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Sample records for ph modulates toxicity

  1. pH modulates arsenic toxicity in Bacillus licheniformis DAS-2.

    Science.gov (United States)

    Tripti, K; Shardendu

    2016-08-01

    The toxic characteristics of arsenic species, As(V) and As(III) result in ecological risks. Arsenic tolerant bacterium was isolated and identified as the Bacillus licheniformis DAS-2 through 16SrDNA sequencing. B. licheniformis DAS-2 was efficient to tolerate and remove both the As(V)[MIC 8mM] and As(III)[MIC 6mM] from the growth medium. The potential for the removal/uptake of arsenic from the 3, 5 and 7mM As(V) enriched growth media was 100%, 60% and 35% respectively and from the 1, 3 and 5mM As(III) enrichment it was 100%, 99% and 58% respectively at neutral pH. 80% of uptake As(V) was reduced to As(III) in 3mM As(V) enrichment which was gradually decreased to only 17% at 7mM As(V) enrichment at neutral pH. The arsenic toxicity in B. licheniformis DAS-2 was found modulated by pH and was examined through alteration in growth, uptake/removal, reduction and measurement of chemical toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The acid test of fluoride: how pH modulates toxicity.

    Science.gov (United States)

    Sharma, Ramaswamy; Tsuchiya, Masahiro; Skobe, Ziedonis; Tannous, Bakhos A; Bartlett, John D

    2010-05-28

    It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-)). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-). Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F(-) into cells. Here, we asked if F(-) was more toxic at low pH, as measured by increased cell stress and decreased cell function. Treatment of ameloblast-derived LS8 cells with F(-) at low pH reduced the threshold dose of F(-) required to phosphorylate stress-related proteins, PERK, eIF2alpha, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F(-) dose and pH. Luciferase secretion significantly decreased within 2 hr of F(-) treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F(-) in their drinking water exhibited increased stress-mediated phosphorylation of eIF2alpha in maturation stage ameloblasts (pHdental fluorosis.

  3. The acid test of fluoride: how pH modulates toxicity.

    Directory of Open Access Journals (Sweden)

    Ramaswamy Sharma

    2010-05-01

    Full Text Available It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F(-. Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F(-. Enamel formation is initiated in a neutral pH environment (secretory stage; however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage. Low pH can facilitate entry of F(- into cells. Here, we asked if F(- was more toxic at low pH, as measured by increased cell stress and decreased cell function.Treatment of ameloblast-derived LS8 cells with F(- at low pH reduced the threshold dose of F(- required to phosphorylate stress-related proteins, PERK, eIF2alpha, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F(- dose and pH. Luciferase secretion significantly decreased within 2 hr of F(- treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F(- in their drinking water exhibited increased stress-mediated phosphorylation of eIF2alpha in maturation stage ameloblasts (pH<6.0 as compared to secretory stage ameloblasts (pH approximately 7.2. Intriguingly, F(--treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn. In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected.The low pH environment of maturation stage ameloblasts facilitates the uptake of F(-, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.

  4. DOPA Decarboxylase Modulates Tau Toxicity.

    Science.gov (United States)

    Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

    2018-03-01

    The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

  5. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  6. Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

    Science.gov (United States)

    Chen, Z L; Huang, R Q

    2014-06-20

    Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

  7. The pH dependent toxicity and bioaccumulation of chloroquine tested on S. viminalis (basket willow)

    DEFF Research Database (Denmark)

    Rendal, Cecilie; Trapp, Stefan; Legind, Charlotte Nielsen

    2010-01-01

    (hydroxymethyl) – aminomethane (pH 8 and 9). Concentrations were determined with spectrophotometer. Toxicity was derived from calculations of normalized transpiration over time, and RCF (root concentration factor) values were calculated. Increasing BCF values were found for increasing pH levels, and the toxicity...

  8. Effect of pH on the toxicity and bioconcentration of sulfadiazine on Daphnia magna

    DEFF Research Database (Denmark)

    Anskjær, Gitte Gotholdt; Rendal, Cecilie; Kusk, Kresten Ole

    2013-01-01

    The antimicrobial sulfonamide sulfadiazine has in the last decades been detected in environmental water bodies, both surface and ground water. Since pH in the environment may vary considerably, this study examined the toxicity of the amphoter sulfadiazine towards Daphnia magna at pH levels of 6.......0, 7.5 and 8.5, thus taking the impact of speciation into consideration, contrary to earlier eco-toxicity studies conducted at standard conditions. Toxicity tests were performed using the standard ISO 6341 test procedure modified to accommodate the three pH levels and the toxicity was expressed as EC50....... After 48h the EC50 was determined to be 27.2, 188 and 310mgL−1 at pH 6.0, 7.5 and 8.5, respectively, thus demonstrating a significant effect of pH on the toxicity of sulfadiazine. Furthermore, the bioconcentration factor (dry weight) was determined to be 50 and 36 at pH 6.0 and 8.5, respectively...

  9. Effects of pH on the toxicity and uptake of [14C]lindane in the midge, Chironomus riparius

    International Nuclear Information System (INIS)

    Fisher, S.W.

    1985-01-01

    The toxicity of the insecticide, lindane, was measured in the midge, Chironomus riparius, at pH 4, 6, and 8 with the finding that lindane is significantly more toxic at pH 6 than at pH 4 and 8. The higher toxicity of lindane at pH 6 is a product of two factors. First the penetration of the compound into the midge is lower at pH 4 than at pH 6 and 8. Second, a greater percentage of total radioactivity is contributed by parent compound at pH 6

  10. Disentangling the effects of low pH and metal mixture toxicity on macroinvertebrate diversity

    Science.gov (United States)

    Fornaroli, Riccardo; Ippolito, Alessio; Tolkkinen, Mari J.; Mykrä, Heikki; Muotka, Timo; Balistrieri, Laurie S.; Schmidt, Travis S.

    2018-01-01

    One of the primary goals of biological assessment of streams is to identify which of a suite of chemical stressors is limiting their ecological potential. Elevated metal concentrations in streams are often associated with low pH, yet the effects of these two potentially limiting factors of freshwater biodiversity are rarely considered to interact beyond the effects of pH on metal speciation. Using a dataset from two continents, a biogeochemical model of the toxicity of metal mixtures (Al, Cd, Cu, Pb, Zn) and quantile regression, we addressed the relative importance of both pH and metals as limiting factors for macroinvertebrate communities. Current environmental quality standards for metals proved to be protective of stream macroinvertebrate communities and were used as a starting point to assess metal mixture toxicity. A model of metal mixture toxicity accounting for metal interactions was a better predictor of macroinvertebrate responses than a model considering individual metal toxicity. We showed that the direct limiting effect of pH on richness was of the same magnitude as that of chronic metal toxicity, independent of its influence on the availability and toxicity of metals. By accounting for the direct effect of pH on macroinvertebrate communities, we were able to determine that acidic streams supported less diverse communities than neutral streams even when metals were below no-effect thresholds. Through a multivariate quantile model, we untangled the limiting effect of both pH and metals and predicted the maximum diversity that could be expected at other sites as a function of these variables. This model can be used to identify which of the two stressors is more limiting to the ecological potential of running waters.

  11. Disentangling the effects of low pH and metal mixture toxicity on macroinvertebrate diversity.

    Science.gov (United States)

    Fornaroli, Riccardo; Ippolito, Alessio; Tolkkinen, Mari J; Mykrä, Heikki; Muotka, Timo; Balistrieri, Laurie S; Schmidt, Travis S

    2018-04-01

    One of the primary goals of biological assessment of streams is to identify which of a suite of chemical stressors is limiting their ecological potential. Elevated metal concentrations in streams are often associated with low pH, yet the effects of these two potentially limiting factors of freshwater biodiversity are rarely considered to interact beyond the effects of pH on metal speciation. Using a dataset from two continents, a biogeochemical model of the toxicity of metal mixtures (Al, Cd, Cu, Pb, Zn) and quantile regression, we addressed the relative importance of both pH and metals as limiting factors for macroinvertebrate communities. Current environmental quality standards for metals proved to be protective of stream macroinvertebrate communities and were used as a starting point to assess metal mixture toxicity. A model of metal mixture toxicity accounting for metal interactions was a better predictor of macroinvertebrate responses than a model considering individual metal toxicity. We showed that the direct limiting effect of pH on richness was of the same magnitude as that of chronic metal toxicity, independent of its influence on the availability and toxicity of metals. By accounting for the direct effect of pH on macroinvertebrate communities, we were able to determine that acidic streams supported less diverse communities than neutral streams even when metals were below no-effect thresholds. Through a multivariate quantile model, we untangled the limiting effect of both pH and metals and predicted the maximum diversity that could be expected at other sites as a function of these variables. This model can be used to identify which of the two stressors is more limiting to the ecological potential of running waters. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Zinc toxicity on antioxidative response in (Zea mays L. at two different pH

    Directory of Open Access Journals (Sweden)

    Hosseini, Zahra

    2013-02-01

    Full Text Available Zn is the second most abundant transition metal after iron (Fe. Excess Zn can have negative effects on plants. The effect of Zn at two different pH on lipid peroxidation (MDA, membrane permeability (EC, hydrogen peroxide (H2O2,non-protein thiols (NPT and the activities of major antioxidant enzymes Zea mays were investigated under controlled growth conditions. Zn-excess conditions increased the EC, MDA, H2O2 content and non-protein thiols and also activities of antioxidant enzymes were increased. Also zinc toxicity was higher in 4.5 pH than 7.5 pH.

  13. High pH ammonia toxicity, and the search for life on the Jovian planets.

    Science.gov (United States)

    Deal, P H; Souza, K A; Mack, H M

    1975-10-01

    Jovian plants have enviroments apparently suitable for the evolution of life, but nevertheless, present severe challenges to organisms. One such challenge arises from the presence of ammonia. Ammonia is an efficient biocide, its effect being dependent on pH as well as on concentration. The effects of pH and ammonia concentration were studied separately, where possible, on a variety of organisms, including some isolated from natural enviornments of high pH and/or ammonia concentration. Escherichia coli and Bacillus subtilis are both extremely sensitive to ammonia. An aerobic organism (growth up to pH 11.4) from an alkaline spring is more resistant, but exhibits a toxic response to ammonia at a pH much lower than its maximum for growth. The greatest ammonia resistance has been found in an unidentified organism growing at near neutral pH. Even in this case, however, survival at ammonia concentrations reasonably expected on the Jovian planets is measured in hours. This is, nevertheless, two to three orders of magnitude longer than for E. coli. Our data support the tentative conclusion that contamination of the Jovian planets with terrestrial organisms that can grow is unlikely. However, the range of toxic response noted, coupled with the observation that terrestrial life has not been exposed to high ammonia concentrations for millions of years, suggests that adaptation to greater ammonia tolerance may be possible.

  14. Dietary compounds as modulators of metals and metalloids toxicity.

    Science.gov (United States)

    Jadán-Piedra, Carlos; Chiocchetti, Gabriela Matuoka; Clemente, María Jesús; Vélez, Dinoraz; Devesa, Vicenta

    2017-07-07

    A large part of the population is exposed to metals and metalloids through the diet. Most of the in vivo studies on its toxicokinetics and toxicity are conducted by means of exposure through drinking water or by intragastric or intraperitoneal administration of aqueous standards, and therefore they do not consider the effect of the food matrix on the exposure. Numerous studies show that some components of the diet can modulate the toxicity of these food contaminants, reducing their effect on a systemic level. Part of this protective role may be due to a reduction of intestinal absorption and subsequent tissue accumulation of the toxic element, although it may also be a consequence of their ability to counteract the toxicity directly by their antioxidant and/or anti-inflammatory activity, among other factors. The present review provides a compilation of existing information about the effect that certain components of the diet have on the toxicokinetics and toxicity of the metals and metalloids of greatest toxicological importance that are present in food (arsenic, cadmium, lead, and mercury), and of their most toxic chemical species.

  15. Gut microbiota modulation of chemotherapy efficacy and toxicity

    OpenAIRE

    Alexander, James L.; Wilson, Ian D.; Teare, Julian; Marchesi, Julian Roberto; Nicholson, Jeremy K.; Kinross, James M.

    2017-01-01

    Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidenc...

  16. Mechanisms behind pH changes by plant roots and shoots caused by elevated concentration of toxic elements

    OpenAIRE

    Javed, Muhammad Tariq

    2011-01-01

    Toxic elements are present in polluted water from mines, industrial outlets, storm water etc. Wetland plants take up toxic elements and increase the pH of the medium. In this thesis was investigated how the shoots of submerged plants and roots of emergent plants affected the pH of the surrounding water in the presence of free toxic ions. The aim was to clarify the mechanisms by which these plants change the surrounding water pH in the presence of toxic ions. The influence of Elodea canadensis...

  17. High Ph, Ammonia Toxicity, and the Search for Life on the Jovian Planets

    Science.gov (United States)

    Deal, P. H.; Souza, K. A.; Mack, H. M.

    1975-01-01

    The effects of pH and ammonia concentration were studied separately, where possible, on a variety of organisms, including some isolated from natural environments of high pH and/or ammonia concentration. Escherichia coli and Bacillus subtilis are both extremely sensitive to ammonia. An aerobic organism (growth up to pH 11.4) from an alkaline spring is more resistant, but exhibits a toxic response to ammonia at a pH much lower than its maximum for growth. The greatest ammonia resistance has been found in an unidentified organism growing at near neutral pH. Even in this case, however, urvival at ammonia concentrations reasonably expected on the Jovian planets is measured in hours. This is two to three orders of magnitude longer than for E. coli. Results support the tentative conclusion that contamination of the Jovian planets with terrestrial organisms that can grow is unlikely. However, the range of toxic response noted, coupled with the observation that terrestrial life has not been exposed to high ammonia concentrations for millions of years, suggests that adaptation to greater ammonia tolerance may be possible.

  18. The effect of pH on chronic aquatic nickel toxicity is dependent on the pH itself: Extending the chronic nickel bioavailability models.

    Science.gov (United States)

    Nys, Charlotte; Janssen, Colin R; Van Sprang, Patrick; De Schamphelaere, Karel A C

    2016-05-01

    The environmental quality standard for Ni in the European Commission's Water Framework Directive is bioavailability based. Although some of the available chronic Ni bioavailability models are validated only for pH ≤ 8.2, a considerable fraction of European surface waters has a pH > 8.2. Therefore, the authors investigated the effect of a change in pH from 8.2 to 8.7 on chronic Ni toxicity in 3 invertebrate (Daphnia magna, Lymnaea stagnalis, and Brachionus calyciflorus) and 2 plant species (Pseudokirchneriella subcapitata and Lemna minor). Nickel toxicity was almost always significantly higher at pH 8.7 than at pH 8.2. To test whether the existing chronic Ni bioavailability models developed for pH ≤ 8.2 can be used at higher pH levels, Ni toxicity at pH 8.7 was predicted based on Ni toxicity observed at pH 8.2. This resulted in a consistent underestimation of toxicity. The results suggest that the effect of pH on Ni(2+) toxicity is dependent on the pH itself: the slope of the pH effect is steeper above than below pH 8.2 for species for which a species-specific bioavailability model exists. Therefore, the existing chronic Ni bioavailability models were modified to allow predictions of chronic Ni toxicity to invertebrates and plants in the pH range of 8.2 to 8.7 by applying a pH slope (SpH ) dependent on the pH of the target water. These modified Ni bioavailability models resulted in more accurate predictions of Ni toxicity to all 5 species (within 2-fold error), without the bias observed using the bioavailability models developed for pH ≤ 8.2. The results of the present study can decrease the uncertainty in implementing the bioavailability-based environmental quality standard under the Water Framework Directive for high-pH regions in Europe. © 2015 SETAC.

