". Additional human-specific changes have been found, affecting at least 10 of the dietary sources, particularly red meat and milk products. As humans also have varying and sometime high levels of circulating anti-Neu5Gc antibodies, there are implications for biotechnology products, and for some human diseases associated with chronic inflammation.

  6. Protective effects of nonionic tri-block copolymers on bile acid-mediated epithelial barrier disruption.

    Energy Technology Data Exchange (ETDEWEB)

    Edelstein, A.; Fink, D.; Musch, M.; Valuckaite, V.; Zabornia, O.; Grubjesic, S.; Firestone, M. A.; Matthews, J. B.; Alverdy, J. C. (Materials Science Division); (Univ. of Chicago)

    2011-11-01

    Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate on Caco-2 enterocyte monolayers using transepithelial electrical resistance to assay barrier function. A bisphenol A coupled triblock polyethylene glycol (PEG), PEG 15-20, was shown to prevent sodium deoxycholate-induced barrier failure. Enzyme-linked immunosorbent assay, lactate dehydrogenase, and caspase 3-based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens 1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weight greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia.

  7. Prefibrillar Tau oligomers alter the nucleic acid protective function of Tau in hippocampal neurons in vivo.

    Science.gov (United States)

    Violet, Marie; Chauderlier, Alban; Delattre, Lucie; Tardivel, Meryem; Chouala, Meliza Sendid; Sultan, Audrey; Marciniak, Elodie; Humez, Sandrine; Binder, Lester; Kayed, Rakez; Lefebvre, Bruno; Bonnefoy, Eliette; Buée, Luc; Galas, Marie-Christine

    2015-10-01

    The accumulation of DNA and RNA oxidative damage is observed in cortical and hippocampal neurons from Alzheimer's disease (AD) brains at early stages of pathology. We recently reported that Tau is a key nuclear player in the protection of neuronal nucleic acid integrity in vivo under physiological conditions and hyperthermia, a strong inducer of oxidative stress. In a mouse model of tauopathy (THY-Tau22), we demonstrate that hyperthermia selectively induces nucleic acid oxidative damage and nucleic acid strand breaks in the nucleus and cytoplasm of hippocampal neurons that display early Tau phosphorylation but no Tau fibrils. Nucleic acid-damaged neurons were exclusively immunoreactive for prefibrillar Tau oligomers. A similar association between prefibrillar Tau oligomers and nucleic acid oxidative damage was observed in AD brains. Pretreatment with Methylene Blue (MB), a Tau aggregation inhibitor and a redox cycler, reduced hyperthermia-induced Tau oligomerization as well as nucleic acid damage. This study clearly highlights the existence of an early and critical time frame for hyperthermia-induced Tau oligomerization, which most likely occurs through increased oxidative stress, and nucleic acid vulnerability during the progression of Tau pathology. These results suggest that at early stages of AD, Tau oligomerization triggers the loss of the nucleic acid protective function of monomeric Tau. This study highlights the existence of a short therapeutic window in which to prevent the formation of pathological forms of Tau and their harmful consequences on nucleic acid integrity during the progression of Tau pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

    Science.gov (United States)

    PLASMID DNA DAMAGE CAOUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITINABSTRACT Both dimethylarsinic acid (DMA(V)) and dimethylarsinous acid (DMA(III)) release iron from human liver ferritin (HLF) with or without the presence of ascorbic acid. ...

  9. Combination of chlorogenic acid and salvianolic acid B protects against polychlorinated biphenyls-induced oxidative stress through Nrf2.

    Science.gov (United States)

    Chen, Lijun; Li, Yuan; Yin, Wenqin; Shan, Wenqi; Dai, Jinfeng; Yang, Ye; Li, Lei

    2016-09-01

    Caffeic acid derivatives (CADs) are well-known phytochemicals with multiple physiological and pharmacological activities. This study aimed to investigate the combined protective effects of CADs on PCB126-induced liver damages and oxidative stress in mice. Here, we used chemiluminescence and chose chlorogenic acid (CGA), salvianolic acid B (Sal B) as the best antioxidants. Then, mice were intragastrically administered with 60mg/kg/d CGA, Sal B, and CGA plus Sal B (1:1) for 3 weeks before exposing to 0.05mg/kg/d PCB126 for 2 weeks. We found that pretreatment with CGA, Sal B, and CGA plus Sal B effectively attenuated liver injury and cytotoxicity caused by PCB126, but improved the expressions of superoxide dismutase (SOD), glutathione reduced (GSH), heme oxygenase-1 (HO-1) and nuclear factor E2-related factor 2 (Nrf2), CGA plus Sal B especially, was found to have the best effects that indicated a synergetic protective effect. Taken together, as the Nrf2 regulates the cyto-protective response by up-regulating the expression of antioxidant genes, we suggested that CGA plus Sal B had a combined protection on PCB126-induced tissue damages and that the Nrf2 signaling might be involved.

  10. Protective effect of hawthorn extract against genotoxicity induced by methyl methanesulfonate in human lymphocytes.

    Science.gov (United States)

    Hosseinimehr, Seyed Jalal; Azadbakht, Mohammad; Tanha, Mohammad; Mahmodzadeh, Aziz; Mohammadifar, Sohila

    2011-05-01

    The preventive effect of hawthorn (Crataegus microphylla) fruit extract against genotoxicity induced by methyl methanesulfonate (MMS) has been investigated in human cultured blood lymphocytes. Peripheral blood samples were collected from human volunteers at 0 (10 minutes before), and at 1 and 2 hours after a single oral ingestion of 1 g hawthorn powder extract. At each time point, the whole blood was treated in vitro with MMS (200 µmol) at 24 hours after cell culture, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cells. The lymphocytes treated with hawthorn and MMS to exhibit a significant decreasing in the incidence of micronucleated binucleated cells, as compared with similarly MMS-treated lymphocytes from blood samples collected at 0 hour. The maximum protection and decreasing in frequency of micronuclei (36%) was observed at 1 hour after ingestion of hawthorn extract. The high performance liquid chromatography (HPLC) analysis showed that hawthorn contained chlorogenic acid, epicatechin and hyperoside. It is obvious that hawthorn, particularly flavonoids constituents with antioxidative activity, reduced the oxidative stress and genotoxicity induced by toxic compounds. This set of data may have an important application for the protection of human lymphocyte from the genetic damage and side effects induced by chemicals hazardous in people.

  11. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

    NARCIS (Netherlands)

    Rhodes, L.E.; Shahbakhti, H.; Azurdia, R.M.; Moison, R.M.W.; Steenwinkel, M.J.S.T.; Homburg, M.I.; Dean, M.P.; McArdle, F.; Beijersbergen van Henegouwen, G.M.J.; Epe, B.; Vink, A.A.

    2003-01-01

    Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although ω-3 PUFAs may influence oxidative stress. We examined the effect of

  12. Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers

    NARCIS (Netherlands)

    Rhodes, L.E.; Shahbakhti, H.; Azurdia, R.M.; Moison, R.M.W.; Steenwinkel, M.J.S.T.; Homburg, M.I.; Dean, M.P.; McArdle, F.; Beijersbergen van Henegouwen, G.M.J.; Epe, B.; Vink, A.A.

    2003-01-01

    Dietary omega-3 polyunsaturated fatty acids (ω-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although ω-3 PUFAs may influence oxidative stress. We examined the effect of supplementatio

  13. Acetylsalicylic acid protects erectile function in diabetic rats.

    Science.gov (United States)

    Hafez, G; Gonulalan, U; Kosan, M; Arioglu, E; Ozturk, B; Cetinkaya, M; Gur, S

    2014-01-01

    We aimed to evaluate the effect of acetylsalicylic acid (ASA) treatment on diabetes-induced erectile dysfunction. Adult male Sprague-Dawley rats were divided into four groups as follows: (i) control (C), (ii) diabetic (D), (iii) ASA-treated control (C+ASA) and (iv) ASA-treated diabetic (D+ASA) groups. In groups 2 and 4, diabetes was induced by injection of 35 mg kg(-1) streptozotocin. ASA (100 mg kg(-1) day(-1) , orally) was administrated to rats in groups 3 and 4 for 8 weeks. Both intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) were measured in in vivo studies. In organ bath, the relaxation responses to acetylcholine (ACh), electrical field stimulation (EFS) and sodium nitroprusside were tested in corpus cavernosum (CC) strips. The mRNA expression for neuronal nitric oxide synthase (nNOS) was calculated using reverse transcription polymerase chain reaction technique. In in vivo experiments, diabetic rats displayed reduced ICP/MAP values, which were normalised with ASA treatment. The relaxant response to high-dose ACh and EFS at low frequencies (1-8 Hz) in CC strips from the D+ASA group were significantly higher when compared to the D group. Treatment with ASA normalised the raised mRNA expressions of nNOS in diabetic penile tissues. ASA may be involved in mRNA of protein synthesis of NO released from nonadrenergic and noncholinergic cavernosal nerve in diabetes.

  14. Incorporation and distribution of dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid in cultured human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1986-02-01

    Human keratinocytes in culture were labelled with /sup 14/C-dihomo-gamma-linolenic acid, /sup 14/C-arachidonic acid or /sup 14/C-eicosapentaenoic acid. All three eicosanoid precursor fatty acids were effectively incorporated into the cells. In phospholipids most of the radioactivity was recovered, in neutral lipids a substantial amount, and as free unesterified fatty acids only a minor amount. Most of the radioactivity was found in phosphatidylethanolamine which was also the major phospholipid as measured by phosphorous assay. The incorporation of dihomo-gamma-linolenic acid and arachidonic acid into lipid subfractions was essentially similar. Eicosapentaenoic acid was, however, much less effectively incorporated into phosphatidylinositol + phosphatidylserine and, correspondingly, more effectively into triacylglycerols as compared to the two other precursor fatty acids. Once incorporated, the distribution of all three precursor fatty acids was relatively stable, and only minor amounts of fatty acids were released into the culture medium during short term culture (two days). Our study demonstrates that eicosanoid precursor fatty acids are avidly taken up by human keratinocytes and esterified into membrane lipids. The clinical implication of this finding is that dietary manipulations might be employed to cause changes in the fatty acid composition of keratinocytes.

  15. Gold Nanoparticles Protected with Thiol-Derivatized Amphiphilic Poly( -caprolactone)-b-poly(acrylic acid)

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Hvilsted, Søren

    2008-01-01

    Amphiphilic poly(c-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) bearing thiol functionality at the PCL terminal has been synthesized by a combination of ring-opening polymerization (ROP) of c-caprolactone (c-CL), esterification of hydroxy chain end with protected mercaptoacetic acid, subsequ......Amphiphilic poly(c-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) bearing thiol functionality at the PCL terminal has been synthesized by a combination of ring-opening polymerization (ROP) of c-caprolactone (c-CL), esterification of hydroxy chain end with protected mercaptoacetic acid......, subsequent chain-extension by atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBA), and final deprotection steps. ROP of c-CL initiated by 2-hydroxyethyl 2-bromoisobutyrate, and catalysed by tin octoate afforded Br-PCL-OH with the degree of polymerization of 30 and narrow molecular weight...

  16. Rapid Extraction of Human DNA Containing Humic Acid

    OpenAIRE

    Sutlović, Davorka; Definis Gojanović, Marija; Anđelinović, Šimun

    2007-01-01

    The identification process of dead bodies or human remains is nowadays conducted in numerous fields of forensic science, archeology and other judicial cases. A particular problem is the isolation and DNA typing of human remains found in mass graves, due to the degradation process, as well as post mortal DNA contamination with bacteria, fungi, humic acids, metals, etc. In this study, the influence of humic acid (HA) on the DNA extraction and typing is investigated. If present in...

  17. Ascorbic Acid Efflux from Human Brain Microvascular Pericytes: Role of Re-uptake

    OpenAIRE

    May, James M.; Qu, Zhi-chao

    2015-01-01

    Microvascular pericytes take up ascorbic acid on the ascorbate transporter SVCT2. Intracellular ascorbate then protects the cells against apoptosis induced by culture at diabetic glucose concentrations. To investigate whether pericytes might also provide ascorbate to the underlying endothelial cells, we studied ascorbate efflux from human pericytes. When loaded with ascorbate to intracellular concentrations of 0.8–1.0 mM, almost two-thirds of intracellular ascorbate effluxed from the cells ov...

  18. Effects of Salvianolic Acid B on Protein Expression in Human Umbilical Vein Endothelial Cells

    OpenAIRE

    Tsong-Min Chang; Guey-Yueh Shi; Hua-Lin Wu; Chieh-Hsi Wu; Yan-Di Su; Hui-Lin Wang; Hsin-Yun Wen; Huey-Chun Huang

    2011-01-01

    Salvianolic acid B (Sal B), a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothe...

  19. Advances on human milk hormones and protection against obesity.

    Science.gov (United States)

    Savino, F; Benetti, S; Liguori, S A; Sorrenti, M; Cordero Di Montezemolo, L

    2013-11-03

    Extensive research shows that breast milk could have positive health effects not limited to infancy, but extend into childhood and adulthood. Recently many studies have provided new evidence on the long—term positive effects of breastfeeding, in particular protection against obesity and type 2 diabetes, suggesting that breast milk may have a role in the programming of later metabolic diseases. The mechanism throughout breastfeeding that exerts these effects has been a major focus of interest for researchers and it is still not completely known. There are some hints for biological plausibility of beneficial effects of breastfeeding including macronutrient intake, hormonal and behavioural mechanisms related to breast milk composition. Breast milk biochemical components, such as protein quantity and quality, polyunsaturated fatty acids, oligosaccharides, cytokines and hormones, in particular leptin, adiponectin and resistin together with the breastfeeding practice itself can influence infants feeding behaviour and regulation of growth and appetite control later in life. Further research is needed to confirm the possibility that hormones present in breast milk exert a metabolic and beneficial effects.

  20. Gold Nanoparticles Protected with Thiol-Derivatized Amphiphilic Poly( -caprolactone)-b-poly(acrylic acid)

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Hvilsted, Søren

    2008-01-01

    Amphiphilic poly(c-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) bearing thiol functionality at the PCL terminal has been synthesized by a combination of ring-opening polymerization (ROP) of c-caprolactone (c-CL), esterification of hydroxy chain end with protected mercaptoacetic acid, subsequ....... As a result stable, aggregation-free nanopaticles with moderate dispersity as estimated from UV-visible spectroscopy and transmission electron microscopy (TEM) data were obtained....

  1. Cleavage and protection of locked nucleic acid-modified DNA by restriction endonucleases

    DEFF Research Database (Denmark)

    Crouzier, Lucile; Dubois, Camille; Wengel, Jesper;

    2012-01-01

    Locked nucleic acid (LNA) is one of the most prominent nucleic acid analogues reported so far. We herein for the first time report cleavage by restriction endonuclease of LNA-modified DNA oligonucleotides. The experiments revealed that RsaI is an efficient enzyme capable of recognizing and cleaving...... LNA-modified DNA oligonucleotides. Furthermore, introduction of LNA nucleotides protects against cleavage by the restriction endonucleases PvuII, PstI, SacI, KpnI and EcoRI....

  2. Folic acid supplementation during pregnancy protects against lipopolysaccharide-induced neural tube defects in mice.

    Science.gov (United States)

    Zhao, Mei; Chen, Yuan-Hua; Chen, Xue; Dong, Xu-Ting; Zhou, Jun; Wang, Hua; Wu, Shu-Xian; Zhang, Cheng; Xu, De-Xiang

    2014-01-13

    Folic acid is a water-soluble B-complex vitamin. Increasing evidence demonstrates that physiological supply of folic acid during pregnancy prevents folic acid deficiency-related neural tube defects (NTDs). Previous studies showed that maternal lipopolysaccharide (LPS) exposure caused NTDs in rodents. The aim of this study was to investigate the effects of high-dose folic acid supplementation during pregnancy on LPS-induced NTDs. Pregnant mice were intraperitoneally injected with LPS (20 μg/kg/d) from gestational day (GD) 8 to GD12. As expected, a five-day LPS injection resulted in 19.96% of fetuses with NTDs. Interestingly, supplementation with folic acid (3mg/kg/d) during pregnancy significantly alleviated LPS-induced NTDs. Additionally, folic acid significantly attenuated LPS-induced fetal growth restriction and skeletal malformations. Additional experiment showed that folic acid attenuated LPS-induced glutathione (GSH) depletion in maternal liver and placentas. Moreover, folic acid significantly attenuated LPS-induced expression of placental MyD88. Additionally, folic acid inhibited LPS-induced c-Jun NH2-terminal kinase (JNK) phosphorylation and nuclear factor kappa B (NF-κB) activation in placentas. Correspondingly, folic acid significantly attenuated LPS-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in placentas, maternal serum and amniotic fluid. In conclusion, supplementation with high-dose folic acid during pregnancy protects against LPS-induced NTDs through its anti-inflammatory and anti-oxidative effects.

  3. Protection against cisplatin-induced nephrotoxicity by recombinant human erythropoietin.

    Science.gov (United States)

    Yalcin, Suayib; Müftüoğlu, Sevda; Cetin, Eren; Sarer, Banu; Yildirim, Berna Akkuş; Zeybek, Dilara; Orhan, Bülent

    2003-01-01

    Cisplatin (CDDP) is a potent nephrotoxin, and nephrotoxicity is its most important dose-limiting toxicity. In this study, we aimed to investigate the role of recombinant human erythropoietin (rhEPO) in the protection of cisplatin-induced nephrotoxicity and compare its efficacy with the cell-protective agent amifostine. All experiments were conducted on female Wistar albino rats. Animals were randomly assigned to four groups, each including six rats. Group A received only CDDP, group B received CDDP plus rhEPO, group C received CDDP plus amifostine, and group D received only rhEPO. At the end of 7 wk, hemoglobin (Hgb), hematocrite (Htc), blood urea nitrogen (BUN), and creatinine (Cr) levels were determined and kidneys of the rats were removed. The weights of the kidneys were measured and sent for histopathological examination. Proximal tubules from four areas of the kidney (outer cortex, inner cortex, the medullary ray, and outer stripe of outer medulla [OSOM]) were evaluated. There were statistically significant differences among the groups in terms of tubular scores, including overall renal tubular score, cortex, inner cortex, OSOM, and medullary ray tubular scores, and Htc levels. Group A rats had the worse tubular scores in all categories when compared to group D rats. When the results of groups B and C were compared, there were no differences in terms of BUN, Cr levels, and tubular scores, but the Htc level was significantly higher in group B. Group B rats had better overall and OSOM tubular scores when compared to group A. Group C also had better overall and OSOM tubular scores compared to group A. The present study showed for the first time that rhEPO plays an important role in the prevention of cisplatin-induced nephrotoxicity and it is as effective as amifostine.

  4. Synthesis of protected (2S,4R)-2-amino-4-methyldecanoic acid, a proposed component of culicinins

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Tian Tian Sun; Duo Mei; Jun Fei Wang; Ying Xia Li

    2008-01-01

    The protected (2S,4R)-2-amino-4-methyldecanoic acid, a proposed component of culicinins has been synthesized over 10 steps and in total 28% yields using Wittig reaction and Schollkopf amino acid synthesis as key steps.

  5. Asiatic acid attenuates malignancy of human metastatic ovarian ...

    African Journals Online (AJOL)

    Methods: Human metastatic ovarian cancer cell line SKOV-3 was treated with various concentrations of asiatic acid for 24 and ... cancer [5], breast cancer [6], melanoma [7], ..... in human keloid fibroblasts via PPAR-gamma activation. Int J Biol ...

  6. Chemical and fatty acids composition of rump cap from young bulls fed protected or unprotected oils

    Directory of Open Access Journals (Sweden)

    Emanuel Almeida de Oliveira

    2015-10-01

    Full Text Available Strategies to improve the nutritional aspects of beef, mainly the fatty acids composition, have become an important goal to the scientific community. The use of different oils sources could be an interesting device due its polyunsaturated fatty acids composition. The chemical and fatty acid composition of rump cap (Biceps femoris from 35 Nellore young bulls finished at feedlot (96 days were analyzed. These animals were fed a control diet with sugar cane and concentrate without oil or diets containing sugar cane and concentrate with different sources of oil (soybean or linseed, protected or not from ruminal degradation. A randomized block design was adopted with five treatments and seven replications. The means were compared using orthogonal contrasts at 0.05 significance level. Animals fed diets with oil showed higher levels (P<0.05 of protein and lower levels (P<0.05 of ash than control diet. Lower cholesterol (P<0.05 levels resulted from linseed oil added treatment compared to soybean oil (37.70 and 43.80 mg/100 g, respectively; on the other hand, cholesterol levels increased (P<0.05 for protected oils compared to non-protected (44.53 and 33.97 mg/100 g. Oil added diets resulted in higher (P<0.05 linolenic acid levels. Linseed oil increased (P<0.05 the levels of the fatty acids C14:1, C16:1 and C18:1 n9. Addition of linseed oil, whether protected or not, to the animal diets improves the fatty acid composition of the rump cap by increasing the amount of omega-3 fatty acids and improving the omega-6:omega-3 ratio.

  7. Photolabile protection for amino acids: studies on the release from novel benzoquinolone cages.

    Science.gov (United States)

    Fonseca, Andrea S C; Soares, Ana M S; Gonçalves, M Sameiro T; Costa, Susana P G

    2015-12-01

    The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson's reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 min).

  8. Salivary a-amylase protects enamel surface against acid induced softening

    DEFF Research Database (Denmark)

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend

    Objectives: Recently we have demonstrated individual differences in protection against acid-induced enamel softening offered by experimentally developed saliva pellicles. Although ethnicity seemed to be related to protection level, the saliva proteins responsible for the differences were not iden......Objectives: Recently we have demonstrated individual differences in protection against acid-induced enamel softening offered by experimentally developed saliva pellicles. Although ethnicity seemed to be related to protection level, the saliva proteins responsible for the differences were......, and one Chinese. After collection, saliva was dialysed and lyophilised and re-dissolved at 0.5% in Type I water. Next, four polished bovine enamel specimens were immersed into each sample under gentle and constant shaking for 12 hours. Last, specimens were exposed to an erosive challenge of pH 2.3 for 4......-TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had...

  9. A novel web server predicts amino acid residue protection against hydrogen-deuterium exchange.

    Science.gov (United States)

    Lobanov, Mikhail Yu; Suvorina, Masha Yu; Dovidchenko, Nikita V; Sokolovskiy, Igor V; Surin, Alexey K; Galzitskaya, Oxana V

    2013-06-01

    To clarify the relationship between structural elements and polypeptide chain mobility, a set of statistical analyses of structures is necessary. Because at present proteins with determined spatial structures are much less numerous than those with amino acid sequence known, it is important to be able to predict the extent of proton protection from hydrogen-deuterium (HD) exchange basing solely on the protein primary structure. Here we present a novel web server aimed to predict the degree of amino acid residue protection against HD exchange solely from the primary structure of the protein chain under study. On the basis of the amino acid sequence, the presented server offers the following three possibilities (predictors) for user's choice. First, prediction of the number of contacts occurring in this protein, which is shown to be helpful in estimating the number of protons protected against HD exchange (sensitivity 0.71). Second, probability of H-bonding in this protein, which is useful for finding the number of unprotected protons (specificity 0.71). The last is the use of an artificial predictor. Also, we report on mass spectrometry analysis of HD exchange that has been first applied to free amino acids. Its results showed a good agreement with theoretical data (number of protons) for 10 globular proteins (correlation coefficient 0.73). We pioneered in compiling two datasets of experimental HD exchange data for 35 proteins. The H-Protection server is available for users at http://bioinfo.protres.ru/ogp/ Supplementary data are available at Bioinformatics online.

  10. Can folic acid protect against congenital heart defects in Down syndrome?

    NARCIS (Netherlands)

    Meijer, Willemijn M.; Werler, Martha M.; Louik, Carol; Hernandez-Diaz, Sonia; de Jong-van den Berg, Lolkje T. W.; Mitchell, Allen A.

    2006-01-01

    BACKGROUND: Several studies have suggested a protective effect of folic acid (FA) on congenital heart anomalies. Down syndrome (DS) infants are known to have a high frequency of heart anomalies. Not all children with DS suffer from heart anomalies, which raises the question whether maternal factors

  11. Syntheses of Nucleoside Derivatives Containing Fmoc- or Trityl-protected Amino Acids

    Institute of Scientific and Technical Information of China (English)

    GUO Hui; ZOU Wu-xin; JI Qi; MA Yu-xin; MENG Ji-ben

    2005-01-01

    Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids via N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactions offer a mild and convenient method to synthesize aminoacylated nucleoside derivatives.

  12. Human migration, protected areas, and conservation outreach in Tanzania.

    Science.gov (United States)

    Salerno, Jonathan D; Borgerhoff Mulder, Monique; Kefauver, Shawn C

    2014-06-01

    A recent discussion debates the extent of human in-migration around protected areas (PAs) in the tropics. One proposed argument is that rural migrants move to bordering areas to access conservation outreach benefits. A counter proposal maintains that PAs have largely negative effects on local populations and that outreach initiatives even if successful present insufficient benefits to drive in-migration. Using data from Tanzania, we examined merits of statistical tests and spatial methods used previously to evaluate migration near PAs and applied hierarchical modeling with appropriate controls for demographic and geographic factors to advance the debate. Areas bordering national parks in Tanzania did not have elevated rates of in-migration. Low baseline population density and high vegetation productivity with low interannual variation rather than conservation outreach explained observed migration patterns. More generally we argue that to produce results of conservation policy significance, analyses must be conducted at appropriate scales, and we caution against use of demographic data without appropriate controls when drawing conclusions about migration dynamics. © 2014 Society for Conservation Biology.

  13. A mint purified extract protects human keratinocytes from short-term, chemically induced oxidative stress.

    Science.gov (United States)

    Berselli, Patrizia Valeria Rita; Zava, Stefania; Montorfano, Gigliola; Corsetto, Paola Antonia; Krzyzanowska, Justyna; Oleszek, Wieslaw; Berra, Bruno; Rizzo, Angela Maria

    2010-11-10

    Oxidative stress is strictly correlated to the pathogenesis of many diseases, and a diet rich in fruits and vegetables, or adequately integrated, is currently considered to be a protective and preventive factor. This study aimed to analyze the efficacy of a 1 h preincubation with the highest nontoxic dose of a characterized Mentha longifolia extract (80 μg/mL) in protecting human keratinocytes (NCTC2544) from chemically induced oxidative stress (500 μM H2O2 for 2, 16, and 24 h). As reference synthetic pure compounds rosmarinic acid (360.31 μg/mL), a major mint phenolic constituent, and resveratrol (31.95 mg/mL), a well-known antioxidant, were used. Cellular viability was significantly protected by mint, which limited protein and DNA damage, decreased lipid peroxidation, and preserved glutathione and superoxide dismutase activity in the shorter phases of oxidative stress induction, in extents comparable to or better than those of pure compounds. These data suggest that mint use as only a flavoring has to be revised, taking into consideration its enrichment in foodstuff and cosmetics.

  14. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  15. 10 CFR 63.321 - Individual protection standard for human intrusion.

    Science.gov (United States)

    2010-01-01

    ... IN A GEOLOGIC REPOSITORY AT YUCCA MOUNTAIN, NEVADA Postclosure Public Health and Environmental Standards Human Intrusion Standard § 63.321 Individual protection standard for human intrusion. (a) DOE...

  16. The role of lactoferrin binding protein B in mediating protection against human lactoferricin.

    Science.gov (United States)

    Morgenthau, Ari; Livingstone, Margaret; Adamiak, Paul; Schryvers, Anthony B

    2012-06-01

    Bacteria that inhabit the mucosal surfaces of the respiratory and genitourinary tracts of mammals encounter an iron-deficient environment because of iron sequestration by the host iron-binding proteins transferrin and lactoferrin. Lactoferrin is also present in high concentrations at sites of inflammation where the cationic, antimicrobial peptide lactoferricin is produced by proteolysis of lactoferrin. Several Gram-negative pathogens express a lactoferrin receptor that enables the bacteria to use lactoferrin as an iron source. The receptor is composed of an integral membrane protein, lactoferrin binding protein A (LbpA), and a membrane-bound lipoprotein, lactoferrin binding protein B (LbpB). LbpA is essential for growth with lactoferrin as the sole iron source, whereas the role of LbpB in iron acquisition is not yet known. In this study, we demonstrate that LbpB from 2 different species is capable of providing protection against the killing activity of a human lactoferrin-derived peptide. We investigated the prevalence of lactoferrin receptors in bacteria and examined their sequence diversity. We propose that the protection against the cationic antimicrobial human lactoferrin-derived peptide is associated with clusters of negatively charged amino acids in the C-terminal lobe of LbpB that is a common feature of this protein.

  17. Human milk oligosaccharides protect bladder epithelial cells against uropathogenic Escherichia coli invasion and cytotoxicity.

    Science.gov (United States)

    Lin, Ann E; Autran, Chloe A; Espanola, Sophia D; Bode, Lars; Nizet, Victor

    2014-02-01

    The invasive pathogen uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). Recurrent infection that can progress to life-threatening renal failure has remained as a serious global health concern in infants. UPEC adheres to and invades bladder epithelial cells to establish infection. Studies have detected the presence of human milk oligosaccharides (HMOs) in urine of breast-fed, but not formula-fed, neonates. We investigated the mechanisms HMOs deploy to elicit protection in human bladder epithelial cells infected with UPEC CFT073, a prototypic urosepsis-associated strain. We found a significant reduction in UPEC internalization into HMO-pretreated epithelial cells without observing any significant effect in UPEC binding to these cells. This event coincides with a rapid decrease in host cell cytotoxicity, recognized by LIVE/DEAD staining and cell detachment, but independent of caspase-mediated or mitochondrial-mediated programmed cell death pathways. Further investigation revealed HMOs, and particularly the sialic acid-containing fraction, reduced UPEC-mediated MAPK and NF-κB activation. Collectively, our results indicate that HMOs can protect bladder epithelial cells from deleterious cytotoxic and proinflammatory effects of UPEC infection, and may be one contributing mechanism underlying the epidemiological evidence of reduced UTI incidence in breast-fed infants.

  18. Protection of Mice from Lethal Endotoxemia by Chimeric Human BPI-Fcγ1 Gene Delivery

    Institute of Scientific and Technical Information of China (English)

    Chen Li; Jing Li; Zhe Lv; Xinghua Guo; Qinghua Chen; Qingli Kong; Yunqing An

    2006-01-01

    To evaluate the potentiality of applying gene therapy to endotoxemia in high-risk patients, we investigated the effects of transferring an adeno-associated virus serotype 2 (AAV2)-mediated BPI-Fcγ1 gene on protecting mice from challenge of lethal endotoxin. The chimeric BPI-Fcγ1 gene consists of two parts, one encods functional N-terminus (1 to 199 amino acidic residues) of human BPI, which is a bactericidal/permeability-increasing protein,and the other encodes Fc segment of human immunoglobulin G1 (Fcγ1). Our results indicated that the target protein could be expressed and secreted into the serum of the gene-transferred mice. After lethal endotoxin challenge, the levels of endotoxin and TNF-α in the gene-transferred mice were decreased. The survival rate of the BPI-Fcγ1 gene-transferred mice was markedly increased. Our data suggest that AAV2-mediated chimeric BPI-Fcγ1 gene delivery can potentially be used clinically for the protection and treatment of endotoxemia and endotoxic shock in high-risk individuals.

  19. Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

    Institute of Scientific and Technical Information of China (English)

    Meghali Nighot; Adam Moeser; Ryuji Ueno; Anthony Blikslager

    2012-01-01

    AIM:To evaluate the protective properties of novel prostone CIC-2 agonist SPI-8811 in porcine model of gastric acid injury.METHODS:Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH =1.5) with or without SP1-8811 (1 μmol/L),cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172,10 μmol/L,apical) and CIC-2 inhibitor ZnCl2,300 μmol/L,apical),on the apical surface of tissues.Transepithelial resistance and mucosal-to-serosal 3H-mannitol fluxes were measured over a 90-min period.Tissues were analyzed by morph metric techniques,Immunofluorescence and by western blots.RESULTS:Compared with control tissues,acid exposure decreased transepithelial electrical resistance (TER)and increased 3H-mannitol flux.Pretreatment of gastric mucosa with SPI-8811 was protective against acidinduced decreases in TER (TER,50 Ω.cm2 vs 100 Ω'cm2)and abolished increases in flux (3H-mannitol flux,0.10 μmol/L.cm2 vs 0.04 μmol/L.cm2).Evidence of histological damage in the presence of acid was markedly attenuated by SPI-0811.Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811.Pretreatment with the CIC-2 inhibitor ZnCl2,but not the selective CFTR inhibitor 172,attenuated SPI-8811-mediated mucosal protection,suggesting a role for CIC-2.Prostone may serve both protective and reparative roles in injured tissues.CONCLUSION:CIC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach.

  20. Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice.

    Science.gov (United States)

    Kaplan, Halil Mahir; Şingirik, Ergin; Erdoğan, Kıvılcım Eren; Doran, Figen

    2017-07-31

    Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i.p; intraperitoneally) and 200 mg/kg alpha-linolenic acid (gavage) are administered to mice for 9 days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation.

  1. Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids.

    Science.gov (United States)

    Akagi, Sosuke; Kono, Nozomu; Ariyama, Hiroyuki; Shindou, Hideo; Shimizu, Takao; Arai, Hiroyuki

    2016-05-01

    The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by dietary consumption of fatty acids such as saturated fatty acids and polyunsaturated fatty acids (PUFAs). Cells must adapt to changes in composition of membrane fatty acids by regulating lipid-metabolizing enzymes. In this study, we investigated how cells respond to loading with excess PUFAs, such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. A lipidomics analysis revealed that dipalmitoylphosphatidylcholine (DPPC) was increased after the production of PUFA-containing phospholipids in cells loaded with PUFAs. An RNA interference screen of lipid-metabolizing enzymes revealed that lysophosphatidylcholine acyltransferase 1 (LPCAT1) was involved in the DPPC production. Moreover, LPCAT1 knockdown markedly enhanced the cytotoxicity induced by excess PUFAs. PUFA-induced cytotoxicity was dependent on caspase and unfolded protein response (UPR) sensor proteins inositol requiring 1α and protein kinase R-like endoplasmic reticulum kinase, suggesting that excess PUFAs trigger UPR-mediated apoptosis. In murine retina, in which PUFAs are highly enriched, DPPC was produced along with increase of PUFA-containing phospholipids. In LPCAT1 knockout mice, DPPC level was reduced and UPR was activated in the retina. Our results provide insight into understanding of the retinal degeneration seen in rd11 mice that lack LPCAT1.-Akagi, S., Kono, N., Ariyama, H., Shindou, H., Shimizu, T., Arai, H. Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids.

  2. The Functions of Selected Human Rights Institutions and Related Role-Players in the Protection of Human Rights in Zimbabwe

    Directory of Open Access Journals (Sweden)

    Howard Chitimira

    2016-12-01

    Full Text Available Various violations of the human rights of ordinary people and human rights defenders have been reported in Zimbabwe since the late 1980s. It is widely acknowledged that such violations have been perpetrated mostly by the government through its different organs for political and other related reasons. Human rights violations were also easily committed against ordinary people and human rights defenders because there was no Constitution that adequately protected such people's fundamental human rights (including their civil and political rights and their socio-economic rights in Zimbabwe. Given this background, the article discusses the protection of human rights in Zimbabwe, in the light of the Zimbabwe Constitution Amendment Act 20 of 2013 (Zimbabwe Constitution 2013. This is done in order to investigate whether the promotion, protection, enforcement and respect for human rights in Zimbabwe has now improved. To this end, the functions of selected national human rights institutions and other related role-players, namely civil society, the judiciary, the law enforcement organs and the Zimbabwe Human Rights Commission, are briefly discussed first. Secondly, the functions of selected regional and international institutions, namely the Southern African Development Community, the African Union and the United Nations are discussed in relation to the protection of human rights in Zimbabwe. Thereafter, concluding remarks and possible recommendations that could be utilised to combat human rights violations and enhance the protection of human rights in Zimbabwe are provided.

  3. Declining human population but increasing residential development around protected areas in Puerto Rico

    Science.gov (United States)

    J. Castro-Prieto; S. Martinuzzi; V.C. Radeloff; D.P. Helmers; M. Quiñones; W.A. Gould

    2017-01-01

    Increasing residential development around protected areas is a major threat for protected areas worldwide, and human population growth is often the most important cause. However, population is decreasing in many regions as a result of socio-economic changes, and it is unclear how residential development around protected areas is affected in these situations. We...

  4. Select human anthrax protective antigen (PA) epitope-specific antibodies provide protection from lethal toxin challenge

    Science.gov (United States)

    Crowe, Sherry R.; Ash, Linda L.; Engler, Renata J. M.; Ballard, Jimmy D.; Harley, John B.; Farris, A. Darise; James, Judith A.

    2010-01-01

    Bacillus anthracis remains a serious bioterrorism concern, and the currently licensed vaccine remains an incomplete solution for population protection from inhalation anthrax and has been associated with concerns regarding efficacy and safety. Thus, understanding how to generate long lasting protective immunity with reduced immunizations or providing protection through post exposure immunotherapeutics are long sought goals. Through evaluation of a large military cohort, we characterized the levels of antibodies against protective antigen and found that over half of anthrax vaccinees had low levels of in vitro toxin neutralization capacity in their sera. Using solid phase epitope mapping and confirmatory assays, we identified several neutralization-associated humoral epitopes and demonstrated that select anti-peptide responses mediated protection in vitro. Finally, passively transferred antibodies specific for select epitopes provided protection in an in vivo lethal toxin mouse model. Identification of these antigenic regions has important implications for vaccine design and the development of directed immunotherapeutics. PMID:20533877

  5. Green chemistry in protected horticulture: the use of peroxyacetic acid as a sustainable strategy.

    Science.gov (United States)

    Carrasco, Gilda; Urrestarazu, Miguel

    2010-05-03

    Global reduction of chemical deposition into the environment is necessary. In protected horticulture, different strategies with biodegradable products are used to control pathogens. This review presents the available tools, especially for the management of protected horticultural species, including vegetables and ornamental plants. An analysis of the potential for degradable products that control pathogens and also encourage other productive factors, such as oxygen in the root system, is presented. Biosecurity in fertigation management of protected horticulture is conducted by using peroxyacetic acid mixtures that serve three basic principles: first, the manufacture of these products does not involve polluting processes; second, they have the same function as other chemicals, and third, after use and management there is no toxic residue left in the environment. The sustainability of protected horticulture depends on the development and introduction of technologies for implementation in the field.

  6. Green Chemistry in Protected Horticulture: The Use of Peroxyacetic Acid as a Sustainable Strategy

    Science.gov (United States)

    Carrasco, Gilda; Urrestarazu, Miguel

    2010-01-01

    Global reduction of chemical deposition into the environment is necessary. In protected horticulture, different strategies with biodegradable products are used to control pathogens. This review presents the available tools, especially for the management of protected horticultural species, including vegetables and ornamental plants. An analysis of the potential for degradable products that control pathogens and also encourage other productive factors, such as oxygen in the root system, is presented. Biosecurity in fertigation management of protected horticulture is conducted by using peroxyacetic acid mixtures that serve three basic principles: first, the manufacture of these products does not involve polluting processes; second, they have the same function as other chemicals, and third, after use and management there is no toxic residue left in the environment. The sustainability of protected horticulture depends on the development and introduction of technologies for implementation in the field. PMID:20559497

  7. Green Chemistry in Protected Horticulture: The Use of Peroxyacetic Acid as a Sustainable Strategy

    Directory of Open Access Journals (Sweden)

    Gilda Carrasco

    2010-05-01

    Full Text Available Global reduction of chemical deposition into the environment is necessary. In protected horticulture, different strategies with biodegradable products are used to control pathogens. This review presents the available tools, especially for the management of protected horticultural species, including vegetables and ornamental plants. An analysis of the potential for degradable products that control pathogens and also encourage other productive factors, such as oxygen in the root system, is presented. Biosecurity in fertigation management of protected horticulture is conducted by using peroxyacetic acid mixtures that serve three basic principles: first, the manufacture of these products does not involve polluting processes; second, they have the same function as other chemicals, and third, after use and management there is no toxic residue left in the environment. The sustainability of protected horticulture depends on the development and introduction of technologies for implementation in the field.

