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Sample records for arsenical-induced phosphatidylserine exposure

  1. Phosphatidylserine exposure on stored red blood cells as a parameter for donor-dependent variation in product quality

    NARCIS (Netherlands)

    Dinkla, S.; Peppelman, M.; Raadt, J. van der; Atsma, F.; Novotny, V.M.J.; Kraaij, M.G.J. van; Joosten, I.; Bosman, G.J.C.G.M.

    2014-01-01

    BACKGROUND: Exposure of phosphatidylserine on the outside of red blood cells contributes to recognition and removal of old and damaged cells. The fraction of phosphatidylserine-exposing red blood cells varies between donors, and increases in red blood cell concentrates during storage. The susceptibi

  2. Indolic Uremic Solutes Enhance Procoagulant Activity of Red Blood Cells through Phosphatidylserine Exposure and Microparticle Release

    Directory of Open Access Journals (Sweden)

    Chunyan Gao

    2015-10-01

    Full Text Available Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs, the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS and indole-3-acetic acid (IAA on procoagulant activity (PCA of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients. Phosphatidylserine (PS exposure of RBCs and their microparticles (MPs release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca2+ ([Ca2+] with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca2+]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process.

  3. Indolic uremic solutes enhance procoagulant activity of red blood cells through phosphatidylserine exposure and microparticle release.

    Science.gov (United States)

    Gao, Chunyan; Ji, Shuting; Dong, Weijun; Qi, Yushan; Song, Wen; Cui, Debin; Shi, Jialan

    2015-11-01

    Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs), the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS) and indole-3-acetic acid (IAA) on procoagulant activity (PCA) of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients). Phosphatidylserine (PS) exposure of RBCs and their microparticles (MPs) release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca(2+) ([Ca(2+)]) with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca(2+)]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process. PMID:26516916

  4. A homogeneous time-resolved fluorescence resonance energy transfer assay for phosphatidylserine exposure on apoptotic cells.

    Science.gov (United States)

    Gasser, Jean-Philippe; Hehl, Michaela; Millward, Thomas A

    2009-01-01

    A simple, "mix-and-measure" microplate assay for phosphatidylserine (PtdSer) exposure on the surface of apoptotic cells is described. The assay exploits the fact that annexin V, a protein with high affinity and specificity for PtdSer, forms trimers and higher order oligomers on binding to membranes containing PtdSer. The transition from soluble monomer to cell-bound oligomer is detected using time-resolved fluorescence resonance energy transfer from europium chelate-labeled annexin V to Cy5-labeled annexin V. PtdSer detection is achieved by a single addition of a reagent mix containing labeled annexins and calcium ions directly to cell cultures in a 96-well plate, followed by a brief incubation before fluorescence measurement. The assay can be used to quantify PtdSer exposure on both suspension cells and adherent cells in situ. This method is simpler and faster than existing annexin V binding assays based on flow cytometry or microscopy, and it yields precise data with Z' values of 0.6-0.7. PMID:18835236

  5. Measurements of Intracellular Ca2+ Content and Phosphatidylserine Exposure in Human Red Blood Cells: Methodological Issues

    Directory of Open Access Journals (Sweden)

    Mauro C. Wesseling

    2016-06-01

    Full Text Available Background/Aims: The increase of the intracellular Ca2+ content as well as the exposure of phosphatidylserine (PS on the outer cell membrane surface after activation of red blood cells (RBCs by lysophosphatidic acid (LPA has been investigated by a variety of research groups. Carrying out experiments, which we described in several previous publications, we observed some discrepancies when comparing data obtained by different investigators within our research group and also between batches of LPA. In addition, we found differences comparing the results of double and single labelling experiments (for Ca2+ and PS. Furthermore, the results of PS exposure depended on the fluorescent dye used (annexin V-FITC versus annexin V alexa fluor® 647. Therefore, it seems necessary to investigate these methodological approaches in more detail to be able to quantify results and to compare data obtained by different research groups. Methods: The intracellular Ca2+ content and the PS exposure of RBCs separated from whole blood have been investigated after treatment with LPA (2.5 µM obtained from three different companies (Sigma-Aldrich, Cayman Chemical Company, and Santa Cruz Biotechnology Inc.. Fluo-4 and x-rhod-1 have been used to detect intracellular Ca2+ content, annexin V alexa fluor® 647 and annexin V-FITC have been used for PS exposure measurements. Both parameters (Ca2+ content, PS exposure were studied using flow cytometry and fluorescence microscopy. Results: The percentage of RBCs showing increased intracellular Ca2+ content as well as PS exposure changes significantly between different LPA manufacturers as well as on the condition of mixing of LPA with the RBC suspension. Furthermore, the percentage of RBCs showing PS exposure is reduced in double labelling compared to single labelling experiments and depends also on the fluorescent dye used. Finally, data on Ca2+ content are slightly affected whereas PS exposure data are not affected significantly

  6. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes

    OpenAIRE

    1995-01-01

    The appearance of phosphatidylserine (PS) on the cell surface during apoptosis in thymocytes and cytotoxic T lymphocyte cell lines provokes PS-dependent recognition by activated macrophages. Flow cytometric analysis of transbilayer lipid movements in T lymphocytes undergoing apoptosis reveals that downregulation of the adenosine triphosphate- dependent amino-phospholipid translocase and activation of a nonspecific lipid scramblase are responsible for PS reaching the surface from its intracell...

  7. Well water arsenic exposure, arsenic induced skin-lesions and self-reported morbidity in Inner Mongolia

    Science.gov (United States)

    Arsenic exposure from contaminated well water is a cause of skin and bladder cancer and linked to numerous other adverse health effects. Residents of the Bayingnormen region of Inner Mongolia, China, have been exposed to arsenic-contaminated well water for over 20 years but few s...

  8. Pleiotropic actions of forskolin result in phosphatidylserine exposure in primary trophoblasts.

    Directory of Open Access Journals (Sweden)

    Meghan R Riddell

    Full Text Available Forskolin is an extract of the Coleus forskholii plant that is widely used in cell physiology to raise intracellular cAMP levels. In the field of trophoblast biology, forskolin is one of the primary treatments used to induce trophoblastic cellular fusion. The syncytiotrophoblast (ST is a continuous multinucleated cell in the human placenta that separates maternal from fetal circulations and can only expand by fusion with its stem cell, the cytotrophoblast (CT. Functional investigation of any aspect of ST physiology requires in vitro differentiation of CT and de novo ST formation, thus selecting the most appropriate differentiation agent for the hypothesis being investigated is necessary as well as addressing potential off-target effects. Previous studies, using forskolin to induce fusion in trophoblastic cell lines, identified phosphatidylserine (PS externalization to be essential for trophoblast fusion and showed that widespread PS externalization is present even after fusion has been achieved. PS is a membrane phospholipid that is primarily localized to the inner-membrane leaflet. Externalization of PS is a hallmark of early apoptosis and is involved in cellular fusion of myocytes and macrophages. We were interested to examine whether PS externalization was also involved in primary trophoblast fusion. We show widespread PS externalization occurs after 72 hours when fusion was stimulated with forskolin, but not when stimulated with the cell permeant cAMP analog Br-cAMP. Using a forskolin analog, 1,9-dideoxyforskolin, which stimulates membrane transporters but not adenylate cyclase, we found that widespread PS externalization required both increased intracellular cAMP levels and stimulation of membrane transporters. Treatment of primary trophoblasts with Br-cAMP alone did not result in widespread PS externalization despite high levels of cellular fusion. Thus, we concluded that widespread PS externalization is independent of trophoblast fusion

  9. Binding of thrombin-activated platelets to a fibrin scaffold through α(IIbβ₃ evokes phosphatidylserine exposure on their cell surface.

    Directory of Open Access Journals (Sweden)

    Tomasz Brzoska

    Full Text Available Recently, by employing intra-vital confocal microscopy, we demonstrated that platelets expose phosphatidylserine (PS and fibrin accumulate only in the center of the thrombus but not in its periphery. To address the question how exposure of platelet anionic phospholipids is regulated within the thrombus, an in-vitro experiment using diluted platelet-rich plasma was employed, in which the fibrin network was formed in the presence of platelets, and PS exposure on the platelet surface was analyzed using Confocal Laser Scanning Microscopy. Almost all platelets exposed PS after treatment with tissue factor, thrombin or ionomycin. Argatroban abrogated fibrin network formation in all samples, however, platelet PS exposure was inhibited only in tissue factor- and thrombin-treated samples but not in ionomycin-treated samples. FK633, an α(IIbβ₃ antagonist, and cytochalasin B impaired platelet binding to the fibrin scaffold and significantly reduced PS exposure evoked by thrombin. Gly-Pro-Arg-Pro amide abrogated not only fibrin network formation, but also PS exposure on platelets without suppressing platelet binding to fibrin/fibrinogen. These results suggest that outside-in signals in platelets generated by their binding to the rigid fibrin network are essential for PS exposure after thrombin treatment.

  10. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  11. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  12. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-01-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered. PMID:27585557

  13. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  14. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

    Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

  15. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. PMID:26485141

  16. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  17. Possible mechanisms for arsenic-induced proliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  18. Arsenic-induced QT dispersion is associated with atherosclerotic diseases and predicts long-term cardiovascular mortality in subjects with previous exposure to arsenic: A 17-Year follow-up study.

    Science.gov (United States)

    Wang, Chih-Hao; Chen, Chi-Ling; Hsiao, Chuhsing Kate; Chiang, Fu-Tien; Hsu, Ling-I; Chiou, Hung-Yi; Hsueh, Yu-Mei; Wu, Meei-Maan; Chen, Chien-Jen

    2010-03-01

    Chronic arsenic poisoning is a major worldwide public health problem. Recently, we had reported chronic arsenic poisoning was dose-dependently associated with ventricular abnormalities quantified by electrocardiographic QT prolongation linking to atherosclerotic diseases. An association of chronic arsenic poisoning with ventricular repolarization inhomogeneity quantified by QT dispersion (QTD) is of particular interest from a theoretical and practical perspective. We aimed to further elucidate (1) the association of chronic arsenic exposure with ventricular abnormalities quantified by QTD, (2) the association of QTD with atherosclerotic diseases and (3) the predictability of QTD for long-term mortality in subjects with chronic arsenic poisoning. We followed up 280 men and 355 women living in arseniasis-endemic area in southwestern coast in Taiwan for 17 years. QTD in electrocardiogram and carotid intima-media thickness by ultrasonography were measured. Coronary artery disease was diagnosed by an abnormal electrocardiogram and a definite history. Cumulative arsenic exposure was significantly associated with QTD showing a dose-response relationship (P cause mortality were 3.9 (2.1-6.2, P = 0.002) and 1.4 (0.9-2.3, P = 0.10), respectively, for QTD > or = 65 ms compared with QTD arsenic exposure.

  19. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism.

    Science.gov (United States)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N; Bibby, Kyle J; Stolz, Donna B; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L; Barchowsky, Aaron; Stolz, John F

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes.

  20. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  1. Piperlongumine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane

    OpenAIRE

    Rosi Bissinger; Abaid Malik; Jamshed Warsi; Kashif Jilani; Florian Lang

    2014-01-01

    Background: Piperlongumine, a component of Piper longum fruit, is considered as a treatment for malignancy. It is effective by inducing apoptosis. Mechanisms involved in the apoptotic action of piperlongumine include oxidative stress and activation of p38 kinase. In analogy to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surfa...

  2. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  3. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  4. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

    Science.gov (United States)

    Wang, Lei; Hitron, John Andrew; Wise, James T F; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.

  5. Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats.

    Science.gov (United States)

    Muthumani, M; Miltonprabu, S

    2015-06-25

    Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin. Environmental exposure to arsenic imposes a serious health hazard to humans and other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than the curcumin. It has been reported that THC has antioxidant efficacy attributable to the presence of identical β-diketone of 3rd and 5th substitution in heptane moiety. In the present study, rats were orally treated with arsenic alone (5 mg kg(-1) bw/day) with THC (80 mg kg(-1) bw/day) for 28 days. Hepatotoxicity was measured by the increased activities of serum hepatospecific enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances. And also elevated levels of serum cholesterol, triglycerides, free fatty acids and phospholipids were observed in arsenic intoxicated rats. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)ATPase and a decrease in mitochondrial calcium content. The toxic effect of arsenic was also indicated by significantly decreased activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase along with non-enzymatic antioxidant such as reduced glutathione. Administration of THC exhibited significant reversal of arsenic induced toxicity in hepatic tissue. All these changes were supported by the reduction of arsenic concentration and histopathological observations of the liver. These results suggest that THC has a protective effect over arsenic induced toxicity in rat.

  6. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

  7. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  8. ARSENIC INDUCES SUSTAINED IMPAIRMENT OF SKELETAL MUSCLE AND MUSCLE PROGENITOR CELL ULTRASTRUCTURE AND BIOENERGETICS

    Science.gov (United States)

    Fabrisia, Ambrosio; Elke, Brown; Donna, Stolz; Ricardo, Ferrari; Bret, Goodpaster; Bridget, Deasy; Giovanna, Distefano; Alexandra, Roperti; Amin, Cheikhi; Yesica, Garciafigueroa; Aaron, Barchowsky

    2014-01-01

    Over 4 million individuals in the US, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10 µg/L to over 1 mg/L, with 100 µg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. When compared to non-exposed controls, mice exposed to drinking water containing 100µg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There was no difference in levels of inorganic arsenic or its mononomethyl- and dimethyl- metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, as compared to cells isolated from non-exposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant. PMID:24960579

  9. Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

    Science.gov (United States)

    Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

    2015-12-01

    Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication.

  10. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited Emax of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  11. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  12. Piperlongumine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane

    Directory of Open Access Journals (Sweden)

    Rosi Bissinger

    2014-10-01

    Full Text Available Background: Piperlongumine, a component of Piper longum fruit, is considered as a treatment for malignancy. It is effective by inducing apoptosis. Mechanisms involved in the apoptotic action of piperlongumine include oxidative stress and activation of p38 kinase. In analogy to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, the suicidal death of erythrocytes characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i, formation of ceramide, oxidative stress and activation of p38 kinase. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca2+]i from Fluo3 fluorescence, reactive oxygen species from 2',7'-dichlorodihydrofluorescein-diacetate fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to piperlongumine (30 µM was followed by significant decrease of forward scatter and increase of annexin-V-binding. Piperlongumine did not significantly modify [Ca2+]i and the effect was not dependent on presence of extracellular Ca2+. Piperlongumine significantly increased ROS formation and ceramide abundance. Conclusions: Piperlongumine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca2+ but at least partially due to ROS and ceramide formation.

  13. 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells.

    Science.gov (United States)

    Gong, Xuezhong; Ivanov, Vladimir N; Hei, Tom K

    2016-09-01

    Our recent study demonstrated that sodium arsenite at a clinically relevant dose induced nephrotoxicity in human renal proximal tubular epithelial cell line HK-2, which could be inhibited by natural product 2,3,5,6-tetramethylpyrazine (TMP) with antioxidant activity. The present study demonstrated that arsenic exposure resulted in protein and enzymatic induction of heme oxygenase-1 (HO-1) in dose- and time-dependent manners in HK-2 cells. Blocking HO-1 enzymatic activity by zinc protoporphyrin (ZnPP) augmented arsenic-induced apoptosis, ROS production and mitochondrial dysfunction, suggesting a critical role for HO-1 as a renal protectant in this procession. On the other hand, TMP, upstream of HO-1, inhibited arsenic-induced ROS production and ROS-dependent HO-1 expression. TMP also prevented mitochondria dysfunction and suppressed activation of the intrinsic apoptotic pathway in HK-2 cells. Our results revealed that the regulation of arsenic-induced HO-1 expression was performed through multiple ROS-dependent signal pathways and the corresponding transcription factors, including p38 MAPK and JNK (but not ERK), AP-1, Nrf2 and NF-κB. TMP inhibited arsenic-induced activations of JNK, p38 MAPK, ERK, AP-1 and Nrf2 and block HO-1 protein expression. The present study, furthermore, demonstrated arsenic-induced expression of arsenic response protein 2 (ARS2) that was regulated by p38 MAPK, ERK and NF-κB. To our knowledge, this is the first report showing that ARS2 involved in arsenic-induced nephrotoxicity, while TMP pretreatment prevented such an up-regulation of ARS2 in HK-2 cells. Given ARS2 and HO-1 sharing the similar regulation mechanism, we speculated that ARS2 might also mediate cell survival in this procession. In summary, our study highlighted a role of HO-1 in the protection against arsenic-induced cytotoxicity downstream from the primary targets of TMP and further indicated that TMP may be used as a potential therapeutic agent in the treatment of arsenic-induced

  14. Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells.

    Science.gov (United States)

    Pan, Xiao; Jiang, Liping; Zhong, Laifu; Geng, Chengyan; Jia, Li; Liu, Shuang; Guan, Huai; Yang, Guang; Yao, Xiaofeng; Piao, Fengyuan; Sun, Xiance

    2016-02-01

    Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4 Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway.

  15. Deciphering the plasma membrane hallmarks of apoptotic cells: Phosphatidylserine transverse redistribution and calcium entry

    Directory of Open Access Journals (Sweden)

    Martínez M Carmen

    2001-10-01

    Full Text Available Abstract Background During apoptosis, Ca2+-dependent events participate in the regulation of intracellular and morphological changes including phosphatidylserine exposure in the exoplasmic leaflet of the cell plasma membrane. The occurrence of phosphatidylserine at the surface of specialized cells, such as platelets, is also essential for the assembly of the enzyme complexes of the blood coagulation cascade, as demonstrated by hemorrhages in Scott syndrome, an extremely rare genetic deficiency of phosphatidylserine externalization, without other apparent pathophysiologic consequences. We have recently reported a reduced capacitative Ca2+ entry in Scott cells which may be part of the Scott phenotype. Results Taking advantage of these mutant lymphoblastoid B cells, we have studied the relationship between this mode of Ca2+ entry and phosphatidylserine redistribution during apoptosis. Ca2+ ionophore induced apoptosis in Scott but not in control cells. However, inhibition of store-operated Ca2+ channels led to caspase-independent DNA fragmentation and decrease of mitochondrial membrane potential in both control and Scott cells. Inhibition of cytochrome P450 also reduced capacitative Ca2+ entry and induced apoptosis at comparable extents in control and Scott cells. During the apoptotic process, both control and more markedly Scott cells externalized phosphatidylserine, but in the latter, this membrane feature was however dissociated from several other intracellular changes. Conclusions The present results suggest that different mechanisms account for phosphatidylserine transmembrane migration in cells undergoing stimulation and programmed death. These observations testify to the plasticity of the plasma membrane remodeling process, allowing normal apoptosis even when less fundamental functions are defective.

  16. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.; Afaq, Farrukh; Athar, Mohammad, E-mail: mathar@uab.edu

    2013-09-06

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.

  17. Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats.

    Science.gov (United States)

    Gupta, Richa; Kannan, Gurusamy M; Sharma, Mamta; S Flora, Swaran J

    2005-11-01

    the seed powder of M. oleifera has significant role in protecting animals from arsenic-induced oxidative stress and in the depletion of arsenic concentration. Further studies thus can be recommended for determining the effect of co-administrating seed powder of M. oleifera during chelation therapy with a thiol chelator. PMID:21783626

  18. Molecular basis for arsenic-induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction.

    Science.gov (United States)

    Kumagai, Yoshito; Pi, Jingbo

    2004-08-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed.

  19. Protective effects of Moringa oleifera Lam. leaves against arsenic-induced toxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Afzal Sheikh; Zahangir Alam Saud; Khaled Hossain; Fouzia Yeasmin; Smita Agarwal; Mashiur Rahman; Khairul Islam; Ekhtear Hossain; Shakhawoat Hossain; Md Rezaul Karim; Farjana Nikkon

    2014-01-01

    Objective: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice.Methods:non-treated control group while, the second, third, and fourth groups were treated with M.oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice.Results:Swiss albino male mice were divided into four groups. The first group was used as induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol.Conclusions:The results indicate that the leaves of M. oleifera may be useful in reducing the It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-effects of arsenic-induced toxicity.

  20. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  1. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  2. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  3. Thymosin α1 Interacts with Exposed Phosphatidylserine in Membrane Models and in Cells and Uses Serum Albumin as a Carrier.

    Science.gov (United States)

    Mandaliti, Walter; Nepravishta, Ridvan; Sinibaldi Vallebona, Paola; Pica, Francesca; Garaci, Enrico; Paci, Maurizio

    2016-03-15

    Thymosin α1 is a peptidic hormone with pleiotropic activity and is used in the therapy of several diseases. It is unstructured in water solution and interacts with negative regions of vesicles by assuming two tracts of helical conformation with a structural break between them. This study reports on Thymosin α1's interaction with mixed phospholipids phosphatidylcholine and phosphatidylserine, the negative component of the membranes, by ¹H and natural abundance ¹⁵N nuclear magnetic resonance (NMR). The results indicate that interaction occurs when the membrane is negatively charged by exposing phosphatidylserine. Moreover, the direct interaction of Thymosin α1 with K562 cells with an overexposure of phosphatidylserine as a consequence of resveratrol-induced apoptosis was conducted. Thymosin α1's interaction with human serum albumin was also investigated by NMR spectroscopy. Steady-state saturation transfer, transfer nuclear Overhauser effect spectroscopy, and diffusion-ordered spectroscopy methodologies all reveal that the C-terminal region of Thymosin α1 is involved in the interaction with serum albumin. These results may shed more light on Thymosin α1's mechanism of action by its insertion in negative regions of membranes due to the exposure of phosphatidylserine. Once Thymosin α1's N-terminus has been inserted into the membrane, the rest may interact with nearby proteins and/or receptors acting as effectors and causing a biological signaling cascade, thus exerting thymosin α1's pleiotropy. PMID:26909491

  4. Subversion of Immunity by Leishmania amazonensis Parasites: Possible Role of Phosphatidylserine as a Main Regulator

    Directory of Open Access Journals (Sweden)

    Joao Luiz Mendes Wanderley

    2012-01-01

    Full Text Available Leishmania amazonensis parasites cause progressive disease in most inbred mouse strains and are associated with the development of diffuse cutaneous leishmaniasis in humans. The poor activation of an effective cellular response is correlated with the ability of these parasites to infect mononuclear phagocytic cells without triggering their activation or actively suppressing innate responses of these cells. Here we discuss the possible role of phosphatidylserine exposure by these parasites as a main regulator of the mechanism underlying subversion of the immune system at different steps during the infection.

  5. 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.)

  6. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis

    Energy Technology Data Exchange (ETDEWEB)

    Feussner, J.R.; Shelburne, J.D.; Bredehoeft, S.; Cohen, H.J.

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-proble analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  7. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  8. Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment

    Institute of Scientific and Technical Information of China (English)

    Garima Sharma; Madhu Kumar

    2012-01-01

    Arsenic has a suppressive influence on spermatogenesis and induces impairment in male reproductive system due to oxidative stress.The present study was aimed to test the arsenic induced toxicity and protection by Chlorophytum borivilianum.The effect of sodium arsenite (4 mg/(kg body weight (bw)·day)) via double distilled water without or with C.borivilianum (800 mg/(kg bw·day)) was evaluated in Swiss albino mice for 30 days.The radical scavenging activity of the aqueous C.borivilianum root extract was measured using DPPH (l,l-diphenyl-2-picryl hydrayzyl) radical.Qualitative assessment of various cell types in the testis,sperm count and motility,testicular activity of lipid peroxidation (LPO),reduced glutathione (GSH),acid and alkaline phosphatase,cholesterol and serum testosterone were monitored.Arsenic treatment showed a significant increase in LPO,acid and alkaline phosphatase,cholesterol and decrease in sperm count,sperm motility,GSH and serum testosterone.Combined treatment showed significant decrease in LPO,acid and alkaline phosphatase,cholesterol and elevation in sperm count,sperm motility,GSH and serum testosterone.Testiculat histopathology showed that C.borivilianum had reduced degeneration of germ cell in the seminiferous tubules and loss of sperms induced by arsenic intoxication.The results thus led us to conclude that administration of C.borivilianum root extract is found to be protective against arsenic induced toxicity.

  9. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis.

    Science.gov (United States)

    Feussner, J R; Shelburne, J D; Bredehoeft, S; Cohen, H J

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-probe analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  10. Selenium ameliorates arsenic induced oxidative stress through modulation of antioxidant enzymes and thiols in rice (Oryza sativa L.).

    Science.gov (United States)

    Kumar, Amit; Singh, Rana Pratap; Singh, Pradyumna Kumar; Awasthi, Surabhi; Chakrabarty, Debasis; Trivedi, Prabodh Kumar; Tripathi, Rudra Deo

    2014-09-01

    Arsenic (As) contamination of rice is a major problem for South-East Asia. In the present study, the effect of selenium (Se) on rice (Oryza sativa L.) plants exposed to As was studied in hydroponic culture. Arsenic accumulation, plant growth, thiolic ligands and antioxidative enzyme activities were assayed after single (As and Se) and simultaneous supplementations (As + Se). The results indicated that the presence of Se (25 µM) decreased As accumulation by threefold in roots and twofold in shoots as compared to single As (25 µM) exposed plants. Arsenic induced oxidative stress in roots and shoots was significantly ameliorated by Se supplementation. The observed positive response was found associated with the increased activities of ascorbate peroxidase (APX; EC 1.11.1.11), catalase (CAT; EC 1.11.1.6) and glutathione peroxidase (GPx; EC 1.11.1.9) and induced levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) in As + Se exposed plants as compared to single As treatment. Selenium supplementation modulated the thiol metabolism enzymes viz., γ-glutamylcysteine synthetase (γ-ECS; EC 6.3.2.2), glutathione-S-transferase (GST; EC 2.5.1.18) and phytochelatin synthase (PCS; EC 2.3.2.15). Gene expression analysis of several metalloid responsive genes (LOX, SOD and MATE) showed upregulation during As stress, however, significant downregulation during As + Se exposure as compared to single As treatment. Gene expressions of enzymes of antioxidant and GSH and PC biosynthetic systems, such as APX, CAT, GPx, γ-ECS and PCS were found to be significantly positively correlated with their enzyme activities. The findings suggested that Se supplementation could be an effective strategy to reduce As accumulation and toxicity in rice plants.

  11. Effects of Echinacea Purpurea on Wound Healing after Arsenic Induced Skin Necrosis

    Directory of Open Access Journals (Sweden)

    Annahita Rezaie

    2013-11-01

    Full Text Available Background: Evaluation of healing effects of Echinacea extract in Arsenic induced dermal necrosis in rat is the objective of this study. Materials and Methods: In this experimental study 20 male Wistar rats were divided to 2 groups. Dermal necrosis was induced by subcutaneously arsenic injection (4mg/kg for 10 days. In group 2, after arsenic receiving, Echinacea were injected intraperitoneally (400mg/kg. After last day of injection, rats were euthanizes and pathologic samples were collected from dermal ulcers.Results: Histopathologic results revealed necrosis of different dermal layers in arsenic group. There were inflammatory exudates instead of impaired structures. In group 2, there were granulation tissue with high cellularity and new vessels.Conclusion: According to this research findings arsenic can induce dermal necrosis which is a good animal model for dermatologic researches and also Echinacea has healing effects and can protect and limit the Arsenic effects.

  12. 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.

  13. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages

    OpenAIRE

    Geelen Tessa; Yeo Sin; Paulis Leonie EM; Starmans Lucas WE; Nicolay Klaas; Strijkers Gustav J

    2012-01-01

    Abstract Background Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS)-containing liposomes were developed for magnetic resonance imaging (MRI) and confocal microscopy imaging of macrophages. Thes...

  14. Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis

    OpenAIRE

    Maiseyeu, Andrei; Mihai, Georgeta; Kampfrath, Thomas; Simonetti, Orlando P.; Sen, Chandan K.; Roy, Sashwati; Rajagopalan, Sanjay; Parthasarathy, Sampath

    2009-01-01

    Exteriorized phosphatidylserine (PS) residues in apoptotic cells trigger rapid phagocytosis by macrophage scavenger receptor pathways. Mimicking apoptosis with liposomes containing PS may represent an attractive approach for molecular imaging of atherosclerosis. We investigated the utility of paramagnetic gadolinium liposomes enriched with PS (Gd-PS) in imaging atherosclerotic plaque. Gd-PS-containing Gd-conjugated lipids, fluorescent rhodamine, and PS were prepared and characterized. Cellula...

  15. ANTI-PHOSPHATIDYLSERINE ANTIBODIES IN ACUTE MYOCARDIAL INFARCTION

    OpenAIRE

    Abdolreza Sotoodeh Jahromi; Mohammad Shojaei; Mohammad Reza Farjam; Abdolhossien Madani

    2013-01-01

    Acute Myocardial Infarction (AMI) is the combined result of environmental factors and personal predispositions. Many factors play a role in AMI including anti-Phospholipid (aPL) antibodies, that may act in the induction of immunological response leading to the development of AMI. Anti-Phosphatidylserine (PS) antibody is detected in various diseases like rheumatoid arthritis, systemic lupus erythematosus and anti-phospholipid antibody syndrome. The study of anti-PS antibody in AMI might shed l...

  16. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  17. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  18. Arsenic Induced Inhibition of δ-aminolevulinate Dehydratase Activity in Rat Blood and its Response To Meso 2,3-dimercaptosuccinic Acid and Monoisoamyl DMSA

    Institute of Scientific and Technical Information of China (English)

    SMRATI BHADAURIA; SWARAN J.S.FLORA

    2004-01-01

    Objective The objective of this study was to investigate arsenic induced changes in blood δ-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (Ⅲ) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (Ⅲ and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (Ⅲ) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (Ⅲ), but at two higher concentrations (0.5and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood

  19. Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats.

    Science.gov (United States)

    Jalaludeen, Abdulkadhar Mohamed; Ha, Woo Tae; Lee, Ran; Kim, Jin Hoi; Do, Jeong Tae; Park, Chankyu; Heo, Young Tae; Lee, Won Young; Song, Hyuk

    2016-01-09

    Biochanin A (BCA) is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was to investigate the protective effects of BCA against arsenic-induced hepatic injury and hematotoxicity in rats. The results suggest that arsenic intoxicated rats showed significantly higher levels of plasma hepatic markers than normal control rats. Furthermore, an increase in lipid peroxidation with depletion of reduced glutathione (GSH) and activities of superoxide dismutase (SOD) and catalase (CAT) occurred in the livers of rats exposed to arsenic. Administration of BCA (20 mg/kg·bw/day) and selenium (3 mg/kg·bw/day) resulted in a significant reversal of hepatic and oxidative stress markers in arsenic-intoxicated rats. A low dose of BCA (10 mg/kg·bw/day) did not show any preventive effect, while a high dose of BCA (40 mg/kg·bw/day) partially prevented all hepatotoxicity events. These biochemical perturbations were supported by histopathological observations of the liver. Our results suggest that administration of BCA (20 mg/kg·bw/day) attenuated the arsenic hepatotoxicity, a property that could contribute to the therapeutic approaches for chronic liver diseases.

  20. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  1. Arsenic-induced morphogenic response in roots of arsenic hyperaccumulator fern Pteris vittata.

    Science.gov (United States)

    Forino, Laura Maria Costantina; Ruffini Castiglione, Monica; Bartoli, Giacomo; Balestri, Mirko; Andreucci, Andrea; Tagliasacchi, Anna Maria

    2012-10-15

    On the assumption that arsenic induces stress morphogenetic responses involved in As tolerance and hyperaccumulation in the Pteris vittata fern, we analyzed the root system of young sporophytes grown in 250, 334, and 500 μM As for five days and for 14 days. Anatomical and histological analyses were performed in plants grown for five days to evaluate the number, position, length and differentiation pattern of root hairs. AgNOR staining, employed to study nucleolus behavior in root apices, showed that arsenic influences nucleolar activity (evaluated by nucleolus size, number and absorbance) in the root meristem. In plants treated with 250 and 334 μM As an acropetal shift of root hair development and an increase in hair length and density were observed, linked to an ectopic pattern of differentiation. The opposite trend was recorded in plants treated with 500 μM As. It is worth noting the presence of living border-like cells, not yet observed in ferns, and their increase following As treatments. Analysis and vitality of border-like cells were surveyed after 14 days of treatments. In conclusion As treatments elicited a stress-induced morphogenic response which, by modifying the differentiation pattern, number and length of root hairs, modulating nucleolar activity and interacting with the rhizosphere by inducing border-like cell production, may adjust the rate of root uptake and its metabolic activity.

  2. Effect of vitamin E supplementation on arsenic induced oxidative stress in goats.

    Science.gov (United States)

    Das, T K; Mani, V; Kaur, H; Kewalramani, N; De, S; Hossain, A; Banerjee, D; Datta, B K

    2012-07-01

    The present study was designed to assess whether supplementation of different levels of vitamin E to long-term arsenic exposed goats affords protection against the oxidative stress caused by the metalloid. Twenty-four crossbred lactating goats were distributed randomly into four groups (control, T(1), T(2) and T(3)) of six in each. The animals in T(1), T(2) and T(3) were given 50 mg/kg DM arsenic daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg DM, respectively, was also supplemented additionally for the period of 12 months. Compared to control, significant (p 63 %), plasma total Ig (22 %) and total antioxidant activity (24 %) was observed in only arsenic treated groups and vitamin E supplementation in both doses produced partial mitigation effect against SOD (23 %, 20 %) and CAT (39 %, 48 %) while complete mitigation against total Ig (16 %, 7 %) and antioxidant activity (10 %, 8 %) was found. Average lymphocyte stimulation index at the end of experiment was (p arsenic exposed groups (1.003 ± 0.01) and significant (p arsenic induced oxidative stress and activities of antioxidant enzymes in goats.

  3. Research Progress on Molecular Mechanisms of Arsenic- induced Oxidative Stress%砷的氧化应激分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    白彩军; 刘丹; 李冰

    2012-01-01

    砷暴露能够引起多种疾病和病理损伤.目前氧化应激机制是砷毒性的研究热点.砷通过扰乱氧化/抗氧化平衡,从而引起细胞信号通路和转录因子活性、细胞周期和细胞凋亡、线粒体、抗氧化物酶的活性、抗氧化防御系统等方面的改变.本文将就砷的氧化应激分子机制的研究进展进行综述.%Arsenic exposure can cause a variety of diseases and pathological damages. In recent years, oxidative stress mechanism has been considered to be the research focus of arsenic toxicity. Arsenic alters multiple cellular pathways and transcription factor activities, cell cycle and cell apoptosis, mitochondria, antioxidant enzymes activity, and antioxidant defense system by disturbing the pro/antioxidant balance. This review summarizes the molecular mechanism of arsenic- induced oxidative stress.

  4. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    International Nuclear Information System (INIS)

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, 122Sb and 124Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  5. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail: samanta@usp.br, e-mail: nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail: jaosso@ipen.br

    2009-07-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  6. Investigation into the Role of Phosphatidylserine in Modifying the Susceptibility of Human Lymphocytes to Secretory Phospholipase A2 using Cells Deficient in the Expression of Scramblase

    OpenAIRE

    Nelson, Jennifer; Francom, Lyndee L.; Anderson, Lynn; Damm, Kelly; Baker, Ryan; Chen, Joseph; Franklin, Sarah; Hamaker, Amy; Izidoro, Izadora; Moss, Eric; Orton, Mikayla; Stevens, Evan; Yeung, Celestine; Allan M. Judd; Bell, John D.

    2012-01-01

    Normal human lymphocytes resisted the hydrolytic action of secretory phospholipase A2 but became susceptible to the enzyme following treatment with a calcium ionophore, ionomycin. To test the hypothesis that this susceptibility requires exposure of the anionic lipid phosphatidylserine on the external face of the cell membrane, experiments were repeated with a human Burkitt’s lymphoma cell line (Raji cells). In contrast to normal lymphocytes or S49 mouse lymphoma cells, most of the Raji cells ...

  7. Enhancement of Anti-Inflammatory Activity of Curcumin Using Phosphatidylserine-Containing Nanoparticles in Cultured Macrophages

    Directory of Open Access Journals (Sweden)

    Ji Wang

    2016-06-01

    Full Text Available Macrophages are one kind of innate immune cells, and produce a variety of inflammatory cytokines in response to various stimuli, such as oxidized low density lipoprotein found in the pathogenesis of atherosclerosis. In this study, the effect of phosphatidylserine on anti-inflammatory activity of curcumin-loaded nanostructured lipid carriers was investigated using macrophage cultures. Different amounts of phosphatidylserine were used in the preparation of curcumin nanoparticles, their physicochemical properties and biocompatibilities were then compared. Cellular uptake of the nanoparticles was investigated using a confocal laser scanning microscope and flow cytometry analysis in order to determine the optimal phosphatidylserine concentration. In vitro anti-inflammatory activities were evaluated in macrophages to test whether curcumin and phosphatidylserine have interactive effects on macrophage lipid uptake behavior and anti-inflammatory responses. Here, we showed that macrophage uptake of phosphatidylserine-containing nanostructured lipid carriers increased with increasing amount of phosphatidylserine in the range of 0%–8%, and decreased when the phosphatidylserine molar ratio reached over 12%. curcumin-loaded nanostructured lipid carriers significantly inhibited lipid accumulation and pro-inflammatory factor production in cultured macrophages, and evidently promoted release of anti-inflammatory cytokines, when compared with curcumin or phosphatidylserine alone. These results suggest that the delivery system using PS-based nanoparticles has great potential for efficient delivery of drugs such as curcumin, specifically targeting macrophages and modulation of their anti-inflammatory functions.

  8. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  9. Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin.

    Science.gov (United States)

    Qadri, Syed M; Donkor, David A; Bhakta, Varsha; Eltringham-Smith, Louise J; Dwivedi, Dhruva J; Moore, Jane C; Pepler, Laura; Ivetic, Nikola; Nazi, Ishac; Fox-Robichaud, Alison E; Liaw, Patricia C; Sheffield, William P

    2016-04-01

    The opportunistic pathogen Pseudomonas aeruginosa causes a wide range of infections in multiple hosts by releasing an arsenal of virulence factors such as pyocyanin. Despite numerous reports on the pleiotropic cellular targets of pyocyanin toxicity in vivo, its impact on erythrocytes remains elusive. Erythrocytes undergo an apoptosis-like cell death called eryptosis which is characterized by cell shrinkage and phosphatidylserine (PS) externalization; this process confers a procoagulant phenotype on erythrocytes as well as fosters their phagocytosis and subsequent clearance from the circulation. Herein, we demonstrate that P. aeruginosa pyocyanin-elicited PS exposure and cell shrinkage in erythrocyte while preserving the membrane integrity. Mechanistically, exposure of erythrocytes to pyocyanin showed increased cytosolic Ca(2+) activity as well as Ca(2+) -dependent proteolytic processing of μ-calpain. Pyocyanin further up-regulated erythrocyte ceramide abundance and triggered the production of reactive oxygen species. Pyocyanin-induced increased PS externalization in erythrocytes translated into enhanced prothrombin activation and fibrin generation in plasma. As judged by carboxyfluorescein succinimidyl-ester labelling, pyocyanin-treated erythrocytes were cleared faster from the murine circulation as compared to untreated erythrocytes. Furthermore, erythrocytes incubated in plasma from patients with P. aeruginosa sepsis showed increased PS exposure as compared to erythrocytes incubated in plasma from healthy donors. In conclusion, the present study discloses the eryptosis-inducing effect of the virulence factor pyocyanin, thereby shedding light on a potentially important mechanism in the systemic complications of P. aeruginosa infection. PMID:26781477

  10. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  11. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    Directory of Open Access Journals (Sweden)

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  12. Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats.

    Science.gov (United States)

    Bhadauria, S; Flora, S J S

    2007-03-01

    -exposed rats compared to that of normal animals. These changes were accompanied by a significant elevation in blood and soft-tissue arsenic concentration. Co-administration of DMSA and MiADMSA at lower dose (0.15 mmol/kg) was most effective not only in reducing arsenic-induced oxidative stress but also in depleting arsenic from blood and soft tissues compared to other treatments. This combination was also able to repair DNA damage caused following arsenic exposure. We thus recommend combined administration of DMSA and MiADMSA for achieving optimum effects of chelation therapy.

  13. Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia.

    Science.gov (United States)

    Fernandez-Arias, Cristina; Rivera-Correa, Juan; Gallego-Delgado, Julio; Rudlaff, Rachel; Fernandez, Clemente; Roussel, Camille; Götz, Anton; Gonzalez, Sandra; Mohanty, Akshaya; Mohanty, Sanjib; Wassmer, Samuel; Buffet, Pierre; Ndour, Papa Alioune; Rodriguez, Ana

    2016-02-10

    Plasmodium species, the parasitic agents of malaria, invade erythrocytes to reproduce, resulting in erythrocyte loss. However, a greater loss is caused by the elimination of uninfected erythrocytes, sometimes long after infection has been cleared. Using a mouse model, we found that Plasmodium infection induces the generation of anti-self antibodies that bind to the surface of uninfected erythrocytes from infected, but not uninfected, mice. These antibodies recognize phosphatidylserine, which is exposed on the surface of a fraction of uninfected erythrocytes during malaria. We find that phosphatidylserine-exposing erythrocytes are reticulocytes expressing high levels of CD47, a "do-not-eat-me" signal, but the binding of anti-phosphatidylserine antibodies mediates their phagocytosis, contributing to anemia. In human patients with late postmalarial anemia, we found a strong inverse correlation between the levels of anti-phosphatidylserine antibodies and plasma hemoglobin, suggesting a similar role in humans. Inhibition of this pathway may be exploited for treating malarial anemia.

  14. Regulation of phospholipid synthesis in phosphatidylserine synthase-deficient (chol) mutants of Saccharomyces cerevisiae.

    OpenAIRE

    Letts, V A; Henry, S. A.

    1985-01-01

    chol mutants of Saccharomyces cerevisiae are deficient in the synthesis of the phospholipid phosphatidylserine owing to lowered activity of the membrane-associated enzyme phosphatidylserine synthase. chol mutants are auxotrophic for ethanolamine or choline and, in the absence of these supplements, cannot synthesize phosphatidylethanolamine or phosphatidylcholine (PC). We exploited these characteristics of the chol mutants to examine the regulation of phospholipid metabolism in S. cerevisiae. ...

  15. Isolation and characterization of a Chinese hamster ovary cell mutant with altered regulation of phosphatidylserine biosynthesis

    International Nuclear Information System (INIS)

    We have screened approximately 10,000 colonies of Chinese hamster ovary (CHO) cells immobilized on polyester cloth for mutants defective in [14C]ethanolamine incorporation into trichloroacetic acid-precipitable phospholipids. In mutant 29, discovered in this way, the activities of enzymes involved in the CDP-ethanolamine pathway were normal; however, the intracellular pool of phosphorylethanolamine was elevated, being more than 10-fold that in the parental CHO-K1 cells. These results suggested that the reduced incorporation of [14C]ethanolamine into phosphatidylethanolamine in mutant 29 was due to dilution of phosphoryl-[14C]ethanolamine with the increased amount of cellular phosphorylethanolamine. Interestingly, the rate of incorporation of serine into phosphatidylserine and the content of phosphatidylserine in mutant 29 cells were increased 3-fold and 1.5-fold, respectively, compared with the parent cells. The overproduction of phosphorylethanolamine in mutant 29 cells was ascribed to the elevated level of phosphatidylserine biosynthesis, because ethanolamine is produced as a reaction product on the conversion of phosphatidylethanolamine to phosphatidylserine, which is catalyzed by phospholipid-serine base-exchange enzymes. Using both intact cells and the particulate fraction of a cell extract, phosphatidylserine biosynthesis in CHO-K1 cells was shown to be inhibited by phosphatidylserine itself, whereas that in mutant 29 cells was greatly resistant to the inhibition, compared with the parental cells. As a conclusion, it may be assumed that mutant 29 cells have a lesion in the regulation of phosphatidylserine biosynthesis by serine-exchange enzyme activity, which results in the overproduction of phosphatidylserine and phosphorylethanolamine as well

  16. Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

    Science.gov (United States)

    Dowall, S. D.; Graham, V. A.; Corbin-Lickfett, K.; Empig, C.; Schlunegger, K.; Bruce, C. B.; Easterbrook, L.; Hewson, R.

    2015-01-01

    Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus. PMID:25815346

  17. Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

    Directory of Open Access Journals (Sweden)

    S. D. Dowall

    2015-01-01

    Full Text Available Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity against Ebola virus.

  18. Cloning, Sequencing, and Disruption of the Bacillus subtilis psd Gene Coding for Phosphatidylserine Decarboxylase

    OpenAIRE

    Matsumoto, Kouji; Okada, Masahiro; Horikoshi, Yuko; Matsuzaki, Hiroshi; Kishi, Tsutomu; Itaya, Mitsuhiro; Shibuya, Isao

    1998-01-01

    The psd gene of Bacillus subtilis Marburg, encoding phosphatidylserine decarboxylase, has been cloned and sequenced. It encodes a polypeptide of 263 amino acid residues (deduced molecular weight of 29,689) and is located just downstream of pss, the structural gene for phosphatidylserine synthase that catalyzes the preceding reaction in phosphatidylethanolamine synthesis (M. Okada, H. Matsuzaki, I. Shibuya, and K. Matsumoto, J. Bacteriol. 176:7456–7461, 1994). Introduction of a plasmid contain...

  19. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages

    Directory of Open Access Journals (Sweden)

    Geelen Tessa

    2012-08-01

    Full Text Available Abstract Background Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and provide a read-out for therapy efficacy. Paramagnetic phosphatidylserine (PS-containing liposomes were developed for magnetic resonance imaging (MRI and confocal microscopy imaging of macrophages. These nanoparticles also provide a platform to combine imaging with targeted drug delivery. Results Incorporation of PS into liposomes did not affect liposomal size and morphology up to 12 mol% of PS. Liposomes containing 6 mol% of PS showed the highest uptake by murine macrophages, while only minor uptake was observed in endothelial cells. Uptake of liposomes containing 6 mol% of PS was dependent on the presence of Ca2+ and Mg2+. Furthermore, these 6 mol% PS-containing liposomes were mainly internalized into macrophages, whereas liposomes without PS only bound to the macrophage cell membrane. Conclusions Paramagnetic liposomes containing 6 mol% of PS for MR imaging of macrophages have been developed. In vitro these liposomes showed specific internalization by macrophages. Therefore, these liposomes might be suitable for in vivo visualization of macrophage content and for (visualization of targeted drug delivery to inflammatory cells.

  20. Phosphatidylserine increases IKBKAP levels in familial dysautonomia cells.

    Directory of Open Access Journals (Sweden)

    Hadas Keren

    Full Text Available Familial Dysautonomia (FD is an autosomal recessive congenital neuropathy that results from abnormal development and progressive degeneration of the sensory and autonomic nervous system. The mutation observed in almost all FD patients is a point mutation at position 6 of intron 20 of the IKBKAP gene; this gene encodes the IκB kinase complex-associated protein (IKAP. The mutation results in a tissue-specific splicing defect: Exon 20 is skipped, leading to reduced IKAP protein expression. Here we show that phosphatidylserine (PS, an FDA-approved food supplement, increased IKAP mRNA levels in cells derived from FD patients. Long-term treatment with PS led to a significant increase in IKAP protein levels in these cells. A conjugate of PS and an omega-3 fatty acid also increased IKAP mRNA levels. Furthermore, PS treatment released FD cells from cell cycle arrest and up-regulated a significant number of genes involved in cell cycle regulation. Our results suggest that PS has potential for use as a therapeutic agent for FD. Understanding its mechanism of action may reveal the mechanism underlying the FD disease.

  1. Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome.

    Science.gov (United States)

    Sousa, Sérgio B; Jenkins, Dagan; Chanudet, Estelle; Tasseva, Guergana; Ishida, Miho; Anderson, Glenn; Docker, James; Ryten, Mina; Sa, Joaquim; Saraiva, Jorge M; Barnicoat, Angela; Scott, Richard; Calder, Alistair; Wattanasirichaigoon, Duangrurdee; Chrzanowska, Krystyna; Simandlová, Martina; Van Maldergem, Lionel; Stanier, Philip; Beales, Philip L; Vance, Jean E; Moore, Gudrun E

    2014-01-01

    Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.

  2. Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome.

    Science.gov (United States)

    Sousa, Sérgio B; Jenkins, Dagan; Chanudet, Estelle; Tasseva, Guergana; Ishida, Miho; Anderson, Glenn; Docker, James; Ryten, Mina; Sa, Joaquim; Saraiva, Jorge M; Barnicoat, Angela; Scott, Richard; Calder, Alistair; Wattanasirichaigoon, Duangrurdee; Chrzanowska, Krystyna; Simandlová, Martina; Van Maldergem, Lionel; Stanier, Philip; Beales, Philip L; Vance, Jean E; Moore, Gudrun E

    2014-01-01

    Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism. PMID:24241535

  3. Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins.

    Science.gov (United States)

    Maeda, Kenji; Anand, Kanchan; Chiapparino, Antonella; Kumar, Arun; Poletto, Mattia; Kaksonen, Marko; Gavin, Anne-Claude

    2013-09-12

    The internal organization of eukaryotic cells into functionally specialized, membrane-delimited organelles of unique composition implies a need for active, regulated lipid transport. Phosphatidylserine (PS), for example, is synthesized in the endoplasmic reticulum and then preferentially associates--through mechanisms not fully elucidated--with the inner leaflet of the plasma membrane. Lipids can travel via transport vesicles. Alternatively, several protein families known as lipid-transfer proteins (LTPs) can extract a variety of specific lipids from biological membranes and transport them, within a hydrophobic pocket, through aqueous phases. Here we report the development of an integrated approach that combines protein fractionation and lipidomics to characterize the LTP-lipid complexes formed in vivo. We applied the procedure to 13 LTPs in the yeast Saccharomyces cerevisiae: the six Sec14 homology (Sfh) proteins and the seven oxysterol-binding homology (Osh) proteins. We found that Osh6 and Osh7 have an unexpected specificity for PS. In vivo, they participate in PS homeostasis and the transport of this lipid to the plasma membrane. The structure of Osh6 bound to PS reveals unique features that are conserved among other metazoan oxysterol-binding proteins (OSBPs) and are required for PS recognition. Our findings represent the first direct evidence, to our knowledge, for the non-vesicular transfer of PS from its site of biosynthesis (the endoplasmic reticulum) to its site of biological activity (the plasma membrane). We describe a new subfamily of OSBPs, including human ORP5 and ORP10, that transfer PS and propose new mechanisms of action for a protein family that is involved in several human pathologies such as cancer, dyslipidaemia and metabolic syndrome. PMID:23934110

  4. Diannexin protects against renal ischemia reperfusion injury and targets phosphatidylserines in ischemic tissue.

    Directory of Open Access Journals (Sweden)

    Kimberley E Wever

    Full Text Available Renal ischemia/reperfusion injury (IRI frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5 homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo.

  5. A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

    OpenAIRE

    Kile, Molly L.; Faraj, Joycelyn M.; Ronnenberg, Alayne G.; Quamruzzaman, Quazi; Rahman, Mahmudar; Mostofa, Golam; Afroz, Sakila; Christiani, David C.