  19. Gut microbiota modulation of chemotherapy efficacy and toxicity.

    Science.gov (United States)

    Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

    2017-06-01

    Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

  20. Multiwall carbon nanotubes modulate paraquat toxicity in Arabidopsis thaliana.

    Science.gov (United States)

    Fan, Xiaoji; Xu, Jiahui; Lavoie, Michel; Peijnenburg, W J G M; Zhu, Youchao; Lu, Tao; Fu, Zhengwei; Zhu, Tingheng; Qian, Haifeng

    2018-02-01

    Carbon nanotubes can be either toxic or beneficial to plant growth and can also modulate toxicity of organic contaminants through surface sorption. The complex interacting toxic effects of carbon nanotubes and organic contaminants in plants have received little attention in the literature to date. In this study, the toxicity of multiwall carbon nanotubes (MWCNT, 50 mg/L) and paraquat (MV, 0.82 mg/L), separately or in combination, were evaluated at the physiological and the proteomic level in Arabidopsis thaliana for 7-14 days. The results revealed that the exposure to MWCNT had no inhibitory effect on the growth of shoots and leaves. Rather, MWCNT stimulated the relative electron transport rate and the effective photochemical quantum yield of PSII value as compared to the control by around 12% and lateral root production up to nearly 4-fold as compared to the control. The protective effect of MWCNT on MV toxicity on the root surface area could be quantitatively explained by the extent of MV adsorption on MWCNT and was related to stimulation of photosynthesis, antioxidant protection and number and area of lateral roots which in turn helped nutrient assimilation. The influence of MWCNT and MV on photosynthesis and oxidative stress at the physiological level was consistent with the proteomics analysis, with various over-expressed photosynthesis-related proteins (by more than 2 folds) and various under-expressed oxidative stress related proteins (by about 2-3 folds). This study brings new insights into the interactive effects of two xenobiotics (MWCNT and MV) on the physiology of a model plant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Extracellular pH Modulates Neuroendocrine Prostate Cancer Cell Metabolism and Susceptibility to the Mitochondrial Inhibitor Niclosamide

    Science.gov (United States)

    Ippolito, Joseph E.; Brandenburg, Matthew W.; Ge, Xia; Crowley, Jan R.; Kirmess, Kristopher M.; Som, Avik; D’Avignon, D. Andre; Arbeit, Jeffrey M.; Achilefu, Samuel; Yarasheski, Kevin E.; Milbrandt, Jeffrey

    2016-01-01

    Neuroendocrine prostate cancer is a lethal variant of prostate cancer that is associated with castrate-resistant growth, metastasis, and mortality. The tumor environment of neuroendocrine prostate cancer is heterogeneous and characterized by hypoxia, necrosis, and numerous mitoses. Although acidic extracellular pH has been implicated in aggressive cancer features including metastasis and therapeutic resistance, its role in neuroendocrine prostate cancer physiology and metabolism has not yet been explored. We used the well-characterized PNEC cell line as a model to establish the effects of extracellular pH (pH 6.5, 7.4, and 8.5) on neuroendocrine prostate cancer cell metabolism. We discovered that alkalinization of extracellular pH converted cellular metabolism to a nutrient consumption-dependent state that was susceptible to glucose deprivation, glutamine deprivation, and 2-deoxyglucose (2-DG) mediated inhibition of glycolysis. Conversely, acidic pH shifted cellular metabolism toward an oxidative phosphorylation (OXPHOS)-dependent state that was susceptible to OXPHOS inhibition. Based upon this mechanistic knowledge of pH-dependent metabolism, we identified that the FDA-approved anti-helminthic niclosamide depolarized mitochondrial potential and depleted ATP levels in PNEC cells whose effects were enhanced in acidic pH. To further establish relevance of these findings, we tested the effects of extracellular pH on susceptibility to nutrient deprivation and OXPHOS inhibition in a cohort of castrate-resistant prostate cancer cell lines C4-2B, PC-3, and PC-3M. We discovered similar pH-dependent toxicity profiles among all cell lines with these treatments. These findings underscore a potential importance to acidic extracellular pH in the modulation of cell metabolism in tumors and development of an emerging paradigm that exploits the synergy of environment and therapeutic efficacy in cancer. PMID:27438712

  2. Role of pH on the acute toxicity of sulfite in water. [Carassius auratus; Leistes reticulatus

    Energy Technology Data Exchange (ETDEWEB)

    Sano, H.

    1976-01-01

    The toxicity of sulfite to fish decreases with increasing pH value, because the HSO/sub 3//sup -/ ion is more toxic than the SO/sub 3//sup 2 -/ ion. An effective sulfite concentration S/sub eff/ which is proportional to the toxicity on fish is expressed by the following equation: S/sub eff/ = (HSO/sub 3//sup -/) + f(SO/sub 3//sup 2 -/), where f is a coefficient which expresses the change of toxicity of sulfite depending on the pH of the water, and varies for each species of fish. For goldfish, owing to the very small toxic contribution of SO/sub 3//sup 2 -/ ion (f = 0.07), the pH dependence of the toxicity of sulfite on pH was so strong that sulfite seemed almost non-toxic in basic solution. However, f for guppy is somewhat larger (f = 0.20) so that the toxicity of sulfite weakly depends on the pH value of water.

  3. Modulation of prion polymerization and toxicity by rationally designed peptidomimetics.

    Science.gov (United States)

    Srivastava, Ankit; Sharma, Sakshi; Sadanandan, Sandhya; Gupta, Sakshi; Singh, Jasdeep; Gupta, Sarika; Haridas, V; Kundu, Bishwajit

    2017-01-01

    Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the anti-prion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, non-fibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-β2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  4. The effect of pH on the bioconcentration and toxicity of weak organic electrolytes

    DEFF Research Database (Denmark)

    Rendal, Cecilie

    to the bioconcentration of ionizing organic compounds showed that this fraction cannot safely be overlooked. The work presented in this thesis suggests that the standard test procedures used to test toxicity and bioconcentration are not sufficient to fully illuminate the ecotoxicity of ionizing organic compounds unless......Many of the compounds in use today have ionizing properties. Investigations have shown that around half of the compounds preregistered for REACH and over 70% of all pharmaceuticals are ionizing organic compounds. These compounds may pose a risk when they are released into the environment....... Ionization, however, complicates the environmental risk assessment of these compounds because the uptake processes of the neutral fraction differ from the processes of the ionized fraction. Acids are increasingly neutral at pH levels below the pKa while bases are increasingly neutral at pH levels above the p...

  5. Toxicity evaluation of pH dependent stable Achyranthes aspera herbal gold nanoparticles

    Science.gov (United States)

    Tripathi, Alok; Kumari, Sarika; Kumar, Arvind

    2016-01-01

    Nanoparticles have gained substantial attention for the control of various diseases. However, any adverse effect of herbal gold nanoparticles (HGNPs) on animals including human being has not been investigated in details. The objectives of current study are to assess the cytotoxicity of HGNPs synthesized by using leaf extract of Achyranthes aspera, and long epoch stability. The protocol deals with stability of HGNPs in pH dependent manner. Visually, HGNPs formation is characterized by colour change of extract from dark brown to dark purple after adding gold chloride solution (1 mM). The 100 μg/ml HGNPs concentration has been found nontoxic to the cultured spleenocyte cells. Spectrophotometric analysis of nanoparticles solution gave a peak at 540 nm which corresponds to surface plasmon resonance absorption band. As per scanning electron microscopy and Transmission electron microscopy (TEM), size of HGNPs are in the range of 50-80 nm (average size 70 nm) with spherical morphology. TEM-selected area electron diffraction observation showed hexagonal texture. HGNPs showed substantial stability at higher temperature (85 °C), pH 10 and salt concentration (5 M). The zeta potential value of HGNPs is -35.9 mV at temperature 25 °C, pH 10 showing its good quality with better stability in comparison to pH 6 and pH 7. The findings advocate that the protocol for the synthesis of HGNPs is easy and quick with good quality and long epoch stability at pH 10. Moreover, non-toxic dose could be widely applicable for human health as a potential nano-medicine in the future to cure diseases.

  6. Abrin Toxicity and Bioavailability after Temperature and pH Treatment

    Directory of Open Access Journals (Sweden)

    Christina C. Tam

    2017-10-01

    Full Text Available Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea, Abrus precatorius and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation. In both the cell culture cytotoxicity model and the mouse bioassay, abrin’s toxic effects were completely abrogated if the toxin was exposed to temperatures of 74 °C or higher. In the cell culture model, 63 °C-treated abrin had a 30% reduction in cytotoxicity which was validated in the in vivo mouse bioassay with all mice dying but with a slight time-to-death delay as compared to the non-treated abrin control. Since temperature inactivation did not affect abrin’s ability to inhibit protein synthesis (A-chain, we hypothesize that high temperature treatment affected abrin’s ability to bind to cellular receptors (affecting B-chain. Our results confirm the absolute need to validate in vitro cytotoxicity assays with in vivo mouse bioassays.

  7. Abrin Toxicity and Bioavailability after Temperature and pH Treatment.

    Science.gov (United States)

    Tam, Christina C; Henderson, Thomas D; Stanker, Larry H; He, Xiaohua; Cheng, Luisa W

    2017-10-13

    Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), Abrus precatorius and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT) assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation. In both the cell culture cytotoxicity model and the mouse bioassay, abrin's toxic effects were completely abrogated if the toxin was exposed to temperatures of 74 °C or higher. In the cell culture model, 63 °C-treated abrin had a 30% reduction in cytotoxicity which was validated in the in vivo mouse bioassay with all mice dying but with a slight time-to-death delay as compared to the non-treated abrin control. Since temperature inactivation did not affect abrin's ability to inhibit protein synthesis (A-chain), we hypothesize that high temperature treatment affected abrin's ability to bind to cellular receptors (affecting B-chain). Our results confirm the absolute need to validate in vitro cytotoxicity assays with in vivo mouse bioassays.

  8. Manganese toxicity in pasture legumes. II. Effects of pH and molybdenum levels in the substrate

    Energy Technology Data Exchange (ETDEWEB)

    Truong, N V; Andrew, C S; Wilson, G L

    1971-06-01

    The effects of pH and Mo levels in the growing media on Mn toxicity were investigated for white clover and five tropical pasture legume species. In solution culture, high Mo supply did not influence Mn toxicity. However, in two species, it caused Mo toxicity. High solution pH intensified Mn toxicity in white clover, probably by way of uptake. The effects of Ca and P on Mn toxicity reported in a previous paper, were not greatly influenced by solution pH. In the soil, Mo application greatly increased dry matter yield of white clover grown on soils high in exchangeable Mn. This effect was more easily attributed to an influence on N metabolism of the legume plant than on Mn toxicity. Measured soil pH was found to have little influence on the level of exchangeable Mn in the soil. However the larger pH changes in small soil pockets, resulting from non-uniform incorporation of chemicals in the soil, might have a more important effect on this fraction of soil Mn. 31 references, 7 tables.

  9. Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

    Science.gov (United States)

    Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

    2008-01-01

    The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

  10. pH and ion strength modulated ionic species loading in mesoporous silica nanoparticles

    International Nuclear Information System (INIS)

    Liu, Wei; Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Yang, Meng; Li, Li; Xu, Jianguo

    2013-01-01

    Mesoporous silica nanoparticles (MSN) have emerged as appealing host materials to accommodate guest molecules for biomedical applications, and recently various methods have been developed to modulate the loading of guest molecules in the silica matrix. Herein, it was demonstrated that pH and ion strength showed great influence on the loading of charged species into the nanoparticles, taking MCM-41 as a host MSN model and methylviologen (MV 2+ ) and 1,5-naphthalene disulfonate (NDS 2− ) as typical charged ionic guest molecules. As the pH increased from 3.0 to 8.0, the loading amount of MV 2+ increased gradually, while on the contrary, it decreased gradually for NDS 2− , for the solution pH changed the electrostatic interaction between the silica matrix and the ionic guest molecules. Additionally, the adding of NaCl reduced the electrostatic interaction, which resulted in a decreasing of the electrostatic rejection and electrostatic accumulation for the molecules carrying the same and the opposite charge to the particle respectively. Thus, pH and ion strength can be employed as simple approaches to modulate the loading of charged molecules and permselectivity in MSN. This work has a definite guidance function for molecule loading, transport modulation, controlled release as well as sensors based on MSN. (paper)

  11. Modulation of homocysteine toxicity by S-nitrosothiol formation: a mechanistic approach.

    Science.gov (United States)

    Morakinyo, Moshood K; Strongin, Robert M; Simoyi, Reuben H

    2010-08-05

    The metabolic conversion of homocysteine (HCYSH) to homocysteine thiolactone (HTL) has been reported as the major cause of HCYSH pathogenesis. It was hypothesized that inhibition of the thiol group of HCYSH by S-nitrosation will prevent its metabolic conversion to HTL. The kinetics, reaction dynamics, and mechanism of reaction of HCYSH and nitrous acid to produce S-nitrosohomocysteine (HCYSNO) was studied in mildly to highly acidic pHs. Transnitrosation of this non-protein-forming amino acid by S-nitrosoglutathione (GSNO) was also studied at physiological pH 7.4 in phosphate buffer. In both cases, HCYSNO formed quantitatively. Copper ions were found to play dual roles, catalyzing the rate of formation of HCYSNO as well as its rate of decomposition. In the presence of a transition-metal ions chelator, HCYSNO was very stable with a half-life of 198 h at pH 7.4. Nitrosation by nitrous acid occurred via the formation of more powerful nitrosating agents, nitrosonium cation (NO(+)) and dinitrogen trioxide (N(2)O(3)). In highly acidic environments, NO(+) was found to be the most effective nitrosating agent with a first-order dependence on nitrous acid. N(2)O(3) was the most relevant nitrosating agent in a mildly acidic environment with a second-order dependence on nitrous acid. The bimolecular rate constants for the direct reactions of HCYSH and nitrous acid, N(2)O(3), and NO(+) were 9.0 x 10(-2), 9.50 x 10(3), and 6.57 x 10(10) M(-1) s(-1), respectively. These rate constant values agreed with the electrophilic order of these nitrosating agents: HNO(2) formation kinetics of HCYSNO. This study has shown that it is possible to modulate homocysteine toxicity by preventing its conversion to a more toxic HTL by S-nitrosation.

  12. Integration into Big Data: First Steps to Support Reuse of Comprehensive Toxicity Model Modules (SOT)

    Science.gov (United States)

    Data surrounding the needs of human disease and toxicity modeling are largely siloed limiting the ability to extend and reuse modules across knowledge domains. Using an infrastructure that supports integration across knowledge domains (animal toxicology, high-throughput screening...

  13. Coral calcifying fluid pH is modulated by seawater carbonate chemistry not solely seawater pH.

    Science.gov (United States)

    Comeau, S; Tambutté, E; Carpenter, R C; Edmunds, P J; Evensen, N R; Allemand, D; Ferrier-Pagès, C; Tambutté, S; Venn, A A

    2017-01-25

    Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pH CF ) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pH CF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (A T ). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pH CF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [A T ], revealing that seawater pH is not the sole driver of pH CF Notably, when we synthesize our results with published data, we identify linear relationships of pH CF with the seawater [DIC]/[H + ] ratio, [A T ]/ [H + ] ratio and [[Formula: see text

  14. Influence of soil pH on the toxicity of zinc oxide nanoparticles to the terrestrial isopod Porcellionides pruinosus.

    Science.gov (United States)

    Tourinho, Paula S; van Gestel, Cornelis A M; Lofts, Stephen; Soares, Amadeu M V M; Loureiro, Susana

    2013-12-01

    The effects of soil pH on the toxicity of ZnO nanoparticles (NPs) to the terrestrial isopod Porcellionides pruinosus were evaluated. Isopods were exposed to a natural soil amended with CaCO3 to reach 3 different pH(CaCl2) levels (4.5, 6.2, and 7.3) and to standard LUFA 2.2 soil (pH 5.5) spiked with ZnO NPs (30 nm), non-nano ZnO (200 nm), and ionic Zn as ZnCl₂. Toxicity was expressed based on total Zn concentration in soil, as well as total Zn and free Zn²⁺ ion concentrations in porewater. Compared with ZnO-spiked soils, the ZnCl₂-spiked soils had lower pH and higher porewater Ca²⁺ and Zn levels. Isopod survival did not differ between Zn forms and soils, but survival was higher for isopods exposed to ZnO NPs at pH 4.5. Median effect concentrations (EC50s) for biomass change showed similar trends for all Zn forms in all soils, with higher values at intermediate pH. Median lethal concentration (LC50) and EC50 values based on porewater Zn or free Zn ion concentrations were much lower for ZnO than for ionic zinc. Zn body concentrations increased in a dose-related manner, but no effect of soil pH was found. It is suggested not only that dissolved or free Zn in porewater contributed to uptake and toxicity, but also that oral uptake (i.e., ingestion of soil particles) could be an important additional route of exposure. © 2013 SETAC.