  8. Land use change around protected areas: management to balance human needs and ecological function.

    Science.gov (United States)

    DeFries, Ruth; Hansen, Andrew; Turner, B L; Reid, Robin; Liu, Jianguo

    2007-06-01

    Protected areas throughout the world are key for conserving biodiversity, and land use is key for providing food, fiber, and other ecosystem services essential for human sustenance. As land use change isolates protected areas from their surrounding landscapes, the challenge is to identify management opportunities that maintain ecological function while minimizing restrictions on human land use. Building on the case studies in this Invited Feature and on ecological principles, we identify opportunities for regional land management that maintain both ecological function in protected areas and human land use options, including preserving crucial habitats and migration corridors, and reducing dependence of local human populations on protected area resources. Identification of appropriate and effective management opportunities depends on clear definitions of: (1) the biodiversity attributes of concern; (2) landscape connections to delineate particular locations with strong ecological interactions between the protected area and its surrounding landscape; and (3) socioeconomic dynamics that determine current and future use of land resources in and around the protected area.

  9. Salvianolic acid B protects the myelin sheath around injured spinal cord axons

    Directory of Open Access Journals (Sweden)

    Zhe Zhu

    2016-01-01

    Full Text Available Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 μg/mL. For in vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of regenerating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

  10. Salvianolic acid B protects the myelin sheath around injured spinal cord axons.

    Science.gov (United States)

    Zhu, Zhe; Ding, Lu; Qiu, Wen-Feng; Wu, Hong-Fu; Li, Rui

    2016-03-01

    Salvianolic acid B, an active pharmaceutical compound present in Salvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study, in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 μg/mL. For in vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of regenerating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

  11. Salvianolic acid B protects the myelin sheath around injured spinal cord axons

    Institute of Scientific and Technical Information of China (English)

    Zhe Zhu; Lu Ding; Wen-feng Qiu; Hong-fu Wu; Rui Li

    2016-01-01

    Salvianolic acid B, an active pharmaceutical compound present inSalvia miltiorrhiza, exerts a neuroprotective effect in animal models of brain and spinal cord injury. Salvianolic acid B can promote recovery of neurological function; however, its protective effect on the myelin sheath after spinal cord injury remains poorly understood. Thus, in this study,in vitro tests showed that salvianolic acid B contributed to oligodendrocyte precursor cell differentiation, and the most effective dose was 20 µg/mL. Forin vivo investigation, rats with spinal cord injury were intraperitoneally injected with 20 mg/kg salvianolic acid B for 8 weeks. The amount of myelin sheath and the number of re-generating axons increased, neurological function recovered, and caspase-3 expression was decreased in the spinal cord of salvianolic acid B-treated animals compared with untreated control rats. These results indicate that salvianolic acid B can protect axons and the myelin sheath, and can promote the recovery of neurological function. Its mechanism of action is likely to be associated with inhibiting apoptosis and promoting the differentiation and maturation of oligodendrocyte precursor cells.

  12. Protective effects of sinapic acid on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats.

    Science.gov (United States)

    Roy, Subhro Jyoti; Stanely Mainzen Prince, Ponnian

    2012-11-01

    In the pathology of myocardial infarction, lysosomal lipid peroxidation and resulting enzyme release play an important role. We evaluated the protective effects of sinapic acid on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats. Male Wistar rats were treated with sinapic acid (12 mg/kg body weight) orally daily for 10 days and isoproterenol (100 mg/kg body weight) was injected twice at an interval of 24 h (9th and 10th day). Then, lysosomal lipid peroxidation, lysosomal enzymes in serum, heart homogenate, lysosomal fraction and myocardial infarct size were measured. Isoproterenol induced myocardial infarcted rats showed a significant increase in serum creatine kinase-MB and lysosomal lipid peroxidation. The activities of β-glucuronidase, β-galactosidase, cathepsin-B and D were significantly increased in serum, heart and the activities of β-glucuronidase and cathepsin-D were significantly decreased in lysosomal fraction of myocardial infarcted rats. Pre-and-co-treatment with sinapic acid normalized all the biochemical parameters and reduced myocardial infarct size in myocardial infarcted rats. In vitro studies confirmed the free radical scavenging effects of sinapic acid. The possible mechanisms for the observed effects are attributed to sinapic acid's free radical scavenging and membrane stabilizing properties. Thus, sinapic acid has protective effects on lysosomal dysfunction in isoproterenol induced myocardial infarcted rats.

  13. 77 FR 6799 - Meeting of the Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2012-02-09

    ... Bioethical Issues on that group's recent report Moral Science: Protecting Participants in Human Subjects... Secretary for Health on issues and topics pertaining to or associated with the protection of human research..., SACHRP, prior to the close of business February 23, 2012. Dated: February 3, 2012. Jerry Menikoff...

  14. The Environmental Right as a Human Right: Scientific Development and the Protection of Rights

    Institute of Scientific and Technical Information of China (English)

    ZHAN ZHONGLE

    2011-01-01

    @@ As environmental issues are attracting domestic and international attention,protection of environmental rights is becoming increasingly important in human rights affairs.Environmental protection involves economic development and social harmony, influences the maintenance and complete realization of people's rights to health, property and life, and is even related to the future existence of the whole human society.

  15. 78 FR 10538 - Protections for Subjects in Human Research Involving Pesticides

    Science.gov (United States)

    2013-02-14

    ... AGENCY 40 CFR Part 26 RIN 2070-AJ76 Protections for Subjects in Human Research Involving Pesticides... human subjects and to persons who submit the results of human research with pesticides to EPA. The amendments broaden the applicability of the rules to cover human testing with pesticides submitted to EPA...

  16. Impact of folic acid supplementation on single- and double-stranded RNA degradation in human colostrum and mature milk.

    Science.gov (United States)

    Kocic, Gordana; Bjelakovic, Ljiljana; Bjelakovic, Bojko; Jevtoci-Stoimenov, Tatjana; Sokolovic, Dusan; Cvetkovic, Tatjana; Kocic, Hristina; Stojanovic, Svetlana; Langerholc, Tomaz; Jonovic, Marina

    2014-07-01

    Sufficient intake of folic acid is necessary for normal embryogenesis, fetal, and neonatal development. Folic acid facilitates nucleic acid internalization, and protects cellular DNA from nuclease degradation. Human milk contains enzymes, antimicrobial proteins, and antibodies, along with macrophages, that protect against infections and allergies. However, little to no information is available on the effects of folic acid supplementation on degradation of nucleic acids in human milk. In the present study, we aimed to determine the RNase activity (free and inhibitor-bound) in colostrum and mature milk, following folic acid supplementation. The study design included a total of 59 women, 27 of whom received 400 μg of folic acid daily periconceptionally and after. Folic acid supplementation increased the free RNase and polyadenylase activity following lactation. However, the increased RNase activity was not due to de novo enzyme synthesis, as the inhibitor-bound (latent) RNase activity was significantly lower and disappeared after one month. Folic acid reduced RNase activity by using double-stranded RNA as substrate. Data suggests that folic acid supplementation may improve viral RNAs degradation and mRNA degradation, but not dsRNA degradation, preserving in this way the antiviral defense.

  17. Microscopic residues of bone from dissolving human remains in acids.

    Science.gov (United States)

    Vermeij, Erwin; Zoon, Peter; van Wijk, Mayonne; Gerretsen, Reza

    2015-05-01

    Dissolving bodies is a current method of disposing of human remains and has been practiced throughout the years. During the last decade in the Netherlands, two cases have emerged in which human remains were treated with acid. In the first case, the remains of a cremated body were treated with hydrofluoric acid. In the second case, two complete bodies were dissolved in a mixture of hydrochloric and sulfuric acid. In both cases, a great variety of evidence was collected at the scene of crime, part of which was embedded in resin, polished, and investigated using SEM/EDX. Apart from macroscopic findings like residual bone and artificial teeth, in both cases, distinct microscopic residues of bone were found as follows: (partly) digested bone, thin-walled structures, and recrystallized calcium phosphate. Although some may believe it is possible to dissolve a body in acid completely, at least some of these microscopic residues will always be found. © 2015 American Academy of Forensic Sciences.

  18. Exogenous salicylic acid protects phospholipids against cadmium stress in flax (Linum usitatissimum L.).

    Science.gov (United States)

    Belkadhi, Aïcha; De Haro, Antonio; Obregon, Sara; Chaïbi, Wided; Djebali, Wahbi

    2015-10-01

    Salicylic acid (SA) promotes plant defense responses against toxic metal stresses. The present study addressed the hypothesis that 8-h SA pretreatment, would alter membrane lipids in a way that would protect against Cd toxicity. Flax seeds were pre-soaked for 8h in SA (0, 250 and 1000µM) and then subjected, at seedling stage, to cadmium (Cd) stress. At 100µM CdCl2, significant decreases in the percentages of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol (MGDG) and changes in their relative fatty acid composition were observed in Cd-treated roots in comparison with controls. However, in roots of 8-h SA pretreated plantlets, results showed that the amounts of PC and PE were significantly higher as compared to non-pretreated plantlets. Additionally, in both lipid classes, the proportion of linolenic acid (18:3) increased upon the pretreatment with SA. This resulted in a significant increase in the fatty acid unsaturation ratio of the root PC and PE classes. As the exogenous application of SA was found to be protective of flax lipid metabolism, the possible mechanisms of protection against Cd stress in flax roots were discussed.

  19. Protective effect of oat bran extracts on human dermal fibroblast injury induced by hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Bing FENG; Lai-ji MA; Jin-jing YAO; Yun FANG; Yan-ai MEI; Shao-min WEI

    2013-01-01

    Oat contains different components that possess antioxidant properties;no study to date has addressed the antioxidant effect of the extract of oat bran on the cellular level.Therefore,the present study focuses on the investigation of the protective effect of oat bran extract by enzymatic hydrolysates on human dermal fibroblast injury induced by hydrogen peroxide(H2O2).Kjeldahl determination,phenol-sulfuric acid method,and high-performance liquid chromatography(HPLC)analysis indicated that the enzymatic products of oat bran contain a protein amount of 71.93%,of which 97.43% are peptides with a molecular range from 438.56 to 1301.01 Da.Assays for 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging activity indicate that oat peptide-rich extract has a direct and concentration-dependent antioxidant activity.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)colorimetric assay and the TdT-mediated digoxigenin-dUTP nick-end labeling(TUNEL)assay for apoptosis showed that administration of H2O2 in human dermal fibroblasts caused cell damage and apoptosis.Pre-incubation of human dermal fibroblasts with the Oatp for 24 h markedly inhibited human dermal fibroblast injury induced by H2O2,but application oat peptides with H2O2 at same time did not.Pre-treatment of human dermal fibroblasts with Oatp significantly reversed the H2O2-induced decrease of superoxide dismutase(SOD)and the inhibition of malondialdehyde(MDA).The results demonstrate that oat peptides possess antioxidant activity and are effective against H2O2-induced human dermal fibroblast injury by the enhanced activity of SOD and decrease in MDA level.Our results suggest that oat bran will have the potential to be further explored as an antioxidant functional food in the prevention of aging-related skin injury.

  20. NUTRITIONAL AND PROTECTIVE VALUES OF FISH – WITH EMPHSIS ON OMEGA-3 FATTY ACID

    Directory of Open Access Journals (Sweden)

    Ivan Bogut

    1996-12-01

    Full Text Available This work presents the importance of fish as a life necessity in view of proteins, vitamins, micro and macro elements and in comparison with high valued necessities of warm-blooded animals (meat, milk and eggs. Most literature information is related to the chemical components of meat, nutritional and biological values. Numerous papers have shown the components of fatty acids in fats of the most important freshwater and sea fish. According the contents of FPA (eicosapentaen fatty acids, 20:5 3 and DHA (docosaheksacn fatty acids, 22:6 3 the meat of the silver carp (Hypophthalmichtis molitrix can be compared to that of the highest quality sea fish. In the last 20 years many authors mentioned the protective role of omega-3 fatty acids in the prevention of heart attack, stroke, artherosclerosis, high blood pressure, psoriasis, thrombosis and arthritis.

  1. Punicic acid a conjugated linolenic acid inhibits TNFalpha-induced neutrophil hyperactivation and protects from experimental colon inflammation in rats.

    Directory of Open Access Journals (Sweden)

    Tarek Boussetta

    Full Text Available BACKGROUND: Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO. The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE: These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases.

  2. Training affects muscle phospholipid fatty acid composition in humans

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Wu, B J; Willer, Mette

    2001-01-01

    Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect...... on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk......, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P

  3. Hyaluronic acid production by irradiated human synovial fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Yaron, M.; Yaron, I.; Levita, M.; Herzberg, M.

    1977-03-01

    Radioactive particles as well as x irradiation from an external source has been used in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In order to clarify effects of ionizing irradiation on synovial cells, radioactive gold (/sup 198/Au) and yttrium (/sup 90/Y) were added to fibroblast cultures derived from human synovial membranes. Other cultures were irradiated by a Picker x-ray machine. Fibroblast growth and hyaluronic acid production were measured. Radioactive gold and yttrium particles induced a significant increase of hyaluronic acid synthesis rate (pg/cell/day) and inhibited fibroblast growth. Fibroblasts continued to overproduce hyaluronic acid and to show growth inhibition 3 weeks after irradiation with radioactive gold. Hydrocortisone inhibited hyaluronic acid overproduction induced by radioactive gold. Overproduction of hyaluronic acid induced by the x-ray machine was inhibited by hydrocortisone, actinomycin-D, and cycloheximide. Fibroblasts derived from normal and rheumatoid patients responded similarly to ionizing irradiation.

  4. Protecting Cell Walls from Binding Aluminum by Organic Acids Contributes to Aluminum Resistance

    Institute of Scientific and Technical Information of China (English)

    Ya-Ying Li; Yue-Jiao Zhang; Yuan Zhou; Jian-Li Yang; Shao-Jian Zheng

    2009-01-01

    Aluminum-induced secretion of organic acids from the root apex has been demonstrated to be one major AI resistance mechanism in plants. However, whether the organic acid concentration is high enough to detoxify AI in the growth medium is frequently questioned. The genotypes of Al-resistant wheat, Cassia tora L. and buckwheat secrete malate, citrate and oxalate, respectively. In the present study we found that at a 35% inhibition of root elongation, the AI activities in the solution were 10, 20, and 50 μM with the corresponding malate, citrate, and oxalate exudation at the rates of 15, 20 and 21 nmol/cm2 per 12 h, respectively, for the above three plant species. When exogenous organic acids were added to ameliorate Al toxicity, twofold and eightfold higher oxalate and malate concentrations were required to produce the equal effect by citrate. After the root apical cell walls were isolated and preincubated in 1 mM malate, oxalate or citrate solution overnight, the total amount of AI adsorbed to the cell walls all decreased significantly to a similar level, implying that these organic acids own an equal ability to protect the cell walls from binding AI. These findings suggest that protection of cell walls from binding Al by organic acids may contribute significantly to AI resistance.

  5. Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats.

    Science.gov (United States)

    Lin, Tzu Yu; Lu, Cheng Wei; Wang, Su Jane; Huang, Shu Kuei

    2015-05-15

    Hispidulin is a flavonoid compound which is an active ingredient in a number of traditional Chinese medicinal herbs, and it has been reported to inhibit glutamate release. The purpose of this study was to investigate whether hispidulin protects against seizures induced by kainic acid, a glutamate analog with excitotoxic properties. The results indicated that intraperitoneally administering hispidulin (10 or 50mg/kg) to rats 30 min before intraperitoneally injecting kainic acid (15 mg/kg) increased seizure latency and decreased seizure score. In addition, hispidulin substantially attenuated kainic acid-induced hippocampal neuronal cell death, and this protective effect was accompanied by the suppression of microglial activation and the production of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampus. Moreover, hispidulin reduced kainic acid-induced c-Fos expression and the activation of mitogen-activated protein kinases in the hippocampus. These data suggest that hispidulin has considerable antiepileptic, neuroprotective, and antiinflammatory effects on kainic acid-induced seizures in rats.

  6. A Convenient, General Synthesis of 1,1-Dimethylallyl Esters as Protecting Groups for Carboxylic Acids

    Science.gov (United States)

    Sedighi, Minoo; Lipton, Mark A.

    2006-01-01

    Carboxylic acids were converted in high yield to their 1,1-dimethylallyl (DMA) esters in two steps. Palladium-catalyzed deprotection of DMA esters was shown to be compatible with tert-butyl, benzyl and Fmoc protecting groups, and Fmoc deprotection could be carried out selectively in the presence of DMA esters. DMA esters were also shown to be resistant to nucleophilic attack, suggesting that they will serve as alternatives to tert-butyl esters when acidic deprotection conditions need to be avoided. PMID:15816730

  7. A convenient, general synthesis of 1,1-dimethylallyl esters as protecting groups for carboxylic acids.

    Science.gov (United States)

    Sedighi, Minoo; Lipton, Mark A

    2005-04-14

    [reaction: see text] Carboxylic acids were converted in high yield to their 1,1-dimethylallyl (DMA) esters in two steps. Palladium-catalyzed deprotection of DMA esters was shown to be compatible with tert-butyl, benzyl, and Fmoc protecting groups, and Fmoc deprotection could be carried out selectively in the presence of DMA esters. DMA esters were also shown to be resistant to nucleophilic attack, suggesting that they will serve as alternatives to tert-butyl esters when acidic deprotection conditions need to be avoided.

  8. Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts.

    Science.gov (United States)

    Maeda-Sano, Katsura; Gotoh, Mari; Morohoshi, Toshiro; Someya, Takao; Murofushi, Hiromu; Murakami-Murofushi, Kimiko

    2014-09-01

    Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway.

  9. Disposition of dodecanedioic acid in humans.

    Science.gov (United States)

    Bertuzzi, A; Mingrone, G; Gandolfi, A; Greco, A V; Salinari, S

    2000-03-01

    The disposition of dodecanedioic acid (C12) was investigated in six overnight-fasting healthy male volunteers, who received a 165-min i. v. infusion of 42.45 mmol of C12 added to 150 microCi of [1-12-(14)C]C12. Blood samples were collected up to 360 min after the start of infusion, and concentration of serum labeled C12 was determined. Expired radioactivity (microCi/min) was measured up to 600 min and at 24 h. The 24-h C12 urinary excretion was around 5% of the administered amount. The percentage of C12 oxidized was 81.7 +/- 9.5% (mean +/- S.D.) of administered amount as estimated from the area under the curve of measured (14)CO(2) expiration rate. C12 kinetics was described by assuming a single compartment. A saturable rate of C12 tissue uptake (model A) and a linear rate of tissue uptake (model B) were considered. The kinetics of CO(2) produced by C12 oxidation was described by a fast pathway acting in parallel to a slow pathway modeled by first order kinetics. Parameters of model B were estimated for each subject, whereas model A was identified by fitting the pooled data of all subjects. On the basis of estimates obtained from model B, an average calorie delivery of 500 kcal/day was predicted in the plateau phase for the infusion rate of our experiments. When estimated from model A, the maximal rate of tissue uptake was 0.38 +/- 0.08 mmol/min, with a maximal calorie delivery of 750 kcal/day. These results appear promising for C12 utilization in parenteral nutrition, because C12 elimination with urine is low, whereas tissue uptake and oxidation are rather efficient.

  10. Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice.

    Science.gov (United States)

    Ince, Sinan; Keles, Hikmet; Erdogan, Metin; Hazman, Omer; Kucukkurt, Ismail

    2012-07-01

    The protective effect of boric acid against liver damage was evaluated by its attenuation of carbon tetrachloride (CCl(4))-induced hepatotoxicity in mice. Male albino mice were treated intraperitoneally (i.p.) with boric acid (50, 100, and 200 mg/kg) or silymarin daily for 7 days and received 0.2% CCl(4) in olive oil (10 mL/kg, i.p.) on day 7. Results showed that administration of boric acid significantly reduced the elevation in serum levels of aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, and the level of malondialdehyde in the liver that were induced by CCl(4) in mice. Boric acid treatment significantly increased glutathione content, as well as the activities of superoxide dismutase and catalase in the liver. Boric acid treatment improved the catalytic activity of cytochrome P450 2E1 and maintained activation of nuclear factor kappa light-chain enhancer of activated B cell gene expression, with no effect on inducible nitric oxide synthase gene expression in the livers of mice. Histopathologically, clear decreases in the severity of CCl(4)-induced lesions were observed, particularly at high boric acid concentrations. Results suggest that boric acid exhibits potent hepatoprotective effects on CCl(4)-induced liver damage in mice, likely the result of both the increase in antioxidant-defense system activity and the inhibition of lipid peroxidation.

  11. The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid*♦

    Science.gov (United States)

    Turell, Lucía; Vitturi, Darío A.; Coitiño, E. Laura; Lebrato, Lourdes; Möller, Matías N.; Sagasti, Camila; Salvatore, Sonia R.; Woodcock, Steven R.; Alvarez, Beatriz; Schopfer, Francisco J.

    2017-01-01

    Nitroalkene fatty acids are formed in vivo and exert protective and anti-inflammatory effects via reversible Michael addition to thiol-containing proteins in key signaling pathways. Nitro-conjugated linoleic acid (NO2-CLA) is preferentially formed, constitutes the most abundant nitrated fatty acid in humans, and contains two carbons that could potentially react with thiols, modulating signaling actions and levels. In this work, we examined the reactions of NO2-CLA with low molecular weight thiols (glutathione, cysteine, homocysteine, cysteinylglycine, and β-mercaptoethanol) and human serum albumin. Reactions followed reversible biphasic kinetics, consistent with the presence of two electrophilic centers in NO2-CLA located on the β- and δ-carbons with respect to the nitro group. The differential reactivity was confirmed by computational modeling of the electronic structure. The rates (kon and koff) and equilibrium constants for both reactions were determined for different thiols. LC-UV-Visible and LC-MS analyses showed that the fast reaction corresponds to β-adduct formation (the kinetic product), while the slow reaction corresponds to the formation of the δ-adduct (the thermodynamic product). The pH dependence of the rate constants, the correlation between intrinsic reactivity and thiol pKa, and the absence of deuterium solvent kinetic isotope effects suggested stepwise mechanisms with thiolate attack on NO2-CLA as rate-controlling step. Computational modeling supported the mechanism and revealed additional features of the transition states, anionic intermediates, and final neutral products. Importantly, the detection of cysteine-δ-adducts in human urine provided evidence for the biological relevance of this reaction. Finally, human serum albumin was found to bind NO2-CLA both non-covalently and to form covalent adducts at Cys-34, suggesting potential modes for systemic distribution. These results provide new insights into the chemical basis of NO2-CLA

  12. Quantitation of glial fibrillary acidic protein in human brain tumours

    DEFF Research Database (Denmark)

    Rasmussen, S; Bock, E; Warecka, K

    1980-01-01

    The glial fibrillary acidic protein (GFA) content of 58 human brain tumours was determined by quantitative immunoelectrophoresis, using monospecific antibody against GFA. Astrocytomas, glioblastomas, oligodendrogliomas, spongioblastomas, ependymomas and medulloblastomas contained relatively high...... amounts of GFA, up to 85 times the concentration in parietal grey substance of normal human brain. GFA was not found in neurinomas, meningiomas, adenomas of the hypophysis, or in a single case of metastasis of adenocarcinoma. Non-glial tumours of craniopharyngioma and haemangioblastoma were infiltrated...

  13. Exploiting Protected Maleimides to Modify Oligonucleotides, Peptides and Peptide Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Clément Paris

    2015-04-01

    Full Text Available This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols.

  14. Phytic acid doped polyaniline containing epoxy coatings for corrosion protection of Q235 carbon steel

    Science.gov (United States)

    Hao, Yongsheng; Sani, Luqman Abdullahi; Ge, Tiejun; Fang, Qinghong

    2017-10-01

    Corrosion protection of epoxy coatings contained with phytic acid-doped polyaniline (PANI-PA) for Q235 carbon steel was studied in this work. Synthesized PANI-PA particles were characterized by XPS, TGA, and FTIR, respectively. The coating performance was investigated by OCP, EIS, and SVET, respectively. The experimental results show that the concentration of PANI-PA has a significant influence to the barrier effect of the epoxy coating. Epoxy coating loaded with 2 wt.% PANI-PA has the best protection ability and self-healing function to a certain degree. The self-healing function of PANI-PA is attributed to the synergistic effect of the passivation of PANI and the chelation of the dedoped phytic acid ions with iron ions. Therefore, PANI-PA can be used as an effective anticorrosion pigment in future.

  15. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Z.Q. [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Greenberg, L. [Centers for Disease Control and Prevention, Atlanta, GA (United States); Ertl, H.C., E-mail: ertl@wistar.upenn.edu [The Wistar Institute of Anatomy and Biology, Philadelphia, PA (United States); Rupprecht, C.E. [The Global Alliance for Rabies Control, Manhattan, KS (United States); Ross University School of Veterinary Medicine, Basseterre (Saint Kitts and Nevis)

    2014-02-15

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protects against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.

  16. Fatty acid synthase cooperates with glyoxalase 1 to protect against sugar toxicity.

    Science.gov (United States)

    Garrido, Damien; Rubin, Thomas; Poidevin, Mickael; Maroni, Brigitte; Le Rouzic, Arnaud; Parvy, Jean-Philippe; Montagne, Jacques

    2015-02-01

    Fatty acid (FA) metabolism is deregulated in several human diseases including metabolic syndrome, type 2 diabetes and cancers. Therefore, FA-metabolic enzymes are potential targets for drug therapy, although the consequence of these treatments must be precisely evaluated at the organismal and cellular levels. In healthy organism, synthesis of triacylglycerols (TAGs)-composed of three FA units esterified to a glycerol backbone-is increased in response to dietary sugar. Saturation in the storage and synthesis capacity of TAGs is associated with type 2 diabetes progression. Sugar toxicity likely depends on advanced-glycation-end-products (AGEs) that form through covalent bounding between amine groups and carbonyl groups of sugar or their derivatives α-oxoaldehydes. Methylglyoxal (MG) is a highly reactive α-oxoaldehyde that is derived from glycolysis through a non-enzymatic reaction. Glyoxalase 1 (Glo1) works to neutralize MG, reducing its deleterious effects. Here, we have used the power of Drosophila genetics to generate Fatty acid synthase (FASN) mutants, allowing us to investigate the consequence of this deficiency upon sugar-supplemented diets. We found that FASN mutants are lethal but can be rescued by an appropriate lipid diet. Rescued animals do not exhibit insulin resistance, are dramatically sensitive to dietary sugar and accumulate AGEs. We show that FASN and Glo1 cooperate at systemic and cell-autonomous levels to protect against sugar toxicity. We observed that the size of FASN mutant cells decreases as dietary sucrose increases. Genetic interactions at the cell-autonomous level, where glycolytic enzymes or Glo1 were manipulated in FASN mutant cells, revealed that this sugar-dependent size reduction is a direct consequence of MG-derived-AGE accumulation. In summary, our findings indicate that FASN is dispensable for cell growth if extracellular lipids are available. In contrast, FA-synthesis appears to be required to limit a cell-autonomous accumulation

  17. Fatty acid synthase cooperates with glyoxalase 1 to protect against sugar toxicity.

    Directory of Open Access Journals (Sweden)

    Damien Garrido

    2015-02-01

    Full Text Available Fatty acid (FA metabolism is deregulated in several human diseases including metabolic syndrome, type 2 diabetes and cancers. Therefore, FA-metabolic enzymes are potential targets for drug therapy, although the consequence of these treatments must be precisely evaluated at the organismal and cellular levels. In healthy organism, synthesis of triacylglycerols (TAGs-composed of three FA units esterified to a glycerol backbone-is increased in response to dietary sugar. Saturation in the storage and synthesis capacity of TAGs is associated with type 2 diabetes progression. Sugar toxicity likely depends on advanced-glycation-end-products (AGEs that form through covalent bounding between amine groups and carbonyl groups of sugar or their derivatives α-oxoaldehydes. Methylglyoxal (MG is a highly reactive α-oxoaldehyde that is derived from glycolysis through a non-enzymatic reaction. Glyoxalase 1 (Glo1 works to neutralize MG, reducing its deleterious effects. Here, we have used the power of Drosophila genetics to generate Fatty acid synthase (FASN mutants, allowing us to investigate the consequence of this deficiency upon sugar-supplemented diets. We found that FASN mutants are lethal but can be rescued by an appropriate lipid diet. Rescued animals do not exhibit insulin resistance, are dramatically sensitive to dietary sugar and accumulate AGEs. We show that FASN and Glo1 cooperate at systemic and cell-autonomous levels to protect against sugar toxicity. We observed that the size of FASN mutant cells decreases as dietary sucrose increases. Genetic interactions at the cell-autonomous level, where glycolytic enzymes or Glo1 were manipulated in FASN mutant cells, revealed that this sugar-dependent size reduction is a direct consequence of MG-derived-AGE accumulation. In summary, our findings indicate that FASN is dispensable for cell growth if extracellular lipids are available. In contrast, FA-synthesis appears to be required to limit a cell

  18. Evaluate the role of organic acids in the protection of ligands from radiolytic degradation

    Energy Technology Data Exchange (ETDEWEB)

    Anneka Miller; Stehpen Mezyk; Dean Peterman

    2016-08-01

    In the Advanced TALSPEAK process, the bis(2-ethylhexyl)phosphoric acid (HDEHP) extractant used in the traditional TALSPEAK process is replaced by the extractant 2-ethylhexylphosphonic acid mono-2-ethylhexyl ester (HEH[EHP]). In addition, the aqueous phase complexant and buffer used in traditional TALSPEAK is replaced with the combination of N-(2-hydroxyethyl)ethylenediamine-N,N’,N’-triacetic acid (HEDTA) and citric acid. In order to evaluate the possible impacts of gamma radiolysis upon the efficacy of the Advanced TALSPEAK flowsheet, aqueous and organic phases corresponding to the extraction section of the proposed flowsheet were irradiated in the INL test loop under an ambient atmosphere. The results of these studies conducted at INL, led INL researchers to conclude that the scarcity of values of rate constants for the reaction of hydroxyl radical with the components of the Advanced TALSPEAK process chemistry was severely limiting the interpretation of the results of radiolysis studies performed at the INL. In this work, the rate of reaction of hydroxyl radical with citric acid at several pH values was measured using a competitive pulse radiolysis technique. This report describes those results and is written in completion of milestone M3FT-16IN030102028, the goal of which was to evaluate the role of organic acids in the protection of ligands from radiolytic degradation. The results reported here demonstrate the importance of obtaining hydroxyl radical reaction rate data for the conditions that closely resemble actual solution conditions expected to be used in an actual solvent extraction process. This report describes those results and is written in completion of milestone M3FT-16IN030102028, the goal of which was to evaluate the role of organic acids in the protection of ligands from radiolytic degradation.

  19. Trifolium pallidum and Trifolium scabrum extracts in the protection of human plasma components.

    Science.gov (United States)

    Kolodziejczyk-Czepas, Joanna; Olas, Beata; Malinowska, Joanna; Wachowicz, Barbara; Moniuszko-Szajwaj, Barbara; Kowalska, Iwona; Oleszek, Wieslaw; Stochmal, Anna

    2013-02-01

    Clovers (genus: Trifolium) have been used in traditional medicine by many cultures, but the biological activity of the most of these plants still remains unknown. The aim of our in vitro study was to assess the antioxidative action of phenolic extracts from aerial parts of Trifolium scabrum and Trifolium pallidum in human blood plasma, exposed to oxidative stress. In the present study we also demonstrate, for the first time the effects of the tested extracts on coagulative properties and fibrinolytic activity of blood plasma. The protective properties of the examined extracts (0.5-50 μg/ml) against peroxynitrite-induced oxidative stress were estimated by the measurements of 3-nitrotyrosine, thiol groups and the thiobarbituric acid-reactive substances levels. The extracts considerably prevented the oxidative and nitrative damage to plasma proteins. Even the lowest doses of the Trifolium extracts (0.5 μg/ml) were able to markedly reduce 3-nitrotyrosine formation (by about 50%) and to increase the level of -SH groups (by about 30%), in comparison to the plasma exposed to ONOO(-) in the absence of the extracts. The protective action of all the used concentrations of the Trifolium extracts in the prevention of lipid peroxidation was also found. The tested extracts influenced neither the coagulative properties nor fibrinolytic activity of plasma. Moreover, the extracts were able to significantly reduce the inhibitory effect of ONOO(-) on fibrinolytic activity of plasma (assessed with the use of a chromogenic substrate for plasmin).

  20. On the Logic Process of Human Rights Protection

    Institute of Scientific and Technical Information of China (English)

    ZHOU YEZHONG; YANG RONG

    2011-01-01

    @@ The values foundation of human rights originates from people's dignity, while the formation of people's dignity was closely related to certain social system and historical conditions.From this aspect, we can say that human rights has natural attribute and social attribute, of which, social attribute plays a decisive role on the values of human rights.

  1. Fatty acid metabolism studies of human epidermal cell cultures.

    Science.gov (United States)

    Marcelo, C L; Dunham, W R

    1993-12-01

    Adult human epidermal keratinocytes grow rapidly in medium that is essential fatty acid (EFA)-deficient. In this medium they exhibit decreased amounts of the fatty acids, 18:2, 20:3, 20:4, and contain increased amounts of monounsaturated fatty acids. [14C]- and [3H]acetate and radiolabeled fatty acids, 16:0, 18:2, and 20:4 were used to study the fatty acid metabolism of these cells. Label from acetate appeared in 14- to 20-carbon fatty acids, both saturated and monounsaturated. No label was seen in the essential fatty acid 18:2, 18:3, and 20:4. Radiolabel from [9, 10-3H]palmitic acid (16:0) was detected in 16:0, 16:1, 18:0, and 18:1. [14C]linoleic acid (18:2) was converted to 18:3, 20:2, 20:3, and 20:4, demonstrating delta 6 and delta 5 desaturase activity in keratinocytes. Label from acetate, 16:0, or 18:2 was found mostly in the cellular phospholipids while only one third of the label from [14C]arachidonic was found in the phospholipids. [14C]acetate and [14C]18:2 time course data were used to construct a model of the metabolism of these reactants, using coupled, first-order differential equations. The data show that EFA-deficient keratinocytes metabolize fatty acids using pathways previously found in liver; they suggest the positioning of 18:2 desaturase and 18:3 elongase near the plasma membrane; they indicate that for the synthesis of nonessential fatty acids the formation of 18:0 from 16:0 is the rate-determining step; and they show that the conversion of 18:2 to 20:3 is rapid. These experiments demonstrate a method to study lipid enzyme kinetics in living cells.

  2. Amino acids and metal ions protect endothelial cells from lethal injury

    Energy Technology Data Exchange (ETDEWEB)

    Varani, J.; Ginsburg, I.; Johnson, K.J.; Gibbs, D.F.; Weinberg, J.M.; Ward, P.A. (Univ. of Michigan, Ann Arbor (United States))

    1991-03-11

    Killing of rat pulmonary artery endothelial cells by activated neutrophils is dependent on generation of hydrogen peroxide and its conversion to a highly toxic radical (presumably the hydroxyl radical) in a ferrous iron-dependent reaction. Glycine (as well as several other amino acids) is capable of inhibiting endothelial cell killing in vitro by either activated neutrophils or reagent hydrogen peroxide. Inhibition of killing is enhanced in the presence of micromolar concentrations of manganous ion (Mn2+). The combined effects of glycine and Mn2+ require concomitant presence of bicarbonate ion and is inhibited by high phosphate levels. Glycine can also protect endothelial cells from lethal injury inducted by ionomycin. There appears to be no enhancement with Mn2+, however against this form of lethal injury. The protective effects of glycine, Mn2+ and bicarbonate ion against injury by hydrogen peroxide is associated with a direct disproportionation of the hydrogen peroxide to water with little generation of molecular oxygen. Either glycine or Mn2+ alone does not have this effect. In addition to protecting endothelial cells from hydrogen peroxide-mediated injury, glycine or MN2+ is almost completely protective. Additionally, treatment of rats with concentrations of EDTA that do not by themselves induce injury greatly accentuates lung injury induced by glucose oxidase. These findings suggest that circulating amino acids in combination with Mn2+ and bicarbonate ions may contribute to the normal anti-oxidant barrier. These findings may also form the basis for a possible new therapeutic approach to oxygen radical-mediated injury.

  3. Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urine.

    Science.gov (United States)

    Salvatore, Sonia R; Vitturi, Dario A; Baker, Paul R S; Bonacci, Gustavo; Koenitzer, Jeffrey R; Woodcock, Steven R; Freeman, Bruce A; Schopfer, Francisco J

    2013-07-01

    The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca-9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 ± 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and coelution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with mercury chloride. This reaction increases the level of free nitroalkene fraction >10-fold and displays a K(D) of 7.5 × 10(-6) M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive noninvasive index of metabolic and inflammatory status.

  4. p-Coumaric acid, a common dietary polyphenol, protects cadmium chloride-induced nephrotoxicity in rats.

    Science.gov (United States)

    Navaneethan, Dhanalakshmi; Rasool, Mahaboobkhan

    2014-03-01

    The present study was conducted to elucidate the protective role of p-coumaric acid, a common dietary polyphenol against cadmium induced nephrotoxicity in rats. For the purpose of comparison, a standard reference drug silymarin (50 mg/kg b. wt) was used. In this experiment, the animals were divided into four groups, with each consisting of six animals. The animals in Group I animals received saline and served as a control group and those in Group II received cadmium chloride (3 mg/kg b. wt) subcutaneously once daily for 3 weeks, but Group III and IV animals received cadmium chloride followed by p-coumaric acid (100 mg/kg b. wt, oral) and silymarin (50 mg/kg b. wt, oral), respectively, daily for 3 weeks. At the end of the treatment, the animals were sacrificed, and the blood and kidney samples were collected. The results obtained in this study revealed the fact that the levels of lipid peroxidation, lysosomal enzymes, glycoprotein, cadmium and metallothionein were increased in the cadmium chloride alone treated rats and antioxidant status was found to be decreased, when compared to the control group. The levels of kidney functional markers (urea, uric acid and creatinine) were also found to be abnormal in serum and urine of cadmium chloride alone treated rats. On the other hand, the administration of p-coumaric acid along with cadmium chloride significantly protected the biochemical alterations as observed in the cadmium chloride alone treated rats as evidenced by histopathology. Thus, the oral administration of p-coumaric acid significantly protected the cadmium-induced nephrotoxicity in rats.

  5. Kinetic characteristics of acidic and alkaline ceramidase in human epidermis

    NARCIS (Netherlands)

    Houben, E.; Uchida, Y.; Nieuwenhuizen, W.F.; Paepe, K. de; Vanhaecke, T.; Holleran, W.M.; Rogiers, V.

    2007-01-01

    It has recently become evident that at least five ceramidase (CDase) isoforms are present in human epidermis, and that specifically acidic CDase (aCDase) and alkaline CDase (alkCDase) activities increase during keratinocyte differentiation, and thus might play a pivotal role(s) in permeability

  6. Kinetic characteristics of acidic and alkaline ceramidase in human epidermis

    NARCIS (Netherlands)

    Houben, E.; Uchida, Y.; Nieuwenhuizen, W.F.; Paepe, K. de; Vanhaecke, T.; Holleran, W.M.; Rogiers, V.

    2007-01-01

    It has recently become evident that at least five ceramidase (CDase) isoforms are present in human epidermis, and that specifically acidic CDase (aCDase) and alkaline CDase (alkCDase) activities increase during keratinocyte differentiation, and thus might play a pivotal role(s) in permeability barri

  7. Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.

    Science.gov (United States)

    Shekhawat, Prem; Bennett, Michael J; Sadovsky, Yoel; Nelson, D Michael; Rakheja, Dinesh; Strauss, Arnold W

    2003-06-01

    The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.