    2016-01-01

    Background In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association betwee...

  6. Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice

    Science.gov (United States)

    Liu, Su; Guo, Xuechao; Wu, Bing; Yu, Haiyan; Zhang, Xuxiang; Li, Mei

    2014-11-01

    Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic β-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic β-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.

  7. Cryptic exposure to arsenic.

    Science.gov (United States)

    Rossy, Kathleen M; Janusz, Christopher A; Schwartz, Robert A

    2005-01-01

    Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic) and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  8. Cryptic exposure to arsenic

    Directory of Open Access Journals (Sweden)

    Rossy Kathleen

    2005-01-01

    Full Text Available Arsenic is an odorless, colorless and tasteless element long linked with effects on the skin and viscera. Exposure to it may be cryptic. Although human intake can occur from four forms, elemental, inorganic (trivalent and pentavalent arsenic and organic arsenic, the trivalent inorganic arsenicals constitute the major human hazard. Arsenic usually reaches the skin from occupational, therapeutic, or environmental exposure, although it still may be employed as a poison. Occupations involving new technologies are not exempt from arsenic exposure. Its acute and chronic effects are noteworthy. Treatment options exist for arsenic-induced pathology, but prevention of toxicity remains the main focus. Vitamin and mineral supplementation may play a role in the treatment of arsenic toxicity.

  9. Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.

    OpenAIRE

    Burns, Fredric J.; Uddin, Ahmed N.; Wu, Feng; Nádas, Arthur; Rossman, Toby G.

    2004-01-01

    The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experi...

  10. Proteomic Analysis of Arsenic-Induced Oxidative Stress in Human Epidermal Keratinocytes

    Science.gov (United States)

    Chronic exposure to inorganic arsenic (IAs) has been associated with the development of several human cancers, including those found in the skin, lung, urinary bladder, liver, prostate and kidney. The precise mechanisms by which arsenic causes cancer are unknown. Defining the mod...

  11. Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

    Science.gov (United States)

    Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

    2013-01-01

    To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

  12. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-01-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

  13. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  14. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation...

  15. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    Science.gov (United States)

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid. PMID:27165637

  16. Combined Administration of Taurine and Monoisoamyl Dmsa Protects Arsenic Induced Oxidative Injury in Rats

    Directory of Open Access Journals (Sweden)

    Swaran J. S. Flora

    2008-01-01

    Full Text Available Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA, administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks were treated with taurine (100 mg/kg, i.p., once daily, monoisoamyl dimercaptosuccinic acid (MiADMSA (50 mg/kg, oral, once daily either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP level. Clinical hematological variables like white blood cells (WBC, mean cell hemoglobin (MCH, and mean cell hemoglobin concentration (MCHC showed significant decrease with a significant elevation in platelet (PLT count. These changes were accompanied by significant decrease in superoxide dismutase (SOD activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH level and an increase in oxidized glutathione (GSSG. These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co

  17. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-07-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage. PMID:26524343

  18. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  19. Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats.

    Science.gov (United States)

    Sankar, Palanisamy; Gopal Telang, Avinash; Kalaivanan, Ramya; Karunakaran, Vijayakaran; Manikam, Kesavan; Sarkar, Souvendra Nath

    2015-01-01

    We investigated the therapeutic effectiveness of the nanoparticle-encapsulated curcumin (CUR-NP) against sodium arsenite-induced hepatic oxidative damage in rats. The CUR-NP prepared by emulsion technique was spherical in shape with an encapsulation efficiency of 86.5%. The particle size ranged between 120 and 140 nm with the mean particle size being 130.8 nm. Rats were divided into five groups of six each. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in group 2, however, they were administered, empty nanoparticles, curcumin (100 mg/kg bw) and CUR-NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic increased the activities of serum alanine aminotransferase and aspartate aminotransferase and caused histological alterations in liver indicating hepatotoxicity. Arsenic increased lipid peroxidation, depleted reduced glutathione and decreased the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in liver. All these effects of arsenic were attenuated with both curcumin and CUR-NP. However, the magnitude of amelioration was more pronounced with CUR-NP. The results indicate that curcumin given in nano-encapsulated form caused better amelioration than free curcumin. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 628-637, 2015.

  20. Monoisoamyl 2,3-dimercaptosuccinic acid attenuates arsenic induced toxicity: behavioral and neurochemical approach.

    Science.gov (United States)

    Ram Kumar, M; Flora, S J S; Reddy, G R

    2013-07-01

    Chronic exposure to arsenic in drinking water is associated with skin lesions, neurological effects, hypertension and high risk of cancer. The treatment in use at present employs administration of thiol chelators, such as meso-2,3-dimercaptosuccinic acid (DMSA) which are compromised with number of limitations due to their lipophobic nature. To address this problem, therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), an analog of DMSA having lipophilic character, was examined against chronic arsenic poisoning in rats. Adult male Wistar rats were orally exposed to arsenic (2mg sodium arsenite/kg body weight) for 10 weeks followed by treatment with MiADMSA (50mg/kg, orally, once daily for 5 consecutive days). As-exposed rats showed significant differences in behavioral functions (open field behavior, total locomotor activity, grip strength and exploratory behavior) and water maze learning. Further, the biochemical studies performed on three brain regions (cerebellum, cortex and hippocampus) also showed significant elevation in malondialdehyde (MDA) levels with a concomitant decrease in the oxidative stress marker enzymes Mn-superoxide dismutase (Mn-SOD), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST). The alterations were more pronounced in cortex compared to cerebellum and hippocampus. The results showed that MiADMSA significantly reversed the As-induced alterations in behavior and biochemical variables suggestive of oxidative injury.

  1. Arsenic induced oxidative stress and the role of antioxidant supplementation during chelation: a review.

    Science.gov (United States)

    Flora, S J S; Bhadauria, Smrati; Kannan, G M; Singh, Nutan

    2007-04-01

    Arsenic is a naturally occurring metalloid, ubiquitously present in the environment in both organic and inorganic forms. Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geoenvironmental disaster to date. Chronic exposure of humans to high concentration of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, Blackfoot disease and high risk of cancer The underlying mechanism of toxicity includes the interaction with the sulphydryl groups and the generation of reactive oxygen species leading to oxidative stress. Chelation therapy with chelating agents like British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3 dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against arsenic poisoning. The treatment with these chelating agents however is compromised with certain serious drawbacks/side effects. The studies show that supplementation of antioxidants along with a chelating agent prove to be a better treatment regimen. This review attempts to provide the readers with a comprehensive account of recent developments in the research on arsenic poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects.

  2. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    Science.gov (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  3. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    International Nuclear Information System (INIS)

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria

  4. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    Energy Technology Data Exchange (ETDEWEB)

    Massey, Veronica L. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Stocke, Kendall S. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Schmidt, Robin H.; Tan, Min [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Ajami, Nadim [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Neal, Rachel E. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Petrosino, Joseph F. [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Barve, Shirish [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2015-05-01

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria.

  5. Arsenic-induced intensity oscillations in reflection high-energy electron diffraction measurements. [during MBE of GaAs and InAs

    Science.gov (United States)

    Lewis, B. F.; Fernandez, R.; Grunthaner, F. J.; Madhukar, A.

    1986-01-01

    A technique of arsenic-induced RHEED intensity oscillations has been used to accurately measure arsenic incorporation rates as a function of substrate temperature during the homoepitaxial growths of both GaAs and InAs by molecular beam epitaxy (MBE). Measurements were made at growth temperatures from 350 to 650 C and at arsenic fluxes of 0.1 to 10.0 monolayer/s. The method measures only the arsenic actually incorporated into the growing film and does not include the arsenic lost in splitting the arsenic tetramers or lost by evaporation from the sample.

  6. Properties of mixtures of cholesterol with phosphatidylcholine or with phosphatidylserine studied by (13)C magic angle spinning nuclear magnetic resonance.

    OpenAIRE

    Epand, Richard M.; Bain, Alex D; Sayer, Brian G; Bach, Diana; Wachtel, Ellen

    2002-01-01

    The behavior of cholesterol is different in mixtures with phosphatidylcholine as compared with phosphatidylserine. In (13)C cross polarization/magic angle spinning nuclear magnetic resonance spectra, resonance peaks of the vinylic carbons of cholesterol are a doublet in samples containing 0.3 or 0.5 mol fraction cholesterol with 1-palmitoyl-2-oleoyl phosphatidylserine (POPS) or in cholesterol monohydrate crystals, but a singlet with mixtures of cholesterol and 1-palmitoyl-2-oleoyl phosphatidy...

  7. Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair

    OpenAIRE

    Harel-Adar, Tamar; Mordechai, Tamar Ben; Amsalem, Yoram; Feinberg, Micha S.; Leor, Jonathan; Cohen, Smadar

    2011-01-01

    Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-infla...

  8. Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity

    OpenAIRE

    Samanta Etel Treiger Borborema; João Alberto Osso Junior; Heitor Franco de Andrade Junior; Nanci do Nascimento

    2016-01-01

    Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine l...

  9. Phosphatidylserine functions as the major precursor of phosphatidylethanolamine in cultured BHK-21 cells.

    OpenAIRE

    Voelker, D R

    1984-01-01

    Pulse-chase experiments with [3H]serine provide evidence that significant amounts of phosphatidylserine turn over to form phosphatidylethanolamine in mammalian cells in tissue culture. Phospholipase C hydrolysis of [3H]phosphatidylethanolamine synthesized from [3H]serine by baby hamster kidney (BHK-21) cells demonstrates that nearly all of the radiolabel remains in the ethanolamine moiety. Uniform labeling experiments with [3H]serine further demonstrate that the distribution of radiolabel in ...

  10. The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

    Directory of Open Access Journals (Sweden)

    Hafner Martin

    2004-08-01

    Full Text Available Abstract Background Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr on phagocytes has been implicated in the recognition and engulfment of apoptotic cells and in anti-inflammatory signaling. To determine the biological function of the phosphatidylserine receptor in vivo, we inactivated the Ptdsr gene in the mouse. Results Ablation of Ptdsr function in mice causes perinatal lethality, growth retardation and a delay in terminal differentiation of the kidney, intestine, liver and lungs during embryogenesis. Moreover, eye development can be severely disturbed, ranging from defects in retinal differentiation to complete unilateral or bilateral absence of eyes. Ptdsr -/- mice with anophthalmia develop novel lesions, with induction of ectopic retinal-pigmented epithelium in nasal cavities. A comprehensive investigation of apoptotic cell clearance in vivo and in vitro demonstrated that engulfment of apoptotic cells was normal in Ptdsr knockout mice, but Ptdsr-deficient macrophages were impaired in pro- and anti-inflammatory cytokine signaling after stimulation with apoptotic cells or with lipopolysaccharide. Conclusion Ptdsr is essential for the development and differentiation of multiple organs during embryogenesis but not for apoptotic cell removal. Ptdsr may thus have a novel, unexpected developmental function as an important differentiation-promoting gene. Moreover, Ptdsr is not required for apoptotic cell clearance by macrophages but seems to be necessary for the regulation of macrophage cytokine responses. These results clearly contradict the current view that the phosphatidylserine receptor primarily functions in apoptotic cell clearance.

  11. Effect of phosphatidylserine on the basal and GABA-activated Cl- permeation across single nerve membranes from rabbit Deiters' neurons

    Energy Technology Data Exchange (ETDEWEB)

    Rapallino, M.V.; Cupello, A.; Mainardi, P.; Besio, G.; Loeb, C.W. (Centro di Studio per la Neurofisiologia Cerebrale, C.N.R., Genova (Italy))

    1990-06-01

    The permeation of labeled Cl- ions across single plasma membranes from Deiters' neurons has been studied in the presence of various concentrations of phosphatidylserine (PS) on their extracellular side. PS reduces significantly basal Cl- permeation only at 10(-5) M on the membrane exterior. No effect was found at other concentrations. GABA activable 36Cl- permeation is heavily reduced and almost abolished at 10(-11) - 10(-5) M phosphatidylserine. This exogenous phosphatidylserine effect is difficult to interpret in relation to the function of the endogenous phospholipid. However, it may be involved in the epileptogenic effect in vivo of exogenous phosphatidylserine administration to rats.

  12. Amelioration of scopolamine-induced amnesia by phosphatidylserine and curcumin in the day-old chick.

    Science.gov (United States)

    Barber, Teresa A; Edris, Edward M; Levinsky, Paul J; Williams, Justin M; Brouwer, Ari R; Gessay, Shawn A

    2016-09-01

    In the one-trial taste-avoidance task in day-old chicks, acetylcholine receptor activation has been shown to be important for memory formation. Injection of scopolamine produces amnesia, which appears to be very similar in type to that of Alzheimer's disease, which is correlated with low levels of acetylcholine in the brain. Traditional pharmacological treatments of Alzheimer's disease, such as cholinesterase inhibitors and glutamate receptor blockers, improve memory and delay the onset of impairments in memory compared with placebo controls. These agents also ameliorate scopolamine-induced amnesia in the day-old chick trained on the one-trial taste-avoidance task. The present experiments examined the ability of two less traditional treatments for Alzheimer's disease, phosphatidylserine and curcumin, to ameliorate scopolamine-induced amnesia in day-old chicks. The results showed that 37.9 mmol/l phosphatidylserine and 2.7 mmol/l curcumin significantly improved retention in chicks administered scopolamine, whereas lower doses were not effective. Scopolamine did not produce state-dependent learning, indicating that this paradigm in day-old chicks might be a useful one to study the effects of possible Alzheimer's treatments. In addition, chicks administered curcumin or phosphatidylserine showed little avoidance of a bead associated with water reward, indicating that these drugs did not produce response inhibition. The current results extend the findings that some nontraditional memory enhancers can ameliorate memory impairment and support the hypothesis that these treatments might be of benefit in the treatment of Alzheimer's disease. PMID:27388114

  13. The Role of Putative Phosphatidylserine-Interactive Residues of Tissue Factor on Its Coagulant Activity at the Cell Surface.

    Directory of Open Access Journals (Sweden)

    Shabbir A Ansari

    Full Text Available Exposure of phosphatidylserine (PS on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF.

  14. The Role of Putative Phosphatidylserine-Interactive Residues of Tissue Factor on Its Coagulant Activity at the Cell Surface.

    Science.gov (United States)

    Ansari, Shabbir A; Pendurthi, Usha R; Sen, Prosenjit; Rao, L Vijaya Mohan

    2016-01-01

    Exposure of phosphatidylserine (PS) on the outer leaflet of the cell membrane is thought to play a critical role in tissue factor (TF) decryption. Recent molecular dynamics simulation studies suggested that the TF ectodomain may directly interact with PS. To investigate the potential role of TF direct interaction with the cell surface phospholipids on basal TF activity and the enhanced TF activity following the decryption, one or all of the putative PS-interactive residues in the TF ectodomain were mutated and tested for their coagulant activity in cell systems. Out of the 9 selected TF mutants, five of them -TFS160A, TFS161A, TFS162A, TFK165A, and TFD180A- exhibited a similar TF coagulant activity to that of the wild-type TF. The specific activity of three mutants, TFK159A, TFS163A, and TFK166A, was reduced substantially. Mutation of the glycine residue at the position 164 markedly abrogated the TF coagulant activity, resulting in ~90% inhibition. Mutation of all nine lipid binding residues together did not further decrease the activity of TF compared to TFG164A. A similar fold increase in TF activity was observed in wild-type TF and all TF mutants following the treatment of THP-1 cells with either calcium ionomycin or HgCl2, two agents that are commonly used to decrypt TF. Overall, our data show that a few select TF residues that are implicated in interacting with PS contribute to the TF coagulant activity at the cell surface. However, our data also indicate that TF regions outside of the putative lipid binding region may also contribute to PS-dependent decryption of TF. PMID:27348126

  15. Regulation of phospholipid synthesis in phosphatidylserine synthase-deficient (chol) mutants of Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Saccharomyces cerevisiae mutants, chol, are deficient in the synthesis of the phospholipid phosphatidylserine owing to lowered activity of the membrane-associated enzyme phosphatidylserine synthase. These mutants are auxotrophic for ethanolamine or choline and, in the absence of these supplements, cannot synthesize phosphatidylethanolamine or phosphatidylcholine (PC). The authors exploited these characteristics of the chol mutants to examine the regulation of phospholipid metabolism in S. cerevisiae. Macromolecular synthesis and phospholipid metabolism were examined in chol cells starved for ethanolamine. Coupled to the decline in PC biosynthesis was a simultaneous decrease in the overall rate of phospholipid synthesis. In particular, the rate of synthesis of phosphatidylinositol decreased in parallel with the decline in PC biosynthesis. However, under conditions of ethanolamine deprivation in chol cells, the cytoplasmic enzyme inositol-1-phosphate synthase could not be repressed by exogenous inositol, and the endogenous synthesis of the phospholipid precursor inositol appeared to be elevated. The implications of these findings with respect to the coordinated regulation of phospholipid synthesis are discussed

  16. ImmunoPET imaging of phosphatidylserine in pro-apoptotic therapy treated tumor models

    International Nuclear Information System (INIS)

    An immunoPET imaging probe for the detection of phosphatidylserine was developed and tested in animal models of human cancer treated with pro-apoptotic therapy. We hypothesized that the relatively long plasma half-life of a probe based on a full-length antibody coupled with a residualizing radionuclide would be able to catch the wave of drug-induced apoptosis and lead to a specific accumulation in apoptotic tumor tissue. Methods: The imaging probe is based on a 89Zr-labeled monoclonal antibody PGN635 targeting phosphatidylserine. The probe was evaluated pre-clinically in four tumor xenograft models: one studied treatment with paclitaxel to trigger the intrinsic apoptotic pathway, and three others interrogated treatment with an agonistic death-receptor monoclonal antibody to engage the extrinsic apoptotic pathway. Results: High accumulation of 89Zr-PGN635 was observed in treated tumors undergoing apoptosis reaching 30 %ID/g and tumor-to-blood ratios up to 13. The tumor uptake in control groups treated with vehicle or imaged with a non-binding antibody probe was significantly lower. Conclusions: The results demonstrate the ability of 89Zr-PGN635 to image drug-induced apoptosis in animal models and corroborate our hypothesis that radiolabeled antibodies binding to intracellular targets transiently exposed on the cell surface during apoptosis can be employed for detection of tumor response to therapy.

  17. Involvement of complex sphingolipids and phosphatidylserine in endosomal trafficking in yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Tani, Motohiro; Kuge, Osamu

    2012-12-01

    Sphingolipids play critical roles in many physiologically important events in the yeast Saccharomyces cerevisiae. In this study, we found that csg2Δ mutant cells defective in the synthesis of mannosylinositol phosphorylceramide exhibited abnormal intracellular accumulation of an exocytic v-SNARE, Snc1, under phosphatidylserine synthase gene (PSS1)-repressive conditions, although in wild-type cells, Snc1 was known to cycle between plasma membranes and the late Golgi via post-Golgi endosomes. The mislocalized Snc1 was co-localized with an endocytic marker dye, FM4-64, upon labelling for a short time. The abnormal distribution of Snc1 was suppressed by deletion of GYP2 encoding a GTPase-activating protein that negatively regulates endosomal vesicular trafficking, or expression of GTP-restricted form of Ypt32 GTPase. Furthermore, an endocytosis-deficient mutant of Snc1 was localized to plasma membranes in PSS1-repressed csg2Δ mutant cells as well as wild-type cells. Thus, the PSS1-repressed csg2Δ mutant cells were indicated to be defective in the trafficking of Snc1 from post-Golgi endosomes to the late Golgi. In contrast, the vesicular trafficking pathways via pre-vacuolar endosomes in the PSS1-repressed csg2Δ mutant cells seemed to be normal. These results suggested that specific complex sphingolipids and phosphatidylserine are co-ordinately involved in specific vesicular trafficking pathway. PMID:23062277

  18. PHOSPHATIDYLSERINE SYNTHASE1 is Required for Inflorescence Meristem and Organ Development in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Chengwu Liu; Hengfu Yin; Peng Gao; Xiaohe Hu; Jun Yang; Zhongchi Liu; Xiangdong Fu

    2013-01-01

    Phosphatidylserine (PS),a quantitatively minor membrane phospholipid,is involved in many biological processes besides its role in membrane structure.One PS synthesis gene,PHOSPHATIDYLSERINE SYNTHASE1 (PSS1),has been discovered to be required for microspore development in Arabidopsis thaliana L.but how PSS1 affects postembryonic development is still largely unknown.Here,we show that PSS1 is also required for inflorescence meristem and organ development in Arabidopsis.Disruption of PSS1 causes severe dwarfism,smaller lateral organs and reduced size of inflorescence meristem.Morphological and molecular studies suggest that both cell division and cell elongation are affected in the pss1-1 mutant.RNA in situ hybridization and promoter GUS analysis show that expression of both WUSCHEL (WUS) and CLAVATA3 (CLV3) depend on PSS1.Moreover,the defect in meristem maintenance is recovered and the expression of WUS and CLV3 are restored in the pss1-1 clv1-1 double mutant.Both SHOOTSTEMLESS (STM) and BREVIPEDICELLUS (BP) are upregulated,and auxin distribution is disrupted in rosette leaves of pss1-1.However,expression of BP,which is also a regulator of internode development,is lost in the pss1-1 inflorescence stem.Our data suggest that PSS1 plays essential roles in inflorescence meristem maintenance through the WUS-CLV pathway,and in leaf and internode development by differentially regulating the class Ⅰ KNOX genes.

  19. In vivo detection and imaging of phosphatidylserine expression during programmed cell death

    Science.gov (United States)

    Blankenberg, Francis G.; Katsikis, Peter D.; Tait, Jonathan F.; Davis, R. Eric; Naumovski, Louis; Ohtsuki, Katsuichi; Kopiwoda, Susan; Abrams, Michael J.; Darkes, Marilyn; Robbins, Robert C.; Maecker, Holden T.; Strauss, H.W.

    1998-01-01

    One of the earliest events in programmed cell death is the externalization of phosphatidylserine, a membrane phospholipid normally restricted to the inner leaflet of the lipid bilayer. Annexin V, an endogenous human protein with a high affinity for membrane bound phosphatidylserine, can be used in vitro to detect apoptosis before other well described morphologic or nuclear changes associated with programmed cell death. We tested the ability of exogenously administered radiolabeled annexin V to concentrate at sites of apoptotic cell death in vivo. After derivatization with hydrazinonicotinamide, annexin V was radiolabeled with technetium 99m. In vivo localization of technetium 99m hydrazinonicotinamide-annexin V was tested in three models: fuminant hepatic apoptosis induced by anti-Fas antibody injection in BALB/c mice; acute rejection in ACI rats with transplanted heterotopic PVG cardiac allografts; and cyclophosphamide treatment of transplanted 38C13 murine B cell lymphomas. External radionuclide imaging showed a two- to sixfold increase in the uptake of radiolabeled annexin V at sites of apoptosis in all three models. Immunohistochemical staining of cardiac allografts for exogenously administered annexin V revealed intense staining of numerous myocytes at the periphery of mononuclear infiltrates of which only a few demonstrated positive apoptotic nuclei by the terminal deoxynucleotidyltransferase-mediated UTP end labeling method. These results suggest that radiolabeled annexin V can be used in vivo as a noninvasive means to detect and serially image tissues and organs undergoing programmed cell death. PMID:9600968

  20. Purification and characterization of thiols in an arsenic hyperaccumulator under arsenic exposure.

    Science.gov (United States)

    Zhang, Weihua; Cai, Yong

    2003-12-15

    Pteris vittata (Chinese brake fern) is the first reported arsenic hyperaccumulator. To investigate the arsenic tolerance mechanism in this plant, reversed-phase HPLC with postcolumn derivatization was used to analyze the thiols induced under arsenic exposure. A major thiol in the plant leaflets was found to be responsive to arsenic exposure. The arsenic-induced compound was purified on a large scale by combining covalent chromatography and preparative reversed-phase HPLC. About 2 mg of this compound was isolated from 1 kg of fresh leaflets. The purified arsenic-induced compound was characterized using electrospray ionization mass spectrometry. A molecular ion (M + 1) of 540 and fragments were obtained, which indicated that the arsenic-induced thiol was a phytochelatin with two subunits (PC(2)). Compared to the classical methods for purification of phytochelatins, this new method is more specific, simple, and rapid and is suitable for purification of PCs in a large scale as well as sample preparation for mass spectrometry analysis. PMID:14670068

  1. Purification and characterization of thiols in an arsenic hyperaccumulator under arsenic exposure.

    Science.gov (United States)

    Zhang, Weihua; Cai, Yong

    2003-12-15

    Pteris vittata (Chinese brake fern) is the first reported arsenic hyperaccumulator. To investigate the arsenic tolerance mechanism in this plant, reversed-phase HPLC with postcolumn derivatization was used to analyze the thiols induced under arsenic exposure. A major thiol in the plant leaflets was found to be responsive to arsenic exposure. The arsenic-induced compound was purified on a large scale by combining covalent chromatography and preparative reversed-phase HPLC. About 2 mg of this compound was isolated from 1 kg of fresh leaflets. The purified arsenic-induced compound was characterized using electrospray ionization mass spectrometry. A molecular ion (M + 1) of 540 and fragments were obtained, which indicated that the arsenic-induced thiol was a phytochelatin with two subunits (PC(2)). Compared to the classical methods for purification of phytochelatins, this new method is more specific, simple, and rapid and is suitable for purification of PCs in a large scale as well as sample preparation for mass spectrometry analysis.

  2. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  3. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    International Nuclear Information System (INIS)

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  4. Uptake of phosphatidylserine-containing liposomes by liver sinusoidal endothelial cells in the serum-free perfused rat liver

    NARCIS (Netherlands)

    Rothkopf, C; Fahr, A; Fricker, G; Scherphof, GL; Kamps, JAAM

    2005-01-01

    We studied the kinetics of hepatic uptake of liposomes during serum-free recirculating perfusion of rat livers. Liposomes consisted of phosphatidylcholine, cholesterol and phosphatidylserine in a 6:4:0 or a 3:43 molar ratio and were radiolabelled with [H-3]cholesteryl oleyl ether. The negatively cha

  5. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer.

    Science.gov (United States)

    Graham, Douglas K; DeRyckere, Deborah; Davies, Kurtis D; Earp, H Shelton

    2014-12-01

    The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies. Rather than functioning as oncogenic drivers, their induction in tumour cells predominately promotes survival, chemoresistance and motility. The unique mode of maximal activation of this RTK family requires an extracellular lipid–protein complex. For example, the protein ligand, growth arrest-specific protein 6 (GAS6), binds to phosphatidylserine (PtdSer) that is externalized on apoptotic cell membranes, which activates MERTK on macrophages. This triggers engulfment of apoptotic material and subsequent anti-inflammatory macrophage polarization. In tumours, autocrine and paracrine ligands and apoptotic cells are abundant, which provide a survival signal to the tumour cell and favour an anti-inflammatory, immunosuppressive microenvironment. Thus, TAM kinase inhibition could stimulate antitumour immunity, reduce tumour cell survival, enhance chemosensitivity and diminish metastatic potential. PMID:25568918

  6. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer.

    Science.gov (United States)

    Graham, Douglas K; DeRyckere, Deborah; Davies, Kurtis D; Earp, H Shelton

    2014-12-01

    The TYRO3, AXL (also known as UFO) and MERTK (TAM) family of receptor tyrosine kinases (RTKs) are aberrantly expressed in multiple haematological and epithelial malignancies. Rather than functioning as oncogenic drivers, their induction in tumour cells predominately promotes survival, chemoresistance and motility. The unique mode of maximal activation of this RTK family requires an extracellular lipid–protein complex. For example, the protein ligand, growth arrest-specific protein 6 (GAS6), binds to phosphatidylserine (PtdSer) that is externalized on apoptotic cell membranes, which activates MERTK on macrophages. This triggers engulfment of apoptotic material and subsequent anti-inflammatory macrophage polarization. In tumours, autocrine and paracrine ligands and apoptotic cells are abundant, which provide a survival signal to the tumour cell and favour an anti-inflammatory, immunosuppressive microenvironment. Thus, TAM kinase inhibition could stimulate antitumour immunity, reduce tumour cell survival, enhance chemosensitivity and diminish metastatic potential.

  7. Leishmania promastigotes lack phosphatidylserine but bind annexin V upon permeabilization or miltefosine treatment.

    Directory of Open Access Journals (Sweden)

    Adrien Weingärtner

    Full Text Available The protozoan parasite Leishmania is an intracellular pathogen infecting and replicating inside vertebrate host macrophages. A recent model suggests that promastigote and amastigote forms of the parasite mimic mammalian apoptotic cells by exposing phosphatidylserine (PS at the cell surface to trigger their phagocytic uptake into host macrophages. PS presentation at the cell surface is typically analyzed using fluorescence-labeled annexin V. Here we show that Leishmania promastigotes can be stained by fluorescence-labeled annexin V upon permeabilization or miltefosine treatment. However, combined lipid analysis by thin-layer chromatography, mass spectrometry and (31P nuclear magnetic resonance (NMR spectroscopy revealed that Leishmania promastigotes lack any detectable amount of PS. Instead, we identified several other phospholipid classes such phosphatidic acid, phosphatidylethanolamine; phosphatidylglycerol and phosphatidylinositol as candidate lipids enabling annexin V staining.

  8. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  9. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis

    International Nuclear Information System (INIS)

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC50 in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  10. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  11. Microprobe XRF mapping and XAS investigations of the intracellular metabolism of arsenic for understanding arsenic-induced toxicity.

    Science.gov (United States)

    Munro, Kristie L; Mariana, Anna; Klavins, Andrejs I; Foster, Amalanie J; Lai, Barry; Vogt, Stefan; Cai, ZhongHou; Harris, Hugh H; Dillon, Carolyn T

    2008-09-01

    Arsenic (As) is responsible for mass-poisonings worldwide following the ingestion of As-contaminated drinking water. Importantly, however, As toxicity is exploited in the antileukemia drug, Trisenox (As2O3), which successfully cures 65-80% of patients suffering relapsed acute promyelocytic leukemia. In an effort to determine the intracellular organelle and biomolecular targets of As, microprobe X-ray fluorescence (XRF) and X-ray absorption spectroscopy (XAS) analyses were performed on HepG2 cells following their exposure to high doses of arsenite (1 mM) or arsenate (20 mM). Microprobe XRF elemental mapping of thin-sectioned cells showed As accumulation in the euchromatin region of the cell nucleus (following arsenite exposure) synonymous with As targeting of DNA or proteins involved in DNA transcription. X-ray absorption near edge spectroscopy (XANES) and extended X-ray absorption fine structure (EXAFS) analysis of arsenite-treated cells, however, showed the predominance of an As tris-sulfur species, providing increased credence to As interactions with nuclear proteins as a key factor in As-induced toxicity. PMID:18597498

  12. The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study

    OpenAIRE

    Richter Y; Herzog Y; Lifshitz Y; Hayun R; Zchut S

    2013-01-01

    Yael Richter, Yael Herzog, Yael Lifshitz, Rami Hayun, Sigalit ZchutEnzymotec Ltd, K’far Baruch, IsraelObjective: To evaluate the efficacy and safety of soybean-derived phosphatidylserine (SB-PS) (300 mg/day) in improving cognitive performance in elderly with memory complaints, following a short duration of 12 weeks’ SB-PS administration.Methods: SB-PS was administered daily for 12 weeks to 30 elderly volunteers with memory complaints (age range 50–90 years). Cogn...

  13. Protein C Inhibitor (PCI) Binds to Phosphatidylserine Exposing Cells with Implications in the Phagocytosis of Apoptotic Cells and Activated Platelets

    OpenAIRE

    Daniela Rieger; Alice Assinger; Katrin Einfinger; Barbora Sokolikova; Margarethe Geiger

    2014-01-01

    Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marke...

  14. Involvement of Sac1 phosphoinositide phosphatase in the metabolism of phosphatidylserine in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Tani, Motohiro; Kuge, Osamu

    2014-04-01

    Sac1 is a phosphoinositide phosphatase that preferentially dephosphorylates phosphatidylinositol 4-phosphate. Mutation of SAC1 causes not only the accumulation of phosphoinositides but also reduction of the phosphatidylserine (PS) level in the yeast Saccharomyces cerevisiae. In this study, we characterized the mechanism underlying the PS reduction in SAC1-deleted cells. Incorporation of (32) P into PS was significantly delayed in sac1∆ cells. Such a delay was also observed in SAC1- and PS decarboxylase gene-deleted cells, suggesting that the reduction in the PS level is caused by a reduction in the rate of biosynthesis of PS. A reduction in the PS level was also observed with repression of STT4 encoding phosphatidylinositol 4-kinase or deletion of VPS34 encoding phophatidylinositol 3-kinase. However, the combination of mutations of SAC1 and STT4 or VPS34 did not restore the reduced PS level, suggesting that both the synthesis and degradation of phosphoinositides are important for maintenance of the PS level. Finally, we observed an abnormal PS distribution in sac1∆ cells when a specific probe for PS was expressed. Collectively, these results suggested that Sac1 is involved in the maintenance of a normal rate of biosynthesis and distribution of PS.

  15. Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Nagarjun V Konduru

    Full Text Available Broad applications of single-walled carbon nanotubes (SWCNT dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid "eat-me" signal, phosphatidylserine (PS, makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells.

  16. Platelet binding sites for factor VIII in relation to fibrin and phosphatidylserine.

    Science.gov (United States)

    Gilbert, Gary E; Novakovic, Valerie A; Shi, Jialan; Rasmussen, Jan; Pipe, Steven W

    2015-09-01

    Thrombin-stimulated platelets expose very little phosphatidylserine (PS) but express binding sites for factor VIII (fVIII), casting doubt on the role of exposed PS as the determinant of binding sites. We previously reported that fVIII binding sites are increased three- to sixfold when soluble fibrin (SF) binds the αIIbβ3 integrin. This study focuses on the hypothesis that platelet-bound SF is the major source of fVIII binding sites. Less than 10% of fVIII was displaced from thrombin-stimulated platelets by lactadherin, a PS-binding protein, and an fVIII mutant defective in PS-dependent binding retained platelet affinity. Therefore, PS is not the determinant of most binding sites. FVIII bound immobilized SF and paralleled platelet binding in affinity, dependence on separation from von Willebrand factor, and mediation by the C2 domain. SF also enhanced activity of fVIII in the factor Xase complex by two- to fourfold. Monoclonal antibody (mAb) ESH8, against the fVIII C2 domain, inhibited binding of fVIII to SF and platelets but not to PS-containing vesicles. Similarly, mAb ESH4 against the C2 domain, inhibited >90% of platelet-dependent fVIII activity vs 35% of vesicle-supported activity. These results imply that platelet-bound SF is a component of functional fVIII binding sites. PMID:26162408

  17. Phosphatidylserine-positive particles in the apical domain of sensory hair cells

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-rui; Alfred Nuttall

    2006-01-01

    Apical membrane recycling has been proposed to be important for normal hair cell function. The current study reports an in vitro work that demonstrates the presence of phosphatidylserine (PS) and PS-positive vesicles labeled by Annexin V in the apical portion of hair cells. The following characteristics of the PS-positive vesicles were noticed using scanning confocal fluorescence microscopy: (1) variable sizes around 200 nm; (2)variable distribution patterns (either uniformly along individual stereocilia in the hair bundle or irregular) in the stereocilia from cell to cell; (3) variable sizes and numbers at locations along the border of the cuticular plate (CP),with a large number of them located at the vestigal kinocilial location; (4) motility with some of the vesicles during the observation period; (5) increase in PS labeling and the number of PS-positive vesicles after loud sound stimulation; and (6) decreased PS labeling and PS-positive vesicle numbers following treatment with LY-294002, a PI3 -kinase inhibitor. These results suggest that the presence of PS-positive vesicles at the apical area of hair cells may be indicative of vesicle shedding or transportation of a protein or rafts.

  18. The effects of phosphatidylserine on endocrine response to moderate intensity exercise

    Directory of Open Access Journals (Sweden)

    Purpura Martin

    2008-07-01

    Full Text Available Abstract Background Previous research has indicated that phosphatidylserine (PS supplementation has the potential to attenuate the serum cortisol response to acute exercise stress. Equivocal findings suggest that this effect might be dose dependent. This study aimed to examine the influence of short-term supplementation with a moderate dose of PS (600 mg per day on plasma concentrations of cortisol, lactate, growth hormone and testosterone before, during, and following moderate intensity exercise in healthy males. Methods 10 healthy male subjects participated in the study. Each subject was assigned to ingest 600 mg PS or placebo per day for 10 days using a double-blind, placebo-controlled, crossover design. Serial venous blood samples were taken at rest, after a 15 minute moderate intensity exercise protocol on a cycle ergometer that consisted of five 3-minute incremental stages beginning at 65% and ending at 85% VO2 max, and during a 65 minute passive recovery. Plasma samples were assessed for cortisol, growth hormone, testosterone, lactate and testosterone to cortisol ratio for treatment (PS or placebo. Results Mean peak cortisol concentrations and area under the curve (AUC were lower following PS (39 ± 1% and 35 ± 0%, respectively when compared to placebo (p Conclusion The findings suggest that PS is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. PS supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels.

  19. Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

    Science.gov (United States)

    Peterson, Lisa K; Willis, Rohan; Harris, E Nigel; Branch, Ware D; Tebo, Anne E

    2016-01-01

    Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts. PMID:26975968

  20. Phosphatidylserine enhances IKBKAP transcription by activating the MAPK/ERK signaling pathway.

    Science.gov (United States)

    Donyo, Maya; Hollander, Dror; Abramovitch, Ziv; Naftelberg, Shiran; Ast, Gil

    2016-04-01

    Familial dysautonomia (FD) is a genetic disorder manifested due to abnormal development and progressive degeneration of the sensory and autonomic nervous system. FD is caused by a point mutation in the IKBKAP gene encoding the IKAP protein, resulting in decreased protein levels. A promising potential treatment for FD is phosphatidylserine (PS); however, the manner by which PS elevates IKAP levels has yet to be identified. Analysis of ChIP-seq results of the IKBKAP promoter region revealed binding of the transcription factors CREB and ELK1, which are regulated by the mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) signaling pathway. We show that PS treatment enhanced ERK phosphorylation in cells derived from FD patients. ERK activation resulted in elevated IKBKAP transcription and IKAP protein levels, whereas pretreatment with the MAPK inhibitor U0126 blocked elevation of the IKAP protein level. Overexpression of either ELK1 or CREB activated the IKBKAP promoter, whereas downregulation of these transcription factors resulted in a decrease of the IKAP protein. Additionally, we show that PS improves cell migration, known to be enhanced by MAPK/ERK activation and abrogated in FD cells. In conclusion, our results demonstrate that PS activates the MAPK/ERK signaling pathway, resulting in activation of transcription factors that bind the promoter region of IKBKAP and thus enhancing its transcription. Therefore, compounds that activate the MAPK/ERK signaling pathway could constitute potential treatments for FD. PMID:26769675

  1. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  2. Depletion of Bcl-2 by an antisense oligonucleotide induces apoptosis accompanied by oxidation and externalization of phosphatidylserine in NCI-H226 lung carcinoma cells.

    Science.gov (United States)

    Koty, Patrick P; Tyurina, Yulia Y; Tyurin, Vladimir A; Li, Shang-Xi; Kagan, Valerian E

    2002-01-01

    Oxidant-induced apoptosis involves oxidation of many different and essential molecules including phospholipids. As a result of this non-specific oxidation, any signaling role of a particular phospholipid-class of molecules is difficult to elucidate. To determine whether preferential oxidation of phosphatidylserine (PS) is an early event in apoptotic signaling related to PS externalization and is independent of direct oxidant exposure, we chose a genetic-based induction of apoptosis. Apoptosis was induced in the lung cancer cell line NCI-H226 by decreasing the amount of Bcl-2 protein expression by preventing the translation of bcl-2 mRNA using an antisense bcl-2 oligonucleotide. Peroxidation of phospholipids was assayed using a fluorescent technique based on metabolic integration of an oxidation-sensitive and fluorescent fatty acid, cis-parinaric acid (PnA), into cellular phospholipids and subsequent HPLC separation of cis-PnA-labeled phospholipids. We found a decrease in Bcl-2 was associated with a selective oxidation of PS in a sub-population of the cells with externalized PS. No significant difference in oxidation of cis-PnA-labeled phospholipids was observed in cells treated with medium alone or a nonsense oligonucleotide. Treatment with either nonsensc or antisense bcl-2 oligonucleotides was not associated with changes in the pattern of individual phospholipid classes as determined by HPTLC. These metabolic and topographical changes in PS arrangement in plasma membrane appear to be early responses to antisense bcl-2 exposure that trigger a PS-dependent apoptotic signaling pathway. This observed externalization of PS may facilitate the 'labeling' of apoptotic cells for recognition by macrophage scavenger receptors and subsequent phagocytic clearance. PMID:12162425

  3. Antimonial drugs entrapped into phosphatidylserine liposomes: physicochemical evaluation and antileishmanial activity

    Directory of Open Access Journals (Sweden)

    Samanta Etel Treiger Borborema

    2016-04-01

    Full Text Available Abstract: INTRODUCTION: Leishmaniasis is a disease caused by the protozoan Leishmania that resides mainly in mononuclear phagocytic system tissues. Pentavalent antimonials are the main treatment option, although these drugs have toxic side effects and high resistance rates. A potentially alternative and more effective therapeutic strategy is to use liposomes as carriers of the antileishmanial agents. The aims of this study were to develop antimonial drugs entrapped into phosphatidylserine liposomes and to analyze their biological and physicochemical characteristics. METHODS: Liposomes containing meglumine antimoniate (MA or pentavalent antimony salt (Sb were obtained through filter extrusion (FEL and characterized by transmission electron microscopy. Promastigotes of Leishmania infantum were incubated with the drugs and the viability was determined with a tetrazolium dye (MTT assay. The effects of these drugs against intracellular amastigotes were also evaluated by optical microscopy, and mammalian cytotoxicity was determined by an MTT assay. RESULTS: Liposomes had an average diameter of 162nm. MA-FEL showed inhibitory activity against intracellular L. infantum amastigotes, with a 50% inhibitory concentration (IC50 of 0.9μg/mL, whereas that of MA was 60μg/mL. Sb-FEL showed an IC50 value of 0.2μg/mL, whereas that of free Sb was 9μg/mL. MA-FEL and Sb-FEL had strong in vitro activity that was 63-fold and 39-fold more effective than their respective free drugs. MA-FEL tested at a ten-times higher concentration than Sb-FEL did not show cytotoxicity to mammalian cells, resulting in a higher selectivity index. CONCLUSIONS: Antimonial drug-containing liposomes are more effective against Leishmania-infected macrophages than the non-liposomal drugs.

  4. Phosphatidylserine translocation to the mitochondrion is an ATP-dependent process in permeabilized animal cells

    International Nuclear Information System (INIS)

    Chinese hamster ovary (CHO-K1) cells were pulse labeled with [3H]serine, and the synthesis of phosphatidyl[3H]ethanolamine from phosphatidyl[3H]serine during the subsequent chase was used as a measure of lipid translocation to the mitochondria. When the CHO-K1 cells were pulse labeled and subsequently permeabilized with 50 μg of saponin per ml, there was no significant turnover of nascent phosphatidyl[3H]serine to form phosphatidyl[3H]ethanolamine during an ensuring chase. Supplementation of the permeabilized cells with 2 mM ATP resulted in significant phosphatidyl[3H]ethanolamine synthesis (83% of that found in intact cells) from phosphatidyl[3H]serine during a subsequent 2-hr chase. Phosphatidyl[3H]ethanolamine synthesis essentially ceased after 2 hr in the permeabilized cells. The translocation-dependent synthesis of phosphatidyl[3H]ethanolamine was a saturable process with respect to ATP concentration in permeabilized cells. The conversion of phosphatidyl[3H]serine to phosphatidyl[3H]ethanolamine did not occur in saponin-treated cultures supplemented with 2 mM AMP, 2 mM 5'-adenylyl imidodiphosphate, or apyrase plus 2 mM ATP. ATP was the most effective nucleotide, but the addition of GTP, CTP, UTP, and ADP also supported the translocation-dependent synthesis of phosphatidyl[3H]ethanolamine albeit to a lesser extent. These data provide evidence that the interorganelle translocation of phosphatidylserine requires ATP and is largely independent of soluble cytosolic proteins

  5. The effects of phosphatidylserine and omega-3 fatty acid-containing supplement on late life depression

    Directory of Open Access Journals (Sweden)

    Teruhisa Komori

    2015-04-01

    Full Text Available Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega-3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17 and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non-responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal

  6. Enhanced Eryptosis Following Gramicidin Exposure

    Directory of Open Access Journals (Sweden)

    Abaid Malik

    2015-04-01

    Full Text Available The peptide antibiotic and ionophore gramicidin has previously been shown to trigger apoptosis of nucleated cells. In analogy to apoptosis, the suicidal death of erythrocytes or eryptosis involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i, and ceramide. The present study explored, whether gramicidin triggers eryptosis. To this end phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, red blood cell distribution width (RDW from electronic particle counting, reactive oxidant species (ROS from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA fluorescence, [Ca2+]i from Fluo3- and Fluo4 fluorescence, and ceramide abundance from binding of specific antibodies. As a result, a 24 h exposure of human erythrocytes to gramicidin significantly increased the percentage of annexin-V-binding cells (≥1 µg/mL, forward scatter (≥0.5 µg/mL and hemolysis. Gramicidin enhanced ROS activity, [Ca2+]i and ceramide abundance at the erythrocyte surface. The stimulation of annexin-V-binding by gramicidin was significantly blunted but not abolished by removal of extracellular Ca2+. In conclusion, gramicidin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance. Despite increase of [Ca2+]i, gramicidin increases cell volume and slightly reduces RWD.

  7. Enhanced eryptosis following gramicidin exposure.

    Science.gov (United States)

    Malik, Abaid; Bissinger, Rosi; Liu, Guoxing; Liu, Guilai; Lang, Florian

    2015-05-01

    The peptide antibiotic and ionophore gramicidin has previously been shown to trigger apoptosis of nucleated cells. In analogy to apoptosis, the suicidal death of erythrocytes or eryptosis involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether gramicidin triggers eryptosis. To this end phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, red blood cell distribution width (RDW) from electronic particle counting, reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca2+]i from Fluo3- and Fluo4 fluorescence, and ceramide abundance from binding of specific antibodies. As a result, a 24 h exposure of human erythrocytes to gramicidin significantly increased the percentage of annexin-V-binding cells (≥1 µg/mL), forward scatter (≥0.5 µg/mL) and hemolysis. Gramicidin enhanced ROS activity, [Ca2+]i and ceramide abundance at the erythrocyte surface. The stimulation of annexin-V-binding by gramicidin was significantly blunted but not abolished by removal of extracellular Ca2+. In conclusion, gramicidin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance. Despite increase of [Ca2+]i, gramicidin increases cell volume and slightly reduces RWD. PMID:25915718

  8. Mercury-Induced Externalization of Phosphatidylserine and Caspase 3 Activation in Human Liver Carcinoma (HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2006-03-01

    Full Text Available Apoptosis arises from the active initiation and propagation of a series of highly orchestrated specific biochemical events leading to the demise of the cell. It is a normal physiological process, which occurs during embryonic development as well as in the maintenance of tissue homeostasis. Diverse groups of molecules are involved in the apoptosis pathway and it functions as a mechanism to eliminate unwanted or irreparably damaged cells. However, inappropriate induction of apoptosis by environmental agents has broad ranging pathologic implications and has been associated with several diseases including cancer. The toxicity of several heavy metals such as mercury has been attributed to their high affinity to sulfhydryl groups of proteins and enzymes, and their ability to disrupt cell cycle progression and/or apoptosis in various tissues. The aim of this study was to assess the potential for mercury to induce early and late-stage apoptosis in human liver carcinoma (HepG2 cells. The Annexin-V and Caspase 3 assays were performed by flow cytometric analysis to determine the extent of phosphatidylserine externalization and Caspase 3 activation in mercury-treated HepG2 cells. Cells were exposed to mercury for 10 and 48 hours respectively at doses of 0, 1, 2, and 3 μg/mL based on previous cytotoxicity results in our laboratory indicating an LD50 of 3.5 ± 0.6 μg/mL for mercury in HepG2 cells. The study data indicated a dose response relationship between mercury exposure and the degree of early and late-stage apoptosis in HepG2 cells. The percentages of cells undergoing early apoptosis were 0.03 ± 0.03%, 5.19 ± 0.04%, 6.36 ± 0.04%, and 8.84 ± 0.02% for 0, 1, 2, and 3 μg/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. The percentages of Caspase 3 positive cells undergoing late apoptosis were 3.58 ± 0.03%, 17.06 ± 0

  9. The effect of soybean-derived phosphatidylserine on cognitive performance in elderly with subjective memory complaints: a pilot study

    Directory of Open Access Journals (Sweden)

    Richter Y

    2013-05-01

    Full Text Available Yael Richter, Yael Herzog, Yael Lifshitz, Rami Hayun, Sigalit ZchutEnzymotec Ltd, K’far Baruch, IsraelObjective: To evaluate the efficacy and safety of soybean-derived phosphatidylserine (SB-PS (300 mg/day in improving cognitive performance in elderly with memory complaints, following a short duration of 12 weeks’ SB-PS administration.Methods: SB-PS was administered daily for 12 weeks to 30 elderly volunteers with memory complaints (age range 50–90 years. Cognitive performance was determined by a computerized test battery and by the Rey Auditory Verbal Learning Test (Rey-AVLT. Physical examination and blood safety parameters were part of the extensive safety analysis of PS that was performed.Results: The computerized test results showed that SB-PS supplementation significantly increased the following cognitive parameters: memory recognition (P = 0.004, memory recall (P = 0.006, executive functions (P = 0.004, and mental flexibility (P = 0.01. The Rey-AVLT indicated that, following SB-PS administration, total learning and immediate recall improved significantly (P = 0.013 and P = 0.007, respectively. Unexpected results from the safety tests suggested that SB-PS significantly reduces both systolic (P = 0.043 and diastolic (P = 0.003 blood pressure. SB-PS consumption was well tolerated and no serious adverse events were reported during the study.Conclusion: This exploratory study demonstrates that SB-PS may have favorable effects on cognitive function in elderly with memory complaints. In addition, the study suggests that SB-PS is safe for human consumption and may serve as a safe alternative to phosphatidylserine extracted from bovine cortex. These results encourage further extended studies in order to establish the safety and efficacy of SB-PS treatment.Keywords: learning, AAMI, memory, cognitive, phosphatidylserine

  10. The linoleic acid derivative DCP-LA selectively activates PKC-epsilon, possibly binding to the phosphatidylserine binding site.