  15. pH modulates the binding of early growth response protein 1 transcription factor to DNA.

    Science.gov (United States)

    Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

    2013-08-01

    The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

  16. Curcumin Modulates α-Synuclein Aggregation and Toxicity

    Science.gov (United States)

    2012-01-01

    In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

  17. pH Modulates the Binding of EGR1 Transcription Factor to DNA

    Science.gov (United States)

    Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

    2013-01-01

    EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

  18. Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines.

    Science.gov (United States)

    Chin, Stephen; Aherne, Noel J; Last, Andrew; Assareh, Hassan; Shakespeare, Thomas P

    2017-12-01

    We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT. © 2017 The Royal Australian and New Zealand College of Radiologists.

  19. Interactive effects of pH, temperature and light during ammonia toxicity events in Elodea canadensis

    NARCIS (Netherlands)

    Netten, J.J.C.; Heide, van der T.; Smolders, A.J.P.

    2013-01-01

    Increased nutrient loading threatens many freshwater ecosystems. Elevated temperatures may increase the sensitivity to eutrophication in these ecosystems. Higher concentrations of possibly toxic reduced nitrogen (NHx) in the water layer may be expected as production and anaerobic breakdown rates

  20. The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

    Science.gov (United States)

    Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

    2014-01-01

    Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. Published by Elsevier B.V.

  1. Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

    Science.gov (United States)

    Nair, Harikrishnan A; Snima, K S; Kamath, Ravindranath C; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

    2015-01-01

    Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

  2. The effect of pH on the toxicity of zinc oxide nanoparticles to Folsomia candida in amended field soil.

    Science.gov (United States)

    Waalewijn-Kool, Pauline L; Ortiz, Maria Diez; Lofts, Stephen; van Gestel, Cornelis A M

    2013-10-01

    The effect of soil pH on the toxicity of 30 nm ZnO to Folsomia candida was assessed in Dorset field soils with pHCaCl2 adjusted to 4.31, 5.71, and 6.39. To unravel the contribution of particle size and dissolved Zn, 200 nm ZnO and ZnCl2 were tested. Zinc sorption increased with increasing pH, and Freundlich kf values ranged from 98.9 (L/kg)(1/n) to 333 (L/kg)(1/n) for 30 nm ZnO and from 64.3 (L/kg)(1/n) to 187 (L/kg)(1/n) for ZnCl2. No effect of particle size was found on sorption, and little difference was found in toxicity between 30 nm and 200 nm ZnO. The effect on reproduction decreased with increasing pH for all Zn forms, with 28-d median effective concentrations (EC50s) of 553 mg Zn/kg, 1481 mg Zn/kg, and 3233 mg Zn/kg for 30 nm ZnO and 331 mg Zn/kg, 732 mg Zn/kg, and 1174 mg Zn/kg for ZnCl2 at pH 4.31, 5.71, and 6.39, respectively. The EC50s based on porewater Zn concentrations increased with increasing pH for 30 nm ZnO from 4.77 mg Zn/L to 18.5 mg Zn/L, while for ZnCl2 no consistent pH-related trend in EC50s was found (21.0-63.3 mg Zn/L). Porewater calcium levels were 10 times higher in ZnCl2 -spiked soils than in ZnO-spiked soils. The authors' results suggest that the decreased toxicity of ZnCl2 compared with 30 nm ZnO based on porewater concentrations was because of a protective effect of calcium and not a particle effect. © 2013 SETAC.

  3. Mitochondrial modulation of phosphine toxicity and resistance in Caenorhabditis elegans.

    Science.gov (United States)

    Zuryn, Steven; Kuang, Jujiao; Ebert, Paul

    2008-03-01

    Phosphine is a fumigant used to protect stored commodities from infestation by pest insects, though high-level phosphine resistance in many insect species threatens the continued use of the fumigant. The mechanisms of toxicity and resistance are not clearly understood. In this study, the model organism, Caenorhabditis elegans, was employed to investigate the effects of phosphine on its proposed in vivo target, the mitochondrion. We found that phosphine rapidly perturbs mitochondrial morphology, inhibits oxidative respiration by 70%, and causes a severe drop in mitochondrial membrane potential (DeltaPsim) within 5 h of exposure. We then examined the phosphine-resistant strain of nematode, pre-33, to determine whether resistance was associated with any changes to mitochondrial physiology. Oxygen consumption was reduced by 70% in these mutant animals, which also had more mitochondrial genome copies than wild-type animals, a common response to reduced metabolic capacity. The mutant also had an unexpected increase in the basal DeltaPsim, which protected individuals from collapse of the membrane potential following phosphine treatment. We tested whether directly manipulating mitochondrial function could influence sensitivity toward phosphine and found that suppression of mitochondrial respiratory chain genes caused up to 10-fold increase in phosphine resistance. The current study confirms that phosphine targets the mitochondria and also indicates that direct alteration of mitochondrial function may be related to phosphine resistance.

  4. USE OF ULVA LACTUCA TO DISTINGUISH PH DEPENDENT TOXICANTS IN MARINE WATERS AND SEDIMENTS

    Science.gov (United States)

    Ulva lactuca (sea lettuce) is a cosmopolitan marine attached green seaweed capable of sequestering high environmental levels of ammonia. Ammonia can be acutely toxic to marine organisms and is often found in dredged sediments from highly industrial areas or from areas with high c...

  5. Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals

    DEFF Research Database (Denmark)

    Rendal, Cecilie; Kusk, Kresten Ole; Trapp, Stefan

    2011-01-01

    a dynamic flux model based on the Fick-Nernst-Planck diffusion equation known as the cell model. The cell model predicts that bases with delocalized charges may in some cases show declining bioaccumulation with increasing pH. Little information is available for amphoteric and zwitterionic compounds; however...

  6. Abrin toxicity and bioavailability after temperature and pH treatment

    Science.gov (United States)

    Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), Abrus precatorius. Due to its potential use as a bioterror weapon, the efficacy of standard food processing methods must be evaluated for its effectiveness against abrin. The temperature and pH stability o...

  7. Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer

    International Nuclear Information System (INIS)

    Flentje, Michael; Guckenberger, Matthias; Ok, Sami; Polat, Buelent; Sweeney, Reinhart A.

    2010-01-01

    Purpose: To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. Patients and Methods: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Results: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). Conclusion: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising. (orig.)

  8. Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Flentje, Michael [Dept. of Radiotherapy, Univ. Hospital Wuerzburg (Germany); Guckenberger, Matthias; Ok, Sami; Polat, Buelent; Sweeney, Reinhart A.

    2010-10-15

    Purpose: To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. Patients and Methods: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Results: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade {>=} 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade {>=} 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade {>=} 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). Conclusion: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising. (orig.)

  9. Postoperative Intensity-Modulated Arc Therapy for Cervical and Endometrial Cancer: A Prospective Report on Toxicity

    International Nuclear Information System (INIS)

    Vandecasteele, Katrien; Tummers, Philippe; Makar, Amin; Eijkeren, Marc van; Delrue, Louke; Denys, Hannelore; Lambert, Bieke; Beerens, Anne-Sophie; Van den Broecke, Rudy; Lambein, Kathleen; Fonteyne, Valérie; De Meerleer, Gert

    2012-01-01

    Purpose: To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC). Methods and Materials: Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m², weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated. Results: Regarding acute toxicity (n = 65), Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n = 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea (57% vs. 9%; p = 0.01), Grade 2 nocturia (24% vs. 4%; p = 0.03), Grade ≥2 hematologic toxicity (38% vs. nil, p = 0.003), Grade ≥2 leukopenia (33% vs. nil, p = 0.009), and a strong trend toward more fatigue (14% vs. 2%; p = 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p = 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p = 0.052). Regarding late toxicity (n = 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates. Conclusions: Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation influences acute but

  10. Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

    International Nuclear Information System (INIS)

    Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

    2007-01-01

    Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

  11. Hypofractionated Intensity-Modulated Radiotherapy for Carcinoma of the Prostate: Analysis of Toxicity

    International Nuclear Information System (INIS)

    Coote, Joanna H.; Wylie, James P.; Cowan, Richard A.; Logue, John P.; Swindell, Ric; Livsey, Jacqueline E.

    2009-01-01

    Purpose: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low α/β ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. Methods and Materials: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score ≥ 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. Results: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. Conclusions: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.

  12. Modulation of the epithelial Ca2+ channel ECaC by extracellular pH.

    NARCIS (Netherlands)

    Vennekens, R.; Prenen, J.; Hoenderop, J.G.J.; Bindels, R.J.M.; Droogmans, G.; Nilius, B.

    2001-01-01

    We investigated the effect of extracellular pH on whole-cell currents through the epithelial Ca2+ channel, ECaC, expressed in HEK 293 cells. Both mono- and divalent current densities were significantly smaller at pH 6.0 than at pH 7.4. At pH 8.5 they were slightly larger. Lowering extracellular pH

  13. Modulating Pluronics micellar rupture with cyclodextrins and drugs: effect of pH and temperature

    International Nuclear Information System (INIS)

    Valero, M; Dreiss, C A

    2014-01-01

    Micelles of the triblock copolymer Pluronic F127 can encapsulate drugs with various chemical structures and their architecture has been studied by small-angle neutron scattering (SANS). Interaction with a derivative of β-cyclodextrin, namely, heptakis(2,6-di-O- methyl)-β-cyclodextrin (DIMEB), induces a complete break-up of the micelles, providing a mechanism for drug release. In the presence of drugs partitioned within the micelles, competitive interactions between polymer, drug and cyclodextrin lead to a modulation of the micellar rupture, depending on the nature of the drug and the exact composition of the ternary system. These interactions can be further adjusted by temperature and pH. While the most widely accepted mechanism for the interaction between Pluronics and cyclodextrins is through polypseudorotaxane (PR) formation, involving the threading of β-CD on the polymer backbone, time-resolved SANS experiments show that de-micellisation takes place in less than 100 ms, thus unambiguously ruling out an inclusion complex between the cyclodextrin and the polymer chains

  14. Effect of pH and ionic strength on exposure and toxicity of encapsulated lambda-cyhalothrin to Daphnia magna.

    Science.gov (United States)

    Son, Jino; Hooven, Louisa A; Harper, Bryan; Harper, Stacey L

    2015-12-15

    Encapsulation of pesticide active ingredients in polymers has been widely employed to control the release of poorly water-soluble active ingredients. Given the high dispersibility of these encapsulated pesticides in water, they are expected to behave differently compared to their active ingredients; however, our current understanding of the fate and effects of encapsulated pesticides is still limited. In this study, we employed a central composite design (CCD) to investigate how pH and ionic strength (IS) affect the hydrodynamic diameter (HDD) and zeta potential of encapsulated λ-cyhalothrin and how those changes affect the exposure and toxicity to Daphnia magna. R(2) values greater than 0.82 and 0.84 for HDD and zeta potential, respectively, irrespective of incubation time suggest those changes could be predicted as a function of pH and IS. For HDD, the linear factor of pH and quadratic factor of pH×pH were found to be the most significant factors affecting the change of HDD at the beginning of incubation, whereas the effects of IS and IS×IS became significant as incubation time increased. For zeta potential, the linear factor of IS and quadratic factor of IS×IS were found to be the most dominant factors affecting the change of zeta potential of encapsulated λ-cyhalothrin, irrespective of incubation time. The toxicity tests with D. magna under exposure conditions in which HDD or zeta potential of encapsulated λ-cyhalothrin was maximized or minimized in the overlying water also clearly showed the worst-case exposure condition to D. magna was when the encapsulated λ-cyhalothrin is either stable or small in the overlying water. Our results show that water quality could modify the fate and toxicity of encapsulated λ-cyhalothrin in aquatic environments, suggesting understanding their aquatic interactions are critical in environmental risk assessment. Herein, we discuss the implications of our findings for risk assessment. Copyright © 2015 Elsevier B.V. All

  15. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Is Selectively Toxic to Primary Dopaminergic Neurons In Vitro

    Science.gov (United States)

    Griggs, Amy M.; Agim, Zeynep S.; Mishra, Vartika R.; Tambe, Mitali A.; Director-Myska, Alison E.; Turteltaub, Kenneth W.; McCabe, George P.; Rochet, Jean-Christophe; Cannon, Jason R.

    2014-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. Much data has linked the etiology of PD to a variety of environmental factors. The majority of cases are thought to arise from a combination of genetic susceptibility and environmental factors. Chronic exposures to dietary factors, including meat, have been identified as potential risk factors. Although heterocyclic amines that are produced during high-temperature meat cooking are known to be carcinogenic, their effect on the nervous system has yet to be studied in depth. In this study, we investigated neurotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a highly abundant heterocyclic amine in cooked meat, in vitro. We tested toxicity of PhIP and the two major phase I metabolites, N-OH-PhIP and 4′-OH-PhIP, using primary mesencephalic cultures from rat embryos. This culture system contains both dopaminergic and nondopaminergic neurons, which allows specificity of neurotoxicity to be readily examined. We find that exposure to PhIP or N-OH-PhIP is selectively toxic to dopaminergic neurons in primary cultures, resulting in a decreased percentage of dopaminergic neurons. Neurite length is decreased in surviving dopaminergic neurons. Exposure to 4′-OH-PhIP did not produce significant neurotoxicity. PhIP treatment also increased formation of oxidative damage markers, 4-hydroxy-2-nonenal (HNE) and 3-nitrotyrosine in dopaminergic neurons. Pretreatment with N-acetylcysteine was protective. Finally, treatment with blueberry extract, a dietary factor with known antioxidant and other protective mechanisms, prevented PhIP-induced toxicity. Collectively, our study suggests, for the first time, that PhIP is selectively toxic to dopaminergic neurons likely through inducing oxidative stress. PMID:24718704

  16. pH controlled gating of toxic protein pores by dendrimers

    Science.gov (United States)

    Mandal, Taraknath; Kanchi, Subbarao; Ayappa, K. G.; Maiti, Prabal K.

    2016-06-01

    Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent bacterial strains, on a target cell membrane is a challenging and active area of research. Here we demonstrate that PAMAM dendrimers can act as effective pH controlled gating devices once the pore has been formed. We have used fully atomistic molecular dynamics (MD) simulations to characterize the cytolysin A (ClyA) protein pores modified with fifth generation (G5) PAMAM dendrimers. Our results show that the PAMAM dendrimer, in either its protonated (P) or non-protonated (NP) states can spontaneously enter the protein lumen. Protonated dendrimers interact strongly with the negatively charged protein pore lumen. As a consequence, P dendrimers assume a more expanded configuration efficiently blocking the pore when compared with the more compact configuration adopted by the neutral NP dendrimers creating a greater void space for the passage of water and ions. To quantify the effective blockage of the protein pore, we have calculated the pore conductance as well as the residence times by applying a weak force on the ions/water. Ionic currents are reduced by 91% for the P dendrimers and 31% for the NP dendrimers. The preferential binding of Cl- counter ions to the P dendrimer creates a zone of high Cl- concentration in the vicinity of the internalized dendrimer and a high concentration of K+ ions in the transmembrane region of the pore lumen. In addition to steric effects, this induced charge segregation for the P dendrimer effectively blocks ionic transport through the pore. Our investigation shows that the bio-compatible PAMAM dendrimers can potentially be used to develop therapeutic protocols based on the pH sensitive gating of pores formed by pore forming toxins to mitigate bacterial infections.Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent

  17. Soil pH effects on the comparative toxicity of dissolved zinc, non-nano and nano ZnO to the earthworm Eisenia fetida.