  8. An ascorbic acid-enriched tomato genotype to fight UVA-induced oxidative stress in normal human keratinocytes.

    Science.gov (United States)

    Petruk, Ganna; Raiola, Assunta; Del Giudice, Rita; Barone, Amalia; Frusciante, Luigi; Rigano, Maria Manuela; Monti, Daria Maria

    2016-10-01

    UVA radiations contribute up to 95% of the total UV exposure and are known to induce cell damage, leading to apoptosis. Since the benefic effects of ascorbic acid on human health are well known, a new tomato genotype (named DHO4), highly rich in ascorbic acid, has been recently obtained. Here, we compared the effects of ascorbic acid and hydrophilic DHO4 extracts in protecting human keratinocytes exposed to UVA stress. Keratinocytes were pre-incubated with ascorbic acid or with extracts from the ascorbic acid enriched tomato genotype and irradiated with UVA light. Then, ROS production, intracellular GSH and lipid peroxidation levels were quantified. Western blots were carried out to evaluate mitogen-activated protein kinases cascade, activation of caspase-3 and inflammation levels. We demonstrated that ROS, GSH and lipid peroxidation levels were not altered in cell exposed to UVA stress when cells were pre-treated with ascorbic acid or with tomato extracts. In addition, no evidence of apoptosis and inflammation were observed in irradiated pre-treated cells. Altogether, we demonstrated the ability of an ascorbic acid enriched tomato genotype to counteract UVA-oxidative stress on human keratinocytes. This protective effect is due to the high concentration of vitamin C that acts as free radical scavenger. This novel tomato genotype may be used as genetic material in breeding schemes to produce improved varieties with higher antioxidant levels.

  9. Fatty acid and sn-2 fatty acid composition in human milk from Granada (Spain) and in infant formulas.

    Science.gov (United States)

    López-López, A; López-Sabater, M C; Campoy-Folgoso, C; Rivero-Urgell, M; Castellote-Bargalló, A I

    2002-12-01

    To investigate differences in fatty acid and sn-2 fatty acid composition in colostrum, transitional and mature human milk, and in term infant formulas. Departament de Nutrició i Bromatologia, University of Barcelona, Spain and University Hospital of Granada, Spain. One-hundred and twenty mothers and 11 available types of infant formulas for term infants. We analysed the fatty acid composition of colostrum (n=40), transitional milk (n=40), mature milk (n=40) and 11 infant formulas. We also analysed the fatty acid composition at sn-2 position in colostrum (n=12), transitional milk (n=12), mature milk (n=12), and the 11 infant formulas. Human milk in Spain had low saturated fatty acids, high monounsaturated fatty acids and high linolenic acid. Infant formulas and mature human milk had similar fatty acid composition. In mature milk, palmitic acid was preferentially esterified at the sn-2 position (86.25%), and oleic and linoleic acids were predominantly esterified at the sn-1,3 positions (12.22 and 22.27%, respectively, in the sn-2 position). In infant formulas, palmitic acid was preferentially esterified at the sn-1,3 positions and oleic and linoleic acids had higher percentages at the sn-2 position than they do in human milk. Fatty acid composition of human milk in Spain seems to reflect the Mediterranean dietary habits of mothers. Infant formulas resemble the fatty acid profile of human milk, but the distribution of fatty acids at the sn-2 position is markedly different.

  10. Protective effects of gallic acid against spinal cord injury-induced oxidative stress.

    Science.gov (United States)

    Yang, Yong Hong; Wang, Zao; Zheng, Jie; Wang, Ran

    2015-08-01

    The present study aimed to investigate the role of gallic acid in oxidative stress induced during spinal cord injury (SCI). In order to measure oxidative stress, the levels of lipid peroxide, protein carbonyl, reactive oxygen species and nitrates/nitrites were determined. In addition, the antioxidant status during SCI injury and the protective role of gallic acid were investigated by determining glutathione levels as well as the activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. Adenosine triphophatase (ATPase) enzyme activities were determined to evaluate the role of gallic acid in SCI-induced deregulation of the activity of enzymes involved in ion homeostasis. The levels of inflammatory markers such as nuclear factor (NF)-κB and cycloxygenase (COX)-2 were determined by western blot analysis. Treatment with gallic acid was observed to significantly mitigate SCI-induced oxidative stress and the inflammatory response by reducing the oxidative stress, decreasing the expression of NF-κB and COX-2 as well as increasing the antioxidant status of cells. In addition, gallic acid modulated the activity of ATPase enzymes. Thus the present study indicated that gallic acid may have a role as a potent antioxidant and anti-inflammatory agent against SCI.

  11. Amino Acid Substitutions Improve the Immunogenicity of H7N7HA Protein and Protect Mice against Lethal H7N7 Viral Challenge.

    Directory of Open Access Journals (Sweden)

    Subaschandrabose Rajesh Kumar

    Full Text Available Avian influenza A H7N7/NL/219/03 virus creates a serious pandemic threat to human health because it can transmit directly from domestic poultry to humans and from human to human. Our previous vaccine study reported that mice when immunized intranasally (i.n with live Bac-HA were protected from lethal H7N7/NL/219/03 challenge, whereas incomplete protection was obtained when administered subcutaneously (s.c due to the fact that H7N7 is a poor inducer of neutralizing antibodies. Interestingly, our recent vaccine studies reported that mice when vaccinated subcutaneously with Bac-HA (H7N9 was protected against both H7N9 (A/Sh2/2013 and H7N7 virus challenge. HA1 region of both H7N7 and H7N9 viruses are differ at 15 amino acid positions. Among those, we selected three amino acid positions (T143, T198 and I211 in HA1 region of H7N7. These amino acids are located within or near the receptor binding site. Following the selection, we substituted the amino acid at these three positions with amino acids found on H7N9HA wild-type. In this study, we evaluate the impact of amino acid substitutions in the H7N7 HA-protein on the immunogenicity. We generated six mutant constructs from wild-type influenza H7N7HA cDNA by site directed mutagenesis, and individually expressed mutant HA protein on the surface of baculovirus (Bac-HAm and compared their protective efficacy of the vaccines with Bac-H7N7HA wild-type (Bac-HA by lethal H7N7 viral challenge in a mouse model. We found that mice immunized subcutaneously with Bac-HAm constructs T143A or T198A-I211V or I211V-T143A serum showed significantly higher hemagglutination inhibition and neutralization titer against H7N7 and H7N9 viruses when compared to Bac-HA vaccinated mice groups. We also observed low level of lung viral titer, negligible weight loss and complete protection against lethal H7N7 viral challenge. Our results indicated that amino acid substitution at position 143 or 211 improve immunogenicity of H7N7HA

  12. LEGAL PROTECTION AGAINST CHILDREN WHO ARE VICTIMS OF HUMAN TRAFFICKING IN CIANJUR DISTRICT STUDIED BY HUMAN RIGHTS PERSPECTIVE

    Directory of Open Access Journals (Sweden)

    Henny Nuraeny

    2015-05-01

    Full Text Available Trafficking in persons is a modern form of slavery. The eradication of human trafficking has been on the agenda in law enforcement because of its effects can interfere with social welfare. One form of trafficking in persons who lately is rampant child trafficking. The problems that can be studied is how the perspective of Human Rights in providing protection to children who are victims of trafficking and whether the implementation of legal protection for child victims of trafficking in Cianjur is in line with the concept of human rights. This study uses normative juridical approach and specification of descriptive analysis. Results from this study is the protection of child victims of trafficking in persons has been referred to the concept of human rights which the regional government make policies on prevention of trafficking, rehabilitation, counseling and empowerment of victims of human trafficking.

  13. Kinetics of saturated, monounsaturated, and polyunsaturated fatty acids in humans.

    Science.gov (United States)

    Nelson, Robert H; Mundi, Manpreet S; Vlazny, Danielle T; Smailovic, Almira; Muthusamy, Kalpana; Almandoz, Jaime P; Singh, Ekta; Jensen, Michael D; Miles, John M

    2013-03-01

    Plasma free fatty acid (FFA) kinetics in humans are often measured with only one tracer. In study 1, healthy volunteers received infusions of [U-¹³C]linoleate, [U-¹³C]oleate, and [U-¹³C]palmitate during continuous feeding with liquid meals low (n = 12) and high (n = 5) in palmitate and containing three labeled fatty acids to measure FFA appearance and fractional spillover of lipoprotein lipase-generated fatty acids. Study 2 used an intravenous lipid emulsion to increase FFA concentrations during infusion of linoleate and palmitate tracers. In study 1, there were no differences in spillover of the three fatty acids for the low-palmitate meal, but linoleate spillover was greater than oleate or palmitate for the high-palmitate meal. In studies 1 and 2, clearance was significantly greater for linoleate than for the other FFAs. There was a negative correlation between clearance and concentration for each fatty acid in the two studies. In study 1, concentration and spillover correlated positively for oleate and palmitate but negatively for linoleate. In conclusion, linoleate spillover is greater than that of other fatty acids under some circumstances. Linoleate clearance is greater than that of palmitate or oleate, indicating a need for caution when using a single FFA to infer the behavior of all fatty acids.

  14. Modulation of human stratum corneum properties by salicylic acid and all-trans-retinoic acid.

    Science.gov (United States)

    Piérard-Franchimont, C; Goffin, V; Piérard, G E

    1998-01-01

    Topical all-trans-retinoic acid (RA) has been reported to decrease the in vivo skin response to sodium lauryl sulfate (SLS). The converse was also shown with a synergistic effect of RA following prior applications of SLS. The reason for such effects is not clear. We employed measures of transepidermal water loss (TEWL), squamometry and sequential corneosurfametry to explore the protective activity of a 0.05% RA cream at the level of the stratum corneum. Nonionic oil-in-water emulsions with or without 5% salicylic acid (SA) served as test product references. Data indicated that the RA formulation was responsible for a stochastic impairment in the TEWL and for an increased intercorneocyte cohesion. SA and the unmedicated emulsion did not lead to similar TEWL changes. The squamometry test proved to be very sensitive to disclose the effects of SA and RA without, however, allowing to distinguish the difference in the physiological processes involved. The corneosurfametry bioassay did not show any protection or synergistic effect between RA or SA and SLS challenge on the stratum corneum. This is in contrast to a previous work showing a positive protective effect afforded by retinol against SLS. The combined effects of irritant compounds affecting the stratum corneum are complex. The precise reason for some of their biological consequences remains a conundrum. On balance, products such as SA and RA do not appear to afford protection or impairment to a surfactant challenge at the level of the stratum corneum.

  15. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-09

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  16. Managing Human Activities in Antarctica : Should Wilderness Protection Count?

    NARCIS (Netherlands)

    Bastmeijer, C.J.

    2005-01-01

    Antarctica is often described as one of the world's last wildernesses. In harmony with this general perception, the wilderness values of Antarctica received legal status with the adoption of the Protocol on Environmental Protection to the Antarctic Treaty. Article 3(1) of the Protocol obliges each C

  17. Synthesis of Orthogonally Protected Muramic Acid Building Blocks for Solid Phase Peptide Synthesis

    Directory of Open Access Journals (Sweden)

    Kristina Vlahoviček-Kahlina

    2015-07-01

    Full Text Available Muramic acid is found in many peptide natural products containing oligo(polysaccharide moieties. Taking into consideration that the Fmoc methodology is routinely used for solid-phase peptide synthesis, preparation of orthogonally protected muramic acid building blocks for total solid-phase synthesis of these natural products is of particular practical importance. Herein a simple and efficient synthesis of benzyl 2-amino-4,6-O-benzylidene-3-O-[(R-1-carboxyethyl]-2-deoxy-N-9-fluorenylmethyloxycarbonyl-α-D-glucopyranoside (6 from N-acetylglucosamine (1 is described. Important improvements over previous synthetic approaches to glucopyranosides 2 (benzyl 2-acetamido-2-deoxy-α-D-glucopyranoside and 3 (benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside, key building blocks in preparation of 6, include synthesis simplification and efficient isolation and purification. Optically pure (S-2-chloropropionic acid 7 was prepared and introduced to the positon 3-O of sugar moiety to give compound 4 (benzyl 2-acetamido-4,6-O-benzylidene-3-O-[(R-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside with the (R-configuration of the lactyl side-chain in excellent overall yield and optical purity. Deacetylation of amino group gave compound 5 (benzyl 2-amino-4,6-O-benzylidene-3-O-[(R-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside suitable for incorporation of the Fmoc protecting group to give protected muramic acid derivative 6, a useful building block in peptide synthesis.

  18. Chronic dietary administration of valproic acid protects neurons of the rat nucleus basalis magnocellularis from ibotenic acid neurotoxicity.

    Science.gov (United States)

    Eleuteri, Simona; Monti, Barbara; Brignani, Sara; Contestabile, Antonio

    2009-02-01

    Valproic acid (VPA) has been used for many years as a drug of choice for epilepsy and mood disorders. Recently, evidence has been proposed for a wide spectrum of actions of this drug, including antitumoral and neuroprotective properties. Valproic acid-mediated neuroprotection in vivo has been so far demonstrated in a limited number of experimental models. In this study, we have tested the neuroprotective potential of chronic (4 + 1 weeks) dietary administration of VPA on degeneration of cholinergic and GABAergic neurons of the rat nucleus basalis magnocellularis (NBM), injected with the excitotoxin, ibotenic acid (IBO), an animal models that is relevant for Alzheimer's disease-like neurodegeneration. We show that VPA treatment significantly protects both cholinergic and GABAergic neurons present in the injected area from the excitotoxic insult. A significant level of neuroprotection, in particular, is exerted towards the cholinergic neurons of the NBM projecting to the cortex, as demonstrated by the substantially higher levels of cholinergic markers maintained in the target cortical area of VPA-treated rats after IBO injection in the NBM. We further show that chronic VPA administration results in increased acetylation of histone H3 in brain, consistent with the histone deacetylase inhibitory action of VPA and putatively linked to a neuroprotective action of the drug mediated at the epigenetic level.

  19. How Should Police Respect and Protect Human Rights?

    Institute of Scientific and Technical Information of China (English)

    WANG XIUHONG

    2007-01-01

    @@ A11 people are equal before law and human rights must be respected and guaranteed.This is an established principle in China in bringing about a harmonious society. But how should police respect and ensure human rights in exercising their powers?

  20. Catabolism of coffee chlorogenic acids by human colonic microbiota.

    Science.gov (United States)

    Ludwig, Iziar A; Paz de Peña, Maria; Concepción, Cid; Alan, Crozier

    2013-01-01

    Several studies have indicated potential health benefits associated with coffee consumption. These benefits might be ascribed in part to the chlorogenic acids (CGAs), the main (poly)phenols in coffee. The impact of these dietary (poly)phenols on health depends on their bioavailability. As they pass along the gastrointestinal tract, CGAs are metabolized extensively and it is their metabolites rather than the parent compounds that predominate in the circulatory system. This article reports on a study in which after incubation of espresso coffee with human fecal samples, high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to monitor CGA breakdown and identify and quantify the catabolites produced by the colonic microflora. The CGAs were rapidly degraded by the colonic microflora and over the 6-h incubation period, 11 catabolites were identified and quantified. The appearance of the initial degradation products, caffeic and ferulic acids, was transient, with maximum quantities at 1 h. Dihydrocaffeic acid, dihydroferulic acid, and 3-(3'-hydroxyphenyl)propionic acid were the major end products, comprising 75-83% of the total catabolites, whereas the remaining 17-25% consisted of six minor catabolites. The rate and extent of the degradation showed a clear influence of the composition of the gut microbiota of individual volunteers. Pathways involved in colonic catabolism of CGAs are proposed and comparison with studies on the bioavailability of coffee CGAs ingested by humans helped distinguish between colonic catabolites and phase II metabolites of CGAs.

  1. A neutralizing monoclonal antibody targeting the acid-sensitive region in chikungunya virus E2 protects from disease.

    Directory of Open Access Journals (Sweden)

    Suganya Selvarajah

    Full Text Available The mosquito-borne alphavirus, chikungunya virus (CHIKV, has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV.

  2. Lactic acid delays the inflammatory response of human monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peter, Katrin, E-mail: katrin.peter@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Rehli, Michael, E-mail: michael.rehli@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Singer, Katrin, E-mail: katrin.singer@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Renner-Sattler, Kathrin, E-mail: kathrin.renner-sattler@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); Kreutz, Marina, E-mail: marina.kreutz@ukr.de [Department of Internal Medicine III, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany); RCI Regensburg Center for Interventional Immunology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg (Germany)

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. - Highlights: • Lactic acid broadly delays LPS-induced gene expression in human monocytes. • Expression of important monocyte effector molecules is affected by lactic acid. • Interference of lactic acid with TLR signaling causes the delayed gene expression. • The profound effect of lactic acid might contribute to immune suppression in tumors.

  3. Patents and the obligation to protect health: examining the significance of human rights considerations in the protection of pharmaceutical patents.

    Science.gov (United States)

    Owoeye, Olasupo Ayodeji

    2014-06-01

    This article discusses the human right to health in the context of patent protection and access to medicines. It considers the limitations in international human rights law, especially in relation to socioeconomic rights, that make it difficult for the right to health to be a potent justification for derogation from trade or intellectual property agreements. It concludes by taking the view that while the right to health may be somewhat unenforceable in international law, its close association with enforceable rights such as the right to life can be a legitimate basis for making maximum use of the flexibilities in the international intellectual property regime to protect public health. The article takes the view that trade and intellectual property agreements must be interpreted in a way that endeavours as much as possible to resolve any seeming inconsistency with the right to health.

  4. Protecting human and ecological health under viral threats in Asia.

    Science.gov (United States)

    Matsui, S

    2005-01-01

    Severe acute respiratory syndrome (SARS) outbroke in 2003, and the avian influenza A (H5N1) also outbroke in 2003 and continued to 2004. These pandemic viral diseases originated in South East Asia. Many human and animal lives were lost. Economic damages due to the pandemics were also very large. The question arises of why did the pandemics originate from South East Asian areas. Human influenza A consists of many sub-types of coronaviruses including the SARS virus and the avian influenza (H5N1) that are all variants of RNA of avian coronavirus. Variants are formed during infection of a coronavirus through not only birds but also mammals, including human beings. There are hot spots where viral infection rates are accelerated among birds, mammals and human beings. Suspicious areas are in South East Asia, where living conditions of birds, mammals and human beings are so close that there are always risks of viral infection. When we see the living conditions of farmers in southern China, northern Vietnam, Laos and northern Myanmar, they commonly raise ducks/chickens with pigs sharing ponds into which they discharge household wastewater, including human excreta, and pig excreta that are significant carriers of viruses. Bird faeces are also key carriers of the viruses. In the ponds, they raise ducks and conduct fish culture. Other important players are migrating birds from North Asia, which are principal vectors of avian influenza viruses. There is an urgent necessity of improving human and ecological health in South East Asia to control viral infection among birds, mammals and human beings. We can hinder the vicious cycle of virus infection through water contamination in ponds by providing good human, pig and chicken sanitation. It is easy to provide good sanitation practices for human, pigs and chickens, introducing collection and treatment of excreta. Our modern water technology can find good solutions for the problem.

  5. Docosahexaenoic acid protects human retinal pigment epithelial cells against oxidative stress-induced apoptosis%二十二碳六烯酸抑制氧化应激状态下人视网膜色素上皮细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    刘越峰; 罗卫民; 张勇; 钟晓东

    2016-01-01

    AIM:To observe the effect of docosahexaenoic acid ( DHA) on H2 O2-induced apoptosis in human retinal pigment epithelium cells and its molecular mechanism .METHODS: Human retinal pigment epithelium cell line ARPE-19 was cultured in vitro, and 12.5 mmol/L H2 O2 was used to mimic the oxidative stress condition .The cells were treated with 30~100μmol/L DHA for 4~24 h.The expression of heme oxygenase-1 (HO-1) at mRNA and protein levels was detected by real-time PCR and Western blot , respectively .The enzymic activity of HO-1 was measured by colorimetry . Production of reactive oxygen species ( ROS) was determined by fluorescent probe .Activation of NF-E2-related factor 2 (Nrf2) was examined by immunofluorescence method .Apoptosis of ARPE-19 cells was analyzed by flow cytometry .RE-SULTS:The mRNA and protein expression and the enzymic activity of HO-1 were significantly increased in the ARPE-19 cells after DHA treatment .Meanwhile , nuclear translocation of Nrf 2 was also observed .Apoptosis appeared and ROS was produced upon H2O2 incubation.In contrast, DHA at 100 μmol/L significantly abrogated H2O2-induced apoptosis and ROS production.Furthermore, silencing of HO-1 by specific siRNA, or treatment with ZnPP, an inhibitor of HO-1, partly counteracted the protective effect against H 2 O2-induced apoptosis and ROS production .CONCLUSION: DHA protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase -1 expression after Nrf2 activation .%目的:观察二十二碳六烯酸( docosahexaenoic acid ,DHA)对外源性H2 O2诱导人视网膜色素上皮细胞凋亡的影响及分子机制。方法:体外培养人视网膜色素上皮细胞系ARPE-19,加入终浓度为12.5 mol/L的H2 O2诱导氧化应激,随后用30~100μmol/L DHA作用细胞4~24 h;real-time PCR和Western blot分别检测血红素氧合酶-1(heme oxygenase-1,HO-1) mRNA和蛋白的表达;比色法分析HO-1酶活性;荧光

  6. Acompañamiento in Colombia: international human rights protection of IDPs

    Directory of Open Access Journals (Sweden)

    Luis Enrique Eguren

    1999-04-01

    Full Text Available The deployment of international observerscan effectively deter human rights violationsagainst displaced people and those workingwith them. This article discusses the role oforganisations such as Peace BrigadesInternational in providing international humanrights protection.

  7. 75 FR 7481 - Meeting of the Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2010-02-19

    ... Menikoff, M.D., J.D., Director, Office for Human Research Protections (OHRP), or Julia Gorey, J.D... who plan to attend the meeting and need special assistance, such as sign language interpretation...

  8. Multilayer Polymeric Shielding to Protect Humans from Galactic Cosmic Radiation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In Sub-topic X4.01, NASA has identified a need for advanced radiation-shielding materials and structures to protect humans from the hazards of galactic cosmic...

  9. Understanding the transformative aspects of the Wilderness and Protected Lands experience upon human health

    Science.gov (United States)

    Alan Ewert; Jillisa Overholt; Alison Voight; Chun Chieh Wang

    2011-01-01

    Wilderness and Protected Landscapes (WPLs) have long been considered special areas for a variety of reasons including baseline data, impact analyses, protected zones, and other tangible and intangible values. Another salient, and some would argue, a more important value offered through WPLs is that of human transformation. Accordingly, three theories have provided the...

  10. Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells

    Directory of Open Access Journals (Sweden)

    Cristina Theoduloz

    2014-01-01

    Full Text Available Carnosic acid (CA and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS and lung fibroblasts (MRC-5 were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT-induced damage, and to increase the cellular reduced glutathione (GSH and prostaglandin E2 (PGE2 content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10–18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16–18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  11. Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model

    Directory of Open Access Journals (Sweden)

    Kyungjin Lee

    2015-06-01

    Full Text Available We recently reported the protective effects of chlorogenic acid (CGA in a transient middle cerebral artery occlusion (tMCAo rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p. dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

  12. ASPECTS OF THE EVOLUTION OF HUMAN RIGHTS PROTECTION IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    NICOLAE PURDĂ

    2013-05-01

    Full Text Available Human rights protection within the European Community and the European Union has developed judicially, the human rights being protected by the Community Courts as general principles of Community law. The Treaty of Maastricht and the Treaty of Amsterdam have codified the Community law within the area of human rights. The codification of European Union’s concept of human rights in a single document was realized by adopting the Charter of Fundamental Rights of the European Union, on 7 December 2000 in Nice, whose provisions acquired legally binding under the Treaty of Lisbon.

  13. Nordihydroguaiaretic Acid Attenuates the Oxidative Stress-Induced Decrease of CD33 Expression in Human Monocytes

    Directory of Open Access Journals (Sweden)

    Silvia Guzmán-Beltrán

    2013-01-01

    Full Text Available Nordihydroguaiaretic acid (NDGA is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs. Oxidative stress was induced by iodoacetate (IAA or hydrogen peroxide (H2O2 and was evaluated using reactive oxygen species (ROS production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H2O2 in human MNs. It was also shown that NDGA (20 μM attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H2O2. These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  14. Nordihydroguaiaretic acid attenuates the oxidative stress-induced decrease of CD33 expression in human monocytes.

    Science.gov (United States)

    Guzmán-Beltrán, Silvia; Pedraza-Chaverri, José; Gonzalez-Reyes, Susana; Hernández-Sánchez, Fernando; Juarez-Figueroa, Ulises E; Gonzalez, Yolanda; Bobadilla, Karen; Torres, Martha

    2013-01-01

    Nordihydroguaiaretic acid (NDGA) is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs). Oxidative stress was induced by iodoacetate (IAA) or hydrogen peroxide (H(2)O(2)) and was evaluated using reactive oxygen species (ROS) production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H(2)O(2) in human MNs. It was also shown that NDGA (20  μ M) attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H(2)O(2). These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  15. Isolation of lactic acid bacteria with potential protective culture characteristics from fruits

    Science.gov (United States)

    Hashim, Nurul Huda; Sani, Norrakiah Abdullah

    2015-09-01

    Lactic acid bacteria are also known as beneficial microorganisms abundantly found in fermented food products. In this study, lactic acid bacteria were isolated from fresh cut fruits obtained from local markets. Throughout the isolation process from 11 samples of fruits, 225 presumptive lactic acid bacteria were isolated on MRS agar medium. After catalase and oxidase tests, 149 resulted to fit the characteristics of lactic acid bacteria. Further identification using Gram staining was conducted to identify the Gram positive bacteria. After this confirmation, the fermentation characteristics of these isolates were identified. It was found that 87 (58.4%) isolates were heterofermentative, while the rest of 62 (41.6%) are homofermentative lactic acid bacteria. Later, all these isolates were investigated for the ability to inhibit growth of Staphylococcus aureus using agar spot assay method. Seven (4.7%) isolates showed strong antagonistic capacity, while 127 (85.2%) and 8 (5.4%) isolates have medium and weak antagonistic capacity, respectively. The other 7 (4.7%) isolates indicated to have no antagonistic effect on S. aureus. Results support the potential of LAB isolated in this study which showed strong antagonistic activity against S. aureus may be manipulated to become protective cultures in food products. While the homofermentative or heterofermentative LAB can be utilized in fermentation of food and non-food products depending on the by-products required during the fermentation.

  16. The protective effects of omega-3 fatty acids on rat testicular tissue

    Directory of Open Access Journals (Sweden)

    İsmail Zararsız

    2011-12-01

    Full Text Available Objectives: In this study, the protective effect of omega-3 fatty acids on testicular tissue was aimed to investigate at biochemical levels.Materials and methods: Totally, 16 adult male Wistar rats were divided into two groups. Rats in Group I were used as control and only saline was given by intragastric gavage. Rats in Group II, 400 mg/kg dose ω-3 fatty acids were given daily by intragastric gavage. At the end of the six-week experimental period, all rats were killed by decapitation. The testicular tissue specimens taken from animals, superoxide dismutase, glutathione peroxidase, malondialdehyde, enzyme activities were measured spectrophotometrically. In addition, blood testosterone levels were examined.Results: In our study, ω-3 fatty acids in rats were given a statistically significant increase in the levels of superoxide dismutase, and glutathione peroxidase a statistically significant decrease in malondialdehyde levels were determined when compared to control group. In addition, ω-3 fatty acids in rats given a statistically significant increase in blood testosterone levels were observed.Conclusion: We concluded that ω-3 fatty acid had favorable effects in rat testis tissue by preventing oxidative damage and increasing the level of testosterone.

  17. Protein and Essential Amino Acids to Protect Musculoskeletal Health during Spaceflight: Evidence of a Paradox?

    Directory of Open Access Journals (Sweden)

    Kyle J. Hackney

    2014-07-01

    Full Text Available Long-duration spaceflight results in muscle atrophy and a loss of bone mineral density. In skeletal muscle tissue, acute exercise and protein (e.g., essential amino acids stimulate anabolic pathways (e.g., muscle protein synthesis both independently and synergistically to maintain neutral or positive net muscle protein balance. Protein intake in space is recommended to be 12%–15% of total energy intake (≤1.4 g∙kg−1∙day−1 and spaceflight is associated with reduced energy intake (~20%, which enhances muscle catabolism. Increasing protein intake to 1.5–2.0 g∙kg−1∙day−1 may be beneficial for skeletal muscle tissue and could be accomplished with essential amino acid supplementation. However, increased consumption of sulfur-containing amino acids is associated with increased bone resorption, which creates a dilemma for musculoskeletal countermeasures, whereby optimizing skeletal muscle parameters via essential amino acid supplementation may worsen bone outcomes. To protect both muscle and bone health, future unloading studies should evaluate increased protein intake via non-sulfur containing essential amino acids or leucine in combination with exercise countermeasures and the concomitant influence of reduced energy intake.

  18. Valproic acid protects neurons and promotes neuronal regeneration after brachial plexus avulsion****

    Institute of Scientific and Technical Information of China (English)

    Qiang Li; Dianxiu Wu; Rui Li; Xiaojuan Zhu; Shusen Cui

    2013-01-01

    Valproic acid has been shown to exert neuroprotective effects and promote neurite outgrowth in several peripheral nerve injury models. However, whether valproic acid can exert its beneficial effect on neurons after brachial plexus avulsion injury is currently unknown. In this study, brachial plexus root avulsion models, established in Wistar rats, were administered daily with valproic acid dis-solved in drinking water (300 mg/kg) or normal water. On days 1, 2, 3, 7, 14 and 28 after avulsion injury, tissues of the C 5-T 1 spinal cord segments of the avulsion injured side were harvested to in-vestigate the expression of Bcl-2, c-Jun and growth associated protein 43 by real-time PCR and western blot assay. Results showed that valproic acid significantly increased the expression of Bcl-2 and growth associated protein 43, and reduced the c-Jun expression after brachial plexus avulsion. Our findings indicate that valproic acid can protect neurons in the spinal cord and enhance neuronal regeneration fol owing brachial plexus root avulsion.

  19. Protection of copper surface with phytic acid against corrosion in chloride solution.

    Science.gov (United States)

    Peca, Dunja; Pihlar, Boris; Ingrid, Milošev

    2014-01-01

    Phytic acid (inositol hexaphosphate) was tested as a corrosion inhibitor for copper in 3% sodium chloride. Phytic acid is a natural compound derived from plants, it is not toxic and can be considered as a green inhibitor. Electrochemical methods of linear polarization and potentiodynamic polarization were used to study the electrochemical behaviour and evaluate the inhibition effectiveness. To obtain the optimal corrosion protection the following experimental conditions were investigated: effect of surface pre-treatment (abrasion and three procedures of surface roughening), pre-formation of the layer of phytic acid, time of immersion and concentration of phytic acid. To evaluate the surface pre-treatment procedures the surface roughness and contact angle were measured. Optimal conditions for formation of phytic layer were selected resulting in the inhibition effectiveness of nearly 80%. Morphology and composition of the layer were further studied by scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The layer of phytic acid with thickness in the nanometer range homogeneously covers the copper surface. The obtained results show that this natural compound can be used as a mildly effective corrosion inhibitor for copper in chloride solution.

  20. Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro.

    Science.gov (United States)

    Jiang, Xu-Shun; Chen, Xue-Mei; Wan, Jiang-Min; Gui, Hai-Bo; Ruan, Xiong-Zhong; Du, Xiao-Gang

    2017-02-22

    Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis.

  1. Autophagy Protects against Palmitic Acid-Induced Apoptosis in Podocytes in vitro

    Science.gov (United States)

    Jiang, Xu-shun; Chen, Xue-mei; Wan, Jiang-min; Gui, Hai-bo; Ruan, Xiong-zhong; Du, Xiao-gang

    2017-01-01

    Autophagy is a highly conserved degradation process that is involved in the clearance of proteins and damaged organelles to maintain intracellular homeostasis and cell integrity. Type 2 diabetes is often accompanied by dyslipidemia with elevated levels of free fatty acids (FFAs). Podocytes, as an important component of the filtration barrier, are susceptible to lipid disorders. The loss of podocytes causes proteinuria, which is involved in the pathogenesis of diabetic nephropathy. In the present study, we demonstrated that palmitic acid (PA) promoted autophagy in podocytes. We further found that PA increased the production of reactive oxygen species (ROS) in podocytes and that NAC (N-acetyl-cysteine), a potent antioxidant, significantly eliminated the excessive ROS and suppressed autophagy, indicating that the increased generation of ROS was associated with the palmitic acid-induced autophagy in podocytes. Moreover, we also found that PA stimulation decreased the mitochondrial membrane potential in podocytes and induced podocyte apoptosis, while the inhibition of autophagy by chloroquine (CQ) enhanced palmitic acid-induced apoptosis accompanied by increased ROS generation, and the stimulation of autophagy by rapamycin (Rap) remarkably suppressed palmitic acid-induced ROS generation and apoptosis. Taken together, these in vitro findings suggest that PA-induced autophagy in podocytes is mediated by ROS production and that autophagy plays a protective role against PA-induced podocyte apoptosis. PMID:28225005

  2. Erosion protection conferred by whole human saliva, dialysed saliva, and artificial saliva

    OpenAIRE

    Baumann, T; J. Kozik; Lussi, A.; T. S. Carvalho

    2016-01-01

    During dental erosion, tooth minerals are dissolved, leading to a softening of the surface and consequently to irreversible surface loss. Components from human saliva form a pellicle on the tooth surface, providing some protection against erosion. To assess the effect of different components and compositions of saliva on the protective potential of the pellicle against enamel erosion, we prepared four different kinds of saliva: human whole stimulated saliva (HS), artificial saliva containing ...

  3. Space toxicology: protecting human health during space operations.

    Science.gov (United States)

    Khan-Mayberry, Noreen; James, John T; Tyl, Rochelle; Lam, Chiu-wing

    2011-02-01

    Space toxicology is a unique and targeted discipline for spaceflight, space habitation, and occupation of celestial bodies including planets, moons, and asteroids. Astronaut explorers face distinctive health challenges and limited resources for rescue and medical care during space operation. A central goal of space toxicology is to protect the health of the astronaut by assessing potential chemical exposures during spaceflight and setting safe limits that will protect the astronaut against chemical exposures while in a physiologically altered state. In order to maintain sustained occupation in space on the International Space Station (ISS), toxicological risks must be assessed and managed within the context of isolation, continuous exposures, reuse of air and water, limited rescue options, and the need to use highly toxic compounds for propulsion and other purposes. As we begin to explore other celestial bodies, in situ toxicological risks, such as inhalation of reactive mineral dusts, must also be managed.

  4. English walnuts (Juglans regia L.) protect endogenous antioxidants in humans

    Science.gov (United States)

    Ellagic acid monomers, polymeric tannins and related phenolic compounds isolated from English walnuts (Juglans regia L.) have been reported to inhibit LDL oxidation ex vivo and decrease biomarkers of oxidative stress in animal models. To determine whether dietary and endogenous antioxidants are pres...

  5. 5-Aminosalicylic acid protection against oxidative damage to synaptosomal membranes by alkoxyl radicals in vitro.

    Science.gov (United States)

    Kanski, J; Lauderback, C; Butterfield, D A

    2001-01-01

    The antioxidant properties of 5-aminosalicylic acid in vitro were evaluated in a synaptosomal membrane system prepared from gerbil cortical synaptosomes using EPR spin labeling and spectroscopic techniques. MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl) and 5-NS (5-nitroxide stearate) spin labels were used to assess changes in protein oxidation and membrane lipid fluidity, respectively. Synaptosomal membranes were subjected to oxidative stress by incubation with 1 mM azo-bis(isobutyronitrile) (AIBN) or 1 mM 2,2'-azobis(amidino propane) dihydrochloride (AAPH) at 37 degrees C for 30 minutes. The EPR analyses of the samples showed significant oxidation of synaptosomal proteins and a decrease in membrane fluidity. 5-Aminosalicylic acid also was evaluated by means of FRAP (the ferric reducing ability of plasma) test as a potential antioxidant. 5-Aminosalicylic acid also showed protection against the oxidation in gerbil cortical synaptosomes system caused by AIBN and AAPH. These results are consistent with the notion of antioxidant protection against free radical induced oxidative stress in synaptosomal membrane system by this agent.

  6. Striatal grafts provide sustained protection from kainic and quinolinic acid-induced damage.

    Science.gov (United States)

    Tulipan, N; Luo, S Q; Allen, G S; Whetsell, W O

    1988-12-01

    Grafts of neonatal striatal tissue were placed into the striata of adult rats. When challenged immediately with intrastriatal injections of either kainic or quinolinic acid, excitotoxic damage was prevented. Thirty days later these same graft recipients received another injection of excitotoxin. The intrastriatal grafts continued to mitigate toxin-induced damage. It is hypothesized that the grafted cells not only survive, but that they may continue to elaborate some substance or substances that prevent excitotoxin-induced injury for at least 30 days. Previous investigations indicated that grafts of neonatal striatal tissue can protect the recipient striatum from kainic acid toxicity. In the following study it is demonstrated that such grafts also protect the striatum from quinolinic acid, an endogenous excitotoxin which induces kainate-like neuronal degeneration and has been implicated in the pathogenesis of Huntington's disease. It is postulated that the salutary effect of striatal grafting may be sufficiently long lasting to mitigate a chronic toxic insult. Such grafting may therefore represent a therapy for Huntington's disease and other neurodegenerative disorders in which an endogenous or exogenous toxin has been implicated as the pathogenetic agent.

  7. Production of gladiolus submitted to gibberellic acid in a protected environment

    Directory of Open Access Journals (Sweden)

    Maristela Pereira Carvalho-Zanão

    2016-12-01

    Full Text Available Gladiolus is an important cut flower commercialized in Brazil, and the use of gibberellic acid (GA3 to cultivate it in a protected environment may promote the production of high quality flower spikes. This study aimed at evaluating the production of flower spikes and corms of gladiolus ('White Friendship' cultivar submitted to high concentrations and application methods of gibberellic acid, in a protected environment. The experimental design was randomized blocks, in a 2 x 4 factorial arrangement, being two application methods (foliar spraying and corm soaking and four concentrations (0 mg L-1, 250 mg L-1, 500 mg L-1 and 1,000 mg L-1 of gibberellic acid, with six replications and two plants per experimental unit. The following traits were evaluated: plant height, number of leaves per plant, marketable harvest point of flower spikes, number of florets per flower spike, flower panicle length, stem and floret diameter, corm perimeter, number of cormels per plant and production of corm fresh matter and leaf dry matter, flower spikes, corms and cormels. High concentrations of GA3 are not recommended for the production of flower spikes and corms of the gladiolus 'White Friendship' cultivar. The corm soaking application method anticipates the harvest of flower spikes and produces a higher number of cormels per plant. Regardless of the application method, the concentration of 550 mg L-1 of GA3 increases the cormel yield of the 'White Friendship' cultivar.

  8. Protective effects of electroacupuncture on acetylsalicylic acid-induced acute gastritis in rats

    Institute of Scientific and Technical Information of China (English)

    Hye Suk Hwang; Kyung-Ju Han; Yeon Hee Ryu; Eun Jin Yang; Yoo Sung Kim; Sang Yong Jeong; Young-Seop Lee; Myeong Soo Lee; Sung Tae Koo; Sun-Mi Choi

    2009-01-01

    AIM: To invest igate the protect ive effects of electroacupuncture (EA) pretreatment on acetylsalicylic acid (ASA)-induced ulceration in rats. METHODS: We randomly divided 72 rats into three groups including control (administered with distilled water), ASA group (administered 100 mg/kg ASA) and EA group (administered EA + 100 mg/kg ASA). Each rat was fasted for 18 to 24 h before experimentation, and lesion scores, gastric acidity, cyclooxygenase (COX)-1 and -2 mRNA levels, and total nitric oxide (NO) concentration were measured. RESULTS: The lesion scores of the EA group were significantly lower than those of the ASA group. Gastric acidity of the ASA and EA groups was reduced compared to the control group. COX-1 and -2 mRNA levels were significantly increased in the EA group as compared to the control and ASA groups, and NO levels were also significantly increased in the EA group as compared to the ASA group. CONCLUSION: These results suggest that EAmediated protection against ASA-induced ulceration in rats may occur via gastric defense components.