    Science.gov (United States)

    Kanno, Takeshi; Yamamoto, Hideyuki; Yaguchi, Takahiro; Hi, Rika; Mukasa, Takeshi; Fujikawa, Hirokazu; Nagata, Tetsu; Yamamoto, Satoshi; Tanaka, Akito; Nishizaki, Tomoyuki

    2006-06-01

    This study examined the effect of 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a newly synthesized linoleic acid derivative with cyclopropane rings instead of cis-double bonds, on protein kinase C (PKC) activity. In the in situ PKC assay with reverse-phase high-performance liquid chromatography, DCP-LA significantly activated PKC in PC-12 cells in a concentration-dependent (10 nM-100 microM) manner, with the maximal effect at 100 nM, and the DCP-LA effect was blocked by GF109203X, a PKC inhibitor, or a selective inhibitor peptide of the novel PKC isozyme PKC-epsilon. Furthermore, DCP-LA activated PKC in HEK-293 cells that was inhibited by the small, interfering RNA against PKC-epsilon. In the cell-free PKC assay, of the nine isozymes examined here, DCP-LA most strongly activated PKC-epsilon, with >7-fold potency over other PKC isozymes, in the absence of dioleoyl-phosphatidylserine and 1,2-dioleoyl-sn-glycerol; instead, the DCP-LA action was inhibited by dioleoyl-phosphatidylserine. DCP-LA also activated PKC-gamma, a conventional PKC, but to a much lesser extent compared with that for PKC-epsilon, by a mechanism distinct from PKC-epsilon activation. Thus, DCP-LA serves as a selective activator of PKC-epsilon, possibly by binding to the phosphatidylserine binding site on PKC-epsilon. These results may provide fresh insight into lipid signaling in PKC activation.

  11. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Poulsen, Lisbeth Rosager

      The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation...

  12. Activation of NADPH-recycling systems in leaves and roots of Arabidopsis thaliana under arsenic-induced stress conditions is accelerated by knock-out of Nudix hydrolase 19 (AtNUDX19) gene.

    Science.gov (United States)

    Corpas, Francisco J; Aguayo-Trinidad, Simeón; Ogawa, Takahisa; Yoshimura, Kazuya; Shigeoka, Shigeru

    2016-03-15

    NADPH is an important cofactor in cell growth, proliferation and detoxification. Arabidopsis thaliana Nudix hydrolase 19 (AtNUDX19) belongs to a family of proteins defined by the conserved amino-acid sequence GX5-EX7REUXEEXGU which has the capacity to hydrolyze NADPH as a physiological substrate in vivo. Given the importance of NADPH in the cellular redox homeostasis of plants, the present study compares the responses of the main NADPH-recycling systems including NADP-isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and NADP-malic enzyme (ME) in the leaves and roots of Arabidopsis wild-type (Wt) and knock-out (KO) AtNUDX19 mutant (Atnudx19) plants under physiological and arsenic-induced stress conditions. Two major features were observed in the behavior of the main NADPH-recycling systems: (i) under optimal conditions in both organs, the levels of these activities were higher in nudx19 mutants than in Wt plants; and, (ii) under 500μM AsV conditions, these activities increase, especially in nudx19 mutant plants. Moreover, G6PDH activity in roots was the most affected enzyme in both Wt and nudx19 mutant plants, with a 4.6-fold and 5.0-fold increase, respectively. In summary, the data reveals a connection between the absence of chloroplastic AtNUDX19 and the rise in all NADP-dehydrogenase activities under physiological and arsenic-induced stress conditions, particularly in roots. This suggests that AtNUDX19 could be a key factor in modulating the NADPH pool in plants and consequently in redox homeostasis. PMID:26878367

  13. INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts.

    Science.gov (United States)

    Chung, Jeeyun; Torta, Federico; Masai, Kaori; Lucast, Louise; Czapla, Heather; Tanner, Lukas B; Narayanaswamy, Pradeep; Wenk, Markus R; Nakatsu, Fubito; De Camilli, Pietro

    2015-07-24

    Lipid transfer between cell membrane bilayers at contacts between the endoplasmic reticulum (ER) and other membranes help to maintain membrane lipid homeostasis. We found that two similar ER integral membrane proteins, oxysterol-binding protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma membrane (PM) via the interaction of their pleckstrin homology domains with phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged these lipids between bilayers. Gain- and loss-of-function experiments showed that ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM, thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P levels and selectively enrich PS in the PM.

  14. Gem1 and ERMES Do Not Directly Affect Phosphatidylserine Transport from ER to Mitochondria or Mitochondrial Inheritance

    DEFF Research Database (Denmark)

    Nguyen, Tammy T; Lewandowska, Agnieszka; Choi, Jae-Yeon;

    2012-01-01

    In yeast, a protein complex termed the ER-Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin......, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no direct role in the transport of phosphatidylserine (PS) from...... the ER to mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE conversion is not affected in ERMES or gem1 mutants. In addition, we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against...

  15. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    Directory of Open Access Journals (Sweden)

    Ling-I Hsu

    2015-01-01

    Full Text Available Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1, reactive oxygen species (ROS related metabolic genes (NQO1, EPHX1, and HO-1, and DNA repair genes (XRCC1, XPD, hOGG1, and ATM together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR and 95% confidence interval (CI using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.. However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

  16. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  17. Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations.

    Science.gov (United States)

    Zhao, Zhenjun; Johnson, Michael S; Chen, Biyi; Grace, Michael; Ukath, Jaysree; Lee, Vivienne S; McRobb, Lucinda S; Sedger, Lisa M; Stoodley, Marcus A

    2016-06-01

    OBJECT Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. METHODS An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. RESULTS Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. CONCLUSIONS Ionizing radiation

  18. Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study

    OpenAIRE

    Zanotta D; Puricelli S; Bonoldi G

    2014-01-01

    Danilo Zanotta, Silvana Puricelli, Guido Bonoldi Unità Operativa di Medicina 2, Ospedale di Circolo di Busto Arsizio, Varese, Italy Abstract: A prospective cohort, noncomparative, multicenter trial was conducted to explore the potential of a phytotherapeutic compound, available as a dietary supplement and containing extracts of Bacopa monnieri and Haematococcus pluvialis (astaxanthin) plus phosphatidylserine and vitamin E, in improving cognition in subjects diagnosed with mild cog...

  19. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine

    OpenAIRE

    Araujo, Joseph A.; Landsberg, Gary M.; Milgram, Norton W.; Miolo, Alda

    2008-01-01

    Aged dogs demonstrate cognitive decline that is linked to brain aging. The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles. Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects w...

  20. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  1. MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

    2011-11-15

    Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

  2. Research advance in extraction and separation of phosphatidylserine%磷脂酰丝氨酸的提取分离研究进展

    Institute of Scientific and Technical Information of China (English)

    李阅兵; 刘承初; 谢晶; 李应森; 李家乐; 陈苏

    2011-01-01

    Phosphatidylserine, as the nootropics substances of human brain, has been concerned widely.The extraction and purification methods of phosphatidylserine were introduced.The extraction methods included chloroform -methanol method, tert -butyl methyl ether method and ethyl acetate -ethanol method.Purification methods included thin layer chromatography,column chromatography and HPLC.The extraction technics of phosphatidylserine were complicated, and abundant organic solvent was consumed, so the optimization of them should be enhanced.%磷脂酰丝氨酸作为人类大脑的益智物质,已经得到了广泛关注.主要对磷脂酰丝氨酸的提取和纯化方法进行介绍.提取方法包括氛仿-甲醉法、叔丁基甲醚法、乙酸乙酯-乙醇法等.纯化的方法涉及薄层色谱法、柱色谱法、高效液相色谱法等.磷脂酰丝氨酸提取工艺复杂,需使用大量有机溶剂,今后需加强提取工艺的优化.

  3. Protein C inhibitor (PCI binds to phosphatidylserine exposing cells with implications in the phagocytosis of apoptotic cells and activated platelets.

    Directory of Open Access Journals (Sweden)

    Daniela Rieger

    Full Text Available Protein C Inhibitor (PCI is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10-30% of cells. PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal.

  4. p85α recruitment by the CD300f phosphatidylserine receptor mediates apoptotic cell clearance required for autoimmunity suppression

    Science.gov (United States)

    Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Morse, Herbert C., III; Qi, Chen-Feng; Krzewski, Konrad; Coligan, John E.

    2014-01-01

    Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcγRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.

  5. Comparative Study of EPA-enriched Phosphatidylcholine and EPA-enriched Phosphatidylserine on Lipid Metabolism in Mice.

    Science.gov (United States)

    Ding, Lin; Wang, Dan; Zhou, Miaomiao; Du, Lei; Xu, Jie; Xue, Changhu; Wang, Yuming

    2016-07-01

    Recent studies have shown that EPA enriched PLs have beneficial effects on lipid metabolism. Our previous study has demonstrated that the anti-obesity and hypolipidemic effects of EPA-PL were superior to DHA-PL. In the present study, we comparatively evaluated the effects of EPA-enriched phosphatidylcholine (EPA-PC) and EPA-enriched phosphatidylserine (EPA-PS) on lipid metabolism in mice. Both 2% dietary EPA-PC and EPA-PS significantly improved serum and hepatic lipid levels in mice. The HDL-c level in mice on EPA-PC diet was significantly higher than the other two groups. The level of DHA in hepatic TG and PL were significantly increased in both EPA-PC and EPA-PS fed groups (98.3 and 117.8%, respectively; p DHA in EPA-PS group was significantly higher than the EPA-PC group. EPA-PC and EPA-PS suppressed hepatic SREBP-1c mediated lipogenesis and activated PPARα mediated fatty acid β-oxidation in the liver. These data are the first to indicate that EPA-PS has beneficial effects on lipid metabolism. PMID:27321119

  6. The influence of dipalmitoyl phosphatidylserine on phase behaviour of and cellular response to lyotropic liquid crystalline dispersions.

    Science.gov (United States)

    Shen, Hsin-Hui; Crowston, Jonathan G; Huber, Florian; Saubern, Simon; McLean, Keith M; Hartley, Patrick G

    2010-12-01

    Lyotropic liquid crystalline nanoparticles (cubosomes) have the potential to act as amphiphilic scaffolds for the presentation of lipids and subsequent application in, for example, bioseparations and therapeutic delivery. In this work we have formulated lyotropic liquid crystalline systems based on the synthetic amphiphile 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane (phytantriol) and containing the lipid dipalmitoyl phosphatidylserine (DPPS). We have prepared a range of DPPS-containing phytantriol cubosome formulations and characterized them using Small Angle X-ray Scattering and Cryo-transmission electron microscopy. These techniques show that increased DPPS content induces marked changes in lyotropic liquid crystalline phase behaviour, characterized by changes in crystallographic dimensions and increases in vesicle content. Furthermore, in vitro cell culture studies indicate that these changes correlate with lipid/surfactant cellular uptake and cytotoxicity. A model cell membrane based on a surface supported phospholipid bilayer was used to gain insights into cubosome-bilayer interactions using Quartz Crystal Microgravimetry. The data show that mass uptake at the supported bilayer increased with DPPS content. We propose that the cytotoxicity of the DPPS-containing dispersions results from changes in lipid/surfactant phase behaviour and the preferential attachment and fusion of vesicles at the cell membrane.

  7. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

    2014-11-15

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  8. Mutational analysis of Raf-1 cysteine rich domain: requirement for a cluster of basic aminoacids for interaction with phosphatidylserine.

    Science.gov (United States)

    Improta-Brears, T; Ghosh, S; Bell, R M

    1999-08-01

    Activation of Raf-1 kinase is preceded by a translocation of Raf-1 to the plasma membrane in response to external stimuli. The membrane localization of Raf-1 is facilitated through its interaction with activated Ras and with membrane phospholipids. Previous evidence suggests that the interaction of Raf-1 with Ras is mediated by two distinct domains within the N-terminal region of Raf-1 comprising amino acid residues 51-131 and residues 139-184, the latter of which codes for a zinc containing cysteine-rich domain. The cysteine-rich domain of Raf-1 is also reported to associate with other proteins, such as 14-3-3, and for selectively binding acidic phospholipids, particularly phosphatidylserine (PS). In the present study, we have investigated the consequences of progressive deletions and point mutations within the cysteine-rich domain of Raf-1 on its ability to bind PS. A reduced interaction with PS was observed in vitro for all deletion mutants of Raf-1 expressed either as full-length proteins or as fragments containing the isolated cysteine-rich domain. In particular, the cluster of basic amino acids R143, K144, and K148 appeared to be critical for interaction with PS, since substitution of all three residues to alanine resulted in a protein that failed to interact with liposomes enriched for PS. Expression of Raf-1 in vivo, containing point mutations in the cysteine-rich domain resulted in a truncated polypeptide that lacked both the Ras and PS binding sites and could no longer translocate to the plasma membrane upon serum stimulation. These results indicate that the basic residues 143, 144 and 148 in the anterior half of Raf-1 cysteine-rich domain play a role in the association with the lipid bilayer and possibly in protein stability, therefore they might contribute to Raf-1 localization and subsequent activation.

  9. Taxol induces concentration-dependent phosphatidylserine (PS) externalization and cell cycle arrest in ASTC-a-1 cells

    Science.gov (United States)

    Guo, Wen-jing; Chen, Tong-sheng

    2010-02-01

    Taxol (Paclitaxel) is an important natural product for the treatment of solid tumors. Different concentrations of taxol can trigger distinct effects on both the cellular microtubule network and biochemical pathways. Apoptosis induced by low concentrations (5-30 nM) of taxol was associated with mitotic arrest, alteration of microtubule dynamics and/or G2/M cell cycle arrest, whereas high concentrations of this drug (0.2-30 μM) caused significant microtubule damage, and was found recently to induce cytoplasm vacuolization in human lung adenocarcinoma (ASTC-a-1) cells. In present study, cell counting kit (CCK-8) assay, confocal microscope, and flow cytometry analysis were used to analyze the cell death form induced by 35 nM and 70 μM of taxol respectively in human lung adenocarcinoma (ASTC-a-1) cells. After treatment of 35 nM taxol for 48 h, the OD450 value was 0.80, and 35 nM taxol was found to induce dominantly cell death in apoptotic pathway such as phosphatidylserine (PS) externalization, G2/M phase arrest after treatment for 24 h, and nuclear fragmentation after treatment for 48 h. After 70 μM taxol treated the cell for 24 h, the OD450 value was 1.01, and 70 μM taxol induced cytoplasm vacuolization programmed cell death (PCD) and G2/M phase as well as the polyploidy phase arrest in paraptotic-like cell death. These findings imply that the regulated signaling pathway of cell death induced by taxol is dependent on taxol concentration in ASTC-a-1 cells.

  10. Calpain-controlled detachment of major glycoproteins from the cytoskeleton regulates adhesive properties of activated phosphatidylserine-positive platelets.

    Science.gov (United States)

    Artemenko, Elena O; Yakimenko, Alena O; Pichugin, Alexey V; Ataullakhanov, Fazly I; Panteleev, Mikhail A

    2016-02-15

    In resting platelets, adhesive membrane glycoproteins are attached to the cytoskeleton. On strong activation, phosphatidylserine(PS)-positive and -negative platelet subpopulations are formed. Platelet activation is accompanied by cytoskeletal rearrangement, although the glycoprotein attachment status in these two subpopulations is not clear. We developed a new, flow cytometry-based, single-cell approach to investigate attachment of membrane glycoproteins to the cytoskeleton in cell subpopulations. In PS-negative platelets, adhesive glycoproteins integrin αIIbβ3, glycoprotein Ib and, as shown for the first time, P-selectin were associated with the cytoskeleton. In contrast, this attachment was disrupted in PS-positive platelets; it was retained to some extent only in the small convex regions or 'caps'. It correlated with the degradation of talin and filamin observed only in PS-positive platelets. Calpain inhibitors essentially prevented the disruption of membrane glycoprotein attachment in PS-positive platelets, as well as talin and filamin degradation. With the suggestion that detachment of glycoproteins from the cytoskeleton may affect platelet adhesive properties, we investigated the ability of PS-positive platelets to resist shear-induced breakaway from the immobilized fibrinogen. Shear rates of 500/s caused PS-positive platelet breakaway, but their adhesion stability increased more than 10-fold after pretreatment of the platelets with calpain inhibitor. In contrast, the ability of PS-positive platelets to adhere to immobilized von Willebrand's factor at 100/s was low, but this was not affected by the preincubation of platelets with a calpain inhibitor. Our data suggest that calpain-controlled detachment of membrane glycoproteins is a new mechanism that is responsible for the loss of ability of the procoagulant platelets to resist detachment from thrombi by high shear stress.

  11. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bei [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang 110001 (China); Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2012-11-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs{sup 3+}) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs{sup 3+} exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs{sup 3+} and monomethylarsonous acid (MMA{sup 3+})-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs{sup 3+}-induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs{sup 3+}. The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs{sup 3+} in β-cells. ► Deficiency of Nrf2 in

  12. Protective role of taurine against arsenic-induced mitochondria-dependent hepatic apoptosis via the inhibition of PKCdelta-JNK pathway.

    Directory of Open Access Journals (Sweden)

    Joydeep Das

    Full Text Available BACKGROUND: Oxidative stress-mediated hepatotoxic effect of arsenic (As is mainly due to the depletion of glutathione (GSH in liver. Taurine, on the other hand, enhances intracellular production of GSH. Little is known about the mechanism of the beneficial role of taurine in As-induced hepatic pathophysiology. Therefore, in the present study we investigated its beneficial role in As-induced hepatic cell death via mitochondria-mediated pathway. METHODOLOGY/PRINCIPAL FINDINGS: Rats were exposed to NaAsO(2 (2 mg/kg body weight for 6 months and the hepatic tissue was used for oxidative stress measurements. In addition, the pathophysiologic effect of NaAsO(2 (10 microM on hepatocytes was evaluated by determining cell viability, mitochondrial membrane potential and ROS generation. As caused mitochondrial injury by increased oxidative stress and reciprocal regulation of Bcl-2, Bcl-xL/Bad, Bax, Bim in association with increased level of Apaf-1, activation of caspase 9/3, cleavage of PARP protein and ultimately led to apoptotic cell death. In addition, As markedly increased JNK and p38 phosphorylation with minimal disturbance of ERK. Pre-exposure of hepatocytes to a JNK inhibitor SP600125 prevented As-induced caspase-3 activation, ROS production and loss in cell viability. Pre-exposure of hepatocytes to a p38 inhibitor SB2035, on the other hand, had practically no effect on these events. Besides, As activated PKCdelta and pre-treatment of hepatocytes with its inhibitor, rottlerin, suppressed the activation of JNK indicating that PKCdelta is involved in As-induced JNK activation and mitochondrial dependent apoptosis. Oral administration of taurine (50 mg/kg body weight for 2 weeks both pre and post to NaAsO(2 exposure or incubation of the hepatocytes with taurine (25 mM were found to be effective in counteracting As-induced oxidative stress and apoptosis. CONCLUSIONS/SIGNIFICANCE: Results indicate that taurine treatment improved As-induced hepatic damages

  13. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  14. Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses.

    Science.gov (United States)

    Choudhury, Sreetama; Gupta, Payal; Ghosh, Sayan; Mukherjee, Sudeshna; Chakraborty, Priyanka; Chatterji, Urmi; Chattopadhyay, Sreya

    2016-05-16

    Arsenic contamination of drinking water is a matter of global concern. Arsenic intake impairs immune responses and leads to a variety of pathological conditions including cancer. In order to understand the intricate tuning of immune responses elicited by chronic exposure to arsenic, a mouse model was established by subjecting mice to different environmentally relevant concentrations of arsenic in drinking water for 30days. Detailed study of the thymus, a primary immune organ, revealed arsenic-mediated tissue damage in both histological specimens and scanning electron micrographs. Analysis of molecular markers of apoptosis by Western blot revealed a dose-dependent activation of the apoptotic cascade. Enzymatic assays supported oxidative stress as an instigator of cell death. Interestingly, assessment of inflammatory responses revealed disparity in the NF-κB/IL-6/STAT3 axis, where it was found that in animals consuming higher amounts of arsenic NF-κB activation did not lead to the classical IL-6 upregulation response. This deviation from the canonical pathway was accompanied with a significant rise in numbers of CD4+ CD25+ FoxP3 expressing cells in the thymus. The cytokine profile of the animals exposed to higher doses of arsenic also indicated an immune-suppressed milieu, thus validating that arsenic shapes the immune environment in context to its dose of exposure and that at higher doses it leads to immune-suppression. Our study establishes a novel role of arsenic in regulating immune homeostasis in context to its dose, where, at higher doses, arsenic related upregulation of NF-κB cascade takes on an alternative role that is correlated with increased immune-suppression.

  15. Arsenic-induced promoter hypomethylation and over-expression of ERCC2 reduces DNA repair capacity in humans by non-disjunction of the ERCC2-Cdk7 complex.

    Science.gov (United States)

    Paul, Somnath; Banerjee, Nilanjana; Chatterjee, Aditi; Sau, Tanmoy J; Das, Jayanta K; Mishra, Prafulla K; Chakrabarti, Partha; Bandyopadhyay, Arun; Giri, Ashok K

    2014-04-01

    Arsenic in drinking water is of critical concern in West Bengal, India, as it results in several physiological symptoms including dermatological lesions and cancers. Impairment of the DNA repair mechanism has been associated with arsenic-induced genetic damage as well as with several cancers. ERCC2 (Excision Repair Cross-Complementing rodent repair, complementation group 2), mediates DNA-repair by interacting with Cdk-activating kinase (CAK) complex, which helps in DNA proof-reading during transcription. Arsenic metabolism alters epigenetic regulation; we tried to elucidate the regulation of ERCC2 in arsenic-exposed humans. Water, urine, nails, hair and blood samples from one hundred and fifty seven exposed and eighty eight unexposed individuals were collected. Dose dependent validation was done in vitro using HepG2 and HEK-293. Arsenic content in the biological samples was higher in the exposed individuals compared with the content in unexposed individuals (p < 0.001). Bisulfite-modified methylation specific PCR showed a significant (p < 0.0001) hypomethylation of the ERCC2 promoter in the arsenic-exposed individuals. Densitometric analysis of immunoblots showed a nearly two-fold increase in expression of ERCC2 in exposed individuals, but there was an enhanced genotoxic insult as measured by micronuclei frequency. Immuno-precipitation and western blotting revealed an increased (p < 0.001) association of Cdk7 with ERCC2 in highly arsenic exposed individuals. The decrease in CAK activity was determined by observing the intensity of Ser(392) phosphorylation in p53, in vitro, which decreased with an increase in arsenic dose. Thus we infer that arsenic biotransformation leads to promoter hypomethylation of ERCC2, which in turn inhibits the normal functioning of the CAK-complex, thus affecting DNA-repair; this effect was highest among the arsenic exposed individuals with dermatological lesions. PMID:24473091

  16. Current conditions of researches in arsenic-induced oxidative stress%砷诱发氧化应激研究现状

    Institute of Scientific and Technical Information of China (English)

    安艳; 李春春; 邓晗依

    2015-01-01

    目前,世界范围内有近2亿人通过饮水和饮食暴露于具有毒性危险的砷,慢性砷中毒已经成为严重威胁人类健康的全球性的公共卫生问题。砷作为确认的人类致癌物,其毒性作用具体分子和细胞机制尚不清楚,氧化应激是目前被广泛接受与研究的砷毒性作用机制。本文主要综述了砷诱发活性氧的生成、相关生物标志和砷对抗氧化酶以及抗氧化防御系统作用的相关研究进展。%Currently ,it is estimated that more than 200 million people are at risk of toxic arsenic exposure from groundwater and food contamination . Arsenicosis is a serious and widespread global public health problem . However ,the exact molecular and cellular mechanisms involved in arsenic toxicity remain unclear .Oxidative stress is currently the most widely accepted and studied mechanism of arsenic toxicity .This review updates recent advances in generation of arsenic‐induced reactive oxygen species ,its relevant biomarkers ,the effects of arsenic on enzyme activities and the cellular defense mechanism .

  17. Enhanced Eryptosis Following Exposure to Carnosic Acid

    Directory of Open Access Journals (Sweden)

    Katja Stockinger

    2015-11-01

    Full Text Available Background/Aims: The phenolic abietane diterpene component of rosemary and sage, carnosic acid, may either induce or inhibit apoptosis of nucleated cells. The mechanisms involved in the effects of carnosic acid include altered mitochondrial function and gene expression. Human erythrocytes lack mitochondria and nuclei but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i, and ceramide formation. The present study explored, whether and how carnosic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to carnosic acid significantly increased the percentage of annexin-V-binding cells (2.5 µg/ml, significantly decreased forward scatter (10 µg/ml, significantly increased Fluo3 fluorescence (10 µg/ml, significantly increased ceramide abundance (10 µg/ml, significantly increased hemolysis (10 µg/ml, but significantly decreased DCFDA fluorescence (10 µg/ml. The effect of carnosic acid on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusion: Carnosic acid triggers cell shrinkage and phospholipid scrambling of the human erythrocyte cell membrane, an effect paralleled by and/or in part due to Ca2+ entry and increased ceramide abundance.

  18. Taxol®-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor® EL

    DEFF Research Database (Denmark)

    Vader, Pieter; Fens, Marcel HAM; Sachini, Nikoleta;

    2013-01-01

    The conventional clinical formulation of paclitaxel (PTX), Taxol®, consists of Cremophor® EL (CrEL) and ethanol. CrEL-formulated PTX is associated with acute hypersensitivity reactions, anemia and cardiovascular events. In this study, the authors investigated the effects of CrEL-PTX on red blood......: These results offer new insights into the side effect profile of Taxol, which is likely to have implications for patients with erythrocyte disorders. Abraxane did not induce any of these effects on RBCs, indicating that the choice of excipients can have a pronounced influence on the efficacy and side effects...

  19. Taxol (R)-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor (R) EL

    NARCIS (Netherlands)

    Vader, Pieter; Fens, Marcel H. A. M.; Sachini, Nikoleta; van Oirschot, Brigitte A.; Andringa, Grietje; Egberts, Antoine C. G.; Gaillard, Carlo A. J. M.; Rasmussen, Jan T.; van Wijk, Richard; van Solinge, Wouter W.; Schiffelers, Raymond M.

    2013-01-01

    The conventional clinical formulation of paclitaxel (PTX), Taxol (R), consists of Cremophor (R) EL (CrEL) and ethanol. CrEL-formulated PTX is associated with acute hypersensitivity reactions, anemia and cardiovascular events. In this study, the authors investigated the effects of CrEL-PTX on red blo

  20. Escherichia coli α-hemolysin triggers shrinkage of erythrocytes via K(Ca)3.1 and TMEM16A channels with subsequent phosphatidylserine exposure

    DEFF Research Database (Denmark)

    Skals, Marianne Gerberg; Jensen, Uffe Birk; Ousingsawat, Jiraporn;

    2010-01-01

    alpha-Hemolysin from Escherichia coli (HlyA) readily lyse erythrocytes from various species. We have recently demonstrated that this pore-forming toxin provokes distinct shrinkage and crenation before it finally leads to swelling and lysis of erythrocytes. The present study documents the underlying...... mechanism for this severe volume reduction. We show that HlyA-induced shrinkage and crenation of human erythrocytes occur subsequent to a significant rise in [Ca(2+)](i). The Ca(2+)-activated K(+) channel K(Ca)3.1 (or Gardos channel) is essential for the initial shrinkage, because both clotrimazole and TRAM......-34 prevent the shrinkage and potentiate hemolysis produced by HlyA. Notably, the recently described Ca(2+)-activated Cl(-) channel TMEM16A contributes substantially to HlyA-induced cell volume reduction. Erythrocytes isolated from TMEM16A(-/-) mice showed significantly attenuated crenation and...

  1. Associations of B- and C-Raf with cholesterol, phosphatidylserine, and lipid second messengers: preferential binding of Raf to artificial lipid rafts.

    Science.gov (United States)

    Hekman, Mirko; Hamm, Heike; Villar, Ana V; Bader, Benjamin; Kuhlmann, Jurgen; Nickel, Joachim; Rapp, Ulf R

    2002-07-01

    The serine/threonine kinase C-Raf is a key mediator in cellular signaling. Translocation of Raf to membranes has been proposed to be facilitated by Ras proteins in their GTP-bound state. In this study we provide evidence that both purified B- and C-Raf kinases possess lipophilic properties and associate with phospholipid membranes. In the presence of phosphatidylserine and lipid second messengers such as phosphatidic acid and ceramides these associations were very specific with affinity constants (K(D)) in the range of 0.5-50 nm. Raf association with liposomes was accompanied by displacement of 14-3-3 proteins and inhibition of Raf kinase activities. Interactions of Raf with cholesterol are of particular interest, since cholesterol has been shown to be involved, together with sphingomyelin and glycerophospholipids in the formation of specialized lipid microdomains called rafts. We demonstrate here that purified Raf proteins have moderate binding affinity for cholesterol. However, under conditions of lipid raft formation, Raf association with cholesterol (or rafts) increased dramatically. Since ceramides also support formation of rafts and interact with Raf we propose that Raf may be present at the plasma membrane in two distinct microdomains: in raft regions via association with cholesterol and ceramides and in non-raft regions due to interaction with phosphatidylserine and phosphatidic acid. At either location Raf kinase activity was inhibited by lipid binding in the absence or presence of Ras. Ras-Raf interactions with full-length C-Raf were studied both in solution and in phospholipid environment. Ras association with Raf was GTP dependent as previously demonstrated for C-Raf-RBD fragments. In the presence of liposomes the recruitment of C-Raf by reconstituted Ras-farnesyl was only marginal, since almost 70% of added C-Raf was bound by the lipids alone. Thus Ras-Raf binding in response to activation of Ras-coupled receptors may utilize Raf protein that is

  2. Removal of spermatozoa with externalized phosphatidylserine from sperm preparation in human assisted medical procreation: effects on viability, motility and mitochondrial membrane potential

    Directory of Open Access Journals (Sweden)

    de Agostini Ariane

    2009-01-01

    Full Text Available Abstract Background Externalization of phosphatidylserine (EPS occurs in apoptotic-like spermatozoa and could be used to remove them from sperm preparations to enhance sperm quality for assisted medical procreation. We first characterized EPS in sperms from infertile patients in terms of frequency of EPS spermatozoa as well as localization of phosphatidylserine (PS on spermatozoa. Subsequently, we determined the impact of depleting EPS spermatozoa on sperm quality. Methods EPS were visualized by fluorescently-labeled annexin V binding assay. Double staining with annexin V and Hoechst differentiates apoptotic from necrotic spermatozoa. We used magnetic-activated cell sorting using annexin V-conjugated microbeads (MACS-ANMB technique to remove EPS spermatozoa from sperm prepared by density gradient centrifugation (DGC. The impact of this technique on sperm quality was evaluated by measuring progressive motility, viability, and the integrity of the mitochondrial membrane potential (MMP by Rhodamine 123. Results Mean percentages of EPS spermatozoa were 14% in DGC sperm. Four subpopulations of spermatozoa were identified: 70% alive, 3% early apoptotic, 16% necrotic and 11% late apoptotic or necrotic. PS were localized on head and/or midpiece or on the whole spermatozoa. MACS efficiently eliminates EPS spermatozoa. MACS combined with DGC allows a mean reduction of 70% in EPS and of 60% in MMP-disrupted spermatozoa with a mean increase of 50% in sperm survival at 24 h. Conclusion Human ejaculates contain EPS spermatozoa which can mostly be eliminated by DGC plus MACS resulting in improved sperm long term viability, motility and MMP integrity. EPS may be used as an indicator of sperm quality and removal of EPS spermatozoa may enhance fertility potential in assisted medical procreation.

  3. Arsenic Induced Decreases in the Vascular Matrix

    OpenAIRE

    Hays, Allison M.; Lantz, R. Clark; Rodgers, Laurel S.; Sollome, James J.; Vaillancourt, Richard R.; Andrew, Angeline S; Hamilton, Joshua W.; Camenisch, Todd D.

    2008-01-01

    Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five or eight weeks. At five and eight weeks, RNA from the lungs of control and AsIII exposed animals was processed for microarray. Sixty-five genes were significantly and differentially expressed. Differential expres...

  4. Induction of glutathione synthesis in human hepatocytes by acute and chronic arsenic exposure: Differential roles of mitogen-activated protein kinases

    International Nuclear Information System (INIS)

    Highlights: • Arsenic exposure increased intracellular levels of glutathione. • Mitogen-activated protein kinases were involved in glutathione homeostasis. • ERK contributed to glutathione synthesis during acute arsenic exposure. • Glutathione synthesis was regulated by p38 at least in part independent of NRF2 during chronic arsenic exposure. - Abstract: Glutathione (GSH) is a vital component of antioxidant defense which protects cells from toxic insults. Previously we found intracellular GSH was involved in cell resistance against arsenic-induced cytotoxicity. However, molecular mechanisms of GSH homeostasis during arsenic exposure are largely undefined. Here, we investigated roles of mitogen-activated protein kinases (MAPKs) in GSH synthesis pathway with two arsenic exposure strategies by using Chang human hepatocytes. In one strategy, acute arsenic exposure (20 μM, 24 h) was applied, as MAPK signaling is generally considered to be transient. In the other one, chronic arsenic exposure (500 nM, 20 weeks) was applied, which mimicked the general human exposure to arsenic. We found that acute arsenic exposure activated extracellular signal-regulated 1/2 kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) in parallel with increased transcription and nuclear translocation of factor-erythroid 2-related factor 2 (NRF2) and enhanced expression of γ-glutamyl cysteine ligase catalytic subunit (GCLC), resulting in elevated intracellular GSH levels. Specific ERK inhibitor abolished arsenic-induced NRF2 nuclear translocation and GSH synthesis. During chronic arsenic exposure which induced a malignant cellular phenotype, continuous p38 activation and NRF2 nuclear translocation were observed with enhanced GSH synthesis. Specific p38 inhibitor attenuated arsenic-enhanced GSH synthesis without changing NRF2 nuclear translocation. Taken together, our results indicate MAPK pathways play an important role in cellular GSH homeostasis in response to arsenic. However, the

  5. Drinking-Water Arsenic Exposure Modulates Gene Expression in Human Lymphocytes from a U.S. Population

    Science.gov (United States)

    Andrew, Angeline S.; Jewell, David A.; Mason, Rebecca A.; Whitfield, Michael L.; Moore, Jason H.; Karagas, Margaret R.

    2008-01-01

    Background Arsenic exposure impairs development and can lead to cancer, cardiovascular disease, and diabetes. The mechanism underlying these effects remains unknown. Primarily because of geologic sources of contamination, drinking-water arsenic levels are above the current recommended maximum contaminant level of 10 μg/L in the northeastern, western, and north central regions of the United States. Objectives We investigated the effects of arsenic exposure, defined by internal biomarkers at levels relevant to the United States and similarly exposed populations, on gene expression. Methods We conducted separate Affymetrix microarray-based genomewide analyses of expression patterns. Peripheral blood lymphocyte samples from 21 controls interviewed (1999–2002) as part of a case–control study in New Hampshire were selected based on high- versus low-level arsenic exposure levels. Results The biologic functions of the transcripts that showed statistically significant abundance differences between high- and low-arsenic exposure groups included an overrepresentation of genes involved in defense response, immune function, cell growth, apoptosis, regulation of cell cycle, T-cell receptor signaling pathway, and diabetes. Notably, the high-arsenic exposure group exhibited higher levels of several killer cell immunoglobulin-like receptors that inhibit natural killer cell activity. Conclusions These findings define biologic changes that occur with chronic arsenic exposure in humans and provide leads and potential targets for understanding and monitoring the pathogenesis of arsenic-induced diseases. PMID:18414638

  6. Adult hippocampal neurogenesis and mRNA expression are altered by perinatal arsenic exposure in mice and restored by brief exposure to enrichment.

    Directory of Open Access Journals (Sweden)

    Christina R Tyler

    Full Text Available Arsenic is a common and pervasive environmental contaminant found in drinking water in varying concentrations depending on region. Exposure to arsenic induces behavioral and cognitive deficits in both human populations and in rodent models. The Environmental Protection Agency (EPA standard for the allotment of arsenic in drinking water is in the parts-per-billion range, yet our lab has shown that 50 ppb arsenic exposure during development can have far-reaching consequences into adulthood, including deficits in learning and memory, which have been linked to altered adult neurogenesis. Given that the morphological impact of developmental arsenic exposure on the hippocampus is unknown, we sought to evaluate proliferation and differentiation of adult neural progenitor cells in the dentate gyrus after 50 ppb arsenic exposure throughout the perinatal period of development in mice (equivalent to all three trimesters in humans using a BrdU pulse-chase assay. Proliferation of the neural progenitor population was decreased by 13% in arsenic-exposed mice, but was not significant. However, the number of differentiated cells was significantly decreased by 41% in arsenic-exposed mice compared to controls. Brief, daily exposure to environmental enrichment significantly increased proliferation and differentiation in both control and arsenic-exposed animals. Expression levels of 31% of neurogenesis-related genes including those involved in Alzheimer's disease, apoptosis, axonogenesis, growth, Notch signaling, and transcription factors were altered after arsenic exposure and restored after enrichment. Using a concentration previously considered safe by the EPA, perinatal arsenic exposure altered hippocampal morphology and gene expression, but did not inhibit the cellular neurogenic response to enrichment. It is possible that behavioral deficits observed during adulthood in animals exposed to arsenic during development derive from the lack of differentiated neural

  7. Exposure Forecaster

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Exposure Forecaster Database (ExpoCastDB) is EPA's database for aggregating chemical exposure information and can be used to help with chemical exposure...

  8. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

    DEFF Research Database (Denmark)

    Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S;

    2014-01-01

    this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...... positively associated with sputum AAT (P=0.004 and P=0.002, respectively). In analyses stratified by town, these relationships remained significant only in Ajo, with the higher arsenic exposure. Reduction in AAT may be a means by which arsenic induces respiratory disease, and selenium may protect against...

  9. Mechanism of Action of Thymosinα1: Does It Interact with Membrane by Recognition of Exposed Phosphatidylserine on Cell Surface? A Structural Approach.

    Science.gov (United States)

    Nepravishta, R; Mandaliti, W; Vallebona, P S; Pica, F; Garaci, E; Paci, M

    2016-01-01

    Thymosinα1 is a peptidic hormone with pleiotropic activity, which is used in the therapy of several diseases. It is unstructured in water solution and interacts with negative regions of micelles and vesicles assuming two tracts of helical conformation with a structural flexible break in between. The studies of the interaction of Thymosinα1 with micelles of mixed dipalmitoylphosphatidylcholine and sodium dodecylsulfate and vesicles with mixed dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylserine, the latter the negative component of the membranes, by (1)H and natural abundance (15)N NMR are herewith reported, reviewed, and discussed. The results indicate that the preferred interactions are those where the surface is negatively charged due to sodium dodecylsulfate or due to the presence of dipalmitoylphosphatidylserine exposed on the surface. In fact the unbalance of dipalmitoylphosphatidylserine on the cellular surface is an important phenomenon present in pathological conditions of cells. Moreover, the direct interaction of Thymosinα1 with K562 cells presenting an overexposure of phosphatidylserine as a consequence of resveratrol-induced apoptosis was carried out. PMID:27450732

  10. Glycation of the muscle-specific enolase by reactive carbonyls: effect of temperature and the protection role of carnosine, pyridoxamine and phosphatidylserine.

    Science.gov (United States)

    Pietkiewicz, Jadwiga; Bronowicka-Szydełko, Agnieszka; Dzierzba, Katarzyna; Danielewicz, Regina; Gamian, Andrzej

    2011-03-01

    Reactive carbonyls such as 4-hydroxy-2-nonenal (4-HNE), trans-2-nonenal (T2 N), acrolein (ACR) can react readily with nucleophilic protein sites forming of advanced glycation end-products (AGE). In this study, the human and pig muscle-specific enolase was used as a protein model for in vitro modification by 4-HNE, T2 N and ACR. While the human enolase interaction with reactive α-oxoaldehyde methylglyoxal (MOG) was demonstrated previously, the effect of 4-HNE, T2N and ACR has not been identified yet. Altering in catalytic function were observed after the enzyme incubation with these active compounds for 1-24 h at 25, 37 and 45 °C. The inhibition degree of enolase activity occurred in following order: 4-HNE > ACR > MOG > T2N and inactivation of pig muscle-specific enolase was more effective relatively to human enzyme. The efficiency of AGE formation depends on time and incubation temperature with glycating agent. More amounts of insoluble AGE were formed at 45 °C. We found that pyridoxamine and natural dipeptide carnosine counteracted AGE formation and protected enolase against the total loss of catalytic activity. Moreover, we demonstrated for the first time that phosphatidylserine may significantly protect enolase against decrease of catalytic activity in spite of AGE production. PMID:21347838

  11. Analysis of Amino Acid Residues of Potential Importance for Phosphati-dylserine Specificity of P4-type ATPase ATP8A2

    DEFF Research Database (Denmark)

    Mogensen, Louise; Vestergaard, Anna Lindeløv; Mikkelsen, Stine;

    The asymmetric structure of the plasma membrane is maintained through internalization of phos-pholipids by the family of P4-ATPases by a poorly characterized mechanism. Studies in yeast point towards a non-classical pathway involving important residues of a two-gate mechanism [1]. Glycine-230...... 302 of ATP8A2 with alanine (N302A), tyrosine (N302Y) and serine (N302S). Furthermore, a triple mutant of ATP8A2 (Q95GQ96AN302S) was studied to reveal any cooperativity between the two gates, as observed in yeast [1]. The affinities of the mutants for phosphatidylserine and phosphatidylethanolamine...... and differences between ATP8A2 and the yeast flippases. The results supplement recent studies of the ATP8A2 flippase revealing a hydro-phobic gate that facilitates the transport along a water-filled pathway in the protein transmembrane domain[2]. 1. Baldridge, R.D. and T.R. Graham, Proceedings of the National...

  12. Alteration of mitochondrial membrane potential (DELTA_PSI_m and phosphatidylserine translocation as early indicators of heavy metal-induced apoptosis in the earthworm Eisenia hortensis

    Directory of Open Access Journals (Sweden)

    FM Bearoff

    2011-06-01

    Full Text Available The effects of the heavy metals cadmium and copper (50-500 ìM on the apoptotic events involving changes in mitochondrial membrane potential (ÄØm and phosphatidylserine (PS translocation were investigated in the immune cells (celomocytes of the earthworm Eisenia hortensis. Using the fluorescent probe JC-1, loss of membrane potential due to depolarization was detected in a greater proportion of cases when induced by cadmium compared to copper (58.7 % vs. 37 % and at a lower concentration (50 ìM vs. 125ìM. With the use of the general caspase inhibitor Z-VAD-fmk, PS translocation detected by annexin V-FITC was found to be caspase-dependent when induced by cadmium at 125-250 ìM but not at 50 ìM or 500 ìM; a high proportion of earthworms (60 % exhibited inhibitory effects. Additionally, the collapse in membrane potential and PS translocation were found to strongly correlate (r > 0.5 in 89 % of cases when induced by cadmium and copper. Thus, heavy metals appear to induce death in celomocytes of E. hortensis through apoptosis by means of caspase dependent pathways

  13. Differences in intracellular calcium dynamics cause differences in α-granule secretion and phosphatidylserine expression in platelets adhering on glass and TiO2.

    Science.gov (United States)

    Gupta, Swati; Donati, Alessia; Reviakine, Ilya

    2016-06-01

    In this study, the activation of purified human platelets due to their adhesion on glass and TiO2 in the absence of extracellular calcium was investigated. Differences in α-granule secretion between platelets adhering on the two surfaces were detected by examining the expression and secretion of the α-granule markers P-selectin (CD62P) and β-thromboglobulin. Similarly, differences in the expression of phosphatidylserine (PS), and in the activation of the major integrin GPIIb/IIIa, on the surfaces of the adhering platelets, were also observed. While all of these activation markers were expressed in platelets adhering on glass, the surface markers were not expressed in platelets adhering on TiO2, and β-thromboglobulin secretion levels were substantially reduced. Differences in marker expression and secretion correlated with differences in the intracellular calcium dynamics. Calcium ionophore treatment triggered α-granule secretion and PS expression in TiO2-adhering platelets but had no effect on the activation of GPIIb/IIIa. These results demonstrate specificity in the way surfaces of artificial materials activate platelets, link differences in the intracellular calcium dynamics observed in the platelets adhering on the two surfaces to the differences in some of the platelet responses (α-granule secretion and PS expression), but also highlight the involvement of synergistic, calcium-independent pathways in platelet activation. The ability to control activation in surface-adhering platelets makes this an attractive model system for studying platelet signaling pathways and for tissue engineering applications. PMID:27124595

  14. Vibrio cholerae proteome-wide screen for immunostimulatory proteins identifies phosphatidylserine decarboxylase as a novel Toll-like receptor 4 agonist.

    Directory of Open Access Journals (Sweden)

    Ann Thanawastien

    2009-08-01

    Full Text Available Recognition of conserved bacterial components provides immediate and efficient immune responses and plays a critical role in triggering antigen-specific adaptive immunity. To date, most microbial components that are detected by host innate immune system are non-proteinaceous structural components. In order to identify novel bacterial immunostimulatory proteins, we developed a new high-throughput approach called "EPSIA", Expressed Protein Screen for Immune Activators. Out of 3,882 Vibrio cholerae proteins, we identified phosphatidylserine decarboxylase (PSD as a conserved bacterial protein capable of activating host innate immunity. PSD in concentrations as low as 100 ng/ml stimulated RAW264.7 murine macrophage cells and primary peritoneal macrophage cells to secrete TNFalpha and IL-6, respectively. PSD-induced proinflammatory response was dependent on the presence of MyD88, a known adaptor molecule for innate immune response. An enzymatically inactive PSD mutant and heat-inactivated PSD induced approximately 40% and approximately 15% of IL-6 production compared to that by native PSD, respectively. This suggests that PSD induces the production of IL-6, in part, via its enzymatic activity. Subsequent receptor screening determined TLR4 as a receptor mediating the PSD-induced proinflammatory response. Moreover, no detectable IL-6 was produced in TLR4-deficient mouse macrophages by PSD. PSD also exhibited a strong adjuvant activity against a co-administered antigen, BSA. Anti-BSA response was decreased in TLR4-deficient mice immunized with BSA in combination with PSD, further proving the role of TLR4 in PSD signaling in vivo. Taken together, these results provide evidence for the identification of V. cholerae PSD as a novel TLR4 agonist and further demonstrate the potential application of PSD as a vaccine adjuvant.

  15. The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

    Directory of Open Access Journals (Sweden)

    Carolina Varela Chavez

    2016-03-01

    Full Text Available Clostridium sordellii lethal toxin (TcsL is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases.

  16. Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems

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    Hyun-Jung Park

    2012-01-01

    Full Text Available The present study examined the effects of squid phosphatidylserine (Squid-PS on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1, p.o. daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT and acetylcholinesterase (AchE immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P<0.05. However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P<0.05. Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P<0.01. Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P<0.05, resp.. These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.

  17. Levels of Arabidopsis thaliana leaf phosphatidic acids, phosphatidylserines, and most trienoate-containing polar lipid molecular species increase during the dark period of the diurnal cycle

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    Sara eMaatta

    2012-03-01

    Full Text Available Previous work has demonstrated that plant leaf polar lipid fatty acid composition varies during the diurnal (dark-light cycle. Fatty acid synthesis occurs primarily during the light, but fatty acid desaturation continues in the absence of light, resulting in polyunsaturated fatty acids reaching their highest levels toward the end of the dark period. In this work, Arabidopsis thaliana were grown at constant (21°C temperature with 12-h light and 12-h dark periods. Collision induced dissociation time-of-flight mass spectrometry demonstrated that 16:3 and 18:3 fatty acid content in membrane lipids of leaves are higher at the end of the dark than at the end of the light period, while 16:1, 16:2, 18:0, and 18:1 content are higher at the end of the light period. Lipid profiling of membrane galactolipids, phospholipids, and lysophospholipids by electrospray ionization triple quadrupole mass spectrometry indicated that the monogalactosyldiacylglycerol, phosphatidylglycerol, and phosphatidylcholine classes include molecular species whose levels are highest at end of the light period and others that are highest at the end of the dark period. The levels of phosphatidic acid and phosphatidylserine classes were higher at the end of the dark period, and molecular species within these classes either followed the class pattern or were not significantly changed in the diurnal cycle. Phospholipase D (PLD is a family of enzymes that hydrolyzes phospholipids to produce phosphatidic acid. Analysis of several PLD mutant lines suggests that PLDζ2 and possibly PLDα1 may contribute to diurnal cycling of phosphatidic acid. The polar lipid compositional changes are considered in relation to recent data that demonstrate phosphatidylcholine acyl editing.

  18. Developmental consequences of in utero sodium arsenate exposure in mice with folate transport deficiencies

    International Nuclear Information System (INIS)

    Previous studies have demonstrated that mice lacking a functional folate binding protein 2 gene (Folbp2-/-) were significantly more sensitive to in utero arsenic exposure than were the wild-type mice similarly exposed. When these mice were fed a folate-deficient diet, the embryotoxic effect of arsenate was further exacerbated. Contrary to expectations, studies on 24-h urinary speciation of sodium arsenate did not demonstrate any significant difference in arsenic biotransformation between Folbp2-/- and Folbp2+/+ mice. To better understand the influence of folate pathway genes on arsenic embryotoxicity, the present investigation utilized transgenic mice with disrupted folate binding protein 1 (Folbp1) and reduced folate carrier (RFC) genes. Because complete inactivation of Folbp1 and RFC genes results in embryonic lethality, we used heterozygous animals. Overall, no RFC genotype-related differences in embryonic susceptibility to arsenic exposure were observed. Embryonic lethality and neural tube defect (NTD) frequency in Folbp1 mice was dose-dependent and differed from the RFC mice; however, no genotype-related differences were observed. The RFC heterozygotes tended to have higher plasma levels of S-adenosylhomocysteine (SAH) than did the wild-type controls, although this effect was not robust. It is concluded that genetic modifications at the Folbp1 and RFC loci confers no particular sensitivity to arsenic toxicity compared to wild-type controls, thus disproving the working hypothesis that decreased methylating capacity of the genetically modified mice would put them at increased risk for arsenic-induced reproductive toxicity

  19. Association between Multi-level Inorganic Arsenic Exposure from Drinking Water and Skin Lesions in China

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    Takesumi Yoshimura

    2006-09-01

    Full Text Available Arsenic is one of the most important toxicants in the environment. In Inner Mongolia of China, 300,000 residents are believed to be drinking water containing >50μg/liter. Skin lesions have been known as the most common consequences resulting from chronic exposure to arsenic. To clarify the prevalence of arsenic-induced skin lesions, it is important to assess the impact of this problem among the target population, and to make future planning. We evaluated the association between multi-levels inorganic arsenic exposure from drinking water and skin lesions in an arsenic-affected area in Inner Mongolia, China. One hundred nine and 32 subjects in high (>50μg/liter and low (150μg/liter were 33.3% (OR =15.50, 95% CI: 1.53-248.70, 46.7% (OR =16.10, 95% CI: 3.73-69.63 and 55.7% (OR= 25.70, 95% CI: 6.43-102.87, respectively. Duration of using well was not associated with increased risk of skin lesions in this population; (OR =1.68, 95% CI: 0.40-6.91 for 6-15 years, OR = 2.30, 95% CI: 0.58-9.14 for over 15 years compared with the duration of less than 5 years.