    Science.gov (United States)

    Heggelund, Laura R; Diez-Ortiz, Maria; Lofts, Stephen; Lahive, Elma; Jurkschat, Kerstin; Wojnarowicz, Jacek; Cedergreen, Nina; Spurgeon, David; Svendsen, Claus

    2014-08-01

    To determine how soil properties influence nanoparticle (NP) fate, bioavailability and toxicity, this study compared the toxicity of nano zinc oxide (ZnO NPs), non-nano ZnO and ionic ZnCl2 to the earthworm Eisenia fetida in a natural soil at three pH levels. NP characterisation indicated that reaction with the soil media greatly controls ZnO properties. Three main conclusions were drawn. First that Zn toxicity, especially for reproduction, was influenced by pH for all Zn forms. This can be linked to the influence of pH on Zn dissolution. Secondly, that ZnO fate, toxicity and bioaccumulation were similar (including relationships with pH) for both ZnO forms, indicating the absence of NP-specific effects. Finally, earthworm Zn concentrations were higher in worms exposed to ZnO compared to ZnCl2, despite the greater toxicity of the ionic form. This observation suggests the importance of considering the relationship between uptake and toxicity in nanotoxicology studies.

  18. Modulation of hexavalent chromium toxicity on Οriganum vulgare in an acidic soil amended with peat, lime, and zeolite.

    Science.gov (United States)

    Antoniadis, Vasileios; Zanni, Anna A; Levizou, Efi; Shaheen, Sabry M; Dimirkou, Anthoula; Bolan, Nanthi; Rinklebe, Jörg

    2018-03-01

    Dynamics of chromate (Cr(VI)) in contaminated soils may be modulated by decreasing its phytoavailability via the addition of organic matter-rich amendments, which might accelerate Cr(VI) reduction to inert chromite (Cr(III)) or high-cation exchange capacity amendments. We studied Cr(VI) phytoavailability of oregano in a Cr(VI)-spiked acidic soil non-treated (S) and treated with peat (SP), lime (SL), and zeolite (SZ). The addition of Cr(VI) increased the concentrations of Cr(VI) and Cr(III) in soils and plants, especially in the lime-amended soil. The plant biomass decreased in the lime-amended soil compared to the un-spiked soil (control) due to decreased plant phosphorus concentrations and high Cr(VI) concentrations in root at that treatment. Oregano in the peat-amended soil exhibited significantly less toxic effects, due to the role of organic matter in reducing toxic Cr(VI) to Cr(III) and boosted plant vigour in this treatment. In the lime-amended soil, the parameters of soil Cr(VI), soil Cr(III), and root Cr(III) increased significantly compared to the non-amended soil, indicating that Cr(VI) reduction to Cr(III) was accelerated at high pH. Added zeolite failed to decreased Cr(VI) level to soil and plant. Oregano achieved a total uptake of Cr(III) and Cr(VI) of 0.275 mg in plant kg -1 soil in a pot in the non-amended soil. We conclude that peat as soil amendment might be considered as a suitable option for decreasing Cr(VI) toxicity in soil and plant, and that oregano as tolerant plant species has a certain potential to be used as a Cr accumulator. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Rationally Engineering Phototherapy Modules of Eosin-Conjugated Responsive Polymeric Nanocarriers via Intracellular Endocytic pH Gradients.

    Science.gov (United States)

    Liu, Guhuan; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

    2015-07-15

    Spatiotemporal switching of respective phototherapy modes at the cellular level with minimum side effects and high therapeutic efficacy is a major challenge for cancer phototherapy. Herein we demonstrate how to address this issue by employing photosensitizer-conjugated pH-responsive block copolymers in combination with intracellular endocytic pH gradients. At neutral pH corresponding to extracellular and cytosol milieu, the copolymers self-assemble into micelles with prominently quenched fluorescence emission and low (1)O2 generation capability, favoring a highly efficient photothermal module. Under mildly acidic pH associated with endolysosomes, protonation-triggered micelle-to-unimer transition results in recovered emission and enhanced photodynamic (1)O2 efficiency, which synergistically actuates release of encapsulated drugs, endosomal escape, and photochemical internalization processes.

  20. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  1. Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongmei [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Cuiling [Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi' an 710069 (China); She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Liu, Ping, E-mail: liuping@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Yaoyu [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Li, Jianli, E-mail: lijianli@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China)

    2015-11-05

    Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H{sup +} in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

  2. Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

    International Nuclear Information System (INIS)

    Li, Hongmei; Wang, Cuiling; She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng; Liu, Ping; Wang, Yaoyu; Li, Jianli

    2015-01-01

    Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H + in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

  3. Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation

    Science.gov (United States)

    Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

    2017-01-01

    Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram. PMID:28467792

  4. Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation.

    Science.gov (United States)

    Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

    2017-06-27

    Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram.

  5. Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

    Science.gov (United States)

    Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

    2017-07-01

    Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

  6. Functional toxicogenomic profiling expands insight into modulators of formaldehyde toxicity in yeast

    Directory of Open Access Journals (Sweden)

    Matthew North

    2016-11-01

    Full Text Available Formaldehyde (FA is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

  7. pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release.

    Science.gov (United States)

    Fundueanu, Gheorghe; Constantin, Marieta; Stanciu, Cristina; Theodoridis, Georgios; Ascenzi, Paolo

    2009-12-01

    Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as "smart" polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37 degrees C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37 degrees C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B(12) (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B(12) was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B(12) was investigated as a function of temperature, pH, and the CAB/SP ratio.

  8. Medium pH in submerged cultivation modulates differences in the intracellular protein profile of Fusarium oxysporum.

    Science.gov (United States)

    da Rosa-Garzon, Nathália Gonsales; Laure, Hélen Julie; Souza-Motta, Cristina Maria de; Rosa, José César; Cabral, Hamilton

    2017-08-09

    Fusarium oxysporum is a filamentous fungus that damages a wide range of plants and thus causes severe crop losses. In fungal pathogens, the genes and proteins involved in virulence are known to be controlled by environmental pH. Here, we report the influence of culture-medium pH (5, 6, 7, and 8) on the production of degradative enzymes involved in the pathogenesis of F. oxysporum URM 7401 and on the 2D-electrophoresis profile of intracellular proteins in this fungus. F. oxysporum URM 7401 was grown in acidic, neutral, and alkaline culture media in a submerged bioprocess. After 96 hr, the crude extract was processed to enzyme activity assays, while the intracellular proteins were obtained from mycelium and analyzed using 2D electrophoresis and mass spectrometry. We note that the diversity of secreted enzymes was changed quantitatively in different culture-medium pH. Also, the highest accumulated biomass and the intracellular protein profile of F. oxysporum URM 7401 indicate an increase in metabolism in neutral-alkaline conditions. The differential profiles of secreted enzymes and intracellular proteins under the evaluated conditions indicate that the global protein content in F. oxysporum URM 7401 is modulated by extracellular pH.

  9. Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

    Science.gov (United States)

    Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

    2016-08-26

    An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-01-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  11. Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

    Science.gov (United States)

    Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

    2018-01-01

    Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

  12. Intensity modulated radiotherapy for localized prostate cancer: rigid compliance to dose-volume constraints as a warranty of acceptable toxicity?

    International Nuclear Information System (INIS)

    Chen, Michael J; Nadalin, Wladmir; Weltman, Eduardo; Hanriot, Rodrigo M; Luz, Fábio P; Cecílio, Paulo J; Cruz, José C da; Moreira, Frederico R; Santos, Adriana S; Martins, Lidiane C

    2007-01-01

    To report the toxicity after intensity modulated radiotherapy (IMRT) for patients with localized prostate cancer, as a sole treatment or after radical prostatectomy. Between August 2001 and December 2003, 132 patients with prostate cancer were treated with IMRT and 125 were evaluable to acute and late toxicity analysis, after a minimum follow-up time of one year. Clinical and treatment data, including normal tissue dose-volume histogram (DVH) constraints, were reviewed. Gastro-intestinal (GI) and genito-urinary (GU) signs and symptoms were evaluated according to the Radiation Therapy Oncology Group (RTOG) toxicity scales. Median prescribed dose was 76 Gy. Median follow-up time was of 26.1 months. From the 125 patients, 73 (58.4%) presented acute Grade 1 or Grade 2 GI and 97 (77.2%) presented acute Grade 1 or Grade 2 GU toxicity. Grade 3 GI acute toxicity occurred in only 2 patients (1.6%) and Grade 3 GU acute toxicity in only 3 patients (2.4%). Regarding Grade 1 and 2 late toxicity, 26 patients (20.8%) and 21 patients (16.8%) presented GI and GU toxicity, respectively. Grade 2 GI late toxicity occurred in 6 patients (4.8%) and Grade 2 GU late toxicity in 4 patients (3.2%). None patient presented any Grade 3 or higher late toxicity. Non-conformity to DVH constraints occurred in only 11.2% of treatment plans. On univariate analysis, no significant risk factor was identified for Grade 2 GI late toxicity, but mean dose delivered to the PTV was associated to higher Grade 2 GU late toxicity (p = 0.042). IMRT is a well tolerable technique for routine treatment of localized prostate cancer, with short and medium-term acceptable toxicity profiles. According to the data presented here, rigid compliance to DHV constraints might prevent higher incidences of normal tissue complication

  13. Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy?

    International Nuclear Information System (INIS)

    Wan, Juefeng; Liu, Kaitai; Li, Kaixuan; Li, Guichao; Zhang, Zhen

    2015-01-01

    To identify dosimetric parameters associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. Ninety-three rectal cancer patients receiving concurrent capecitabine and pelvic intensity-modulated radiation therapy (IMRT) were analyzed. Pelvic bone marrow (PBM) was contoured for each patient and divided into three subsites: lumbosacral spine (LSS), ilium, and lower pelvis (LP). The volume of each site receiving 5–40 Gy (V 5, V10, V15, V20, V30, and V40, respectively) as well as patient baseline clinical characteristics was calculated. The endpoint for hematologic toxicity was grade ≥ 2 (HT2+) leukopenia, neutropenia, anemia or thrombocytopenia. Logistic regression was used to analyze correlation between dosimetric parameters and grade ≥ 2 hematologic toxicity. Twenty-four in ninety-three patients experienced grade ≥ 2 hematologic toxicity. Only the dosimetric parameter V40 of lumbosacral spine was correlated with grade ≥ 2 hematologic toxicity. Increased pelvic lumbosacral spine V40 (LSS-V40) was associated with an increased grade ≥ 2 hematologic toxicity (p = 0.041). Patients with LSS-V40 ≥ 60 % had higher rates of grade ≥ 2 hematologic toxicity than did patients with lumbosacral spine V40 < 60 % (38.3 %, 18/47 vs.13 %, 6/46, p =0.005). On univariate and multivariate logistic regression analysis, lumbosacral spine V40 and gender was also the variable associated with grade ≥ 2 hematologic toxicity. Female patients were observed more likely to have grade ≥ 2 hematologic toxicity than male ones (46.9 %, 15/32 vs 14.8 %, 9/61, p =0.001). Lumbosacral spine -V40 was associated with clinically significant grade ≥ 2 hematologic toxicity. Keeping the lumbosacral spine -V40 < 60 % was associated with a 13 % risk of grade ≥ 2 hematologic toxicity in rectal cancer patients undergoing concurrent chemoradiotherapy

  14. Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose-Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A. [Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL (United States)

    2012-01-01

    Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints

  15. Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose–Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

    International Nuclear Information System (INIS)

    Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A.; Liauw, Stanley L.

    2012-01-01

    Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose–volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V 70 ), 65 Gy (V 65 ), and 40 Gy (V 40 ). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V 70 ≤10%, V 65 ≤20%, and V 40 ≤40%; 92% for men with rectal V 70 ≤20%, V 65 ≤40%, and V 40 ≤80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose–volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

  16. Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

    International Nuclear Information System (INIS)

    Tang, Lili; Guan Hongxia; Ding Xiaolin; Wang Jiasheng

    2007-01-01

    Modulation by lycopene of aflatoxin B 1 (AFB 1 )-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB 1 (250 μg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB 1 (250 μg/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB 1 and greatly modulated AFB 1 metabolism and metabolic activation. Urinary excretion of AFB 1 phase 1 metabolites, AFM 1 , AFQ 1 , and AFP 1 , was significantly decreased in lycopene-treated animals. Formation of serum AFB 1 -albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p 1 -DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p 1 -N 7 -guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB 1 -mecapturic acid, was significantly increased in lycopene-intervened animals. AFB 1 -induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene

  17. Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Maclean, Jillian, E-mail: jillian.maclean@uclh.nhs.uk [Radiotherapy Department, University College London Hospital, London (United Kingdom); Fersht, Naomi [Radiotherapy Department, University College London Hospital, London (United Kingdom); Bremner, Fion [Neuro-Ophthalmology Department, National Hospital for Neurology and Neurosurgery, London (United Kingdom); Stacey, Chris; Sivabalasingham, Suganya [Radiotherapy Department, University College London Hospital, London (United Kingdom); Short, Susan [Radiotherapy Department, University College London Hospital, London (United Kingdom); Leeds Institute of Molecular Medicine, St James University Hospital, Leeds (United Kingdom)

    2013-03-15

    Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.

  18. Sorption, dissolution and pH determine the long-term equilibration and toxicity of coated and uncoated ZnO nanoparticles in soil.

    Science.gov (United States)

    Waalewijn-Kool, Pauline L; Diez Ortiz, Maria; van Straalen, Nico M; van Gestel, Cornelis A M

    2013-07-01

    To assess the effect of long-term dissolution on bioavailability and toxicity, triethoxyoctylsilane coated and uncoated zinc oxide nanoparticles (ZnO-NP), non-nano ZnO and ZnCl2 were equilibrated in natural soil for up to twelve months. Zn concentrations in pore water increased with time for all ZnO forms but peaked at intermediate concentrations of ZnO-NP and non-nano ZnO, while for coated ZnO-NP such a clear peak only was seen after 12 months. Dose-related increases in soil pH may explain decreased soluble Zn levels due to fixation of Zn released from ZnO at higher soil concentrations. At T = 0 uncoated ZnO-NP and non-nano ZnO were equally toxic to the springtail Folsomia candida, but not as toxic as coated ZnO-NP, and ZnCl2 being most toxic. After three months equilibration toxicity to F. candida was already reduced for all Zn forms, except for coated ZnO-NP which showed reduced toxicity only after 12 months equilibration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Evaluation of buffers toxicity in tobacco cells: Homopiperazine-1,4-bis (2-ethanesulfonic acid) is a suitable buffer for plant cells studies at low pH.