  9. Antibody protection reveals extended epitopes on the human TSH receptor.

    Directory of Open Access Journals (Sweden)

    Rauf Latif

    Full Text Available Stimulating, and some blocking, antibodies to the TSH receptor (TSHR have conformation-dependent epitopes reported to involve primarily the leucine rich repeat region of the ectodomain (LRD. However, successful crystallization of TSHR residues 22-260 has omitted important extracellular non-LRD residues including the hinge region which connects the TSHR ectodomain to the transmembrane domain and which is involved in ligand induced signal transduction. The aim of the present study, therefore, was to determine if TSHR antibodies (TSHR-Abs have non-LRD binding sites outside the LRD. To obtain this information we employed the method of epitope protection in which we first protected TSHR residues 1-412 with intact TSHR antibodies and then enzymatically digested the unprotected residues. Those peptides remaining were subsequently delineated by mass spectrometry. Fourteen out of 23 of the reported stimulating monoclonal TSHR-Ab crystal contact residues were protected by this technique which may reflect the higher binding energies of certain residues detected in this approach. Comparing the protected epitopes of two stimulating TSHR-Abs we found both similarities and differences but both antibodies also contacted the hinge region and the amino terminus of the TSHR following the signal peptide and encompassing cysteine box 1 which has previously been shown to be important for TSH binding and activation. A monoclonal blocking TSHR antibody revealed a similar pattern of binding regions but the residues that it contacted on the LRD were again distinct. These data demonstrated that conformationally dependent TSHR-Abs had epitopes not confined to the LRDs but also incorporated epitopes not revealed in the available crystal structure. Furthermore, the data also indicated that in addition to overlapping contact regions within the LRD, there are unique epitope patterns for each of the antibodies which may contribute to their functional heterogeneity.

  10. Omega-3 fatty acids (ῳ-3 fatty acids) in epilepsy: animal models and human clinical trials.

    Science.gov (United States)

    DeGiorgio, Christopher M; Taha, Ameer Y

    2016-10-01

    There is growing interest in alternative and nutritional therapies for drug resistant epilepsy. ῳ-3 fatty acids such as fish or krill oil are widely available supplements used to lower triglycerides and enhance cardiovascular health. ῳ-3 fatty acids have been studied extensively in animal models of epilepsy. Yet, evidence from randomized controlled clinical trials in epilepsy is at an early stage. This report focuses on the key ῳ-3 fatty acids DHA and EPA, their incorporation into the lipid bilayer, modulation of ion channels, and mechanisms of action in reducing excitability within the central nervous system. This paper presents pre-clinical evidence from mouse, rat, and canine models, and reports the efficacy of n-3 fatty acids in randomized controlled clinical trials. An English language search of PubMed and Google scholar for the years 1981-2016 was performed for animal studies and human randomized controlled clinical trials. Expert commentary: Basic science and animal models provide a cogent rationale and substantial evidence for a role of ῳ-3 fatty acids in reducing seizures. Results in humans are limited. Recent Phase II RCT evidence suggests that low to moderate dose of ῳ-3 fatty acids reduce seizures; however, larger multicenter randomized trials are needed to confirm or refute the evidence. The safety, health effects, low cost and ease of use make ῳ-3 fatty acids an intriguing alternative therapy for drug resistant epilepsy. Though safety of profile is excellent, the human data is not yet sufficient to support efficacy in drug resistant epilepsy at this time.

  11. Identification of tetrahydro-beta-carboline-3-carboxylic acid in foodstuffs, human urine and human milk.

    Science.gov (United States)

    Adachi, J; Mizoi, Y; Naito, T; Ogawa, Y; Uetani, Y; Ninomiya, I

    1991-05-01

    1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA), both precursors of mutagenic N-nitroso compounds (N-nitrosamines, 1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid and 2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid), were detected in various food-stuffs, urine from healthy human subjects and human milk. A purification procedure, involving a chemically-bonded material followed by HPLC combined with fluorometric detection, was used for the quantitative determination of these compounds, allowing the separation of two diastereoisomers of MTCA. An HPLC and mass spectrometry method was also developed for their identification. Comparing the concentration of MTCA and TCCA in fermented products and raw materials suggested that tetrahydro-beta-carbolines may have been produced through fermentation or by condensation of tryptophan and acetaldehyde formed from ethanol added as a food preservative. This is the first report of excretion of tetrahydro-beta-carbolines in human urine and human milk. A comparison of the concentrations of tetrahydro-beta-carbolines in urine from human infants and human milk indicates that tetrahydro-beta-carbolines may be synthesized endogenously in humans. A possible pathway of tryptophan metabolism in plants and animals is presented.

  12. Acetyl salicylic acid protected against heat stress damage in chicken myocardial cells and may associate with induced Hsp27 expression

    National Research Council Canada - National Science Library

    Di Wu; Jiao Xu; Erbao Song; Shu Tang; Xiaohui Zhang; N. Kemper; J. Hartung; Endong Bao

    2015-01-01

    We investigated whether acetyl salicylic acid (ASA) protects chicken myocardial cells from heat stress-mediated damage in vivo and whether the induction of Hsp27 expression is connected with this function...

  13. Oral Administration of Lipopolysaccharide of Acetic Acid Bacteria Protects Pollen Allergy in a Murine Model.

    Science.gov (United States)

    Amano, Satoko; Inagawa, Hiroyuki; Nakata, Yoko; Ohmori, Masaki; Kohchi, Chie; Soma, Gen-Ichiro

    2015-08-01

    Lipopolysaccharide (LPS), a major component of the cell wall of Gram-negative bacteria, is known to possess strong immune-regulatory activity. We have found and reported the existence of biologically-active LPS in acetic acid bacteria. The LPS shows Limulus-positive activity and activation of macrophages to produce nitric oxide and tumor necrosis factor. In this study, we investigated the anti-allergic effect of an orally-administrated acetic acid bacteria extract containing LPS; the cedar pollinosis model was used. Acetic acid bacteria were isolated from various fruits by Nodai kaihen medium. Then, the anti-allergic effect of acetic acid bacteria extracts was investigated. BALB/c mice were immunized with a mixture of cedar pollen and alum into their peritoneal cavity; they also received additional immunizations of pollen to nasal cavity. After immunizing the mice with pollen into their nasal cavity to trigger an allergic reaction, the frequency of nose scratching was counted for 5 min. The bacteria were cultured and prepared and the water-extract contained about 1-10 mg/ml of Limulus positive substances. The extract of acetic acid bacteria induced higher levels of interleukin (IL)-10 and FOXP3 mRNA expression in macrophages (RAW246.7 cell), as assessed by DNA microarray analysis. Oral administration of the acetic acid bacteria extract demonstrated significantly less scratching numbers than control water group with pollen immunization. These results showed that LPS in acetic acid bacteria has the potential to protect from an allergic reaction, especially from cedar pollinosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Protection of asylum seekers and illegal migrants human rights: Practice of the European Court of Human Rights

    Directory of Open Access Journals (Sweden)

    Đukanović Anđela

    2015-01-01

    Full Text Available Protection of asylum seeker and Illegal migrants human rights, has often been difficult due to the need of states to regulate unwanted migration flows. European Court of Human Rights plays an important role in protecting the rights of these individuals, through a set of human rights. Requests for interim measures under Rule 39 of the Rules of Court also have great importance. In cases involving illegal migrants and asylum-seekers, Court was often in difficult position, given the contradictions that could arise from the protection of human rights and the legitimate aim of the Contracting States to control the entry, residence and expulsion of aliens. Recent Courts judgment in case of M. S. S. against Belgium is particularly important, because of its remarkable influence on the perception of a common asylum system in the EU, as well as the judgment in the case of Jama Hirsi and Others v. Italy.

  15. Lysophosphatidic Acid (LPA Signaling in Human and Ruminant Reproductive Tract

    Directory of Open Access Journals (Sweden)

    Izabela Wocławek-Potocka

    2014-01-01

    Full Text Available Lysophosphatidic acid (LPA through activating its G protein-coupled receptors (LPAR 1–6 exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance.

  16. Escherichia coli O157:H7 Glutamate- and Arginine-dependent Acid Resistance Systems Protect Against Oxidative Stress During Extreme Acid Challenge

    Science.gov (United States)

    To investigate the protection that several known Escherichia coli O157:H7 acid resistance systems provide against oxidative stress, the addition of diamide or hydrogen peroxide were used concomitant with acid challenge at pH 2.5 to determine bacterial survival. Diamide and hydrogen peroxide both de...

  17. Nerve growth factor protects against palmitic acid-induced injury in retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    Pan-shi Yan; Shu Tang; Hai-feng Zhang; Yuan-yuan Guo; Zhi-wen Zeng; Qiang Wen

    2016-01-01

    Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of dia-betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF signiifcantly attenuated the levels of reactive oxygen species (ROS) and malondialde-hyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 sig-naling pathways.

  18. Capillary electrophoresis of acidic oligosaccharides from human milk.

    Science.gov (United States)

    Bao, Yuanwu; Newburg, David S

    2008-06-01

    Interest in defining the array of oligosaccharides of human milk has been increasing. Pathogens that bind glycans on their host mucosal surfaces may be inhibited by human milk oligosaccharides. It has been postulated that acidic oligosaccharides in human milk may inhibit binding by pathogens that bind acidic glycans in the gut, but testing this hypothesis requires their reliable quantification in milk. Sialyloligosaccharides of human milk have been quantified by HPLC and CE. A recent CE technique uses the MEKC mode with direct detection at 205 nm to resolve and quantify, in the native form, the 12 most dominant sialyloligosaccharides of human milk in a single 35-min run. The method gives a linear response from 39 to 2500 microg/mL with a coefficient of variation between 2 to 9% and accuracy from 93 to 109%. This was used to detect variation in expression of specific sialyloligosaccharides in milk. Individual sialyloligosaccharide concentrations in milk differ among individual donors and between less and more mature milk. Thus, CE can be used to measure variation in sialyloligosaccharide expression in milk, and thereby test the relationship of this variation-to-variation in risk of specific diseases in breastfed infants.

  19. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Jonas Ahlstedt

    2015-12-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  20. Radioimmunoassay for prostatic acid phosphatase in human serum. Methodologic aspects

    Energy Technology Data Exchange (ETDEWEB)

    Pradalier, N.; Canal, P.; Pujol, A.; Fregevu, Y. (Groupe de Recherches du Centre Claudius-Regaud, Toulouse (France)); Soula, G. (Faculte des Sciences Pharmaceutiques, Toulouse (France))

    1982-01-01

    We propose a double antibody radioimmunoassay for human prostatic acid phosphatase (PAP) in serum for diagnosis and management of prostatic adenocarcinoma under treatment. The antigen is purified from human prostatic fluid by a gel-filtration on Sephadex G 100 followed by affinity chromatography on Con A Sepharose. A specific antibody is raised in rabbits and purified by immunoadsorption with a female serum. The described technique offers both radioisotopic sensibility and immunologic specificity. Physiological values determined in the serum of 125 healthy males are below 2 ng/ml. No significative differences are observed with age. The proposed technique also shows significant differences between values evaluated for benign prostatic hyperplasia and prostatic adenocarcinoma.

  1. Excretion of amino acids by humans during space flight

    Science.gov (United States)

    Stein, T. P.; Schluter, M. D.

    1998-01-01

    We measured the urine amino acid distribution patterns before, during and after space flight on the Space Shuttle. The urine samples were collected on two separate flights of the space shuttle. The first flight lasted 9.5 days and the second flight 15 days. Urine was collected continuously on 8 subjects for the period beginning 10 d before launch to 6 d after landing. Results: In contrast to the earlier Skylab missions where a pronounced amino aciduria was found, on shuttle the urinary amino acids showed little change with spaceflight except for a marked decrease in all of the amino acids on FD (flight day) 1 (pvaline on FD3 and FD4 (p<0.05). Conclusions: (i) Amino aciduria is not an inevitable consequence of space flight. (ii) The occurrence of amino aciduria, like muscle protein breakdown is a mission specific effect rather than part of the general human response to microgravity.

  2. Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species.

    Science.gov (United States)

    Selma, María V; Beltrán, David; García-Villalba, Rocío; Espín, Juan C; Tomás-Barberán, Francisco A

    2014-08-01

    Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large human interindividual variability and this has been associated with differences in the colon microbiota. In the present study we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins. Both human intestinal bacteria grew similarly in the presence and absence of ellagic acid at 30 μM concentration. Ellagic acid catabolism and urolithin formation occurred during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy-urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin B) were not produced in pure cultures. Consequently, either other bacteria from the gut or the physiological conditions found in vivo are necessary for completing metabolism until the final urolithins (dihydroxy and monohydroxy urolithins) are produced. This is the first time that the urolithin production capacity of pure strains has been demonstrated. The identification of the urolithin-producing bacteria is a relevant outcome as urolithin implication in health (cardiovascular protection, anti-inflammatory and anticarcinogenic properties) has been supported by different bioassays and urolithins can be used in the development of functional foods and nutraceuticals. This study represents an initial work that opens interesting possibilities of describing enzymatic activities involved in urolithin production that can

  3. The relevance of coagulation factor X protection of adenoviruses in human sera.

    Science.gov (United States)

    Duffy, M R; Doszpoly, A; Turner, G; Nicklin, S A; Baker, A H

    2016-07-01

    Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.

  4. Branched Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) Protect against Colitis by Regulating Gut Innate and Adaptive Immune Responses.

    Science.gov (United States)

    Lee, Jennifer; Moraes-Vieira, Pedro M; Castoldi, Angela; Aryal, Pratik; Yee, Eric U; Vickers, Christopher; Parnas, Oren; Donaldson, Cynthia J; Saghatelian, Alan; Kahn, Barbara B

    2016-10-14

    We recently discovered a structurally novel class of endogenous lipids, branched palmitic acid esters of hydroxy stearic acids (PAHSAs), with beneficial metabolic and anti-inflammatory effects. We tested whether PAHSAs protect against colitis, which is a chronic inflammatory disease driven predominantly by defects in the innate mucosal barrier and adaptive immune system. There is an unmet clinical need for safe and well tolerated oral therapeutics with direct anti-inflammatory effects. Wild-type mice were pretreated orally with vehicle or 5-PAHSA (10 mg/kg) and 9-PAHSA (5 mg/kg) once daily for 3 days, followed by 10 days of either 0% or 2% dextran sulfate sodium water with continued vehicle or PAHSA treatment. The colon was collected for histopathology, gene expression, and flow cytometry. Intestinal crypt fractions were prepared for ex vivo bactericidal assays. Bone marrow-derived dendritic cells pretreated with vehicle or PAHSA and splenic CD4(+) T cells from syngeneic mice were co-cultured to assess antigen presentation and T cell activation in response to LPS. PAHSA treatment prevented weight loss, improved colitis scores (stool consistency, hematochezia, and mouse appearance), and augmented intestinal crypt Paneth cell bactericidal potency via a mechanism that may involve GPR120. In vitro, PAHSAs attenuated dendritic cell activation and subsequent T cell proliferation and Th1 polarization. The anti-inflammatory effects of PAHSAs in vivo resulted in reduced colonic T cell activation and pro-inflammatory cytokine and chemokine expression. These anti-inflammatory effects appear to be partially GPR120-dependent. We conclude that PAHSA treatment regulates innate and adaptive immune responses to prevent mucosal damage and protect against colitis. Thus, PAHSAs may be a novel treatment for colitis and related inflammation-driven diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. α-linolenic omega-3 fatty acid for stroke protection: from brain preconditioning paradigm to nutrition

    Directory of Open Access Journals (Sweden)

    Blondeau Nicolas

    2011-09-01

    Full Text Available Stroke is the third leading cause of death, due to its high incidence, the severity of the insult, and lack of treatment options. The only therapeutic is restoration of cerebral blood flow achieved by recombinant tissue plasminogen activator treatment, but only approximately 5% of patients receive it. In addition, therapeutics aimed at achieving neuroprotection by blocking the ischemic cascade, as identified in numerous preclinical studies, failed in clinical trials. This failure in translation from experimental models to clinical trials led to a re-evaluation of properties which would constitute the ‘‘best-in class’’ therapeutics to be used against stroke. Given that neuroprotection appears ineffective per se, an emerging direction is to identify therapies, probably combinatorial in nature, which protect the whole neurovascular unit and target timedependent neurotoxic mechanisms. Molecules that activate complex cellular signaling cascades that render the brain resistant to subsequent ischemia, known as preconditioners, offer a novel perspective in stroke protection. Preconditioning elicits complex endogenous neuroprotective responses that act by pleiotropic mechanisms to block death pathways, promote survival pathways and increase resistance. In addition to chemical preconditioners, natural/endogenous compounds such as adenosine, glutamate, lysophospholipids, and omega-3 polyunsaturated fatty acids have been demonstrated to be excellent preconditioners. Consequently, a major new concept in preconditioning to combat stroke is introduced, which is preconditioning achieved through supplementation of an essential item in diet or as a nutraceutical. Several epidemiologic studies suggested a beneficial effect of a seafood/omega-3-enriched diet in cerebral diseases, but the omega-3-induced protective mechanisms are still poorly identified. This review highlights how α-linolenic acid (ALA, the omega-3 polyunsaturated fatty acid precursor

  6. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation.

    Directory of Open Access Journals (Sweden)

    José Manuel Tirado-Vélez

    Full Text Available Multiple myeloma is a haematological malignancy characterized by the clonal proliferation of plasma cells. It has been proposed that targeting cancer cell metabolism would provide a new selective anticancer therapeutic strategy. In this work, we tested the hypothesis that inhibition of β-oxidation and de novo fatty acid synthesis would reduce cell proliferation in human myeloma cells. We evaluated the effect of etomoxir and orlistat on fatty acid metabolism, glucose metabolism, cell cycle distribution, proliferation, cell death and expression of G1/S phase regulatory proteins in myeloma cells. Etomoxir and orlistat inhibited β-oxidation and de novo fatty acid synthesis respectively in myeloma cells, without altering significantly glucose metabolism. These effects were associated with reduced cell viability and cell cycle arrest in G0/G1. Specifically, etomoxir and orlistat reduced by 40-70% myeloma cells proliferation. The combination of etomoxir and orlistat resulted in an additive inhibitory effect on cell proliferation. Orlistat induced apoptosis and sensitized RPMI-8226 cells to apoptosis induction by bortezomib, whereas apoptosis was not altered by etomoxir. Finally, the inhibitory effect of both drugs on cell proliferation was associated with reduced p21 protein levels and phosphorylation levels of retinoblastoma protein. In conclusion, inhibition of fatty acid metabolism represents a potential therapeutic approach to treat human multiple myeloma.

  7. Protective Effect of Ocimum basilicum Essential Oil Against Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Rashidian, Amir; Roohi, Parnia; Mehrzadi, Saeed; Ghannadi, Ali Reza; Minaiyan, Mohsen

    2016-10-01

    Ocimum basilicum L has been traditionally used for the treatment of inflammatory bowel disease in Iran. This study investigates the ameliorative effect of Ocimum basilicum essential oil on an acetic acid-induced colitis model in rats. Ocimum basilicum essential oil with 2 doses (200 and 400 μL/kg) significantly ameliorated wet weight/length ratio of colonic tissue compared to the control group. Higher doses of essential oil (200 and 400 μL/kg) significantly reduced ulcer severity, ulcer area, and ulcer index. On the other hand, histological examination revealed the diminution of total colitis index as a marker for inflammatory cell infiltration in the colonic segments of rats treated with Ocimum basilicum essential oil (200 and 400 μL/kg). The increased level of myeloperoxidase was significantly decreased after the treatment with the essential oil (200 and 400 μL/kg). These results suggest that Ocimum basilicum exhibits protective effect against acetic acid-induced colitis.

  8. In silico evidence for gluconeogenesis from fatty acids in humans.

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    Christoph Kaleta

    2011-07-01

    Full Text Available The question whether fatty acids can be converted into glucose in humans has a long standing tradition in biochemistry, and the expected answer is "No". Using recent advances in Systems Biology in the form of large-scale metabolic reconstructions, we reassessed this question by performing a global investigation of a genome-scale human metabolic network, which had been reconstructed on the basis of experimental results. By elementary flux pattern analysis, we found numerous pathways on which gluconeogenesis from fatty acids is feasible in humans. On these pathways, four moles of acetyl-CoA are converted into one mole of glucose and two moles of CO₂. Analyzing the detected pathways in detail we found that their energetic requirements potentially limit their capacity. This study has many other biochemical implications: effect of starvation, sports physiology, practically carbohydrate-free diets of inuit, as well as survival of hibernating animals and embryos of egg-laying animals. Moreover, the energetic loss associated to the usage of gluconeogenesis from fatty acids can help explain the efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet.

  9. Capillary electrophoresis separation of human milk neutral and acidic oligosaccharides derivatized with 2-aminoacridone.

    Science.gov (United States)

    Galeotti, Fabio; Coppa, Giovanni V; Zampini, Lucia; Maccari, Francesca; Galeazzi, Tiziana; Padella, Lucia; Santoro, Lucia; Gabrielli, Orazio; Volpi, Nicola

    2014-03-01

    Human milk is a unique fluid in glycobiology due to the presence of many free structurally complex oligosaccharides emerging as important dietary factors during early life and having many biological and protective functions. Methods that allow accurate profiling of oligosaccharide mixtures in this complex biological fluid with quantification of the four known genetically determined groups are welcomed. A high-voltage CE separation and detection at 254 nm of 17 neutral and acidic human milk oligosaccharide (HMO) standard along with lactose derivatized with 2-aminoacridone, using a BGE containing 20% methanol as an organic modifier and borate, able to form on-capillary anionic borate-polyol complexes, is reported. This CE approach was able to separate both neutral HMOs and acidic HMOs, with the sialic acid residue, also in the presence of lactose in high content. This method was applied to the four secretory groups individually extracted by a rapid and simple preparative step. LODs were found ranging from ∼50 to 700 fmol. We were able to measure HMO content also in the presence of excess fluorophore, or interference from proteins, peptides, salts, and other impurities normally present in this complex biological fluid. Overall, CE equipped with a UV detector is a common analytical approach and this simple CE separation offers high resolution and sensitivity for the differentiation of human milk samples related to genetic groups and days of lactation by considering that important changes in HMO content are a reflection of the lactation day.

  10. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria.

    Science.gov (United States)

    Huang, Jing; Li, Xiangming; Coelho-dos-Reis, Jordana G A; Zhang, Min; Mitchell, Robert; Nogueira, Raquel Tayar; Tsao, Tiffany; Noe, Amy R; Ayala, Ramses; Sahi, Vincent; Gutierrez, Gabriel M; Nussenzweig, Victor; Wilson, James M; Nardin, Elizabeth H; Nussenzweig, Ruth S; Tsuji, Moriya

    2015-12-01

    In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen.

  11. The Protection of Human Rights in Saudi Counter-terrorism Laws

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    Faleh Salem Alkahtani

    2016-12-01

    Full Text Available Human rights constitute a significant aspect of the law. Human rights are protected by national and international legal and judicial apparatuses. In addition, promoting respect for human rights is a key purpose of the United Nations (UN and its international bodies, such as the UN Human Rights Council, established in 2006, and the International Criminal Court, created in 1998. The UN has also issued a variety of protocols, declarations and agreements regarding human rights and their protection, specifically the Universal Declaration of Human Rights in 1948 and the International Convention on Civil and Political Rights in 1966. In the Kingdom of Saudi Arabia, Saudi legislation has initiated and allowed various Saudi human rights institutions, namely the Saudi Human Rights Commission and Saudi National Society for Human Rights. In particular, Saudi legislation has focused on Sharia principles when it comes to the interpretation and implementation of secular international human rights laws. Saudi legislation has enacted a variety of contemporary human rights laws, including the Child Protection Law and the Law of Protection from Abuse. The human cost of terrorism has been felt virtually in every part of the globe. Terrorism has disrupted peace, security, liberty and physical integrity of individuals at every level. Protection and security of its individuals is a fundamental obligation of the state. Accordingly, the Kingdom of Saudi Arabia has taken several legal measures, allowed under Islamic Sharia and International laws, to ensure the protection of human rights of its citizens and residents and safeguard the society against possible threats of terrorism and bring the criminals to justice. Saudi legislation has ensured human rights applications in other Saudi criminal laws, such as the Saudi Criminal Procedure Law of 2002, amended in 2014 (hereinafter SCPL, and the Saudi Law of Terrorist Crimes of 2014 (hereinafter SLTC. This short commentary

  12. Vanillin protects human keratinocyte stem cells against ultraviolet B irradiation.

    Science.gov (United States)

    Lee, Jienny; Cho, Jae Youl; Lee, Sang Yeol; Lee, Kyung-Woo; Lee, Jongsung; Song, Jae-Young

    2014-01-01

    Ultraviolet-B (UVB) irradiation is one of major factors which induce cellular damages in the epidermis. We investigated protective effects and mechanisms of vanillin, a main constituent of vanilla beans, against UVB-induced cellular damages in keratinocyte stem cells (KSC). Here, vanillin significantly attenuated UVB irradiation-induced cytotoxicity. The vanillin effects were also demonstrated by the results of the senescence-associated β-galactosidase and alkaline comet assays. In addition, vanillin induced production of pro-inflammatory cytokines. Attempts to elucidate a possible mechanism underlying the vanillin-mediated effects revealed that vanillin significantly reduced UVB-induced phosphorylation of ataxia telangiectasia mutated (ATM), serine threonine kinase checkpoint kinase 2 (Chk2), tumor suppressor protein 53 (p53), p38/mitogen-activated protein kinase (p38), c-Jun N-terminal kinase/stress-activated protein kinase (JNK), S6 ribosomal protein (S6RP), and histone 2A family member X (H2A.X). UVB-induced activation of p53 luciferase reporter was also significantly inhibited by vanillin. In addition, while ATM inhibitor had no effect on the vanillin effects, mouse double minute 2 homolog (MDM2) inhibitor significantly attenuated suppressive effects of vanillin on UVB-induced activation of p53 reporter in KSC. Taken together, these findings suggest that vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation.

  13. Salicylic acid and heat acclimation pretreatment protects Laminaria japonica sporophyte (Phaeophyceae) from heat stress

    Science.gov (United States)

    Zhou, Bin; Tang, Xuexi; Wang, You

    2010-07-01

    Possible mediatory roles of heat acclimation and salicylic acid in protecting the sporophyte of marine macroalga Laminaria japonica (Phaeophyceae) from heat stress were studied. Heat stress resulted in oxidative injury in the kelp blades. Under heat stress significant accumulation of hydrogen peroxide (H2O2) and malonaldehyde (MDA), a membrane lipid peroxidation product, and a drastic decrease in chlorophyll a content were recorded. Activity of the enzymatic antioxidant system was drastically affected by heat stress. The activity of superoxide dismutase (SOD) was significantly increased while peroxidase (POD), catalase (CAT) and glutathione peroxidase (GPX) were greatly inhibited and, simultaneously, phenylalanine ammonia-lyase was activated while polyphenol oxidase (PPO) was inhibited. Both heat acclimation pretreatment and exogenous application of salicylic acid alleviated oxidative damage in kelp blades. Blades receiving heat acclimation pretreatment and exogenous salicylic acid prior to heat stress exhibited a reduced increase in H2O2 and MDA content, and a lower reduction in chlorophyll a content. Pretreatment with heat acclimation and salicylic acid elevated activities of SOD, POD, CAT, GPX and PPO. Considering these results collectively, we speculate that the inhibition of antioxidant enzymes is a possible cause of the heat-stress-induced oxidative stress in L. japonica, and enhanced thermotolerance may be associated, at least in part, with the elevated activity of the enzymatic antioxidant system.

  14. Protective effect of Cratoxylum formosum extract against acid/alcohol-induced gastric mucosal damage in rats.

    Science.gov (United States)

    Sripanidkulchai, Kittisak; Teepsawang, Somsuda; Sripanidkulchai, Bungorn

    2010-10-01

    Cratoxylum formosum is an edible plant that is commonly consumed among the people in Northeast Thailand. This study aimed to investigate the gastroprotective effect of the ethanolic extract of C. formosum leaves (C. formosum ethanolic extract [CFE]). Gastric ulceration was induced in Wistar male rats by oral administration of acid/alcohol. Oral dosing with CFE at 250 and 500 mg/kg of body weight after the acid/alcohol induction significantly decreased the number of bleeding spots, area of bleeding, ulcer score, and ulcer index. Pretreatment with 500 mg/kg CFE significantly prevented the gastric damage. Histological studies of the acid/alcohol-induced animals indicated the gastric inflammation with lesion depth through the mucosal layer. Whereas the gastric lesion of the CFE-treated animals at both 250 and 500 mg/kg doses was decreased to be one-fourth of the mucosal layers, pretreatment with 500 mg/kg CFE prior to acid/alcohol induction completely protected against the mucosal damage. Biochemical analysis of gastric mucosa revealed a significant decrease of malondialdehyde in the CFE-treated group in a dose-response manner. These findings suggest that the gastroprotective activity of CFE could be mediated possibly through its antioxidant effect.

  15. Coffee polyphenols protect human plasma from postprandial carbonyl modifications.

    Science.gov (United States)

    Sirota, Roman; Gorelik, Shlomit; Harris, Raviv; Kohen, Ron; Kanner, Joseph

    2013-05-01

    The antioxidant capability of coffee polyphenols to inhibit red-meat lipid peroxidation in stomach medium and absorption into blood of malondialdehyde (MDA) in humans was studied. Roasted-ground coffee polyphenols that were found to inhibit lipid peroxidation in stomach medium are 2- to 5-fold more efficient antioxidant than those found in instant coffee. Human plasma from ten volunteers analyzed after a meal of red-meat cutlets (250 g) revealed a rapid accumulation of MDA. The accumulation of MDA in human plasma modified low-density lipoprotein is known to trigger atherogenesis. Consumption of 200 mL roasted coffee by ten volunteers during a meal of red-meat cutlets, resulted after 2 and 4 h in the inhibition by 80 and 50%, respectively, of postprandial plasma MDA absorption. The results obtained in vitro simulated stomach model on MDA accumulation were predictive for the amount of MDA absorbed into circulating human plasma, in vivo. Timing the consumption of coffee during the meals may make it a very active functional food.

  16. 77 FR 58383 - Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2012-09-20

    ... Julia Gorey, J.D., Executive Director, SACHRP; U.S. Department of Health and Human Services, 1101...: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the authority of 42 U.S.C. 217a, Section 222 of.... Individuals who plan to attend the meeting and need special assistance, such as sign language...

  17. 75 FR 59264 - Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2010-09-27

    ... (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP; U.S. Department of Health and Human Services... address: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the authority of 42 U.S.C. 217a, Section.... Individuals who plan to attend the meeting and need special assistance, such as sign language...

  18. Distribution of glycolipid and unsaturated fatty acids in human hair.

    Science.gov (United States)

    Takahashi, Toshie; Yoshida, Satoshi

    2014-09-01

    It has been recognized that human hair lipids play crucial roles in the integrity of cells and matrices, while the details of distribution and structure of the minor lipids are hardly known. Here we investigated the lipids at the hair surface, at the interface between cuticle and cortex and in the interior of hair (cortex, medulla and melanin granules). Hair lipids and fatty acids and their metabolites were detected and characterized by using infrared spectroscopy and several mass spectrometry techniques (FTIR, ToF-SIMS, GCMS, and ESI-MS). As a result, it was found that unsaturated fatty acids were present more in the cortex of hair than at the hair surface. At the interface between cuticle and cortex, it is suggested that steryl glycoside-like lipids containing N-acetylglucosamine were present, and contributing to the adhesion between the cuticle and cortex of hair. Oxidative metabolites derived from integral fatty acids such as linoleic and alpha-linolenic acids were found in the hair bulb and melanin granules. Especially the oxidative metabolites of alpha-linolenic acid were integrated into the lipids non-covalently and tightly bound to melanin granules (namely, melanin lipids) and suggested as being involved in the biosynthetic processes of melanosome.

  19. Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Zeghichi-Hamri, Sabrina; de Lorgeril, Michel; Salen, Patricia; Chibane, Mohamed; de Leiris, Joël; Boucher, François; Laporte, François

    2010-12-01

    Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.

  20. HEW Proposed Policy on the Protection of Human Subjects: Experimentation and the Institutionalized Mentally Disabled

    Science.gov (United States)

    Washington University Law Quarterly, 1975

    1975-01-01

    Underlying bases for federal interest in experimentation on human subjects, including abuses of investigative processes and efforts at regulation, are explored. Focus is on recent HEW rules on the protection of human subjects, which will have a significant impact on many research institutions. (LBH)

  1. Antioxidative Peptides Derived from Enzyme Hydrolysis of Bone Collagen after Microwave Assisted Acid Pre-Treatment and Nitrogen Protection

    Directory of Open Access Journals (Sweden)

    Jin Sun

    2010-11-01

    Full Text Available This study focused on the preparation method of antioxidant peptides by enzymatic hydrolysis of bone collagen after microwave assisted acid pre-treatment and nitrogen protection. Phosphoric acid showed the highest ability of hydrolysis among the four other acids tested (hydrochloric acid, sulfuric acid and/or citric acid. The highest degree of hydrolysis (DH was 9.5% using 4 mol/L phosphoric acid with a ratio of 1:6 under a microwave intensity of 510 W for 240 s. Neutral proteinase gave higher DH among the four protease tested (Acid protease, neutral protease, Alcalase and papain, with an optimum condition of: (1 ratio of enzyme and substrate, 4760 U/g; (2 concentration of substrate, 4%; (3 reaction temperature, 55 °C and (4 pH 7.0. At 4 h, DH increased significantly (P < 0.01 under nitrogen protection compared with normal microwave assisted acid pre-treatment hydrolysis conditions. The antioxidant ability of the hydrolysate increased and reached its maximum value at 3 h; however DH decreased dramatically after 3 h. Microwave assisted acid pre-treatment and nitrogen protection could be a quick preparatory method for hydrolyzing bone collagen.

  2. Priming for JA-dependent defenses using hexanoic acid is an effective mechanism to protect Arabidopsis against B. cinerea.

    Science.gov (United States)

    Kravchuk, Zhana; Vicedo, Begonya; Flors, Víctor; Camañes, Gemma; González-Bosch, Carmen; García-Agustín, Pilar

    2011-03-01

    Soil drench treatments with hexanoic acid can effectively protect Arabidopsis plants against Botrytis cinerea through a mechanism based on a stronger and faster accumulation of JA-dependent defenses. Plants impaired in ethylene, salicylic acid, abscisic acid or glutathion pathways showed intact protection by hexanoic acid upon B. cinerea infection. Accordingly, no significant changes in the SA marker gene PR-1 in either the SA or ABA hormone balance were observed in the infected and treated plants. In contrast, the JA signaling pathway showed dramatic changes after hexanoic acid treatment, mainly when the pathogen was present. The impaired JA mutants, jin1-2 and jar1, were unable to display hexanoic acid priming against the necrotroph. In addition, hexanoic acid-treated plants infected with B. cinerea showed priming in the expression of the PDF1.2, PR-4 and VSP1 genes implicated in the JA pathways. Moreover, JA and OPDA levels were primed at early stages by hexanoic acid. Treatments also stimulated increased callose accumulation in response to the pathogen. Although callose accumulation has proved an effective IR mechanism against B. cinerea, it is apparently not essential to express hexanoic acid-induced resistance (HxAc-IR) because the mutant pmr4.1 (callose synthesis defective mutant) is protected by treatment. We recently described how hexanoic acid treatments can protect tomato plants against B. cinerea by stimulating ABA-dependent callose deposition and by priming OPDA and JA-Ile production. We clearly demonstrate here that Hx-IR is a dependent plant species, since this acid protects Arabidopsis plants against the same necrotroph by priming JA-dependent defenses without enhancing callose accumulation.

  3. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition.

    Science.gov (United States)

    Bogan, Katrina L; Brenner, Charles

    2008-01-01

    Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

  4. Dietary requirements of "nutritionally non-essential amino acids" by animals and humans.

    Science.gov (United States)

    Wu, Guoyao; Wu, Zhenlong; Dai, Zhaolai; Yang, Ying; Wang, Weiwei; Liu, Chuang; Wang, Bin; Wang, Junjun; Yin, Yulong

    2013-04-01

    Amino acids are necessary for the survival, growth, development, reproduction and health of all organisms. They were traditionally classified as nutritionally essential or non-essential for mammals, birds and fish based on nitrogen balance or growth. It was assumed that all "non-essential amino acids (NEAA)" were synthesized sufficiently in the body to meet the needs for maximal growth and health. However, there has been no compelling experimental evidence to support this assumption over the past century. NEAA (e.g., glutamine, glutamate, proline, glycine and arginine) play important roles in regulating gene expression, cell signaling, antioxidative responses, neurotransmission, and immunity. Additionally, glutamate, glutamine and aspartate are major metabolic fuels for the small intestine to maintain its digestive function and protect its mucosal integrity. Therefore, based on new research findings, NEAA should be taken into consideration in revising the classical "ideal protein" concept and formulating balanced diets to improve protein accretion, food efficiency, and health in animals and humans.

  5. TOWARDS THE PROTECTION OF HUMAN RIGHTS: DO THE NEW ZIMBABWEAN CONSTITUTIONAL PROVISIONS ON JUDICIAL INDEPENDENCE SUFFICE?

    Directory of Open Access Journals (Sweden)

    Lovemore Chiduza

    2014-04-01

    Full Text Available If human rights are to be effectively protected in any country, the judiciary has to recognise that it also has a role to play in this regard. The rationale for this is that the judiciary has a duty to enhance and protect human rights. Across Africa and most notably in Zimbabwe political interference has been noted as a factor that limits judicial independence. In Zimbabwe the weak protection of judicial independence has contributed to gross human rights violations. Constitutional reforms have been conducted in order to improve the independence of the judiciary and consequently the judicial protection of human rights. These efforts have resulted in the adoption of a new Constitution in Zimbabwe which has replaced the Lancaster House Constitution. The Constitutional reforms have captured legal principles which will ensure an improvement in the human rights situation. Key to the reforms has been the independence of the judiciary. The Constitution guarantees the independence of the judiciary. Despite such guarantees there are a number of challenges with regards to this independence. The aim of this paper is therefore to analyse the judicial reforms introduced by the Constitution of Zimbabwe with a view to establishing whether or not such reforms are likely to improve judicial independence and in turn the protection of human rights in Zimbabwe.

  6. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Science.gov (United States)

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity.