  20. A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases.

    Science.gov (United States)

    Wang, Chih-Hao; Hsiao, Chuhsing Kate; Chen, Chi-Ling; Hsu, Lin-I; Chiou, Hung-Yi; Chen, Shu-Yuan; Hsueh, Yu-Mei; Wu, Meei-Maan; Chen, Chien-Jen

    2007-08-01

    Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is an independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality.

  1. Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study

    Directory of Open Access Journals (Sweden)

    Zanotta D

    2014-02-01

    Full Text Available Danilo Zanotta, Silvana Puricelli, Guido Bonoldi Unità Operativa di Medicina 2, Ospedale di Circolo di Busto Arsizio, Varese, Italy Abstract: A prospective cohort, noncomparative, multicenter trial was conducted to explore the potential of a phytotherapeutic compound, available as a dietary supplement and containing extracts of Bacopa monnieri and Haematococcus pluvialis (astaxanthin plus phosphatidylserine and vitamin E, in improving cognition in subjects diagnosed with mild cognitive impairment. Enrolled subjects (n=104 were aged 71.2±9.9 years and had a mini-mental state examination score of 26.0±2.0 (mean ± standard deviation. They underwent the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog test and the clock drawing test at baseline and upon completion of a 60-day period of dietary supplementation with one tablet daily of the tested compound. In 102 assessable subjects, total ADAS-cog scores improved from 13.7±5.8 at baseline to 9.7±4.9 on day 60, and the clock drawing test scores improved from 8.5±2.3 to 9.1±1.9. Both changes were statistically significant (P<0.001. Memory tasks were the individual components of ADAS-cog showing the largest improvements. In a multivariate analysis, larger improvements in total ADAS-cog score were associated with less compromised baseline mini-mental state examination scores. Perceived efficacy was rated as excellent or good by 62% of study subjects. The tested compound was well tolerated; one nonserious adverse event was reported in the overall study population, and perceived tolerability was rated excellent or good by 99% of the subjects. In conclusion, dietary supplementation with the tested compound shows potential for counteracting cognitive impairment in subjects with mild cognitive impairment and warrants further investigation in adequately controlled, longer-term studies. Keywords: mild cognitive impairment, Bacopa monnieri, astaxanthin, ADAS-cog test, clock drawing

  2. CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure

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    S. Huang

    2013-01-01

    Full Text Available Inorganic arsenic is a well-known human skin carcinogen. Chronic arsenic exposure results in various types of human skin lesions, including squamous cell carcinoma (SCC. To investigate whether mutant stem cells participate in arsenic-associated carcinogenesis, we repeatedly exposed the HaCaT cells line to an environmentally relevant level of arsenic (0.05 ppm in vitro for 18 weeks. Following sodium arsenic arsenite administration, cell cycle, colony-forming efficiency (CFE, cell tumorigenicity, and expression of CD44v6, NF-κB and p53, were analyzed at different time points (0, 5, 10, 15, 20, 25 and 30 passages. We found that a chronic exposure of HaCaT cells to a low level of arsenic induced a cancer stem- like phenotype. Furthermore, arsenic-treated HaCaT cells also became tumorigenic in nude mice, their growth cycle was predominantly in G2/M and S phases. Relative to nontreated cells, they exhibited a higher growth rate and a significant increase in CFE. Western blot analysis found that arsenic was capable of increasing cell proliferation and sprouting of cancer stem-like phenotype. Additionally, immunohistochemical analysis demonstrated that CD44v6 expression was up-regulated in HaCaT cells exposed to a low level of arsenic during early stages of induction. The expression of CD44v6 in arsenic-treated cells was positively correlated with their cloning efficiency in soft agar (r=0.949, P=0.01. Likewise, the expressions of activating transcription factor NF-κB and p53 genes in the arsenic-treated HaCaT cells were significantly higher than that in non-treated cells. Higher expressions of CD44v6, NF-κB and p53 were also observed in tumor tissues isolated from Balb/c nude mice. The present results suggest that CD44v6 may be a biomarker of arsenic-induced neoplastic transformation in human skin cells, and that arsenic promotes malignant transformation in human skin lesions through a NF-κB signaling pathway-stimulated expression of CD44v6.

  3. 樱桃汁和草莓汁激活Nrf2信号通路对砷诱导的人支气管上皮细胞损伤的保护作用%Juices of cherry and strawberry confer protection of human bronchial epithelial cells against arsenic-induced toxicity via activation of Nrf2 signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孔得刚; 王莉莉; 周洪雷; 任冬梅; 娄红祥; 沈涛

    2014-01-01

    目的:研究草莓汁和樱桃汁对NF-E2相关因子2(Nrf2)信号通路的影响,以及两种果汁对砷诱导的人支气管上皮(HBE)细胞损伤的保护作用。方法选择人乳腺癌MDA-MB-231细胞系,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40和1∶80组(果汁稀释比例分别为1∶10、1∶20、1∶40和1∶80),采用抗氧化反应原件(ARE)荧光素酶报告基因和Westerm blotting筛选并确证两种果汁对Nrf2信号通路的影响;选择HBE细胞,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40组(果汁稀释比例分别为1∶10、1∶20和1∶40),采用QuantiChrom谷胱甘肽(GSH)试剂盒测定两种果汁对内源性抗氧化剂GSH水平的影响;采用MTT法和细胞转染技术评价两种果汁对砷诱导的HB E细胞的保护作用。结果草莓汁和樱桃汁能够剂量依赖地增强ARE荧光强度,上调MDA-MB-231细胞中Nrf2及其下游基因NADPH苯醌氧化还原醇(NQO1)和γ-谷氨酰半胱氨酸合成酶(γGCS)蛋白的表达;两种果汁能够提高HBE细胞内源性抗氧化剂GSH水平;两种果汁和砷处理HBE细胞后,果汁预处理的细胞生存率高于砷单独处理的细胞生存率,两种果汁表现出对砷诱导细胞毒性的保护作用,而这种保护作用在转染Nrf2-siRNA后消失。结论草莓汁和樱桃汁通过激活Nrf2信号通路抑制砷诱导的细胞毒性,对HBE细胞具有保护作用。%Objective To investigate the effects of cherry and strawberry juices on NF-E2-related factor 2(Nrf2)signa-ling pathway,and to evaluate their protection effects on arsenic-induced toxicity in human bronchial epithelial (HBE) cells.Methods Human breast cancer 23 1 cells were randomly divided into the control group,sulforaphen treated group,and juice treated groups (juice dilution ratios were 1∶10,1∶20,1∶40 and 1∶80,respectively

  4. Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatidic acid. Phosphatidic acid regulates the translocation of Raf-1 in 12-O-tetradecanoylphorbol-13-acetate-stimulated Madin-Darby canine kidney cells.

    Science.gov (United States)

    Ghosh, S; Strum, J C; Sciorra, V A; Daniel, L; Bell, R M

    1996-04-01

    Previous studies demonstrated that the cysteine-rich amino-terminal domain of Raf-1 kinase interacts selectively with phosphatidylserine (Ghosh, S., Xie, W. Q., Quest, A. F. G., Mabrouk, G. M., Strum, J. C., and Bell, R. M. (1994) J. Biol. Chem. 269, 10000-10007). Further analysis showed that full-length Raf-1 bound to both phosphatidylserine and phosphatidic acid (PA). Specifically, a carboxyl-terminal domain of Raf-1 kinase (RafC; residues 295 648 of human Raf-1) interacted strongly with phosphatidic acid. The binding of RafC to PA displayed positive cooperativity with Hill numbers between 3.3 and 6.2; the apparent Kd ranged from 4.9 +/- 0.6 to 7.8 +/- 0.9 mol % PA. The interaction of RafC with PA displayed a pH dependence distinct from the interaction between the cysteine-rich domain of Raf-1 and PA. Also, the RafC-PA interaction was unaffected at high ionic strength. Of all the lipids tested, only PA and cardiolipin exhibited high affinity binding; other acidic lipids were either ineffective or weakly effective. By deletion mutagenesis, the PA binding site within RafC was narrowed down to a 35-amino acid segment between residues 389 and 423. RafC did not bind phosphatidyl alcohols; also, inhibition of PA formation in Madin-Darby canine kidney cells by treatment with 1% ethanol significantly reduced the translocation of Raf-1 from the cytosol to the membrane following stimulation with 12-O-tetradecanoylphorbol-13-acetate. These results suggest a potential role of the lipid second messenger, PA, in the regulation of translocation and subsequent activation of Raf-1 in vivo.

  5. Development and pharmacokinetic of antimony encapsulated in liposomes of phosphatidylserine using radioisotopes in experimental leishmaniasis; Desenvolvimento e farmacocinetica de antimonio encapsulado em lipossomas de fosfatidilserina utilizando radioisotopos em leishmaniose experimental

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta Etel Treiger

    2010-07-01

    Leishmaniasis are a complex of parasitic diseases caused by intra macrophage protozoa of the genus Leishmania, and is fatal if left untreated. Pentavalent antimonials, though toxic and their mechanism of action being unclear, remain the first-line drugs for treatment. Effective therapy could be achieved by delivering antileishmanial drugs to these sites of infection. Liposomes are phospholipid vesicles that promote improvement in the efficacy and action of drugs in target cell. Liposomes are taken up by the cells of mononuclear phagocytic system (MPS). The purpose of this study was to develop a preparation of meglumine antimonate encapsulated in liposomes of phosphatidylserine and to study its pharmacokinetic in healthy mice to establish its metabolism and distribution. Quantitative analysis of antimony from liposomes demonstrated that Neutron Activation Analysis was the most sensitive technique with almost 100 % of accuracy. All liposome formulations presented a mean diameter size of 150 nm. The determination of IC{sub 50} in infected macrophage showed that liposome formulations were between 10 - 63 fold more effective than the free drug, indicating higher selectivity index. By fluorescence microscopy, an increased uptake of fluorescent-liposomes was seen in infected macrophages during short times of incubation compared with non-infected macrophages. Biodistribution studies showed that meglumine antimonate irradiated encapsulated in liposomes of phosphatidylserine promoted a targeting of antimony for MPS tissues and maintained high doses in organs for a prolonged period. In conclusion, these data suggest that meglumine antimonate encapsulated in liposomes showed higher effectiveness than the non-liposomal drug against Leishmania infection. The development of liposome formulations should be a new alternative for the chemotherapy of infection diseases, especially Leishmaniasis, as they are used to sustain and target pharmaceuticals to the local of infection. (author)

  6. Enhanced Eryptosis Following Gramicidin Exposure

    OpenAIRE

    Abaid Malik; Rosi Bissinger; Guoxing Liu; Guilai Liu; Florian Lang

    2015-01-01

    The peptide antibiotic and ionophore gramicidin has previously been shown to trigger apoptosis of nucleated cells. In analogy to apoptosis, the suicidal death of erythrocytes or eryptosis involves cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+] i ), and ceramide. The present study explored, whether gramicidin triggers eryptosis. To this end ...

  7. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh

    Science.gov (United States)

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G.; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Paul-Brutus, Rachelle; Islam, Tariqul; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin; Jiang, Jieying; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T.; Desvarieux, Moise; Ahsan, Habibul; Chen, Yu

    2014-01-01

    Epidemiologic studies that evaluated genetic susceptibility to the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1,078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-medial thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. PMID:24593923

  8. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima-media thickness in Bangladesh.

    Science.gov (United States)

    Wu, Fen; Jasmine, Farzana; Kibriya, Muhammad G; Liu, Mengling; Cheng, Xin; Parvez, Faruque; Paul-Brutus, Rachelle; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin; Jiang, Jieying; Islam, Tariqul; Slavkovich, Vesna; Rundek, Tatjana; Demmer, Ryan T; Desvarieux, Moise; Ahsan, Habibul; Chen, Yu

    2014-05-01

    Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = -5.1 μm, 95% CI = -31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = -3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.

  9. Association between occupational exposure to arsenic and neurological, respiratory and renal effects.

    Science.gov (United States)

    Halatek, Tadeusz; Sinczuk-Walczak, Halina; Rabieh, Sasan; Wasowicz, Wojciech

    2009-09-01

    Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n=16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and beta(2)-microglobulin (beta(2)M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m(3)). The contents of lead did not exceed the TLV (0.05 mg/m(3)). Low CC16 levels in serum (12.1 microg/l) of workers with SNS and VEP symptoms and highest level As-U (x(a) 39.0 microg/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum beta(2)M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system. PMID:19410594

  10. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    Science.gov (United States)

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  11. Association between occupational exposure to arsenic and neurological, respiratory and renal effects

    International Nuclear Information System (INIS)

    Occupational exposure by inhalation in copper smelter is associated with several subclinical health phenomena. The respiratory tract is usually involved in the process of detoxication of inhaled noxious agents which, as arsenic, can act as inductors of oxidative stress (Lantz, R.C., Hays, A.M., 2006. Role of oxidative stress in arsenic-induced toxicity. Drug Metab. Rev. 38, 791-804). It is also known that irritating fumes affect distal bronchioles of non-ciliated, epithelial Clara cells, which secrete anti-inflammatory and immunosuppressive Clara cell protein (CC16) into the respiratory tract. The study group comprised 39 smelters employed at different workplaces in a copper foundry, matched for age and smoking habits with the control group (n = 16). Subjective neurological symptoms (SNS), visual evoked potentials (VEP), electroneurographic (EneG) and electroencephalographic (EEG) results were examined in the workers and the relationships between As concentration in the air (As-Air) and urine (As-U) were assessed. Effects of exposure were expressed in terms of biomarkers: CC16 as early pulmonary biomarker and β2-microglobulin (β2M) in urine and serum and retinol binding protein (RBP) as renal markers, measured by sensitive latex immunoassay. The concentrations of arsenic exceeded about two times the Threshold Limit Values (TLV) (0.01 mg/m3). The contents of lead did not exceed the TLV (0.05 mg/m3). Low CC16 levels in serum (12.1 μg/l) of workers with SNS and VEP symptoms and highest level As-U (xa 39.0 μg/l) were noted earliest in relation to occupational time. Moreover, those effects were associated with increased levels of urinary and serum β2M and urinary RBP. Results of our study suggested the initiative key role of oxidative stress in triggering the processes that eventually lead to the subclinical effects of arsenic on the nervous system.

  12. Studies into the mechanism of arsenic-induced neurotoxicity

    NARCIS (Netherlands)

    Vahidnia, Ali

    2008-01-01

    Arsenic (As) is a notoriously poisonous metalloid with known hazardous effects to human health. The project described in this thesis was aimed at elucidating the probable mechanism of As-induced neurotoxicity in vivo and in vitro. The animal studies in this thesis were designed to answer questions a

  13. Influence of prenatal arsenic exposure and newborn sex on global methylation of cord blood DNA.

    Directory of Open Access Journals (Sweden)

    J Richard Pilsner

    Full Text Available BACKGROUND: An emerging body of evidence indicates that early-life arsenic (As exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown. OBJECTIVE: The objective of this study was to investigate the influence of prenatal As exposure on global methylation of cord blood DNA in a study of mother/newborn pairs in Matlab, Bangladesh. DESIGN: Maternal and cord blood DNA were available from a convenience sample of 101 mother/newborn pairs. Measures of As exposure included maternal urinary As (uAs, maternal blood As (mbAs and cord blood As (cbAs. Several measures of global DNA methylation were assessed, including the [3H]-methyl-incorporation assay and three Pyrosequencing assays: Alu, LINE-1 and LUMA. RESULTS: In the total sample, increasing quartiles of maternal uAs were associated with an increase in covariate-adjusted means of newborn global DNA methylation as measured by the [3H]-methyl-incorporation assay (quartile 1 (Q1 and Q2 vs. Q4; p = 0.06 and 0.04, respectively. Sex-specific linear regression analyses, while not reaching significance level of 0.05, indicated that the associations between As exposures and Alu, LINE-1 and LUMA were positive among male newborns (N = 58 but negative among female newborns (N = 43; tests for sex differences were borderline significant for the association of cbAs and mbAs with Alu (p = 0.05 and 0.09, respectively and for the association between maternal uAs and LINE-1 (p = 0.07. Sex-specific correlations between maternal urinary creatinine and newborn methyl-incorporation, Alu and LINE-1 were also evident (p<0.05. CONCLUSIONS: These results suggest that prenatal As exposure is associated with global DNA methylation in cord blood DNA, possibly in a sex-specific manner. Arsenic-induced epigenetic modifications in utero may potentially influence disease outcomes later in life. Additional studies are needed to confirm

  14. Differential effect of maternal diet supplementation with α-Linolenic adcid or n-3 long-chain polyunsaturated fatty acids on glial cell phosphatidylethanolamine and phosphatidylserine fatty acid profile in neonate rat brains

    Directory of Open Access Journals (Sweden)

    Cruz-Hernandez Cristina

    2010-01-01

    Full Text Available Abstract Background Dietary long-chain polyunsaturated fatty acids (LC-PUFA are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE and phosphatidylserine (PS in the neonates. Methods Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55% and eicosapentaenoic acid (EPA, 0.75% of total fatty acids or α-linolenic acid (ALA, 2.90%. At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA profile. Data were analyzed by bivariate and multivariate statistics. Results In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P Conclusion The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.

  15. Medium wave exposure characterisation using exposure quotients.

    Science.gov (United States)

    Paniagua, Jesús M; Rufo, Montaña; Jiménez, Antonio; Antolín, Alicia; Pinar, Iván

    2010-06-01

    One of the aspects considered in the International Commission on Non-Ionizing Radiation Protection guidelines is that, in situations of simultaneous exposure to fields of different frequencies, exposure quotients for thermal and electrical stimulation effects should be examined. The aim of the present work was to analyse the electromagnetic radiation levels and exposure quotients for exposure to multiple-frequency sources in the vicinity of medium wave radio broadcasting antennas. The measurements were made with a spectrum analyser and a monopole antenna. Kriging interpolation was used to prepare contour maps and to estimate the levels in the towns and villages of the zone. The results showed that the exposure quotient criterion based on electrical stimulation effects to be more stringent than those based on thermal effects or power density levels. Improvement of dosimetry evaluations requires the spectral components of the radiation to be quantified, followed by application of the criteria for exposure to multiple-frequency sources. PMID:20159912

  16. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  17. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Fen [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Jasmine, Farzana; Kibriya, Muhammad G. [Department of Health Studies, The University of Chicago, Chicago, IL (United States); The University of Chicago Comprehensive Cancer Center, Chicago, IL (United States); Liu, Mengling; Cheng, Xin [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Parvez, Faruque [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY (United States); Paul-Brutus, Rachelle [Department of Health Studies, The University of Chicago, Chicago, IL (United States); The University of Chicago Comprehensive Cancer Center, Chicago, IL (United States); Islam, Tariqul; Paul, Rina Rani; Sarwar, Golam; Ahmed, Alauddin [U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh); Jiang, Jieying [Department of Population Health, New York University School of Medicine, New York, NY (United States); Department of Environmental Medicine, New York University School of Medicine, New York, NY (United States); Islam, Tariqul [U-Chicago Research Bangladesh, Ltd., Dhaka (Bangladesh); Slavkovich, Vesna [Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY (United States); Rundek, Tatjana [Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL (United States); Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL (United States); Demmer, Ryan T.; Desvarieux, Moise [Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY (United States); and others

    2014-05-01

    Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. - Highlights: • Nine SNPs had a nominally significant interaction with well-water arsenic in cIMT. • Three SNPs in AS3MT showed nominally significant interactions with urinary arsenic. • cIMT was much higher among subjects with higher arsenic exposure and AS3MT

  18. Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

    International Nuclear Information System (INIS)

    Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings. - Highlights: • Nine SNPs had a nominally significant interaction with well-water arsenic in cIMT. • Three SNPs in AS3MT showed nominally significant interactions with urinary arsenic. • cIMT was much higher among subjects with higher arsenic exposure and AS3MT

  19. Exposure scenarios for workers

    NARCIS (Netherlands)

    Marquart, H.; Northage, C.; Money, C.

    2007-01-01

    The new European chemicals legislation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) requires the development of Exposure Scenarios describing the conditions and risk management measures needed for the safe use of chemicals. Such Exposure Scenarios should integrate con

  20. Virtual reality exposure therapy

    OpenAIRE

    Rothbaum, BO; Hodges, L; Kooper, R

    1997-01-01

    It has been proposed that virtual reality (VR) exposure may be an alternative to standard in vivo exposure. Virtual reality integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer- generated virtual environment. Virtual reality exposure is potentially an efficient and cost-effective treatment of anxiety disorders. VR exposure therapy reduced the fear of heights in the first control...

  1. A Technique: Exposure Therapy

    Directory of Open Access Journals (Sweden)

    Serkan AKKOYUNLU

    2013-07-01

    Full Text Available Introduction: Exposure with response prevention is an effective treatment for all anxiety disorders. According to the behavioral learning theories, fears which are conditioned via classical conditioning are reinforced by respondent conditioning. Avoidance and safety seeking behaviors prevent disconfirmation of anxious beliefs. In exposure client faces stimulates or cues that elicit fear or distress, by this avoidance is inhibited. Clients are also encouraged to resists performing safety seeking behaviors or rituals that they utilize to reduce fear or distress. Accomplishing these habituation or extinction is achieved. In addition to this clients learn that feared consequences does not realize or not harmful as they believed by experiencing. Emotional processing is believed to be the mechanism of change in exposure.Objective: The aim of this review is to provide a definition of exposure and its effectiveness briefly, and describe how to implement exposure, its steps and remarkable aspects using. Exposure therapies and treatments that involve exposure are proved to be effective in all anxiety disorders. Exposure therapy can be divided in three parts: Assessment and providing a treatment rationale, creating an exposure hierarchy and response prevention plan, implementing exposure sessions. Clients must also continue to perform exposure between sessions. Therapy transcripts are also provided to exemplify these parts. Conclusion: Exposure with response prevention is a basic and effective technique. Every cognitive behavior therapist must be able to implement this technique and be cognizant of pearls of this procedure.

  2. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  3. Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure

    International Nuclear Information System (INIS)

    Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (AsIII). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to AsIII through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to AsIII and to its more toxic metabolite monomethylarsonous acid (MMAIII) at doses relevant to high environmental human exposures. In addition, both AsIII and MMAIII treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

  4. Exposures to lead.

    Science.gov (United States)

    Callan, Anna C; Hinwood, Andrea L

    2011-01-01

    The Pacific Basin Consortium for Environment and Health hosted a workshop on Exposures to Lead. Speakers from Australia and the United States of America addressed current research knowledge on lead exposures and health effects in children, risk assessment and communication issues in dealing with lead exposure sources, different methods for assessing exposure, and the variety of scenarios where lead still remains a pollutant of concern. Mining continues to be a source of lead for many communities, and approaches to reducing exposures in these settings present particular challenges. A Perth Declaration for the Global Reduction of Childhood Lead Exposure was signed by participants of the meeting and is aimed at increasing attention to the need to continue to assess lead in the environment and to develop strategies to reduce lead in the environment and exposure by communities. PMID:21714377

  5. OCCUPATIONAL EXPOSURE AND COPD

    DEFF Research Database (Denmark)

    Würtz, Else Toft

    Chronic Obstructive Pulmonary Disease (COPD) is a common disease. The main risk factor is smoking although 15% of the COPD cases are expected to be preventable if the occupational exposures from vapour, gas, dust, and fume were eliminated; the population attributable fraction (PAF). The thesis...... addresses the association between occupational exposure and COPD in a population-based cohort of Danes aged 45-84-years. 4717 participants were included at baseline and 2624 at the four year follow-up. COPD was defined by spirometry and the occupational exposure was based on specialist defined jobs and...... questionnaires. The main occupational exposure was organic dust and 49% reported no lifetime occupational exposure. The results suggest occupational exposures to be associated to COPD also in never smokers and women. We found an exposure-response relation in the cross sectional analyses. The results are in...

  6. Exposures to lead.

    Science.gov (United States)

    Callan, Anna C; Hinwood, Andrea L

    2011-01-01

    The Pacific Basin Consortium for Environment and Health hosted a workshop on Exposures to Lead. Speakers from Australia and the United States of America addressed current research knowledge on lead exposures and health effects in children, risk assessment and communication issues in dealing with lead exposure sources, different methods for assessing exposure, and the variety of scenarios where lead still remains a pollutant of concern. Mining continues to be a source of lead for many communities, and approaches to reducing exposures in these settings present particular challenges. A Perth Declaration for the Global Reduction of Childhood Lead Exposure was signed by participants of the meeting and is aimed at increasing attention to the need to continue to assess lead in the environment and to develop strategies to reduce lead in the environment and exposure by communities.

  7. Mechanism of erythrocyte death in human population exposed to arsenic through drinking water

    International Nuclear Information System (INIS)

    Arsenic contamination in drinking water is one of the biggest natural calamities, which has become an imperative threat to human health throughout the world. Abbreviation of erythrocyte lifespan leading to the development of anemia is a common sequel in arsenic exposed population. This study was undertaken to explore the mechanism of cell death in human erythrocytes during chronic arsenic exposure. Results revealed transformation of smooth discoid red cells into evaginated echinocytic form in the exposed individuals. Further distortion converted reversible echinocytes to irreversible spheroechinocytes. Arsenic toxicity increased membrane microviscosity along with an elevation of cholesterol/phospholipid ratio, which hampered the flexibility of red cell membrane and made them less deformable. Significant increase in the binding of merocyanine 540 with erythrocyte membrane due to arsenic exposure indicated disruption of lipid packing in the outer leaflet of the cell membrane resulting from altered transbilayer phospholipid asymmetry. Arsenic induced eryptosis was characterized by cell shrinkage and exposure of phosphatidylserine at the cell surface. Furthermore, metabolic starvation with depletion of cellular ATP triggered apoptotic removal of erythrocytes from circulation. Significant decrease in reduced glutathione content indicating defective antioxidant capacity was coupled with enhancement of malondialdehyde and protein carbonyl levels, which pointed to oxidative damage to erythrocyte membrane. Arsenic toxicity intervened into red cell membrane integrity eventually leading to membrane destabilization and hemoglobin release. The study depicted the involvement of both erythrophagocytosis and hemolysis in the destruction of human erythrocytes during chronic arsenic exposure

  8. Differential effects of cocaine exposure on the abundance of phospholipid species in rat brain and blood*

    Science.gov (United States)

    Cummings, Brian S.; Pati, Sumitra; Sahin, Serap; Scholpa, Natalie E.; Monian, Prashant; Trinquero, Paul O.; Clark, Jason K.; Wagner, John J.

    2015-01-01

    Background Lipid profiles in the blood are altered in human cocaine users, suggesting that cocaine-exposure can induce lipid remodeling. Methods Cocaine-induced locomotor sensitization in rats was followed by shotgun lipidomics using electrospray ionization-mass spectrometry (ESI-MS) and determined changes in brain tissues. To determine if any lipidomic changes were also reflected in the blood, we performed principal component analysis (PCA) of lipidomic spectra isolated from cocaine-treated animals. Alterations in the abundance of phospholipid species were correlated with behavioral changes in the magnitude of either the initial response to drug or locomotor sensitization. Results Behavioral sensitization altered the relative abundance of several phospholipid species in the hippocampus and cerebellum, measured one week following the final exposure to cocaine. In contrast, relatively few effects on phospholipids in either the dorsal or the ventral striatum were observed. PCA analysis demonstrated that cocaine altered the relative abundance of several glycerophospholipid species as compared to saline-injected controls. Subsequent MS/MS analysis identified some of these lipids as phosphatidylethanolamines, phosphatidylserines and phosphatidylcholines. The relative abundance of some of these phospholipid species were well correlated (R2 of 0.7 or higher) with either the initial response to cocaine or locomotor sensitization. Conclusion Taken together, these data demonstrate that a cocaine-conditioning experience results in the remodeling of specific phospholipids in rat brain tissue in a region-specific manner and also alters the intensities and types of phospholipid species in rat blood. These results further suggest that such changes may serve as biomarkers to assess the neuroadaptations occurring following repeated exposure to cocaine. PMID:25960140

  9. EXAMPLE EXPOSURE SCENARIOS ASSESSMENT TOOL

    Science.gov (United States)

    Exposure scenarios are a tool to help the assessor develop estimates of exposure, dose, and risk. An exposure scenario generally includes facts, data, assumptions, inferences, and sometimes professional judgment about how the exposure takes place. The human physiological and beh...

  10. 强化磷脂酰丝氨酸纯牛奶改善记忆力人群试食研究%Research on human memory enhancement by phosphatidylserine fortified milk

    Institute of Scientific and Technical Information of China (English)

    唐勇; 张乾勇; 糜漫天; 胡刚; 闻景

    2011-01-01

    目的 研究牛奶中强化磷脂酰丝氨酸(PS)对人的记忆力改善作用.方法 将50%纯度的PS原料以0.08%的比例添加入纯鲜牛奶,经超高温(UHT)灭菌奶工艺制作为"PS奶",将120名17~18岁中学生随机分为干预组和对照组,采用双盲法,前者每日服用PS奶250 mL,后者服用未添加PS的纯牛奶,试验期40 d.试验前后对受试者进行记忆力评分,评分方式采用临床记忆量表标准方法,分量表包括指向记忆、联想学习、图像自由回忆、无意义图形再认、人像特点联系回忆.结果 对照组服用前后各分量表得分和总分差异均无统计学意义,而PS干预组试验后各分量表得分和总分比试验前有显著性提高(P<0.05),同时,试验结束后PS干预组的各分量表得分及总分显著高于对照组,差异有统计学意义(P<0.05).结论 试验证明PS奶对学生记忆力有显著的改善和提高作用.%Objective To research whether phosphatidylserine (PS) fortified milk may have beneficial effects on memory of human being. Methods 120 students at the age of 17-18 were randomized to receive either 250 mL PS-milk which was added with 50% of PB to 0.08% (100 mg PS) and placebo(250 mL milk) for 40 days. Memory assessed by clinical memory scale with computerized multimedia method(CM) before and after consumption of milk. Results There was no significant changement(P>0.05)of MQ(memory quotation) and CM in placebo group before and after treatment. But there was significant improvement of MQ and CM in PS-milk group before and after treatment. After treatment, MQ(memory quotation) and can was significantly improved in the PS milk group compared to the placebo group(P<0.05). Conclusion This study indicates that PS milk treatment may improve cognirive performance in high school students.

  11. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    International Nuclear Information System (INIS)

    Highlights: → In 3T3-L1 adipocytes iAs3+ decreases insulin-stimulated glucose uptake. → iAs3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs3+ activates the cellular adaptive oxidative stress response. → iAs3+ impairs insulin-stimulated ROS signaling. → iAs3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs3+) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes

  12. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    expression may also be involved in arsenic-induced insulin resistance in adipocytes. Taken together our studies suggest that prolonged low-level iAs{sup 3+} exposure activates the cellular adaptive oxidative stress response, which impairs insulin-stimulated ROS signaling that is involved in ISGU, and thus causes insulin resistance in adipocytes.

  13. MANAGING TRANSACTION EXPOSURE

    OpenAIRE

    Dalina Dumitrescu

    2009-01-01

    In the period of crisis the volatility of foreign exchange is one of most importantelements to be consider in the risk management strategy at corporate level .The paper will focus onthe main types of foreign exchange exposure, the role of hedging in managing the currency risk andthe measurement of transaction exposure. The risk management in practice is illustrated by a casestudy designed to capture and contrast the effects of different types of options for hedging thetransaction exposure.

  14. Sleep enhances exposure therapy

    OpenAIRE

    Kleim, Birgit; Wilhelm, F. H.; Temp, L; Margraf, J.; Wiederhold, B. K.; Rasch, Björn

    2014-01-01

    Background: Sleep benefits memory consolidation. Here, we tested the beneficial effect of sleep on memory consolidation following exposure psychotherapy of phobic anxiety. Method: A total of 40 individuals afflicted with spider phobia according to DSM-IV underwent a one-session virtual reality exposure treatment and either slept for 90 min or stayed awake afterwards. Results: Sleep following exposure therapy compared with wakefulness led to better reductions in self-reported fear (p = 0...

  15. Monitoring of radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-02-01

    The guide specifies the requirements for the monitoring of radiation exposure in instances where radiation is used. In addition to workers, the guide covers students, apprentices and visitors. The guide shall also apply to exposure from natural radiation. However, the monitoring of radiation exposure in nuclear power plants is dealt with in YVL Guide 7.10 and 7.11. The guide defines the concepts relevant to the monitoring of radiation exposure and provides guidelines for determining the necessity of monitoring and subsequently arranging such in different operations. In addition, the guide specifies the criteria for the approval and regulatory control of the dosimetric service.

  16. BATSE sky exposure

    International Nuclear Information System (INIS)

    Angular sky exposure is presented for a number of published BATSE gamma-ray burst catalogs. A new algorithm was required due to telemetry gaps resulting from onboard tape recorder failures; the new algorithm improves the 1B Catalog exposure calculation. The most influential effects limiting BATSE's exposure are (1) deadtime due to triggering, (2) sky blockage by the Earth, and (3) trigger disabling when the spacecraft is in the SAA and over other specific Earth locations. Exposure has improved during the Compton Gamma-Ray Observatory (CGRO) mission as a result of decreased Solar flares and magnetospheric particle events

  17. Conflict exposure and competitiveness

    NARCIS (Netherlands)

    Cecchi, Francesco; Leuveld, Koen; Voors, Maarten

    2016-01-01

    We use data from a street football tournament and a series of lab-in-field experiments in postconflict Sierra Leone to examine the impact of exposure to conflict violence on competitive behavior. We find that football players who experienced more intense exposure to violence are more likely to get a

  18. Norm Exposure in China

    International Nuclear Information System (INIS)

    The paper gives a brief introduction to exposure to NORM and other natural sources in China. The number of workers monitored for occupational exposure to natural sources exceeds 10.5 million, of whom 6.5 million work in underground coal mines and 3 million work in other non-metal mines. The average annual dose received by monitored workers, mainly due to inhalation of radon, is 2.1 mSv overall. For workers in metal mines, the average dose is more than 5.5 mSv. The paper also reviews the exposure of workers in the production of thorium containing gas mantles and welding electrodes, the exposure of aircrew to cosmic radiation and exposure to radon in underground workplaces other than mines, in hot spring facilities and in homes. (author)

  19. Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jonathan Choiniere

    2016-09-01

    Full Text Available Arsenic is a carcinogenic environmental factor found in food and drinking water around the world. The mechanisms in which arsenic alters homeostasis are not fully understood. Over the past few decades, light has been shed on varying mechanisms in which arsenic induces cancer. Such mechanisms include gut microbe perturbations, genotoxic effects, and epigenetic modification. Gut microbe perturbations have been shown to increase the level of pathogen-associated molecular patterns such as lipopolysaccharide (LPS leading to uncontained inflammation. Increase in inflammation is the major factor in cirrhosis leading to hepatocellular carcinoma. Alterations in gut permeability and metabolites have also been observed as a fallout of arsenic induced gut microbe modification. The guts proximity and interaction through portal flow make the liver susceptible to gut perturbations and ensuing inflammatory responses. Genotoxic and epigenetic dysregulation induced by arsenic and its toxic metabolites present a more direct mechanism that works synergistically with gut microbe perturbations to induce the incidence of cancers. These pathways combined could be some of the main causes of arsenic-induced carcinogenesis.

  20. Phosphotidylserine exposure and neutrophil extracellular traps enhance procoagulant activity in patients with inflammatory bowel disease.

    Science.gov (United States)

    He, Zhangxiu; Si, Yu; Jiang, Tao; Ma, Ruishuang; Zhang, Yan; Cao, Muhua; Li, Tao; Yao, Zhipeng; Zhao, Lu; Fang, Shaohong; Yu, Bo; Dong, Zengxiang; Thatte, Hemant S; Bi, Yayan; Kou, Junjie; Yang, Shufen; Piao, Daxun; Hao, Lirong; Zhou, Jin; Shi, Jialan

    2016-04-01

    Inflammatory bowel disease (IBD)-associated thromboembolic event often lacks precise aetiology. The aim of this study was to investigate the contribution of phosphatidylserine (PS) exposure and neutrophil extracellular traps (NETs) towards the hypercoagulable state in IBD. We demonstrated that the levels of PS exposed MPs and the sources of MP-origin, platelets, erythrocytes, leukocytes and cultured endothelial cells (ECs) were higher in IBD groups than in healthy controls using flow cytometry and confocal microscopy. Wright-Giemsa and immunofluorescence staining demonstrated that the elevated NETs were released by activated IBD neutrophils or by control neutrophils treated with IBD sera obtained from patients with the active disease. MPs and MP-origin cells in IBD groups, especially in active stage, markedly shortened coagulation time and had increased levels of fibrin, thrombin and FXa production as assessed by coagulation function assays. Importantly, we found that on stimulated ECs, PS rich membranes provided binding sites for FXa and FVa, promoting fibrin formation while TNF blockage or IgG depletion attenuated this effect. Treatment of control neutrophils with TNF and isolated IgG from PR3-ANCA-positive active IBD patients also resulted in the release of NETs. Blockade of PS with lactadherin prolonged coagulation time, decreased fibrin formation to control levels, and inhibited the procoagulant enzymes production in the MPs and MP-origin cells. NET cleavage by DNase I partly decreased PCA in IBD or stimulated neutrophils. Our study reveals a previously unrecognised link between hypercoagulable state and PS exposure or NETs, and may further explain the epidemiological association of thrombosis within IBD patients. PMID:26660948

  1. Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India.

    Science.gov (United States)

    Chatterjee, Debmita; Bhattacharjee, Pritha; Sau, Tanmoy J; Das, Jayanta K; Sarma, Nilendu; Bandyopadhyay, Apurba K; Roy, Sib Sankar; Giri, Ashok K

    2015-09-01

    Arsenic (As) induces pre-malignant and malignant dermatological lesions, non-dermatological health effects and cancers in humans. Senescence involves telomere length changes and acquisition of senescence-associated secretory phenotype (SASP), which promotes carcinogenesis. Though in vitro studies have shown that As induces senescence, population based studies are lacking. We investigated the arsenic-induced senescence, telomere length alteration and its contribution towards development of As-induced skin cancer. The study participants included 60 each of As-exposed individuals with skin lesion (WSL), without skin lesions (WOSL) and 60 unexposed controls. Exposure assessment of drinking water and urine was done. SA β-gal activity, ELISA, and quantification of senescence proteins, alternative lengthening of telomere (ALT) associated proteins and telomerase activity were performed. Relative telomere length (RTL) was determined by qPCR. A significantly higher number of senescent cells, over-expression of p53 and p21 were observed in the As-exposed individuals when compared to unexposed. SASP markers, MMP-1/MMP-3 were significantly higher in the WSL but not IL-6/IL-8. A significant increase of RTL was observed in the WSL group, which was telomerase-independent but exhibited an over-expression of ALT associated proteins TRF-1 and TRF-2 with higher increase in TRF-2. An increased risk for developing As-induced skin lesions was found for individuals having RTL greater than 0.827 (odds ratio, 13.75; 95% CI: 5.66-33.41; P telomere length might be useful for predicting the risk of development of As-induced skin lesions. PMID:24665044

  2. Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India.

    Science.gov (United States)

    Chatterjee, Debmita; Bhattacharjee, Pritha; Sau, Tanmoy J; Das, Jayanta K; Sarma, Nilendu; Bandyopadhyay, Apurba K; Roy, Sib Sankar; Giri, Ashok K

    2015-09-01

    Arsenic (As) induces pre-malignant and malignant dermatological lesions, non-dermatological health effects and cancers in humans. Senescence involves telomere length changes and acquisition of senescence-associated secretory phenotype (SASP), which promotes carcinogenesis. Though in vitro studies have shown that As induces senescence, population based studies are lacking. We investigated the arsenic-induced senescence, telomere length alteration and its contribution towards development of As-induced skin cancer. The study participants included 60 each of As-exposed individuals with skin lesion (WSL), without skin lesions (WOSL) and 60 unexposed controls. Exposure assessment of drinking water and urine was done. SA β-gal activity, ELISA, and quantification of senescence proteins, alternative lengthening of telomere (ALT) associated proteins and telomerase activity were performed. Relative telomere length (RTL) was determined by qPCR. A significantly higher number of senescent cells, over-expression of p53 and p21 were observed in the As-exposed individuals when compared to unexposed. SASP markers, MMP-1/MMP-3 were significantly higher in the WSL but not IL-6/IL-8. A significant increase of RTL was observed in the WSL group, which was telomerase-independent but exhibited an over-expression of ALT associated proteins TRF-1 and TRF-2 with higher increase in TRF-2. An increased risk for developing As-induced skin lesions was found for individuals having RTL greater than 0.827 (odds ratio, 13.75; 95% CI: 5.66-33.41; P telomere length might be useful for predicting the risk of development of As-induced skin lesions.

  3. Pesticide-Exposure Matrix

    Science.gov (United States)

    The "Pesticide-exposure Matrix" was developed to help epidemiologists and other researchers identify the active ingredients to which people were likely exposed when their homes and gardens were treated for pests in past years.

  4. Pregnancy and Radiation Exposure

    Science.gov (United States)

    ... had that might impact the development of their sperm or their eggs (ova) and their risk of ... your concerns with them. Radiation Exposure to the Sperm from Diagnostic X-Ray Studies There are no ...

  5. Personal Chemical Exposure informatics

    Science.gov (United States)

    Chemical Exposure science is the study of human contact with chemicals (from manufacturing facilities, everyday products, waste) occurring in their environments and advances knowledge of the mechanisms and dynamics of events that cause or prevent adverse health outcomes. (adapted...

  6. Fetal exposure to pimozide

    DEFF Research Database (Denmark)

    Bjarnason, Nina H; Rode, Line; Dalhoff, Kim

    2006-01-01

    Pimozide is an antidopaminergic, antipsychotic drug. Exposure during human pregnancy has not been reported previously, and recommendations on its use are based on extrapolation from other antipsychotics with antidopaminergic activity....

  7. Poinsettia plant exposure

    Science.gov (United States)

    Christmas flower poisoning; Lobster plant poisoning; Painted leaf poisoning ... Leaves, stem, sap of the poinsettia plant ... Poinsettia plant exposure can affect many parts of the body. EYES (IF DIRECT CONTACT OCCURS) Burning Redness STOMACH AND ...

  8. Occupational Noise Exposure

    Science.gov (United States)

    ... the ear drum and are transmitted to the middle and inner ear. In the middle ear three small bones called the malleus (or ... quiet area). Restricting worker presence to a suitable distance away from noisy equipment. Controlling noise exposure through ...

  9. Inhalation exposure methodology.

    OpenAIRE

    Phalen, R F; Mannix, R C; Drew, R T

    1984-01-01

    Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and ga...

  10. Autoimmunity and Asbestos Exposure

    Directory of Open Access Journals (Sweden)

    Jean C. Pfau

    2014-01-01

    Full Text Available Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA, a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a a lack of statistical power due to relatively small or diffuse exposure cohorts, (b exposure misclassification, (c latency of clinical disease, (d mild or subclinical entities that remain undetected or masked by other pathologies, or (e effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

  11. Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Qiuling, E-mail: 924969007@qq.com [Department of Toxicology, Public Health College, Shanxi Medical University, No 56 Xin Jian Nan Lu, Taiyuan (030001) (China); Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, 510-0293 (Japan); Zhang, Jing; Xu, Wenchao; Li, Yong; Ma, Zhifeng; Li, Yunyun; Tian, Fengjie; Zhang, Wenping [Department of Toxicology, Public Health College, Shanxi Medical University, No 56 Xin Jian Nan Lu, Taiyuan (030001) (China); Mu, Jinjun [The Second Hospital, Shanxi Medical University, Taiyuan (030001) (China); Li, Yuanfei [The First Hospital, Shanxi Medical University, Taiyuan (030001) (China); Wang, Dongxing; Liu, Haifang; Yang, Mimi; Ma, Caifeng; Yun, Fen [Department of Toxicology, Public Health College, Shanxi Medical University, No 56 Xin Jian Nan Lu, Taiyuan (030001) (China)

    2013-01-01

    There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs).

  12. Asbestos Exposure Assessment Database

    Science.gov (United States)

    Arcot, Divya K.

    2010-01-01

    Exposure to particular hazardous materials in a work environment is dangerous to the employees who work directly with or around the materials as well as those who come in contact with them indirectly. In order to maintain a national standard for safe working environments and protect worker health, the Occupational Safety and Health Administration (OSHA) has set forth numerous precautionary regulations. NASA has been proactive in adhering to these regulations by implementing standards which are often stricter than regulation limits and administering frequent health risk assessments. The primary objective of this project is to create the infrastructure for an Asbestos Exposure Assessment Database specific to NASA Johnson Space Center (JSC) which will compile all of the exposure assessment data into a well-organized, navigable format. The data includes Sample Types, Samples Durations, Crafts of those from whom samples were collected, Job Performance Requirements (JPR) numbers, Phased Contrast Microscopy (PCM) and Transmission Electron Microscopy (TEM) results and qualifiers, Personal Protective Equipment (PPE), and names of industrial hygienists who performed the monitoring. This database will allow NASA to provide OSHA with specific information demonstrating that JSC s work procedures are protective enough to minimize the risk of future disease from the exposures. The data has been collected by the NASA contractors Computer Sciences Corporation (CSC) and Wyle Laboratories. The personal exposure samples were collected from devices worn by laborers working at JSC and by building occupants located in asbestos-containing buildings.

  13. Radiographic constant exposure technique

    DEFF Research Database (Denmark)

    Domanus, Joseph Czeslaw

    1985-01-01

    The constant exposure technique has been applied to assess various industrial radiographic systems. Different X-ray films and radiographic papers of two producers were compared. Special attention was given to fast film and paper used with fluorometallic screens. Radiographic image quality...... was tested by the use of ISO wire IQI's and ASTM penetrameters used on Al and Fe test plates. Relative speed and reduction of kilovoltage obtained with the constant exposure technique were calculated. The advantages of fast radiographic systems are pointed out...

  14. Singlet oxygen mediated apoptosis by anthrone involving lysosomes and mitochondria at ambient UV exposure

    Energy Technology Data Exchange (ETDEWEB)

    Mujtaba, Syed Faiz [Photobiology Division, (CSIR)-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); College of Pharmacy, Faculty of Pharmaceutical Sciences, Pt. B.D.S University of Health Sciences, Rohtak, Haryana (India); Dwivedi, Ashish; Yadav, Neera [Photobiology Division, (CSIR)-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Ray, R.S., E-mail: ratanray.2011@rediffmail.com [Photobiology Division, (CSIR)-Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh (India); Singh, Gajendra [College of Pharmacy, Faculty of Pharmaceutical Sciences, Pt. B.D.S University of Health Sciences, Rohtak, Haryana (India)

    2013-05-15

    Highlights: ► Photomodification of anthrone at ambient environmental intensities of UV-radiation. ► Phototoxicity of anthrone through type-II photodynamic reaction by generating {sup 1}O{sub 2}. ► Role of DNA damage and lipid peroxidation in anthrone phototoxicity. ► Apototic cell death and involvement of lysosomes and mitochondria. ► Up-regulation of p21 and bax concomitantly down regulation of bcl2 genes expression. -- Abstract: Anthrone a tricyclic aromatic hydrocarbon which is toxic environmental pollutant comes in the environment through photooxidation of anthracene. We have studied the photomodification of anthrone under environmental conditions. Anthrone generates reactive oxygen species (ROS) like {sup 1}O{sub 2} through Type-II photodynamic reaction. Significant intracellular ROS generation was measured through dichlorohydrofluorescein fluorescence intensity. The generation of {sup 1}O{sub 2} was further substantiated by using specific quencher like sodium azide. UV induced photodegradation of 2-deoxyguanosine and photoperoxidation of linoleic acid accorded the involvement of {sup 1}O{sub 2} in the manifestation of anthrone phototoxicity. Phototoxicity of anthrone was done on human keratinocytes (HaCaT) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake assays. Anthrone induced cell cycle arrest (G2/M-phase) and DNA damage in a concentration dependent manner. We found apoptosis as a pattern of cell death which was confirmed through sub-G1 fraction, morphological changes, caspase-3 activation, acridine orange/ethidium bromide staining and phosphatidylserine translocation. Mitochondrial depolarization and lysosomal destabilization was parallel to apoptotic process. Our RT-PCR results strongly supports our view point of apoptotic cell death through up-regulation of pro-apoptotic genes p21 and Bax, and down regulation of anti-apoptotic gene Bcl{sub 2}. Therefore, much attention should be paid to concomitant

  15. Singlet oxygen mediated apoptosis by anthrone involving lysosomes and mitochondria at ambient UV exposure

    International Nuclear Information System (INIS)

    Highlights: ► Photomodification of anthrone at ambient environmental intensities of UV-radiation. ► Phototoxicity of anthrone through type-II photodynamic reaction by generating 1O2. ► Role of DNA damage and lipid peroxidation in anthrone phototoxicity. ► Apototic cell death and involvement of lysosomes and mitochondria. ► Up-regulation of p21 and bax concomitantly down regulation of bcl2 genes expression. -- Abstract: Anthrone a tricyclic aromatic hydrocarbon which is toxic environmental pollutant comes in the environment through photooxidation of anthracene. We have studied the photomodification of anthrone under environmental conditions. Anthrone generates reactive oxygen species (ROS) like 1O2 through Type-II photodynamic reaction. Significant intracellular ROS generation was measured through dichlorohydrofluorescein fluorescence intensity. The generation of 1O2 was further substantiated by using specific quencher like sodium azide. UV induced photodegradation of 2-deoxyguanosine and photoperoxidation of linoleic acid accorded the involvement of 1O2 in the manifestation of anthrone phototoxicity. Phototoxicity of anthrone was done on human keratinocytes (HaCaT) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake assays. Anthrone induced cell cycle arrest (G2/M-phase) and DNA damage in a concentration dependent manner. We found apoptosis as a pattern of cell death which was confirmed through sub-G1 fraction, morphological changes, caspase-3 activation, acridine orange/ethidium bromide staining and phosphatidylserine translocation. Mitochondrial depolarization and lysosomal destabilization was parallel to apoptotic process. Our RT-PCR results strongly supports our view point of apoptotic cell death through up-regulation of pro-apoptotic genes p21 and Bax, and down regulation of anti-apoptotic gene Bcl2. Therefore, much attention should be paid to concomitant exposure of anthrone and UV-R for its total

  16. Mercury exposure in Ireland

    DEFF Research Database (Denmark)

    Cullen, Elizabeth; Evans, David S; Davidson, Fred;

    2014-01-01

    BACKGROUND: Monitoring of human exposure to mercury is important due to its adverse health effects. This study aimed to determine the extent of mercury exposure among mothers and their children in Ireland, and to identify factors associated with elevated levels. It formed part of the Demonstration...... of a study to Coordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES) pilot biomonitoring study. METHODS: Hair mercury concentrations were determined from a convenience sample of 120 mother/child pairs. Mothers also completed a questionnaire. Rigorous quality assurance within DEMOCOPHES...... guaranteed the accuracy and international comparability of results. RESULTS: Mercury was detected in 79.2% of the samples from mothers, and 62.5% of children's samples. Arithmetic mean levels in mothers (0.262 µg/g hair) and children (0.149 µg /g hair) did not exceed the US EPA guidance value. Levels were...