    Science.gov (United States)

    Borgo, Lucélia

    2017-06-01

    Low pH is an important environmental stressor of plant root cells. Understanding the mechanisms of stress and tolerance to acidity is critical; however, there is no widely accepted pH buffer for studies of plant cells at low pH. Such a buffer might also benefit studies of Al toxicity, in which buffering at low pH is also important. The challenge is to find a buffer with minimal cellular effects. We examined the cytotoxicity and possible metabolic disturbances of four buffers that have adequate pK a values and potential use for studies in the pH range of 4.0-5.0. These were homopipes (homopiperazine-1,4-bis (2-ethanesulfonic acid); pK a1 4.4), 3,3-dimethylglutaric acid (pK a1 3.73), β-alanine (pK a1 3.70) and potassium biphthalate (pK a1 2.95; pK a2 5.41). First, tobacco BY-2 cells were grown in a rich medium containing 10 mM of each buffer or MES (2-(N-morpholino) ethanesulfonic acid) as a control, with the pH initially adjusted to 5.7. β-alanine was clearly toxic and dimethylgluturate and biphthalate were found to be cytostatic, in which no culture growth occurred but cell viability was either unaffected or decreased only after 5 days. Only homopipes allowed normal culture growth and cell viability. Homopipes (10 mM) was then tested in cell cultures with an initial pH of 4.3 ± 0.17 in minimal medium to examine whether its undissociated species (H 2 A) displayed any cellular effects and no cytotoxic effects were observed. It is possible to conclude that among tested buffers, homopipes is the most suitable for studies at low pH, and may be especially useful for aluminum toxicity experiments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. The effects of salinity, pH, and dissolved organic matter on acute copper toxicity to the rotifer, Brachionus plicatilis ("L" strain).

    Science.gov (United States)

    Arnold, W R; Diamond, R L; Smith, D S

    2010-08-01

    This paper presents data from original research for use in the development of a marine biotic ligand model and, ultimately, copper criteria for the protection of estuarine and marine organisms and their uses. Ten 48-h static acute (unfed) copper toxicity tests using the euryhaline rotifer Brachionus plicatilis ("L" strain) were performed to assess the effects of salinity, pH, and dissolved organic matter (measured as dissolved organic carbon; DOC) on median lethal dissolved copper concentrations (LC50). Reconstituted and natural saltwater samples were tested at seven salinities (6, 11, 13, 15, 20, 24, and 29 g/L), over a pH range of 6.8-8.6 and a range of dissolved organic carbon of <0.5-4.1 mg C/L. Water chemistry analyses (alkalinity, calcium, chloride, DOC, hardness, magnesium, potassium, sodium, salinity, and temperature) are presented for input parameters to the biotic ligand model. In stepwise multiple regression analysis of experimental results where salinity, pH, and DOC concentrations varied, copper toxicity was significantly related only to the dissolved organic matter content (pH and salinity not statistically retained; alpha=0.05). The relationship of the 48-h dissolved copper LC50 values and dissolved organic carbon concentrations was LC50 (microg Cu/L)=27.1xDOC (mg C/L)1.25; r2=0.94.

  1. pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

    Science.gov (United States)

    McCrimmon, Donald R.; Martina, Marco

    2013-01-01

    The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

  2. Effect of soil organic matter content and pH on the toxicity of ZnO nanoparticles to Folsomia candida.

    Science.gov (United States)

    Waalewijn-Kool, Pauline L; Rupp, Svenja; Lofts, Stephen; Svendsen, Claus; van Gestel, Cornelis A M

    2014-10-01

    Organic matter (OM) and pH may influence nanoparticle fate and effects in soil. This study investigated the influence of soil organic matter content and pH on the toxicity of ZnO-NP and ZnCl2 to Folsomia candida in four natural soils, having between 2.37% and 14.7% OM and [Formula: see text] levels between 5.0 and 6.8. Porewater Zn concentrations were much lower in ZnO-NP than in ZnCl2 spiked soils, resulting in higher Freundlich sorption constants for ZnO-NP. For ZnCl2 the porewater Zn concentrations were significantly higher in less organic soils, while for ZnO-NP the highest soluble Zn level (23mgZn/l) was measured in the most organic soil, which had the lowest pH. Free Zn(2+) ion concentrations were higher for ZnCl2 than for ZnO-NP and were greatly dependent on pH (pHpw) and dissolved organic carbon content of the pore water. The 28-d EC50 values for the effect of ZnCl2 on the reproduction of F. candida increased with increasing OM content from 356 to 1592mgZn/kg d.w. For ZnO-NP no correlation between EC50 values and OM content was found and EC50 values ranged from 1695 in the most organic soil to 4446mgZn/kg d.w. in the higher pH soil. When based on porewater and free Zn(2+) concentrations, EC50 values were higher for ZnCl2 than for ZnO-NP, and consistently decreased with increasing pHpw. This study shows that ZnO-NP toxicity is dependent on soil properties, but is mainly driven by soil pH. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Release of copper from sintered tungsten-bronze shot under different pH conditions and its potential toxicity to aquatic organisms

    International Nuclear Information System (INIS)

    Thomas, Vernon G.; Santore, Robert C.; McGill, Ian

    2007-01-01

    Sintered tungsten-bronze is a new substitute for lead shot, and is about to be deposited in and around the wetlands of North America. This material contains copper in the alloyed form of bronze. This in vitro study was performed according to U.S. Fish and Wildlife Service criteria to determine the dissolution rate of copper from the shot, and to assess the toxic risk that it may present to aquatic organisms. The dissolution of copper from tungsten-bronze shot, pure copper shot, and glass beads was measured in a buffered, moderately hard, synthetic water of pH 5.5, 6.6, and 7.8 over a 28-day period. The dissolution of copper from both the control copper shot and the tungsten-bronze shot was affected significantly by the pH of the water and the duration of dissolution (all p values < 0.000). The rate of copper release from tungsten bronze shot was 30 to 50 times lower than that from the copper shot, depending on pH (p < 0.0000). The observed expected environmental concentration of copper released from tungsten-bronze shot after 28 days was 0.02 μg/L at pH 7.8, and 0.4 μg/L at pH 5.6, using a loading and exposure scenario specific in a U.S. Fish and Wildlife Service protocol. Ratio Quotient values derived from the highest EEC observed in this study (0.4 μg/L), and the copper toxic effect levels for all aquatic species listed in the U.S. Environmental Protection Agency ambient water quality criteria database, were all far less than the 0.1 criterion value. Given the conditions stipulated by the U.S. Fish and Wildlife Service and the U.S. Environmental Protection Agency, heavy loading from discharged tungsten-bronze shot would not pose a toxic risk to potable water, or to soil. Consequently, it would appear that no toxic risks to aquatic organisms will attend the use of tungsten-bronze shot of the approved composition. Given the likelihood that sintered tungsten-bronze of the same formula will be used for fishing weights, bullets, and wheel balance weights, it is

  4. How pH Modulates the Reactivity and Selectivity of a Siderophore-Associated Flavin Monooxygenase

    Science.gov (United States)

    2015-01-01

    Flavin-containing monooxygenases (FMOs) catalyze the oxygenation of diverse organic molecules using O2, NADPH, and the flavin adenine dinucleotide (FAD) cofactor. The fungal FMO SidA initiates peptidic siderophore biosynthesis via the highly selective hydroxylation of l-ornithine, while the related amino acid l-lysine is a potent effector of reaction uncoupling to generate H2O2. We hypothesized that protonation states could critically influence both substrate-selective hydroxylation and H2O2 release, and therefore undertook a study of SidA’s pH-dependent reaction kinetics. Consistent with other FMOs that stabilize a C4a-OO(H) intermediate, SidA’s reductive half reaction is pH independent. The rate constant for the formation of the reactive C4a-OO(H) intermediate from reduced SidA and O2 is likewise independent of pH. However, the rate constants for C4a-OO(H) reactions, either to eliminate H2O2 or to hydroxylate l-Orn, were strongly pH-dependent and influenced by the nature of the bound amino acid. Solvent kinetic isotope effects of 6.6 ± 0.3 and 1.9 ± 0.2 were measured for the C4a-OOH/H2O2 conversion in the presence and absence of l-Lys, respectively. A model is proposed in which l-Lys accelerates H2O2 release via an acid–base mechanism and where side-chain position determines whether H2O2 or the hydroxylation product is observed. PMID:24490904

  5. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    International Nuclear Information System (INIS)

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, José

    2012-01-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m²). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D mean and D max of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade ≥2 and grade ≥3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade ≥2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade ≥3 AET (P=.012). The derived V50 model was shown to predict grade ≥2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade ≥3 AET. There was no difference in the incidence of grade ≥2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  6. Modulating β-lactoglobulin nanofibril self-assembly at pH 2 using glycerol and sorbitol.

    Science.gov (United States)

    Dave, Anant C; Loveday, Simon M; Anema, Skelte G; Jameson, Geoffrey B; Singh, Harjinder

    2014-01-13

    β-Lactoglobulin (β-lg) forms fibrils when heated at 80 °C, pH 2, and low ionic strength (sorbitol (0-50% w/v) on β-lg self-assembly at pH 2. Glycerol and sorbitol stabilize native protein structure and modulate protein functionality by preferential exclusion. In our study, both polyols decreased the rate of β-lg self-assembly but had no effect on the morphology of fibrils. The mechanism of these effects was studied using circular dichroism spectroscopy and SDS-PAGE. Sorbitol inhibited self-assembly by stabilizing β-lg against unfolding and hydrolysis, resulting in fewer fibrillogenic species, whereas glycerol inhibited nucleation without inhibiting hydrolysis. Both polyols increased the viscosity of the solutions, but viscosity appeared to have little effect on fibril assembly, and we believe that self-assembly was not diffusion-limited under these conditions. This is in agreement with previous reports for other proteins assembling under different conditions. The phenomenon of peptide self-assembly can be decoupled from protein hydrolysis using glycerol.

  7. Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages.

    Directory of Open Access Journals (Sweden)

    Lydia Kasper

    Full Text Available Candida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine, differentiation (M1-/M2-type or activation status (vitamin D3 stimulation. We observed no differential activation of macrophage MAPK or NFκB signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NFκB signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore

  8. Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies

    International Nuclear Information System (INIS)

    Brixey, Clark J.; Roeske, John C.; Lujan, Anthony E.; Yamada, S. Diane; Rotmensch, Jacob; Mundt, Arno J.

    2002-01-01

    Purpose: To evaluate the impact of intensity-modulated whole pelvic radiotherapy (IM-WPRT) on acute hematologic toxicity (HT) in gynecology patients. Methods and Materials: Between February 2000 and June 2001, 36 patients (24 cervix, 12 uterus) received IM-WPRT. The target consisted of the upper vagina, parametria, uterus, and presacral and pelvic lymph nodes. Using commercially available software, seven or nine coplanar IM-WPRT plans were generated. The planning goals were to irradiate the target while minimizing the dose to the small bowel, bladder, and rectum. Pelvic bone marrow (BM) was not a constraint in the planning process. The variables analyzed included white blood count (WBC), absolute neutrophil count (ANC), platelets, and hemoglobin (Hgb) obtained before and weekly during RT. As a comparison, the HT in 88 patients (44 cervix, 44 uterus) treated to the same target volume and total dose (45 Gy) with conventional four-field WPRT was analyzed. In addition, the medullary spaces within the pelvic bones in 10 women were contoured and the average dose-volume histograms representing the pelvic BM were compared between the two groups. Results: IM-WPRT patients had a lower median age (p=0.008), higher percentage of squamous histologic features (p=0.04), and were more likely to receive chemotherapy (CTX) (p=0.02) than were the WPRT patients. No differences were seen in the baseline WBC, ANC, platelet, or Hgb levels between the two groups. Grade 2 or greater WBC, ANC, and Hgb toxicity was seen in 19.4%, 9.1%, and 8.6% of the IM-WPRT patients, respectively. Comparable rates were seen in the WPRT patients (WBC 21.6%, p=0.79; ANC 8.3%, p=0.91; Hgb 9.2%, p=0.94). No Grade 2 or greater platelet toxicity was seen in either group. Significant HT was infrequent in women treated with RT alone and was comparable in the two groups. In contrast, WPRT + CTX patients experienced more Grade 2 or greater WBC toxicity (60% vs. 31.2%, p=0.08) and developed lower median WBC (2.8 vs

  9. The concept of bio-corona in modulating the toxicity of engineered nanomaterials (ENM)

    International Nuclear Information System (INIS)

    Westmeier, Dana; Stauber, Roland H.; Docter, Dominic

    2016-01-01

    Besides the wide use of engineered nanomaterials (ENM) in technical products, their application spectrum in biotechnology and biomedicine is steadily increasing. In complex physiological environments the physico-chemical properties and the behavior of nanoparticles (NPs) are challenging to characterize. Biomolecules rapidly adsorb to the nanomaterial, leading to the formation of the protein/biomolecule corona, which critically affects the nanomaterials' (patho)biological and technical identities. This formation can trigger an immune response and affect nanoparticles' toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the (protein)corona-nanoparticle interaction and discuss how the corona modulates both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers. - Highlights: • “Nanotoxicology” has emerged an autonomous field with an explosive growth. • Nanomaterials adsorb (bio)molecules forming the so-called (bio)molecule corona. • (Fine-)tune of the corona composition could enable new possibilities in nanomedicine.

  10. The concept of bio-corona in modulating the toxicity of engineered nanomaterials (ENM)

    Energy Technology Data Exchange (ETDEWEB)

    Westmeier, Dana; Stauber, Roland H.; Docter, Dominic, E-mail: docter@uni-mainz.de

    2016-05-15

    Besides the wide use of engineered nanomaterials (ENM) in technical products, their application spectrum in biotechnology and biomedicine is steadily increasing. In complex physiological environments the physico-chemical properties and the behavior of nanoparticles (NPs) are challenging to characterize. Biomolecules rapidly adsorb to the nanomaterial, leading to the formation of the protein/biomolecule corona, which critically affects the nanomaterials' (patho)biological and technical identities. This formation can trigger an immune response and affect nanoparticles' toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the (protein)corona-nanoparticle interaction and discuss how the corona modulates both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers. - Highlights: • “Nanotoxicology” has emerged an autonomous field with an explosive growth. • Nanomaterials adsorb (bio)molecules forming the so-called (bio)molecule corona. • (Fine-)tune of the corona composition could enable new possibilities in nanomedicine.

  11. Bovine colostrum modulates myeloablative chemotherapy-induced gut toxicity in piglets

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko; Shen, René Liang; Cilieborg, Malene Skovsted

    2015-01-01

    BACKGROUND: Intensive chemotherapy frequently results in gut toxicity, indicated by oral and intestinal mucositis, resulting in poor treatment outcomes and increased mortality. There are no effective preventive strategies against gut toxicity and the role of diet is unknown. OBJECTIVE: We...