  7. Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines

    Directory of Open Access Journals (Sweden)

    SezenYılmaz

    2016-02-01

    Full Text Available Objective: Many studies have been published on the antioxidative effects of boric acid (BA and sodium borates in in vitro studies. However, the boron (B concentrations tested in these in vitro studies have not been selected by taking into account the realistic blood B concentrations in humans due to the lack of comprehensive epidemiological studies. The recently published epidemiological studies on B exposure conducted in China and Turkey provided blood B concentrations for both humans in daily life and workers under extreme exposure conditions in occupational setting. The results of these studies have made it possible to test antioxidative effects of BA in in vitro studies within the concentration range relevant to humans. The aim of this study was to investigate the protective effects of BA against oxidative DNA damage in V79 (Chinese hamster lung fibroblast cells. The concentrations of BA tested for its protective effect was selected by taking the blood B concentrations into account reported in previously published epidemiological studies. Therefore, the concentrations of BA tested in this study represent the exposure levels for humans in both daily life and occupational settings. Materials and Methods: In this experimental study, comet assay and neutral red uptake (NRU assay methods were used to determinacy to toxicity and genotoxicity of BA and hydrogen peroxide (H2O2. Results: The results of the NRU assay showed that BA was not cytotoxic within the tested concentrations (3, 10, 30, 100 and 200 μM. These non-cytotoxic concentrations were used for comet assay. BA pre-treatment significantly reduced (P<0.05, one-way ANOVA the DNA damaging capacity of H2O2 at each tested BA concentrations in V79 cells. Conclusion: Consequently, pre-incubation of V79 cells with BA has significantly reduced the H2O2-induced oxidative DNA damage in V79 cells. The protective effect of BA against oxidative DNA damage in V79 cells at 5, 10, 50, 100 and 200 μM (54

  8. Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines

    Science.gov (United States)

    Yılmaz, Sezen; Ustundag, Aylin; Cemiloglu Ulker, Ozge; Duydu, Yalcın

    2016-01-01

    Objective Many studies have been published on the antioxidative effects of boric acid (BA) and sodium borates in in vitro studies. However, the boron (B) concentrations tested in these in vitro studies have not been selected by taking into account the realistic blood B concentrations in humans due to the lack of comprehensive epidemiological studies. The recently published epidemiological studies on B exposure conducted in China and Turkey provided blood B concentrations for both humans in daily life and workers under extreme exposure conditions in occupational setting. The results of these studies have made it possible to test antioxidative effects of BA in in vitro studies within the concentra- tion range relevant to humans. The aim of this study was to investigate the protective ef- fects of BA against oxidative DNA damage in V79 (Chinese hamster lung fibroblast) cells. The concentrations of BA tested for its protective effect was selected by taking the blood B concentrations into account reported in previously published epidemiological studies. Therefore, the concentrations of BA tested in this study represent the exposure levels for humans in both daily life and occupational settings. Materials and Methods In this experimental study, comet assay and neutral red uptake (NRU) assay methods were used to determinacy to toxicity and genotoxicity of BA and hydrogen peroxide (H2O2). Results The results of the NRU assay showed that BA was not cytotoxic within the tested concentrations (3, 10, 30, 100 and 200 µM). These non-cytotoxic concentrations were used for comet assay. BA pre-treatment significantly reduced (P<0.05, one-way ANOVA) the DNA damaging capacity of H2O2 at each tested BA concentrations in V79 cells. Conclusion Consequently, pre-incubation of V79 cells with BA has significantly reduced the H2O2-induced oxidative DNA damage in V79 cells. The protective effect of BA against oxidative DNA damage in V79 cells at 5, 10, 50, 100 and 200 μM (54, 108, 540

  9. Effect of phytic acid, ethylenediaminetetraacetic acid, and chitosan solutions on microhardness of the human radicular dentin

    Directory of Open Access Journals (Sweden)

    Vineeta Nikhil

    2016-01-01

    Full Text Available Aim: The purpose of this study was to evaluate the effect of phytic acid, ethylenediaminetetraacetic acid (EDTA, and chitosan solutions on the microhardness of human radicular dentin. Materials and Methods: Thirty dentin specimens were randomly divided into three groups of 10 specimens each according to the irrigant used: G1 - 1% phytic acid, G2 - 17% EDTA, and G3 - 0.2% chitosan. A standardized volume of each chelating solution was used for 3 min. Dentin microhardness was measured before and after application at the cervical, middle, and apical levels with a Vickers indenter under a 200-g load and a 10-s dwell time. The results were analyzed using one-way analysis of variance (ANOVA and Student′s t test. Results: Microhardness of the radicular dentin varied at the cervical, middle, and apical levels. EDTA had the greatest overall effect, causing a sharp percentage reduction in dentin microhardness with a significant difference from phytic acid and chitosan (P = 0.002. However, phytic acid and chitosan differed insignificantly from each other (P = 0.887. Conclusion: All tested chelating solutions reduced microhardness of the radicular dentin layer at all the levels. However, reduction was least at the apical level. EDTA caused more reduction in dentin microhardness than chitosan while phytic acid reduced the least.

  10. Inhibition of fungal spore adhesion by zosteric Acid as the basis for a novel, nontoxic crop protection technology.

    Science.gov (United States)

    Stanley, Michele S; Callow, Maureen E; Perry, Ruth; Alberte, Randall S; Smith, Robert; Callow, James A

    2002-04-01

    ABSTRACT To explore the potential for nontoxic crop protection technologies based on the inhibition of fungal spore adhesion, we have tested the effect of synthetic zosteric acid (p-(sulfo-oxy) cinnamic acid), a naturally occurring phenolic acid in eelgrass (Zostera marina L.) plants, on spore adhesion and infection in two pathosystems: rice blast caused by Magnaporthe grisea and bean anthracnose caused by Colletotrichum lindemuthianum. We have shown that zosteric acid inhibits spore adhesion to model and host leaf surfaces and that any attached spores fail to develop appressoria, and consequently do not infect leaf cells. Low concentrations of zosteric acid that are effective in inhibiting adhesion are not toxic to either fungus or to the host. The inhibition of spore adhesion in the rice blast pathogen is fully reversible. On plants, zosteric acid reduced (rice) or delayed (bean) lesion development. These results suggest that there is potential for novel and environmentally benign crop protection technologies based on manipulating adhesion.

  11. Fall Protection Characteristics of Safety Belts and Human Impact Tolerance.

    Science.gov (United States)

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-08-23

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt(1)), which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness(2, 3)), which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference(4-9)) to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model(10)) was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls.

  12. Protective effect of trehalose-loaded liposomes against UVB-induced photodamage in human keratinocytes

    Science.gov (United States)

    EMANUELE, ENZO; BERTONA, MARCO; SANCHIS-GOMAR, FABIAN; PAREJA-GALEANO, HELIOS; LUCIA, ALEJANDRO

    2014-01-01

    Trehalose, a naturally occurring non-reducing disaccharide, is known to act as a major protein stabilizer that can reduce ultraviolet B (UVB)-induced corneal damage when topically applied to the eye. However, due to the low skin permeability of trehalose, which makes the development of topical formulations difficult, its use as a skin photoprotective agent has been limited. Previous findings demonstrated that liposomes may significantly improve the intracellular delivery of trehalose. Therefore, the present study aimed to assess the protective effects of trehalose-loaded liposomes against UVB-induced photodamage using the immortalized human keratinocyte cell line, HaCaT. The effects were also compared to those of the common skin photoprotective compounds, including L-carnosine, L-(+)-ergothioneine, L-ascorbic acid and DL-α-tocopherol. The levels of cyclobutane pyrimidine dimers, 8-hydroxy-2′-deoxyguanosine and protein carbonylation in HaCaT cells were used as biological markers of UVB-induced damage. Compared to other compounds, trehalose-loaded liposomes showed the highest efficacy in reducing the levels of the three markers following UVB irradiation of HaCaT cells (all P<0.001 when compared to each of the four other photoprotective compounds). Therefore, these findings indicate that there may be a clinical application for trehalose-loaded liposomes, and further studies should be performed to assess the potential usefulness in skin photoprotection and the prevention of non-melanoma skin cancer. PMID:25054023

  13. Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis.

    Science.gov (United States)

    Darendelioglu, Ekrem; Aykutoglu, Gurkan; Tartik, Musa; Baydas, Giyasettin

    2016-05-01

    Chronic cardiovascular and neurodegenerative complications induced by hyperhomocysteinemia have been most relatively associated with endothelial cell injury. Elevated homocysteine (Hcy) generates reactive oxygen species (ROS) accompanying with oxidative stress which is hallmarks of the molecular mechanisms responsible for cardiovascular disease. Propolis is a natural product, obtained by honeybee from various oils, pollens, special resins and wax materials, conventionally used with the purpose of treatment by folks Propolis has various biological activities and powerful antioxidant capacity. The flavonoids and phenolic acids, most bioactive components of propolis, have superior antioxidant ability to defend cell from free radicals. This study was designed to examine the protective effects of Turkish propolis (from east of country) on Hcy induced ROS production and apoptosis in human vascular endothelial cells (HUVECs). According to results, co-treatment of HUVECs with propolis decreased Hcy-induced ROS overproduction and lipid peroxidation (LPO) levels. Furthermore, overproductions of Bax, caspase-9 and caspase-3 protein, elevation of cytochrome c release in Hcy-treated HUVECs were significantly reduced by propolis. It was concluded that propolis has cytoprotective ability against cytotoxic effects of high Hcy in HUVECs.

  14. Bimane: A Visible Light Induced Fluorescent Photoremovable Protecting Group for the Single and Dual Release of Carboxylic and Amino Acids.

    Science.gov (United States)

    Chaudhuri, Amrita; Venkatesh, Yarra; Behara, Krishna Kalyani; Singh, N D Pradeep

    2017-03-10

    A series of ester conjugates of carboxylic and amino acids were synthesized based on bimane fluorescent photoremovable protecting group (FPRPG). The photorelease of single and dual (same as well as different) carboxylic and amino acids is demonstrated from a single bimane molecule on irradiation with visible light (λ ≥ 410 nm). The detailed mechanistic study of photorelease revealed that the release of two caged acids is simultaneous but in a stepwise pathway.

  15. Synthesis of alkynes and alkynyl iodides bearing a protected amino alcohol moiety as functionalized amino acids precursors

    Institute of Scientific and Technical Information of China (English)

    AYED; Charfedinne; PICARD; Julien; LUBIN-GERMAIN; Nadège; UZIEL; Jacques; AUGE; Jacques

    2010-01-01

    Amino acid precursors in protected amino alcohol form are important synthons that can be used as building-blocks for the hemisynthesis of non-natural amino acids.Serine can be used as a common starting material for the synthesis of such compounds differently protected.Particularly,protected amino alcohols bearing an ethynyl and/or an iodoethynyl group can be used in cross-couplings,in 1,3-dipolar cycloadditions and/or in Nozaki-Hiyama-Kishi type reactions.We thus demonstrated that the efficiently protected amino alcohols derived from serine can be coupled to a sugar derivative by an indium mediated alkynylation reaction.The conditions of this coupling are compatible with such functionalized derivatives and allow envisaging an access to C-glycosylated amino acids.

  16. Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

    Directory of Open Access Journals (Sweden)

    Nur Shafika Mohd Sairazi

    2015-01-01

    Full Text Available Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS. In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA. KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.

  17. Synergistic interactions between grafted hyaluronic acid and lubricin provide enhanced wear protection and lubrication.

    Science.gov (United States)

    Das, Saurabh; Banquy, Xavier; Zappone, Bruno; Greene, George W; Jay, Gregory D; Israelachvili, Jacob N

    2013-05-13

    Normal (e.g., adhesion) and lateral (friction) forces were measured between physisorbed and chemically grafted layers of hyaluronic acid (HA), an anionic polyelectrolyte in the presence of lubricin (Lub), a mucinous glycoprotein, on mica surfaces using a surface forces apparatus (SFA). This work demonstrates that high friction coefficients between the surfaces do not necessarily correlate with surface damage and that chemically grafted HA acts synergistically with Lub to provide friction reduction and enhanced wear protection to the surfaces. Surface immobilization of HA by grafting is necessary for such wear protection. Increasing the concentration of Lub enhances the threshold load that a chemically grafted HA surface can be subjected to before the onset of wear. Addition of Lub does not have any beneficial effect if HA is physisorbed to the mica surfaces. Damage occurs at loads less than 1 mN regardless of the amount of Lub, indicating that the molecules in the bulk play little or no role in protecting the surfaces from damage. Lub penetrates into the chemically bound HA to form a visco-elastic gel that reduces the coefficient of friction as well as boosts the strength of the surface against abrasive wear (damage).

  18. Caffeic acid phenethyl ester protects against the dopaminergic neuronal loss induced by 6-hydroxydopamine in rats.

    Science.gov (United States)

    Barros Silva, R; Santos, N A G; Martins, N M; Ferreira, D A S; Barbosa, F; Oliveira Souza, V C; Kinoshita, A; Baffa, O; Del-Bel, E; Santos, A C

    2013-03-13

    Caffeic acid phenethyl ester (CAPE) is a botanical compound abundant in honeybees' propolis. It has anti-inflammatory, antiviral, antioxidant, immunomodulatory and antitumor properties. Its beneficial effects against neurodegenerative diseases, including Parkinson's disease, have also been suggested and some mechanisms have been proposed. Mitochondrial damage and oxidative stress are critical events in neurodegeneration. Release of cytochrome c from mitochondria to cytosol and the downstream activation of caspase-3 have been suggested as targets of the protective mechanism of CAPE. Most of the studies addressing the protective effect of CAPE have been performed in cell culture. This is the first study to demonstrate the protective effect of CAPE against the dopaminergic neuronal loss induced by 6-hydroxydopamine (6-OHDA) in rats. It also demonstrates, for the first time, the inhibitory effect of CAPE on mitochondrial permeability transition (MPT), a mediator of neuronal death that triggers cytochrome c release and caspase-3 activation. Scavenging of reactive oxygen species (ROS) and metal chelation was demonstrated in the brain-affected areas of the rats treated with 6-OHDA and CAPE. Additionally, we demonstrated that CAPE does not affect brain mitochondrial function. Based on these findings and on its ability to cross the blood-brain barrier, CAPE is a promising compound to treat Parkinson's and other neurodegenerative diseases.

  19. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats.

    Science.gov (United States)

    Chu, JianJun; Zhang, Xiaojun; Jin, Liugen; Chen, Junliang; Du, Bin; Pang, Qingfeng

    2015-03-01

    Caffeic acid phenyl ester (CAPE) is a potent anti-inflammatory agent and it can eliminate the free radicals. The current study was intended to evaluate the protective effect of CAPE against the acute radiation-induced liver damage in rats. Male Sprague-Dawley rats were intraperitoneally administered with CAPE (30 mg/kg) for 3 consecutive days before exposing them to a single dose of 30 Gy of β-ray irradiation to upper abdomen. We found that pretreatment with CAPE significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase and increased the activity of superoxide dismutase and glutathione. Histological evaluation further confirmed the protection of CAPE against radiation-induced hepatotoxicity. TUNEL assay showed that CAPE pretreatment inhibited hepatocyte apoptosis. Moreover, CAPE inhibited the nuclear transport of NF-κB p65 subunit, decreased the level of tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthase. Taken together, these results suggest that pretreatment with CAPE offers protection against radiation-induced hepatic injury.

  20. Rice Bran and Probiotics Alter the Porcine Large Intestine and Serum Metabolomes for Protection against Human Rotavirus Diarrhea

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Ryan

    2017-04-01

    Full Text Available Human rotavirus (HRV is a leading cause of severe childhood diarrhea, and there is limited vaccine efficacy in the developing world. Neonatal gnotobiotic pigs consuming a prophylactic synbiotic combination of probiotics and rice bran (Pro+RB did not exhibit HRV diarrhea after challenge. Multiple immune, gut barrier protective, and anti-diarrheal mechanisms contributed to the prophylactic efficacy of Pro+RB when compared to probiotics (Pro alone. In order to understand the molecular signature associated with diarrheal protection by Pro+RB, a global non-targeted metabolomics approach was applied to investigate the large intestinal contents and serum of neonatal gnotobiotic pigs. The ultra-high performance liquid chromatography-tandem mass spectrometry platform revealed significantly different metabolites (293 in LIC and 84 in serum in the pigs fed Pro+RB compared to Pro, and many of these metabolites were lipids and amino acid/peptides. Lipid metabolites included 2-oleoylglycerol (increased 293.40-fold in LIC of Pro+RB, p = 3.04E-10, which can modulate gastric emptying, andhyodeoxycholate (decreased 0.054-fold in the LIC of Pro+RB, p = 0.0040 that can increase colonic mucus production to improve intestinal barrier function. Amino acid metabolites included cysteine (decreased 0.40-fold in LIC, p = 0.033, and 0.62-fold in serum, p = 0.014 of Pro+RB, which has been found to reduce inflammation, lower oxidative stress and modulate mucosal immunity, and histamine (decreased 0.18-fold in LIC, p = 0.00030, of Pro+RB and 1.57-fold in serum, p = 0.043, which modulates local and systemic inflammatory responses as well as influences the enteric nervous system. Alterations to entire LIC and serum metabolic pathways further contributed to the anti-diarrheal and anti-viral activities of Pro+RB such as sphingolipid, mono/diacylglycerol, fatty acid, secondary bile acid, and polyamine metabolism. Sphingolipid and long chain fatty acid profiles influenced the

  1. Peptide Targeted by Human Antibodies Associated with HIV Vaccine-Associated Protection Assumes a Dynamic α-Helical Structure

    Science.gov (United States)

    Dominguez, Lorenzo; Goger, Michael; Battacharya, Shibani; deCamp, Allan C.; Gilbert, Peter B.; Berman, Phillip W.; Cardozo, Timothy

    2017-01-01

    The only evidence of vaccine-induced protection from HIV acquisition in humans was obtained in the RV144 HIV vaccine clinical trial. One immune correlate of risk in RV144 was observed to be higher titers of vaccine-induced antibodies (Abs) reacting with a 23-mer non-glycosylated peptide with the same amino acid sequence as a segment in the second variable (V2) loop of the MN strain of HIV. We used NMR to analyze the dynamic 3D structure of this peptide. Distance restraints between spatially proximate inter-residue protons were calculated from NOE cross peak intensities and used to constrain a thorough search of all possible conformations of the peptide. α–helical folding was strongly preferred by part of the peptide. A high-throughput structure prediction of this segment in all circulating HIV strains demonstrated that α–helical conformations are preferred by this segment almost universally across all subtypes. Notably, α–helical conformations of this segment of the V2 loop cluster cross-subtype-conserved amino acids on one face of the helix and the variable amino acid positions on the other in a semblance of an amphipathic α–helix. Accordingly, some Abs that protected against HIV in RV144 may have targeted a specific, conserved α–helical peptide epitope in the V2 loop of HIV’s surface envelope glycoprotein. PMID:28107435

  2. Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo.

    Science.gov (United States)

    Varghese, Mathews V; Abhilash, M; Paul, M V Sauganth; Alex, Manju; Nair, R Harikumaran

    2017-04-01

    Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O3 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3 significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with As2O3. ω-3 fatty acid co-administration with As2O3 significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3 treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψm). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψm. These findings suggested that the ω-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity.

  3. Age estimation based on aspartic acid racemization in human sclera.

    Science.gov (United States)

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  4. Effects of Rumen-Protected Methionine on Dairy Performance and Amino Acid Metabolism in Lactating Cows

    Directory of Open Access Journals (Sweden)

    W. R. Yang

    2010-01-01

    Full Text Available Problem statement: Free Met as one of the most limiting AA in dairy cows would be mostly degraded in the rumen. This study was to determine the effect of different levels of Rumen-Protected Met (RPMet on dairy performance and serum amino acid metabolism. Approach: Thirty-six Holstein cows in similar condition were randomly assigned to six experimental treatments with six replicates each. Levels of RPMet in six treatments were 0(control, 14, 28, 42, 56 and 70 g day-1 per cow, respectively. Results: Treatment had no effect on percentage of milk protein, lactose and SNF. However, milk yield of cows fed 42 g day-1 RPMet was significantly higher than that of the control group and milk fat percentage was significantly increased with 56 g day-1 RPMet supplementation. There was the trend to decrease the concentration of serum amino acids except Met and Arg with the supplementation of RPMet. Serum EAA contents of the group supplementation of 42 g day-1 RPMet were lowest although there were no significant differences among all treatments. Serum BCAA concentrations of cows fed 28 g RPMet were significantly lower than that of the control group. Supplementation of 42 g RPMet could significantly decrease the concentration of NEAA and TAA compared to the control group. Conclusion/Recommendations: Supplementation of rumen-protected methionine improved dairy performance and promoted amino acid utilization in lactating cows in the present experiment. The optimal level of RPMet in the diet was 42 g per cow day-1.

  5. A Path to Planetary Protection Requirements for Human Exploration: A Literature Review and Systems Engineering Approach

    Science.gov (United States)

    Johnson, James E.; Conley, Cassie; Siegel, Bette

    2015-01-01

    As systems, technologies, and plans for the human exploration of Mars and other destinations beyond low Earth orbit begin to coalesce, it is imperative that frequent and early consideration is given to how planetary protection practices and policy will be upheld. While the development of formal planetary protection requirements for future human space systems and operations may still be a few years from fruition, guidance to appropriately influence mission and system design will be needed soon to avoid costly design and operational changes. The path to constructing such requirements is a journey that espouses key systems engineering practices of understanding shared goals, objectives and concerns, identifying key stakeholders, and iterating a draft requirement set to gain community consensus. This paper traces through each of these practices, beginning with a literature review of nearly three decades of publications addressing planetary protection concerns with respect to human exploration. Key goals, objectives and concerns, particularly with respect to notional requirements, required studies and research, and technology development needs have been compiled and categorized to provide a current 'state of knowledge'. This information, combined with the identification of key stakeholders in upholding planetary protection concerns for human missions, has yielded a draft requirement set that might feed future iteration among space system designers, exploration scientists, and the mission operations community. Combining the information collected with a proposed forward path will hopefully yield a mutually agreeable set of timely, verifiable, and practical requirements for human space exploration that will uphold international commitment to planetary protection.

  6. Single amino acid radiocarbon dating of Upper Paleolithic modern humans.

    Science.gov (United States)

    Marom, Anat; McCullagh, James S O; Higham, Thomas F G; Sinitsyn, Andrey A; Hedges, Robert E M

    2012-05-01

    Archaeological bones are usually dated by radiocarbon measurement of extracted collagen. However, low collagen content, contamination from the burial environment, or museum conservation work, such as addition of glues, preservatives, and fumigants to "protect" archaeological materials, have previously led to inaccurate dates. These inaccuracies in turn frustrate the development of archaeological chronologies and, in the Paleolithic, blur the dating of such key events as the dispersal of anatomically modern humans. Here we describe a method to date hydroxyproline found in collagen (~10% of collagen carbon) as a bone-specific biomarker that removes impurities, thereby improving dating accuracy and confidence. This method is applied to two important sites in Russia and allows us to report the earliest direct ages for the presence of anatomically modern humans on the Russian Plain. These dates contribute considerably to our understanding of the emergence of the Mid-Upper Paleolithic and the complex suite of burial behaviors that begin to appear during this period.

  7. Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and exogenous reactive oxygen species.

    Science.gov (United States)

    Russo, A; Troncoso, N; Sanchez, F; Garbarino, J A; Vanella, A

    2006-02-23

    Many environmental, physiological and genetic factors have been implicated in defective sperm function, the most common cause of infertility. In addition, sperm preparation techniques such as centrifugation, used prior to in vitro fertilization, are associated with the generation of reactive oxygen species (ROS) and an increase in the level of DNA damage. Factors that can offer spermatozoa protection are, therefore, of great importance. This study was designed to examine in vitro the effect of a Chilean propolis ethanolic extract on human spermatozoa treated with benzo[a]pyrene and exogenous reactive oxygen species. Our experimental evidence demonstrated that the natural drug under investigation is able to protect genomic DNA by damage induced by benzo[a]pyrene, hydrogen peroxide (H2O2) and hydrogen peroxide in combination with adenosine 5'-diphosphate (ADP) and ferrous sulfate (FeSO4), determining a significant reduction of the intracellular oxidants. An increase in membrane damage, measured by monitoring the formation of thiobarbituric acid-reactive substances (TBARS) and lactic dehydrogenase (LDH) release, was observed only in sperm treated with H2O2, ADP and FeSO4. The propolis extract was shown to possess the capacity to protect sperm membrane from the deleterious action of oxidative attack, reducing TBARS formation and LDH release. In summary, our results evidence that the protective effect exhibited by this natural compound in human spermatozoa is correlated, at least in part, to the antioxidant capacity of its active components, and suggest that propolis may have a role in protection against male infertility.

  8. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  9. Release of Propolis Phenolic Acids from Semisolid Formulations and Their Penetration into the Human Skin In Vitro

    OpenAIRE

    2013-01-01

    Antioxidant and free radical scavenging effects are attributed to phenolic compounds present in propolis, and when delivered to the skin surface and following penetration into epidermis and dermis, they can contribute to skin protection from damaging action of free radicals that are formed under UV and premature skin aging. This study was designed to determine the penetration of phenolic acids and vanillin into the human skin in vitro from experimentally designed vehicles. Results of the stud...

  10. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Directory of Open Access Journals (Sweden)

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  11. DNA-protective effects of sumach (Rhus coriaria L.), a common spice: Results of human and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Asima; Ferk, Franziska; Simic, Tatjana [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Brantner, Adelheid [Institute of Pharmacognosy, University of Graz, Universitaetsplatz 4/I, A-8010 Graz (Austria); Dusinska, Maria [Center for Ecological Economics, Norwegian Institute for Air Research, Instituttveien 18, NO-2027 Kjeller (Norway); Kundi, Michael [Institute of Environmental Health, Center for Public Health, Medical Unviversity of Vienna (Austria); Hoelzl, Christine; Nersesyan, Armen [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Knasmueller, Siegfried [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)], E-mail: siegfried.knasmueller@meduniwien.ac.at

    2009-02-10

    Sumach (Rhus coriaria L.) is widely used as a spice. The aim of this study was the investigation of its DNA-protective effects in humans and animals. Prevention of the formation of strand breaks and oxidized DNA bases as well as the protection against H{sub 2}O{sub 2}- and ({+-})-anti-benzo[a]pyrene-7,8-dihydro-diol-9,10-epoxide (BPDE)-induced DNA-damage were monitored in human lymphocytes in a placebo controlled trial (N = 8/group) with ethanolic extract of sumach (3.0 g/day, 3 days) in single cell gel electrophoresis assays. Furthermore, DNA-protective effects of sumach were monitored in different inner organs of rats under identical conditions. No alteration of DNA-migration was detectable in human lymphocytes under standard conditions, but a decrease of the tail-lengths due to formation of oxidized purines and pyrimidines (52% and 36%) was found with lesion-specific enzymes. Also damage caused by H{sub 2}O{sub 2} and BPDE was significantly reduced by 30% and 69%, respectively. The later effect may be due to induction of glutathione S-transferase (GST). After the intervention, the overall GST (CDNB) activity in plasma was increased by 40%, GST-{alpha} by 52% and GST-{pi} by 26% (ELISA). The antioxidant effects of extract are probably due to scavenging which was observed in in vitro experiments, which also indicated that gallic acid is the active principle of sumach. The animal experiments showed that sumach also causes protection in inner organs. Supplementation of the drinking water (0.02 g/kg per animal) decreased the formation of oxidized DNA bases in colon, liver, lung and lymphocytes; also after {gamma}-irradiation pronounced effects were seen.

  12. Angelica Sinensis May Provide Protection Against Human Immunodeficiency Virus Infection

    Directory of Open Access Journals (Sweden)

    mohammad Zarenezhad

    2008-05-01

    Full Text Available Increased oxidative stress and disturbed glutathione redox system play an important role in the pathogenesis of human immunodeficiency virus (HIV infection. Depletion in intracellular levels of reduced glutathione (GSH contributes to an increment in tumor necrosis factor α (TNF-α-stimulated-HIV-1-transcription, activation of HIV-1-replication, sensitivity to TNF-α-induced cell death, and impairment of CD4+ cell function and survival. Therefore, several studies have investigated the effect of GSH-enhancer agents such as N-acetyl cystein in the treatment of patients with HIV infection. With regard to the beneficial effects of Angelica sinensis, a Chinese medicinal herb, on GSH redox system and the pathogenic role of GSH depletion in HIV infection and the immunomodulator effects of active ingredients of this herb, we postulated that Angelica sinensis may be of value in the treatment of HIV-infected patients.

  13. Recombinant Human Prolactin Protects against Irradiation Induced Myelosuppression

    Institute of Scientific and Technical Information of China (English)

    Weici Zhang; Rui Sun; Jianhua Zhang; Jian Zhang; Zhigang Tian

    2005-01-01

    Prolactin is a multifunctional hormone that exerts many separate functions and acts as an important connection between the endocrine and immune systems. There are increasing researches implicating the role of prolactin in hematopoiesis. Enhanced erythropoiesis in pregnant women and direct erythropoietic effects in vitro of plasma either from pregnant or lactating mice have been reported. Furthermore, regression of erythroblastic leukemia has been observed in a significant number of rats after hypophysectomy. In this study, the effects of recombinant human prolactin (rhPRL) on hematopoiesis were assessed in irradiated mice. Mice were treated with rhPRL for five consecutive days after exposure to a lethal dose or a sub-dose irradiation. Prolonged survival rate and increased erythropoiesis were observed in the irradiation-induced myelosuppressive mice. It was concluded that rhPRL might act on erythropoiesis and could be a potential candidate for the treatment of irradiation-induced myelosuppresion in clinic. Cellular & Molecular Immunology.

  14. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

    Science.gov (United States)

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2008-02-01

    Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.

  15. Support of protective work of human error in a nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizawa, Yuriko [Tokyo Electric Power Co., Inc. (Japan)

    1999-12-01

    The nuclear power plant human factor group of the Tokyo Electric Power Co., Ltd. supports various protective work of human error conducted at the nuclear power plant. Its main researching theme are studies on human factor on operation of a nuclear power plant, and on recovery and common basic study on human factor. In addition, on a base of the obtained informations, assistance to protective work of human error conducted at the nuclear power plant as well as development for its actual use was also promoted. Especially, for actions sharing some dangerous informations, various assistances such as a proposal on actual example analytical method to effectively understand a dangerous information not facially but faithfully, construction of a data base to conveniently share such dangerous information, and practice on non-accident business survey for a hint of effective promotion of the protection work, were promoted. Here were introduced on assistance and investigation for effective sharing of the dangerous informations for various actions on protection of human error mainly conducted in nuclear power plant. (G.K.)

  16. Planetary Protection Knowledge Gaps for Human Extraterrestrial Missions Workshop Booklet - 2015

    Science.gov (United States)

    Fonda, Mark L.

    2015-01-01

    Although NASA's preparations for the Apollo lunar missions had only a limited time to consider issues associated with the protection of the Moon from biological contamination and the quarantine of the astronauts returning to Earth, they learned many valuable lessons (both positive and negative) in the process. As such, those efforts represent the baseline of planetary protection preparations for sending humans to Mars. Neither the post-Apollo experience or the Shuttle and other follow-on missions of either the US or Russian human spaceflight programs could add many additional insights to that baseline. Current mission designers have had the intervening four decades for their consideration, and in that time there has been much learned about human-associated microbes, about Mars, and about humans in space that has helped prepare us for a broad spectrum of considerations regarding potential biological contamination in human Mars missions and how to control it. This paper will review the approaches used in getting this far, and highlight some implications of this history for the future development of planetary protection provisions for human missions to Mars. The role of NASA and ESA's planetary protection offices, and the aegis of COSPAR have been particularly important in the ongoing process.

  17. Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.

    Science.gov (United States)

    Oscherwitz, Jon; Feldman, Daniel; Yu, Fen; Cease, Kemp B

    2015-01-09

    Anthrax represents a formidable bioterrorism threat for which new, optimized vaccines are required. We previously demonstrated that epitope-focused multiple antigenic peptides or a recombinant protein in Freund's adjuvant can elicit Ab against the loop neutralizing determinant (LND), a cryptic linear neutralizing epitope in the 2ß2-2ß3 loop of protective antigen from Bacillus anthracis, which mediated protection of rabbits from inhalation challenge with B. anthracis Ames strain. However, demonstration of efficacy using human-use adjuvants is required before proceeding with further development of an LND vaccine for testing in non-human primates and humans. To optimize the LND immunogen, we first evaluated the protective efficacy and immune correlates associated with immunization of rabbits with mixtures containing two molecular variants of multiple antigenic peptides in Freunds adjuvant, termed BT-LND(2) and TB-LND(2). TB-LND(2) was then further evaluated for protective efficacy in rabbits employing human-use adjuvants. Immunization of rabbits with TB-LND(2) in human-use adjuvants elicited protection from Ames strain spore challenge which was statistically indistinguishable from that elicited through immunization with protective antigen. All TB-LND(2) rabbits with any detectable serum neutralization prior to challenge were protected from aerosolized spore exposure. Remarkably, rabbits immunized with TB-LND(2) in Alhydrogel/CpG had significant anamnestic increases in post-challenge LND-specific Ab and neutralization titers despite little evidence of spore germination in these rabbits. An LND-specific epitope-focused vaccine may complement PA-based vaccines and may represent a complementary stand-alone vaccine for anthrax. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Protection of arsenic-induced testicular oxidative stress by arjunolic acid.

    Science.gov (United States)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C

    2008-01-01

    Arsenic-induced tissue damage is a major concern to the human population. An impaired antioxidant defense mechanism followed by oxidative stress is the major cause of arsenic-induced toxicity, which can lead to reproductive failure. The present study was carried out to investigate the preventive role of arjunolic acid, a triterpenoid saponin isolated from the bark of Terminalia arjuna, against arsenic-induced testicular damage in mice. Administration of arsenic (in the form of sodium arsenite, NaAsO(2), at a dose of 10 mg/kg body weight) for 2 days significantly decreased the intracellular antioxidant power, the activities of the antioxidant enzymes, as well as the levels of cellular metabolites. In addition, arsenic intoxication enhanced testicular arsenic content, lipid peroxidation, protein carbonylation and the level of glutathione disulfide (GSSG). Exposure to arsenic also caused significant degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. Pretreatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days could prevent the arsenic-induced testicular oxidative stress and injury to the histological structures of the testes. Arjunolic acid had free radical scavenging activity in a cell-free system and antioxidant power in vivo. In summary, the results suggest that the chemopreventive role of arjunolic acid against arsenic-induced testicular toxicity may be due to its intrinsic antioxidant property.

  19. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    Science.gov (United States)

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  20. Rosuvastatin and ellagic acid protect against isoproterenol-induced myocardial infarction in hyperlipidemic rats

    Directory of Open Access Journals (Sweden)

    Mai A. Elhemely

    2014-12-01

    Full Text Available Hyperlipidemia (HL with subsequent coronary atherosclerosis is the major trigger of ischemia and hence, myocardial infarction (MI occurs. The present study aimed to elucidate the effects of pretreatment with rosuvastatin and ellagic acid, as well as their combination on isoproterenol-induced MI in hyperlipidemic rats. Adult rats were fed with a cholesterol-rich diet for seven weeks and received rosuvastatin (10 mg/kg and/or ellagic acid (30 mg/kg by oral gavage daily starting from the fifth week then subcutaneously injected with two doses 24-h apart of 100 mg/kg isoproterenol in the last two days. ECG pattern was monitored and both cardiac biomarkers (cTnI, CK-MB, LDH and AST and lipid profile (TC, TG, HDL-c and LDL-c were measured in serum. MDA and GSH levels were quantified in cardiac homogenates and heart tissue damage was examined by histopathology. Furthermore, the expression levels of iNOS, eNOS, Bax and Bcl-2 in heart samples were assessed by western blotting. Three-week pretreatment with rosuvastatin and/or ellagic acid markedly ameliorated HL- and isoproterenol-induced alterations in ECG, cardiac markers, oxidation markers, lipid profile and heart architecture. Both drugs downregulated iNOS and upregulated eNOS, while only rosuvastatin and the combination downregulated Bax. This study provides evidence that rosuvastatin and ellagic acid possess cardioprotective effect on the hyperlipidemic-myocardial infarction rat model and the combination does not offer extra protection than monotherapy.

  1. Uric Acid Is Protective After Cerebral Ischemia/Reperfusion in Hyperglycemic Mice.

    Science.gov (United States)

    Justicia, Carles; Salas-Perdomo, Angélica; Pérez-de-Puig, Isabel; Deddens, Lisette H; van Tilborg, Geralda A F; Castellví, Clara; Dijkhuizen, Rick M; Chamorro, Ángel; Planas, Anna M

    2016-12-15

    Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective. Hyperglycemia was induced by i.p. administration of dextrose 45 min before transient occlusion of the middle cerebral artery. Magnetic resonance imaging (MRI) was performed at 24 h to measure lesion volume. A group of normoglycemic and hyperglycemic mice received an i.v. injection of micron-sized particles of iron oxide (MPIOs), conjugated with either anti-ICAM-1 antibody or control IgG, followed by T2*w MRI. Neutrophil infiltration was studied by immunofluorescence and flow cytometry. A group of hyperglycemic mice received an i.v. infusion of uric acid (16 mg/kg) or the vehicle starting after 45 min of reperfusion. ICAM-1-targeted MPIOs induced significantly larger MRI contrast-enhancing effects in the ischemic brain of hyperglycemic mice, which also showed more infiltrating neutrophils and larger lesions than normoglycemic mice. Uric acid reduced infarct volume in hyperglycemic mice but it did not prevent vascular ICAM-1 upregulation and did not significantly reduce the number of neutrophils in the ischemic brain tissue. In conclusion, hyperglycemia enhances stroke-induced vascular ICAM-1 and neutrophil infiltration and exacerbates the brain lesion. Uric acid reduces the lesion size after ischemia/reperfusion in hyperglycemic mice.

  2. Protection of Human Beings Trafficked for the Purpose of Organ Removal: Recommendations.

    Science.gov (United States)

    Pascalev, Assya; Van Assche, Kristof; Sándor, Judit; Codreanu, Natalia; Naqvi, Anwar; Gunnarson, Martin; Frunza, Mihaela; Yankov, Jordan

    2016-02-01

    This report presents a comprehensive set of recommendations for protection of human beings who are trafficked for the purpose of organ removal or are targeted for such trafficking. Developed by an interdisciplinary group of international experts under the auspices of the project Trafficking in Human Beings for the Purpose of Organ Removal (also known as the HOTT project), these recommendations are grounded in the view that an individual who parts with an organ for money within an illegal scheme is ipso facto a victim and that the crime of trafficking in human beings for the purpose of organ removal (THBOR) intersects with the crime of trafficking in organs. Consequently, the protection of victims should be a priority for all actors involved in antitrafficking activities: those combating organ-related crimes, such as health organizations and survivor support services, and those combating trafficking in human beings, such as the criminal justice sectors. Taking into account the special characteristics of THBOR, the authors identify 5 key stakeholders in the protection of human beings trafficked for organ removal or targeted for such trafficking: states, law enforcement agencies and judiciary, nongovernmental organizations working in the areas of human rights and antitrafficking, transplant centers and health professionals involved in transplant medicine, and oversight bodies. For each stakeholder, the authors identify key areas of concern and concrete measures to identify and protect the victims of THBOR. The aim of the recommendations is to contribute to the development of a nonlegislative response to THBOR, to promote the exchange of knowledge and best practices in the area of victim protection, and to facilitate the development of a policy-driven action plan for the protection of THBOR victims in the European Union and worldwide.

  3. Advanced UV Absorbers for the Protection of Human Skin.

    Science.gov (United States)

    Hüglin, Dietmar

    The increasing awareness of the damaging effects of UV radiation to human skin triggered the market introduction of new cosmetic UV absorbers. This article summarizes the outcome of a multi-year research program, in which the author contributed to the development of different new UV filters. First of all, the molecular design and the basic properties of bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) will be presented. This oil-soluble filter, which today is widely used in both beach products and skin care products, exhibits inherent photostability and strong broad-spectrum UV-A+B absorbance. Based on the concept of micronized organic UV absorbers, the UV-B filter tris biphenyl triazine (TBPT) will be introduced. At present TBPT exhibits the highest efficacy of all cosmetic UV absorbers in the market (measured by area under the UV spectrum). Finally, the concept of liposomogenic UV absorbers will be featured. This approach was developed to create water-resistant UV filters, as liposomogenic structures are thought to integrate into the lipids of the horny layer. Due to prohibitively high costs, this technology did not result in a commercial product so far.

  4. Implication of conjugated linoleic acid (CLA) in human health.

    Science.gov (United States)

    Dilzer, Allison; Park, Yeonhwa

    2012-01-01

    Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its variety of biologically beneficial effects. CLA reduces body fat, cardiovascular diseases and cancer, and modulates immune and inflammatory responses as well as improves bone mass. It has been suggested that the overall effects of CLA are the results of interactions between two major isomers, cis-9,trans-11 and trans-10,cis-12. This review will primarily focus on current CLA publications involving humans, which are also summarized in the tables. Along with a number of beneficial effects of CLA, there are safety considerations for CLA supplementation in humans, which include effects on liver functions, milk fat depression, glucose metabolism, and oxidative stresses.