  17. Exposure, Uptake, and Barriers

    Science.gov (United States)

    Baeza-Squiban, Armelle; Lanone, Sophie

    The nanotechnologies market is booming, e.g., in the food industry (powder additives, etc.) and in medical applications (drug delivery, prosthetics, diagnostic imaging, etc.), but also in other industrial sectors, such as sports, construction, cosmetics, and so on. In this context, with an exponential increase in the number of current and future applications, it is particularly important to evaluate the problem of unintentional (i.e., non-medical) exposure to manufactured nanoparticles (so excluding nanoparticles found naturally in the environment). In this chapter, we begin by discussing the various parameters that must be taken into account in any serious assessment of exposure to man-made nanoparticles. We then list the potential routes by which nanoparticles might enter into the organism, and outline the mechanisms whereby they could get past the different biological barriers. Finally, we describe the biodistribution of nanoparticles in the organism and the way they are eliminated.

  18. Doses from radiation exposure

    CERN Document Server

    Menzel, H G

    2012-01-01

    Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effecti...

  19. Trade and Exposure

    OpenAIRE

    Dominguez, Kathryn M. E.; Tesar, Linda L.

    2001-01-01

    Are firms that engage in trade more vulnerable to exchange rate risk? Or, put another way, that exchange rate movements will influence firm asset value through the trade channel. In this paper we examine the relationship between exchange rate movements, firm value and trade. Our empirical work tests whether exchange rate exposure can be explained by variables that proxy for the level of international activity, firm size, industry affiliation and country affiliation. The results suggest that w...

  20. Occupational exposure in hemodynamic

    International Nuclear Information System (INIS)

    This paper has an objective to perform a radiometric survey at a hemodynamic service. Besides, it was intended to evaluate the effective dose of health professionals and to provide data which can contribute with minimization of exposures during the realization of hemodynamic procedure. The radiometric survey was realized in the real environment of work simulating the conditions of a hemodynamic study with a ionization chamber

  1. Human Exposure Database System (HEDS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Human Exposure Database System (HEDS) provides public access to data sets, documents, and metadata from EPA on human exposure. It is primarily intended for...

  2. Respiratory exposure control valve

    International Nuclear Information System (INIS)

    We have designed a new, three-way valve that separates inhaled and exhaled air in systems for inhalation exposure. A single-channel model of the valve was constructed and tested: with a control fluid pressure of 10 psi, the valve was cycled 36,000 times without diaphragm failure. No valve leakage was detected before or after the completion of the test. A 3-channel valve model was constructed this year and will undergo testing in FY 1979, followed by development and testing of the control system

  3. Exposure history of shergottites

    International Nuclear Information System (INIS)

    The cosmogenic nuclides 36Cl(tsub(1/2)=3.0x105 years), 26Al(7.05x105 years), 10Be(1.6x106 years) and 53Mn(3.7x106 years) were measured in three shergottites, ALHA 77005, EETA 79001, and Shergotty by accelerator mass spectrometry and neutron activation. The cosmogenic nuclide data constrain the history and origin of shergottites. ALHA 77005 was ejected from its parent body about 2.7 My ago and was exposed to cosmic rays as a body of 5-6 cm radius. Solar cosmic ray produced 26Al and 53Mn were first clearly observed in this meteorite. The exposure age of EETA 79001 was 0.6 My and the preatmospheric radius was about 15 cm. The exposure age of Shergotty was calculated to be 2.2 My and the preatmospheric size was about 10-15 cm in radius. the terrestrial age of ALHA 77005 was 0.2 My and that of EETA 79001 was less than 0.06 My. All cosmogenic nuclide data indicate that the three shergottites were never exposed to cosmic rays in their parent bodies whether that parent body was Mars or an asteroid. All shergottites were ejected from greater than a 3 m depth in their parent bodies. The ejection of EETA 79001 was a different event from that of the other shergottites. (author)

  4. Accelerated GLAS exposure station

    International Nuclear Information System (INIS)

    The Geoscience Laser Altimeter System (GLAS) is being developed by NASA/GSFC to measure the dynamics of the ice sheet mass balance, land, and cloud and atmospheric properties. An instrument altimetric resolution of 10 cm per shot is required. The laser transmitter will be a diode pumped, Q-switched, Nd:YAG laser producing 1064 nm, 100 mJ, 4 ns pulses at 40 Hz repetition rate in a TEM∞ mode. A minimum lifetime goal of 2 billion shots is required per laser transmitter. The performance of the GLAS laser can be limited by physical damage to the optical components caused by the interaction of intense laser energy with the optical coatings and substrates. Very little data exists describing the effects of long duration laser exposure, of 4 ns pulses, on an optical component. An Accelerated GLAS Exposure Station (AGES) is being developed which will autonomously operate and monitor the GLAS laser at an accelerated rate of 500 Hz. The effects of a large number of laser shots will be recorded. Parameters to be monitored include: laser power, pulsewidth, beam size, laser diode drive current and power, Q-switch drive voltage, temperature, and humidity. For comparison, one set of AGES-sister optical components will be used in the non-accelerated GLAS laser and another will be evaluated by a commercial optical damage test facility

  5. Occupational exposure to manganese.

    Science.gov (United States)

    Sarić, M; Markićević, A; Hrustić, O

    1977-05-01

    The relationship between the degree of exposure and biological effects of manganese was studied in a group of 369 workers employed in the production of ferroalloys. Two other groups of workers, from an electrode plant and from an aluminium rolling mill, served as controls. Mean manganese concentrations at work places where ferroalloys were produced varied from 0-301 to 20-442 mg/m3. The exposure level of the two control groups was from 2 to 30 microgram/m3 and from 0-05 to 0-07 microgram/m3, in the electrode plant and rolling mill respectively. Sixty-two (16-8%) manganese alloy workers showed some signs of neurological impairment. These signs were noticeably less in the two control groups (5-8% and 0%) than in the occupationally exposed group. Subjective symptoms, which are nonspecific but may be symptoms of subclinical manganism, were not markedly different in the three groups. However, in the manganese alloy workers some of the subjective symptoms occurred more frequently in heavier smokers than in light smokers or nonsmokers. Heavier smokers engaged in manganese alloy production showed some of the subjective symptoms more often than heavier smokers from the control groups.

  6. Exposures from aquatic pathways

    International Nuclear Information System (INIS)

    Methods for estimation aquatic pathways contribution to the total population exposure are discussed. Aquatic pathways are the major factor for radionuclides spreading from the Chernobyl Exclusion zone. An annual outflow of 90Sr and 137Cs comprised 10-20 TBq and 2-4 TBq respectively and the population exposed by this effluence constitutes almost 30 million people. The dynamic of doses from 90Sr and 'Cs, which Dnieper water have to delivered, is calculated. The special software has been developed to simulate the process of dose formation in the of diverse Dnieper regions. Regional peculiarities of municipal tap, fishing and irrigation are considered. Seventy-year prediction of dose structure and function of dose forming is performed. The exposure is estimated for 12 regions of the Dnieper basin and the Crimea. The maximal individual annual committed effective doses due to the use of water by ordinary members of the population in Kiev region from 90Sr and 137Cs in 1986 are 1.7*10-5 Sv and 2.7*10-5 Sv respectively. A commercial fisherman on Kiev reservoir in 1986 received 4.7*10-4 Sv and 5*10-3 Sv from 90Sr and 137Cs, respectively. The contributions to the collective cumulative (over 70 years) committed effective dose (CCCED70) of irrigation, municipal tap water and fish consumption for members of the population respectively are 18%, 43%, 39% in Kiev region, 8%, 25%, 67% in Poltava region, and 50%, 50%, 0% (consumption of Dnieper fish is absent) in the Crimea. The predicted contribution of the Strontium-90 to CCCED70 resulting from the use of water is 80%. The CCCED70 to the population of the Dnieper regions (32.5 million people) is 3000 person-Sv due to the use the Dnieper water

  7. Pesticide exposure - Indian scene

    International Nuclear Information System (INIS)

    Use of pesticides in India began in 1948 when DDT was imported for malaria control and BHC for locust control. India started pesticide production with manufacturing plant for DDT and benzene hexachloride (BHC) (HCH) in the year 1952. In 1958, India was producing over 5000 metric tonnes of pesticides. Currently, there are approximately 145 pesticides registered for use, and production has increased to approximately 85,000 metric tonnes. Rampant use of these chemicals has given rise to several short-term and long-term adverse effects of these chemicals. The first report of poisoning due to pesticides in India came from Kerala in 1958 where, over 100 people died after consuming wheat flour contaminated with parathion. Subsequently several cases of pesticide-poisoning including the Bhopal disaster have been reported. Despite the fact that the consumption of pesticides in India is still very low, about 0.5 kg/ha of pesticides against 6.60 and 12.0 kg/ha in Korea and Japan, respectively, there has been a widespread contamination of food commodities with pesticide residues, basically due to non-judicious use of pesticides. In India, 51% of food commodities are contaminated with pesticide residues and out of these, 20% have pesticides residues above the maximum residue level values on a worldwide basis. It has been observed that their long-term, low-dose exposure are increasingly linked to human health effects such as immune-suppression, hormone disruption, diminished intelligence, reproductive abnormalities, and cancer. In this light, problems of pesticide safety, regulation of pesticide use, use of biotechnology, and biopesticides, and use of pesticides obtained from natural plant sources such as neem extracts are some of the future strategies for minimizing human exposure to pesticides

  8. Opportunity Structures for Selective Exposure

    DEFF Research Database (Denmark)

    Skovsgaard, Morten; Shehata, Adam; Strömbäck, Jesper

    2016-01-01

    is to investigate the two types of selective exposure in a country—Sweden—where the opportunity structures for selective exposure differ from the American context. This study investigates both types of selective exposure in relation to televised party-leader interviews. Based on panel survey data, the findings show...... interest. Evidence for both has been found primarily in an American context, while there is less research on European countries. This is problematic, as the opportunity structures for different forms of selectivity vary across media environments. Against this background, the purpose of this study...... that selective exposure based on political interest is substantially more important than selective exposure based on ideological preferences in explaining exposure to party-leader interviews. To substantiate this finding, the results are replicated with partisan learning as the dependent variable....

  9. Domestic Asbestos Exposure: A Review of Epidemiologic and Exposure Data

    Directory of Open Access Journals (Sweden)

    Emily Goswami

    2013-10-01

    Full Text Available Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12 of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE of 5.02 (95% confidence interval [CI]: 2.48–10.13. This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners. The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6, though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2. Several exposure-related studies describe results from airborne samples collected within the home (n = 3, during laundering of contaminated clothing (n = 1 or in controlled exposure simulations (n = 5 of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6 were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers’ exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically.

  10. Domestic Asbestos Exposure: A Review of Epidemiologic and Exposure Data

    Science.gov (United States)

    Goswami, Emily; Craven, Valerie; Dahlstrom, David L.; Alexander, Dominik; Mowat, Fionna

    2013-01-01

    Inhalation of asbestos resulting from living with and handling the clothing of workers directly exposed to asbestos has been established as a possible contributor to disease. This review evaluates epidemiologic studies of asbestos-related disease or conditions (mesothelioma, lung cancer, and pleural and interstitial abnormalities) among domestically exposed individuals and exposure studies that provide either direct exposure measurements or surrogate measures of asbestos exposure. A meta-analysis of studies providing relative risk estimates (n = 12) of mesothelioma was performed, resulting in a summary relative risk estimate (SRRE) of 5.02 (95% confidence interval [CI]: 2.48–10.13). This SRRE pertains to persons domestically exposed via workers involved in occupations with a traditionally high risk of disease from exposure to asbestos (i.e., asbestos product manufacturing workers, insulators, shipyard workers, and asbestos miners). The epidemiologic studies also show an elevated risk of interstitial, but more likely pleural, abnormalities (n = 6), though only half accounted for confounding exposures. The studies are limited with regard to lung cancer (n = 2). Several exposure-related studies describe results from airborne samples collected within the home (n = 3), during laundering of contaminated clothing (n = 1) or in controlled exposure simulations (n = 5) of domestic exposures, the latter of which were generally associated with low-level chrysotile-exposed workers. Lung burden studies (n = 6) were also evaluated as a surrogate of exposure. In general, available results for domestic exposures are lower than the workers’ exposures. Recent simulations of low-level chrysotile-exposed workers indicate asbestos levels commensurate with background concentrations in those exposed domestically. PMID:24185840

  11. Occupational exposure to ionizing radiation

    International Nuclear Information System (INIS)

    An overview of occupational exposure is presented. Concepts and quantities used for radiation protection are explained as well as the ICRP system of dose limitation. The risks correlated to the limits are discussed. However, the actual exposure are often much lower than the limits and the average risk in radiation work is comparable with the average risk in other safe occupations. Actual exposures in various occupations are presented and discussed. (author)

  12. Phthalate exposure and health outcomes

    Directory of Open Access Journals (Sweden)

    Rastogi S

    2006-01-01

    Full Text Available Phthalates are used in commercial products as softners of plastics, solvents in perfumes and additives to hair sprays, lubricants and insect repellents. The wide spread use of phthalate results in multiple human exposure routes i.e., ingestion, inhalation and dermal exposure. In the present review, a detailed account of respiratory toxicity, reproductive toxicity, developmental toxicity, endocrine disruptors and genotoxicity of human exposure to phthalate is mentioned in detail.

  13. Environmental Source of Arsenic Exposure

    OpenAIRE

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a ...

  14. The Exchange Rate Exposure Puzzle

    OpenAIRE

    Bartram, Söhnke M.; Bodnar, Gordon

    2005-01-01

    Based on basic financial models and reports in the business press, exchange rate movements are generally believed to affect the value of nonfinancial firms. In contrast, the empirical research on nonfinancial firms typically produces fewer significant exposures estimates than researchers ex-pect, independent of the sample studied and the methodology used, giving rise to a situation known as “the exposure puzzle”. This paper provides a survey of the existing research on the exposure phenomenon...

  15. Medical exposure in Russia

    International Nuclear Information System (INIS)

    Recently there have been considerable changes in radiology, which is because of coming to a new form of property, reforms of health services and crisis in the society. Big area, bad means of communication and low density of population in most regions of the country should be also mentioned among the factors influencing the level of both health protection and radiology services. All these factors don't allow to create an effective radiology system in a short time. Meanwhile the main nearest task of radiology is the integration and optimization of all means of visualization on the basis of solving fundamental problems of health protection according to the Federal program, normative acts and decrees of the government. In this connection it seemed to be an urgent task to estimate various aspects of radiology activity of Russian health in the dynamics for the recent period of time. The data of the state statistics are to be used to cope with this task. These data on the basis of the computer program 'Region', the quantity indices of various visualization methods used in Russia and the doses of exposure of the population have been estimated and the reference book 'Medical irradiation of the population in Russia. 1980-1997 years' has been published. It turned out that the average annual number of X-ray examinations per thousand population in Russia before 1988 year was constantly up to 1600. And only then because of Chernobyl accident its increase stopped and its gradual decline began (table 1). Such high frequency of the examinations was caused mainly by the large scales of mass preventive photofluorography (more than 40%), held for early tuberculosis exposure. It was as a result of reorganization of fluorographic examination system started in the late 80s and early 90s that this pernicious tendency was overcome and the number of fluorography was reduced almost twice from 90 to 56 millions a year, which considerably contributed to reducing the exposure. Unfortunately as

  16. Occupational solvent exposure and cognition

    Science.gov (United States)

    Sabbath, E.L.; Glymour, M.M.; Berr, C.; Singh-Manoux, A.; Zins, M.; Goldberg, M.

    2012-01-01

    Objective: Chronic occupational solvent exposure is associated with long-term cognitive deficits. Cognitive reserve may protect solvent-exposed workers from cognitive impairment. We tested whether the association between chronic solvent exposure and cognition varied by educational attainment, a proxy for cognitive reserve. Methods: Data were drawn from a prospective cohort of French national gas and electricity (GAZEL) employees (n = 4,134). Lifetime exposure to 4 solvent types (chlorinated solvents, petroleum solvents, benzene, and nonbenzene aromatic solvents) was assessed using a validated job-exposure matrix. Education was dichotomized at less than secondary school or below. Cognitive impairment was defined as scoring below the 25th percentile on the Digit Symbol Substitution Test at mean age 59 (SD 2.8; 88% of participants were retired at testing). Log-binomial regression was used to model risk ratios (RRs) for poor cognition as predicted by solvent exposure, stratified by education and adjusted for sociodemographic and behavioral factors. Results: Solvent exposure rates were higher among less-educated patients. Within this group, there was a dose-response relationship between lifetime exposure to each solvent type and RR for poor cognition (e.g., for high exposure to benzene, RR = 1.24, 95% confidence interval 1.09–1.41), with significant linear trends (p < 0.05) in 3 out of 4 solvent types. Recency of solvent exposure also predicted worse cognition among less-educated patients. Among those with secondary education or higher, there was no significant or near-significant relationship between any quantification of solvent exposure and cognition. Conclusions: Solvent exposure is associated with poor cognition only among less-educated individuals. Higher cognitive reserve in the more-educated group may explain this finding. PMID:22641403

  17. Occupational radiation exposure

    International Nuclear Information System (INIS)

    The X-ray and Radiation Protection Ordinances in the Federal Republic of Germany and Austria were discussed. The demands of protection ordinances can only be met if the monitoring of the radiation dose is ensured to a large extent. This was stated in the lectures on dosimetry, but also in those on the technical know-how and knowledge and the quality control in radiodiagnostics. The leukemia and cancer risk for persons exposed to radiation at work came also up for discussion, and the report on the re-evaluation of data about Hiroshima and Nagasaki showing a statistically recordable rise in cancer mortality has to be seen in connection with the radiation protection laws. A lecture was held on a radiation accident in Brazil in 1987 in order to give an example of an increased radiation exposure with a fatal result. It was an off-plant radiation accident. Since a physical dosimetry naturally cannot take place in such cases, it becomes necessary to inform oneself on the extent of the detriment by means of the detrimental characteristics of the irradiated organism. Also reported was the ''biological dosimetry'' of the radiation accident in Brazil. The 23 contributions have been separately recorded in the data base. (orig./DG) With 43 figs., 41 tabs

  18. Dermal route in systemic exposure

    NARCIS (Netherlands)

    Benford, D.J.; Cocker, J.; Sartorelli, P.; Schneider, T.; Hemmen, J. van; Firth, J.G.

    1999-01-01

    To evaluate risk from dermal exposure, the amount of material on the skin must first be measured. The potential for dermal uptake must then be assessed for the potential health effects from systemic exposure. No standard methods exist for studying these processes, and published data are not comparab

  19. Exposures related to hand eczema

    DEFF Research Database (Denmark)

    Ibler, K.S.; Jemec, G.B.E.; Agner, T.

    2012-01-01

    Background. Hand eczema is common in healthcare workers, owing to intensive exposure to wet work and skin irritants. Targeted interventions and vocational guidance based on documented exposures and risk factors are needed. Objectives. The aims of the study were to investigate the relationship bet...

  20. Noise exposure and public health

    NARCIS (Netherlands)

    Passchier-Vermeer, W.; Passchier, W.F.

    2000-01-01

    Exposure to noise constitutes a health risk. There is sufficient scientific evidence that noise exposure can induce hearing impairment, hypertension and ischemic heart disease, annoyance, sleep disturbance, and decreased school performance. For other effects such as changes in the immune system and

  1. Radiation exposure and infant cancer

    International Nuclear Information System (INIS)

    Medical exposures accompanied by an increase in radiation use in the field of pediatrics were described. Basic ideas and countermeasures to radiation injuries were outlined. In order to decrease the medical exposure, it is necessary for the doctor, x-ray technician and manufacturer to work together. The mechanism and characteristics of radio carcinogenesis were also mentioned. Particularly, the following two points were described: 1) How many years does it take before carcinogenesis appears as a result of radiation exposure in infancy 2) How and when does the effect of fetus exposure appear. Radiosensitivity in infants and fetuses is greater than that of an adult. The occurrence of leukemia caused by prenatal exposure was reviewed. The relation between irradiation for therapy and morbidity of thyroid cancer was mentioned. Finally, precautions necessary for infants, pregnant women and nursing mothers when using radioisotopes were mentioned. (K. Serizawa)

  2. Primary prevention: exposure reduction, skin exposure and respiratory protection

    Directory of Open Access Journals (Sweden)

    D. Heederik

    2012-06-01

    Full Text Available Interventions for the primary prevention of occupational asthma have been reported in the medical literature, understanding the effectiveness of these efforts could help future interventions. The aim of our study was to evaluate the existing knowledge regarding the impact of controlling work exposure on the prevention of occupational asthma. We conducted systematic literature searches through April 2010 to examine if control of workplace exposures is effective for primary prevention of sensitisation and occupational asthma. The literature search for primary prevention of occupational asthma yielded 29 studies. Assessment of the available information led to the following conclusions and recommendations concerning primary prevention of occupational asthma. Exposure elimination is the strongest and preferred primary preventive approach to reduce the burden of occupational asthma. If elimination is not possible, exposure reduction is the second best option for primary prevention of occupational asthma. The evidence for the effectiveness of respirators in preventing occupational asthma is limited, and other options higher in the list of controls for occupational exposures, notably eliminating or minimising exposures at the source or in the environment, should be used preferentially. There is strong evidence to recommend not using powdered allergen-rich natural rubber latex gloves. There is weak evidence that suggests workers should minimise skin exposure to asthma-inducing agents.

  3. Noise exposure among construction electricians.

    Science.gov (United States)

    Seixas, N S; Ren, K; Neitzel, R; Camp, J; Yost, M

    2001-01-01

    Data-logging noise dosimetry was used to assess the exposure levels of electricians working for a major electrical subcontractor in Washington State at five sites using four types of construction methods. Subjects documented activities and work environment information throughout their work shift, resulting in an activity/exposure record for each of the 174 full-shift samples collected over the 4-month duration of the study. Over 24% of the TWA samples exceeded 85 dBA; 5.2% exceeded the federal Occupational Safety and Health Administration permissible exposure limit of 90 dBA. The National Institute for Occupational Safety and Health exposure metric, which specifies a 3-dB ER, was also utilized; using this metric, 67.8% of the samples exceeded 85 dBA and 27% exceeded 90 dBA. Subjects were directly observed for a subset of 4469 min during which more detailed activity and environmental information was recorded. Linear and logistic regression models using this subset were used to identify the determinants of average exposure, and exposure exceedences, respectively. These models demonstrated the importance of multiple variable modeling in interpreting exposure assessments, and the feasibility and utility of modeling exposure exceedences using logistic regression. The results further showed that presumably quiet trades such as electrician are at risk of exposure to potentially harmful noise exposures, and that other workers' activities and the general environment contribute substantially to that risk. These results indicate that noise control strategies will have to address the construction work environment as an integrated system.

  4. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    Science.gov (United States)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  5. ARSENIC-INDUCED SKIN CONDITIONS IDENTIFIED IN SOUTHWEST DERMATOLOGY PRACTICE: AN EPIDEMIOLOGIC TOOL?

    Science.gov (United States)

    Populations living in the Southwest United States are more likely to be exposed to elevated drinking water arsenic levels compared to other areas of the country. Skin changes, including hyperpigmentation and generalized hyperkeratosis, are the most common signs of chronic arsenic...

  6. Arsenic-induced histopathology and synthesis of stress proteins in liver and kidney of Channa punctatus.

    Science.gov (United States)

    Roy, Sonali; Bhattacharya, Shelley

    2006-10-01

    As3+, considered effective for aquatic weed control, has been found to be harmful to several species of freshwater teleosts. Channa punctatus (Bloch) exposed for 14 days to nonlethal concentrations (1/20 LC50 and 1/10 LC50) of As2O3 were sampled on days 0, 1, 2, 7, and 14. Tissue disorientation, peliosis, and vacuolization accompanied by karyolysis, apoptosis, and necrosis of hepatocytes were significant on days 1, 2, and 7. In the kidney shrinkage of the glomerulus and increase in the Bowman's space were observed on days 1, 2, and 7. Irregularities in the renal tubule including apoptotic and necrotic cells were also common. Decreased intertubular space and enlargement of the height of the brush border cells were noteworthy. Corresponding with the histopathological lesions, dose-dependent disturbances in liver and renal functions and induction of heat shock protein 70 were significant at the early phase of arsenic treatment while metallothionein was induced at a later phase of treatment.

  7. Nitric oxide alleviates arsenic-induced toxic effects in ridged Luffa seedlings.

    Science.gov (United States)

    Singh, Vijay Pratap; Srivastava, Prabhat Kumar; Prasad, Sheo Mohan

    2013-10-01

    Hydroponic experiments were conducted to investigate whether exogenous addition of nitric oxide (NO) as sodium nitroprusside (SNP) alleviates arsenic (As) toxicity in Luffa acutangula (L.) Roxb. seedlings. Arsenic (5 and 50 μM) declined growth of Luffa seedlings which was accompanied by significant accumulation of As. SNP (100 μM) protected Luffa seedlings against As toxicity as it declined As accumulation significantly. The photosynthetic pigments and chlorophyll fluorescence parameters such as Fv/Fm, Fv/F0, Fm/F0 and qP were decreased while NPQ was raised by As. However, the toxic effects of As on photosynthesis were significantly ameliorated by SNP. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As, however, these oxidative indices were diminished significantly in the presence of SNP. As treatment stimulated the activities of SOD and CAT while the activities of APX and GST, and AsA content and AsA/DHA ratio were decreased. Upon SNP addition, along with further rise in SOD and CAT activity, APX and GST activity, and levels of AsA and AsA/DHA ratio were restored considerably. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, APX and GST activities and decreased AsA content, hence led to the oxidative stress. However, the addition of SNP protected seedlings against As stress by regulating As accumulation, oxidative stress and antioxidant defense system.

  8. Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia faba L.

    Science.gov (United States)

    Shukla, Pratiksha; Singh, A K

    2015-09-01

    The protective effects of nitric oxide (NO) against arsenic (As)-induced structural disturbances in Vicia faba have been investigated. As treatment (0.25, 0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic treatment stimulates the activity of SOD and CAT while the activities of APX and GST content were decreased. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST activity), mitotic index, and induction of different chromosomal abnormalities, hence led to oxidative stress. The concentration of SNP (0.02 mM) was very effective in counteracting the adverse effect of As toxicity. These abnormalities use partially or fully reversed by a simultaneous application of As and NO donor and sodium nitroprusside and has an ameliorating effect against As-induced oxidative stress and genotoxicity in V. faba roots.

  9. Arsenic-induced phosphate limitation under experimental Early Proterozoic oceanic conditions

    Science.gov (United States)

    Chi Fru, Ernest; Hemmingsson, Christoffer; Holm, Mikaela; Chiu, Beverly; Iñiguez, Enrique

    2016-01-01

    Comparison of phosphorus concentrations associated with modern hydrothermal Fe(III)(oxyhydr)oxides and ancient Fe(III) oxide-rich iron formations, is used to estimate bioavailable Precambrian marine phosphorus (P) concentrations. This led to the proposition of a low dissolved P budget of ˜10-25% of present-day levels, before ˜1.9 billion years ago. Estimates incorporating ancient marine Si levels ≥ 0.67 mM instead suggested global dissolved P levels greater than today. Here we unite current experimental models that have considered NaCl solutions containing elevated dissolved Fe(II), Si, Ca2+ and Mg2+ ions in the incorporation of P in Precambrian marine Fe(III)(oxyhydr)oxides, in addition to arsenic as a hydrothermal proxy. We show that the coprecipitation of dissolved P and Fe(III)(oxyhydr)oxides from arsenic-rich marine waters produces an average P distribution coefficient of ˜0.072 (± 0.01) μM-1. This is comparable to the ˜ 0.07 μM-1 predicted for Fe(III)(oxyhydr)oxides in modern arsenic-rich, submarine hydrothermal settings, from which the lower Early Proterozoic dissolved marine P concentrations were predicted. As/P molar ratios below modern seawater ratios removed the negative feedback effect high Si impose on P scavenging by Fe(III)(oxyhydr)oxides. The binding of As(III) to Fe(III)(oxyhydr)oxides exhibits a lower competitive influence on P fixation. As(V) that likely became prominent in the surficially oxidized Early Proterozoic oceans induced dissolved P limitation because of preferential P sequestration at the expense of dissolved As(V) enrichment. The control of As on P scavenging by the precipitating Fe(III)(oxyhydr)oxides is strong regardless of common seawater cations (Mg2+ and Ca2+). The data suggest that the application of Si and Fe(III)(oxyhydr)oxides as an ancient seawater P proxy should consider chemical variability between depositional basins, taking into account the rather strong role hydrothermal arsenic has on the distribution of P in Fe(III)(oxyhydr)oxides. We propose that the generalized lower dissolved P budgets estimated from Early Proterozoic iron formations are consistent with oceans thought to be at least 3-4 times more hydrothermally active than at present.

  10. Influence Of Acacia nilotica On Arsenic Induced Genotoxicity In Male and Female Mice

    Directory of Open Access Journals (Sweden)

    INAS S. Ghaly AND ZEINAB E. HANAFY

    2010-06-01

    Full Text Available For centuries, plants have been used in traditional medicine and there has been recent interest in the chemopreventive properties of compounds derived from plants. In the present study, we investigated the effects of extracts of Acacia nilotica leaves on the genotoxicity of arsinic . Arsenic contamination in groundwater a global human health hazard .There is no effective remedial action of chronic arsenicsis. However, a well-nourished diet can modulate the onset of adverse health effects and delayed the effect of arsenic in drinking water. In the present work, genotoxic effects were induced by sodium arsenate through oral administration,and the protective effect of Acacia nilotica was studied. Chromosomal aberrations were more pronounced in sodium arsenate treated mice, while supplementation of Acacia nilotica with sodium arsenate reduced the incidence of the aberrations. The mean of DNA fragmentation induced by sodium arsenate was highly significant increase. However, the administration of Acacia nilotica significantly decreased DNA fragmentation induced by sodium arsenate. The mean number of sperms, were decreased significantly after treatment with sodium arsenate, while administration of Acacia nilotica increased the number of sperm in mice treated with sodium arsenate, and also decreased the percentage of sperm abnormalities induced by sodium arsenate. The outcome of study showed that Acacia nilotica has the efficiency to encounter the genotoxic effects induced by arsenic.

  11. Probabilistic exposure fusion.

    Science.gov (United States)

    Song, Mingli; Tao, Dacheng; Chen, Chun; Bu, Jiajun; Luo, Jiebo; Zhang, Chengqi

    2012-01-01

    The luminance of a natural scene is often of high dynamic range (HDR). In this paper, we propose a new scheme to handle HDR scenes by integrating locally adaptive scene detail capture and suppressing gradient reversals introduced by the local adaptation. The proposed scheme is novel for capturing an HDR scene by using a standard dynamic range (SDR) device and synthesizing an image suitable for SDR displays. In particular, we use an SDR capture device to record scene details (i.e., the visible contrasts and the scene gradients) in a series of SDR images with different exposure levels. Each SDR image responds to a fraction of the HDR and partially records scene details. With the captured SDR image series, we first calculate the image luminance levels, which maximize the visible contrasts, and then the scene gradients embedded in these images. Next, we synthesize an SDR image by using a probabilistic model that preserves the calculated image luminance levels and suppresses reversals in the image luminance gradients. The synthesized SDR image contains much more scene details than any of the captured SDR image. Moreover, the proposed scheme also functions as the tone mapping of an HDR image to the SDR image, and it is superior to both global and local tone mapping operators. This is because global operators fail to preserve visual details when the contrast ratio of a scene is large, whereas local operators often produce halos in the synthesized SDR image. The proposed scheme does not require any human interaction or parameter tuning for different scenes. Subjective evaluations have shown that it is preferred over a number of existing approaches. PMID:21609883

  12. Measuring exposure to organochlorinated pesticides

    Directory of Open Access Journals (Sweden)

    Gulnar Azevedo e Silva Mendonça

    1998-01-01

    Full Text Available Environmental epidemiological investigations in cancer remain, with rare exceptions, inconclusive. The difficulties of establishing patterns of measurements of exposure in the human body is one of the limitations of these studies. The findings of six recent epidemiological studies that analyzed the association between organochlorinated compounds and breast cancer are reviewed in considering the problems of measuring environmental exposure through biological markers. The epidemiological evidence based on these studies do not indicate a risk of breast cancer related to organochlorines. Some aspects that may partially explain this absence of risk are discussed regarding the investigation of environmental carcinogenic agents in populations with low but homogeneously sprayed levels of exposure.

  13. Fetal exposure in diagnostic radiology

    International Nuclear Information System (INIS)

    The problem of possible radiation damage to the fetus or embryo as a result of diagnostic radiography during pregnancy, particularly in the early stages, is discussed. Recommendations of therapeutic abortion after fetal exposure require an adequate knowledge of the doses involved. In the absence of actual dose measurements or estimates, approximate exposure levels may be determined from the literature. A summary of published values for radiography involving the lower abdomen is given. Data is also presented from a series of fetal exposures resulting mostly from routine diagnostic radiography when pregnancy was not known at the time but was established later. Results of actual dose measurements using a phantom and of dose calculations based on published values are in reasonable agreement indicating that literature values of dose provide a satisfactory alternative to measurement. These data suggest that diagnostic radiography rarely, if ever, results in fetal exposures high enough to justify therapeutic abortion. (author)

  14. Tuberculosis Facts - Exposure to TB

    Science.gov (United States)

    Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

  15. DOE 2008 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2009-10-01

    The U.S. Department of Energy (DOE) Office of Corporate Safety Analysis (HS-30) within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE. The DOE 2008 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. This report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  16. DOE 2010 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2011-11-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE.* The DOE 2010 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  17. DOE 2009 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2010-09-01

    The U.S. Department of Energy (DOE) Office of Corporate Safety Analysis (HS-30) within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE.* The DOE 2009 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  18. DOE 2011 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2012-12-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2011 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past five years.

  19. DOE 2012 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2013-10-01

    The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site.

  20. Early Life Exposures and Cancer

    Science.gov (United States)

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  1. Carcinogenesis by internal radiation exposures

    International Nuclear Information System (INIS)

    Radiation carcinogenesis is based on the same molecular mechanisms, while spatial and temporal dose distribution in target cells is differed between internal and external radiation exposures. Animal models on dose-carcinogenic response relationships are required to complement an uncertainties in human epidemiological studies and finally to estimate human risk of internal exposures to radionuclides. Several dose response models for experimental carcinogenesis by internally administered radionuclides in laboratory animals were reviewed and discussed in this paper. (J.P.N.)

  2. Occupational exposure and urological cancer.

    Science.gov (United States)

    Golka, Klaus; Wiese, Andreas; Assennato, Giorgio; Bolt, Hermann M

    2004-02-01

    Occupational exposure is definitely a major cause of cancer. In the field of urology, the urinary bladder is the most important target. A classical cause of bladder cancer is exposure to carcinogenic aromatic amines, especially benzidine and beta-naphthylamine. Such exposures were related to work places in the chemical industry, implying production and processing of classical aromatic amines, and in the rubber industry. Occupational bladder cancer has also been observed in dyers, painters and hairdressers. Even some occupations with much lower exposures to carcinogenic aromatic amines, like coke oven workers or workers in the rubber industry after the ban on beta-naphthylamine, are at risk. In these occupations, exposure to complex mixtures of substances containing combustion products (e.g. polycyclic aromatic hydrocarbons) or nitrosamines is common. Renal cell cancer has been observed as an occupational disease in cases of very high exposure to trichloroethylene having led to narcotic or prenarcotic symptoms. Occupationally related cancers of the prostate or the testes appear currently not relevant.

  3. Environmental Source of Arsenic Exposure

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made. PMID:25284196

  4. Environmental source of arsenic exposure.

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  5. pgpA和tdcG基因的敲除对大肠杆菌磷脂酰丝氨酸合成的影响%Effect of Gene pgpA and tdcG Knock-off on the Phosphatidylserine Biosynthesis in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    刘逸寒; 乔婧; 李玉; 佟新伟; 刘晓光; 路福平

    2014-01-01

    Phosphatidylserine(PS)is an important active ingredient for medicine and food industry which could improve the cognitive ability and memory. In order to improve the content of PS in Escherichia coli, the Red recombinant system was used for deleting the gene pgpA and tdcG in E. coli K12(∆sdaA ∆sdaB ∆pgpB)which can accumulate PS to block the L-serine degradation and cutting off the phosphatidylglycerophosphate catabolic pathway. After fermentation,the results showed that the total PS phospholipids synthesized by the mutant strain E. coli K12(∆pgpA∆pgpB∆sdaA∆sdaB∆tdcG)was 2.5%which was 1.5 times higher than that in the starting strain(1%).%磷脂酰丝氨酸具有改善大脑的认知和记忆的功能,是医药和食品行业重要的原料.为进一步提高大肠杆菌(Escherichia coli)中磷脂酰丝氨酸含量,利用 Red 重组系统,以可积累磷脂酰丝氨酸的 E. coli K12(∆sdaA ∆sdaB∆pgpB)为出发菌株,敲除 pgpA 和 tdcG 基因,切断与磷脂酰丝氨酸合成相关的 L-丝氨酸和磷脂酰甘油磷酸的分解代谢途径.摇瓶发酵后的检测结果表明,重组菌株E. coli K12(∆sdaA∆sdaB∆pgpA∆pgpB∆tdcG)中磷脂酰丝氨酸占菌体总磷脂的比例为2.5%,较出发菌株(1%)提高了1.5倍.

  6. Effects of Exposure Imprecision on Estimation of the Benchmark Dose

    DEFF Research Database (Denmark)

    Budtz-Jørgensen, Esben; Keiding, Niels; Grandjean, Philippe

    Environmental epidemiology; exposure measurement error; effect of prenatal mercury exposure; exposure standards; benchmark dose......Environmental epidemiology; exposure measurement error; effect of prenatal mercury exposure; exposure standards; benchmark dose...

  7. Heat exposure effects among firefighters

    Directory of Open Access Journals (Sweden)

    Patel Harshad

    2006-01-01

    Full Text Available Background: Firefighting is a hazardous occupation. The firefighters (FF in extinguishing fire are often exposed to extreme heat of 1200oC to 1400oC temperature. The heat exposure effects may occur from hot air, radiant heat, contact with hot surfaces, endogenous heat produced by the body during exercise, which cannot be cooled during fire. A significant morbidity and mortality from exposure to heat was reported in other countries but not from India. Aims : Present study focuses on prevalence of heat exposure effects i.e., heat exhaustion, heat syncope, heat pyrexia and heat cramps recorded among fire fighters of Ahmedabad fire brigade. Settings: Ahmedabad fire brigade (AFB of Ahmedabad municipal corporation. Design: Cross sectional. Materials and Methods: Present study focuses on prevalence of heat exposure effects i.e., heat exhaustion, heat syncope, heat pyrexia and heat cramps recorded between 262 FF of AFB. This prevalence′s were observed among firemen those directly exposed to heat in combating fire and others (load trucks, pump trucks etc. that assist the firemen. These were seen in different age groups (< 30; 31-45 and> 45 yrs, duration of exposure (< 10; 11-20 and> 21 yrs.The number of accidents associated with heat exposure was analyzed. Statistical Analysis: Prevalence comparison by Chi-square test. Results: The results revealed that a total of 53 (20.0% FF reported health exposure effects and were higher among firemen than other groups. Heat exhaustion 48 (18.3%; heat syncope 11(4.2%; heat pyrexia 11 (4.2% and heat cramps 16(6.1% were reported indicating significant occurrence of heat stress among firefighters. In majority of FF, the frequency of occurrence was observed at only one instance. There were no differences according to age or duration of exposure. Among 53 FF with heat exposure effects, accident were reported in 10 (18.9% suggesting that heat stress may be responsible for this. Conclusion: Overall, Significant occurrence

  8. The immunomodulatory effects of phosphatidylserine containing liposomes in EAE rats

    OpenAIRE

    Mailleux, Jo

    2012-01-01

    Multiple Sclerosis is an autoimmune disease, characterized by chronic inflammation and demyelination in the central nervous system (CNS). Macrophages play a central role in the disease process of MS and its animal model experimental autoimmune encephalomyelitis (EAE) by phagocytizing myelin and releasing inflammatory and toxic mediators in the CNS. Although tradiionally regarded to be detrimental, it was recently demonstrated that myelin-laden macrophages present in MS and EAE lesions seem to...

  9. Internalization of paramagnetic phosphatidylserine-containing liposomes by macrophages

    NARCIS (Netherlands)

    Geelen, T.; Yeo, S.Y.; Paulis, L.E.M.; Starmans, L.W.; Nicolay, K.; Strijkers, G.J.

    2012-01-01

    ABSTRACT: BACKGROUND: Inflammation plays an important role in many pathologies, including cardiovascular diseases, neurological conditions and oncology, and is considered an important predictor for disease progression and outcome. In vivo imaging of inflammatory cells will improve diagnosis and prov

  10. Radiation exposure in coronary intervention

    Energy Technology Data Exchange (ETDEWEB)

    Furuta, Motomu [Kokura Memorial Hospital, Kitakyushu, Fukuoka (Japan)

    1999-01-01

    Percutaneous transluminal coronary angioplasty (PTCA) based on plain old balloon angioplasty is the representative surgery in cardiac interventional radiography, which, with accompanying the increase of patients, causing the serious exposure problem to patients and staff. Recent progress in PTCA practice owes to the development of new devices like the stent with which reduction of exposure dose has been somewhat attained due to the short operation time. Further, standardization of the operation procedure helps to shorten the time. In author`s facility, the pulse fluoroscopy stands from four modes: low-dose, normal, high-quality and slow ones. In these modes, the exposure dose, not the irradiation dose, is taken into consideration according to the FDA concept. The respective modes resulted in the reduction to 33, 70, 70 and 50% of the ordinary fluoroscopy skin dose (12.96 mGy/min: 1.49 R/min). As for exposure to operating staff, the scattering radiation was measured with the DIGITEX 2400 CX apparatus, WAC water phantom and VICTOREEN 450 ionization chamber survey meters and with shielding curtains and lead-acryl board. Shielding was found important for reduction of exposure to the staff. (K.H.)

  11. Sarcoma risk after radiation exposure

    Directory of Open Access Journals (Sweden)

    Berrington de Gonzalez Amy

    2012-10-01

    Full Text Available Abstract Sarcomas were one of the first solid cancers to be linked to ionizing radiation exposure. We reviewed the current evidence on this relationship, focusing particularly on the studies that had individual estimates of radiation doses. There is clear evidence of an increased risk of both bone and soft tissue sarcomas after high-dose fractionated radiation exposure (10 + Gy in childhood, and the risk increases approximately linearly in dose, at least up to 40 Gy. There are few studies available of sarcoma after radiotherapy in adulthood for cancer, but data from cancer registries and studies of treatment for benign conditions confirm that the risk of sarcoma is also increased in this age-group after fractionated high-dose exposure. New findings from the long-term follow-up of the Japanese atomic bomb survivors suggest, for the first time, that sarcomas can be induced by acute lower-doses of radiation (

  12. Psychiatric disorders after radiation exposure

    International Nuclear Information System (INIS)

    This review focuses on the mental and psychological effects of medical radiation exposure, the nuclear accident at Three Mile Island, the Chernobyl disaster, atomic bomb explosions at Nagasaki and Hiroshima, and accidents at nuclear power plants and nuclear waste plants. Studies have shown that anxiety about the adverse effects of radiation in medicine (such as infertility, carcinogenicity, and genotoxicity) and fear for exposure has caused psychiatric disorders. Several studies on the mental health effects of the nuclear accident at Three Mile Island were conducted, and the results indicated that psychiatric distress persisted for a certain period of time, particularly in pregnant women and women who have children, even when no evidence of substantial of radiation exposure is seen clinically. The psychological consequences of the Chernobyl disaster have been investigated continuously, and various problems, e.g., acute stress reaction, neurosis, and psychosis, have been identified, although no physical damage due to the radiation or PTSD have been reported. By contrast, PTSD has been seen in survivors of the Nagasaki and Hiroshima nuclear explosions. A study in Ohio, (United States), which has a nuclear waste plant, investigated PTSD in people living near the plant and found that the symptom level was mild. In general, the most common symptoms among people with mental and psychological disorders due to radiation exposure are depression and anxiety, with many people having associated somatoform disorders, and some people complain of PTSD. Vague anxiety and fear of sequelae, regardless of the exposure dose, appears to cause such psychiatric disorders. Although it is rare for psychiatrists to see such cases of psychiatric disorders due to radiation exposure, their number may increase as psychiatric services become more widely available. (K.H.)

  13. Psychiatric disorders after radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kokai, Masahiro [Hyogo Coll. of Medicine, Nishinomiya (Japan); Soejima, Toshinori; Wang, Shangdong; Shinfuku, Naotaka

    2001-04-01

    This review focuses on the mental and psychological effects of medical radiation exposure, the nuclear accident at Three Mile Island, the Chernobyl disaster, atomic bomb explosions at Nagasaki and Hiroshima, and accidents at nuclear power plants and nuclear waste plants. Studies have shown that anxiety about the adverse effects of radiation in medicine (such as infertility, carcinogenicity, and genotoxicity) and fear for exposure has caused psychiatric disorders. Several studies on the mental health effects of the nuclear accident at Three Mile Island were conducted, and the results indicated that psychiatric distress persisted for a certain period of time, particularly in pregnant women and women who have children, even when no evidence of substantial of radiation exposure is seen clinically. The psychological consequences of the Chernobyl disaster have been investigated continuously, and various problems, e.g., acute stress reaction, neurosis, and psychosis, have been identified, although no physical damage due to the radiation or PTSD have been reported. By contrast, PTSD has been seen in survivors of the Nagasaki and Hiroshima nuclear explosions. A study in Ohio, (United States), which has a nuclear waste plant, investigated PTSD in people living near the plant and found that the symptom level was mild. In general, the most common symptoms among people with mental and psychological disorders due to radiation exposure are depression and anxiety, with many people having associated somatoform disorders, and some people complain of PTSD. Vague anxiety and fear of sequelae, regardless of the exposure dose, appears to cause such psychiatric disorders. Although it is rare for psychiatrists to see such cases of psychiatric disorders due to radiation exposure, their number may increase as psychiatric services become more widely available. (K.H.)

  14. Gamma radiographic exposure time indicator

    International Nuclear Information System (INIS)

    In industrial radiography, with the proper selection of source and film, the radiographic quality depends very much on the exposure time, which in turn depends upon the source strength and the source to film distance. Conventional methods to arrive at correct exposure time involve time consuming calculations and in these methods the knowledge of the above mentioned parameters is imperative. An instrument to determine the required exposure time has been developed which indicates exposure times in about 30 secs. This covers two commonly used gamma radiography sources, viz., 192Ir and 60Co and six commonly used radiography films of different speeds. Knowledge of source strength and source to film distance is not required with the use of this instrument. With a knowledge of the total exposure required by the film to give the required sensitivity and by the measurement of radiation level at the film location, the correct exposure time is determined. The radiation level is measured by placing a GM counter behind the radiographic specimen at the film location. To match the responses of the film and the GM counter, the counter is incorporated in a suitably designed probe. In this instruments, an integrator to integrate the GM-pulses and a constant current integrator (timer) are started simultaneously. The voltage at the GM-pulse integrator is compared with a preselected voltage, (selected on the basis of film type, source, source strength and order of object thickness) by a comparator. The comparator is so adjusted that when the GM-pulse integrator voltage exceeds the preselected voltage, it switches its state and stops the integration of constant current. The constant current integrator output which is proportional to the time taken for the GM-pulse integrator to reach the preselected voltage, is read on a meter graduated in terms of exposure time. The instrument can measure exposure times from 5 minutes to 10 hours read in two ranges, the range-changing being automatic

  15. Occupational RF Exposures (invited paper)

    Energy Technology Data Exchange (ETDEWEB)

    Jokela, K.; Puranen, L

    1999-07-01

    Potentially adverse levels of RF electromagnetic fields, exceeding the present limits for occupational exposure, arise near industrial high frequency (HF) heaters, high power broadcast antennas, and high power radar antennas. Other significant emitters of RF fields in the occupational environment are radiotelephones, induction heaters, short-wave and microwave therapy devices, base station antennas, magnetic resonance imaging devices, microwave ovens, and industrial microwave heaters. In terms of the intensity and duration of the exposure as well as the number of exposed workers, the HF sealers, particularly plastic sealers, constitute the most significant RF radiation safety problem in the working environment. (author)

  16. Residential RF Exposures (invited paper)

    Energy Technology Data Exchange (ETDEWEB)

    Dahme, M

    1999-07-01

    In many areas of the world there are publications on Governmental Regulations, Standards or Guidelines to protect workers and the general public against harmful effects of exposure to electromagnetic fields. Against this background, information is given about different radiation sources of electromagnetic fields in the RF part of the spectrum, which may be typical for residential exposure. Relevant radiation characteristics of the sources and field strength numbers and distributions are given. In addition some general aspects of field structure in the near- and far-field of RF radiation sources are described. On this basis principles of measurement and calculation of RF fields are explained. (author)

  17. Personal exposure to ultrafine particles.

    Science.gov (United States)

    Wallace, Lance; Ott, Wayne

    2011-01-01

    Personal exposure to ultrafine particles (UFP) can occur while people are cooking, driving, smoking, operating small appliances such as hair dryers, or eating out in restaurants. These exposures can often be higher than outdoor concentrations. For 3 years, portable monitors were employed in homes, cars, and restaurants. More than 300 measurement periods in several homes were documented, along with 25 h of driving two cars, and 22 visits to restaurants. Cooking on gas or electric stoves and electric toaster ovens was a major source of UFP, with peak personal exposures often exceeding 100,000 particles/cm³ and estimated emission rates in the neighborhood of 10¹² particles/min. Other common sources of high UFP exposures were cigarettes, a vented gas clothes dryer, an air popcorn popper, candles, an electric mixer, a toaster, a hair dryer, a curling iron, and a steam iron. Relatively low indoor UFP emissions were noted for a fireplace, several space heaters, and a laser printer. Driving resulted in moderate exposures averaging about 30,000 particles/cm³ in each of two cars driven on 17 trips on major highways on the East and West Coasts. Most of the restaurants visited maintained consistently high levels of 50,000-200,000 particles/cm³ for the entire length of the meal. The indoor/outdoor ratios of size-resolved UFP were much lower than for PM₂.₅ or PM₁₀, suggesting that outdoor UFP have difficulty in penetrating a home. This in turn implies that outdoor concentrations of UFP have only a moderate effect on personal exposures if indoor sources are present. A time-weighted scenario suggests that for typical suburban nonsmoker lifestyles, indoor sources provide about 47% and outdoor sources about 36% of total daily UFP exposure and in-vehicle exposures add the remainder (17%). However, the effect of one smoker in the home results in an overwhelming increase in the importance of indoor sources (77% of the total).

  18. Clustering of Sun Exposure Measurements

    DEFF Research Database (Denmark)

    Have, Anna Szynkowiak; Larsen, Jan; Hansen, Lars Kai;

    2002-01-01

    In a medically motivated Sun-exposure study, questionnaires concerning Sun-habits were collected from a number of subjects together with UV radiation measurements. This paper focuses on identifying clusters in the heterogeneous set of data for the purpose of understanding possible relations between...... Sun-habits exposure and eventually assessing the risk of skin cancer. A general probabilistic framework originally developed for text and Web mining is demonstrated to be useful for clustering of behavioral data. The framework combines principal component subspace projection with probabilistic...