  12. Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy

    International Nuclear Information System (INIS)

    Zheng, YingJie; Han, Fei; Xiao, WeiWei; Xiang, YanQun; Lu, LiXia; Deng, XiaoWu; Cui, NianJi; Zhao, Chong

    2015-01-01

    To observe the late toxicities in nasopharyngeal carcinoma (NPC) patients who achieved long-term survival after intensity modulated radiation therapy (IMRT). 208 untreated NPC patients who received IMRT and survived more than five years with locoregional disease control and no metastasis were evaluated in this study. The prescription dose to the gross target volume of nasopharynx (GTVnx), positive neck lymph nodes (GTVnd), clinical target volume 1 (CTV1) and 2 (CTV2) was 68Gy/30f, 60-66Gy/30f, 60 Gy/30f and 54Gy/30f, respectively. The nasopharynx and upper neck targets were irradiated using IMRT, and the lower neck and supraclavicular fossae targets were irradiated using the half-beam technique with conventional irradiation. The late toxicities were evaluated according to the LENT/SOMA criteria of 1995. The median follow-up time was 78 months (60–96 months). The occurrence rates of cervical subcutaneous fibrosis, hearing loss, skin dystrophy, xerostomia, trismus, temporal lobe injury, cranial nerve damage, cataract, and brain stem injury induced by radiotherapy were 89.9%, 67.8%, 47.6%, 40.9%, 7.21%, 4.33%, 2.88%, 1.44%, and 0.48%, respectively. No spinal cord injury and mandible damage were found. Grade 3–4 late injuries were observed as follows: 1 (0.48%) skin dystrophy, 4 (1.92%) cervical subcutaneous fibrosis, 2 (0.96%) hearing loss, 2 (0.96%) cranial nerve palsy, and 1 (0.48%) temporal lobe necrosis. No grade 3–4 late injuries occurred in parotid, temporomandibular joints and eyes. Xerostomia decreased gradually over time and then showed only slight changes after 4 years. The change in the incisor distance stabilised by 1 year after RT, however, the incidence of hearing loss, skin dystrophy, subcutaneous fibrosis and nervous system injuries increased over time after RT. The late injuries in most NPC patients who had long-term survivals after IMRT are alleviated. Within the 5 years of follow-up, we found xerostomia decreased gradually; The change in the

  13. Salicylic Acid Alleviates Aluminum Toxicity in Soybean Roots through Modulation of Reactive Oxygen Species Metabolism

    Directory of Open Access Journals (Sweden)

    Ning Liu

    2017-11-01

    Full Text Available As an important signal molecule, salicylic acid (SA improves plant tolerance to aluminum (Al stress. The objective of this study was to investigate the effects of exogenous SA application on the dynamics of endogenous SA and reactive oxygen species in soybean (Glycine max L. exposed to Al stress. The roots of soybean seedlings were exposed to a combination of AlCl3 (30 μM and SA (10 μM/PAC (100 μM, paclobutrazol, SA biosynthesis inhibitor for 3, 6, 9, and 12 h. Al stress induced an increase in endogenous SA concentration in a time-dependent manner, also verified by the up-regulated expression of GmNPR1, an SA-responsive gene. Al stress increased the activities of phenylalanine ammonia-lyase (PAL and benzoic acid 2-hydroxylase (BA2H, and the contents of SA, O2- and malondialdehyde (MDA in the root apex. The application of exogenous SA increased PAL and BA2H, and reduced O2- and MDA contents in soybean roots under Al stress. PAC inhibited the SA induced increase in BA2H activity. In addition, the SA application resulted in a rapid increase in hydrogen peroxide (H2O2 concentration under Al stress, followed by a sharp decrease. Compared with the plants exposed to Al alone, Al+SA plants possessed higher activities of superoxide dismutase, peroxidase, and ascorbate peroxidase, and lower catalase activity, indicating that SA alleviated Al-induced oxidative damage. These results suggested that PAL and BA2H were involved in Al-induced SA production and showed that SA alleviated the adverse effects of Al toxicity by modulating the cellular H2O2 level and the antioxidant enzyme activities in the soybean root apex.

  14. Salicylic acid alleviates aluminum toxicity in soybean roots through modulation of reactive oxygen species metabolism

    Science.gov (United States)

    Liu, Ning; Song, Fengbin; Zhu, Xiancan; You, Jiangfeng; Yang, Zhenming; Li, Xiangnan

    2017-11-01

    As an important signal molecule, salicylic acid (SA) improves plant tolerance to aluminum (Al) stress. The objective of this study was to investigate the effects of exogenous SA application on the dynamics of endogenous SA and reactive oxygen species in soybean (Glycine max L.) exposed to Al stress. The roots of soybean seedlings were exposed to a combination of AlCl3 (30 μM) and SA (10 μM)/PAC (100 μM, paclobutrazol, SA biosynthesis inhibitor) for 3, 6, 9 and 12 h. Al stress induced an increase in endogenous SA concentration in a time-dependent manner, also verified by the up-regulated expression of GmNPR1, an SA-responsive gene. Al stress increased the activities of phenylalanine ammonia-lyase (PAL) and benzoic acid 2-hydroxylase (BA2H), and the contents of SA, O2- and malondialdehyde (MDA) in the root apex. The application of exogenous SA increased PAL and BA2H, and reduced O2- and MDA contents in soybean roots under Al stress. PAC inhibited the SA induced increase in BA2H activity. In addition, the SA application resulted in a rapid increase in hydrogen peroxide (H2O2) concentration under Al stress, followed by a sharp decrease. Compared with the plants exposed to Al alone, Al+SA plants possessed higher activities of superoxide dismutase, peroxidase and ascorbate peroxidase, and lower catalase activity, indicating that SA alleviated Al-induced oxidative damage. These results suggested that PAL and BA2H were involved in Al-induced SA production and showed that SA alleviated the adverse effects of Al toxicity by modulating the cellular H2O2 level and the antioxidant enzyme activities in the soybean root apex.

  15. CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

    Science.gov (United States)

    Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

    2017-01-01

    The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500-2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2.

  16. Leaching characteristics of toxic constituents from coal fly ash mixed soils under the influence of pH

    Energy Technology Data Exchange (ETDEWEB)

    Komonweeraket, Kanokwan [Department of Civil and Environmental Engineering, University of Wisconsin, Madison, WI 53706 (United States); Cetin, Bora, E-mail: bora.cetin@sdsmt.edu [College of Engineering, University of Georgia, Athens, GA 30602 (United States); Benson, Craig H., E-mail: chbenson@wisc.edu [Department of Civil and Environmental Engineering, University of Wisconsin, Madison, WI 53706 (United States); Aydilek, Ahmet H., E-mail: aydilek@umd.edu [Department of Civil and Environmental Engineering, University of Maryland, College Park, MD 20742 (United States); Edil, Tuncer B., E-mail: edil@engr.wisc.edu [Department of Civil and Environmental Engineering, University of Wisconsin, Madison, WI 53706 (United States)

    2015-04-15

    Highlights: • The impact of pH on the leaching of elements and metals from fly ash mixed soils. • Generally Ca, Cd, Mg, and Sr follows a cationic leaching pattern. • The leaching of As and Se shows an oxyanionic leaching pattern. • The leaching behavior of elements does not change based on material type. • Different fly ash types show different abilities in immobilizing trace elements. - Abstract: Leaching behaviors of Arsenic (As), Barium (Ba), Calcium (Ca), Cadmium (Cd), Magnesium (Mg), Selenium (Se), and Strontium (Sr) from soil alone, coal fly ash alone, and soil-coal fly ash mixtures, were studied at a pH range of 2–14 via pH-dependent leaching tests. Seven different types of soils and coal fly ashes were tested. Results of this study indicated that Ca, Cd, Mg, and Sr showed cationic leaching pattern while As and Se generally follows an oxyanionic leaching pattern. On the other hand, leaching of Ba presented amphoteric-like leaching pattern but less pH-dependent. In spite of different types and composition of soil and coal fly ash investigated, the study reveals the similarity in leaching behavior as a function of pH for a given element from soil, coal fly ash, and soil-coal fly ash mixtures. The similarity is most likely due to similar controlling mechanisms (e.g., solubility, sorption, and solid-solution formation) and similar controlling factors (e.g., leachate pH and redox conditions). This offers the opportunity to transfer knowledge of coal fly ash that has been extensively characterized and studied to soil stabilized with coal fly ash. It is speculated that unburned carbon in off-specification coal fly ashes may provide sorption sites for Cd resulting in a reduction in concentration of these elements in leachate from soil-coal fly ash mixture. Class C fly ash provides sufficient CaO to initiate the pozzolanic reaction yielding hydrated cement products that oxyanions, including As and Se, can be incorporated into.

  17. Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer: Early late toxicity and 3-year clinical outcome

    International Nuclear Information System (INIS)

    Fonteyne, Valérie; Lumen, Nicolaas; Ost, Piet; Van Praet, Charles; Vandecasteele, Katrien; De Gersem Ir, Werner; Villeirs, Geert; De Neve, Wilfried; Decaestecker, Karel; De Meerleer, Gert

    2013-01-01

    Background and purpose: For patients with N1 prostate cancer (PCa) aggressive local therapies can be advocated. We evaluated clinical outcome, gastro-intestinal (GI) and genito-urinary (GU) toxicity after intensity modulated arc radiotherapy (IMAT) + androgen deprivation (AD) for N1 PCa. Material and methods: Eighty patients with T1-4N1M0 PCa were treated with IMAT and 2–3 years of AD. A median dose of 69.3 Gy (normalized isoeffective dose at 2 Gy per fraction: 80 Gy [α/β = 3]) was prescribed in 25 fractions to the prostate. The pelvic lymph nodes received a minimal dose of 45 Gy. A simultaneous integrated boost to 72 Gy and 65 Gy was delivered to the intraprostatic lesion and/or pathologically enlarged lymph nodes, respectively. GI and GU toxicity was scored using the RTOG/RILIT and RTOG-SOMA/LENT-CTC toxicity scoring system respectively. Three-year actuarial risk of grade 2 and 3/4 GI–GU toxicity and biochemical and clinical relapse free survival (bRFS and cRFS) were calculated with Kaplan–Meier statistics. Results: Median follow-up was 36 months. Three-year actuarial risk for late grade 3 and 2 GI toxicity is 8% and 20%, respectively. Three-year actuarial risk for late grade 3–4 and 2 GU toxicity was 6% and 34%, respectively. Actuarial 3-year bRFS and cRFS was 81% and 89%, respectively. Actuarial 3-year bRFS and cRFS was, respectively 26% and 32% lower for patients with cN1 disease when compared to patients with cN0 disease. Conclusion: IMAT for N1 PCa offers good clinical outcome with moderate toxicity. Patients with cN1 disease have poorer outcome

  18. Effect of Low pH and Aluminum Toxicity on the Photosynthetic Characteristics of Different Fast-Growing Eucalyptus Vegetatively Propagated Clones.

    Science.gov (United States)

    Yang, Mei; Tan, Ling; Xu, Yuanyuan; Zhao, Yihui; Cheng, Fei; Ye, Shaoming; Jiang, Weixin

    2015-01-01

    Knowing how acid soils and aluminum in soils may limit the growth of Eucalyptus trees in plantations is important because these plantations grow in many tropical and subtropical regions. Seedlings of four vegetatively propagated Eucalyptus clones, E. grandis × E. urophylla 'GLGU9'(G9), E. grandis × E. urophylla 'GLGU12' (G12), E. urophylla × E. camaldulensis 'GLUC3' (G3) and E. urophylla 'GLU4'(G4), were subjected to liquid culture with Hoagland nutrient solution for 40 days, then treated with four different treatments of acid and aluminum for 1 day. The four treatments used either pH 3.0 or 4.0 with or without added aluminum (4.4 mM) in all possible combinations; a control used no added aluminum at pH 4.8. Subsequently, the photosynthetic parameters and morphology of leaves from eucalypt seedlings were determined and observed. The results showed that the tested chlorophyll content, net photosynthetic rate, transpiration rate and water use efficiency were apparently inhibited by aluminum. Under uniform Al concentration (4.4 mM), the Al-induced limitation to photosynthetic parameters increased with pH, indicating acid stimulation to Al toxicity. Among all treatments, the most significant reduction was found in the combination of pH 3.0 and 4.4 mM Al. The photosynthetic and transpiration rates showed similar trends with G9 > G12 > G3 > G4, suggesting that G9 and G12 had higher Al-tolerance than other two clones. Microscopic observation revealed changes in leaf morphology when exposed to Al stress; for example, a reduced thickness of leaf epidermis and palisade tissue, the descendant palisade tissue/spongy tissue ratio and leaf tissue looseness. Overall, the acid and aluminum stress exerted negative effects on the photosynthetic activity of eucalypt seedlings, but the differences in tolerance to Al toxicity between the clones were favorable, offering potential to improve Eucalyptus plantation productivity by selecting Al tolerant clones.

  19. Effect of Low pH and Aluminum Toxicity on the Photosynthetic Characteristics of Different Fast-Growing Eucalyptus Vegetatively Propagated Clones

    Science.gov (United States)

    Yang, Mei; Tan, Ling; Xu, Yuanyuan; Zhao, Yihui; Cheng, Fei; Ye, Shaoming; Jiang, Weixin

    2015-01-01

    Knowing how acid soils and aluminum in soils may limit the growth of Eucalyptus trees in plantations is important because these plantations grow in many tropical and subtropical regions. Seedlings of four vegetatively propagated Eucalyptus clones, E. grandis × E. urophylla ‘GLGU9’(G9), E. grandis × E. urophylla ‘GLGU12’ (G12), E. urophylla × E. camaldulensis ‘GLUC3’ (G3) and E. urophylla ‘GLU4’(G4), were subjected to liquid culture with Hoagland nutrient solution for 40 days, then treated with four different treatments of acid and aluminum for 1 day. The four treatments used either pH 3.0 or 4.0 with or without added aluminum (4.4 mM) in all possible combinations; a control used no added aluminum at pH 4.8. Subsequently, the photosynthetic parameters and morphology of leaves from eucalypt seedlings were determined and observed. The results showed that the tested chlorophyll content, net photosynthetic rate, transpiration rate and water use efficiency were apparently inhibited by aluminum. Under uniform Al concentration (4.4 mM), the Al-induced limitation to photosynthetic parameters increased with pH, indicating acid stimulation to Al toxicity. Among all treatments, the most significant reduction was found in the combination of pH 3.0 and 4.4 mM Al. The photosynthetic and transpiration rates showed similar trends with G9 > G12 > G3 > G4, suggesting that G9 and G12 had higher Al-tolerance than other two clones. Microscopic observation revealed changes in leaf morphology when exposed to Al stress; for example, a reduced thickness of leaf epidermis and palisade tissue, the descendant palisade tissue/spongy tissue ratio and leaf tissue looseness. Overall, the acid and aluminum stress exerted negative effects on the photosynthetic activity of eucalypt seedlings, but the differences in tolerance to Al toxicity between the clones were favorable, offering potential to improve Eucalyptus plantation productivity by selecting Al tolerant clones. PMID

  20. Effect of Low pH and Aluminum Toxicity on the Photosynthetic Characteristics of Different Fast-Growing Eucalyptus Vegetatively Propagated Clones.

    Directory of Open Access Journals (Sweden)

    Mei Yang

    Full Text Available Knowing how acid soils and aluminum in soils may limit the growth of Eucalyptus trees in plantations is important because these plantations grow in many tropical and subtropical regions. Seedlings of four vegetatively propagated Eucalyptus clones, E. grandis × E. urophylla 'GLGU9'(G9, E. grandis × E. urophylla 'GLGU12' (G12, E. urophylla × E. camaldulensis 'GLUC3' (G3 and E. urophylla 'GLU4'(G4, were subjected to liquid culture with Hoagland nutrient solution for 40 days, then treated with four different treatments of acid and aluminum for 1 day. The four treatments used either pH 3.0 or 4.0 with or without added aluminum (4.4 mM in all possible combinations; a control used no added aluminum at pH 4.8. Subsequently, the photosynthetic parameters and morphology of leaves from eucalypt seedlings were determined and observed. The results showed that the tested chlorophyll content, net photosynthetic rate, transpiration rate and water use efficiency were apparently inhibited by aluminum. Under uniform Al concentration (4.4 mM, the Al-induced limitation to photosynthetic parameters increased with pH, indicating acid stimulation to Al toxicity. Among all treatments, the most significant reduction was found in the combination of pH 3.0 and 4.4 mM Al. The photosynthetic and transpiration rates showed similar trends with G9 > G12 > G3 > G4, suggesting that G9 and G12 had higher Al-tolerance than other two clones. Microscopic observation revealed changes in leaf morphology when exposed to Al stress; for example, a reduced thickness of leaf epidermis and palisade tissue, the descendant palisade tissue/spongy tissue ratio and leaf tissue looseness. Overall, the acid and aluminum stress exerted negative effects on the photosynthetic activity of eucalypt seedlings, but the differences in tolerance to Al toxicity between the clones were favorable, offering potential to improve Eucalyptus plantation productivity by selecting Al tolerant clones.