  5. Cyclic adenosine monophosphate-mediated protection against bile acid-induced apoptosis in cultured rat hepatocytes.

    Science.gov (United States)

    Webster, C R; Anwer, M S

    1998-05-01

    Cyclic adenosine monophosphate (cAMP) has been shown to modulate apoptosis. To evaluate the role of cAMP in bile acid-induced hepatocyte apoptosis, we studied the effect of agents that increase cAMP on the induction of apoptosis by glycochenodeoxycholate (GCDC) in cultured rat hepatocytes. GCDC induced apoptosis in 26.5%+/-1.1% of hepatocytes within 2 hours. Twenty-minute pretreatment of hepatocytes with 100 micromol/L 8-(4-chlorothiophenyl) cAMP (CP-cAMP) resulted in a reduction in the amount of apoptosis to 35.2%+/-3.8% of that seen in hepatocytes treated with GCDC alone. Other agents that increase intracellular cAMP, including dibutyryl cAMP (100 micromol/L), glucagon (200 nmol/L), and a combination of forskolin (20 micromol/L) and 3-isobutyl-1-methylxanthine (20 micromol/L), also inhibited GCDC-induced apoptosis to a similar extent. Pretreatment with the protein kinase A (PKA) inhibitor, KT5720, prevented the protective effect of CP-cAMP and inhibited CP-cAMP-induced activation of PKA activity. Inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin (50 nmol/L), or Ly 294002 (20 micromol/L) also prevented the cytoprotective effect of cAMP. PI3K assays confirmed that wortmannin (50 nmol/L) inhibited PI3K activity, while CP-cAMP had no effect on the activity of this lipid kinase. GCDC increased mitogen-activated protein kinase (MAPK) activity, but had no effect on stress-activated protein kinase (SAPK) activity in hepatocytes. cAMP decreased basal and GCDC-induced MAPK activity and increased SAPK activity. The MAPK kinase inhibitor, PD 98059, inhibited both GCDC-mediated MAPK activation and GCDC-induced apoptosis. 1) agents that increase intracellular cAMP protect against hepatocyte apoptosis induced by hydrophobic bile acids; 2) activation of MAPK by GCDC may be involved in bile acid-induced apoptosis; and 3) cAMP-mediated cytoprotection against bile acid-induced apoptosis appears to involve PKA, MAPK, and PI3K.

  6. Monomethylarsonous acid inhibited endogenous cholesterol biosynthesis in human skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lei [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Xiao, Yongsheng [Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States); Wang, Yinsheng, E-mail: yinsheng.wang@ucr.edu [Environmental Toxicology Graduate Program, University of California, Riverside, CA 92521-0403 (United States); Department of Chemistry, University of California, Riverside, CA 92521-0403 (United States)

    2014-05-15

    Human exposure to arsenic in drinking water is a widespread public health concern, and such exposure is known to be associated with many human diseases. The detailed molecular mechanisms about how arsenic species contribute to the adverse human health effects, however, remain incompletely understood. Monomethylarsonous acid [MMA(III)] is a highly toxic and stable metabolite of inorganic arsenic. To exploit the mechanisms through which MMA(III) exerts its cytotoxic effect, we adopted a quantitative proteomic approach, by coupling stable isotope labeling by amino acids in cell culture (SILAC) with LC-MS/MS analysis, to examine the variation in the entire proteome of GM00637 human skin fibroblasts following acute MMA(III) exposure. Among the ∼ 6500 unique proteins quantified, ∼ 300 displayed significant changes in expression after exposure with 2 μM MMA(III) for 24 h. Subsequent analysis revealed the perturbation of de novo cholesterol biosynthesis, selenoprotein synthesis and Nrf2 pathways evoked by MMA(III) exposure. Particularly, MMA(III) treatment resulted in considerable down-regulation of several enzymes involved in cholesterol biosynthesis. In addition, real-time PCR analysis showed reduced mRNA levels of select genes in this pathway. Furthermore, MMA(III) exposure contributed to a distinct decline in cellular cholesterol content and significant growth inhibition of multiple cell lines, both of which could be restored by supplementation of cholesterol to the culture media. Collectively, the present study demonstrated that the cytotoxicity of MMA(III) may arise, at least in part, from the down-regulation of cholesterol biosynthesis enzymes and the resultant decrease of cellular cholesterol content. - Highlights: • MMA(III)-induced perturbation of the entire proteome of GM00637 cells is studied. • Quantitative proteomic approach revealed alterations of multiple cellular pathways. • MMA(III) inhibits de novo cholesterol biosynthesis. • MMA

  7. A synergistic combination of tetraethylorthosilicate and multiphosphonic acid offers excellent corrosion protection to AA1100 aluminum alloy

    Energy Technology Data Exchange (ETDEWEB)

    Dalmoro, Viviane [Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS) Av. Bento Gonçalves 9500 - CEP 91501-970, Porto Alegre, RS (Brazil); Departament d’Enginyeria Química, ETSEIB, Universitat Politècnica de Catalunya (UPC), Avda. Diagonal 647, Barcelona E-08028 (Spain); Center for Research in Nano-Engineering (CRnE), Universitat Politècnica de Catalunya (UPC), Campus Sud, Edifici C’, C/Pasqual i Vila s/n, Barcelona E-08028 (Spain); Santos, João H.Z. dos [Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS) Av. Bento Gonçalves 9500 - CEP 91501-970, Porto Alegre, RS (Brazil); Armelin, Elaine, E-mail: elaine.armelin@upc.edu [Departament d’Enginyeria Química, ETSEIB, Universitat Politècnica de Catalunya (UPC), Avda. Diagonal 647, Barcelona E-08028 (Spain); Center for Research in Nano-Engineering (CRnE), Universitat Politècnica de Catalunya (UPC), Campus Sud, Edifici C’, C/Pasqual i Vila s/n, Barcelona E-08028 (Spain); Alemán, Carlos, E-mail: carlos.aleman@upc.edu [Departament d’Enginyeria Química, ETSEIB, Universitat Politècnica de Catalunya (UPC), Avda. Diagonal 647, Barcelona E-08028 (Spain); Center for Research in Nano-Engineering (CRnE), Universitat Politècnica de Catalunya (UPC), Campus Sud, Edifici C’, C/Pasqual i Vila s/n, Barcelona E-08028 (Spain); and others

    2013-05-15

    This work describes a new mechanism for the incorporation of organophosphonic acid into silane self-assembly monolayers, which has been used to protect AA1100 aluminum alloy. The protection improvement has been attributed to the fact that phosphonic structures promote the formation of strongly bonded and densely packed monolayer films, which show higher surface coverage and better adhesion than conventional silane systems. In order to evaluate the linking chemistry offered by phosphonic groups, two functionalized organophosphonic groups have been employed, 1,2-diaminoethanetetrakis methylenephosphonic acid (EDTPO) and aminotrimethylenephosphonic acid (ATMP), and combined with tetraethylorthosilicate (TEOS) films prepared by sol–gel synthesis. Results suggest that phosphonic acids may interact with the surface through a monodentate and bidentate coordination mode and, in addition, form one or more strong and stable linkages with silicon through non-hydrolysable bonds. Therefore, the incorporation of a very low concentration of phosphonic acids on TEOS solutions favors the complete coverage of the aluminum substrate during the silanization process, which is not possible using TEOS alone. The linking capacity of phosphonic acid has been investigated by FTIR-RA spectroscopy, SEM and EDX analysis, X-ray photoelectron spectroscopy (XPS), and quantum mechanical calculations. Finally, electrochemical impedance spectroscopy has been used to study the corrosion protection revealing that EDTPO-containing films afforded more protection to the AA1100 substrate than ATMP-containing films.

  8. A synergistic combination of tetraethylorthosilicate and multiphosphonic acid offers excellent corrosion protection to AA1100 aluminum alloy

    Science.gov (United States)

    Dalmoro, Viviane; dos Santos, João H. Z.; Armelin, Elaine; Alemán, Carlos; Azambuja, Denise S.

    2013-05-01

    This work describes a new mechanism for the incorporation of organophosphonic acid into silane self-assembly monolayers, which has been used to protect AA1100 aluminum alloy. The protection improvement has been attributed to the fact that phosphonic structures promote the formation of strongly bonded and densely packed monolayer films, which show higher surface coverage and better adhesion than conventional silane systems. In order to evaluate the linking chemistry offered by phosphonic groups, two functionalized organophosphonic groups have been employed, 1,2-diaminoethanetetrakis methylenephosphonic acid (EDTPO) and aminotrimethylenephosphonic acid (ATMP), and combined with tetraethylorthosilicate (TEOS) films prepared by sol-gel synthesis. Results suggest that phosphonic acids may interact with the surface through a monodentate and bidentate coordination mode and, in addition, form one or more strong and stable linkages with silicon through non-hydrolysable bonds. Therefore, the incorporation of a very low concentration of phosphonic acids on TEOS solutions favors the complete coverage of the aluminum substrate during the silanization process, which is not possible using TEOS alone. The linking capacity of phosphonic acid has been investigated by FTIR-RA spectroscopy, SEM and EDX analysis, X-ray photoelectron spectroscopy (XPS), and quantum mechanical calculations. Finally, electrochemical impedance spectroscopy has been used to study the corrosion protection revealing that EDTPO-containing films afforded more protection to the AA1100 substrate than ATMP-containing films.

  9. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  10. Radiation Protection Challenges for a Human Mission to Mars

    Science.gov (United States)

    Zeitlin, C. J.; Hassler, D.; Wimmer-Schweingruber, R. F.; Schwadron, N.; Spence, H. E.

    2015-12-01

    A human mission to Mars presents many challenges, not least of which is the radiation exposure that crew members will certainly receive in all phases of the journey, but most critically during the transits to and from Mars. Measurements from the Radiation Assessment Detector (RAD) aboard the Mars Science Laboratory Curiosity rover, made both in flight and on the surface of Mars, confirm previous estimates that crew members under reasonable shielding would receive a dose equivalent of about 1 Sievert on a 1000-day mission. In standard radiation biology, an acute exposure to 1 Sievert would be expected to increase lifetime fatal cancer risk by about 5%. This is well beyond the currently allowed 3% risk increase limit used by NASA and JAXA. Perhaps more significantly, the nature of exposure in space differs greatly from the terrestrial exposures that lead to the 5% estimate -- in space, the exposure is received at a very low dose rate, and includes a significant component from heavy ions in the Galactic Cosmic Rays (GCRs). Acute exposures to Solar Energetic Particles are also possible, but the generally lower energies of SEPs (kinetic energies typically below 100 MeV/nuc) mean that modest amounts of shielding are effective against them. Thus the greater concern for long-duration deep-space missions is the GCR exposure. In this presentation, I will briefly review the MSL-RAD data and discuss current approaches to radiation risk estimation, including the NASA limit of 3% at the 95% confidence level. Recent results from the NASA radiation biology program indicate that cancer may not be the only risk that needs to be considered, with emerging concerns about cardiovascular and central nervous system health. These health effects are not accounted for in the current methodology and could potentially be threatening to mission success if they manifest in the course of the mission, rather than appearing many years after the exposure as radiation-induced cancer typically does.

  11. STUDY OF LACTIC ACID BACTERIA AS A BIO-PROTECTIVE CULTURE FOR MEAT

    Directory of Open Access Journals (Sweden)

    L. Vinnikova,

    2016-08-01

    Full Text Available Loss prevention and food quality maintenance are primarily associated with protection against the negativeimpact of microorganisms and their metabolites during manufacture and storage. In this regard, in recent years, the issue of thegoods safety is of the top- priority in the food production. Meat and meat products are the most labour-intensive and expensiveto manufacture. Their main components (protein, fat, etc. are a favourable environment for development of a variety of microorganisms.This paper presents the results of the biotechnological property research of the Lactobacillus genus collection strains,their effect on the microorganisms directly isolated from meat and on the collection strains (saprophytic, conditionally pathogenicand pathogenic microorganisms. In particular, the antagonistic activity regarding the indicator and collection microorganisms,acid activity and ability to survive at high salt concentrations and low above-zero temperatures have been studied.Based on the experimental results, the most active strains for further study and use in the me

  12. Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

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    Xinhua Zhou

    2015-01-01

    Full Text Available Edaravone (EDA is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA- induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

  13. Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

    Science.gov (United States)

    Zhou, Xinhua; Zhu, Longjun; Wang, Liang; Guo, Baojian; Zhang, Gaoxiao; Sun, Yewei; Zhang, Zaijun; Lee, Simon Ming-Yuen; Yu, Pei; Wang, Yuqiang

    2015-01-01

    Edaravone (EDA) is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA-) induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs) and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities. PMID:26557222

  14. Protection of ultrastructure in chilling-stressed banana leaves by salicylic acid

    Institute of Scientific and Technical Information of China (English)

    KANG Guo-zhang; WANG Zheng-xun; XIA Kuai-fei; SUN Gu-chou

    2007-01-01

    Objective: Chilling tolerance of salicylic acid (SA) in banana seedlings (Musa acuminata cv., Williams 8818) was investigated by changes in ultrastructure in this study. Methods: Light and electron microscope observation. Results: Pretreatment with 0.5 mmol/L SA under normal growth conditions (30/22 ℃) by foliar spray and root irrigation resulted in many changes in ultrastructure of banana cells, such as cells separation from palisade parenchymas, the appearance of crevices in cell walls, the swelling of grana and stromal thylakoids, and a reduction in the number of starch granules. These results implied that SA treatment at 30/22 ℃ could be a type of stress. During 3 d of exposure to 7 ℃ chilling stress under low light, however, cell ultrastructure of SA-pretreated banana seedlings showed less deterioration than those of control seedlings (distilled water-pretreated). Conclusion:SA could provide some protection for cell structure of chilling-stressed banana seedling.

  15. Structure of the human 4-hydroxyphenylpyruvic acid dioxygenase gene (HPD)

    Energy Technology Data Exchange (ETDEWEB)

    Awata, H.; Endo, F.; Matsuda, I. [Kumamoto Univ. (Japan)

    1994-10-01

    4-Hydroxyphenylpyruvic acid dioxygenase (HPD) is an important enzyme in tyrosine catabolism in most organisms. The activity of this enzyme is expressed mainly in the liver and developmentally regulated in mammals, and a genetic deficiency in this enzyme in humans and mice leads to hereditary tyrosinemia type 3. Using human HPD cDNA as a probe, a chromosomal gene related to HPD was isolated from human gene libraries. The human HPD gene is over 30 kb long and is split into 14 exons. The extract sizes and boundaries of exon blocks were determined, and all of the splice donor and acceptor sites conformed to the GT/AG rule. Analysis of the 5{prime} flanking sequence of the gene suggests that expression of the gene is regulated by hepatocyte-specific and liver-enriched transcription factors, as well as by hormones. These features of the 5{prime} flanking region of the gene are similar to those of other genes that are specifically expressed in hepatocytes and that are developmentally regulated. 41 refs., 2 figs., 1 tab.

  16. Protection of the right to privacy in the practice of the European Court of Human Rights

    Directory of Open Access Journals (Sweden)

    Mladenov Marijana

    2013-01-01

    Full Text Available The right to privacy is a fundamental human right and an essential component of the protection of human autonomy and freedom. The development of science and information systems creates various opportunities for interferences with physical and moral integrity of a person. Therefore, it is necessary to determine the precise content of the right to privacy. The European Convention on Human Rights and Fundamental Freedoms guarantees this right under Article 8. The European Court of Human Rights did not precisely define the content of the right to privacy and thereby the applicants could bring different aspects of life into the scope of respect for private life. According to the Court, the concept of privacy and private life includes the following areas of human life: the right to establish and maintain relationships with other human beings, protection of the physical and moral integrity of persons, protection of personal data, change of personal name, various issues related to sexual orientation and transgender. The subject of this paper is referring to previously mentioned spheres of human life in the light of interpretation of Article 8 of the Convention.

  17. The protection of the accused in international criminal law according to the Human Rights Law Standard

    Directory of Open Access Journals (Sweden)

    Karolina Kremens

    2011-12-01

    Full Text Available The presented paper discusses the influence of international human rights law on international criminal law. It tries to give an answer to the question of whether rules protecting the accused in international criminal proceedings meet the human rights law standard provided by international declarations and covenants. Meaning, if the proceedings before the International Criminal Tribunal for Former Yugoslavia (ICTY, International Criminal Tribunal for Rwanda (ICTR and International Criminal Court (ICC meet the standard provided by international human rights law, in particular the International Covenant on Civil and Political Rights. The paper proves that international human rights law has affected international criminal law tremendously. Moreover, it is argued that the protection of the accused in the law of the international courts and tribunals with regard to his rights has improved when compared to the international human rights law standard. In particular the Rome Statute of the ICC provides the accused with the most comprehensive protection. This is especially visible in the case of such rights as the presumption of innocence, right to an interpreter and right to remain silent. Nevertheless, some shortcomings in the law of the ad hoc tribunals and ICC can be observed, in particular when it comes to identifying the commencement of protection of the accused.

  18. Acetylsalicylic acid provides cerebrovascular protection from oxidant damage in salt-loaded stroke-prone rats.

    Science.gov (United States)

    Ishizuka, Toshiaki; Niwa, Atsuko; Tabuchi, Masaki; Ooshima, Kana; Higashino, Hideaki

    2008-03-26

    Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Recent reports revealed that acetylsalicylic acid (aspirin) has anti-oxidative properties and elicits nitric oxide release by a direct activation of the endothelial NO synthase. The present study was designed to determine whether low-dose aspirin might prevent cerebrovascular injury in salt-loaded SHRSP by protecting oxidative damage. Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without treatment by naproxen (20 mg/kg/day), salicylic acid (5 mg/kg/day), or aspirin (5 mg/kg/day) for 5 weeks. Blood pressure, blood brain barrier impairment, mortality, and the parameters of cerebrovascular inflammation and damage were compared among them. High salt intake in SHRSP significantly increased blood brain barrier impairment and early mortality, which were suppressed by treatment with aspirin independent of changes in blood pressure. Salt loading significantly increased superoxide production in basilar arteries of SHRSP, which were significantly suppressed by treatment with aspirin. Salt loading also significantly decreased NOS activity in the basilar arteries of SHRSP, which were significantly improved by treatment with aspirin. At 5 weeks after salt loading, macrophage accumulation and matrix metalloproteinase-9 activity at the stroke-negative area in cerebral cortex of SHRSP were significantly reduced by treatment with aspirin. These results suggest that low-dose aspirin may exert protective effects against cerebrovascular inflammation and damage by salt loading through down-regulation of superoxide production and induction of nitric oxide synthesis.

  19. Histopathologic investigation of the protective effects of omega-3 fatty acids against boric acid-induced injury in kidney and testis tissue

    Directory of Open Access Journals (Sweden)

    1 Hacettepe Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Ankara, Türkiye 2 Mustafa Kemal Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Hatay, Türkiye 3 Mustafa Kemal Üniversitesi, Hatay Sağlık Hizmetleri Meslek Yüksek Okulu, Hatay , Türkiye 4 Antakya Doğumevi, Hatay, Türkiye 5 Fatih Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İstanbul, Türkiye 6 Turgut Özal Üniversitesi, Sağlık Bilimleri Meslek Yüksek Okulu, Ankara, Türkiye Yazışma Adresi / Correspondence : Ahmet Nacar, Hacettepe Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Ankara, Türkiye Email: drnacar@gmail.com Geliş Tarihi / Received: 09.01.2014, Kabul Tarihi / Accepted: 10.02.2014 Copyright © Dicle Tıp Dergisi 2014, Her hakkı saklıdır / All rights reserved Dicle Tıp Dergisi / 2014; 41 (2: 385-390 Dicle Medical Journal doi: 10.5798/diclemedj.0921.2014.02.0436 ÖZGÜN ARAŞTIRMA / ORIGINAL ARTICLE Borik asit uygulamasının sıçan böbrek ve testis dokusunda oluşturduğu hasara karşı Omega-3 yağ asitlerinin koruyucu etkisinin histopatolojik olarak incelenmesi Histopathologic investigation of the protective effects of omega-3 fatty acids against boric acid-induced injury in kidney and testis tissue Ahmet Nacar

    2014-06-01

    Full Text Available Objective: In this study, it was aimed to evaluate the effects of boric acid on rat kidney and testis tissues histopathologically. Secondly, the protective effects of omega-3 fatty acid against boric acid-induced renal and testicular toxicity were investigated. Methods: 32 wistar albino rats were divided into 4 groups as follows: Control, Omega-3 (400 mg/kg/day for 10 days, Boric acid (375 mg/kg/day for 10 days and Boric acid+omega-3 (both drugs same dosage for same day. Kidney and testis tissues were evaluated using a scoring system based on the extent of certain histopathological changes. Results: In histopathological examination, boric acid caused significant degeneration in both testis and kidney tissues. Most evident findings were glomerular shrinkage and necrosis, hemorrhage and tubular cell degeneration in kidneys, and exfoliation of seminiferous tubule cells, detachement of epithelium from basement membrane, decreased cellularity and degeneration in epithelial cells in testis tissues. Omega-3 administration significantly attenuated these changes. Conclusion: To our literature search, this is the first study reporting protective effects of omega-3 fatty acid against boric-acid-induced testicular and renal injury.

  20. HPLC determination of valproic acid in human serum.

    Science.gov (United States)

    Kishore, P; Rajani Kumar, V; Satyanarayana, V; Krishna, D R

    2003-06-01

    A HPLC method for the determination of valproic acid (VA) in human serum using diazepam as internal standard (I.S.) is described. The eluates were separated with a C18 250 x 4.6 mm internal diameter reversed phase column maintained at a temperature of 50 degrees C. A mobile phase consisting of acetonitrile and 0.05 M phosphate buffer (pH 3.0) 45:55 v/v was used at a flow rate of 1.2 ml/min. Wavelength was switched from 360 nm to 210 nm during valproic acid retention. The method was linear over a concentration range of 20 to 160 microg/ml for valproic acid. Recovery was greater than 94% over a concentration range of 20 to 120 microg/ml and the limit of quantitation was 1 microg/ml. The intra day and inter day relative standard deviation (R.S.D.) measured at 20, 60, 80 and 120 microg/ml ranged from 1.46 to 5.34% and 0.83 to 5.03% respectively. The method is simple, rapid, accurate and sensitive and it was used for Therapeutic Drug Monitoring (TDM) in Indian epileptic patient population. The results obtained with this method correlated well with clinical practice.

  1. Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats.

    Science.gov (United States)

    Oyagbemi, A A; Omobowale, T O; Saba, A B; Adedara, I A; Olowu, E R; Akinrinde, A S; Dada, R O

    2016-05-01

    The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione-S-transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA-treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

  2. All Biomass and UV Protective Composite Composed of Compatibilized Lignin and Poly (Lactic-acid)

    Science.gov (United States)

    Kim, Youngjun; Suhr, Jonghwan; Seo, Hee-Won; Sun, Hanna; Kim, Sanghoon; Park, In-Kyung; Kim, Soo-Hyun; Lee, Youngkwan; Kim, Kwang-Jin; Nam, Jae-Do

    2017-03-01

    Utilization of carbon-neutral biomass became increasingly important due to a desperate need for carbon reduction in the issue of global warming in light of replacing petroleum-based materials. We used lignin, which was an abundant, low cost, and non-food based biomass, for the development of all biomass-based films and composites through reactive compatibilization with poly (lactic-acid) (PLA). Using a facile and practical route, the hydrophilic hydroxyl groups of lignin were acetylated to impose the compatibility with PLA. The solubility parameter of the pristine lignin at 26.3 (J/cm3)0.5 was altered to 20.9 (J/cm3)0.5 by acetylation allowing the good compatibility with PLA at 20.2 (J/cm3)0.5. The improved compatibility of lignin and PLA provided substantially decreased lignin domain size in composites (12.7 μm), which subsequently gave transparent and UV-protection films (visual transmittance at 76% and UV protection factor over 40). The tensile strength and elongation of the developed composite films were increased by 22% and 76%, respectively, and the biobased carbon content was confirmed as 96 ± 3%. The developed PLA/lignin composites provided 100% all-biomass contents and balanced optical and mechanical properties that could broaden its eco-friendly applications in various industries.

  3. All Biomass and UV Protective Composite Composed of Compatibilized Lignin and Poly (Lactic-acid)

    Science.gov (United States)

    Kim, Youngjun; Suhr, Jonghwan; Seo, Hee-Won; Sun, Hanna; Kim, Sanghoon; Park, In-Kyung; Kim, Soo-Hyun; Lee, Youngkwan; Kim, Kwang-Jin; Nam, Jae-Do

    2017-01-01

    Utilization of carbon-neutral biomass became increasingly important due to a desperate need for carbon reduction in the issue of global warming in light of replacing petroleum-based materials. We used lignin, which was an abundant, low cost, and non-food based biomass, for the development of all biomass-based films and composites through reactive compatibilization with poly (lactic-acid) (PLA). Using a facile and practical route, the hydrophilic hydroxyl groups of lignin were acetylated to impose the compatibility with PLA. The solubility parameter of the pristine lignin at 26.3 (J/cm3)0.5 was altered to 20.9 (J/cm3)0.5 by acetylation allowing the good compatibility with PLA at 20.2 (J/cm3)0.5. The improved compatibility of lignin and PLA provided substantially decreased lignin domain size in composites (12.7 μm), which subsequently gave transparent and UV-protection films (visual transmittance at 76% and UV protection factor over 40). The tensile strength and elongation of the developed composite films were increased by 22% and 76%, respectively, and the biobased carbon content was confirmed as 96 ± 3%. The developed PLA/lignin composites provided 100% all-biomass contents and balanced optical and mechanical properties that could broaden its eco-friendly applications in various industries.

  4. Cardio-Protection of Salvianolic Acid B through Inhibition of Apoptosis Network

    Science.gov (United States)

    Xu, Lingling; Deng, Yanping; Feng, Lixin; Li, Defang; Chen, Xiaoyan; Ma, Chao; Liu, Xuan; Yin, Jun; Yang, Min; Teng, Fukang; Wu, Wanying; Guan, Shuhong; Jiang, Baohong; Guo, Dean

    2011-01-01

    Targeting cellular function as a system rather than on the level of the single target significantly increases therapeutic potency. In the present study, we detect the target pathway of salvianolic acid B (SalB) in vivo. Acute myocardial infarction (AMI) was induced in rats followed by the treatment with 10 mg/kg SalB. Hemodynamic detection and pathological stain, 2-dimensional electrophoresis, MALDI-TOF MS/MS, Western blot, pathway identification, apoptosis assay and transmission electron microscope were used to elucidate the effects and mechanism of SalB on cardioprotection. Higher SalB concentration was found in ischemic area compared to no-ischemic area of heart, correlating with improved heart function and histological structure. Thirty-three proteins regulated by SalB in AMI rats were identified by biochemical analysis and were classified as the components of metabolism and apoptosis networks. SalB protected cardiomyocytes from apoptosis, inhibited poly (ADP-ribose) polymerase-1 pathway, and improved the integrity of mitochondrial and nucleus of heart tissue during AMI. Furthermore, the protective effects of SalB against apoptosis were verified in H9c2 cells. Our results provide evidence that SalB regulates multi-targets involved in the apoptosis pathway during AMI and therefore may be a candidate for novel therapeutics of heart diseases. PMID:21915278

  5. Cardio-protection of salvianolic acid B through inhibition of apoptosis network.

    Directory of Open Access Journals (Sweden)

    Lingling Xu

    Full Text Available Targeting cellular function as a system rather than on the level of the single target significantly increases therapeutic potency. In the present study, we detect the target pathway of salvianolic acid B (SalB in vivo. Acute myocardial infarction (AMI was induced in rats followed by the treatment with 10 mg/kg SalB. Hemodynamic detection and pathological stain, 2-dimensional electrophoresis, MALDI-TOF MS/MS, Western blot, pathway identification, apoptosis assay and transmission electron microscope were used to elucidate the effects and mechanism of SalB on cardioprotection. Higher SalB concentration was found in ischemic area compared to no-ischemic area of heart, correlating with improved heart function and histological structure. Thirty-three proteins regulated by SalB in AMI rats were identified by biochemical analysis and were classified as the components of metabolism and apoptosis networks. SalB protected cardiomyocytes from apoptosis, inhibited poly (ADP-ribose polymerase-1 pathway, and improved the integrity of mitochondrial and nucleus of heart tissue during AMI. Furthermore, the protective effects of SalB against apoptosis were verified in H9c2 cells. Our results provide evidence that SalB regulates multi-targets involved in the apoptosis pathway during AMI and therefore may be a candidate for novel therapeutics of heart diseases.

  6. Alpha-lipoic acid protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Xueming; Chen, Aihua, E-mail: aihuachen2012@sina.com; Yang, Pingzhen; Song, Xudong; Liu, Yingfeng; Li, Zhiliang; Wang, Xianbao; Wang, Lizi; Li, Yunpeng

    2013-11-29

    Highlights: •We observed the cell viability and death subjected to H/R in H9c2 cardiomyocytes. •We observed the degree of autophagy subjected to H/R in H9c2 cardiomyocytes. •LA inhibited the degree of autophagy in parallel to the enhanced cell survival. •LA inhibited the autophagy in parallel to the decreased total cell death. •We concluded that LA protected cardiomyocytes against H/R by inhibiting autophagy. -- Abstract: Hypoxia/reoxygenation (H/R) is an important in vitro model for exploring the molecular mechanisms and functions of autophagy during myocardial ischemia/reperfusion (I/R). Alpha-lipoic acid (LA) plays an important role in the etiology of cardiovascular disease. Autophagy is widely implicated in myocardial I/R injury. We assessed the degree of autophagy by pretreatment with LA exposed to H/R in H9c2 cell based on the expression levels of Beclin-1, LC3II/LC3I, and green fluorescent protein-labeled LC3 fusion proteins. Autophagic vacuoles were confirmed in H9c2 cells exposed to H/R using transmission electron microscopy. Our findings indicated that pretreatment with LA inhibited the degree of autophagy in parallel to the enhanced cell survival and decreased total cell death in H9c2 cells exposed to H/R. We conclude that LA protects cardiomyocytes against H/R injury by inhibiting autophagy.

  7. Imputing amino acid polymorphisms in human leukocyte antigens.

    Directory of Open Access Journals (Sweden)

    Xiaoming Jia

    Full Text Available DNA sequence variation within human leukocyte antigen (HLA genes mediate susceptibility to a wide range of human diseases. The complex genetic structure of the major histocompatibility complex (MHC makes it difficult, however, to collect genotyping data in large cohorts. Long-range linkage disequilibrium between HLA loci and SNP markers across the major histocompatibility complex (MHC region offers an alternative approach through imputation to interrogate HLA variation in existing GWAS data sets. Here we describe a computational strategy, SNP2HLA, to impute classical alleles and amino acid polymorphisms at class I (HLA-A, -B, -C and class II (-DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 loci. To characterize performance of SNP2HLA, we constructed two European ancestry reference panels, one based on data collected in HapMap-CEPH pedigrees (90 individuals and another based on data collected by the Type 1 Diabetes Genetics Consortium (T1DGC, 5,225 individuals. We imputed HLA alleles in an independent data set from the British 1958 Birth Cohort (N = 918 with gold standard four-digit HLA types and SNPs genotyped using the Affymetrix GeneChip 500 K and Illumina Immunochip microarrays. We demonstrate that the sample size of the reference panel, rather than SNP density of the genotyping platform, is critical to achieve high imputation accuracy. Using the larger T1DGC reference panel, the average accuracy at four-digit resolution is 94.7% using the low-density Affymetrix GeneChip 500 K, and 96.7% using the high-density Illumina Immunochip. For amino acid polymorphisms within HLA genes, we achieve 98.6% and 99.3% accuracy using the Affymetrix GeneChip 500 K and Illumina Immunochip, respectively. Finally, we demonstrate how imputation and association testing at amino acid resolution can facilitate fine-mapping of primary MHC association signals, giving a specific example from type 1 diabetes.

  8. Bile salt recognition by human liver fatty acid binding protein.

    Science.gov (United States)

    Favretto, Filippo; Santambrogio, Carlo; D'Onofrio, Mariapina; Molinari, Henriette; Grandori, Rita; Assfalg, Michael

    2015-04-01

    Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is prominent among FABPs for its wide ligand repertoire, which includes long-chain fatty acids as well as bile acids (BAs). In this work, we performed a detailed molecular- and atomic-level analysis of the interactions established by human L-FABP with nine BAs to understand the binding specificity for this important class of cholesterol-derived metabolites. Protein-ligand complex formation was monitored using heteronuclear NMR, steady-state fluorescence spectroscopy, and mass spectrometry. BAs were found to interact with L-FABP with dissociation constants in the narrow range of 0.6-7 μm; however, the diverse substitution patterns of the sterol nucleus and the presence of side-chain conjugation resulted in complexes endowed with various degrees of conformational heterogeneity. Trihydroxylated BAs formed monomeric complexes in which single ligand molecules occupied similar internal binding sites, based on chemical-shift perturbation data. Analysis of NMR line shapes upon progressive addition of taurocholate indicated that the binding mechanism departed from a simple binary association equilibrium, and instead involved intermediates along the binding path. The co-linear chemical shift behavior observed for L-FABP complexes with cholate derivatives added insight into conformational dynamics in the presence of ligands. The observed spectroscopic features of L-FABP/BA complexes, discussed in relation to ligand chemistry, suggest possible molecular determinants of recognition, with implications regarding intracellular BA transport. Our findings suggest that human L-FABP is a poorly selective, universal BA binder.

  9. Edaravone, a free radical scavenger, protects liver against valproic acid induced toxicity

    Directory of Open Access Journals (Sweden)

    Cakmak Neziha Hacihasanoglu

    2015-01-01

    Full Text Available Valproic acid (VPA, is a well established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Edaravone (EDA; 3-methyl-1-phenyl-2-pyrazoline-5-one is a potent free radical scavenger. In this study, we aimed to investigate the effects of EDA on VPA-induced hepatic damage. Male Sprague Dawley rats were divided into four groups. Group I was control animals. Group II was control rats given valproic acid (500 mg kg-1 day for seven days. Group III was given only EDA (30 mg kg-1day for seven days. Group IV was given VPA+EDA (in same dose and time. EDA and VPA were given intraperitoneally. On the 8th day of experiment, blood samples and liver tissue were taken. Serum aspartate and alanine aminotransferase, alkaline phosphatase and bilirubin levels, liver myeloperoxidase, xanthine oxidase, adenosine deaminase, Na+/K+ATPase, sorbitol dehydrogenase, glutamate dehydrogenase, DT-diaphorase, arginase and thromboplastic activities, lipid peroxidation, protein carbonyl levels were increased whereas paraoxonase, biotinidase activities and glutathione levels were decreased in VPA group. Application of EDA with VPA protected against VPA-induced effects. These results demonstrated that administration of EDA is a potentially beneficial agent to reduce hepatic damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.

  10. Protective role of metallothionein (Ⅰ/Ⅱ) against pathological damage and apoptosis induced by dimethylarsinic acid

    Institute of Scientific and Technical Information of China (English)

    Guang Jia; Yi-Qun Gu; Kung-Tung Chen; You-Yong Lu; Lei Yan; Jian-Ling Wang; Ya-Ping Su; J. C. Gaston Wu

    2004-01-01

    AIM: To better clarify the main target organs of dimethylarsinic acid toxicity and the role of metallothionein (MTs) in modifying dimethylarsinic acid (DMAA) toxicity.METHODS: MT-Ⅰ/Ⅱ null (MT-/-) mice and the corresponding wild-type mice (MT+/+), six in each group, were exposed to DMAA (0-750 mg/kg body weight) by a single oral injection.Twenty four hours later, the lungs, livers and kidneys were collected and undergone pathological analysis, induction of apoptotic cells as determined by TUNEL and MT concentration was detected by radio-immunoassay.RESULTS: Remarkable pathological lesions were observed at the doses ranging from 350 to 750 mg/kg body weight in the lungs, livers and kidneys and MT+/+ mice exhibited a relatively slight destruction when compared with that in dose matched MT-/- mice. The number of apoptotic cells was increased in a dose dependent manner in the lungs and livers in both types of mice. DMAA produced more necrotic cells rather than apoptotic cells at the highest dose of 750 mg/kg,however, no significant increase was observed in the kidney.Hepatic MT level in MT+/+ mice was significantly increased by DMAA in a dose-dependent manner and there was nodetectable amount of hepatic MT in untreated MT-/- mice.CONCLUSION: DMAA treatment can lead to the induction of apoptosis and pathological damage in both types of mice.MT exhibits a protective effect against DMAA toxicity.

  11. A sensitive RNase protection assay to detect transcripts from potentially functional human endogenous L1 retrotransposons

    DEFF Research Database (Denmark)

    Woodcock, D M; Williamson, M R; Doherty, J P

    1996-01-01

    A high background of read-through transcripts from degenerate human L1 retrotransposons is present in almost all human cell types. This prevents the detection of RNA transcripts from potentially functional elements. To overcome this, we have developed an RNase protection assay based on the recons...... transcripts from divergent L1 families but are either discrete shorter transcripts or specifically processed products from longer initial transcripts....

  12. Assessment of human exposure effects of nitrous acid

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, T.R.; Kjaergaard, S.K. (University of Aarhus. Institute of Environmental and Occupational Medicine (Denmark)); Brauer, M. (Harvard School of Public Health. Department of Environmental Health, Exposure Assessment and Engineering Program (United States))

    1993-01-01

    The study aimed at an estimation of the relative contribution of nitrous acid to measurable human exposure effects in relation to indoor environments with unvented gas combustion. Fifteen medically examined totally healthy non-smoker adults aged between 22 and 57 years were exposed in a double-blind, balanced design (3x3 latin square) to clean air and nitrous acid (HONO) concentration in an empty 74 m[sup 3] climate chamber. 3 teams of 5 subjects each were randomly exposed and the latin square was selected at random. Each exposure period was 3.5 hours and preceded by a 1 hour base-line pre-exposure measurement period. After 1 hr 40 minutes the subjects exercised for ten minutes on bicycle ergometers in order to increase the uptake of HONO by increasing ventilatory rate 3-4 fold. Workloads were calculated individually and ranged from 21800-34600 kpm/h. During the 10 minutes the test subjects were mouth-breathing to encourage deeper penetration of nitrous acid in the respiratory system so as to induce a mild cooling which would increase their responsiveness to irritants. The amount of deliverable H[sup +] was estimated at 16.350 nmoles with exposure to 395 ppb HONO with subjects breathing at the rate of 5 L min[sup -1]. It was assumed that HONO is efficiently absorbed into the respiratory system. Details are given of the results. Findings were highly variable, largely negative effects of exposure to nitrous acid which appear similiar to results seen in nitrogen dioxide exposure studies. It is concluded to be unlikely that HONO exposures alone can be responsible for exposure misclassification in NO[sub 2] exposure studies. (AB) (52 refs.).

  13. Assessment of human exposure effects of nitrous acid

    Energy Technology Data Exchange (ETDEWEB)

    Rasmussen, T.R.; Kjaergaard, S.K. [University of Aarhus. Institute of Environmental and Occupational Medicine (Denmark); Brauer, M. [Harvard School of Public Health. Department of Environmental Health, Exposure Assessment and Engineering Program (United States)

    1993-01-01

    The study aimed at an estimation of the relative contribution of nitrous acid to measurable human exposure effects in relation to indoor environments with unvented gas combustion. Fifteen medically examined totally healthy non-smoker adults aged between 22 and 57 years were exposed in a double-blind, balanced design (3x3 latin square) to clean air and nitrous acid (HONO) concentration in an empty 74 m{sup 3} climate chamber. 3 teams of 5 subjects each were randomly exposed and the latin square was selected at random. Each exposure period was 3.5 hours and preceded by a 1 hour base-line pre-exposure measurement period. After 1 hr 40 minutes the subjects exercised for ten minutes on bicycle ergometers in order to increase the uptake of HONO by increasing ventilatory rate 3-4 fold. Workloads were calculated individually and ranged from 21800-34600 kpm/h. During the 10 minutes the test subjects were mouth-breathing to encourage deeper penetration of nitrous acid in the respiratory system so as to induce a mild cooling which would increase their responsiveness to irritants. The amount of deliverable H{sup +} was estimated at 16.350 nmoles with exposure to 395 ppb HONO with subjects breathing at the rate of 5 L min{sup -1}. It was assumed that HONO is efficiently absorbed into the respiratory system. Details are given of the results. Findings were highly variable, largely negative effects of exposure to nitrous acid which appear similiar to results seen in nitrogen dioxide exposure studies. It is concluded to be unlikely that HONO exposures alone can be responsible for exposure misclassification in NO{sub 2} exposure studies. (AB) (52 refs.).