  19. Occupational exposure to polychlorinated biphenyls (PCBs).

    OpenAIRE

    Wolff, M S

    1985-01-01

    Human occupational exposure to polychlorinated biphenyls (PCBs) with varying chlorine content has been reported by several investigators, using analyses of blood or adipose samples or skin wipes to evaluate levels in the body. The intensity of occupational exposure is related to both duration and intensity of exposure. The qualitative nature of occupational exposure, as well as casual environmental exposure, has been shown to consist of less readily metabolized PCB congeners. The pattern of P...

  20. Exposure to captan in fruit growing.

    Science.gov (United States)

    de Cock, J; Heederik, D; Kromhout, H; Boleij, J S; Hoek, F; Wegh, H; Tjoe Ny, E

    1998-03-01

    This study characterized occupational exposure to pesticides in fruit growing in The Netherlands to assess determinants of exposure. Large-scale exposure surveys were carried out during application of pesticides and during reentry activities. Data on contamination inside the fruit growers' homes were obtained, and total potential exposure for the fruit grower and his family during the growing and harvesting season was estimated. Repeated measurements on the same subject were collected to study components of exposure variability. Relative contribution of the respiratory route and different skin sites to total exposure were assessed. Captan was used as a marker for exposure. Inhalable dust exposure was measured with a personal monitor and potential dermal exposure with skin pads and hand rinsing. Dislodgeable foliar residue was measured by taking leaf punches. For respiratory exposure and potential dermal exposure, differences were observed between several tasks. Workers were categorized according to tasks performed depending on the exposure measure(s) (e.g., hands, forehead, inhalable dust) considered relevant for a specific study purpose. In general, within-worker variability of all exposure measurements was larger than between-worker variability. Variability in dermal exposure on the same body location was small relative to variability between different body locations. Differences in total exposure, including exposure inside the home, between the fruit grower and the son were small. Exposure of the wife was two to three times lower than for the fruit grower and the son. As exposure per unit of time was in the same order of magnitude for different tasks, individual time spent on these tasks is crucial for estimating total potential exposure. Repeated measurements are necessary to estimate individual exposure accurately because of the large within-worker variability.

  1. Noise Exposures of Rural Adolescents

    Science.gov (United States)

    Humann, Michael; Sanderson, Wayne; Flamme, Greg; Kelly, Kevin M.; Moore, Genna; Stromquist, Ann; Merchant, James A.

    2011-01-01

    Purpose: This project was conducted to characterize the noise exposure of adolescents living in rural and agricultural environments. Methods: From May to October, 25 adolescents ages 13 through 17, living either on a farm or a rural nonfarm, were enrolled in the study. Subjects received training on the correct operation and use of personal noise…

  2. [Occupational noise exposure and hypertension].

    Science.gov (United States)

    Santana, V S; Barberino, J L

    1995-12-01

    The hypothesis that occupational noise exposure is positively associated with hypertension was examined in a cross-sectional study carried out on a group of patients who were enrolled at the Occupational Health Unit of the Unified Health System, situated in Salvador city, the capital of Bahia state, Brazil. Data were obtained from 276 medical records, corresponding to all patients newly registered during the first six months of 1992. Data on noise exposure come from both reported occupational exposure history and clinical diagnosis of occupational noise-induced hearing loss. Hypertension diagnosis complies with World Health Organization criteria, as well as with the history of antihypertensive treatment. Stratified analysis and unconditional logistic regression modeling show results that do not support the study hypothesis: there are no differences between systolic or diastolic blood pressure or between proportion of hypertension for exposed and non exposed groups. However, statiscally significant (alpha = 0.05) increment of the effect measured was reported among workers who reported low educational level (below elementary). This could be another evidence of socially related inequalities underlying exposure distribution among workers at the workplace, which should be addressed, at greater depth, in future studies.

  3. Mitochondrial Epigenetics and Environmental Exposure.

    Science.gov (United States)

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration. PMID:27344144

  4. Chemical exposure and leukemia clusters

    International Nuclear Information System (INIS)

    This paper draws attention to the heterogeneous distribution of leukemia in childhood and in adults. The topic of cluster reports and generalized clustering is addressed. These issues are applied to what is known of the risk factor for both adult and childhood leukemia. Finally, the significance of parental occupational exposure and childhood leukemia is covered. (author). 23 refs

  5. DOE 2013 occupational radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2014-11-01

    The Office of Analysis within the U.S. Department of Energy (DOE) Office of Environment, Health, Safety and Security (EHSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2013 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protection of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past five-year period, the occupational radiation exposure information has been analyzed in terms of aggregate data, dose to individuals, and dose by site.

  6. Nonpulmonary outcomes of asbestos exposure.

    Science.gov (United States)

    Bunderson-Schelvan, Melisa; Pfau, Jean C; Crouch, Robert; Holian, Andrij

    2011-01-01

    The adverse pulmonary effects of asbestos are well accepted in scientific circles. However, the extrapulmonary consequences of asbestos exposure are not as clearly defined. In this review the potential for asbestos to produce diseases of the peritoneum, immune, gastrointestinal (GIT), and reproductive systems are explored as evidenced in published, peer-reviewed literature. Several hundred epidemiological, in vivo, and in vitro publications analyzing the extrapulmonary effects of asbestos were used as sources to arrive at the conclusions and to establish areas needing further study. In order to be considered, each study had to monitor extrapulmonary outcomes following exposure to asbestos. The literature supports a strong association between asbestos exposure and peritoneal neoplasms. Correlations between asbestos exposure and immune-related disease are less conclusive; nevertheless, it was concluded from the combined autoimmune studies that there is a possibility for a higher-than-expected risk of systemic autoimmune disease among asbestos-exposed populations. In general, the GIT effects of asbestos exposure appear to be minimal, with the most likely outcome being development of stomach cancer. However, IARC recently concluded the evidence to support asbestos-induced stomach cancer to be "limited." The strongest evidence for reproductive disease due to asbestos is in regard to ovarian cancer. Unfortunately, effects on fertility and the developing fetus are under-studied. The possibility of other asbestos-induced health effects does exist. These include brain-related tumors, blood disorders due to the mutagenic and hemolytic properties of asbestos, and peritoneal fibrosis. It is clear from the literature that the adverse properties of asbestos are not confined to the pulmonary system. PMID:21534087

  7. Environmental exposure assessment in European birth cohorts

    DEFF Research Database (Denmark)

    Gehring, Ulrike; Casas, Maribel; Brunekreef, Bert;

    2013-01-01

    hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N......=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite...

  8. Importance of reducing medical radiation exposure

    International Nuclear Information System (INIS)

    Medical exposure primarily refers to intentional irradiation of patients for diagnostic and therapeutic purposes. Among the man-made sources, diagnostic radiology is the major contributor of radiation dose to the public. This article (1) reviews the recommendations of International Commission of Radiological Protection pertaining to medical exposures, (2) stresses the importance of reducing exposure, (3) deals with the present status of medical exposure in India and (4) discusses the methodology for achieving reduction of medical exposure. Awareness, good equipment, safe work practices, discipline, trained personnel and continuing education will go a long way in achieving the goal of reduction of medical exposure. (author)

  9. Malignant mesothelioma following radiation exposure

    International Nuclear Information System (INIS)

    Mesothelioma developed in proximity to the field of therapeutic radiation administered 10-31 years previously in four patients. In three, mesothelioma arose within the site of prior therapeutic radiation for another cancer. Mesothelioma in the fourth patient developed adjacent to the site of cosmetic radiation to a thyroidectomy scar. None of these four patients recalled an asbestos exposure or had evidence of asbestosis on chest roentgenogram. Lung tissue in one patient was negative for ferruginous bodies, a finding considered to indicate no significant asbestos exposure. Five other patients with radiation-associated mesothelioma have been reported previously, suggesting that radiation is an uncommon cause of human mesothelioma. Problems in the diagnosis of radiation-associated mesotheliomas are considered

  10. [Isocyanates: occupational exposures and disorders].

    Science.gov (United States)

    Baur, X

    2003-09-01

    Isocyanates are extensively used for the production of different foams and elastomers. They also serve as glues, lacquer hardeners, inks, adhesives, fillers, finishes, sealants, coating and insulation materials. Usually, their application results in inhalative, partly also in cutaneous uptake. This review describes occupational exposures to isocyanates as well as hazardous effects. Isocyanates are used in the automotive/mechanical engineering/building and construction/mining/casting/electricity and electronic/plastics/printing/timber and furniture/white goods and textile industry, partly also in medicine. Hazardous exposures to thermal degradation products of isocyanate-based polyurethanes and other materials have also be taken into consideration. Obstructive airway diseases are the major disorder caused by isocyanates. Rare cases suffer from extrinsic allergic alveolitis or eczema. In addition to regulation-based primary prevention qualitative medical surveillance mostly prevents disorders. There is also a need for the establishment of a validated biomonitoring of endangered employees. PMID:13680473

  11. High Exposure Facility Technical Description

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Gregory L.; Stithem, Arthur R.; Murphy, Mark K.; Smith, Alex K.

    2008-02-12

    The High Exposure Facility is a collimated high-level gamma irradiator that is located in the basement of the 318 building. It was custom developed by PNNL back in 1982 to meet the needs for high range radiological instrument calibrations and dosimeter irradiations. At the time no commercially available product existed that could create exposure rates up to 20,000 R/h. This document is intended to pass on the design criteria that was employed to create this unique facility, while maintaining compliance with ANSI N543-1974, "General Safety Standard for Installations Using Non-Medical X-Ray and Sealed Gamma-Ray Sources, Energies up to 10 MeV."

  12. Double exposure. Environmental tobacco smoke.

    OpenAIRE

    Manuel, J

    1999-01-01

    One study after another is finding strong associations between a variety of human illness and exposure to environmental tobacco smoke (ETS). A 1986 report by the U.S. Surgeon General concluded that ETS is a cause of disease, including lung cancer, in healthy nonsmokers. Other reports have documented causal associations between ETS and lower respiratory tract infections, middle ear disease and exacerbation of asthma in children, heart disease, retardation of fetal growth, sudden infant death s...

  13. Exposure to Nanoparticles and Hormesis

    OpenAIRE

    Iavicoli, Ivo; Calabrese, Edward J.; Nascarella, Marc A.

    2010-01-01

    Nanoparticles are particles with lengths that range from 1 to 100 nm. They are increasingly being manufactured and used for commercial purpose because of their novel and unique physicochemical properties. Although nanotechnology-based products are generally thought to be at a pre-competitive stage, an increasing number of products and materials are becoming commercially available. Human exposure to nanoparticles is therefore inevitable as they become more widely used and, as a result, nanotox...

  14. Elemental mercury exposure: peripheral neurotoxicity.

    OpenAIRE

    Levine, S P; Cavender, G D; Langolf, G D; Albers, J W

    1982-01-01

    Nerve conduction tests were performed on the right ulnar nerve of factory workers exposed to elemental mercury vapour. Time integrated urine mercury indices were used to measure the degree of exposure. Workers with prolonged distal latencies had significantly higher urine mercury concentrations when compared with those with normal latencies. Significant correlations between increasing urine mercury concentrations and prolonged motor and sensory distal latencies were established. Elemental mer...

  15. Society's general exposure to risk

    International Nuclear Information System (INIS)

    Canadian and world experience with accidents and disease is reviewed in order to identify risk information that might extend the societal perspective on health risk beyond daily concerns. The level of exposure to catastrophic risks is compared to that associated with commonly experienced risks. An examination of current and historical levels of Canadian mortality risk is included. The association between mortality risk and Canadian industrial activity is also examined. Some prospects for utilizing these risk benchmarks are then discussed

  16. A paediatric X-ray exposure chart

    International Nuclear Information System (INIS)

    The aim of this review was to develop a radiographic optimisation strategy to make use of digital radiography (DR) and needle phosphor computerised radiography (CR) detectors, in order to lower radiation dose and improve image quality for paediatrics. This review was based on evidence-based practice, of which a component was a review of the relevant literature. The resulting exposure chart was developed with two distinct groups of exposure optimisation strategies – body exposures (for head, trunk, humerus, femur) and distal extremity exposures (elbow to finger, knee to toe). Exposure variables manipulated included kilovoltage peak (kVp), target detector exposure and milli-ampere-seconds (mAs), automatic exposure control (AEC), additional beam filtration, and use of antiscatter grid. Mean dose area product (DAP) reductions of up to 83% for anterior–posterior (AP)/posterior–anterior (PA) abdomen projections were recorded postoptimisation due to manipulation of multiple-exposure variables. For body exposures, the target EI and detector exposure, and thus the required mAs were typically 20% less postoptimisation. Image quality for some distal extremity exposures was improved by lowering kVp and increasing mAs around constant entrance skin dose. It is recommended that purchasing digital X-ray equipment with high detective quantum efficiency detectors, and then optimising the exposure chart for use with these detectors is of high importance for sites performing paediatric imaging. Multiple-exposure variables may need to be manipulated to achieve optimal outcomes

  17. Dust exposure in Finnish foundries.

    Science.gov (United States)

    Siltanen, E; Koponen, M; Kokko, A; Engström, B; Reponen, J

    1976-01-01

    Dust measurements were made in 51 iron, 9 steel, and 8 nonferrous foundries, at which 4,316 foundrymen were working. The sampling lasted at least two entire shifts or work days continuously during various operations in each foundry. The dust samples were collected at fixed sites or in the breathing zones of the workers. The mass concentration was determined by weighing and the respirable dust fraction was separated by liquid sedimentation. The free silica content was determined by X-ray diffraction. In the study a total of 3,188 samples were collected in the foundries and 6,505 determinations were made in the laboratory. The results indicated a definite difference in the dust exposure during various operations. The highest dust exposures were found during furnace, cupola, and pouring ladle repair. During cleaning work, sand mixing, and shake-out operations excessive silica dust concentrations were also measured. The lowest dust concentrations were measured during melting and pouring operations. Moderate dust concentrations were measured during coremaking and molding operations. The results obtained during the same operations of iron and steel foundries were similar. The distribution of the workers into various exposure categories, the content of respirable dust and quartz, the correlation between respirable dust and total dust, and the correlation between respirable silica and total dust concentrations are discussed. Observations concerning dust suppression and control methods are briefly considered.

  18. Diagnostic and therapeutic radiation exposure

    International Nuclear Information System (INIS)

    Diagnostic and therapeutic radiology were studied as possible contaminants in the evaluations of A-bomb survivors in the ABCC-JNIH Adult Health Study for radiation effects. Hiroshima and Nagasaki subjects received X-ray examinations elsewhere within three months of their ABCC visits at rates of 23 and 12%, respectively. Medical X-ray examinations were more frequent among survivors than comparison subjects. Hiroshima and Nagasaki radiologic practice steadily increased since 1948, and differed markedly by city. From 1946-70 the Hiroshima and Nagasaki X-ray bone marrow doses were 2,300 and 1,000 g-rads, respectively. By 1970, cumulated medical X-ray doses approximated A-bomb doses at distances from the hypocenters of 2,000 m in Hiroshima and 2,800 m in Nagasaki. ABCC X-ray examination doses per subject are routinely updated for comparison with A-bomb doses. Each subject's reported fluoroscopy, photofluorography and radiation therapy exposure elsewhere are for future reference. Dental radiography, though increasing, was not currently an important contributor to survivors' overall exposure. Radiation therapy exposures of 137 subjects were confirmed, and doses estimated for most. Two-thirds the treatments were for malignancies; therapy differed markedly by city; and five cancers possibly arose from earlier radiation therapy. This underscores the importance of considering diagnostic and therapeutic radiology when attributing diseases to the atomic bombs. (auth.)

  19. Noise exposure under hyperbaric conditions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-01

    Objective evidence exists that divers demonstrate a hearing deficit greater than would be expected from ageing effects alone. Deafness in divers may be caused by a number of factors other than exposure to excessive noise levels, eg barotrauma, ear infection etc. This review concentrates on the concern that exposure of commercial divers to noise while at work may cause a hearing deficit. Sound pressure levels recorded both underwater and in diving chambers often exceed those allowable to workers onshore. However, the sound perceived by the diver is modified both in amplitude and in frequency when he is either underwater or in pressurised chambers. Broadly the effect of this modification is to attenuate the sound and thus offer some protection from high noise levels. The degree of attentuation varies with the frequency of the sound, however it is also possible under specific conditions associated with gas density for the sensitivity to particular frequencies to be amplified above that for normal atmospheric air. The levels of sound observed from some underwater tools are of concern even after allowing for a significant de-sensitisation of the divers` hearing. Reports of tinnitus and temporary hearing loss following a dive are sure signs that the noise levels have been harmful. It is not possible at present to describe risk criteria for hearing damage due to noise exposure associated with diving. (author)

  20. Exposure from Appliances (invited paper)

    Energy Technology Data Exchange (ETDEWEB)

    Cartwright, R.A

    1999-07-01

    The dosemeter studies on exposures to ELF electromagnetic irradiation from domestic equipment all suggest the whole-body doses are low, whilst some exposure to extremities could be high but of brief duration. Old style electric overblankets, however, are an exception and produce high fields and relatively high whole-body doses if switched on during the night. Relatively few epidemiological studies have addressed these issues. All of the studies have associated problems of interpretations. Two isolated studies throw up on association with the frequency of spontaneous abortion and electric blanket use whilst another links adult AML and electric shaver usage. Both results could be fortuitous. More consistency appears from three studies of childhood leukaemia. Here statistically significant associations between electric blanket use in pregnancies appear in two separate studies, as does hair dryer use in the case of children: other appliances use associations have been reported. These results are critically assessed. The United Kingdom Childhood Cancer Study (UKCCS) addresses some of these issues as part of a wider ranging assessment of EMF at home and at school. External sources are incorporated with the measurement of domestic ambient conditions in an attempt to make an overall assessment of total exposure. (author)

  1. Cardiovascular complications of radiation exposure.

    Science.gov (United States)

    Finch, William; Shamsa, Kamran; Lee, Michael S

    2014-01-01

    The cardiovascular sequelae of radiation exposure are an important cause of morbidity and mortality following radiation therapy for cancer, as well as after exposure to radiation after atomic bombs or nuclear accidents. In the United States, most of the data on radiation-induced heart disease (RIHD) come from patients treated with radiation therapy for Hodgkin disease and breast cancer. Additionally, people exposed to radiation from the atomic bombs in Hiroshima and Nagasaki, Japan, and the Chernobyl, Ukraine, nuclear accident have an increased risk of cardiovascular disease. The total dose of radiation, as well as the fractionation of the dose, plays an important role in the development of RIHD. All parts of the heart are affected, including the pericardium, vasculature, myocardium, valves, and conduction system. The mechanism of injury is complex, but one major mechanism is injury to endothelium in both the microvasculature and coronary arteries. This likely also contributes to damage and fibrosis within the myocardium. Additionally, various inflammatory and profibrotic cytokines contribute to injury. Diagnosis and treatment are not significantly different from those for conventional cardiovascular disease; however, screening for heart disease and lifelong cardiology follow-up is essential in patients with past radiation exposure. PMID:25290729

  2. Radiation exposure in diagnostic medicine

    International Nuclear Information System (INIS)

    This volume includes the manuscripts of the papers read at the conference as well as a summary and assessment of its results. The scientific discussions were centred upon the following issues: - International surveys and comparisons of rdiation exposures in diagnostic radiology and nuclear medicine, frequency of the individual diagnostic procedures and age distribution of patients examined; - policies and regulations for the radiation protection of patients, charcteristic dosimetric values and practical usefulness of the effective dose concept during medical examinations; - assessments of the relative benefits and risks and measures to reduce the radiation exposure in the light of quality assurance aspects. The main objective of this conference not only was to evaluate the risks from diagnostic radiology and nuclear medicine but also to encourgage a critical analysis and adjustment of examination routines followed in everyday practice. Among the measures recommended were quality assurance, maintenace of international standards, development of guidelines, introduction of standard doses, improved training and professional education of personnel as well as surveys and analyses of certain examination procedures associated with substantial radiation exposure. (orig./MG)

  3. Dust exposure in Finnish foundries.

    Science.gov (United States)

    Siltanen, E; Koponen, M; Kokko, A; Engström, B; Reponen, J

    1976-01-01

    Dust measurements were made in 51 iron, 9 steel, and 8 nonferrous foundries, at which 4,316 foundrymen were working. The sampling lasted at least two entire shifts or work days continuously during various operations in each foundry. The dust samples were collected at fixed sites or in the breathing zones of the workers. The mass concentration was determined by weighing and the respirable dust fraction was separated by liquid sedimentation. The free silica content was determined by X-ray diffraction. In the study a total of 3,188 samples were collected in the foundries and 6,505 determinations were made in the laboratory. The results indicated a definite difference in the dust exposure during various operations. The highest dust exposures were found during furnace, cupola, and pouring ladle repair. During cleaning work, sand mixing, and shake-out operations excessive silica dust concentrations were also measured. The lowest dust concentrations were measured during melting and pouring operations. Moderate dust concentrations were measured during coremaking and molding operations. The results obtained during the same operations of iron and steel foundries were similar. The distribution of the workers into various exposure categories, the content of respirable dust and quartz, the correlation between respirable dust and total dust, and the correlation between respirable silica and total dust concentrations are discussed. Observations concerning dust suppression and control methods are briefly considered. PMID:184524

  4. Accounting for Unobservable Exposure Time Bias Wh...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Accounting for Unobservable Exposure Time Bias When Using Medicare Prescription Drug Data Unobservable exposure time is common among Medicare Part D beneficiaries,...

  5. Maternal exposure to metals—Concentrations and predictors of exposure

    Energy Technology Data Exchange (ETDEWEB)

    Callan, A.C., E-mail: a.callan@ecu.edu.au [Centre for Ecosystem Management, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027 (Australia); Hinwood, A.L.; Ramalingam, M.; Boyce, M. [Centre for Ecosystem Management, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027 (Australia); Heyworth, J. [School Population Health, The University of Western Australia, 35 Stirling Highway Crawley, WA 6009 (Australia); McCafferty, P. [ChemCentre, PO Box 1250, Bentley, WA 6983 (Australia); Odland, J.Ø. [Department of Community Medicine, University of Tromsø, N-9037 Tromsø (Norway)

    2013-10-15

    A variety of metals are important for biological function but have also been shown to impact health at elevated concentrations, whereas others have no known biological function. Pregnant women are a vulnerable population and measures to reduce exposure in this group are important. We undertook a study of maternal exposure to the metals, aluminium, arsenic, copper, cobalt, chromium, lithium, manganese, nickel, selenium, tin, uranium and zinc in 173 participants across Western Australia. Each participant provided a whole blood and urine sample, as well as drinking water, residential soil and dust samples and completed a questionnaire. In general the concentrations of metals in all samples were low with the notable exception of uranium (blood U mean 0.07 µg/L, range <0.01–0.25 µg/L; urinary U mean 0.018 µg/g creatinine, range <0.01–0.199 µg/g creatinine). Factors that influenced biological concentrations were consumption of fish which increased urinary arsenic concentrations, hobbies (including mechanics and welding) which increased blood manganese concentrations and iron/folic acid supplement use which was associated with decreased concentrations of aluminium and nickel in urine and manganese in blood. Environmental concentrations of aluminium, copper and lithium were found to influence biological concentrations, but this was not the case for other environmental metals concentrations. Further work is underway to explore the influence of diet on biological metals concentrations in more detail. The high concentrations of uranium require further investigation. -- Highlights: • High concentrations of uranium with respect to international literature. • Environmental concentrations of Al, Cu and Li influenced urinary concentrations. • Exposure to mechanics/welding hobbies increased blood Mn concentrations. • Iron/Folic acid supplements reduced biological concentrations of Al, Ni and Mn.

  6. Economic Exposure and Integrated Risk Management

    OpenAIRE

    Miller, Kent D.

    1994-01-01

    Most corporate risk management research focuses on particular risk exposures to the exclusion of other interrelated exposures. By contrast, this study models corporate risk exposures using a multivariate approach integrating the distinct exposures of interest to finance and strategy researchers. The paper addresses the implications of multivariate modeling for corporate risk management, some key methodological issues arising in empirical estimation of corporate economic exposrues, and direc...

  7. Mercury Exposure and Children’s Health

    OpenAIRE

    Bose-O’Reilly, Stephan; McCarty, Kathleen M; Steckling, Nadine; Lettmeier, Beate

    2010-01-01

    Acute or chronic mercury exposure can cause adverse effects during any period of development. Mercury is a highly toxic element; there is no known safe level of exposure. Ideally, neither children nor adults should have any mercury in their bodies because it provides no physiological benefit. Prenatal and postnatal mercury exposures occur frequently in many different ways. Pediatricians, nurses, and other health care providers should understand the scope of mercury exposures and health proble...

  8. Cytogenetic damage and occupational exposure. I. Exposure to stone dust.

    Science.gov (United States)

    Sobti, R C; Bhardwaj, D K

    1991-10-01

    Cytogenetic investigations were carried out on 50 workers exposed to stone dust in a stone crusher industry and on 25 control subjects never exposed to such dust. The frequency of chromosomal aberrations and sister chromatid exchanges in exposed individuals was significantly higher than that in controls (P less than 0.01). The cytogenetic indices demonstrated a clear dependence on the working environment. The effect of smoking and/or alcoholic habits coupled with exposure to stone dust has also been investigated. The results indicate that the mutagenic risk in the working environment is probably associated with silica dust in the area. PMID:1655400

  9. Cytogenetic damage and occupational exposure. 1. Exposure to stone dust

    Energy Technology Data Exchange (ETDEWEB)

    Sobti, R.C.; Bhardwaj, D.K. (Panjab Univ., Chandigarh (India))

    1991-10-01

    Cytogenetic investigations were carried out on 50 workers exposed to stone dust in a stone crusher industry and on 25 control subjects never exposed to such dust. The frequency of chromosomal aberrations and sister chromatid exchanges in exposed individuals was significantly higher than that in controls. The cytogenetic indices demonstrated a clear dependence on the working environment. The effect of smoking and/or alcoholic habits coupled with exposure to stone dust has also been investigated. The results indicate that the mutagenic risk in the working environment is probably associated with silica dust in the area.

  10. Exposure fusion using boosting Laplacian pyramid.

    Science.gov (United States)

    Shen, Jianbing; Zhao, Ying; Yan, Shuicheng; Li, Xuelong

    2014-09-01

    This paper proposes a new exposure fusion approach for producing a high quality image result from multiple exposure images. Based on the local weight and global weight by considering the exposure quality measurement between different exposure images, and the just noticeable distortion-based saliency weight, a novel hybrid exposure weight measurement is developed. This new hybrid weight is guided not only by a single image's exposure level but also by the relative exposure level between different exposure images. The core of the approach is our novel boosting Laplacian pyramid, which is based on the structure of boosting the detail and base signal, respectively, and the boosting process is guided by the proposed exposure weight. Our approach can effectively blend the multiple exposure images for static scenes while preserving both color appearance and texture structure. Our experimental results demonstrate that the proposed approach successfully produces visually pleasing exposure fusion images with better color appearance and more texture details than the existing exposure fusion techniques and tone mapping operators. PMID:25137687

  11. Kiln emissions and potters' exposures.

    Science.gov (United States)

    Hirtle, B; Teschke, K; van Netten, C; Brauer, M

    1998-10-01

    Some ten thousand British Columbia potters work in small private studios, cooperative facilities, educational institutions, or recreation centers. There has been considerable concern that this diffuse, largely unregulated activity may involve exposures to unacceptable levels of kiln emissions. Pottery kiln emissions were measured at 50 sites--10 from each of 5 categories: professional studios, recreation centers, elementary schools, secondary schools, and colleges. Area monitoring was done 76 cm from firing kilns and 1.6 m above the floor to assess breathing zone concentrations of nitrogen dioxide, carbon monoxide, sulfur dioxide, fluorides, aldehydes, aluminum, antimony, arsenic, barium, beryllium, boron, cadmium, chromium, cobalt, copper, gold, iron, lead, lithium, magnesium, manganese, mercury, nickel, selenium, silver, vanadium, and zinc. Personal exposures to the same metals were measured at 24 sites. Almost all measured values were well below permissible concentrations for British Columbia work sites and American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs) with the following two exceptions. A single firing duration (495 minute) acrolein measurement adjacent to an electric kiln (0.109 ppm) exceeded these guidelines. One 15-minute sulfur dioxide measurement collected adjacent to a gas kiln (5.7 ppm) exceeded the ACGIH short-term exposure limit. The fact that concentrations in small, ventilated kiln rooms ranked among the highest measured gives rise to concern that unacceptable levels of contamination may exist where small kiln rooms remain unventilated. Custom designed exhaust hoods and industrial heating, ventilating, and air-conditioning systems were the most effective ventilation strategies. Passive diffusion and wall/window fans were least effective. PMID:9794068

  12. Hand protection from ultraviolet exposure

    Energy Technology Data Exchange (ETDEWEB)

    Khazova, M.; O' Hagan, J.B. [Health Protection Agency, Radiation Protection Division, Chilton, Did cot (United Kingdom)

    2006-07-01

    Full text of publication follows: A number of industrial applications and public services involve exposure to ultraviolet radiation (U.V.R.) from a variety of lamps and lasers, for example, in forensic examination, biological trans-illuminators, dentistry, laser material processing, microelectronics, etc. The proposed European Union Directive on Optical Radiation would place specific requirements on employers to provide adequate safety measures to reduce exposure to U.V.R., including gloves for hand protection. The selection of gloves should be based on a risk assessment and on the performance characteristics of the gloves for the task. However, current International and national standards do not describe evaluation procedures of disposable gloves for hand protection against non-ionising radiation. A methodology for assessment of the UV protection level for disposable gloves and a simple measurement protocol are proposed, based on a common approach with UV protection by clothing and sunscreens. Glove Ultraviolet Protection Factor is defined as a time-scale increase in exposure permitted for the hand protected by a glove with respect to an unprotected hand. However, the wide variety of U.V.R. sources and the real-life conditions of glove use (stretching and wetting the surface by liquids) bring substantial challenges to the assessment method. Our study of {approx} 50 samples of widely used disposable gloves made of different materials (nitrile, vinyl, latex and chloroprene) showed that for all tested gloves a change in U.V.R. attenuation with stretching is characteristic for the type of glove material and can be included as a scaling factor in the definition of U.V.R. protection. Glove material has a bigger effect on U.V.R. protection level than variations in the glove thickness or its colour. The following approaches are suggested to overcome the problem of variable U.V.R. sources: - Worst case scenario minimal protection level, most restrictive case - Application

  13. Hand protection from ultraviolet exposure

    International Nuclear Information System (INIS)

    Full text of publication follows: A number of industrial applications and public services involve exposure to ultraviolet radiation (U.V.R.) from a variety of lamps and lasers, for example, in forensic examination, biological trans-illuminators, dentistry, laser material processing, microelectronics, etc. The proposed European Union Directive on Optical Radiation would place specific requirements on employers to provide adequate safety measures to reduce exposure to U.V.R., including gloves for hand protection. The selection of gloves should be based on a risk assessment and on the performance characteristics of the gloves for the task. However, current International and national standards do not describe evaluation procedures of disposable gloves for hand protection against non-ionising radiation. A methodology for assessment of the UV protection level for disposable gloves and a simple measurement protocol are proposed, based on a common approach with UV protection by clothing and sunscreens. Glove Ultraviolet Protection Factor is defined as a time-scale increase in exposure permitted for the hand protected by a glove with respect to an unprotected hand. However, the wide variety of U.V.R. sources and the real-life conditions of glove use (stretching and wetting the surface by liquids) bring substantial challenges to the assessment method. Our study of ∼ 50 samples of widely used disposable gloves made of different materials (nitrile, vinyl, latex and chloroprene) showed that for all tested gloves a change in U.V.R. attenuation with stretching is characteristic for the type of glove material and can be included as a scaling factor in the definition of U.V.R. protection. Glove material has a bigger effect on U.V.R. protection level than variations in the glove thickness or its colour. The following approaches are suggested to overcome the problem of variable U.V.R. sources: - Worst case scenario minimal protection level, most restrictive case - Application

  14. Exposure data for radium patients

    International Nuclear Information System (INIS)

    This appendix summarizes exposure data collected as of 31 December 1981 for 2282 radium cases under study at the Center for Human Radiobiology. It includes all persons meaasured for radium since the start of te Center in 1969 and all persons for whom we have analytic data from earlier work at the Radioactivity Center of the Massachusetts Institute of Technology, the New Jersey Radium Research Project of the New Jersey department of Health, and the Argonne Radium Studies at the Argonne National Laboratory and the Argonne Cancer Research Hospital

  15. Rheumatoid factor and tobacco exposure

    Directory of Open Access Journals (Sweden)

    Skare Thelma Larocca

    2002-01-01

    Full Text Available This study was carried out to analyse the possible influence of smoking on the positivity of rheumatoid factor (RF in healthy individuals in the region of Curitiba, Brazil. One hundred fifty blood donors (84 smokers and 66 non-smokers were studied for the presence of RF using nephelometry. Smoking was found not to be correlated to the positivity of RF, independently of the smokers sex (men with p=0.09 and women with p=0.49, the number of cigarettes/day (p=0.20, duration of smoking (p=0.18 and cumulative exposure (time X quantity to cigarettes (p=0.13.

  16. Cross-classified occupational exposure data.

    Science.gov (United States)

    Jones, Rachael M; Burstyn, Igor

    2016-09-01

    We demonstrate the regression analysis of exposure determinants using cross-classified random effects in the context of lead exposures resulting from blasting surfaces in advance of painting. We had three specific objectives for analysis of the lead data, and observed: (1) high within-worker variability in personal lead exposures, explaining 79% of variability; (2) that the lead concentration outside of half-mask respirators was 2.4-fold higher than inside supplied-air blasting helmets, suggesting that the exposure reduction by blasting helmets may be lower than expected by the Assigned Protection Factor; and (3) that lead concentrations at fixed area locations in containment were not associated with personal lead exposures. In addition, we found that, on average, lead exposures among workers performing blasting and other activities was 40% lower than among workers performing only blasting. In the process of obtaining these analyses objectives, we determined that the data were non-hierarchical: repeated exposure measurements were collected for a worker while the worker was a member of several groups, or cross-classified among groups. Since the worker is a member of multiple groups, the exposure data do not adhere to the traditionally assumed hierarchical structure. Forcing a hierarchical structure on these data led to similar within-group and between-group variability, but decreased precision in the estimate of effect of work activity on lead exposure. We hope hygienists and exposure assessors will consider non-hierarchical models in the design and analysis of exposure assessments. PMID:27029937

  17. Medical exposure and the effects of radiation

    International Nuclear Information System (INIS)

    Radiation gives cracks to genes. The influence is divided into deterministic effect with a threshold value, and the stochastic effect (tumor and genetic effect) which increases according to the exposure amount. Although we are put to various non-artificial radiations, which we cannot be avoided, on the earth, the contamination by artificial radiation can be defended. Artificial radioactive exposure includes medical exposure and non-medical exposure for example by nuclear power plant. As to medical examinations using radiation, the inquiry about the radiation exposure is increasing after the occurrence of the first nuclear power plant disaster of Fukushima. While concern about non-medical radioactive exposure increases, the uneasiness to medical irradiation is also increasing. The dose limit by artificial radioactive exposure other than medical exposure is set up in order to prevent the influence on the health. While the dose limit of the public exposure is set to the lower value than the total dose of non-artificial exposure concerning of a safety margin for all people, the dose limit of medical exposure is not defined, since it is thought that medical irradiation has a benefit for those who receive irradiation. Making an effort to decrease the radiation dose in performing the best medical treatment is the responsibility with which we are burdened. (author)

  18. Exploring Global Exposure Factors Resources for Use in Consumer Exposure Assessments

    Science.gov (United States)

    Zaleski, Rosemary T.; Egeghy, Peter P.; Hakkinen, Pertti J.

    2016-01-01

    This publication serves as a global comprehensive resource for readers seeking exposure factor data and information relevant to consumer exposure assessment. It describes the types of information that may be found in various official surveys and online and published resources. The relevant exposure factors cover a broad range, including general exposure factor data found in published compendia and databases and resources about specific exposure factors, such as human activity patterns and housing information. Also included are resources on exposure factors related to specific types of consumer products and the associated patterns of use, such as for a type of personal care product or a type of children’s toy. Further, a section on using exposure factors for designing representative exposure scenarios is included, along with a look into the future for databases and other exposure science developments relevant for consumer exposure assessment. PMID:27455300

  19. Non-occupational exposure to silica dust

    Directory of Open Access Journals (Sweden)

    L J Bhagia

    2012-01-01

    Full Text Available Occupational exposure to silica occurs at workplaces in factories like quartz crushing facilities (silica flour milling, agate, ceramic, slate pencil, glass, stone quarries and mines, etc., Non-occupational exposure to silica dust can be from industrial sources in the vicinity of the industry as well as non-industrial sources. Recently, public concern regarding non-occupational or ambient exposure to crystalline silica has emerged making it important to gather information available on non-occupational exposures to silica dust and non-occupational silicosis. This paper reviews various non-occupational exposures reported in literature including some studies by the author. Methodology used in assessment of non-occupational exposures, standards for non-occupational exposures to silica dust and indirect estimation of cumulative risk % are also discussed.

  20. Environmental exposures and respiratory outcomes in children.

    Science.gov (United States)

    Turner, Steve

    2012-12-01

    Asthma is a complex condition where genetic and environmental interactions occur at critical periods in development. The focus of this review was the role of environmental exposures on asthma causation. Selected studies published in 2010 and 2011 were reviewed to illustrate the challenge in relating environmental exposure(s) on asthma causation and also to focus on some exposures currently thought to be important to asthma pathogenesis. Challenges in understanding how environmental exposures may translate into asthma causation are summarised. Inhaled and ingested exposures are described, including microbial products, swimming pools, diet and antenatal tobacco exposure. A final synthesis summarises what is currently understood about childhood asthma causation and what advice might be given to parents and governments interested in reducing asthma risk. PMID:23069125

  1. Outdoor ultraviolet exposure of children and adolescents

    International Nuclear Information System (INIS)

    The weekday and weekend outdoor ultraviolet exposure of young people from primary and secondary schools in three geographically distinct regions of England was determined over a 3-month period in summer. Ultraviolet exposure was measured using personal film badges worn by each young person and time spent outdoors, in hourly intervals, assessed using exposure records. In each area a class of 9-10 year-old children from a primary school and a class of 14-15-year-old adolescents from a secondary school took part, giving a total of 180 subjects. We found that primary school children received higher outdoor ultraviolet exposure than young people in secondary schools, and geographical differences in exposure could not be accounted for solely by differences in ambient ultraviolet. There was little difference between the exposure of males and females. Children and adolescents did not behave as homogeneous groups with regard to exposure. (Author)

  2. Monitoring of occupational radiation exposures

    International Nuclear Information System (INIS)

    The most widely used tool for occupational radiation exposure monitoring is a badge worn on the trunk to measure Hp(10) and Hp(0.07) of photon radiation. Monitoring of exposure to beta and neutron radiations is performed for about 20% and 5%, respectively, of the workers occupationally exposed to radiation. Monitoring for internal deposition of radionuclides is, in general, less well regulated, and the results of internal dosimetry programmes are scarcely available. Dose to workers can also be determined from the results of workplace monitoring. In the case of aircrews, dose is normally computed on the basis of data on cosmic radiation fields and flight profiles. New techniques are emerging for the individual monitoring of external radiation. Active and passive electronic dosimeter systems are providing new dimensions for dosimetry and data handling, including direct dose readout capabilities and application of modern data networks. A number of problems remain to be solved. Neutron and beta dosimeters are not yet fully satisfactory. Internal dosimetry, still the subject of major research activities, has a need for more standardized routine programmes and systematic reporting. Monitoring for naturally occurring radioactive materials has to be improved and included in existing programmes. For global exchange, standards on dose record formats, and most particularly, unique quantities and units, are indispensable. (author)

  3. Environmental Exposures and Parkinson's Disease.

    Science.gov (United States)

    Nandipati, Sirisha; Litvan, Irene

    2016-01-01

    Parkinson's disease (PD) affects millions around the world. The Braak hypothesis proposes that in PD a pathologic agent may penetrate the nervous system via the olfactory bulb, gut, or both and spreads throughout the nervous system. The agent is unknown, but several environmental exposures have been associated with PD. Here, we summarize and examine the evidence for such environmental exposures. We completed a comprehensive review of human epidemiologic studies of pesticides, selected industrial compounds, and metals and their association with PD in PubMed and Google Scholar until April 2016. Most studies show that rotenone and paraquat are linked to increased PD risk and PD-like neuropathology. Organochlorines have also been linked to PD in human and laboratory studies. Organophosphates and pyrethroids have limited but suggestive human and animal data linked to PD. Iron has been found to be elevated in PD brain tissue but the pathophysiological link is unclear. PD due to manganese has not been demonstrated, though a parkinsonian syndrome associated with manganese is well-documented. Overall, the evidence linking paraquat, rotenone, and organochlorines with PD appears strong; however, organophosphates, pyrethroids, and polychlorinated biphenyls require further study. The studies related to metals do not support an association with PD. PMID:27598189

  4. Clementine auto exposure control software

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, E. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The primary mission of the Clementine program was to test technology developed under the auspices of BMDO (the Ballistic Missile Defense Organization). A secondary goal of the program was to provide astronomical data to the scientific and educational community. The mission plan developed to accomplish these goals included complete mapping of the lunar surface and a close fly-by of a near-Earth asteroid, 1620 Geographos. Exposure control for the Clementine mission was driven by mission phase requirements and sensor characteristics. Thus, there were a total of twelve algorithms developed for three primary mission phases and the four imaging sensors (two additional sensors operated as star trackers). The three mission phases in question were lunar mapping, distant observation of the asteroid for the purpose of tracking, and close-up viewing (as close as 100 Km) of Geographos. The four non-star tracker sensors consisted of an Ultra Violet/Visible (UV/Vis) camera, a High Resolution (HiRes) camera with a built-in LIDAR (Light Detection And Ranging) unit, a Near Infrared (NIR) camera, and a Long Wave InfraRed (LWIR) camera. Due to lack of test time and uncertainties about the imaging environment, numerous input parameters were provided in the algorithms to allow extensive tuning of the exposure control during the mission.

  5. Use of dose constraints in medical exposure

    International Nuclear Information System (INIS)

    Medical-related radiation is the largest source of controllable radiation exposure to humans and it accounts for more than 95% of radiation exposure from man-made sources. Medical exposure to radiation is exposure incurred by patients as part of their own medical or dental diagnosis or treatment; by persons, other than those occupationally exposed, knowingly, while voluntarily helping in the support and comfort of patients; and by volunteers in a programme of biomedical research involving their exposure. Because it is planned exposure, medical exposure has to conform to a set of principles of protection that apply equally to all controllable exposure situations: the principle of justification, the principle of optimisation of protection, and the principle of application of limits on maximum doses in planned situations. In this study the concept of dose constraints is being scrutinized to see if it can be applied in medical exposures and the benefits of such restrictions. Dose constraints can only be applied to exposure to persons voluntary helping in the support and comfort of patients as well as volunteers in the programme of biomedical research. There are no dose constraints for patients but the concept of reference levels applies. (au)

  6. Non-medical exposures - Ethical concerns

    International Nuclear Information System (INIS)

    The scope of the Medical Exposure Directive (MED), 97/43/Euratom (Council Directive 97/43/EURATOM, on the health protection of individuals against the dangers of ionising radiation in relation to medical exposures. OJ L 180 of 09.07.1997), is such that it includes not only those exposures which are part of the normal diagnosis and treatment of patients but also exposures for occupational health surveillance, health-screening programmes, research and medico-legal exposures. This is the first time that radiation protection legislation has tried to deal explicitly with the issue of medico-legal exposures in a European Directive. However, it has done so in the context of a Directive whose primary focus is the protection of patients undergoing diagnostic or therapeutic medical exposures. This may not be an appropriate framework for medico-legal exposures. In considering medico-legal exposures, a significant number of ethical considerations arise. The MED may not adequately take account of these matters and in fact may not be a suitable legal instrument for dealing with them. This paper looks specifically at the issues surrounding medico-legal exposures and considers whether or not the current system provides adequate protection for the individuals exposed. (authors)

  7. Relevance of protection quantities in medical exposures

    International Nuclear Information System (INIS)

    International Commission on Radiological Protection (ICRP) continues to classify the exposures to radiation in three categories; namely 1- occupational exposure, 2- public exposure, and 3- medical exposure. Protection quantities are primarily meant for the regulatory purpose in radiological protection for controlling and limiting stochastic risks in occupational and public exposures. These are based on two basic assumptions of 1- linear no-threshold dose-effect relationship (LNT) at low doses and 2- long-term additivity of low doses. Medical exposure are predominantly delivered to individuals (patients) undergoing diagnostic examinations, interventional procedures and radiation therapy but also include individual caring for or comforting patients incurring exposure and the volunteers of biomedical medical research programmes. Radiation protection is as relevant to occupational and public exposure as to medical exposures except that the dose limits set for the formers are not applicable to medical exposure but reference levels and dose constrains are recommended for diagnostic and interventional medical procedures. In medical institutions, both the occupational and medical exposure takes place. Since the doses in diagnostic examinations are low, it has been observed that not only the protection quantities are often used in such cases but these are extended to estimate the number of cancer deaths due to such practices. One of the striking features of the new ICRP recommendations has been to elaborate the concepts of the dosimetric quantities. The limitation of protection quantities ((Effective dose, E=ΣRT DTR.WT.WR and Equivalent Dose HT=ΣRT DTR.WR) have been brought out and this has raised a great concern and initiated debates on the use of these quantities in medical exposures. Consequently, ICRP has set a task group to provide more details and the recommendations. It has, therefore, became important to draw the attention of medical physics community on relevance

  8. Elaboration of a quantitative job-exposure matrix for historical exposure to airborne exposures in the Polish rubber industry.

    OpenAIRE

    de Vocht, F; Sobala, W; Peplonska, B.; Wilczynska, U.; Gromiec, J.; Szeszenia-Dabrowska, N.; Kromhout, H

    2008-01-01

    BACKGROUND: A job-exposure matrix (JEM) for inhalable aerosols, aromatic amines, and cyclohexane soluble matter (CSM) was elaborated based on measurements collected routinely between 1981 and 1996. METHODS: The data were grouped based on similarities in exposure levels and time trends in different departments, and were analyzed using smoothing splines and mixed effects models. RESULTS: Although higher than in western European countries, inhalable aerosol exposure decreased after changes in pr...

  9. Y-12 Uranium Exposure Study

    Energy Technology Data Exchange (ETDEWEB)

    Eckerman, K.F.; Kerr, G.D.

    1999-08-05

    Following the recent restart of operations at the Y-12 Plant, the Radiological Control Organization (RCO) observed that the enriched uranium exposures appeared to involve insoluble rather than soluble uranium that presumably characterized most earlier Y-12 operations. These observations necessitated changes in the bioassay program, particularly the need for routine fecal sampling. In addition, it was not reasonable to interpret the bioassay data using metabolic parameter values established during earlier Y-12 operations. Thus, the recent urinary and fecal bioassay data were interpreted using the default guidance in Publication 54 of the International Commission on Radiological Protection (ICRP); that is, inhalation of Class Y uranium with an activity median aerodynamic diameter (AMAD) of 1 {micro}m. Faced with apparently new workplace conditions, these actions were appropriate and ensured a cautionary approach to worker protection. As additional bioassay data were accumulated, it became apparent that the data were not consistent with Publication 54. Therefore, this study was undertaken to examine the situation.

  10. Animal Exposure During Burn Tests

    Science.gov (United States)

    Gaume, J. G.

    1978-01-01

    An animal exposure test system (AETS) was designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consisted of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram (ECG) and respiration. Cage temperature is measured by a thermistor located in the upper portion of the rat compartment. Animal activity is monitored by the ECG and the records indicate an increase in EMG (electromyograph) noise super-imposed by the increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases and specific events occurring during the test. The AETS was shown to be a useful tool in screening materials for the relative toxicity of their outgassing products during pyrolysis and combustion.

  11. Prenatal radiation exposure. Dose calculation

    International Nuclear Information System (INIS)

    The unborn child requires special protection. In this context, the indication for an X-ray examination is to be checked critically. If thereupon radiation of the lower abdomen including the uterus cannot be avoided, the examination should be postponed until the end of pregnancy or alternative examination techniques should be considered. Under certain circumstances, either accidental or in unavoidable cases after a thorough risk assessment, radiation exposure of the unborn may take place. In some of these cases an expert radiation hygiene consultation may be required. This consultation should comprise the expected risks for the unborn while not perturbing the mother or the involved medical staff. For the risk assessment in case of an in-utero X-ray exposition deterministic damages with a defined threshold dose are distinguished from stochastic damages without a definable threshold dose. The occurrence of deterministic damages depends on the dose and the developmental stage of the unborn at the time of radiation. To calculate the risks of an in-utero radiation exposure a three-stage concept is commonly applied. Depending on the amount of radiation, the radiation dose is either estimated, roughly calculated using standard tables or, in critical cases, accurately calculated based on the individual event. The complexity of the calculation thereby increases from stage to stage. An estimation based on stage one is easily feasible whereas calculations based on stages two and especially three are more complex and often necessitate execution by specialists. This article demonstrates in detail the risks for the unborn child pertaining to its developmental phase and explains the three-stage concept as an evaluation scheme. It should be noted, that all risk estimations are subject to considerable uncertainties.

  12. Occupational Exposures and Chronic Airflow Limitation

    Directory of Open Access Journals (Sweden)

    Helen Dimich-Ward

    1996-01-01

    Full Text Available The recent literature was reviewed to evaluate whether chronic airflow limitation is associated with occupational exposures to dusts. Only those studies that controlled for the effects of smoking were included. There is compelling evidence that exposure to inorganic dusts, such as from coal and hardrock mining or asbestos, are associated with the development of chronic airflow limitation, independently of pneumoconiosis. Nonsmoking gold miners are particularly at high risk of airflow obstruction and emphysema. Findings from studies of organic dusts, such as exposures to wood, cotton, grain or other agricultural dusts, or to mixed dust exposures, were less consistent but tended to show positive dose-response associations. In the majority of studies, no statistical interaction was shown between dust exposures and smoking; however, the effects of the dust exposures were often more pronounced. An occupational history should be considered, in addition to a smoking history, as an integral part of an investigation of chronic airflow limitation in a patient.