  1. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-01-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; ≥6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. ≥6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  2. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients

    International Nuclear Information System (INIS)

    Zelefsky, Michael J.; Fuks, Zvi; Hunt, Margie; Yamada, Yoshiya; Marion, Christine; Ling, C. Clifton; Amols, Howard; Venkatraman, E.S.; Leibel, Steven A.

    2002-01-01

    Purpose: To report the acute and late toxicity and preliminary biochemical outcomes in 772 patients with clinically localized prostate cancer treated with high-dose intensity-modulated radiotherapy (IMRT). Methods and Materials: Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. Treatment was planned using an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. A total of 698 patients (90%) were treated to 81.0 Gy, and 74 patients (10%) were treated to 86.4 Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined according to The American Society of Therapeutic Radiation Oncology Consensus Statement. The median follow-up time was 24 months (range: 6-60 months). Results: Thirty-five patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3). Eleven patients (1.5%) developed late Grade 2 rectal bleeding. Four patients (0.1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 3-year actuarial likelihood of ≥ late Grade 2 rectal toxicity was 4%. Seventy-two patients (9%) experienced late Grade 2 urinary toxicity, and five (0.5%) developed Grade 3 urinary toxicity (urethral stricture). The 3-year actuarial likelihood of ≥ late Grade 2 urinary toxicity was 15%. The 3-year actuarial PSA relapse-free survival rates for favorable, intermediate, and unfavorable risk group patients were 92%, 86%, and 81%, respectively. Conclusions: These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be

  3. Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes

    International Nuclear Information System (INIS)

    Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J.; Shakespeare, Thomas P.

    2013-01-01

    There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64Gy (19%) or 66Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy<60% and V60Gy<40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy<35% and V65Gy<17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy<50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastrointestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy.

  4. Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

    Science.gov (United States)

    Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J; Shakespeare, Thomas P

    2013-08-01

    There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  5. Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral Absorption of the Salt of a Weak Acid - Case Study of GDC-0810.

    Science.gov (United States)

    Hou, Hao Helen; Jia, Wei; Liu, Lichuan; Cheeti, Sravanthi; Li, Jane; Nauka, Ewa; Nagapudi, Karthik

    2018-01-29

    The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human. The pH-solubility profile of GDC-0810 free acid and pH max of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food. Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pH max of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of C max and AUC 0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant. Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.

  6. Remote loading of doxorubicin into liposomes by transmembrane pH gradient to reduce toxicity toward H9c2 cells

    Directory of Open Access Journals (Sweden)

    Mohamed Alyane

    2016-03-01

    Full Text Available The use of doxorubicin (DOX is limited by its dose-dependent cardiotoxicity. Entrapped DOX in liposome has been shown to reduce cardiotoxicity. Results showed that about 92% of the total drug was encapsulated in liposome. The release experiments showed a weak DOX leakage in both culture medium and in PBS, more than 98% and 90% of the encapsulated DOX respectively was still retained in liposomes after 24 h of incubation. When the release experiments were carried out in phosphate buffer pH5.3, the leakage of DOX from liposomes reached 37% after 24 h of incubation. Evaluation of cellular uptake of the liposomal DOX indicated the possible endocytosis of liposomes because the majority of visible fluorescence of DOX was mainly in the cytoplasm, whereas the nuclear compartment showed a weak intensity. When using unloaded fluorescent-liposomes, the fluorescence was absent in nuclei suggests that liposomes cannot cross the nuclear membrane. MTT assay and measurement of LDH release suggest that necrosis is the form of cellular death predominates in H9c2 cells exposed to high doses of DOX, while for weak doses apoptosis could be the predominate form. Entrapped DOX reduced significantly DOX toxicity after 3 and 6 h of incubation, but after 20 h entrapped DOX is more toxic than free one.

  7. One-step synthesis, toxicity assessment and degradation in tumoral pH environment of SiO2@Ag core/shell nanoparticles

    Science.gov (United States)

    De Matteis, Valeria; Rizzello, Loris; Di Bello, Maria Pia; Rinaldi, Rosaria

    2017-06-01

    The unique physicochemical properties of SiO2@Ag core/shell nanoparticles make them a promising tool in nanomedicine, where they are used as nanocarriers for several biomedical applications, including (but not restricted to) cancer treatment. However, a comprehensive estimation of their potential toxicity, as well as their degradation in the tumor microenvironment, has not been extensively addressed yet. We investigated in vitro the viability, the reactive oxygen species (ROS) production, the DNA damage level, and the nanoparticle uptake on HeLa cells, used as model cancer cells. In addition, we studied the NPs degradation profile at pH 6.5, to mimic the tumor microenvironment, and at the neutral and physiological (pH 7-7.4). Our experiments demonstrate that the silver shell dissolution is promoted under acidic conditions, which could be related to cell death induction. Our evidences demonstrate that SiO2@Ag nanoparticles possess the ability of combining an effective cancer cell treatment (through local silver ions release) together with a possible controlled release of bioactive compounds encapsulated in the silica as future application.

  8. Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

    2010-05-01

    Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

  9. UV-photodegradation of desipramine: Impact of concentration, pH and temperature on formation of products including their biodegradability and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Khaleel, Nareman D.H.; Mahmoud, Waleed M.M. [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststraße 1 C13, DE 21335 Lüneburg (Germany); Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522 (Egypt); Olsson, Oliver [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststraße 1 C13, DE 21335 Lüneburg (Germany); Kümmerer, Klaus, E-mail: klaus.kuemmerer@leuphana.de [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststraße 1 C13, DE 21335 Lüneburg (Germany)

    2016-10-01

    Desipramine (DMI) is a widely used tricyclic antidepressant, and it is the major metabolite of imipramine (IMI) and lofepramine (LMI); IMI and LMI are two of the most commonly used tricyclic antidepressants. If DMI enters the aquatic environment, it can be transformed by the environmental bacteria or UV radiation. Therefore, photolysis of DMI in water was performed using a simulated sunlight Xenon-lamp and a UV-lamp. Subsequently, the biodegradability of DMI and its photo-transformation products (PTPs) formed during its UV photolysis was studied. The influence of variable conditions, such as initial DMI concentration, solution pH, and temperature, on DMI UV photolysis behavior was also studied. The degree of mineralization of DMI and its PTPs was monitored. A Shimadzu HPLC-UV apparatus was used to follow the kinetic profile of DMI during UV-irradiation; after that, ion-trap and high-resolution mass spectrometry coupled with chromatography were used to monitor and identify the possible PTPs. The environmentally relevant properties and selected toxicity properties of DMI and the non-biodegradable PTPs were predicted using different QSAR models. DMI underwent UV photolysis with first-order kinetics. Quantum yields were very low. DOC values indicated that DMI formed new PTPs and was not completely mineralized. Analysis by means of high-resolution mass spectrometry revealed that the photolysis of DMI followed three main photolysis pathways: isomerization, hydroxylation, and ring opening. The photolysis rate was inversely proportional to initial DMI concentration. The pH showed a significant impact on the photolysis rate of DMI, and on the PTPs in terms of both formation kinetics and mechanisms. Although temperature was expected to increase the photolysis rate, it showed a non-significant impact in this study. Results from biodegradation tests and QSAR analysis revealed that DMI and its PTPs are not readily biodegradable and that some PTPs may be human and/or eco-toxic

  10. Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

    International Nuclear Information System (INIS)

    Kim Tiam, Sandra; Laviale, Martin; Feurtet-Mazel, Agnès; Jan, Gwilherm; Gonzalez, Patrice; Mazzella, Nicolas; Morin, Soizic

    2015-01-01

    Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F 0 ), optimal and effective quantum yields of photosystem II (F v /F m and Φ PSII ). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L −1 ), its main degradation product (DCPMU) (from 1.0 to 1014 μg L −1 ) and norflurazon (from 0.6 to 585 μg L −1 ) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR max and I k ) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F 0 and F v /F m ) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors

  11. Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

    Directory of Open Access Journals (Sweden)

    William Dott

    2014-01-01

    Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a

  12. Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

    Energy Technology Data Exchange (ETDEWEB)

    Kim Tiam, Sandra, E-mail: sandra.kimtiam@gmail.com [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Laviale, Martin [Departamento de Biologia and CESAM – Centro de Estudos do Ambiente e do Mar Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Sorbonne Universités, UPMC Univ Paris 06, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer (France); CNRS, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer France (France); Feurtet-Mazel, Agnès [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Jan, Gwilherm [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Gonzalez, Patrice [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Mazzella, Nicolas; Morin, Soizic [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France)

    2015-08-15

    Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F{sub 0}), optimal and effective quantum yields of photosystem II (F{sub v}/F{sub m} and Φ{sub PSII}). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L{sup −1}), its main degradation product (DCPMU) (from 1.0 to 1014 μg L{sup −1}) and norflurazon (from 0.6 to 585 μg L{sup −1}) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR{sub max} and I{sub k}) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F{sub 0} and F{sub v}/F{sub m}) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors.

  13. Modulation of phosducin-like protein 3 (PhLP3 levels promotes cytoskeletal remodelling in a MAPK and RhoA-dependent manner.

    Directory of Open Access Journals (Sweden)

    Nandini V L Hayes

    Full Text Available Phosducin-like protein 3 (PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in β-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of β-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems.As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO cell lines. We show that over-expression of PhLP3 promotes an imbalance of α and β tubulin subunits, microtubule disassembly and cell death. In contrast, β-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state.Our results support the hypothesis that PhLP3 is important for the maintenance of β-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially

  14. Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity

    International Nuclear Information System (INIS)

    Ferrigno, Robson; Santos, Adriana; Martins, Lidiane C; Weltman, Eduardo; Chen, Michael J; Sakuraba, Roberto; Lopes, Cleverson P; Cruz, José C

    2010-01-01

    This retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors. From January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria. Absence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99). This comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups

  15. Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

    Science.gov (United States)

    Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

    2009-08-25

    The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

  16. Modulation of the toxicity and antitumour activity of alkylating drugs by steroids.

    OpenAIRE

    Shepherd, R.; Harrap, K. R.

    1982-01-01

    The steroids prednisolone and progesterone significantly altered the therapeutic indices of the alkylating agents, nitrogen mustard, melphalan, cyclophosphamide, phenyl acetic mustard and chlorambucil. For nitrogen mustard, chlorambucil and phenyl acetic mustard, prednisolone reduced host toxicity in the rat and enhanced the antitumour effectiveness against alkylating-agent-resistant strains of the Yoshida sarcoma and Walker carcinosarcoma. Progesterone also increased the therapeutic index of...

  17. Sulfate transport kinetics and toxicity are modulated by sodium in aquatic insects.

    Science.gov (United States)

    Scheibener, Shane; Conley, Justin M; Buchwalter, David

    2017-09-01

    The salinization of freshwater ecosystems is emerging as a major ecological issue. Several anthropogenic causes of salinization (e.g. surface coal mining, hydro-fracking, road de-icing, irrigation of arid lands, etc.) are associated with biodiversity losses in freshwater ecosystems. Because insects tend to dominate freshwater ecology, it is important that we develop a better understanding of how and why different species respond to salinity matrices dominated by different major ions. This study builds upon previous work demonstrating that major ion toxicity to the mayfly Neocloeon triangulifer was apparently due to the ionic composition of water rather than specific conductance. Synthetic waters with low Ca:Mg ratios and high SO 4 :Na ratios produced toxicity, whereas waters with higher Ca:Mg ratios and lower SO 4 :Na ratios were not toxic to mayflies at comparable conductivities. Here we used a radiotracer approach to show that Mg did not competitively exclude Ca uptake at environmentally realistic ratios in 4 aquatic insect species. We characterized SO 4 uptake kinetics in 5 mayflies and assessed the influence of different ions on SO 4 uptake. Dual label experiments show an inverse relationship between SO 4 and Na transport rates as SO 4 was held constant and Na was increased, suggesting that Na (and not Cl or HCO 3 ) is antagonistic to SO 4 transport. Based on this observation, we tested the hypothesis that increasing Na would protect against SO 4 induced toxicity in a Na-dependent manner. Increasing Na from 0.7 to 10.9mM improved 96-h survivorship associated with 20.8mM SO 4 from 44% to 73% in a concentration dependent manner. However, when Na reached 21.8mM, survivorship decreased to 16%, suggesting that other interactive effects of major ions caused toxicity under those conditions. Thus, the combination of elevated sulfate and low sodium commonly observed in streams affected by mountaintop coal mining has the potential to cause toxicity in sensitive aquatic

  18. Modulation of Ras signaling alters the toxicity of hydroquinone, a benzene metabolite and component of cigarette smoke

    International Nuclear Information System (INIS)

    North, Matthew; Shuga, Joe; Fromowitz, Michele; Loguinov, Alexandre; Shannon, Kevin; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

    2014-01-01

    Benzene is an established human leukemogen, with a ubiquitous environmental presence leading to significant population exposure. In a genome-wide functional screen in the yeast Saccharomyces cerevisiae, inactivation of IRA2, a yeast ortholog of the human tumor suppressor gene NF1 (Neurofibromin), enhanced sensitivity to hydroquinone, an important benzene metabolite. Increased Ras signaling is implicated as a causal factor in the increased pre-disposition to leukemia of individuals with mutations in NF1. Growth inhibition of yeast by hydroquinone was assessed in mutant strains exhibiting varying levels of Ras activity. Subsequently, effects of hydroquinone on both genotoxicity (measured by micronucleus formation) and proliferation of WT and Nf1 null murine hematopoietic precursors were assessed. Here we show that the Ras status of both yeast and mammalian cells modulates hydroquinone toxicity, indicating potential synergy between Ras signaling and benzene toxicity. Specifically, enhanced Ras signaling increases both hydroquinone-mediated growth inhibition in yeast and genotoxicity in mammalian hematopoetic precursors as measured by an in vitro erythroid micronucleus assay. Hydroquinone also increases proliferation of CFU-GM progenitor cells in mice with Nf1 null bone marrow relative to WT, the same cell type associated with benzene-associated leukemia. Together our findings show that hydroquinone toxicity is modulated by Ras signaling. Individuals with abnormal Ras signaling could be more vulnerable to developing myeloid diseases after exposure to benzene. We note that hydroquinone is used cosmetically as a skin-bleaching agent, including by individuals with cafe-au-lait spots (which may be present in individuals with neurofibromatosis who have a mutation in NF1), which could be unadvisable given our findings

  19. Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis

    International Nuclear Information System (INIS)

    Cox, Maurice C.; Kusters, Johannes M.; Gidding, Corrie E.; Schieving, Jolanda H.; Lindert, Erik J. van; Kaanders, Johannes H.; Janssens, Geert O.

    2015-01-01

    To report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions. Newly diagnosed patients, aged 3–21, with standard-risk (SR) or high-risk (HR) medulloblastoma were eligible. A dose of 23.4 or 36.0Gy in daily fractions of 1.8Gy was prescribed to the craniospinal axis, followed by a boost to the primary tumor bed (54 or 55.8Gy) and metastases (39.6–55.8Gy), when indicated. Weekly, an intravenous bolus of vincristine was combined for patients with SR medulloblastoma and patients participating in the COG-ACNS-0332 study. Common toxicity criteria (CTC, version 2.0) focusing on skin, alopecia, voice changes, conjunctivitis, anorexia, dysphagia, gastro-intestinal symptoms, headache, fatigue and hematological changes were scored weekly during radiotherapy. From 2010 to 2014, data from 15 consecutive patients (SR, n = 7; HR, n = 8) were collected. Within 72 h from onset of treatment, vomiting (66 %) and headache (46 %) occurred. During week 3 of treatment, a peak incidence in constipation (33 %) and abdominal pain/cramping (40 %) was observed, but only in the subgroup of patients (n = 9) receiving vincristine (constipation: 56 vs 0 %, P = .04; pain/cramping: 67 vs 0 %, P = .03). At week 6, 73 % of the patients developed faint erythema of the cranial skin with dry desquamation (40 %) or moist desquamation confined to the skin folds of the auricle (33 %). No reaction of the skin overlying the spinal target volume was observed. Headache at onset and gastro-intestinal toxicity, especially in patients receiving weekly vincristine, were the major complaints of patients with medulloblastoma undergoing craniospinal irradiation with IMRT

  20. Temporal viscosity modulations driven by a pH sensitive polymer coupled to a pH-changing chemical reaction.

    Science.gov (United States)

    Escala, D M; Muñuzuri, A P; De Wit, A; Carballido-Landeira, J

    2017-05-17

    The Formaldehyde-Sulfite (FS) and the Formaldehyde-Sulfite-Gluconolactone (FSG) systems are examples of complex chemical reactions accompanied by well-controlled variations in pH. While the FS system exhibits a clock behavior, in the FSG reaction, this mechanism is coupled with the hydrolysis of the gluconolactone which gives the possibility to show large temporal oscillations of pH in an open reactor. In this work, we show how these reactive systems, due to their organic nature, can be coupled with pH sensitive polymers, particularly with polyacrylic acid (PAA) to trigger temporal changes of viscosity. We characterize this coupled reactive system showing the effects of changes in the initial concentrations of the polymer and in the chemical reagents on the induction time, the magnitude of the pH variations and the temporal modifications of the viscosity.