  14. Expression of retinoic acid receptors in human endometrial carcinoma.

    Science.gov (United States)

    Tanabe, Kojiro; Utsunomiya, Hiroki; Tamura, Mitsutoshi; Niikura, Hitoshi; Takano, Tadao; Yoshinaga, Kohsuke; Nagase, Satoru; Suzuki, Takashi; Ito, Kiyoshi; Matsumoto, Mitsuyo; Hayashi, Shin-ichi; Yaegashi, Nobuo

    2008-02-01

    The retinoids (vitamin A and its biologically active derivatives) are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) beta is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RAR beta could act as a tumor suppressor. However, the status of RAR beta in human endometrial carcinoma has not been examined. In the present study, we initially studied the effects of retinoic acid on cell proliferation and the expression of RAR alpha, RAR beta, and RAR gamma using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RAR in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally, we correlated these findings with the clinicopathological parameters. In vitro, cell growth was inhibited and RAR beta and RAR gamma mRNA was significantly induced by AM580, compared with vehicle controls, whereas RAR alpha mRNA was significantly attenuated by AM580, compared with vehicle. RAR beta was detected predominantly in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. The results of our study demonstrate that AM580 inhibits cell growth and induces RAR beta mRNA expression in the Ishikawa cell line, and the expression level of RAR beta in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma.

  15. Melissa officinalis Acidic Fraction Protects Cultured Cerebellar Granule Neurons Against Beta Amyloid-Induced Apoptosis and Oxidative Stress.

    Science.gov (United States)

    Soodi, Maliheh; Dashti, Abolfazl; Hajimehdipoor, Homa; Akbari, Shole; Ataei, Nasim

    2017-01-01

    Extracellular deposition of the beta-amyloid (Aβ) peptide, which is the main finding in the pathophysiology of Alzheimer's disease (AD), leads to oxidative damage and apoptosis in neurons. Melissa officinalis (M. officinalis) is a medicinal plant from the Lamiaceae family that has neuroprotective activity. In the present study we have investigated the protective effect of the acidic fraction of M. officinalis on Aβ-induced oxidative stress and apoptosis in cultured cerebellar granule neurons (CGN). Additionally, we investigated a possible role of the nicotinic receptor. This study was an in vitro experimental study performed on mice cultured CGNs. CGNs were pre-incubated with different concentrations of the acidic fraction of M. officinalis for 24 hours, followed by incubation with Aβ for an additional 48 hours. CGNs were also pre-incubated with the acidic fraction of M. officinalis and mecamylamin, followed by incubation with Aβ. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay to measure cell viability. Acetylcholinesterase (AChE) activity, reactive oxygen species (ROS) production, lipidperoxidation, and caspase-3 activity were measured after incubation. Hochst/annexin Vfluorescein isothiocyanate (FITC)/propidium iodide (PI) staining was performed to detect apoptotic cells. The acidic fraction could protect CGNs from Aβ-induced cytotoxicity. Mecamylamine did not abolish the protective effect of the acidic fraction. AChE activity, ROS production, lipid peroxidation, and caspase-3 activity increased after Aβ incubation. Preincubation with the acidic fraction of M. officinalis ameliorated these factors and decreased the number of apoptotic cells. Our results indicated that the protective effect of the acidic fraction of M. officinalis was not mediated through nicotinic receptors. This fraction could protect CGNs through antioxidant and anti-apoptotic activities.

  16. Dietary monounsaturated fatty acids are protective against metabolic syndrome and cardiovascular disease risk factors.

    Science.gov (United States)

    Gillingham, Leah G; Harris-Janz, Sydney; Jones, Peter J H

    2011-03-01

    Over 50 years of research has sought to define the role dietary fat plays in cardiovascular disease (CVD) risk. Although optimal dietary fat quantity has been keenly pursued over past decades, attention has recently centered on the value of dietary fat quality. The purpose of the present review is to provide a critical assessment of the current body of evidence surrounding efficacy of dietary monounsaturated fatty acids (MUFA) for reduction of traditional risk factors defining metabolic syndrome (MetS) and CVD. Due to existing and emerging research on health attributes of MUFA rich diets, and to the low prevalence of chronic disease in populations consuming MUFA rich Mediterranean diets, national dietary guidelines are increasingly recommending dietary MUFA, primarily at the expense of saturated fatty acids (SFA). Consumption of dietary MUFA promotes healthy blood lipid profiles, mediates blood pressure, improves insulin sensitivity and regulates glucose levels. Moreover, provocative newer data suggest a role for preferential oxidation and metabolism of dietary MUFA, influencing body composition and ameliorating the risk of obesity. Mounting epidemiological and human clinical trial data continue to demonstrate the cardioprotective activity of the MUFA content of dietary fat. As the debate on the optimal fatty acid composition of the diet continues, the benefit of increasing MUFA intakes, particularly as a substitute for dietary SFA, deserves considerable attention.

  17. Ursolic Acid Mediates Hepatic Protection through Enhancing of anti-aging Biomarkers.

    Science.gov (United States)

    Gharibi, Shadi; Bakhtiari, Nuredin; Jalalvand, Elham-Moslemee

    2017-05-30

    Age-associated loss of liver function has been recognized for decades. But, the mechanism driving liver regeneration and its decline with age remains elusive. Hence, to support of our previous studies about anti-aging effects of Ursolic Acid (UA), a compound which extensively present in apple peels. The aim of this study is to address whether UA might alter sensors of the cell metabolic state such as SIRT1, SIRT6, PGC-1β and Klotho proteins. To evaluate the effect of UA on hepatic indicated proteins, mice were administrated with UA twice daily for 7 days. The involvements of these proteins in the UA-mediated effect harmony hepatic protection were investigated by immunofluorescence microscopy technique. Our findings clearly illustrated that UA enhanced SIRT1 (~ 5 ± 0.2 folds) and SIRT6 (~ 8 ± 0.5 folds) proteins levels in hepatic, p<0.001. In addition, the data showed that UA increased PGC-1β (~ 7 ± 0.4 folds) protein overexpression, p<0.001. Moreover, we showed that UA up-regulated Klotho (~ 3.5 ± 0.2 folds) protein in order to improve hepatic performance, p<0.01. Our results suggest that UA through increasing of SIRT1 up-regulation ameliorate reverse cholesterol transport, fatty acid use and oxidative stress defense. In addition, it seems that UA by enhancing of SIRT6 expression promotes cholesterol homeostasis through repressing of SREBP1 and SREBP2. Reciprocally, UA might be involved in VLDL synthesis and exportation through PGC-1β up-regulation. Finally, UA might be as key regulators of mineral homeostasis and bile acid/cholesterol metabolism, by inducing of Klotho overexpression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. DNA damage protecting and free radical scavenging properties of mycosporine-2-glycine from the Dead Sea cyanobacterium in A375 human melanoma cell lines.

    Science.gov (United States)

    Cheewinthamrongrod, Vipaporn; Kageyama, Hakuto; Palaga, Tanapat; Takabe, Teruhiro; Waditee-Sirisattha, Rungaroon

    2016-11-01

    Mycosporine-like amino acids (MAAs) are a group of natural sunscreen compounds that possess highly photoprotective properties. The most commonly found MAAs in marine organisms is shinorine, porphyra-334, and mycosporine-glycine. However, the halophilic species accumulate mycosporine-2-glycine (M2G) as the major MAA. In this study, we have investigated the protective effect of M2G against oxidative stress. In vitro radical scavenging activity revealed that M2G exhibited a significant inhibition with scavenging concentration (SC) 50 value of 22±1.4μM. In vivo analysis using the human melanoma A375 and a control cell line (NHSF) showed that M2G at low concentration (i.e. micromolar range) protected the cells against the oxidative stress (H2O2)-induced cell death. Comet assay to assess total DNA strand breaks demonstrated that M2G was not genotoxic and protected against the DNA damage by H2O2 treatment at the same level as ascorbic acid. To our knowledge, this is the first evidence demonstrating potential protective role of the natural sunscreen compound M2G against oxidative stress-induced DNA damage in human cell lines. The potent antioxidant activity combined with DNA protection ability of M2G may support its endorsement as a potential natural sunscreen with antioxidant property. These findings provide important clues for possible use of M2G in pharmaceutical and biotechnological applications.

  19. Mx1 gene protects mice against the highly lethal human H5N1 influenza virus.

    Science.gov (United States)

    Salomon, Rachelle; Staeheli, Peter; Kochs, Georg; Yen, Hui-Ling; Franks, John; Rehg, Jerold E; Webster, Robert G; Hoffmann, Erich

    2007-10-01

    We investigated the importance of the host Mx1 gene in protection against highly pathogenic H5N1 avian influenza virus. Mice expressing the Mx1 gene survived infection with the lethal human H5N1 isolate A/Vietnam/1203/04 and with reassortants combining its genes with those of the non-lethal virus A/chicken/Vietnam/C58/04, while all Mx1-/- mice succumbed. Mx1-expressing mice showed lower organ virus titers, fewer lesions, and less pulmonary inflammation. Our data support the hypothesis that Mx1 expression protects mice against the high pathogenicity of H5N1 virus through inhibition of viral polymerase activity ultimately resulting in reduced viral growth and spread. Drugs that mimic this mechanism may be protective in humans.

  20. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  1. Protecting the Home and Adequate Housing - Living in a Caravan or Trailer as a Human Right

    NARCIS (Netherlands)

    Donders, Y.

    2016-01-01

    Many Roma, gypsies and travellers live in caravans or trailers, sometimes in together trailer parks or camps. This article analyses how this specific lifestyle connected to their housing is protected under the various regimes and provisions of international human rights law. Home and adequate housin

  2. 76 FR 11248 - Secretary's Advisory Committee on Human Research Protections; Notice of Meeting

    Science.gov (United States)

    2011-03-01

    ...: Jerry Menikoff, M.D., J.D., Director, Office for Human Research Protections, or Julia Gorey, J.D..., Rockville, Maryland 20852; 240-453-6900, fax: 240-453-6909; e-mail address: Julia.Gorey@hhs.gov... as sign language interpretation or other reasonable accommodations, should notify the...

  3. 76 FR 58006 - Meeting of the Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2011-09-19

    ... Protections (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP; U.S. Department of Health and Human...-mail address: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the authority of 42 U.S.C. 217a... who plan to attend the meeting and need special assistance, such as sign language interpretation...

  4. 76 FR 37354 - Meeting of the Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2011-06-27

    ... Protections (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP; U.S. Department of Health and Human...-mail address: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the authority of 42 U.S.C. 217a... sign language interpretation or other reasonable accommodations, should notify the designated...

  5. 78 FR 12061 - Meeting of the Secretary's Advisory Committee on Human Research Protections

    Science.gov (United States)

    2013-02-21

    ... Protections (OHRP), or Julia Gorey, J.D., Executive Director, SACHRP; U.S. Department of Health and Human...; email address: Julia.Gorey@hhs.gov . SUPPLEMENTARY INFORMATION: Under the authority of 42 U.S.C. 217a.... Individuals who plan to attend the meeting and need special assistance, such as sign language...

  6. Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hong Sun; Juan Ren; Qing Zhu; Fan-Zhong Kong; Lei Wu; Bo-Rong Pan

    2009-01-01

    AIM: To study the effects of lysophosphatidic acid (LPA) on proliferation, adhesion, migration, and apoptosisin the human colon cancer cell line, SW480, and its mechanisms of action. METHODS: Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transwell migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol.RESULTS: LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group (P < 0.05) while the mitogen-activated protein kinase (MAPK) inhibitor,PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner (P < 0.05). Rho kinase inhibitor,Y-27632, significantly inhibited the up-regulatory effect of LPA on adhesion and migration (P < 0.05). LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU (P < 0.05),but the phosphoinositide 3-kinase (PI3K) inhibitor,LY294002, significantly blocked the protective effect of LPA on apoptosis.CONCLUSION: LPA stimulated proliferation, adhesion,migration of SW480 cells, and protected from apoptosis.The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3KAKT/ PKB signal pathways may be involved.

  7. Enhancement of corrosion protection efficiency of iron by poly(aniline-co-amino-naphthol-sulphonic acid) nanowires coating in highly acidic medium

    Energy Technology Data Exchange (ETDEWEB)

    Bhandari, Hema [Polymeric and Soft Materials Section National Physical Laboratory (CSIR) Dr. K. S. Krishnan, Road New Delhi, 110 012 (India); Centre for Polymer Science and Engineering, Indian Institute of Technology New Delhi, 110, 016 (India); Srivastav, Ritu [Polymeric and Soft Materials Section National Physical Laboratory (CSIR) Dr. K. S. Krishnan, Road New Delhi, 110 012 (India); Choudhary, Veena [Centre for Polymer Science and Engineering, Indian Institute of Technology New Delhi, 110, 016 (India); Dhawan, S.K., E-mail: skdhawan@mail.nplindia.ernet.i [Polymeric and Soft Materials Section National Physical Laboratory (CSIR) Dr. K. S. Krishnan, Road New Delhi, 110 012 (India)

    2010-11-30

    Nanowires of copolymers film based on aniline and 1-amino-2-naphthol-4-sulphonic acid were electrochemically synthesized on the iron electrode by cyclic voltammetry using oxalic acid as a supporting electrolyte. Protective properties of copolymer film on the iron surface in 1.0 M HCl solution was investigated by chronoamperometry, potentiodynamic polarization technique and electrochemical impedance spectroscopy (EIS). The results showed that the copolymer film showed the significant shifting in the corrosion potential and greater charge transfer resistance. Moreover, the copolymer showed the larger degree of surface coverage onto the iron surface, reflecting the higher protection for corrosion of the iron in acidic medium. In addition, the film constitutes a physical as well as a chemical barrier layer due to the presence of -OH and -NH groups in ANSA unit, which provides passivity protection in polymer coatings. The mechanism of corrosion protection of iron by these copolymers was investigated by surface morphology and EIS techniques. In addition, by using scanning electron microscopy, the effect of morphology of copolymer on corrosion protection of metal was investigated.

  8. Influence of acid and bile acid on ERK activity, PPARY expression and cell proliferation in normal human esophageal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Zhi-Ru Jiang; Jun Gong; Zhen-Ni Zhang; Zhe Qiao

    2006-01-01

    AIM: To observe the effects of acid and bile acid exposure on cell proliferation and the expression of extracellular signal-regulated protein kinase (ERK) and peroxisome proliferator-activated receptor Y (PPARy) in normal human esophageal epithelial cells in vitro.METHODS: In vitro cultured normal human esophageal epithelial cells were exposed to acidic media (pH 4.0-6.5), media containing different bile acid (250 μmol/L), media containing acid and bile acid, respectively.Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK1/2 and PPARy protein were determined by the immunoblotting technique.RESULTS: Acid-exposed (3 min) esophageal cells exhibited a significant increase in proliferation ratio,S phase of the cell cycle (P<0.05) and the level of phosphorylated ERK1/2 protein. When the acid-exposure period exceeded 6 min, we observed a decrease in proliferation ratio and S phase of the cell cycle, with an increased apoptosis ratio (P<0.05). Bile acid exposure (3-12 min) also produced an increase in proliferation ratio, S phase of the cell cycle (P<0.05)and phosphorylated ERK1/2 expression. On the contrary,deoxycholic acid (DCA) exposure (>20 min) decreased proliferation ratio. Compared with bile acid exposure (pH 7.4), bile acid exposure (pH 6.5, 4) significantly decreased proliferation ratio (P<0.05). There was no expression of PPARY in normal human esophageal epithelial cells.CONCLUSION: The rapid stimuli of acid or bile acid increase proliferation in normal human esophageal epithelial cells by activating the ERK pathway.

  9. Cloning and characterization of a functional human ¿-aminobutyric acid (GABA) transporter, human GAT-2

    DEFF Research Database (Denmark)

    Christiansen, Bolette; Meinild, Anne-Kristine; Jensen, Anders A.

    2007-01-01

    Plasma membrane gamma-aminobutyric acid (GABA) transporters act to terminate GABA neurotransmission in the mammalian brain. Intriguingly four distinct GABA transporters have been cloned from rat and mouse, whereas only three functional homologs of these transporters have been cloned from human....... The aim of this study therefore was to search for this fourth missing human transporter. Using a bioinformatics approach, we successfully identified and cloned the full-length cDNA of a so far uncharacterized human GABA transporter (GAT). The predicted protein displays high sequence similarity to rat GAT......-2 and mouse GAT3, and in accordance with the nomenclature for rat GABA transporters, we therefore refer to the transporter as human GAT-2. We used electrophysiological and cell-based methods to demonstrate that this protein is a functional transporter of GABA. The transport was saturable...

  10. Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes.

    Directory of Open Access Journals (Sweden)

    Lucia Mališová

    Full Text Available Stress of endoplasmic reticulum (ERS is one of the molecular triggers of adipocyte dysfunction and chronic low inflammation accompanying obesity. ERS can be alleviated by chemical chaperones from the family of bile acids (BAs. Thus, two BAs currently used to treat cholestasis, ursodeoxycholic and tauroursodeoxycholic acid (UDCA and TUDCA, could potentially lessen adverse metabolic effects of obesity. Nevertheless, BAs effects on human adipose cells are mostly unknown. They could regulate gene expression through pathways different from their chaperone function, namely through activation of farnesoid X receptor (FXR and TGR5, G-coupled receptor. Therefore, this study aimed to analyze effects of UDCA and TUDCA on human preadipocytes and differentiated adipocytes derived from paired samples of two distinct subcutaneous adipose tissue depots, abdominal and gluteal. While TUDCA did not alter proliferation of cells from either depot, UDCA exerted strong anti-proliferative effect. In differentiated adipocytes, acute exposition to neither TUDCA nor UDCA was able to reduce effect of ERS stressor tunicamycin. However, exposure of cells to UDCA during whole differentiation process decreased expression of ERS markers. At the same time however, UDCA profoundly inhibited adipogenic conversion of cells. UDCA abolished expression of PPARγ and lipogenic enzymes already in the early phases of adipogenesis. This anti-adipogenic effect of UDCA was not dependent on FXR or TGR5 activation, but could be related to ability of UDCA to sustain the activation of ERK1/2 previously linked with PPARγ inactivation. Finally, neither BAs did lower expression of chemokines inducible by TLR4 pathway, when UDCA enhanced their expression in gluteal adipocytes. Therefore while TUDCA has neutral effect on human preadipocytes and adipocytes, the therapeutic use of UDCA different from treating cholestatic diseases should be considered with caution because UDCA alters functions of

  11. Vaccines against human papillomavirus infections: protection against cancer, genital warts or both?

    Science.gov (United States)

    Joura, E A; Pils, S

    2016-12-01

    Since 2006, three vaccines against infections and disease caused by human papillomavirus (HPV) became available in Europe-in 2006 a quadrivalent HPV 6/11/16/18 vaccine, in 2007 a bivalent HPV 16/18 vaccine and in 2015 a nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine. HPV 16 and 18 are the most oncogenic HPV strains, causing about 70% of cervical and other HPV-related cancers, HPV 6 and 11 cause 85% of all genital warts. The additional types of the polyvalent vaccine account for about 20% of invasive cervical cancer and >35% of pre-cancer. The potential differences between these vaccines caused some debate. All three vaccines give a robust and long-lasting protection against the strains in the various vaccines. The promise of cross-protection against other types (i.e. HPV 31/33/45) and hence a broader cancer protection was not fulfilled because these observations were confounded by the vaccine efficacy against the vaccine types. Furthermore, cross-protection was not consistent over various studies, not durable and not consistently seen in the real world experience. The protection against disease caused by oncogenic HPV strains was not compromised by the protection against low-risk types causing genital warts. The most effective cancer protection to date can be expected by the nonavalent vaccine, data indicate a 97% efficacy against cervical and vulvovaginal pre-cancer caused by these nine HPV types.

  12. Probucol increases striatal glutathione peroxidase activity and protects against 3-nitropropionic acid-induced pro-oxidative damage in rats.

    Science.gov (United States)

    Colle, Dirleise; Santos, Danúbia Bonfanti; Moreira, Eduardo Luiz Gasnhar; Hartwig, Juliana Montagna; dos Santos, Alessandra Antunes; Zimmermann, Luciana Teixeira; Hort, Mariana Appel; Farina, Marcelo

    2013-01-01

    Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disease characterized by symptoms attributable to the death of striatal and cortical neurons. The molecular mechanisms mediating neuronal death in HD involve oxidative stress and mitochondrial dysfunction. Administration of 3-nitropropionic acid (3-NP), an irreversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, in rodents has been proposed as a useful experimental model of HD. This study evaluated the effects of probucol, a lipid-lowering agent with anti-inflammatory and antioxidant properties, on the biochemical parameters related to oxidative stress, as well as on the behavioral parameters related to motor function in an in vivo HD model based on 3-NP intoxication in rats. Animals were treated with 3.5 mg/kg of probucol in drinking water daily for 2 months and, subsequently, received 3-NP (25 mg/kg i.p.) once a day for 6 days. At the end of the treatments, 3-NP-treated animals showed a significant decrease in body weight, which corresponded with impairment on motor ability, inhibition of mitochondrial complex II activity and oxidative stress in the striatum. Probucol, which did not rescue complex II inhibition, protected against behavioral and striatal biochemical changes induced by 3-NP, attenuating 3-NP-induced motor impairments and striatal oxidative stress. Importantly, probucol was able to increase activity of glutathione peroxidase (GPx), an enzyme important in mediating the detoxification of peroxides in the central nervous system. The major finding of this study was that probucol protected against 3-NP-induced behavioral and striatal biochemical changes without affecting 3-NP-induced mitochondrial complex II inhibition, indicating that long-term probucol treatment resulted in an increased resistance against neurotoxic events (i.e., increased oxidative damage) secondary to mitochondrial dysfunction. These data appeared to be of great relevance when

  13. Protective effects of dietary glycine and glutamic acid toward the toxic effects of oxidized mustard oil in rabbits.

    Science.gov (United States)

    Zeb, Alam; Rahman, Saleem Ur

    2017-01-25

    The protective role of glycine and glutamic acid against the toxic effects of oxidized oil was studied for the first time. Mustard seed oil was thermally oxidized and characterized for quality characteristics and polyphenolic composition using reversed phase HPLC-DAD. Significant changes in the quality characteristics occurred with thermal oxidation. Fourteen polyphenolic compounds were identified and quantified in oils. Quercetin-3-glucoside, quercetin-3-feruloylsophoroside, catechin, quercetin-3-rutinoside, quercetin-3,7-diglucoside, sinapic acid and vanillic acid hexoside were the major compounds in the fresh and oxidized oil. Oxidized, un-oxidized mustard oils, glycine and glutamic acid were given to rabbits alone or in combination. The biochemical responses were studied in terms of haematological and biochemical parameters and histopathology. It has been observed that biochemical and haematological parameters were adversely affected by the oxidized oil, while supplementation of both amino acids was beneficial in normalizing these parameters. Both amino acids alone have no significant effects, however, oxidized oil affected the liver by enhancing fat accumulation, causing hepatitis, reactive Kupffer cells and necrosis. The co-administration of oxidized oils with glycine or glutamic acid revealed significant recovery of the liver structure and function. In conclusion, glycine or glutamic acid is beneficial and protective against food toxicity and can be considered as an ameliorative food supplement.

  14. Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1.

    Science.gov (United States)

    Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

    2015-11-05

    As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels.

  15. Effects of Salvianolic Acid B on Protein Expression in Human Umbilical Vein Endothelial Cells

    Science.gov (United States)

    Chang, Tsong-Min; Shi, Guey-Yueh; Wu, Hua-Lin; Wu, Chieh-Hsi; Su, Yan-Di; Wang, Hui-Lin; Wen, Hsin-Yun; Huang, Huey-Chun

    2011-01-01

    Salvianolic acid B (Sal B), a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothelial cells (HUVECs) were incubated at Sal B concentrations that can be reached in human plasma by pharmacological intervention. Results indicated that caldesmon, an actin-stabilizing protein, was downregulated in Sal B-exposed HUVECs. Proteins that showed increased expression levels upon Sal B treatment were vimentin, T-complex protein 1, protein disulfide isomerase, tropomyosin alpha, heat shock protein beta-1, UBX domain-containing protein 1, alpha enolase, and peroxiredoxin-2. Additionally, Sal B leads to increased phosphorylation of nucleophosmin in a dose-dependent manner and promotes proliferation of HUVECs. We found that Sal B exhibited a coordinated regulation of enzymes and proteins involved in cytoskeletal reorganization, oxidative stress, and cell growth. Our investigation would provide understanding to the endothelium protection information of Sal B. PMID:21423689

  16. Effects of Salvianolic Acid B on Protein Expression in Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Tsong-Min Chang

    2011-01-01

    Full Text Available Salvianolic acid B (Sal B, a pure water-soluble compound extracted from Radix Salviae miltiorrhizae, has been reported to possess potential cardioprotective efficacy. To identify proteins or pathways by which Sal B might exert its protective activities on the cardiovascular system, two-dimensional gel electrophoresis-based comparative proteomics was performed, and proteins altered in their expression level after Sal B treatment were identified by MALDI-TOF MS/MS. Human umbilical vein endothelial cells (HUVECs were incubated at Sal B concentrations that can be reached in human plasma by pharmacological intervention. Results indicated that caldesmon, an actin-stabilizing protein, was downregulated in Sal B-exposed HUVECs. Proteins that showed increased expression levels upon Sal B treatment were vimentin, T-complex protein 1, protein disulfide isomerase, tropomyosin alpha, heat shock protein beta-1, UBX domain-containing protein 1, alpha enolase, and peroxiredoxin-2. Additionally, Sal B leads to increased phosphorylation of nucleophosmin in a dose-dependent manner and promotes proliferation of HUVECs. We found that Sal B exhibited a coordinated regulation of enzymes and proteins involved in cytoskeletal reorganization, oxidative stress, and cell growth. Our investigation would provide understanding to the endothelium protection information of Sal B.

  17. Spotted hyaena space use in relation to human infrastructure inside a protected area

    Science.gov (United States)

    Belton, Lydia E.; Cameron, Elissa Z.

    2016-01-01

    Increasing human population growth has led to elevated levels of human-carnivore conflict. However, some carnivore populations have adapted to urban environments and the resources they supply. Such associations may influence carnivore ecology, behaviour and life-history. Pockets of urbanisation sometimes occur within protected areas, so that anthropogenic influences on carnivore biology are not necessarily confined to unprotected areas. In this study we evaluated associations between human infrastructure and related activity and space use of spotted hyaenas within one of the largest protected areas in South Africa, the Kruger National Park. Home range size was smaller for the dominant female of a clan living in close proximity to humans than that of the dominant female of a clan without direct access to human infrastructure. The home range including human infrastructure was also used less evenly during the night, presumably when the animals were active. Within this home range, a village area was preferred during the night, when the least modified areas within the village were preferred and administration and highly modified areas were avoided. During the day, however, there were no preference or avoidance of the village area, but all habitats except unmodified habitats within the village area were avoided. We suggest that human infrastructure and associated activity influenced hyaena space use, primarily through alterations in the spatial distribution of food. However, these effects may have been indirectly caused by habitat modification that generated favourable hunting habitat rather than a direct effect caused by access to human food such as garbage. Because of the often pivotal effects of apex predators in terrestrial ecosystems, we encourage further work aimed to quantify how human presence influences large carnivores and associated ecosystem processes within protected areas. PMID:27781175

  18. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Landbo, A K; Christensen, L P

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4-diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid...

  19. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins

    DEFF Research Database (Denmark)

    Andreasen, M.F.; Landbo, Anne-Katrine Regel; Christensen, L.P.

    2001-01-01

    Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were...... investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4- diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid...

  20. Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Lindsay Crickard

    Full Text Available Smallpox (variola virus is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs against smallpox are a conservative approach to this problem, as the licensed human smallpox vaccine (vaccinia virus, VACV primarily works on the basis of protective antibody responses against smallpox. Fully human mAbs (hmAbs against vaccinia H3 (H3L and B5 (B5R, targeting both the mature virion (MV and extracellular enveloped virion (EV forms, have been developed as potential therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP studies examining severe combined immunodeficiency mice (SCID given a lethal VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection against disease and death than either single hmAb or vaccinia immune globulin (VIG. Post-exposure combination mAb therapy provided significant protection against disease and death, and appeared to fully cure the VACV infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV. In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling smallpox disease in immunocompetent or immunodeficient humans.

  1. Simultaneous determination of acetylsalicylic acid and salicylic acid in human plasma by isocratic high-pressure liquid chromatography with post-column hydrolysis and fluorescence detection.

    Science.gov (United States)

    Hobl, Eva-Luise; Jilma, Bernd; Ebner, Josef; Schmid, Rainer W

    2013-06-01

    A selective, sensitive and rapid high-performance liquid chromatography method with post-column hydrolysis and fluorescence detection was developed for the simultaneous quantification of acetylsalicylic acid and its metabolite salicylic acid in human plasma. Following the addition of 2-hydroxy-3-methoxybenzoic acid as internal standard and simple protein precipitation with acetonitrile, the analytes were separated on a ProntoSIL 120 C18 ace-EPS column (150 × 2 mm, 3 µm) protected by a C8 guard column (5 µm). The mobile phase, 10 mm formic acid in water (pH 2.9) and acetonitrile (70:30, v/v), was used at a flow rate of 0.35 mL/min. After on-line post-column hydrolysis of acetylsalicylic acid (ASA) to salicylic acid (SA) by addition of alkaline solution, the analytes were measured at 290 nm (λex ) and 400 nm (λem ). The method was linear in the concentration ranges between 0.05 and 20 ng/μL for both ASA and SA with a lower limit of quantification of 25 pg/μL for SA and 50 pg/μL for ASA. The limit of detection was 15 pg/μL for SA and 32.5 pg/μL for ASA. The analysis of ASA and SA can be carried out within 8 min; therefore this method is suitable for measuring plasma concentrations of salicylates in clinical routine.

  2. Lewis acid catalysed methylation of N-(9H-fluoren-9-yl)methanesulfonyl (Fms) protected lipophilic α-amino acid methyl esters.

    Science.gov (United States)

    Leggio, Antonella; Alò, Danila; Belsito, Emilia Lucia; Di Gioia, Maria Luisa; Romio, Emanuela; Siciliano, Carlo; Liguori, Angelo

    2015-08-01

    This work reports an efficient Lewis acid catalysed N-methylation procedure of lipophilic α-amino acid methyl esters in solution phase. The developed methodology involves the use of the reagent system AlCl3/diazomethane as methylating agent and α-amino acid methyl esters protected on the amino function with the (9H-fluoren-9-yl)methanesulfonyl (Fms) group. The removal of Fms protecting group is achieved under the same conditions to those used for Fmoc removal. Thus the Fms group can be interchangeable with the Fmoc group in the synthesis of N-methylated peptides using standard Fmoc-based strategies. Finally, the absence of racemization during the methylation reaction and the removal of Fms group were demonstrated by synthesising a pair of diastereomeric dipeptides. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  3. Biochemical study on the protective role of folic acid in rabbits treated with chromium (VI).

    Science.gov (United States)

    El-Demerdash, Fatma M; Yousef, Mokhtar I; Elaswad, Fathia A M

    2006-01-01

    biochemical parameters. In conclusion, folic acid could be effective in the protection of chromium-induced toxicity.

  4. Human monocyte differentiation stage affects response to arachidonic acid.

    Science.gov (United States)

    Escobar-Alvarez, Elizabeth; Pelaez, Carlos A; García, Luis F; Rojas, Mauricio

    2010-01-01

    AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.

  5. Kinetics of fatty acid binding ability of glycated human serum albumin

    Indian Academy of Sciences (India)

    Eiji Yamazaki; Minoru Inagaki; Osamu Kurita; Tetsuji Inoue

    2005-09-01

    Kinetics of fatty acid binding ability of glycated human serum albumin (HSA) were investigated by fluorescent displacement technique with 1-anilino-8-naphtharene sulphonic acid (ANS method), and photometric detection of nonesterified-fatty-acid (NEFA method). Changing of binding affinities of glycated HSA toward oleic acid, linoleic acid, lauric acid, and caproic acid, were not observed by the ANS method. However, decreases of binding capacities after 55 days glycation were confirmed by the NEFA method in comparison to control HSA. The decrease in binding affinities was: oleic acid (84%), linoleic acid (84%), lauric acid (87%), and caproic acid (90%), respectively. The decreases were consistent with decrease of the intact lysine residues in glycated HSA. The present observation indicates that HSA promptly loses its binding ability to fatty acid as soon as the lysine residues at fatty acid binding sites are glycated.

  6. Scientific Opinion on the substantiation of a health claim related to hyaluronic acid and protection of the skin against dehydration pursuant to Article 13(5 of Regulation (EC No 1924/2006

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies

    2012-07-01

    Full Text Available

    Following an application from Nutrilinks Sarl, submitted for authorisation of a health claim pursuant to Article 13(5 of Regulation (EC No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA was asked to deliver an opinion on the scientific substantiation of a health claim related to hyaluronic acid and protection of the skin against dehydration. The food constituent that is the subject of the health claim, hyaluronic acid, is sufficiently characterised. The claimed effect, protection of the skin against dehydration, is a beneficial physiological effect. The target population proposed by the applicant is the general population. No human studies have been provided from which conclusions could be drawn for the scientific substantiation of the claim. A cause and effect relationship has not been established between the consumption of hyaluronic acid and protection of the skin against dehydration.

  7. Unsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages[S

    Science.gov (United States)

    L'homme, Laurent; Esser, Nathalie; Riva, Laura; Scheen, André; Paquot, Nicolas; Piette, Jacques; Legrand-Poels, Sylvie

    2013-01-01

    The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared with unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. PMID:24006511

  8. A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

    Directory of Open Access Journals (Sweden)

    Belayev Ludmila

    2016-01-01

    Full Text Available Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3 complexed to human albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.

  9. Characterization of the human MSX-1 promoter and an enhancer responsible for retinoic acid induction.

    Science.gov (United States)

    Shen, R; Chen, Y; Huang, L; Vitale, E; Solursh, M

    1994-01-01

    Previous studies have shown that the expression of some human HOX genes can be induced by retinoic acid (RA) in cultured embryonal carcinoma (EC) cells. However, the mechanisms for the regulation of HOX gene expression by RA are still unclear. We have examined the effects of RA on the human MSX-1 (formerly named HOX-7) gene expression in cultured EC cells (NT2/D1). Furthermore, we have cloned and characterized the human MSX-1 promoter and analyzed the activities of the promoter in response to RA. Our results demonstrate that transcription of human MSX-1 is activated by RA in cultured EC cells. This activation is dose and time responsive. The MSX-1 promoter was shown to be TATA-box independent and able to promote transcription in RA-treated EC cells. DNase-I footprinting studies revealed protection of several GAGA factor binding sites and an NF-kappa B site upstream to the transcription start site by nuclear extracts prepared from EC cells. A downstream sequence was differentially protected by the nuclear extract from RA treated cells. This differential binding of the sequence with the nuclear extract was further confirmed by gel shift assays. This sequence confers to a heterologous promoter with the ability to respond to RA induction. Point mutation within this DNA fragment abolished the binding of the fragment to the nuclear extract and the response of this element in a heterologous promoter to RA induction. Deletion of this enhancer element together with the adjacent NF-kappa B and GAGA sites abolished the ability of the promoter to direct transcription in RA-treated EC cells. However, removal of a downstream DNA fragment from the promoter endowed the promoter with the ability to direct transcription in RA-untreated cells. Taken together, both positive and negative regulatory cis-elements are involved in the regulation of the MSX-1 promoter and coordinate to control the gene expression.

  10. Lactic acid delays the inflammatory response of human monocytes.

    Science.gov (United States)

    Peter, Katrin; Rehli, Michael; Singer, Katrin; Renner-Sattler, Kathrin; Kreutz, Marina

    2015-02-13

    Lactic acid (LA) accumulates under inflammatory conditions, e.g. in wounds or tumors, and influences local immune cell functions. We previously noted inhibitory effects of LA on glycolysis and TNF secretion of human LPS-stimulated monocytes. Here, we globally analyze the influence of LA on gene expression during monocyte activation. To separate LA-specific from lactate- or pH-effects, monocytes were treated for one or four hours with LPS in the presence of physiological concentrations of LA, sodium lactate (NaL) or acidic pH. Analyses of global gene expression profiles revealed striking effects of LA during the early stimulation phase. Up-regulation of most LPS-induced genes was significantly delayed in the presence of LA, while this inhibitory effect was attenuated in acidified samples and not detected after incubation with NaL. LA targets included genes encoding for important monocyte effector proteins like cytokines (e.g. TNF and IL-23) or chemokines (e.g. CCL2 and CCL7). LA effects were validated for several targets by quantitative RT-PCR and/or ELISA. Further analysis of LPS-signaling pathways revealed that LA delayed the phosphorylation of protein kinase B (AKT) as well as the degradation of IκBα. Consistently, the LPS-induced nuclear accumulation of NFκB was also diminished in response to LA. These results indicate that the broad effect of LA on gene expression and function of human monocytes is at least partially caused by its interference with immediate signal transduction events after activation. This mechanism might contribute to monocyte suppression in the tumor environment. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Shedding light on proteins, nucleic acids, cells, humans and fish

    Science.gov (United States)

    Setlow, Richard B.

    2002-01-01

    I was trained as a physicist in graduate school. Hence, when I decided to go into the field of biophysics, it was natural that I concentrated on the effects of light on relatively simple biological systems, such as proteins. The wavelengths absorbed by the amino acid subunits of proteins are in the ultraviolet (UV). The wavelengths that affect the biological activities, the action spectra, also are in the UV, but are not necessarily parallel to the absorption spectra. Understanding these differences led me to investigate the action spectra for affecting nucleic acids, and the effects of UV on viruses and cells. The latter studies led me to the discovery of the important molecular nature of the damages affecting DNA (cyclobutane pyrimidine dimers) and to the discovery of nucleotide excision repair. Individuals with the genetic disease xeroderma pigmentosum (XP) are extraordinarily sensitive to sunlight-induced skin cancer. The finding, by James Cleaver, that their skin cells were defective in DNA repair strongly suggested that DNA damage was a key step in carcinogenesis. Such information was important for estimating the wavelengths in sunlight responsible for human skin cancer and for predicting the effects of ozone depletion on the incidence of non-melanoma skin cancer. It took experiments with backcross hybrid fish to call attention to the probable role of the longer UV wavelengths not absorbed by DNA in the induction of melanoma. These reflections trace the biophysicist's path from molecules to melanoma.

  12. Protective

    Directory of Open Access Journals (Sweden)

    Wessam M. Abdel-Wahab

    2013-10-01

    Full Text Available Many active ingredients extracted from herbal and medicinal plants are extensively studied for their beneficial effects. Antioxidant activity and free radical scavenging properties of thymoquinone (TQ have been reported. The present study evaluated the possible protective effects of TQ against the toxicity and oxidative stress of sodium fluoride (NaF in the liver of rats. Rats were divided into four groups, the first group served as the control group and was administered distilled water whereas the NaF group received NaF orally at a dose of 10 mg/kg for 4 weeks, TQ group was administered TQ orally at a dose of 10 mg/kg for 5 weeks, and the NaF-TQ group was first given TQ for 1 week and was secondly administered 10 mg/kg/day NaF in association with 10 mg/kg TQ for 4 weeks. Rats intoxicated with NaF showed a significant increase in lipid peroxidation whereas the level of reduced glutathione (GSH and the activity of superoxide dismutase (SOD, catalase (CAT, glutathione S-transferase (GST and glutathione peroxidase (GPx were reduced in hepatic tissues. The proper functioning of the liver was also disrupted as indicated by alterations in the measured liver function indices and biochemical parameters. TQ supplementation counteracted the NaF-induced hepatotoxicity probably due to its strong antioxidant activity. In conclusion, the results obtained clearly indicated the role of oxidative stress in the induction of NaF toxicity and suggested hepatoprotective effects of TQ against the toxicity of fluoride compounds.