  13. Medical exposures requirements, present situation and prospects

    International Nuclear Information System (INIS)

    Scope of medical exposures is studied, these include: exposure to patients as part of their diagnosis or treatment, exposures to persons who knowingly have assisted patients, exposures volunteers included in biomedical research programs. Medical exposures have contributed their benefits for human health improvement: possess a necessary character that people have to be exposed to radiation doses to achieve their goals, convergence of risk and benefit in the same individual is presented, variability is implicated in dose given to patients in terms of size and distribution, have contributed significantly to the doses received by the world population. Despite the above attributes and generally contribute to the direct benefit of the patient, long has been given less attention than other forms of exposure, there still potential for dose reduction to patients as a result of the applications of ionizing radiation. Currently have used for nuclear medicine diagnostic x-ray procedures, exams MN, radiotherapy, tomography, both medical and dental radiology. (author)

  14. Double blind placebo controlled exposure to molds

    DEFF Research Database (Denmark)

    Meyer, H W; Jensen, K A; Nielsen, K F;

    2005-01-01

    The objective was to develop an experimental setup for human exposure to mold spores, and to study the clinical effect of this exposure in sensitive subjects who had previously experienced potentially building-related symptoms (BRS) at work. From three water-damaged schools eight employees....... In conclusion this is, to our knowledge, the first study to successfully conduct a human exposure to a highly controlled dose of fungal material aerosolized directly from wet building materials. This short-term exposure to high concentrations of two different molds induced no more reactions than exposure...... to placebo in eight sensitive school employees. However, a statistical type II error cannot be excluded because of the small sample size. PRACTICAL IMPLICATIONS: In this double blind, placebo controlled study of mold exposure changes in symptoms, objective measurements and blood samples were small and mostly...

  15. Low-exposure tritium radiotoxicity in mammals

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, R.L.

    1982-02-11

    Studies of tritium radiotoxicity involving chronic /sup 3/H0H exposures in mammals demonstrate in both mice and monkeys that biological effects can be measured following remarkably low levels of exposure - levels in the range of serious practical interest to radiation protection. These studies demonstrate also that deleterious effects of /sup 3/H beta radiation do not differ significantly from those of gamma radiation at high exposures. In contrast, however, at low exposures tritium is significantly more effective than gamma rays, rad for rad, by a factor approaching 3. This is important for hazard evaluation and radiation protection because knowledge concerning biological effects of chronic low-level radiation exposure has come mainly from gamma-ray data; and predictions based on gamma-ray data will underestimate tritium effects - especially at low exposures - unless the RBE is fully taken into account.

  16. Sound Exposure of Symphony Orchestra Musicians

    DEFF Research Database (Denmark)

    Schmidt, Jesper Hvass; Pedersen, Ellen Raben; Juhl, Peter Møller;

    2011-01-01

    exposure depends significantly on the specific instrument and the repertoire played by the exposed musician. Concerts, group rehearsals and individual practice were all significant contributors to the sound exposure. The highest LAeq of 86 –98 dB was found among the brass players. High string players were......Background: Assessment of sound exposure by noise dosimetry can be challenging especially when measuring the exposure of classical orchestra musicians where sound originate from many different instruments. A new measurement method of bilateral sound exposure of classical musicians was developed and...... levels exceeding LAeq8h of 85 dB.Conclusions: Binaural recording of the individual sound exposure showed that orchestra musicians could be exposed differently to the left and right ear and that they were primarily exposed from their own instruments. Specific repertoires as well as the specific instrument...

  17. Current chemical exposures among Ontario construction workers.

    Science.gov (United States)

    Verma, Dave K; Kurtz, Lawrence A; Sahai, Dru; Finkelstein, Murray M

    2003-12-01

    Current occupational exposures to chemical agents were assessed as part of an epidemiological study pertaining to the cancer and mortality patterns of Ontario construction workers. The task-based exposure assessment involved members from nine construction trade unions. Air samples were taken using personal sampling pumps and collection media. A DustTrak direct-reading particulate monitor was also employed. Exposure assessments included measurements of airborne respirable, inhalable, total, and silica dust; solvents; metals; asbestos; diesel exhaust and man-made mineral fibers (MMMF). In total, 396 single- or multi-component (filter/tube), 798 direct-reading, and 71 bulk samples were collected. The results showed that Ontario construction workers are exposed to potentially hazardous levels of chemical agents. The findings are similar to those reported by other researchers, except for silica exposure. In our study, silica exposure is much lower than reported elsewhere. The difficulty associated with assessing construction workers' exposures is highlighted. PMID:14612300

  18. An Overview of Foreign Currency Exposure

    OpenAIRE

    Harris, Peter; Kaur, Simran

    2013-01-01

    Foreign exchange exposure is defined as the assessment of potential of a firm’s profitability, net cash flow, and market value to change due to unpredictable changes of foreign exchange rates, which can be financially unfavorable to the global firm. This paper discusses the three various types of major foreign exchange exposure which are, translation, transaction, and economic; the risks associated with each exposure, and how to minimize specific currency risks.

  19. Epidemiology of cancer from exposure to arylamines.

    OpenAIRE

    Vineis, P

    1994-01-01

    Occupational exposure to arylamines such as benzidine, 2-naphthylamine, and 4-aminobiphenyl is associated with exceptionally elevated risks of bladder cancer (up to 100-fold or more). In one plant, all 15 workers involved in distilling naphthylamine developed bladder cancer, suggesting that for high levels of exposure to potent carcinogens individual susceptibility is irrelevant. More recently, exposure to other arylamines also has been suggested to increase the risk of bladder cancer in huma...

  20. New approaches to reduce radiation exposure.

    Science.gov (United States)

    Hill, Kevin D; Einstein, Andrew J

    2016-01-01

    Exposure to ionizing radiation is associated with a long-term risk of health effects, including cancer. Radiation exposure to the U.S. population from cardiac imaging has increased markedly over the past three decades. Initiatives to reduce radiation exposure have focused on the tenets of appropriate study "justification" and "optimization" of imaging protocols. This article reviews ways to optimally reduce radiation dose across the spectrum of cardiac imaging.

  1. Managing workers' compensation exposures in healthcare.

    Science.gov (United States)

    McDonald, L

    1998-01-01

    Employees in healthcare are exposed to numerous and varied risks that pose the threat of injury. Management of those exposures by the organization will ultimately help create a safe environment for staff, patients and the public. Incorporating workers' compensation into the risk management program is the first step toward managing and reducing these exposures. This article presents a suggested outline for a written risk management plan for workers' compensation exposures. PMID:10182134

  2. Measuring and exposures from National Media Surveys

    DEFF Research Database (Denmark)

    Mortensen, Peter Stendahl

    2000-01-01

    Natinal media surveys inform about the number and kind of people being exposed to the media in question. This paper discusses to what extent these numbers may be used as measures for the exposure to ads in the media in question. In this context attention is also focussed on elements in the media...... surveys themselves that might invalidate or give unreliable measures, both when measuring a single exposure and accumulated exposures. Four media types will be discussed: TV, radio, print and the internet....

  3. Reducing medical exposure to ionizing radiation

    International Nuclear Information System (INIS)

    The author discusses the dangers of indiscriminate and uninformed use of medical x-ray facilities. He points out a lack of effective standards, controls, and practices to minimize exposures to x ray and to prevent the excessive use of diagnostic x-ray examinations. A list of practices whereby an individual can minimize his possible exposures to x rays is presented. Several approaches to the question of acceptable exposure levels are considered. (U.S.)

  4. Mycotoxins: occurrence, toxicology, and exposure assessment.

    Science.gov (United States)

    Marin, S; Ramos, A J; Cano-Sancho, G; Sanchis, V

    2013-10-01

    Mycotoxins are abiotic hazards produced by certain fungi that can grow on a variety of crops. Consequently, their prevalence in plant raw materials may be relatively high. The concentration of mycotoxins in finished products is usually lower than in raw materials. In this review, occurrence and toxicology of the main mycotoxins are summarised. Furthermore, methodological approaches for exposure assessment are described. Existing exposure assessments, both through contamination and consumption data and biomarkers of exposure, for the main mycotoxins are also discussed.

  5. Psychiatric epidemiologic study of occupational lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, D.K.; Ryan, C.; Bromet, E.J.; Connell, M.M.

    1986-02-01

    The association of occupational lead exposure with neuropsychiatric functioning was evaluated using data collected in 1982 in eastern Pennsylvania from 288 lead-exposed workers and 181 nonexposed subjects. Both current and cumulative exposure indices were used. After controlling for age, education, and income, few meaningful differences between exposed and control workers were found on either neuropsychologic or psychosocial variables. Dose-response analyses indicated that among lead-exposed workers, cumulative and current exposure were unrelated to neuropsychologic performance. The only meaningful associations occurred between exposure and level of conflict in interpersonal relationships. The results thus give evidence against hypotheses suggesting adverse neuropsychologic effects.

  6. DOE Occupational Radiation Exposure, 2001 report

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2001-12-31

    The goal of the U.S. Department of Energy (DOE) is to conduct its operations, including radiological, to ensure the safety and health of all DOE employees, contractors, and subcontractors. The DOE strives to maintain radiation exposures to its workers below administrative control levels and DOE limits and to further reduce these exposures to levels that are “As Low As Reasonably Achievable” (ALARA). The 2001 DOE Occupational Radiation Exposure Report provides a summary and analysis of the occupational radiation exposure received by individuals associated with DOE activities. The DOE mission includes stewardship of the nuclear weapons stockpile and the associated facilities, environmental restoration of DOE, and energy research.

  7. Mercury exposure in children: a review

    International Nuclear Information System (INIS)

    Exposure to toxic mercury (Hg) is a growing health hazard throughout the world today. Recent studies show that mercury exposure may occur in the environment, and increasingly in occupational and domestic settings. Children are particularly vulnerable to Hg intoxication, which may lead to impairment of the developing central nervous system, as well as pulmonary and nephrotic damage. Several sources of toxic Hg exposure in children have been reported in biomedical literature: (1) methylmercury, the most widespread source of Hg exposure, is most commonly the result of consumption of contaminated foods, primarily fish; (2) ethylmercury, which has been the subject of recent scientific inquiry in relation to the controversial pediatric vaccine preservative thimerosal; (3) elemental Hg vapor exposure through accidents and occupational and ritualistic practices; (4) inorganic Hg through the use of topical Hg-based skin creams and in infant teething powders; (5) metallic Hg in dental amalgams, which release Hg vapors, and Hg2+ in tissues. This review examines recent epidemiological studies of methylmercury exposure in children. Reports of elemental Hg vapor exposure in children through accidents and occupational practices, and the more recent observations of the increasing use of elemental Hg for magico-religious purposes in urban communities are also discussed. Studies of inorganic Hg exposure from the widespread use of topical beauty creams and teething powders, and fetal/neonatal Hg exposure from maternal dental amalgam fillings are reviewed. Considerable attention was given in this review to pediatric methylmercury exposure and neurodevelopment because it is the most thoroughly investigated Hg species. Each source of Hg exposure is reviewed in relation to specific pediatric health effects, particularly subtle neurodevelopmental disorders

  8. Reconstructing Exposures from Biomarkers using Exposure-Pharmacokinetic Modeling - A Case Study with Carbaryl

    Science.gov (United States)

    Sources of uncertainty involved in exposure reconstruction for a short half-life chemical, carbaryl, were characterized using the Cumulative and Aggregate Risk Evaluation System (CARES), an exposure model, and a human physiologically based pharmacokinetic (PBPK) model. CARES was...

  9. INFLUENCE OF EXPOSURE ASSESSMENT METHOD IN AN EPIDEMIOLOGIC STUDY OF TRIHALOMETHANE EXPOSURE AND SPONTANEOUS ABORTION

    Science.gov (United States)

    Trihalomethanes are common contaminants of chlorinated drinking water. Studies of their health effects have been hampered by exposure misclassification, due in part to limitations inherent in using utility sampling records. We used two exposure assessment methods, one based on ut...

  10. Estimating Exposure of Terrestrial Wildlife to Contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E.

    1994-01-01

    This report presents a general model for exposure of terrestrial wildlife to contaminants (Sect. 2), methods for estimating parameters of the model (Sect. 3), species specific parameters for endpoint species on the Oak Ridge Reservation (ORR) (Sect. 4), and a sample application (Sect. 5). Exposure can be defined as the coincidence in both space and time of a receptor and a stressor, such that the receptor and stressor come into contact and interact (Risk Assessment Forum 1992). In the context of ecological risk assessment, receptors include all endpoint species or communities identified for a site [see Suter (1989) and Suter et al. (1994) for discussions of ecological endpoints for waste sites]. In the context of waste site assessments, stressors are chemical contaminations, and the contact and interaction are uptake of the contaminant by the receptor. Without sufficient exposure of the receptor to the contaminants, there is no ecological risk. Unlike some other endpoint assemblages, terrestrial wildlife are significantly exposed to contaminants in multiple media. They may drink or swim in contaminated water, ingest contaminated food and soil, and breath contaminated air. In addition, because most wildlife are mobile, moving among and within habitats, exposure is not restricted to a single location. They may integrate contamination from several spatially discrete sources. Therefore, exposure models for terrestrial wildlife must include multiple media. This document provides models and parameters for estimating exposure of birds and mammals. Reptiles and amphibians are not considered because few data exist with which to assess exposure to these organisms. In addition, because toxicological data are scarce for both classes, evaluation of the significance of exposure estimates is problematic. However, the general exposure estimation procedure developed herein for birds and mammals is applicable to reptiles and amphibians. Exposure models must be appropriate to the

  11. Rabies Exposures, Post-Exposure Prophylaxis and Deaths in a Region of Endemic Canine Rabies

    OpenAIRE

    Hampson, K.; Dobson, A.; Kaare, M.; Dushoff, J.; Magoto, M.; Sindoya, E.; Cleaveland, S.

    2008-01-01

    Background Thousands of human deaths from rabies occur annually despite the availability of effective vaccines following exposure, and for disease control in the animal reservoir. Our aim was to assess risk factors associated with exposure and to determine why human deaths from endemic canine rabies still occur. Methods and Findings Contact tracing was used to gather data on rabies exposures, post-exposure prophylaxis (PEP) delivered and deaths in two rural districts in northwestern Tanzania ...

  12. Risk from fast neutron exposure

    International Nuclear Information System (INIS)

    The recommendations made by Rossi and Mays imply that the risk associated with the current annual dose equivalent limit of 5 rem for all radiations is unacceptably high, that this limit must be reduced by a factor of 10 or more, and that the conservative linear, no threshold hypothesis must be abandoned. It is shown here that these recommendations are not supported by the newly-analyzed neutron data, and certainly cannot be applied selectively to the annual absorbed dose limit for neutrons. In particular, the judgment that the risk of an annual exposure from 0.5 rad (5 rem) of neutrons is unacceptable high, although perhaps defensible as a personal opinion of the authors, does not follow either from the assumption of a linear-quadratic dose effect relation for low-LET radiation or from other radiobiological considerations. At issue is the level of risk that is to be considered acceptable, a question that is societal and thus not resolvable on purely technical or scientific grounds

  13. Occupational radiation exposures in Cyprus

    International Nuclear Information System (INIS)

    For the first time ever the occupational radiation exposure data of all the radiation workers of Cyprus, as obtained by the personnel monitoring service of the Dosimetry Laboratory of the Medical Physics Department of the Ministry of Health, is published and compared with that of other countries. The presented data shows a systematic trend of improvement both with regards to the methodology of monitoring and data recording. The efforts of the past few years in educating and training the users of ionising radiation with regards to the importance of the personnel monitoring service and the hazards of ionising radiation, has paid off and this is evident from the doses recorded in the past three years which are compared favourably with those of other countries, as given by the UNSCEAR 1993 report. The introduction of extremity monitoring, promises even better improvement in the methodology of monitoring the doses received by personnel working in Interventional Radiology, as well as other groups whose hands, unavoidably, come close to radiation sources. (authors)

  14. Animal exposure during burn tests

    Science.gov (United States)

    Gaume, J. G.

    1976-01-01

    An animal exposure test system has been designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consists of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram and respiration. The ECG and respiration sensors are located in a belt placed around the torso of the subject, electrode wires forming an umbilical to a connector in the top of the compartment. A cable extends from the connector to the power supply and signal conditioning electronics. These are connected to a dual-beam oscilloscope for real time monitoring and a magnetic tape recorder having three or more channels. Endpoints observed are bradycardia, cardiac arrhythmias, changes in respiratory pattern, respiratory arrest and cardiac arrest. The ECG record also appears to be a good method of monitoring animal activity as indicated by an increase in EMG noise superimposed on the record during increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases.

  15. Is cumulated pyrethroid exposure associated with prediabetes?

    DEFF Research Database (Denmark)

    Hansen, Martin Rune; Jørs, Erik; Lander, Flemming;

    2014-01-01

    , cumulative exposure) was assessed from questionnaire data. Participants were asked about symptoms of diabetes. Blood samples were analyzed for glycosylated hemoglobin (HbA1c), a measure of glucose regulation. No association was found between pyrethroid exposure and diabetes symptoms. The prevalence...

  16. Influences on radiation exposure in diagnostic radiology

    International Nuclear Information System (INIS)

    In 1,553 single examinations of 25 roentgendiagnostic procedures and measurements of interventional radiology, the patients' doses were determined. Influence of patient features and training of the radiologist for average radiation exposure were examined. Special control measurements examinations with highest radiation exposures showed up to 20% diminishing of dose. (orig.)

  17. Occupational blood exposure accidents in the Netherlands.

    NARCIS (Netherlands)

    Wijk, P.T.L. van; Schneeberger, P.M.; Heimeriks, K.; Boland, G.J.; Karagiannis, I.; Geraedts, J.; Ruijs, W.L.M.

    2010-01-01

    BACKGROUND: To make proper evaluation of prevention policies possible, data on the incidence and associated medical costs of occupational blood exposure accidents in the Netherlands are needed. METHODS: Descriptive analysis of blood exposure accidents and risk estimates for occupational groups. Cost

  18. 46 CFR 169.551 - Exposure suits.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Exposure suits. 169.551 Section 169.551 Shipping COAST... and Firefighting Equipment Additional Lifesaving Equipment § 169.551 Exposure suits. (a) This section applies to each vessel operating in exposed or partially protected waters service except those—...

  19. Violence Exposure and Victimization among Rural Adolescents

    Science.gov (United States)

    Mykota, David B.; Laye, Adele

    2015-01-01

    Violence exposure is a serious public health concern for adolescents in schools today. Violence exposure can be quite severe and frequent with multiple acts of indirect and direct victimization having lasting effects on the physical, emotional, and intellectual well-being of adolescents. The purpose of the present study is to examine the rates of…

  20. 30 CFR 57.5040 - Exposure records.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Exposure records. 57.5040 Section 57.5040 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... daughters as follows: (1) Where uranium is mined—the complete individual exposures of all mine...

  1. The Foreign Exchange Rate Exposure of Nations

    OpenAIRE

    Entorf, Horst; Möbert, Jochen; Sonderhof, Katja

    2007-01-01

    Following the well-known approach by Adler and Dumas (1984), we evaluate the foreign exchange rate exposure of nations. Results based on data from 27 countries show that national foreign exchange rate exposures are significantly related to the current trade balance variables of corresponding economies.

  2. Local Exhaust Optimization and Worker Exposure

    DEFF Research Database (Denmark)

    Heiselberg, Per; Pedersen, Morten; Plath, Thomas

    This paper describes a process of optimisation of exhaust efficiency and of minimisation of worker exposure at a semiautomatic printing machine at a printing office.......This paper describes a process of optimisation of exhaust efficiency and of minimisation of worker exposure at a semiautomatic printing machine at a printing office....

  3. Virtual Reality Exposure and Imaginal Exposure in the Treatment of Fear of Flying: A Pilot Study

    Science.gov (United States)

    Rus-Calafell, Mar; Gutierrez-Maldonado, Jose; Botella, Cristina; Banos, Rosa M.

    2013-01-01

    Fear of flying (FF) is an impairing psychological disorder that is extremely common in developed countries. The most effective treatment for this particular type of phobia is exposure therapy. However, there are few studies comparing imaginal exposure (IE) and virtual reality (VR) exposure for the treatment of FF. The present study compared the…

  4. Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

    NARCIS (Netherlands)

    Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

    2003-01-01

    Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

  5. Estimating exposure of terrestrial wildlife to contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Sample, B.E.; Suter, G.W. II

    1994-09-01

    This report describes generalized models for the estimation of contaminant exposure experienced by wildlife on the Oak Ridge Reservation. The primary exposure pathway considered is oral ingestion, e.g. the consumption of contaminated food, water, or soil. Exposure through dermal absorption and inhalation are special cases and are not considered hereIN. Because wildlife mobile and generally consume diverse diets and because environmental contamination is not spatial homogeneous, factors to account for variation in diet, movement, and contaminant distribution have been incorporated into the models. To facilitate the use and application of the models, life history parameters necessary to estimate exposure are summarized for 15 common wildlife species. Finally, to display the application of the models, exposure estimates were calculated for four species using data from a source operable unit on the Oak Ridge Reservation.

  6. Estimating exposure of terrestrial wildlife to contaminants

    International Nuclear Information System (INIS)

    This report describes generalized models for the estimation of contaminant exposure experienced by wildlife on the Oak Ridge Reservation. The primary exposure pathway considered is oral ingestion, e.g. the consumption of contaminated food, water, or soil. Exposure through dermal absorption and inhalation are special cases and are not considered hereIN. Because wildlife mobile and generally consume diverse diets and because environmental contamination is not spatial homogeneous, factors to account for variation in diet, movement, and contaminant distribution have been incorporated into the models. To facilitate the use and application of the models, life history parameters necessary to estimate exposure are summarized for 15 common wildlife species. Finally, to display the application of the models, exposure estimates were calculated for four species using data from a source operable unit on the Oak Ridge Reservation

  7. Hedging and Managing Exchange Rate and Related Macroeconomic Exposure

    OpenAIRE

    Oxelheim, Lars; Wihlborg, Clas G.

    1987-01-01

    Hedging transaction and translation exposures to exchange rate changes may increase the economic exposure of the firm and reduce the information value of firms' quarterly statements. In this paper hedging macroeconomic exposures, of which exchange rate exposure is one type, is discussed in terms of choice of macroeconomic variables for which exposures could be measured, choice of strategy for managing exposures, and choice of financial instruments for hedging different exposures.

  8. Intermittent heat exposure and thirst in rats.

    Science.gov (United States)

    Barney, Christopher C; Kuhrt, David M

    2016-04-01

    Adequate water intake, supporting both cardiovascular function and evaporative cooling, is a critical factor in mitigating the effects of heat waves, which are expected to increase with global warming. However, the regulation of water intake during periods of intermittent heat exposure is not well understood. In this study, the effects of access to water or no access during intermittent heat exposure were assessed using male Sprague-Dawley rats exposed to 37.5°C for 4 h/day. After 7 days of intermittent heat exposure, reductions in evaporative water loss were observed in all animals and reductions in water intake following heat exposure occurred as the days of heat exposure increased. Rats that were not allowed water during the 7 days of exposure had decreased rehydration levels, however, rats allowed access to water increased water intake during exposure and exhibited higher overall rehydration levels over the same time period. Peripheral administration of angiotensinII, mimicking activation of volemic thirst, or hypertonic saline solution, activating intracellular thirst, did not result in alteration of water intake in rats exposed to heat with access to water compared to control rats. In contrast, rats exposed to heat without access to water had reduced water intake after administration of hypertonic saline and increased water intake after administration of angiotensinIIcompared to control rats. These experiments demonstrate that thirst responses to intermittent heat exposure are altered by providing water during heat exposure and that intermittent heat exposure without access to water alters drinking responses to both intracellular and extracellular thirst challenges. PMID:27095836

  9. Nanosilver – Occupational exposure limits

    Directory of Open Access Journals (Sweden)

    Anna Maria Świdwińska-Gajewska

    2015-07-01

    Full Text Available Historically, nanosilver has been known as colloidal silver composed of particles with a size below 100 nm. Silver nanoparticles are used in many technologies, creating a wide range of products. Due to antibacterial properties nanosilver is used, among others, in medical devices (wound dressings, textiles (sport clothes, socks, plastics and building materials (paints. Colloidal silver is considered by many as an ideal agent in the fight against pathogenic microorganisms, unlike antibiotics, without side effects. However, in light of toxicological research, nanosilver is not inert to the body. The inhalation of silver nanoparticles have an adverse effect mainly on the liver and lung of rats. The oxidative stress caused by reactive oxygen species is responsible for the toxicity of nanoparticles, contributing to cytotoxic and genotoxic effects. The activity of the readily oxidized nanosilver surface underlies the molecular mechanism of toxicity. This leads to the release of silver ions, a known harmful agent. Occupational exposure to silver nanoparticles may occur in the process of its manufacture, formulation and also usage during spraying, in particular. In Poland, as well as in other countries of the world, there is no separate hygiene standards applicable to nanomaterials. The present study attempts to estimate the value of MAC-TWA (maximum admissible concentration – the time-weighted average for silver – a nano-objects fraction, which amounted to 0.01 mg/m3. The authors are of the opinion that the current value of the MAC-TWA for silver metallic – inhalable fraction (0.05 mg/m3 does not provide sufficient protection against the harmful effects of silver in the form of nano-objects. Med Pr 2015;66(3:429–442

  10. Affecting Factors of Secondhand Smoke Exposure in Korea: Focused on Different Exposure Locations.

    Science.gov (United States)

    Sun, Li Yuan; Cheong, Hae Kwan; Lee, Eun Whan; Kang, Kyeong Jin; Park, Jae Hyun

    2016-09-01

    Exposure to secondhand smoke (SHS) not only can cause serious illness, but is also an economic and social burden. Contextual and individual factors of non-smoker exposure to SHS depend on location. However, studies focusing on this subject are lacking. In this study, we described and compared the factors related to SHS exposure according to location in Korea. Regarding individual factors related to SHS exposure, a common individual variable model and location-specific variable model was used to evaluate SHS exposure at home/work/public locations based on sex. In common individual variables, such as age, and smoking status showed different relationships with SHS exposure in different locations. Among home-related variables, housing type and family with a single father and unmarried children showed the strongest positive relationships with SHS exposure in both males and females. In the workplace, service and sales workers, blue-collar workers, and manual laborers showed the strongest positive association with SHS exposure in males and females. For multilevel analysis in public places, only SHS exposure in females was positively related with cancer screening rate. Exposure to SHS in public places showed a positive relationship with drinking rate and single-parent family in males and females. The problem of SHS embodies social policies and interactions between individuals and social contextual factors. Policy makers should consider the contextual factors of specific locations and regional and individual context, along with differences between males and females, to develop effective strategies for reducing SHS exposure. PMID:27510378

  11. Measuring water ingestion from spray exposures.

    Science.gov (United States)

    Sinclair, Martha; Roddick, Felicity; Nguyen, Thang; O'Toole, Joanne; Leder, Karin

    2016-08-01

    Characterisation of exposure levels is an essential requirement of health risk assessment; however for water exposures other than drinking, few quantitative exposure data exist. Thus, regulatory agencies must use estimates to formulate policy on treatment requirements for non-potable recycled water. We adapted the use of the swimming pool chemical cyanuric acid as a tracer of recreational water ingestion to permit detection of small water volumes inadvertently ingested from spray exposures. By using solutions of 700-1000 mg/L cyanuric acid in an experimental spray exposure scenario, we were able to quantify inadvertent water ingestion in almost 70% of participants undertaking a 10 min car wash activity using a high pressure spray device. Skin absorption was demonstrated to be negligible under the experimental conditions, and the measured ingestion volumes ranged from 0.06 to 3.79 mL. This method could be applied to a range of non-potable water use activities to generate exposure data for risk assessment processes. The availability of such empirical measurements will provide greater assurance to regulatory agencies and industry that potential health risks from exposure to non-potable water supplies are well understood and adequately managed to protect public health. PMID:27130966

  12. Health risks associated with environmental radiation exposures

    International Nuclear Information System (INIS)

    Much is known about health effects associated with exposure to ionising radiation. Numerous epidemiologic studies of populations exposed to radiation under a variety of circumstances have been conducted. These studies have clearly shown that radiation exposure can result in an increased risk of many types of cancer, and the findings are supported by a substantial body of literature from experimental studies. Despite the fact that radiation exposures from environmental sources comprise a relatively minor component of total population exposure, this type of exposure is often the most feared by the public. An accident like Chernobyl or a natural disaster like that at Fukushima provides a unique opportunity to learn more about the health risks from environmental radiation exposures. However, establishing the infrastructure and expertise required to design and conduct all aspects of a complex field study presents formidable challenges. This paper summarises the principal findings from the main studies of environmental radiation exposure that have been successfully undertaken. Although such studies are often exceedingly difficult to conduct, and may be limited by an ecologic design, they can be informative in assessing risk. Any new environmental study that is initiated should focus on special circumstances; additional ecological studies are not recommended. (note)

  13. Minimizing radiation exposure during percutaneous nephrolithotomy.

    Science.gov (United States)

    Chen, T T; Preminger, G M; Lipkin, M E

    2015-12-01

    Given the recent trends in growing per capita radiation dose from medical sources, there have been increasing concerns over patient radiation exposure. Patients with kidney stones undergoing percutaneous nephrolithotomy (PNL) are at particular risk for high radiation exposure. There exist several risk factors for increased radiation exposure during PNL which include high Body Mass Index, multiple access tracts, and increased stone burden. We herein review recent trends in radiation exposure, radiation exposure during PNL to both patients and urologists, and various approaches to reduce radiation exposure. We discuss incorporating the principles of As Low As reasonably Achievable (ALARA) into clinical practice and review imaging techniques such as ultrasound and air contrast to guide PNL access. Alternative surgical techniques and approaches to reducing radiation exposure, including retrograde intra-renal surgery, retrograde nephrostomy, endoscopic-guided PNL, and minimally invasive PNL, are also highlighted. It is important for urologists to be aware of these concepts and techniques when treating stone patients with PNL. The discussions outlined will assist urologists in providing patient counseling and high quality of care.

  14. Minimizing radiation exposure during percutaneous nephrolithotomy.

    Science.gov (United States)

    Chen, T T; Preminger, G M; Lipkin, M E

    2015-12-01

    Given the recent trends in growing per capita radiation dose from medical sources, there have been increasing concerns over patient radiation exposure. Patients with kidney stones undergoing percutaneous nephrolithotomy (PNL) are at particular risk for high radiation exposure. There exist several risk factors for increased radiation exposure during PNL which include high Body Mass Index, multiple access tracts, and increased stone burden. We herein review recent trends in radiation exposure, radiation exposure during PNL to both patients and urologists, and various approaches to reduce radiation exposure. We discuss incorporating the principles of As Low As reasonably Achievable (ALARA) into clinical practice and review imaging techniques such as ultrasound and air contrast to guide PNL access. Alternative surgical techniques and approaches to reducing radiation exposure, including retrograde intra-renal surgery, retrograde nephrostomy, endoscopic-guided PNL, and minimally invasive PNL, are also highlighted. It is important for urologists to be aware of these concepts and techniques when treating stone patients with PNL. The discussions outlined will assist urologists in providing patient counseling and high quality of care. PMID:26354615

  15. Prospective study of definite caterpillar exposures.

    Science.gov (United States)

    Balit, Corrine R; Geary, Merilyn J; Russell, Richard C; Isbister, Geoffrey K

    2003-11-01

    Exposure to caterpillars results in a variety of clinical effects depending on the species involved. The aim of this study was to describe the clinical effects from caterpillar exposures within Australia. Cases were recruited prospectively from calls to a poison information centre. Subjects were included if they had a definite exposure and they had collected the caterpillar or cocoon. The caterpillars were identified to genus and species level where possible. There were 36 included cases: two were contact exposures to caterpillar contents, one was an ingestion of a caterpillar and the remaining 33 patients had definite reactions from caterpillar or cocoon exposure. There were five families of caterpillars identified in the study: Arctiidae, Limacodidae, Anthelidae, Lymantriidae and Sphingidae, many of which occur worldwide. Clinical effects ranged from severe pain to an urticarial response depending on the species involved. There were no adverse effects following ingestion in this study. Treatment consisted primarily of removal of the caterpillar or cocoon. Other treatment measures consisted of symptomatic treatment such as ice packs and antihistamines. This is the first prospective study of caterpillar exposures within Australia and demonstrates that exposures can result in a variety of reactions depending on the family and species involved. PMID:14602121

  16. Arsenic Induced Toxicity in Broiler Chicks and Its Amelioration with Ascorbic Acid: Clinical, Hematological and Pathological Study

    Directory of Open Access Journals (Sweden)

    Rabia Sharaf, Ahrar Khan*, Muhammad Zargham Khan, Iftikhar Hussain, Rao Zahid Abbas, S. T. Gul, Fazal Mahmood and Muhammad Kashif Saleemi

    2013-07-01

    Full Text Available This study was conducted to observe the arsenic (As toxicity lesions in birds and to know either Vit C ameliorates these toxic effects or not. One-day-old broilers chicks (n=72 procured from a local hatchery were randomly divided into four equal groups. First group was kept as control and second group was given As (50 mg/kg BW via crop tubing. Third group received in addition to As, Vit C (250 mg/kg BW whereas fourth group received only Vit C. Killing by neck dislocation of randomly selected six birds from each group was carried out on experimental days 0, 16 and 32 for collection of blood and tissues specimens. Arsenic treated birds showed clinical signs of toxicity throughout the experiment than all other groups. These clinical signs included decreased body weight and feed intake, dullness, open mouth breathing, increased thirst, ruffled feathers, pale comb, skin irritation and watery diarrhea which were not significant in any other group. As treated group showed a significant (P<0.05 decrease in hematological parameters. Severe gross and histopathological changes were observed in intestines, spleen and lungs of birds fed with As than all other groups. Decreased height of villi of middle portion of small intestines was also observed in As treated birds. Villi height in Vit C treated group increased as compared to control group. It was concluded that As induces severe toxic effects in broiler birds; however, these toxic effects can be partially ameliorated by Vit C.

  17. Arsenic-Induced Straighthead: An Impending Threat to Sustainable Rice Production in South and South-East Asia!

    OpenAIRE

    Rahman, M. Azizur; Rahman, M. Mamunur; Hasegawa, Hiroshi

    2012-01-01

    Straighthead is a physiological disorder of rice (Oryza sativa L.) that results in sterile florets with distorted lemma and palea, and the panicles or heads may not form at all in extreme cases. Heads remain upright at maturity, hence the name 'straighthead'. The diseased panicles may not emerge from the flag leaf sheath when the disease is severe. Straighthead disease in rice results in poorly developed panicles and significant yield loss. Although other soil physicochemical factors involved...

  18. Arsenic-induced straighthead: an impending threat to sustainable rice production in South and South-East Asia!

    Science.gov (United States)

    Rahman, M Azizur; Rahman, M Mamunur; Hasegawa, Hiroshi

    2012-03-01

    Straighthead is a physiological disorder of rice (Oryza sativa L.) that results in sterile florets with distorted lemma and palea, and the panicles or heads may not form at all in extreme cases. Heads remain upright at maturity, hence the name 'straighthead'. The diseased panicles may not emerge from the flag leaf sheath when the disease is severe. Straighthead disease in rice results in poorly developed panicles and significant yield loss. Although other soil physicochemical factors involved, arsenic contamination in soil has also been reported to be closely associated with straighthead of rice. Monosodium methanearsonate has been a popular herbicide in cotton production in the USA, which has shown to cause injuries in rice that are similar to straighthead. Since toxicity of inorganic arsenic (iAs) is higher than other forms of arsenic, it may produce a more severe straighthead disorder in rice. The use of iAs-rich groundwater for irrigation, and the increase of iAs concentrations in agricultural soil in arsenic epidemic South and South-East Asia may cause a high incidence of straighthead in rice, resulting in a threat to sustainable rice production in this region. PMID:22139332

  19. Arsenic-induced straighthead: An impending threat to sustainable rice production in South and South-East Asia!

    OpenAIRE

    Rahman M., Azizur; Rahman M., Mamunur; Hasegawa, Hiroshi

    2012-01-01

    Straighthead is a physiological disorder of rice (Oryza sativa L.) that results in sterile florets with distorted lemma and palea, and the panicles or heads may not form at all in extreme cases. Heads remain upright at maturity, hence the name 'straighthead'. The diseased panicles may not emerge from the flag leaf sheath when the disease is severe. Straighthead disease in rice results in poorly developed panicles and significant yield loss. Although other soil physicochemical factors involved...

  20. Arsenic-induced plant growth of arsenic-hyperaccumulator Pteris vittata: Impact of arsenic and phosphate rock.

    Science.gov (United States)

    Han, Yong-He; Yang, Guang-Mei; Fu, Jing-Wei; Guan, Dong-Xing; Chen, Yanshan; Ma, Lena Q

    2016-04-01

    Phosphate rock (PR) has been shown to promote plant growth and arsenic (As) uptake by As-hyperaccumulator Pteris vittata (PV). However, little is known about its behaviors in agricultural soils. In this study, impact of 50 mg kg(-1) As and/or 1.5% PR amendment on plant As accumulation and growth was investigated by growing PV for 90 d in three agricultural soils. While As amendment significantly increased plant As uptake and substantially promoted PV growth, the opposite was observed with PR amendment. Arsenic amendment increased plant frond As from 16.9-265 to 961-6017 mg kg(-1),whereas PR amendment lowered frond As to 10.2-216 mg kg(-1). The As-induced plant growth stimulation was 69-71%. While PR amendment increased plant Ca and P uptake, As amendment showed opposite results. The PV biomass was highly correlated with plant As at r = 0.82, but with weak correlations with plant Ca or P at r < 0.30. This study confirmed that 1) As significantly promoted PV growth, probably independent of Ca or P uptake, 2) PR amendment didn't enhance plant growth or As uptake by PV in agricultural soils with adequate available P, and 3) PV effluxed arsenite (AsIII) growing in agricultural soils. PMID:26874625

  1. Neurobehavioral effects of developmental methylmercury exposure

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, S.G.; Grant-Webster, K.S. [Univ. of Washington, Seattle, WA (United States)

    1995-09-01

    Methylmercury (MeHg) is a global environmental problem and is listed by the International Program of Chemical Safety as one of the six most dangerous chemicals in the world`s environment. Human exposure to MeHg primarily occurs through the consumption of contaminated food such as fish, although catastrophic exposures due to industrial pollution have occurred. The fetus is particularly sensitive to MeHg exposure and adverse effects on infant development have been associated with levels of exposure that result in few, if any, signs of maternal clinical illness or toxicity. High levels of prenatal exposure in humans result in neurobehavioral effects such as cerebral palsy and severe mental retardation. Prenatal exposure to MeHg in communities with chronic low-level exposure is related to decreased birthweight and early sensorimotor dysfunction such as delayed onset of walking. Neurobehavioral alterations have also been documented in studies with non human primates and rodents. Available information on the developmental neurotoxic effects of MeHg, particularly the neurobehavioral effects, indicates that the fetus and infant are more sensitive to adverse effects of MEHg. It is therefore recommended that pregnant women and women of childbearing age be strongly advised to limit their exposure to potential sources of MeHg. Based on results from human and animal studies on the developmental neurotoxic effects of methylmercury, the accepted reference dose should be lowered to 0.025 to 0.06 MeHg {mu}g/kg/day. Continued research on the neurotoxic effects associated with low level developmental exposure is needed. 107 refs., 3 tabs.

  2. Personal exposure of children to air pollution

    Science.gov (United States)

    Ashmore, M. R.; Dimitroulopoulou, C.

    Changes over recent decades in outdoor concentrations of air pollutants are well documented. However, the impacts of air pollution on an individual's health actually relate not to these outdoor concentrations but to their personal exposure in the different locations in which they spend time. Assessing how personal exposures differ from outdoor concentrations, and how they have changed over recent decades, is challenging. This review focuses on the exposure of children, since they are a particularly sensitive group. Much of children's time is spent indoors, and childhood exposure is closely related to concentrations in the home, at school, and in transport. For this reason, children's personal exposures to air pollutants differ significantly from both those of adults and from outdoor concentrations. They depend on a range of factors, including urbanisation, energy use, building design, travel patterns, and activity profiles; analysis of these factors can identify a wider range of policy measures to reduce children's exposure than direct emission control. There is a very large variation in personal exposure between individual children, caused by differences in building design, indoor and outdoor sources, and activity patterns. Identifying groups of children with high personal exposure, and their underlying causes, is particularly important in regions of the world where emissions are increasing, but there are limited resources for environmental and health protection. Although the science of personal exposure assessment, with the associated measurement and modelling techniques, has developed to maturity in North America and western Europe over the last 50 years, there is an urgent need to apply this science in other parts of the world where the effects of air pollution are now much more serious.

  3. Occupational exposure of grain farmers to carbofuran.

    Science.gov (United States)

    Hussain, M; Yoshida, K; Atiemo, M; Johnston, D

    1990-01-01

    Six prairie grain farmers were monitored for pesticide exposure and related adverse effects while they mixed and/or sprayed carbofuran (Furadan 480F) with ground rig application equipment to control grasshoppers in southern Alberta, Canada. Dermal exposure was estimated with Tegaderm patches placed at seventeen locations on the skin beneath the work clothes. Hand and wrist exposure was determined by the amount of chemical found in hand rinses and on wrist patches. Potential inhalation exposure was measured with an air sampler using polyurethane foam as the adsorbent. Urine samples were collected at 24-hr intervals after exposure and monitored for carbofuran. Blood samples were analyzed for acetylcholinesterase (AChE), pseudocholinesterase (ChE) and several other blood parameters. The results indicated that during the mixing and/or spraying operation, a farmer could potentially be exposed to a total of 1,264 micrograms carbofuran per kg of active ingredient (a.i.) used. Of this amount, 1,262 micrograms/kg (or 99.8%) was dermal and 2 micrograms/kg (or 0.2%) could be through the inhalation route. Hand and wrist exposure was about 1,100 micrograms/kg a.i. (or 87% of total exposure). Excretion of the chemical in the urine amounted to 28 micrograms/kg a.i. No ChE inhibition was observed. Other blood measurements were within normal ranges. The farmers showed no acute adverse effects during exposure and for four days after exposure. These results are discussed in relation to the mammalian toxicity of carbofuran. PMID:2322020

  4. Effects of Drilling Fluid Exposure to Oil and Gas Workers Presented with Major Areas of Exposure and Exposure Indicators

    Directory of Open Access Journals (Sweden)

    Eric Broni-Bediako

    2010-12-01

    Full Text Available Drilling fluid is any fluid which is circulated through a well in order to remove cuttings from a wellbore. They are used broadly in the oil and gas industry, on exploration rigs, and are critical to ensuring a safe and productive oil or gas well. During drilling, a large volume of fluids are circulated through the well and into open, partially enclosed or completely enclosed systems at elevated temperatures. When these drilling fluids are agitated during circulating process there is significant potential for chemical exposure to workers and subsequent health effects. This study seeks to identify major areas of drilling fluid exposure and health hazard associated with the use of drilling fluid. The study also presents some challenges in setting drilling fluid exposure standard which has always not been given the same attention or concern as effects and risk management of drilling fluid. Some exposure indicators are also presented.

  5. Security considerations in blinded exposure experiments using electromagnetic waves.

    Science.gov (United States)

    Wolf, Christian

    2008-12-01

    Whether exposure to electromagnetic fields well below accepted exposure limits has a cytogenetic effect on human cells has long been debated. It is widely published and generally accepted that the exposure unit invariably used in these experiments is capable of providing blinded exposure conditions. The following short report illustrates, however, that exposure conditions might not always be as effectively masked as is generally assumed.

  6. Environmental arsenic exposure and sputum metalloproteinase concentrations.

    OpenAIRE

    Josyula, Arun B.; Poplin, Gerald S.; Kurzius-Spencer, Margaret; McClellen, Hannah E.; Kopplin, Michael J.; Stürup, Stefan; Clark Lantz, R.; Jefferey L. Burgess

    2006-01-01

    Biomarkers of exposure & early effects: field studiesBiomarker: arsenic, creatinin, MMP levelsExposure/effect represented: arsenicStudy design: cross-sectionalStudy size: 73 subjectsAnalytical technique: ELISA, HPLCTissue/biological material/sample size: urine samplesRelationship with exposure or effect of interest (including dose-response): inorganic arsenic positively correlated with logMMP-9/TIMP-1 ratio in sputum (Pearson's r Ό 0:351, P Ό 0:009) and negatively correlated with the log of s...

  7. Bladder cancer and occupational exposure to leather.

    OpenAIRE

    Marrett, L D; Hartge, P; Meigs, J W

    1986-01-01

    A large case-control study of bladder cancer (2982 cases; 5782 controls) included information about occupational exposure to leather. Occupational histories of exposed white study subjects were reviewed and 150 were determined to have had "true" on the job exposure to leather. The odds ratio estimate (OR) of bladder cancer associated with such exposure in white subjects (n = 8063) was 1.4 (95% confidence limits = 1.0, 1.9) after adjustment for sex, age, and cigarette smoking. The risk was hig...

  8. Occupational Exposure in Ammonium Phosphate Fertilizer Plants

    International Nuclear Information System (INIS)

    Occupational exposures and activity concentrations have been assessed in two industrial plants producing mono-ammonium phosphate and di-ammonium phosphate fertilizers, located in south-western Spain. The annual effective doses received by the workers are below 1 mSv/a, with the contribution from external exposure being similar to that from internal exposure. The dose contribution from inhalation of dust has been estimated to be about 0.12 mSv/a, while the 222Rn concentrations inside the plants are of no concern. Consequently, no additional radiation protection measures need to be taken to protect the workers in these facilities. (author)

  9. DOE occupational radiation exposure 2006 report

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2006-12-31

    The U.S. Department of Energy (DOE) Office of Corporate Safety Analysis (HS-30) within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE. This report provides a summary and an analysis of occupational radiation exposure information for all monitored individuals associated with DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past five years.

  10. DOE occupational radiation exposure 2005 report

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2005-12-31

    The U.S. Department of Energy (DOE) Offi ce of Corporate Safety Analysis (HS-30) within the Office of Health Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE. This report provides a summary and an analysis of occupational radiation exposure information for all monitored individuals associated with the DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past 5 years.

  11. Firm-Specific Foreign Exchange Exposure Identification

    DEFF Research Database (Denmark)

    Aabo, Tom; Brodin, Danielle

    2014-01-01

    Previous studies have used the stock market approach to find the aggregate number of (firms with) foreign exchange exposures in a given country, region, or industry. Methodologies have differed in many aspects but two of the most basic differences relate to observation frequency and the choice......-financial firms and find limited consistency in the detected exchange rate exposures when altering methodology in terms of observation frequency and choice of market index. The results put a question mark to the validity of the stock market approach for exchange rate exposure identification at the firm...

  12. Aircrew radiation exposure assessment for Yugoslav airlines

    International Nuclear Information System (INIS)

    The presented study shows that the crews of the intercontinental flights can receive significant annual effective doses (1.5-2.0 mSv). The exposure of the crews is comparable with natural radiation level on the ground level (it can be up to 5 times higher for some air crew members in the intercontinental flights), but smaller than maximum permissible dose for general population. The annual exposures of the passengers are generally smaller than the exposures of tile air crews. because the passengers have a limited number of flights per year compared with the members of the air-crews. (author)

  13. Noise exposure in oil mills

    Directory of Open Access Journals (Sweden)

    Prasanna Kumar G

    2008-01-01

    Full Text Available Context: Noise of machines in various agro-based industries was found to be the major occupational hazard for the workers of industries. The predominant noise sources need to be identified and the causes of high noise need to be studied to undertake the appropriate measures to reduce the noise level in one of the major agro-based industries, oil mills. Aims: To identify the predominant noise sources in the workrooms of oil mills. To study the causes of noise in oil mills. To measure the extent of noise exposure of oil mill workers. To examine the response of workers towards noise, so that appropriate measures can be undertaken to minimize the noise exposure. Settings and Design: A noise survey was conducted in the three renowned oil mills of north-eastern region of India. Materials and Methods: Information like output capacity, size of power source, maintenance condition of the machines and workroom configurations of the oil mills was collected by personal observations and enquiry with the owner of the mill. Using a Sound Level Meter (SLM (Model-824, Larson and Davis, USA, equivalent SPL was measured at operator′s ear level in the working zone of the workers near each machine of the mills. In order to study the variation of SPL in the workrooms of the oil mill throughout its operation, equivalent SPL was measured at two appropriate locations of working zone of the workers in each mill. For conducting the noise survey, the guidelines of Canadian Centre for Occupational Health and Safety (CCOHS were followed. Grid points were marked on the floor of the workroom of the oil mill at a spacing of 1 m x 1 m. SPL at grid points were measured at about 1.5 m above the floor. The direction of the SLM was towards the nearby noisy source. To increase accuracy, two replications were taken at each grid point. All the data were recorded for 30 sec. At the end of the experiment, data were downloaded to a personal computer. With the help of utility software of

  14. Ambient radiation exposure: measurements and effects

    International Nuclear Information System (INIS)

    A brief review of the available literature, data and reports of various radiation exposure and protection studies and various measurements techniques are presented. A linear quadratic model has been given illustrating the validity of radiation hormesis

  15. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima;

    2014-01-01

    BACKGROUND: In 2012, the International Agency for Research on Cancer classified tetrachloroethylene, used in the production of chemicals and the primary solvent used in dry cleaning, as "probably carcinogenic to humans" based on limited evidence of an increased risk of bladder cancer in dry...... cleaners. OBJECTIVES: We assessed the epidemiological evidence for the association between tetrachloroethylene exposure and bladder cancer from published studies estimating occupational exposure to tetrachloroethylene or in workers in the dry-cleaning industry. METHODS: Random-effects meta-analyses were...... carried out separately for occupational exposure to tetrachloroethylene and employment as a dry cleaner. We qualitatively summarized exposure-response data because of the limited number of studies available. RESULTS: The meta-relative risk (mRR) among tetrachloroethylene-exposed workers was 1.08 (95% CI...

  16. Occupational Exposure in Angiography (Prague Workplaces)

    International Nuclear Information System (INIS)

    The results of measurements, which were performed at angiography departments, are presented. The aim of this work was not only to assess patient exposure but also to perform a survey of the occupational exposures of physicians during common angiography examinations of the skull, chest, abdomen and limbs. Patient data, type of examination, fluoroscopy time, the whole number of film frames, dose-area product (Diameter E) and physician dose (Stephen 6000) were also recorded. There are many factors influencing the level of measured exposures. They include input parameters of X ray performance (kV, mA, projection, diaphragms, ZOOM, type of record etc) and individual approach of the physicians. This paper contributes to the discussion about the increasing exposures of the physicians specialising in diagnostic and interventional angiography. (author)

  17. Exploring Global Exposure Factors Resources URLs

    Data.gov (United States)

    U.S. Environmental Protection Agency — The dataset is a compilation of hyperlinks (URLs) for resources (databases, compendia, published articles, etc.) useful for exposure assessment specific to consumer...

  18. Neurobehavioral and neurodevelopmental effects of pesticide exposures

    DEFF Research Database (Denmark)

    London, Leslie; Beseler, Cheryl; Bouchard, Maryse F;

    2012-01-01

    The association between pesticide exposure and neurobehavioral and neurodevelopmental effects is an area of increasing concern. This symposium brought together participants to explore the neurotoxic effects of pesticides across the lifespan. Endpoints examined included neurobehavioral, affective ...