  13. Poly-γ-Glutamic Acid: Biodegradable Polymer for Potential Protection of Beneficial Viruses

    Directory of Open Access Journals (Sweden)

    Ibrahim R. Khalil

    2016-01-01

    Full Text Available Poly-γ-glutamic acid (γ-PGA is a naturally occurring polymer, which due to its biodegradable, non-toxic and non-immunogenic properties has been used successfully in the food, medical and wastewater industries. A major hurdle in bacteriophage application is the inability of phage to persist for extended periods in the environment due to their susceptibility to environmental factors such as temperature, sunlight, desiccation and irradiation. Thus, the aim of this study was to protect useful phage from the harmful effect of these environmental factors using the γ-PGA biodegradable polymer. In addition, the association between γ-PGA and phage was investigated. Formulated phage (with 1% γ-PGA and non-formulated phage were exposed to 50 °C. A clear difference was noticed as viability of non-formulated phage was reduced to 21% at log10 1.3 PFU/mL, while phage formulated with γ-PGA was 84% at log10 5.2 PFU/mL after 24 h of exposure. In addition, formulated phage remained viable at log10 2.5 PFU/mL even after 24 h of exposure at pH 3 solution. In contrast, non-formulated phages were totally inactivated after the same time of exposure. In addition, non-formulated phages when exposed to UV irradiation died within 10 min. In contrast also phages formulated with 1% γ-PGA had a viability of log10 4.1 PFU/mL at the same exposure time. Microscopy showed a clear interaction between γ-PGA and phages. In conclusion, the results suggest that γ-PGA has an unique protective effect on phage particles.

  14. Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage

    OpenAIRE

    Lai, Ying-Jang

    2014-01-01

    Amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer’s disease (AD). Moreover, it has been reported that oxidative stress is involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Recently, docosahexaenoic acid (DHA; C22:6) and eicosapentaenoic acid (EPA; C20:5n-3) have been reported to protect against AD. However, these omega-3 fatty acids are frequently obtained from fish oil and may contain heavy metals. In this study, we utilized Nann...

  15. Protective Roles of α-lipoic Acid in Rat Model of Mitochondrial DNA4834bp Deletion in Inner Ear

    Institute of Scientific and Technical Information of China (English)

    彭炜; 胡钰娟; 钟毅; 陈蓓; 孙宇; 杨阳; 孔维佳

    2010-01-01

    The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and...

  16. Melissa Officinalis L. Extracts Protect Human Retinal Pigment Epithelial Cells against Oxidative Stress-Induced Apoptosis.

    Science.gov (United States)

    Jeung, In Cheul; Jee, Donghyun; Rho, Chang-Rae; Kang, Seungbum

    2016-01-01

    We evaluated the protective effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) against oxidative stress-induced apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). ARPE-19 cells were incubated with ALS-L1023 for 24 h and then treated with hydrogen peroxide (H2O2). Oxidative stress-induced apoptosis and intracellular generation of reactive oxygen species (ROS) were assessed by flow cytometry. Caspase-3/7 activation and cleaved poly ADP-ribose polymerase (PARP) were measured to investigate the protective role of ALS-L1023 against apoptosis. The protective effect of ALS-L1023 against oxidative stress through activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was evaluated by Western blot analysis. ALS-L1023 clearly reduced H2O2-induced cell apoptosis and intracellular production of ROS. H2O2-induced oxidative stress increased caspase-3/7 activity and apoptotic PARP cleavage, which were significantly inhibited by ALS-L1023. Activation of the PI3K/Akt pathway was associated with the protective effect of ALS-L1023 on ARPE-19 cells. ALS-L1023 protected human RPE cells against oxidative damage. This suggests that ALS-L1023 has therapeutic potential for the prevention of dry age-related macular degeneration.

  17. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  18. Exogenous alpha-1-acid glycoprotein protects against renal ischemia-reperfusion injury by inhibition of inflammation and apoptosis

    NARCIS (Netherlands)

    de Vries, B; Walter, SJ; Wolfs, TGAM; Hochepied, T; Rabina, J; Heeringa, P; Parkkinen, J; Libert, C; Buurman, WA

    2004-01-01

    Background. Although ischemia-reperfusion (I/R) injury represents a major problem in posttransplant organ failure, effective treatment is not available. The acute phase protein a-l-acid glycoprotein (AGP) has been shown to be protective against experimental I/R injury. The effects of AGP are thought

  19. Review (laws for compliance and human rights multi-level protection in Inter-American Human Rights System

    Directory of Open Access Journals (Sweden)

    Natalia Torres Zúñiga

    2013-12-01

    Full Text Available This article addresses diverse perspectives concerning relationship between reviewing (laws for compliance and the process of putting international law of human rights on a constitutional footing. Therefore, a parallel is established between reviewing (laws for compliance and constitutional review (laws in order to outline features and application impact of this research. The design of a multi-level protection system for fundamental rights in Latin America is also discussed in this article.

  20. Protection against fine particle-induced pulmonary and systemic inflammation by omega-3 polyunsaturated fatty acids.

    Science.gov (United States)

    Li, Xiang-Yong; Hao, Lei; Liu, Ying-Hua; Chen, Chih-Yu; Pai, Victor J; Kang, Jing X

    2017-03-01

    Exposure to fine particulate matter, such as through air pollution, has been linked to the increased incidence of chronic diseases. However, few measures have been taken to reduce the health risks associated with fine particle exposure. The identification of safe and effective methods to protect against fine particle exposure-related damage is urgently needed. We used synthetic, non-toxic, fluorescent fine particles to investigate the physical distribution of inhaled fine particles and their effects on pulmonary and systemic inflammation in mice. Tissue levels of omega-3 fatty acids were elevated via dietary supplementation or the fat-1 transgenic mouse model. Markers of pulmonary and systemic inflammation were assessed. We discovered that fine particulate matter not only accumulates in the lungs but can also penetrate the pulmonary barrier and travel into other organs, including the brain, liver, spleen, kidney, and testis. These particles induced both pulmonary and systemic inflammation and increased oxidative stress. We also show that elevating tissue levels of omega-3 fatty acids was effective in reducing fine particle-induced inflammation, whether as a preventive method (prior to exposure) or as an intervention (after exposure). These results advance our understanding of how fine particles contribute to disease development and suggest that increasing tissue omega-3 levels may be a promising nutritional means for reducing the risk of diseases induced by particle exposure. Our findings demonstrate that elevating tissue omega-3 levels can prevent and treat fine particle-induced health problems and thereby present an immediate, practical solution for reducing the disease burden of air pollution. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    Science.gov (United States)

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-04

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

  2. Incretin effect after oral amino Acid ingestion in humans

    DEFF Research Database (Denmark)

    Lindgren, Ola; Pacini, Giovanni; Tura, Andrea

    2015-01-01

    is also present after amino acid ingestion is not known. OBJECTIVE: The objective of the study was to explore insulin secretion and incretin hormones after oral and iv amino acid administration at matched total amino acid concentrations in healthy subjects. DESIGN: An amino acid mixture (Vaminolac......: Oral amino acid mixture ingestion elicits a stronger insulin secretory response than iv amino acid at matching amino acid levels and this is associated with increased GIP level, suggesting that an incretin effect exists also after oral amino acids, possibly mediated by GIP....

  3. Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARδ Activation.

    Science.gov (United States)

    Tumova, Jana; Malisova, Lucia; Andel, Michal; Trnka, Jan

    2015-10-01

    Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

  4. Human anti-plague monoclonal antibodies protect mice from Yersinia pestis in a bubonic plague model.

    Directory of Open Access Journals (Sweden)

    Xiaodong Xiao

    Full Text Available Yersinia pestis is the etiologic agent of plague that has killed more than 200 million people throughout the recorded history of mankind. Antibiotics may provide little immediate relief to patients who have a high bacteremia or to patients infected with an antibiotic resistant strain of plague. Two virulent factors of Y. pestis are the capsid F1 protein and the low-calcium response (Lcr V-protein or V-antigen that have been proven to be the targets for both active and passive immunization. There are mouse monoclonal antibodies (mAbs against the F1- and V-antigens that can passively protect mice in a murine model of plague; however, there are no anti-Yersinia pestis monoclonal antibodies available for prophylactic or therapeutic treatment in humans. We identified one anti-F1-specific human mAb (m252 and two anti-V-specific human mAb (m253, m254 by panning a naïve phage-displayed Fab library against the F1- and V-antigens. The Fabs were converted to IgG1s and their binding and protective activities were evaluated. M252 bound weakly to peptides located at the F1 N-terminus where a protective mouse anti-F1 mAb also binds. M253 bound strongly to a V-antigen peptide indicating a linear epitope; m254 did not bind to any peptide from a panel of 53 peptides suggesting that its epitope may be conformational. M252 showed better protection than m253 and m254 against a Y, pestis challenge in a plague mouse model. A synergistic effect was observed when the three antibodies were combined. Incomplete to complete protection was achieved when m252 was given at different times post-challenge. These antibodies can be further studied to determine their potential as therapeutics or prophylactics in Y. pestis infection in humans.

  5. Protecting Children Victims of Crimes of Human Trafficking in the EU

    Directory of Open Access Journals (Sweden)

    Minodora-Ioana Balan-Rusu

    2013-08-01

    Full Text Available Within the paper there were examined the main provisions of the European legislative act framework in the domain of protecting children victims of human trafficking offenses, with some critical remarks. The paper can be useful to the European and Romanian legislator, practitioners and academics in the field. The novelty consists of analyzing the provisions of the European legislative act, focusing on the practical ways provided for the protection of children victims of this kind of crime, and the formulated critical remarks.

  6. Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.

    1987-05-01

    There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of /sup 14/C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three /sup 14/C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin.

  7. Protective effects of ascorbic acid and garlic extract against lead-induced apoptosis in developing rat hippocampus.

    Science.gov (United States)

    Ebrahimzadeh-Bideskan, Ali-Reza; Hami, Javad; Alipour, Fatemeh; Haghir, Hossein; Fazel, Ali-Reza; Sadeghi, Akram

    2016-10-01

    Lead exposure has negative effects on developing nervous system and induces apoptosis in newly generated neurons. Natural antioxidants (i.e. Ascorbic acid and Garlic) might protect against lead-induced neuronal cell damage. The aim of the present study was to investigate the protective effects of Ascorbic acid and Garlic administration during pregnancy and lactation on lead-induced apoptosis in rat developing hippocampus. Timed pregnant Wistar rats were administrated with Lead (1500 ppm) via drinking water (Pb group) or lead plus Ascorbic acid (Pb + AA Group, 500 mg/kg, IP), or lead plus Garlic Extract (Pb + G Group, 1 ml garlic juice/100 g BW, via Gavage) from early gestation (GD 0) until postnatal day 50 (PN 50). At the end of experiments, the pups' brains were carefully dissected. To identify neuronal death, the brain sections were stained with TUNEL assay. Mean of blood and brain lead levels increased significantly in Pb group comparing to other studied groups (P Ascorbic acid or Garlic (P Ascorbic acid and Garlic during pregnancy and lactation protect against lead-induced neuronal cell apoptosis in the hippocampus of rat pups partially via the reduction of Pb concentration in the blood and in the brain.

  8. Direct and indirect inactivation of tumor cell protective catalase by salicylic acid and anthocyanidins reactivates intercellular ROS signaling and allows for synergistic effects.

    Science.gov (United States)

    Scheit, Katrin; Bauer, Georg

    2015-03-01

    Salicylic acid and anthocyanidins are known as plant-derived antioxidants, but also can provoke paradoxically seeming prooxidant effects in vitro. These prooxidant effects are connected to the potential of salicylic acid and anthocyanidins to induce apoptosis selectively in tumor cells in vitro and to inhibit tumor growth in animal models. Several epidemiological studies have shown that salicylic acid and its prodrug acetylsalicylic acid are tumor-preventive for humans. The mechanism of salicylic acid- and anthocyanidin-dependent antitumor effects has remained enigmatic so far. Extracellular apoptosis-inducing reactive oxygen species signaling through the NO/peroxynitrite and the HOCl signaling pathway specifically induces apoptosis in transformed cells. Tumor cells have acquired resistance against intercellular reactive oxygen species signaling through expression of membrane-associated catalase. Here, we show that salicylic acid and anthocyanidins inactivate tumor cell protective catalase and thus reactive apoptosis-inducing intercellular reactive oxygen species signaling of tumor cells and the mitochondrial pathway of apoptosis Salicylic acid inhibits catalase directly through its potential to transform compound I of catalase into the inactive compound II. In contrast, anthocyanidins provoke a complex mechanism for catalase inactivation that is initiated by anthocyanidin-mediated inhibition of NO dioxygenase. This allows the formation of extracellular singlet oxygen through the reaction between H(2)O(2) and peroxynitrite, amplification through a caspase8-dependent step and subsequent singlet oxygen-mediated inactivation of catalase. The combination of salicylic acid and anthocyanidins allows for a remarkable synergistic effect in apoptosis induction. This effect may be potentially useful to elaborate novel therapeutic approaches and crucial for the interpretation of epidemiological results related to the antitumor effects of secondary plant compounds.

  9. Strengthening the human rights framework to protect breastfeeding: a focus on CEDAW.

    Science.gov (United States)

    Galtry, Judith

    2015-01-01

    There have been recent calls for increased recognition of breastfeeding as a human right. The United Nations Convention on the Elimination of All Forms of Discrimination against Women, 1979 (CEDAW) is the core human rights treaty on women. CEDAW's approach to breastfeeding is considered from an historical perspective. A comparison is drawn with breastfeeding protection previously outlined in the International Labour Organization's Maternity Protection Convention, 1919 (ILO C3), and its 1952 revision (ILO C103), and subsequently, in the United Nations Convention on the Rights of the Child, 1989 (CRC). Despite breastfeeding's sex-specific significance to an international human rights treaty on women and CEDAW's emphasis on facilitating women's employment, CEDAW is, in reality, a relatively weak instrument for breastfeeding protection. In both its text and subsequent interpretations explicit recognition of breastfeeding is minimal or nonexistent. Explanations for this are proposed and contextualised in relation to various political, social and economic forces, especially those influencing notions of gender equality. During the mid to late 1970s -when CEDAW was formulated - breastfeeding posed a strategic challenge for key feminist goals, particularly those of equal employment opportunity, gender neutral childrearing policy and reproductive rights. Protective legislation aimed at working women had been rejected as outdated and oppressive. Moreover, the right of women to breastfeed was generally assumed, with choice over infant feeding practices often perceived as the right NOT to breastfeed. There was also little awareness or analysis of the various structural obstacles to breastfeeding's practice, such as lack of workplace support, that undermine 'choice'. Subsequent interpretations of CEDAW show that despite significant advances in scientific and epidemiological knowledge about breastfeeding's importance for short-term and long-term maternal health, breastfeeding

  10. Protective effects of vitamin B12, ginseng saponin, and folic acid against murine fetal deformities caused by hyperthermia

    Institute of Scientific and Technical Information of China (English)

    李荷莲; 王博蔚; 赵丹; 韩丽英

    2003-01-01

    Objective To investigate the protective effects of vitamin B12, ginseng saponin, and folic acid on mouse embryos subjected to high heat.Methods Mice were used for the experiment.Results After exposure of pregnant mice to high heat, the rates of teratism, stillbirth, and fetal absorption were markedly lower in mice treated with ginseng saponin and folic acid following heat exposure than in untreated mice. There were no significant differences in these rates when comparing mice treated with vitamin B12 with the untreated mice.Conclusions Ginseng saponin and folic acid can lessen injuries to murine embryos caused by high heat, while vitamin B12 has little protective effect against high temperature except for promoting overall embryonic growth.

  11. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    Science.gov (United States)

    Race, Margaret; Conley, Catharine

    Planetary protection (PP) policies established by the Committee on Space Research (COSPAR) of the International Council for Science have been in force effectively for five decades, ensuring responsible exploration and the integrity of science activities, for both human and robotic missions in the Solar System beyond low Earth orbit (LEO). At present, operations on most bodies in the solar system are not constrained by planetary protection considerations because they cannot be contaminated by Earth life in ways that impact future space exploration. However, operations on Mars, Europa, and Enceladus, which represent locations with biological potential, are subject to strict planetary protection constraints for missions of all types because they can potentially be contaminated by organisms brought from Earth. Forward contamination control for robotic missions is generally accomplished through a combination of activities that reduce the bioload of microbial hitchhikers on outbound spacecraft prior to launch. Back contamination control for recent robotic missions has chiefly been accomplished by selecting sample-return targets that have little or no potential for extant life (e.g., cometary particles returned by Stardust mission). In the post-Apollo era, no human missions have had to deal with planetary protection constraints because they have never left Earth orbit. Future human missions to Mars, for example, will experience many of the challenges faced by the Apollo lunar missions, with the added possibility that astronauts on Mars may encounter habitable environments in their exploration or activities. Current COSPAR PP Principles indicate that safeguarding the Earth from potential back contamination is the highest planetary protection priority in Mars exploration. While guidelines for planetary protection controls on human missions to Mars have been established by COSPAR, detailed engineering constraints and processes for implementation of these guidelines have not

  12. Protective Effects of Intralipid and Caffeic Acid Phenethyl Ester on Nephrotoxicity Caused by Dichlorvos in Rats

    Directory of Open Access Journals (Sweden)

    Muhammet Murat Celik

    2015-01-01

    Full Text Available The protective effects of Caffeic Acid Phenethyl Ester (CAPE and intralipid (IL on nephrotoxicity caused by acute Dichlorvos (D toxicity were investigated in this study. Forty-eight Wistar Albino rats were divided into 7 groups as follows: Control, D, CAPE, intralipid, D + CAPE, D + IL, and D + CAPE + IL. When compared to D group, the oxidative stress index (OSI values were significantly lower in Control, CAPE, and D + IL + CAPE groups. When compared to D + IL + CAPE group, the TOS and OSI values were significantly higher in D group (P<0.05. When mitotic cell counts were assessed in the renal tissues, it was found that mitotic cell count was significantly higher in the D group while it was lower in the D + CAPE, D + IL, and D + IL + CAPE groups when compared to the control group (P<0.05. Also, immune reactivity showed increased apoptosis in D group and low profile of apoptosis in the D + CAPE group when compared to the Control group. The apoptosis level was significantly lower in D + IL + CAPE compared to D group (P<0.05 in the kidneys. As a result, we concluded that Dichlorvos can be used either alone or in combination with CAPE and IL as supportive therapy or as facilitator for the therapeutic effect of the routine treatment in the patients presenting with pesticide poisoning.

  13. The Protective Role of Carnosic Acid against Beta-Amyloid Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    H. Rasoolijazi

    2013-01-01

    Full Text Available Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer’s disease (AD. Previous studies have demonstrated the role of carnosic acid (CA, an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1–40 was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aβ groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1–40 can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aβ + CA group, in comparison with the Aβ group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus.

  14. Protective effect of alpha-lipoic acid on cypermethrin-induced oxidative stress in Wistar rats.

    Science.gov (United States)

    Mignini, F; Nasuti, C; Fedeli, D; Mattioli, L; Cosenza, M; Artico, M; Gabbianelli, R

    2013-01-01

    Cypermethrin (CY), a class II pyrethroid pesticide, is globally used to control insects in the household and in agriculture. Despite beneficial roles, its uncontrolled and repetitive application leads to unintended effects in non-target organisms. In light of the relevant anti-oxidant properties of alpha-lipoic acid (ALA), in the work described herein we tested the effect of a commercially available ALA formulation on cypermethrin CY)-induced oxidative stress in Wistar rats. The rats were orally administered with 53.14 mg/kg of ALA and 35.71 mg/kg of CY for 60 days. The treatment with CY did not induce changes in either locomotor activities or in body weight. Differences were observed on superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation that were re-established by ALA treatment at similar levels of the placebo group. Furthermore, ALA formulation increased glutathione (GSH) level and glutathione peroxidase (GPx) activity. Because of the widespread use of CY, higher amounts of pesticide residues are present in food, and a diet supplementation with ALA could be an active free radical scavenger protecting against diseases associated with oxidative stress.

  15. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Directory of Open Access Journals (Sweden)

    Heidi Wichmann

    2016-05-01

    Full Text Available The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP, produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA, a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2. Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.

  16. Protective effects of alpha lipoic acid versus N-acetylcysteine on ifosfamide-induced nephrotoxicity.

    Science.gov (United States)

    El-Sisi, Alaa El-Din E; El-Syaad, Magda E; El-Desoky, Karima I; Moussa, Ethar A

    2015-02-01

    Ifosfamide (IFO) is a highly effective chemotherapeutic agent for treating a variety of pediatric solid tumors. However, its use is limited due to its serious side effect on kidneys. The side-chain oxidation of IFO in renal tubular cells produces a reactive toxic metabolite that is believed to be responsible for its nephrotoxic effect. Therefore, this study was carried out to investigate the possible underlying mechanisms that may be involved in IFO-induced nephrotoxicity, including free radical generation and the possible role of alpha lipoic acid (ALA) versus N-acetylcysteine (NAC) in protection against this toxicity. Male albino rats were injected intraperitoneally with saline, IFO (50 mg/kg daily for 5 days), IFO + ALA (100 mg/kg daily for 8 days) and IFO + NAC (200 mg/kg daily for 8 days). Kidney malondialdehyde, nitric oxide and glutathione contents and serum biochemical parameters and histopathological analysis were determined. Both ALA and NAC markedly reduced the severity of renal dysfunction induced by IFO. NAC was more nephroprotective than ALA. This study suggests that oxidative stress is possibly involved in the IFO-induced nephrotoxicity in rats. The study also suggests the potential therapeutic role for ALA and NAC against IFO-induced nephrotoxicity.

  17. Salidroside protects against kainic acid-induced status epilepticus via suppressing oxidative stress.

    Science.gov (United States)

    Si, Pei-Pei; Zhen, Jun-Li; Cai, Yun-Lei; Wang, Wen-Jing; Wang, Wei-Ping

    2016-04-01

    There are numerous mechanisms by which the brain generates seizures. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Salidroside (SDS) extracted from Rhodiola rosea L. shows multiple bioactive properties, such as neuroprotection and antioxidant activity in vitro and in vivo. This study explored the role of SDS in kainic acid (KA)-induced SE and investigated the underlying mechanism. Latency to SE increased in the SDS-pretreated mice compared to the KA group, while the percentage of incidence of SE was significantly reduced. These results suggested that pretreatment with SDS not only delayed SE, but it also decreased the incidence of SE induced by KA. KA increased MDA level and reduced the production of SOD and GSH at multiple timepoints after KA administration. SDS inhibited the change of MDA, SOD and GSH induced by KA prior to SE onset, indicating that SDS protects against KA-induced SE via suppressing oxidative stress. Based on these results, we investigated the possible molecular mechanism of SDS. Pretreatment with SDS reversed the KA-induced decrease in AMP-activated protein kinase (AMPK); increased the sirtuin 1 (SIRT1) deacetylase activity in KA-treated mice, which had no demonstrable effect on SIRT1 mRNA and protein; and suppressed the KA-induced increase in Ace-FoxO1. These results showed that AMPK/SIRT1/FoxO1 signaling is possibly the molecular mechanism of neuroprotection by SDS.

  18. Acidic HEPES-KH Reperfusion Enhances Myocardial Protection in Immature Rabbits

    Institute of Scientific and Technical Information of China (English)

    孙忠东; 杨辰垣; 邢建洲; 陈涛; 董念国; 罗军

    2002-01-01

    Summary: To study the effects of different pH HEPES-KH reperfusate solution on immature myocardial protection, isolated perfused Langendorff model from immature rabbit hearts were developed formed. Control group (C) was perfused only with pH 7. 4 HEPES-KH solution for 90 min. Is chemia/reperfusion group (group I/R) was perfused with pH 7. 4 HEPES-KH solution before is chemia or after ischemia. Experimental group (group E), after ischemia, was perfused with pH 6.8,pH 7. 1 and pH7.4 HEPES-KH solutions for 5 min, 5 min, and 20 min, respectively. The left ven tricular function recovery, MWC, LDH and CK leakage, MDA, ATP content, and SOD activity were determined. Our results showed that the left ventricular function recovery, ATP content and SOD activity in group E were higher than those of group I/R (P<0. 05). MWC, MDA content,LDH and CK leakage in group E were lower than those of group I/R (P<0. 05). These findings suggested that pH paradox might be one of important mechanisms for immature myocardial ischemia reperfusion injury, and acidic perfusate, at the beginning of reperfusion, might attenuate pH paradox and ameliorate functional recovery in isolated perfused immature rabbit hearts.

  19. Mycosporines and mycosporine-like amino acids: UV protectants or multipurpose secondary metabolites?

    Science.gov (United States)

    Oren, Aharon; Gunde-Cimerman, Nina

    2007-04-01

    Mycosporines and mycosporine-like amino acids (MAAs) are low-molecular-weight water-soluble molecules absorbing UV radiation in the wavelength range 310-365 nm. They are accumulated by a wide range of microorganisms, prokaryotic (cyanobacteria) as well as eukaryotic (microalgae, yeasts, and fungi), and a variety of marine macroalgae, corals, and other marine life forms. The role that MAAs play as sunscreen compounds to protect against damage by harmful levels of UV radiation is well established. However, evidence is accumulating that MAAs may have additional functions: they may serve as antioxidant molecules scavenging toxic oxygen radicals, they can be accumulated as compatible solutes following salt stress, their formation is induced by desiccation or by thermal stress in certain organisms, they have been suggested to function as an accessory light-harvesting pigment in photosynthesis or as an intracellular nitrogen reservoir, and they are involved in fungal reproduction. Here, the evidence for these additional roles of MAAs as 'multipurpose' secondary metabolites is reviewed, with special emphasis on their functions in the microbial world.

  20. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    OpenAIRE

    Zhao, Bing; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

  1. Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.

    Directory of Open Access Journals (Sweden)

    Xianpeng Ge

    Full Text Available Cartilage acidic protein 1 (CRTAC1 was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA.

  2. Palmitic acid but not palmitoleic acid induces insulin resistance in a human endothelial cell line by decreasing SERCA pump expression.

    Science.gov (United States)

    Gustavo Vazquez-Jimenez, J; Chavez-Reyes, Jesus; Romero-Garcia, Tatiana; Zarain-Herzberg, Angel; Valdes-Flores, Jesus; Manuel Galindo-Rosales, J; Rueda, Angelica; Guerrero-Hernandez, Agustin; Olivares-Reyes, J Alberto

    2016-01-01

    Palmitic acid is a negative regulator of insulin activity. At the molecular level, palmitic acid reduces insulin stimulated Akt Ser473 phosphorylation. Interestingly, we have found that incubation with palmitic acid of human umbilical vein endothelial cells induced a biphasic effect, an initial transient elevation followed by a sustained reduction of SERCA pump protein levels. However, palmitic acid produced a sustained inhibition of SERCA pump ATPase activity. Insulin resistance state appeared before there was a significant reduction of SERCA2 expression. The mechanism by which palmitic acid impairs insulin signaling may involve endoplasmic reticulum stress, because this fatty acid induced activation of both PERK, an ER stress marker, and JNK, a kinase associated with insulin resistance. None of these effects were observed by incubating HUVEC-CS cells with palmitoleic acid. Importantly, SERCA2 overexpression decreased the palmitic acid-induced insulin resistance state. All these results suggest that SERCA pump might be the target of palmitic acid to induce the insulin resistance state in a human vascular endothelial cell line. Importantly, these data suggest that HUVEC-CS cells respond to palmitic acid-exposure with a compensatory overexpression of SERCA pump within the first hour, which eventually fades out and insulin resistance prevails.

  3. Neighbor Preferences of Amino Acids and Context-Dependent Effects of Amino Acid Substitutions in Human, Mouse, and Dog

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    Mingchuan Fu

    2014-09-01

    Full Text Available Amino acids show apparent propensities toward their neighbors. In addition to preferences of amino acids for their neighborhood context, amino acid substitutions are also considered to be context-dependent. However, context-dependence patterns of amino acid substitutions still remain poorly understood. Using relative entropy, we investigated the neighbor preferences of 20 amino acids and the context-dependent effects of amino acid substitutions with protein sequences in human, mouse, and dog. For 20 amino acids, the highest relative entropy was mostly observed at the nearest adjacent site of either N- or C-terminus except C and G. C showed the highest relative entropy at the third flanking site and periodic pattern was detected at G flanking sites. Furthermore, neighbor preference patterns of amino acids varied greatly in different secondary structures. We then comprehensively investigated the context-dependent effects of amino acid substitutions. Our results showed that nearly half of 380 substitution types were evidently context dependent, and the context-dependent patterns relied on protein secondary structures. Among 20 amino acids, P elicited the greatest effect on amino acid substitutions. The underlying mechanisms of context-dependent effects of amino acid substitutions were possibly mutation bias at a DNA level and natural selection. Our findings may improve secondary structure prediction algorithms and protein design; moreover, this study provided useful information to develop empirical models of protein evolution that consider dependence between residues.

  4. Neighbor preferences of amino acids and context-dependent effects of amino acid substitutions in human, mouse, and dog.

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    Fu, Mingchuan; Huang, Zhuoran; Mao, Yuanhui; Tao, Shiheng

    2014-09-10

    Amino acids show apparent propensities toward their neighbors. In addition to preferences of amino acids for their neighborhood context, amino acid substitutions are also considered to be context-dependent. However, context-dependence patterns of amino acid substitutions still remain poorly understood. Using relative entropy, we investigated the neighbor preferences of 20 amino acids and the context-dependent effects of amino acid substitutions with protein sequences in human, mouse, and dog. For 20 amino acids, the highest relative entropy was mostly observed at the nearest adjacent site of either N- or C-terminus except C and G. C showed the highest relative entropy at the third flanking site and periodic pattern was detected at G flanking sites. Furthermore, neighbor preference patterns of amino acids varied greatly in different secondary structures. We then comprehensively investigated the context-dependent effects of amino acid substitutions. Our results showed that nearly half of 380 substitution types were evidently context dependent, and the context-dependent patterns relied on protein secondary structures. Among 20 amino acids, P elicited the greatest effect on amino acid substitutions. The underlying mechanisms of context-dependent effects of amino acid substitutions were possibly mutation bias at a DNA level and natural selection. Our findings may improve secondary structure prediction algorithms and protein design; moreover, this study provided useful information to develop empirical models of protein evolution that consider dependence between residues.

  5. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.

    Science.gov (United States)

    Schlemmer, Ulrich; Frølich, Wenche; Prieto, Rafel M; Grases, Felix

    2009-09-01

    The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.

  6. Identification of cyclopropaneoctanoic acid 2-hexyl in human adipose tissue and serum.

    Science.gov (United States)

    Sledzinski, Tomasz; Mika, Adriana; Stepnowski, Piotr; Proczko-Markuszewska, Monika; Kaska, Lukasz; Stefaniak, Tomasz; Swierczynski, Julian

    2013-08-01

    Fatty acids containing a cyclopropane ring in their structure (cyclopropane FA) have been found in a wide variety of bacteria, a number of protozoa, and Myriapoda. Little is known about cyclopropane FA in mammal, especially in human tissues. The present study deals with the identification of cyclopropane FA in adipose tissue and serum of humans and rats. Fatty acids extracted from the adipose tissue and serum obtained from obese women during bariatric surgery were methylated and analyzed on GC-MS. We have identified: cyclopropaneoctanoic acid 2-hexyl, cyclopropaneoctanoic acid 2-octyl, cyclopropanenonanoic acid, and 2-[[2-[(2-ethylcyclopropyl)methyl]cyclopropyl]methyl] acid in human adipose tissue. We confirmed the presence of cyclopropaneoctanoic acid 2-hexyl by derivatization of FA extracted from human adipose tissue to picolinyl esters. Cyclopropaneoctanoic acid 2-hexyl was the main cyclopropane FA (approximately 0.4 % of total fatty acids in human adipose tissue, and about 0.2 % of total fatty acids in the serum). In adipose tissue cyclopropaneoctanoic acid 2-hexyl was found mainly in triacylglycerols, whereas in serum in phospholipids and triacylglycerols. The cyclopropaneoctanoic acid 2-hexyl has also been found in serum, and adipose tissue of rats in amounts comparable to humans. The content of cyclopropaneoctanoic acid 2-hexyl decreased in adipose tissue of rats maintained on a restricted diet for 1 month. In conclusion, we demonstrated that cyclopropaneoctanoic acid 2-hexyl is present in human adipose tissue and serum. Adipose tissue cyclopropaneoctanoic acid 2-hexyl is stored mainly in triacylglycerols and the storage of this cyclopropane FA is affected by food restriction.

  7. The protective role of ascorbic acid on hippocampal CA1 pyramidal neurons in a rat model of maternal lead exposure.

    Science.gov (United States)

    Sepehri, Hamid; Ganji, Farzaneh

    2016-07-01

    Oxidative stress is a major pathogenic mechanism of lead neurotoxicity. The antioxidant ascorbic acid protects hippocampal pyramidal neurons against cell death during congenital lead exposure; however, critical functions like synaptic transmission, integration, and plasticity depend on preservation of dendritic and somal morphology. This study was designed to examine if ascorbic acid also protects neuronal morphology during developmental lead exposure. Timed pregnant rats were divided into four treatment groups: (1) control, (2) 100mg/kg ascorbic acid once a day via gavage, (3) 0.05% lead acetate in drinking water, and (4) 0.05% lead+100mg/kg oral ascorbic acid. Brains of eight male pups (P25) per treatment group were processed for Golgi staining. Changes in hippocampal CA1 pyramidal neurons' somal size were estimated by cross-sectional area and changes in dendritic arborization by Sholl's analysis. One-way ANOVA was used to compare results among treatment groups. Lead-exposed pups exhibited a significant decrease in somal size compared to controls (Pascorbic acid. Sholl's analysis revealed a significant increase in apical dendritic branch points near cell body (PAscorbic acid significantly but only partially reversed the somal and dendritic damage caused by developmental lead exposure. Oxidative stress thus contributes to lead neurotoxicity but other pathogenic mechanisms are also involved.

  8. Salvianolic Acid B (Sal B Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1

    Directory of Open Access Journals (Sweden)

    Xiaobin Liu

    2016-11-01

    Full Text Available Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG between cysteine residues and glutathione (GSH, can lead to cell death. Glutaredoxin 1 (Grx1 is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B, a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H2O2-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2, the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H2O2-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

  9. Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

    Science.gov (United States)

    Liu, Xiaobin; Xavier, Christy; Jann, Jamieson; Wu, Hongli

    2016-11-03

    Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

  10. Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants

    Directory of Open Access Journals (Sweden)

    Uitterlinden EJ

    2008-09-01

    Full Text Available Abstract Background Glucosamine (GlcN used by patients with osteoarthritis was demonstrated to reduce pain, but the working mechanism is still not clear. Viscosupplementation with hyaluronic acid (HA is also described to reduce pain in osteoarthritis. The synthesis of HA requires GlcN as one of its main building blocks. We therefore hypothesized that addition of GlcN might increase HA production by synovium tissue. Methods Human osteoarthritic synovium explants were obtained at total knee surgery and pre-cultured for 1 day. The experimental conditions consisted of a 2 days continuation of the culture with addition of N-Acetyl-glucosamine (GlcN-Ac; 5 mM, glucosamine-hydrochloride (GlcN-HCl; 0.5 and 5 mM, glucose (Gluc; 0.5 and 5 mM. Hereafter HA production was measured in culture medium supernatant using an enzyme-linked binding protein assay. Real time RT-PCR was performed for hyaluronic acid synthase (HAS 1, 2 and 3 on RNA isolated from the explants. Results 0.5 mM and 5 mM GlcN-HCl significantly increased HA production compared to control (approximately 2 – 4-fold, whereas GlcN-Ac had no significant effect. Addition of 5 mM Gluc also increased HA production (approximately 2-fold, but 0.5 mM Gluc did not. Gene expression of the HA forming enzymes HAS 1, 2 and 3 was not altered by the addition of GlcN or Gluc. Conclusion Our data suggest that exogenous GlcN can increase HA production by synovium tissue and is more effective at lower concentrations than Gluc. This might indicate that GlcN exerts its potential analgesic properties through stimulation of synovial HA production.

  11. [Lactic acid bacteria and health: are probiotics safe for human?].

    Science.gov (United States)

    Kubiszewska, Izabela; Januszewska, Milena; Rybka, Joanna; Gackowska, Lidia

    2014-11-17

    The effect of Lactobacillus and Bifidobacterium on human health has been examined for many years. Numerous in vivo and in vitro studies have confirmed the beneficial activity of some exogenous lactic acid bacteria in the treatment and prevention of rotaviral infection, antibiotic-associated diarrhea, inflammatory bowel disease and other gastrointestinal disorders. Probiotics support the action of the intestinal microflora and exhibit a favorable modulatory effect on the host's immune system. However, it should be remembered that relatively harmless lactobacilli can occasionally induce opportunistic infections. Due to reaching almost 20x10(12) probiotic doses per year which contain live cultures of bacteria, it is essential to monitor the safety aspect of their administration. In recent years, infections caused by Lactobacillus and Bifidobacterium made up 0.05% to 0.4% of cases of endocarditis and bacteremia. In most cases, the infections were caused by endogenous microflora of the host or bacterial strains colonizing the host's oral cavity. According to a review of cases of infections caused by bacteria of the genus Lactobacillus from 2005 (collected by J.P. Cannot'a), 1.7% of infections have been linked directly with intensive dairy probiotic consumption by patients. Additionally, due to the lack of a precise description of most individuals' eating habits, the possible effect of probiotics on infection development definitively should not be ruled out. The present paper describes cases of diseases caused by lactic acid bacteria, a potential mechanism for the adverse action of bacteria, and the possible hazard connected with probiotic supplementation for seriously ill and hospitalized patients.

  12. Endothelial Differentiation of Human Adipose-Derived Stem Cells on Polyglycolic Acid/Polylactic Acid Mesh.

    Science.gov (United States)

    Deng, Meng; Gu, Yunpeng; Liu, Zhenjun; Qi, Yue; Ma, Gui E; Kang, Ning

    2015-01-01

    Adipose-derived stem cell (ADSC) is considered as a cell source potentially useful for angiogenesis in tissue engineering and regenerative medicine. This study investigated the growth and endothelial differentiation of human ADSCs on polyglycolic acid/polylactic acid (PGA/PLA) mesh compared to 2D plastic. Cell adhesion, viability, and distribution of hADSCs on PGA/PLA mesh were observed by CM-Dil labeling, live/dead staining, and SEM examination while endothelial differentiation was evaluated by flow cytometry, Ac-LDL/UEA-1 uptake assay, immunofluorescence stainings, and gene expression analysis of endothelial related markers. Results showed hADSCs gained a mature endothelial phenotype with a positive ratio of 21.4 ± 3.7% for CD31+/CD34- when induced in 3D mesh after 21 days, which was further verified by the expressions of a comprehensive range of endothelial related markers, whereas hADSCs in 2D induced and 2D/3D noninduced groups all failed to differentiate into endothelial cells. Moreover, compared to 2D groups, the expression for α-SMA was markedly suppressed in 3D cultured hADSCs. This study first demonstrated the endothelial differentiation of hADSCs on the PGA/PLA mesh and pointed out the synergistic effect of PGA/PLA 3D culture and growth factors on the acquisition of mature characteristic endothelial phenotype. We believed this study would be the initial step towards the generation of prevascularized tissue engineered constructs.

  13. Human retroviruses and AIDS 1996. A compilation and analysis of nucleic acid and amino acid sequences

    Energy Technology Data Exchange (ETDEWEB)

    Myers, G.; Foley, B.; Korber, B. [eds.] [Los Alamos National Lab., NM (United States). Theoretical Div.; Mellors, J.W. [ed.] [Univ. of Pittsburgh, PA (United States); Jeang, K.T. [ed.] [National Institutes of Health, Bethesda, MD (United States). Molecular Virology Section; Wain-Hobson, S. [Pasteur Inst., Paris (France)] [ed.

    1997-04-01

    This compendium and the accompanying floppy diskettes are the result of an effort to compile and rapidly publish all relevant molecular data concerning the human immunodeficiency viruses (HIV) and related retroviruses. The scope of the compendium and database is best summarized by the five parts that it comprises: (1) Nuclear Acid Alignments and Sequences; (2) Amino Acid Alignments; (3) Analysis; (4) Related Sequences; and (5) Database Communications. Information within all the parts is updated throughout the year on the Web site, http://hiv-web.lanl.gov. While this publication could take the form of a review or sequence monograph, it is not so conceived. Instead, the literature from which the database is derived has simply been summarized and some elementary computational analyses have been performed upon the data. Interpretation and commentary have been avoided insofar as possible so that the reader can form his or her own judgments concerning the complex information. In addition to the general descriptions of the parts of the compendium, the user should read the individual introductions for each part.

  14. Protection of human upper respiratory tract cell lines against sulphur mustard toxicity by hexamethylenetetramine (HMT).