  19. Assessment of exposure to depleted uranium

    International Nuclear Information System (INIS)

    In most circumstances, measurement of uranium excreted in urine at known times after exposure is potentially the most sensitive method for determining the amount of depleted uranium (DU) incorporated. The problems associated with this approach are that natural uranium is always present in urine because of the ingestion of natural uranium in food and drink, and that the uncertainties in the intakes as assessed from excretion measurements can be quite large, because many assumptions concerning the exposure characteristics (time pattern of exposure, route of intake, chemical form, solubility, biokinetics within the body) must be made. Applying currently available methods and instruments for the measurement of uranium in urine samples, DU incorporations of levels relevant with respect to potential health hazards can be detected reliably, even a long time after exposure. (author)

  20. Prenatal Cocaine Exposure and Infantile Psychomotor Outcome

    OpenAIRE

    J Gordon Millichap

    2002-01-01

    The effects of prenatal cocaine exposure on child development outcomes were studied prospectively in an obstetric unit of a large US urban teaching hospital at Case Western Reserve University, Cleveland, OH.

  1. PEP (Post-Exposure Prophylaxis) 101

    Science.gov (United States)

    ... AIDS PEP Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir PEP (post-exposure prophylaxis) means taking antiretroviral medicines (ART) after being potentially exposed to HIV to prevent ...

  2. TELOMERASE AND CHRONIC ARSENIC EXPOSURE IN HUMANS

    Science.gov (United States)

    Arsenic exposure has been associated with increased risk of skin, lung and bladder cancer in humans. The mechanisms of carcinogenesis are not well understood. Telomerase, a ribonucleoprotein containing human telomerase reverse transcriptase (hTERT), can extend telomeres of eukary...

  3. DOE occupational radiation exposure 2007 report

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2007-12-31

    The U.S. Department of Energy (DOE) Office of Corporate Safety Analysis (HS-30) within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE.* The annual DOEOccupational Radiation Exposure 2007 Report provides an evaluation of DOE-wide performance regarding compliance with DOE Part 835 dose limits and ALARA process requirements. In addition the report provides data to DOE organizations responsible for developing policies for protection of individuals from the effects of radiation. This report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. The occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site over the past five years.

  4. PARTNERING TO IMPROVE HUMAN EXPOSURE METHODS

    Science.gov (United States)

    Methods development research is an application-driven scientific area that addresses programmatic needs. The goals are to reduce measurement uncertainties, address data gaps, and improve existing analytical procedures for estimating human exposures. Partnerships have been develop...

  5. Skin Exposures & Effects in the Workplace

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . Workplace Safety & Health Topics Skin Exposures and Effects Recommendations ... Pinterest Twitter YouTube NIOSH Homepage NIOSH A-Z Workplace Safety & Health Topics Publications and Products Programs Contact ...

  6. Bases for establishing radiation exposure limits

    International Nuclear Information System (INIS)

    It is an essential requirement of good radiation protection that all unnecessary exposure of people should be avoided and that any necessary exposure, whether of workers or of members of the general public, should be minimized. It is, however, an additional requirement that such necessary exposures should not exceed certain stated limits. These principles are based on the possibility that even the smallest exposures may involve some risk of harm, that any risk of harm should be justifiable by the circumstances necessitating it, and that risk should always be limited to an appropriately low level. The bases for establishing exposure limits must therefore involve an assessment of the risk involved in any form of radiation exposure, and an opinion as to the degree of safety that should be ensured in circumstances which necessitate any occupational or public exposure to radiation. There is increasing quantitative evidence on the frequency on which harm, and particularly the induction of malignancies, may be caused in people exposed to radiation at high doses; and somewhat clearer bases than previously for inferring the possible frequencies at low doses. It is therefore easier to assess the degree of safety ensured by restricting radiation exposure to particular levels. It is clear also that a comparable degree of safety should be ensured whether the radiation exposure involves the whole body more of less uniformly, or individual tissues or organs selectively. The ''weighting'' factors appropriate to irradiation of particular tissues from internal emitters can thus be defined in terms of their likely individual contributions to the harm of whole-body irradiation. In this way the limits for different modes of exposure by external or internal radiation can be related so as to ensure that protection should be equally effective for different distributions of absorbed dose in the body. In particular, the over-simplified concept of a single critical organ determining the

  7. ALLERGIC CONTACT DERMATITIS FROM FORMALDEHYDE EXPOSURE.

    OpenAIRE

    Maya Lyapina; Angelina Kisselova-Yaneva; Assya Krasteva; Mariana Tzekova–Yaneva; Maria Dencheva-Garova

    2012-01-01

    Formaldehyde is a ubiquitous chemical agent, a part of our outdoor and indoor working and residential environment. Healthcare workers in difficult occupations are among the most affected by formaldehyde exposure. Formaldehyde is an ingredient of some dental materials. Formaldehyde is well-known mucous membrane irritant and a primary skin sensitizing agent associated with both contact dermatitis (Type IV allergy), and immediate, anaphylactic reactions (Type I allergy). Inhalation exposure to f...

  8. Biomarkers of Mercury Exposure in the Amazon

    OpenAIRE

    Nathália Santos Serrão de Castro; Marcelo de Oliveira Lima

    2014-01-01

    Mercury exposure in the Amazon has been studied since the 1980s decade and the assessment of human mercury exposure in the Amazon is difficult given that the natural occurrence of this metal is high and the concentration of mercury in biological samples of this population exceeds the standardized value of normality established by WHO. Few studies have focused on the discovery of mercury biomarkers in the region's population. In this way, some studies have used genetics as well as immunologica...

  9. Radioactivity in water and radiation exposure

    International Nuclear Information System (INIS)

    The radiation exposure of man via waters is outlined. Natural as well as man-made radionuclides are taken into account, also considering the influence by man on the activity distribution in the environment. Relations between air and water pollution are treated. The measured values in hand do not indicate a significant increase of radiation exposure of man by man-made radionuclides in drinking water. The importance is discussed of international agreements in order to overcome environmental problems. (orig.)

  10. Case of child abuse by radiation exposure

    International Nuclear Information System (INIS)

    On 2 May 1974, a father was convicted of castrating his 13-year-old son by exposing him to a 1-curie source of 137Cs to be used for oil gas well logging. The child was subjected to perhaps eight exposures or attempted exposures over a six-month period. A brief discussion of the medical descriptions of the radiation effects upon the skin and testes and the chromosomal system is included

  11. Prenatal Insecticide Exposure and Children's Cognitive Development

    OpenAIRE

    Gaspar, Fraser William

    2014-01-01

    Although approximately 123 million people may be exposed to high levels of insecticides through the use of indoor residual spraying (IRS) for malaria control, very little data exists on exposure levels and risk to residents. In addition, certain populations may be more susceptible to the unintended health effects of insecticide exposure from IRS including the developing fetus. The aims of this dissertation were as follows: 1) build indoor transport and fate models to estimate insecticide expo...

  12. Systemic Absorption of Nanomaterials by Oral Exposure

    DEFF Research Database (Denmark)

    Binderup, Mona-Lise; Bredsdorff, Lea; Beltoft, Vibe Meister;

    This report and accompanying database systematically evaluates the reliability and relevance of the existing scientific literature regarding systemic absorption of nanomaterials by oral exposure and makes specific recommendations for future testing approaches.......This report and accompanying database systematically evaluates the reliability and relevance of the existing scientific literature regarding systemic absorption of nanomaterials by oral exposure and makes specific recommendations for future testing approaches....

  13. Media Exposure: How Models Simplify Sampling

    DEFF Research Database (Denmark)

    Mortensen, Peter Stendahl

    1998-01-01

    In media planning, the distribution of exposures to more ad spots in more media (print, TV, radio) is crucial to the evaluation of the campaign. If such information should be sampled, it would only be possible in expensive panel-studies (eg TV-meter panels). Alternatively, the distribution...... of exposures may be modelled statistically, using the Beta distribution combined with the Binomial Distribution. Examples are given....

  14. Mycosis fungoides progression and chronic solvent exposure

    OpenAIRE

    Nikkels, Arjen; Quatresooz, Pascale; Delvenne, Philippe; Balsat, A.; Pierard, Gérald

    2004-01-01

    The effect of repeated exposure to specific chemicals on the initiation or progression of mycosis fungoides (MF) remains unsettled. A patient with low-grade patch stage MF progressively developed MF plaques restricted to his arms, and a tumour on his right thigh. These areas were subject to repeated exposure to solvents. His thigh was indeed in close contact with his trousers pocket where he used to store a wiping rag drenched into white spirit and cellulosic thinner. Immunophenotyping these ...

  15. Residential Exposure to Traffic and Spontaneous Abortion

    OpenAIRE

    Green, Rochelle S; Malig, Brian; Windham, Gayle C.; Fenster, Laura; Ostro, Bart; Swan, Shanna

    2009-01-01

    Background Studies have shown associations between air pollution or traffic exposure and adverse birth outcomes, such as low birth weight. However, very few studies have examined the effect of traffic emissions on spontaneous abortion (SAB). Objective The goal of this study was to determine whether residential exposure to vehicular traffic was associated with SAB. Methods Pregnant women from a prepaid health plan in California were recruited into a prospective cohort study in 1990–1991. Three...

  16. Urban Jamaican children's exposure to community violence.

    Science.gov (United States)

    Samms-Vaughan, M E; Jackson, M A; Ashley, D E

    2005-01-01

    Exposure to violence in childhood is associated with aggression in adulthood. The high level of community violence in Jamaica is likely to expose Jamaican children to violence. There has been no detailed study of the exposure of Jamaican children to violence in their daily lives. Some 1674 urban 11-12-year-old children, previously part of a national birth cohort study, completed a questionnaire detailing their exposure to violence as witnesses, victims and aggressors. Their parents completed a socio-economic questionnaire. Jamaican children had high levels of exposure to physical violence. A quarter of the children had witnessed severe acts of physical violence such as robbery, shooting and gang wars, a fifth had been victims of serious threats or robbery and one in every twelve had been stabbed. Children reported being least exposed to sexual violence and to being shot at. Robbery was an almost universal experience affecting children from all schools and socio-economic groups. The single commonest experience as a victim of violence was the loss of a family member or close friend to murder, affecting 36.8% of children. Children's experiences of witnessing violence occurred chiefly in their communities but their personal experiences of violence occurred at school. Boys and children attending primary school had greater exposure to violence as witnesses and victims. Socio-economic status discriminated exposure to physical violence as witnesses but not as victims. Intervention strategies to reduce children's exposure to violence should include community education on the impact of exposure to violence on children, particularly the loss of a significant person, and the development of a range of school-based violence prevention programmes.

  17. Human exposure to urban air pollution.

    OpenAIRE

    Boström, C E; Almén, J; Steen, B; Westerholm, R

    1994-01-01

    This study deals with some methods of making human exposure estimates, aimed at describing the human exposure for selected air pollutants in Sweden that are suspected carcinogens. Nitrogen oxides (NOx) have been chosen as an indicator substance for estimating the concentration of the urban plume. Earlier investigations have shown that the traffic in Swedish cities contributes around 85% to the measured NOx concentrations, and that most of the mutagenicity in urban air originates from traffic....

  18. Virtual reality exposure therapy for social phobia

    OpenAIRE

    Herbelin, Bruno

    2005-01-01

    This thesis presents researches and experiments performed in collaboration with a psychiatrist in order to validate and improve the use of virtual reality in social phobia psychotherapy. Cognitive and behavioral therapies are strongly based on the exposure to anxiety provoking stimuli. Virtual reality seems to be appropriate for such exposures as it allows for on-demand reproduction of reality. The idea has been validated for the treatment of various phobias but is more delicate in the case o...

  19. Virtual reality exposure therapy for social phobia

    OpenAIRE

    Herbelin, Bruno; Thalmann, Daniel

    2007-01-01

    This thesis presents researches and experiments performed in collaboration with a psychiatrist in order to validate and improve the use of virtual reality in social phobia psychotherapy. Cognitive and behavioral therapies are strongly based on the exposure to anxiety provoking stimuli. Virtual reality seems to be appropriate for such exposures as it allows for on-demand reproduction of reality. The idea has been validated for the treatment of various phobias but is more delicate in the case o...

  20. Radiation Worker Protection by Exposure Scheduling

    OpenAIRE

    Blankenbecler, Richard

    2011-01-01

    The discovery of the protective adaptive response of cells to a low dose of radiation suggests applications to radiation worker/first responder protection. Its use in cancer radiotherapy has been discussed in a separate publication. This paper describes simple changes in scheduling that can make use of these beneficial adaptive effects for protection. No increase in total exposure is necessary, only a simple change in the timing of radiation exposure. A low dose of radiation at a sufficient d...

  1. Blood transfusion exposure in Denmark and Sweden

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Edgren, Gustaf; Rostgaard, Klaus;

    2009-01-01

    Although essential for the evaluation of blood transfusion safety, the prevalence of blood transfusion in the general population is not presently known. This study estimated the exposure to blood transfusion in the general Scandinavian population.......Although essential for the evaluation of blood transfusion safety, the prevalence of blood transfusion in the general population is not presently known. This study estimated the exposure to blood transfusion in the general Scandinavian population....

  2. Peripheral blood signatures of lead exposure.

    Directory of Open Access Journals (Sweden)

    Heather G LaBreche

    Full Text Available BACKGROUND: Current evidence indicates that even low-level lead (Pb exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

  3. Occupational exposure to pesticides and respiratory health

    OpenAIRE

    Ali Mamane; Isabelle Baldi; Jean-François Tessier; Chantal Raherison; Ghislaine Bouvier

    2015-01-01

    This article aims to review the available literature regarding the link between occupational exposure to pesticides and respiratory symptoms or diseases. Identification of epidemiological studies was performed using PubMed. 41 articles were included, 36 regarding agricultural workers and five regarding industry workers. Among the 15 cross-sectional studies focusing on respiratory symptoms and agricultural pesticide exposure, 12 found significant associations with chronic cough, wheeze, dyspno...

  4. Fetal lead exposure: Encephalopathy in a child

    OpenAIRE

    Dsouza, Herman S.; Menezes, Geraldine; Venkatesh, T

    2002-01-01

    It is well known that lead exposure in the early period of pre pregnancy and antenatal life leads to serious health complications. In this case report, a five month old child who was suffering from encephalopathy was finally confirmed a victim of lead exposure, the source being the environment and the family. We report this case with complete clinical investigation including blood lead analysis. This case report highlights the various ways in which lead may accumulate in the body. It is also ...

  5. Mechanism-based drug exposure classification in pharmacoepidemiological studies

    NARCIS (Netherlands)

    Verdel, B.M.

    2010-01-01

    Mechanism-based classification of drug exposure in pharmacoepidemiological studies In pharmacoepidemiology and pharmacovigilance, the relation between drug exposure and clinical outcomes is crucial. Exposure classification in pharmacoepidemiological studies is traditionally based on pharmacotherapeu

  6. Dust exposures in the wood processing industry.

    Science.gov (United States)

    Alwis, U; Mandryk, J; Hocking, A D; Lee, J; Mayhew, T; Baker, W

    1999-01-01

    Workers at four different woodworking processes--two logging sites, four sawmills, one major woodchipping operation, and five joineries situated in the state of New South Wales in Australia--were studied for personal inhalable dust exposures (N = 182). The geometric mean exposure at logging sites was 0.6 mg/m3 (N = 7), sawmills 1.6 mg/m3 (N = 93), woodchipping 1.9 mg/m3 (N = 9), and joineries 3.7 mg/m3 (N = 66). Overall, 62% of the exposures exceeded the current standards. Among joineries, 95% of the hardwood exposures and 35% of the softwood exposures were above the relevant standards. A majority of workers (approximately 90%) did not wear appropriate respirators approved for wood dust, while the ones who did wear them, used them on average less than 50% of the time. The significant determinants of personal wood dust exposures (n = 163) were found to be local exhaust ventilation, job title, use of handheld tools, cleaning method used, use of compressed air, and green or dry wood processed. Type of wood processed (softwood or hardwood) was not found to be statistically significant.

  7. DOE occupational radiation exposure 1996 report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    The goal of the US Department of Energy (DOE) is to conduct its radiological operations to ensure the health and safety of all DOE employees including contractors and subcontractors. The DOE strives to maintain radiation exposures to its workers below administrative control levels and DOE limits and to further reduce these exposures and releases to levels that are ``As Low As Reasonably Achievable`` (ALARA). The DOE Occupational Radiation Exposure Report, 1996 provides summary and analysis of the occupational radiation exposure received by individuals associated with DOE activities. The DOE mission includes stewardship of the nuclear weapons stockpile and the associated facilities, environmental restoration of DOE and precursor agency sites, and energy research. Collective exposure at DOE has declined by 80% over the past decade due to a cessation in opportunities for exposure during the transition in DOE mission from weapons production to cleanup, deactivation and decommissioning, and changes in reporting requirements and dose calculation methodology. In 1996, the collective dose decreased by 10% from the 1995 value due to decreased doses at five of the seven highest-dose DOE sites. For 1996, these sites attributed the reduction in collective dose to the completion of several decontamination and decommissioning projects, reduced spent fuel storage activities, and effective ALARA practices. This report is intended to be a valuable tool for managers in their management of radiological safety programs and commitment of resources.

  8. Exposure to food contaminants during pregnancy.

    Science.gov (United States)

    Chan-Hon-Tong, Anne; Charles, Marie-Aline; Forhan, Anne; Heude, Barbara; Sirot, Véronique

    2013-08-01

    During pregnancy, the fetus is exposed to contaminants from its mother's diet. This work provides an assessment of the dietary exposure of pregnant women to inorganic contaminants (aluminum, mercury, lead, inorganic arsenic, cobalt), polychlorodibenzodioxins, polychlorodibenzofurans, dioxin-like and non-dioxin-like polychlorobiphenyls (DL-PCBs, NDL-PCBs), polybromodiphenyl ethers (PBDEs), perfluoroalkyl acids, mycotoxins (zearalenone, patulin, trichothecenes), and heat-generated compounds (acrylamide and polycyclic aromatic hydrocarbons). Consumption data of 2002 pregnant women aged 18 to 45 from the EDEN cohort study were combined with contamination data from the second French total diet study to assess the exposure before pregnancy (n=1861) and during the third trimester of pregnancy (n=1775). Exposure was also assessed considering the season during which the third trimester of pregnancy occurred. Significant changes in consumptions during pregnancy and between seasons were associated with differences in exposures for some substances. Some contaminant exposures appeared to be of health concern. Margins of exposure to acrylamide (635 to 1094 for mean), inorganic arsenic, lead, and BDE-99 (≤100) were too low to exclude all risks. For NDL-PCBs, T-2 and HT-2 toxins, and deoxynivalenol, significant exceedings of toxicological reference values were found before pregnancy, but there was no significant exceeding in the third trimester.

  9. Exposure to food contaminants during pregnancy.

    Science.gov (United States)

    Chan-Hon-Tong, Anne; Charles, Marie-Aline; Forhan, Anne; Heude, Barbara; Sirot, Véronique

    2013-08-01

    During pregnancy, the fetus is exposed to contaminants from its mother's diet. This work provides an assessment of the dietary exposure of pregnant women to inorganic contaminants (aluminum, mercury, lead, inorganic arsenic, cobalt), polychlorodibenzodioxins, polychlorodibenzofurans, dioxin-like and non-dioxin-like polychlorobiphenyls (DL-PCBs, NDL-PCBs), polybromodiphenyl ethers (PBDEs), perfluoroalkyl acids, mycotoxins (zearalenone, patulin, trichothecenes), and heat-generated compounds (acrylamide and polycyclic aromatic hydrocarbons). Consumption data of 2002 pregnant women aged 18 to 45 from the EDEN cohort study were combined with contamination data from the second French total diet study to assess the exposure before pregnancy (n=1861) and during the third trimester of pregnancy (n=1775). Exposure was also assessed considering the season during which the third trimester of pregnancy occurred. Significant changes in consumptions during pregnancy and between seasons were associated with differences in exposures for some substances. Some contaminant exposures appeared to be of health concern. Margins of exposure to acrylamide (635 to 1094 for mean), inorganic arsenic, lead, and BDE-99 (≤100) were too low to exclude all risks. For NDL-PCBs, T-2 and HT-2 toxins, and deoxynivalenol, significant exceedings of toxicological reference values were found before pregnancy, but there was no significant exceeding in the third trimester. PMID:23639909

  10. Occupational exposures and risk of pancreatic cancer.

    Science.gov (United States)

    Santibañez, Miguel; Vioque, Jesús; Alguacil, Juan; de la Hera, Manuela García; Moreno-Osset, Eduardo; Carrato, Alfredo; Porta, Miquel; Kauppinen, Timo

    2010-10-01

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  11. DOE occupational radiation exposure 1996 report

    International Nuclear Information System (INIS)

    The goal of the US Department of Energy (DOE) is to conduct its radiological operations to ensure the health and safety of all DOE employees including contractors and subcontractors. The DOE strives to maintain radiation exposures to its workers below administrative control levels and DOE limits and to further reduce these exposures and releases to levels that are ''As Low As Reasonably Achievable'' (ALARA). The DOE Occupational Radiation Exposure Report, 1996 provides summary and analysis of the occupational radiation exposure received by individuals associated with DOE activities. The DOE mission includes stewardship of the nuclear weapons stockpile and the associated facilities, environmental restoration of DOE and precursor agency sites, and energy research. Collective exposure at DOE has declined by 80% over the past decade due to a cessation in opportunities for exposure during the transition in DOE mission from weapons production to cleanup, deactivation and decommissioning, and changes in reporting requirements and dose calculation methodology. In 1996, the collective dose decreased by 10% from the 1995 value due to decreased doses at five of the seven highest-dose DOE sites. For 1996, these sites attributed the reduction in collective dose to the completion of several decontamination and decommissioning projects, reduced spent fuel storage activities, and effective ALARA practices. This report is intended to be a valuable tool for managers in their management of radiological safety programs and commitment of resources

  12. Occupational exposures and risk of pancreatic cancer

    International Nuclear Information System (INIS)

    The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

  13. Radiation exposure for human Mars exploration.

    Science.gov (United States)

    Simonsen, L C; Wilson, J W; Kim, M H; Cucinotta, F A

    2000-11-01

    One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human space flight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle events was of great concern. A new challenge appears in deep-space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays since the missions are of long duration, and accumulated exposures can be high. Because cancer induction rates increase behind low to moderate thicknesses of aluminum shielding, according to available biological data on mammalian exposures to galactic cosmic ray-like ions, aluminum shield requirements for a Mars mission may be prohibitively expensive in terms of mission launch costs. Alternative materials for vehicle construction are under investigation to provide lightweight habitat structures with enhanced shielding properties. In the present paper, updated estimates for astronaut exposures on a Mars mission are presented and shielding properties of alternative materials are compared with aluminum. PMID:11045525

  14. Foreign exchange transaction exposure of enterprises in Serbia

    OpenAIRE

    Bogićević Jasmina; Dmitrović-Šaponja Ljiljana; Pantelić Marija

    2016-01-01

    Enterprises involved in international business face transaction exposure to foreign exchange risk. This type of exposure occurs when an enterprise trades, borrows, or lеnds in foreign currency. Transaction exposure has a direct effect on an enterprise’s financial position and profitability. It is one of the three forms of exposure to exchange rate fluctuations, the other two being translation exposure and operating exposure. The aim of this paper is to asse...

  15. PEPTIDE BINDING AS A MODE OF ACTION FOR THE CARCINOGENICITY AND TOXICITY OF ARSENIC

    Science.gov (United States)

    Arsenic exposure leads to tumors in human skin, lung, urinary bladder, kidney and liver. Three likely initial stages of arsenical-macromolecular interaction are (1) binding of trivalent arsenicals to the sulfhydryl groups of peptides and proteins, (2) arsenical-induced generation...

  16. Existing Default Values and Recommendations for Exposure Assessment - A Nordic Exposure Group Project 2011

    DEFF Research Database (Denmark)

    Höglund, Lena; Räisänen, Jouni; Hämäläinen, Anne-Maija;

    range of more or less well-documented values originating from many different sources. The purpose of this report is to give an overview and to evaluate exposure factors that are currently used by the authorities and industry in the exposure assessments for both adults (occupational and consumer exposure...... and dust ingestion, drinking water, food intake, non-dietary ingestion factors, lifetime expectancy, activity factors and consumer products...

  17. Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

    Science.gov (United States)

    Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

    2003-01-01

    Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

  18. Occupational blood exposure among health care workers: II. Exposure mechanisms and universal precautions

    DEFF Research Database (Denmark)

    Nelsing, S; Nielsen, T L; Nielsen, Jens Ole

    1993-01-01

    We investigated mechanisms of mucocutaneous exposure (MCE) and percutaneous exposure (PCE) to blood, and compliance with protective barriers among all former and presently employed medical staff at a Danish Department of Infectious Diseases. All subjects were asked to complete an anonymous questi...... protective barriers. To further reduce the frequency of blood exposure, the development of safer instruments and unceasing education in safer technique and use of protective barriers are of major importance....

  19. Heat exposure on farmers in northeast Ghana

    Science.gov (United States)

    Frimpong, Kwasi; Van Etten E J, Eddie; Oosthuzien, Jacques; Fannam Nunfam, Victor

    2016-08-01

    Environmental health hazards faced by farmers, such as exposure to extreme heat stress, are a growing concern due to global climate change, particularly in tropical developing countries. In such environments, farmers are considered to be a population at risk of environmental heat exposure. The situation is exacerbated due to their farming methods that involve the use of primitive equipment and hard manual labour conducted in full sunshine under hot and humid conditions. However, there is inadequate information about the extent of heat exposure to such farmers, both at the household and farm levels. This paper presents results from a study assessing environmental heat exposure on rural smallholder farmers in Bawku East, Northern Ghana. From January to December 2013, Lascar USB temperature and humidity sensors and a calibrated Questemp heat stress monitor were deployed to farms and homes of rural farmers at Pusiga in Bawku East to capture farmers' exposure to heat stress in both their living and working environments as they executed regular farming routines. The Lascar sensors have the capability to frequently, accurately and securely measure temperature and humidity over long periods. The Questemp heat stress monitor was placed in the same vicinity and showed strong correlations to Lascar sensors in terms of derived values of wet-bulb globe temperature (WBGT). The WBGT in the working environment of farmers peaked at 33.0 to 38.1 °C during the middle of the day in the rainy season from March to October and dropped to 14.0-23.7 °C in the early morning during this season. A maximum hourly WBGT of 28.9-37.5 °C (March-October) was recorded in the living environment of farmers, demonstrating little relief from heat exposure during the day. With these levels of heat stress, exposed farmers conducting physically demanding outdoor work risk suffering serious health consequences. The sustainability of manual farming practices is also under threat by such high levels of

  20. Dose level of occupational exposure in China

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Y.; Zhang, L.A.; Ju, Y.J. [Peking Union Medical College, Tianjin (China)

    2008-03-15

    This paper discusses the dose level of Chinese occupational exposures during 1986-2000. Data on occupational exposures from the main categories in nuclear fuel cycle (uranium enrichment and conversion, fuel fabrication, reactor operation, waste management and research activity, except for uranium mining and milling because of the lack of data), medical uses of radiation (diagnostic radiation, nuclear medicine and radiotherapy) and industrial uses of radiation (industrial radiography and radioisotope production) are presented and summarised in detail. These are the main components of occupational exposures in China. In general, the average annual effective doses show a steady decreasing trend over periods: from 2.16 to 1.16 mSv in medical uses of radiation during 1990-2000; from 1.92 to 1.18 mSv in industrial radiography during 1990-2000; from 8.79 to 2.05 mSv in radioisotope production during the period 1980-2000. Almost all the average annual effective doses in discussed occupations were lower than 5 mSv in recent years (except for well-logging: 6.86 mSv in 1999) and no monitored workers were found to have received the occupational exposure exceeding 50 mSv in a single year or 100 mSv in a five-year period. So the Chinese protection status of occupation exposure has been improved in recent years. However, the average annual effective doses in some occupations, such as diagnostic radiology and coal mining, were still much higher than that of the whole world. There are still needs for further improvement and careful monitoring of occupational exposure to protect every worker from excessive occupational exposure, especially for the workers who were neglected before.

  1. Silica dust exposures during selected construction activities.

    Science.gov (United States)

    Flanagan, Mary Ellen; Seixas, Noah; Majar, Maria; Camp, Janice; Morgan, Michael

    2003-01-01

    This study characterized exposure for dust-producing construction tasks. Eight common construction tasks were evaluated for quartz and respirable dust exposure by collecting 113 personal task period samples for cleanup; demolition with handheld tools; concrete cutting; concrete mixing; tuck-point grinding; surface grinding; sacking and patching concrete; and concrete floor sanding using both time-integrating filter samples and direct-reading respirable dust monitors. The geometric mean quartz concentration was 0.10 mg/m(3) (geometric standard deviation [GSD]=4.88) for all run time samples, with 71% exceeding the threshold limit value. Activities with the highest exposures were surface grinding, tuck-point grinding, and concrete demolition (GM[GSD] of 0.63[4.12], 0.22[1.94], and 0.10[2.60], respectively). Factors recorded each minute were task, tool, work area, respiratory protection and controls used, estimated cross draft, and whether anyone nearby was making dust. Factors important to exposure included tool used, work area configuration, controls employed, cross draft, and in some cases nearby dust. More protective respirators were employed as quartz concentration increased, although respiratory protection was found to be inadequate for 42% of exposures. Controls were employed for only 12% of samples. Exposures were reduced with three controls: box fan for surface grinding and floor sanding, and vacuum/shroud for surface grinding, with reductions of 57, 50, and 71%, respectively. Exposures were higher for sweeping compound, box fan for cleanup, ducted fan dilution, and wetted substrate. Construction masons and laborers are frequently overexposed to silica. The usual protection method, respirators, was not always adequate, and engineering control use was infrequent and often ineffective.

  2. Dose level of occupational exposure in China.

    Science.gov (United States)

    Tian, Yuan; Zhang, Liang'an; Ju, Yongjian

    2008-01-01

    This paper discusses the dose level of Chinese occupational exposures during 1986-2000. Data on occupational exposures from the main categories in nuclear fuel cycle (uranium enrichment and conversion, fuel fabrication, reactor operation, waste management and research activity, except for uranium mining and milling because of the lack of data), medical uses of radiation (diagnostic radiation, nuclear medicine and radiotherapy) and industrial uses of radiation (industrial radiography and radioisotope production) are presented and summarised in detail. These are the main components of occupational exposures in China. In general, the average annual effective doses show a steady decreasing trend over periods: from 2.16 to 1.16 mSv in medical uses of radiation during 1990-2000; from 1.92 to 1.18 mSv in industrial radiography during 1990-2000; from 8.79 to 2.05 mSv in radioisotope production during the period 1980-2000. Almost all the average annual effective doses in discussed occupations were lower than 5 mSv in recent years (except for well-logging: 6.86 mSv in 1999) and no monitored workers were found to have received the occupational exposure exceeding 50 mSv in a single year or 100 mSv in a five-year period. So the Chinese protection status of occupation exposure has been improved in recent years. However, the average annual effective doses in some occupations, such as diagnostic radiology and coal mining, were still much higher than that of the whole world. There are still needs for further improvement and careful monitoring of occupational exposure to protect every worker from excessive occupational exposure, especially for the workers who were neglected before.

  3. Development of a spatial stochastic multimedia exposure model to assess population exposure at a regional scale

    International Nuclear Information System (INIS)

    Analyzing the relationship between the environment and health has become a major focus of public health efforts in France, as evidenced by the national action plans for health and the environment. These plans have identified the following two priorities: -identify and manage geographic areas where hotspot exposures are a potential risk to human health; and -reduce exposure inequalities. The aim of this study is to develop a spatial stochastic multimedia exposure model for detecting vulnerable populations and analyzing exposure determinants at a fine resolution and regional scale. A multimedia exposure model was developed by INERIS to assess the transfer of substances from the environment to humans through inhalation and ingestion pathways. The RESPIR project adds a spatial dimension by linking GIS (Geographic Information System) to the model. Tools are developed using modeling, spatial analysis and geostatistic methods to build and discretize interesting variables and indicators from different supports and resolutions on a 1-km2 regular grid. We applied this model to the risk assessment of exposure to metals (cadmium, lead and nickel) using data from a region in France (Nord-Pas-de-Calais). The considered exposure pathways include the atmospheric contaminant inhalation and ingestion of soil, vegetation, meat, egg, milk, fish and drinking water. Exposure scenarios are defined for different reference groups (age, dietary properties, and the fraction of food produced locally). The two largest risks correspond to an ancient industrial site (Metaleurop) and the Lille agglomeration. In these areas, cadmium, vegetation ingestion and soil contamination are the principal determinants of the computed risk. -- Highlights: ► We present a multimedia exposure model for mapping environmental disparities. ► We perform a risk assessment on a region of France at a fine scale for three metals. ► We examine exposure determinants and detect vulnerable population. ► The largest

  4. Occupational exposure to pesticides and respiratory health

    Directory of Open Access Journals (Sweden)

    Ali Mamane

    2015-06-01

    Full Text Available This article aims to review the available literature regarding the link between occupational exposure to pesticides and respiratory symptoms or diseases. Identification of epidemiological studies was performed using PubMed. 41 articles were included, 36 regarding agricultural workers and five regarding industry workers. Among the 15 cross-sectional studies focusing on respiratory symptoms and agricultural pesticide exposure, 12 found significant associations with chronic cough, wheeze, dyspnoea, breathlessness or chest tightness. All four studies on asthma found a relationship with occupational exposure, as did all three studies on chronic bronchitis. The four studies that performed spirometry reported impaired respiratory function linked to pesticide exposure, suggestive of either obstructive or restrictive syndrome according to the chemical class of pesticide. 12 papers reported results from cohort studies. Three out of nine found a significant relationship with increased risk of wheeze, five out of nine with asthma and three out of three with chronic bronchitis. In workers employed in pesticide production, elevated risks of chronic obstructive pulmonary disease (two studies out of three and impaired respiratory function suggestive of an obstructive syndrome (two studies out of two were reported. In conclusion, this article suggests that occupational exposure to pesticides is associated with an increased risk of respiratory symptoms, asthma and chronic bronchitis, but the causal relationship is still under debate.

  5. Environmental exposure to pesticides and respiratory health

    Directory of Open Access Journals (Sweden)

    Ali Mamane

    2015-09-01

    Full Text Available Respiratory effects of environmental exposure to pesticides are debated. Here we aimed to review epidemiological studies published up until 2013, using the PubMed database. 20 studies dealing with respiratory health and non-occupational pesticide exposure were identified, 14 carried out on children and six on adults. In four out of nine studies in children with biological measurements, mothers' dichlorodiphenyldichloroethylene (DDE blood levels during pregnancy were associated with asthma and wheezing in young children. An association was also found between permethrin in indoor air during pregnancy and wheezing in children. A significant association between asthma and DDE measured in children's blood (aged 7–10 years was observed in one study. However, in three studies, no association was found between asthma or respiratory infections in children and pesticide levels in breast milk and/or infant blood. Lastly, in three out of four studies where post-natal pesticide exposure of children was assessed by parental questionnaire an association with respiratory symptoms was found. Results of the fewer studies on pesticide environmental exposure and respiratory health of adults were much less conclusive: indeed, the associations observed were weak and often not significant. In conclusion, further studies are needed to confirm whether there is a respiratory risk associated with environmental exposure to pesticides.

  6. Inhalation exposure systems: design, methods and operation.

    Science.gov (United States)

    Wong, Brian A

    2007-01-01

    The respiratory system, the major route for entry of oxygen into the body, provides entry for external compounds, including pharmaceutic and toxic materials. These compounds (that might be inhaled under environmental, occupational, medical, or other situations) can be administered under controlled conditions during laboratory inhalation studies. Inhalation study results may be controlled or adversely affected by variability in four key factors: animal environment; exposure atmosphere; inhaled dose; and individual animal biological response. Three of these four factors can be managed through engineering processes. Variability in the animal environment is reduced by engineering control of temperature, humidity, oxygen content, waste gas content, and noise in the exposure facility. Exposure atmospheres are monitored and adjusted to assure a consistent and known exposure for each animal dose group. The inhaled dose, affected by changes in respiration physiology, may be controlled by exposure-specific monitoring of respiration. Selection of techniques and methods for the three factors affected by engineering allows the toxicologic pathologist to study the reproducibility of the fourth factor, the biological response of the animal. PMID:17325967

  7. ASSESSMENT OF HUMAN EXPOSURE TO TOLUENE DIISOCYANATE

    Directory of Open Access Journals (Sweden)

    OLIVIA ANCA RUSU

    2011-03-01

    Full Text Available Assessment of human exposure to toluene diisocyanate. Toluene diisocyanate (TDI, an aromatic compound, may be dangerous for human health. Diisocyanates have wide industrial use in the fabrication of flexible and rigid foams, fibers, elastomers, and coatings such as paints and varnishes. Isocyanates are known skin and respiratory sensitizers, and proper engineering controls should be in place to prevent exposure to isocyanate liquid and vapor; exposure to TDI vapors is well documented to increase asthma risk. The study focused on the exposure of workers and nearby populations to toluene diisocyanate in a Polyurethane Foam Factory located in Baia Mare, Romania. Workplace air measurements were performed in different departments of the plant, after sampling either in fixed points or as personal monitoring. Sampling in four different locations of Baia Mare town was carried out, - during and after the foaming process. TDI sampling was performed on silica cartridge followed by GC-MS analysis. TDI concentration at workplace was lower than 0,035 mg/m³, which represents the permissible exposure limit, while in the city the TDI concentration had shown values below 0,20 μg/m³. Health assessment of a group of 49 workers was based on questionnaire interview, determination of TDI antibodies and lung function tests. Data collected until this stage do not show any negative effects of TDI on the employees health. Since this plant had only recently begun operating, continuous workplace and ambient air TDI monitoring, along with workers health surveillance, is deemed necessary.

  8. Radiation risk due to occupational exposure

    International Nuclear Information System (INIS)

    Exposure to ionizing radiation occurs in many occupations. Workers can be exposed to both natural and artificial sources of radiation. Any exposure to ionizing radiation incurs some risk, either to the individual or to the individual's progeny. This dissertation investigated the radiation risk due to occupational exposure in industrial radiography. Analysis of the reported risk estimates to occupational exposure contained in the UNSCEAR report of 2008 in industrial radiography practice was done. The causes of accidents in industrial radiography include: Lack of or inadequate regulatory control, inadequate training, failure to follow operational procedures, human error, equipment malfunction or defect, inadequate maintenance and wilful violation have been identified as primary causes of accidents. To minimise radiation risks in industrial radiography exposure devices and facilities should be designed such that there is intrinsic safety and operational safety ensured by establishing a quality assurance programme, safety culture fostered and maintained among all workers, industrial radiography is performed in compliance with approved local rules, workers engaged have appropriate qualifications and training, available safe operational procedures are followed, a means is provided for detecting incidents and accidents and an analysis of the causes and lessons learned. (author)

  9. Music exposure and hearing disorders: an overview.

    Science.gov (United States)

    Zhao, Fei; Manchaiah, Vinaya K C; French, David; Price, Sharon M

    2010-01-01

    It has been generally accepted that excessive exposure to loud music causes various hearing symptoms (e.g. tinnitus) and consequently leads to a risk of permanent hearing damage, known as noise-induced hearing loss (NIHL). Such potential risk of NIHL due to loud music exposure has been widely investigated in musicians and people working in music venues. With advancements in sound technology and rapid developments in the music industry, increasing numbers of people, particularly adolescents and young adults, are exposing themselves to music on a voluntary basis at potentially harmful levels, and over a substantial period of time, which can also cause NIHL. However, because of insufficient audiometric evidence of hearing loss caused purely by music exposure, there is still disagreement and speculation about the risk of hearing loss from music exposure alone. Many studies have suggested using advanced audiological measurements as more sensitive and efficient tools to monitor hearing status as early indicators of cochlear dysfunction. The purpose of this review is to provide further insight into the potential risk of hearing loss caused by exposure to loud music, and thus contribute to further raising awareness of music induced hearing loss. PMID:20001447

  10. Exposure influences expressive timing judgments in music.

    Science.gov (United States)

    Honing, Henkjan; Ladinig, Olivia

    2009-02-01

    This study is concerned with the question whether, and to what extent, listeners' previous exposure to music in everyday life, and expertise as a result of formal musical training, play a role in making expressive timing judgments in music. This was investigated by using a Web-based listening experiment in which listeners with a wide range of musical backgrounds were asked to compare 2 recordings of the same composition (15 pairs, grouped in 3 musical genres), 1 of which was tempo-transformed (manipulating the expressive timing). The results show that expressive timing judgments are not so much influenced by expertise levels, as is suggested by the expertise hypothesis, but by exposure to a certain musical idiom, as is suggested by the exposure hypothesis. As such, the current study provides evidence for the idea that some musical capabilities are acquired through mere exposure to music, and that these abilities are more likely enhanced by active listening (exposure) than by formal musical training (expertise).

  11. Exposure of Nurses to Electromagnetic Fields

    International Nuclear Information System (INIS)

    Devices that produce electromagnetic fields (EMF) within the range of 0-300 GHz are widely used in surgical and diagnostic procedures. As a result a large number of physicians and other groups of medical personnel may be exposed to EMF. Even if patients' exposure, sometimes quite high, is inevitable or even recommended, medical personnel should be substantially protected against EMF exposure. Evaluation of nurses' exposure to EMF was based on an analysis of EMF magnitudes in the surrounding of magnetic resonance imaging (MRI) and electrosurgical units. These two kinds of apparatus are the strongest EMF sources in health service facilities. The measurements were performed according to the norms and hygiene regulations binding in Poland. Measurements performed by the Nofer Institute of Medicine in Lodz, and data collected by the Central Database on EMF Sources were used in the analysis. The Central Database is run by the Nofer Institute of Medicine at the behest of the Chief Sanitary Inspector. The study showed that nurses' exposure to EMF emitted by MRI and electrosurgical units complies with Polish norms and hygiene regulations and can be classified as negligible or allowable. It was found that work of nurses in exposure to EMF emitted by MRI and electrosurgical units can be regarded as safe, which means that their health should not be endangered by the performed job. (author)

  12. Magnetic field exposure among utility workers

    Energy Technology Data Exchange (ETDEWEB)

    Bracken, T.D.; Senior, R.S. [T. Dan Bracken, Inc., Portland, OR (United States); Rankin, R.F. [Applied Research Services, Inc., Lake Oswego, OR (United States); Alldredge, J.R. [Washington State Univ., Pullman, WA (United States); Sussman, S.S. [Electric Power Research Institute, Palo Alto, CA (United States)

    1995-09-01

    The Electric and Magnetic Field Measurement Project for Utilities -- the Electric Power Research Institute (EPRI) Electric and Magnetic Field Digital Exposure (EMDEX) Project (the EPRI EMDEX Project) -- was a multifaceted project that entailed technology transfer, measurement protocol design, data management, and exposure assessment analyses. This paper addresses one specific objective of the project: the collection, analysis, and documentation of power-frequency magnetic filed exposures for a diverse population of utility employees at 59 sites in four countries between September, 1988, and September, 1989. Specially designed sampling procedures and data collection protocols were used to ensure uniform implementation across sites. Volunteers within 13 job classifications recorded which of eight work or three nonwork environments they occupied while wearing an EMDEX meter. Approximately 50,000 hours of magnetic field exposure records taken at 10 s intervals were obtained, about 70% of which were from work environments. Exposures and time spent in environments were analyzed by primary work environment, by occupied environment, and by job classification.

  13. The Epigenetic Effects of Prenatal Cadmium Exposure.

    Science.gov (United States)

    Vilahur, Nadia; Vahter, Marie; Broberg, Karin

    2015-06-01

    Prenatal exposure to the highly toxic and common pollutant cadmium has been associated with adverse effects on child health and development. However, the underlying biological mechanisms of cadmium toxicity remain partially unsolved. Epigenetic disruption due to early cadmium exposure has gained attention as a plausible mode of action, since epigenetic signatures respond to environmental stimuli and the fetus undergoes drastic epigenomic rearrangements during embryogenesis. In the current review, we provide a critical examination of the literature addressing prenatal cadmium exposure and epigenetic effects in human, animal, and in vitro studies. We conducted a PubMed search and obtained eight recent studies addressing this topic, focusing almost exclusively on DNA methylation. These studies provide evidence that cadmium alters epigenetic signatures in the DNA of the placenta and of the newborns, and some studies indicated marked sexual differences for cadmium-related DNA methylation changes. Associations between early cadmium exposure and DNA methylation might reflect interference with de novo DNA methyltransferases. More studies, especially those including environmentally relevant doses, are needed to confirm the toxicoepigenomic effects of prenatal cadmium exposure and how that relates to the observed health effects of cadmium in childhood and later life.

  14. Physiological responses to daily light exposure

    Science.gov (United States)

    Yang, Yefeng; Yu, Yonghua; Yang, Bo; Zhou, Hong; Pan, Jinming

    2016-04-01

    Long daylength artificial light exposure associates with disorders, and a potential physiological mechanism has been proposed. However, previous studies have examined no more than three artificial light treatments and limited metabolic parameters, which have been insufficient to demonstrate mechanical responses. Here, comprehensive physiological response curves were established and the physiological mechanism was strengthened. Chicks were illuminated for 12, 14, 16, 18, 20, or 22 h periods each day. A quadratic relationship between abdominal adipose weight (AAW) and light period suggested that long-term or short-term light exposure could decrease the amount of AAW. Quantitative relationships between physiological parameters and daily light period were also established in this study. The relationships between triglycerides (TG), cholesterol (TC), glucose (GLU), phosphorus (P) levels and daily light period could be described by quadratic regression models. TG levels, AAW, and BW positively correlated with each other, suggesting long-term light exposure significantly increased AAW by increasing TG thus resulting in greater BW. A positive correlation between blood triiodothyronine (T3) levels and BW suggested that daily long-term light exposure increased BW by thyroid hormone secretion. Though the molecular pathway remains unknown, these results suggest a comprehensive physiological mechanism through which light exposure affects growth.

  15. Lightning detection and exposure algorithms for smartphones

    Science.gov (United States)

    Wang, Haixin; Shao, Xiaopeng; Wang, Lin; Su, Laili; Huang, Yining

    2015-05-01

    This study focuses on the key theory of lightning detection, exposure and the experiments. Firstly, the algorithm based on differential operation between two adjacent frames is selected to remove the lightning background information and extract lighting signal, and the threshold detection algorithm is applied to achieve the purpose of precise detection of lightning. Secondly, an algorithm is proposed to obtain scene exposure value, which can automatically detect external illumination status. Subsequently, a look-up table could be built on the basis of the relationships between the exposure value and average image brightness to achieve rapid automatic exposure. Finally, based on a USB 3.0 industrial camera including a CMOS imaging sensor, a set of hardware test platform is established and experiments are carried out on this platform to verify the performances of the proposed algorithms. The algorithms can effectively and fast capture clear lightning pictures such as special nighttime scenes, which will provide beneficial supporting to the smartphone industry, since the current exposure methods in smartphones often lost capture or induce overexposed or underexposed pictures.

  16. Plant Species Sensitivity Distributions for ozone exposure

    International Nuclear Information System (INIS)

    This study derived Species Sensitivity Distributions (SSD), representing a cumulative stressor-response distribution based on single-species sensitivity data, for ozone exposure on natural vegetation. SSDs were constructed for three species groups, i.e. trees, annual grassland and perennial grassland species, using species-specific exposure–response data. The SSDs were applied in two ways. First, critical levels were calculated for each species group and compared to current critical levels for ozone exposure. Second, spatially explicit estimates of the potentially affected fraction of plant species in Northwestern Europe were calculated, based on ambient ozone concentrations. We found that the SSD-based critical levels were lower than for the current critical levels for ozone exposure, with conventional critical levels for ozone relating to 8–20% affected plant species. Our study shows that the SSD concept can be successfully applied to both derive critical ozone levels and estimate the potentially affected species fraction of plant communities along specific ozone gradients. -- Highlights: ► Plant Species Sensitivity Distributions were derived for ozone exposure. ► Annual grassland species, as a species assemblage, tend to be most sensitive to ozone. ► Conventional critical levels for ozone relate to 8–20% affected plant species. ► The affected fraction of plant species for current ozone exposure in Northwestern Europe is estimated. -- Species Sensitivity Distributions offer opportunities in ozone risk assessment to both derive critical levels and estimate the affected fraction of a plant community

  17. EMF exposure assessment in the Finnish garment industry: evaluation of proposed EMF exposure metrics.

    Science.gov (United States)

    Hansen, N H; Sobel, E; Davanipour, Z; Gillette, L M; Niiranen, J; Wilson, B W

    2000-01-01

    Recently published studies indicate that having worked in occupations that involve moderate to high electromagnetic field (EMF) exposure is a risk factor for neurodegenerative diseases, including Alzheimer's disease. In these studies, the occupational groups most over-represented for EMF exposure comprised seamstresses, dressmakers, and tailors. Future epidemiologic studies designed to evaluate the possibility of a causal relationship between exposure to EMF and a neuro degenerative disease endpoint such as incidence of Alzheimer's disease, will benefit from the measurement of electromagnetic field metrics with potential biological relevance. Data collection methodology in such studies would be highly dependent upon how the metrics are defined. In this research the authors developed and demonstrated (1) protocols for collecting EMF exposure data suitable for estimating a variety of exposure metrics that may have biological relevance, and (2) analytical methods for calculation of these metrics. The authors show how exposure might be estimated under each of the three prominent EMF health-effects mechanism theories and evaluate the assertion that relative exposure ranking is dependent on which mechanism is assumed. The authors also performed AC RMS magnetic flux density measurements, confirming previously reported findings. The results indicate that seamstresses, as an occupational group, should be considered for study of the possible health effects of long-term EMF exposure.

  18. Exposure-response relationships for inhalant wheat allergen exposure and asthma

    NARCIS (Netherlands)

    Baatjies, R; Meijster, T; Heederik, D; Jeebhay, M F

    2015-01-01

    BACKGROUND: A few studies have investigated exposure-response relationships for sensitisation to wheat, work-related symptoms and wheat allergen exposure. IgG4 is suggested to protect against the development of allergic sensitisation. The main aim of this current study was to explore the nature of e

  19. Occupational exposure to potential endocrine disruptors: further development of a job exposure matrix.

    NARCIS (Netherlands)

    Brouwers, M.M.; Tongeren, M. van; Hirst, A.A.; Bretveld, R.W.; Roeleveld, N.

    2009-01-01

    OBJECTIVES: The aim was to develop a new up-to-date and comprehensive job exposure matrix (JEM) for estimating exposure to potential endocrine disruptors in epidemiological research. METHODS: Chemicals with endocrine disrupting properties were identified from the literature and classified into 10 ch

  20. Exposure to fungicides in fruit growing: Re-entry time as a predictor for dermal exposure

    NARCIS (Netherlands)

    Tielemans, E.; Louwerse, E.; Cock, J. de; Brouwer, D.; Zielhuis, G.; Heederik, D.

    1999-01-01

    As part of a European Concerted Action on Male Reproduction Capability an exposure assessment survey was conducted among seasonal workers in the fruit growing sector in the Netherlands. Dermal exposure to the fungicides captan and tolylfluanid was measured using cotton gloves (12 persons) and skin p