  1. Therapeutic Down-Modulators of Staphylococcal Superantigen-Induced Inflammation and Toxic Shock

    Directory of Open Access Journals (Sweden)

    Teresa Krakauer

    2010-07-01

    Full Text Available Staphylococcal enterotoxin B (SEB and related superantigenic toxins are potent stimulators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to toxic shock. These toxins bind directly to major histocompatibility complex (MHC class II molecules on antigen-presenting cells and specific Vb regions of T-cell receptors (TCR, resulting in hyperactivation of both monocytes/macrophages and T lymphocytes. Activated host cells produce massive amounts of proinflammatory cytokines and chemokines, activating inflammation and coagulation, causing clinical symptoms that include fever, hypotension, and shock. This review summarizes the in vitro and in vivo effects of staphylococcal superantigens, the role of pivotal mediators induced by these toxins in the pathogenic mechanisms of tissue injury, and the therapeutic agents to mitigate the toxic effects of superantigens.

  2. Mycorrhizal fungi modulate phytochemical production and antioxidant activity of Cichorium intybus L. (Asteraceae) under metal toxicity.

    Science.gov (United States)

    Rozpądek, P; Wężowicz, K; Stojakowska, A; Malarz, J; Surówka, E; Sobczyk, Ł; Anielska, T; Ważny, R; Miszalski, Z; Turnau, K

    2014-10-01

    Cichorium intybus (common chicory), a perennial plant, common in anthropogenic sites, has been the object of a multitude of studies in recent years due to its high content of antioxidants utilized in pharmacy and food industry. Here, the role of arbuscular mycorrhizal fungi (AMF) in the biosynthesis of plant secondary metabolites and the activity of enzymatic antioxidants under toxic metal stress was studied. Plants inoculated with Rhizophagus irregularis and non-inoculated were grown on non-polluted and toxic metal enriched substrata. The results presented here indicate that AMF improves chicory fitness. Fresh and dry weight was found to be severely affected by the fungi and heavy metals. The concentration of hydroxycinnamates was increased in the shoots of mycorrhizal plants cultivated on non-polluted substrata, but no differences were found in plants cultivated on metal enriched substrata. The activity of SOD and H2O2 removing enzymes CAT and POX was elevated in the shoots of mycorrhizal plants regardless of the cultivation environment. Photochemical efficiency of inoculated chicory was significantly improved. Our results indicate that R. irregularis inoculation had a beneficial role in sustaining the plants ability to cope with the deleterious effects of metal toxicity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

    Science.gov (United States)

    Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

    2016-01-20

    The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

  4. Vitamin E modulates reproductive toxicity of pyrethroid lambda-cyhalothrin in male rabbits.

    Science.gov (United States)

    Yousef, Mokhtar I

    2010-05-01

    The objective of the current study was to analyze the reproductive toxicity caused by lambda-cyhalothrin (LCT) in male rabbits, and to evaluate the possible protective effect of vitamin E (Vit. E) as antioxidant. Animals were orally administered their respective doses of LCT every other day and given drinking water supplemented with vitamin E for 16 weeks. Results showed that semen quality was deteriorated following treatment with LCT. Also, testosterone levels, body weight (BW), feed intake (FI), and relative testes (RTW) and epididymis (REW) weights were significantly decreased. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly increased in seminal plasma of rabbits treated with LCT compared with control. While, activities of glutathione S-transferase (GST), transaminases and acid phosphatase (AcP) were significantly decreased. Vitamin E alone significantly increased testosterone levels, BW, FI, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of TBARS. Also, the present study showed that vitamin E might be effective against LCT-induced reproductive toxicity. It was suggested that LCT exerted a significant adverse effect on reproductive performance of male rabbits. Furthermore, vitamin E antagonized the toxic effects of LCT and improved semen quality of male rabbit. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  5. pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial

    Directory of Open Access Journals (Sweden)

    SVSG Nirmala

    2016-01-01

    Full Text Available Background: Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. Objectives: To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Materials and Methods: Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate, filled (wafer and fruit and nuts chocolate, and candy (hard milk and mango-flavored candy groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Results: Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P < 0.05. Conclusion: Dark chocolate had a high fall in pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

  6. pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial.

    Science.gov (United States)

    Nirmala, Svsg; Quadar, Mohammed Akhil; Veluru, Sindhuri

    2016-01-01

    Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate), filled (wafer and fruit and nuts chocolate), and candy (hard milk and mango-flavored candy) groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

  7. Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

    Science.gov (United States)

    Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

    2015-09-01

    Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Fermentation pH Modulates the Size Distributions and Functional Properties of Gluconobacter albidus TMW 2.1191 Levan

    Directory of Open Access Journals (Sweden)

    Tharalinee Ua-Arak

    2017-05-01

    Full Text Available Bacterial levan has gained an increasing interest over the last decades due to its unique characteristics and multiple possible applications. Levan and other exopolysaccharides (EPSs production are usually optimized to obtain the highest concentration or yield while a possible change of the molecular size and mass during the production process is mostly neglected. In this study, the molar mass and radius of levan samples were monitored during fermentations with the food-grade, levan-producing acetic acid bacterium Gluconobacter (G. albidus TMW 2.1191 in shake flasks (without pH control and bioreactors (with pH control at 4.5, 5.5 and 6.5, respectively. In uncontrolled fermentations, the levan size/molar mass continuously decreased concomitantly with the continuous acidification of the nutrient medium. On the contrary, the amount, molar mass and size of levan could be directly influenced by controlling the pH during fermentation. Using equal initial substrate amounts, the largest weight average molar mass and geometric radius of levan were observed at constant pH 6.5, while the highest levan concentration was obtained at constant pH 4.5. Since there is a special demand to find suitable hydrocolloids from food-grade bacteria to develop novel gluten-free (GF products, these differently produced levans were used for baking of GF breads, and the best quality improvement was obtained by addition of levan with the highest mass and radius. This work, therefore, demonstrates for the first time that one bacterial strain can produce specific high molecular weight fractions of one EPS type, which differ in properties and sizes among each other in dependence of the controllable production conditions.

  9. Short - Term Exposure To Visible And Ultraviolet Light Modulates Dacarbazine Toxicity To Human Blood Cells In Vitro

    International Nuclear Information System (INIS)

    Kopjar, N.; Zunec, S.; Lucic Vrdoljak, A.; Zeljezic, D.; Mladinic, M.

    2015-01-01

    Dacarbazine (DTIC), i.e. 5-(3,3-dimethyltriazeno)imidazol-4-carboxamide, is an alkylating cytostatic used in the treatment of various types of human cancer. It is prone to photodegradation, the products of which cause adverse effects in treated patients. In the present study, we evaluated the relationships between photo genotoxicity, cytotoxicity, lipid peroxidation and AChE activity in in vitro DTIC - treated human blood after illumination with visible and ultraviolet light for 30 and 60 minutes. AChE activity was measured in erythrocytes. The extent of lipid peroxidation was measured in plasma. Cell death and morphological changes in the nuclei were studied in isolated peripheral blood lymphocytes using the fluorescent dye exclusion method. Primary DNA damage in lymphocytes was studied by alkaline comet assay immediately after treatment and 60 minutes later. The obtained results suggest that short-term exposure to UV and visible light modulated DTIC toxicity. Most of the effects were dose-dependent. We assume that photodegradation products, together with the parent compound, were responsible for increased LPO in plasma, along with cytotoxicity and infliction of primary DNA damage in lymphocytes. Erythrocyte AChE activity, on the other hand, was strongly impaired by the parent drug. Our findings suggest the need for a simultaneous evaluation of cyto-/genotoxicity and biochemical markers, as such an approach would provide much better insight into the mechanisms underlying drug toxicity in general. (author).

  10. Light modulated toxicity of isoproturon toward natural stream periphyton photosynthesis: a comparison between constant and dynamic light conditions.

    Science.gov (United States)

    Laviale, Martin; Prygiel, Jean; Créach, Anne

    2010-05-10

    This study tested if a variation in light intensity, in comparison to constant light required in well-designed toxicity test, could have measurable consequences on the sensitivity of phototrophic biofilms (periphyton) to isoproturon. Two independent experiments were carried out to investigate the combined effects of light and isoproturon on the photochemical behavior of intact natural biofilms by measurements of chlorophyll fluorescence and pigment composition. Experiment 1 consisted of exposing biofilms to series of isoproturon concentrations (0-2 mg L(-1)) for 7 h under constant light at different irradiance levels (25-300 micromol m(-2) s(-1)). In experiment 2, biofilms were exposed using more environmentally realistic conditions to three selected concentrations of isoproturon (2, 6 and 20 microg L(-1)) during a 7-h-simulated daily light cycle. Our results demonstrated that light, considered here as a direct physical stressor, slightly modulated the acute toxicity of isoproturon on these diatom dominated communities. This was attributed to the fact that these two factors act specifically on the photosynthetic activity. Furthermore, it was shown that a dynamic light regime increased periphyton sensitivity to isoproturon by challenging its photoprotective mechanisms such as the xanthophyll cycle, therefore implying that traditional ecotoxicological bioassays lead to underestimate the effect of isoproturon. 2010 Elsevier B.V. All rights reserved.

  11. A plant-wide aqueous phase chemistry module describing pH variations and ion speciation/pairing in wastewater treatment process models

    DEFF Research Database (Denmark)

    Flores Alsina, Xavier; Kazadi Mbamba, Christian; Solon, Kimberly

    2015-01-01

    at different cationic/anionic loads. In this way, the general applicability/flexibility of the proposed approach is demonstrated, by implementing the aqueous phase chemistry module in some of the most frequently used WWTP process simulation models. Finally, it is shown how traditional wastewater modelling......, but unavoidable, additional degree of complexity when representing cationic/anionic behaviour in Activated Sludge (AS)/Anaerobic Digestion (AD) systems. In this paper, a plant-wide aqueous phase chemistry module describing pH variations plus ion speciation/pairing is presented and interfaced with industry......) in order to reduce the overall stiffness of the system, thereby enhancing simulation speed. Additionally, a multi-dimensional version of the Newton-Raphson algorithm is applied to handle the existing multiple algebraic inter-dependencies. The latter is reinforced with the Simulated Annealing method...

  12. Polyoxyethylene hydrogenated castor oil modulates benzalkonium chloride toxicity: comparison of acute corneal barrier dysfunction induced by travoprost Z and travoprost.

    Science.gov (United States)

    Uematsu, Masafumi; Kumagami, Takeshi; Shimoda, Kenichiro; Kusano, Mao; Teshima, Mugen; To, Hideto; Kitahara, Takashi; Kitaoka, Takashi; Sasaki, Hitoshi

    2011-10-01

    To determine the element that modulates benzalkonium chloride (BAC) toxicity by using a new electrophysiological method to evaluate acute corneal barrier dysfunction induced by travoprost Z with sofZia (Travatan Z(®)), travoprost with 0.015% BAC (Travatan(®)), and its additives. Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay. Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC. Travoprost Z with sofZia and travoprost with BAC do not induce acute corneal barrier dysfunction. HCO-40 provides protection against BAC-induced corneal toxicity.

  13. PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Petriello, Michael C. [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); University of Kentucky Superfund Research Center, Lexington, KY 40536 (United States); Han, Sung Gu [University of Kentucky Superfund Research Center, Lexington, KY 40536 (United States); Department of Food Science and Biotechnology of Animal Resources, College of Animal Bioscience and Technology, Konkuk University, Seoul 143-701 (Korea, Republic of); Newsome, Bradley J. [University of Kentucky Superfund Research Center, Lexington, KY 40536 (United States); Department of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY 40506 (United States); Hennig, Bernhard [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); University of Kentucky Superfund Research Center, Lexington, KY 40536 (United States); Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, KY 40506 (United States)

    2014-06-01

    Environmental toxicants such as polychlorinated biphenyls (PCBs) have been implicated in the promotion of multiple inflammatory disorders including cardiovascular disease, but information regarding mechanisms of toxicity and cross-talk between relevant cell signaling pathways is lacking. To examine the hypothesis that cross-talk between membrane domains called caveolae and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways alters PCB-induced inflammation, caveolin-1 was silenced in vascular endothelial cells, resulting in a decreased PCB-induced inflammatory response. Cav-1 silencing (siRNA treatment) also increased levels of Nrf2-ARE transcriptional binding, resulting in higher mRNA levels of the antioxidant genes glutathione s-transferase and NADPH dehydrogenase quinone-1 in both vehicle and PCB-treated systems. Along with this upregulated antioxidant response, Cav-1 siRNA treated cells exhibited decreased mRNA levels of the Nrf2 inhibitory protein Keap1 in both vehicle and PCB-treated samples. Silencing Cav-1 also decreased protein levels of Nrf2 inhibitory proteins Keap1 and Fyn kinase, especially in PCB-treated cells. Further, endothelial cells from wildtype and Cav-1 −/− mice were isolated and treated with PCB to better elucidate the role of functional caveolae in PCB-induced endothelial inflammation. Cav-1 −/− endothelial cells were protected from PCB-induced cellular dysfunction as evidenced by decreased vascular cell adhesion molecule (VCAM-1) protein induction. Compared to wildtype cells, Cav-1 −/− endothelial cells also allowed for a more effective antioxidant response, as observed by higher levels of the antioxidant genes. These data demonstrate novel cross-talk mechanisms between Cav-1 and Nrf2 and implicate the reduction of Cav-1 as a protective mechanism for PCB-induced cellular dysfunction and inflammation. - Highlights: • Reduction of caveolin-1 protein protects against polychlorinated biphenyl toxicity. • Decreasing

  14. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

    2013-01-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

  15. External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

    Science.gov (United States)

    Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

    2013-06-01

    The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

  16. Modulation of the toxicity of photons by non-conventional drugs

    International Nuclear Information System (INIS)

    Bohm, L.; Theron, T.; Serafin, A.; Verheye, F.

    1997-01-01

    The 3 drugs under investigation Pentoxifylline, Ouabain and Thalidomide are non-conventional in the sense that they have a low toxicity and do not damage DNA. Pentoxifylline reduces blood viscosity ad enhances peripheral blood flow. When combined with irradiation in a mouse rhabdomyosarcoma model we found markedly enhanced tumour growth delay and in cultured cells dose modifying factors for SF2 and alpha in the region of 1.2-1.7 (Strahlentherapie 1995;170:595-01). The drug also alters cell regulation by inhibiting the radiation induced G2/M block and suppressing control of DNA synthesis (Theron and Boehm, unpubl.). When Thalidomide was added in the absence of irradiation to the myelo-blastic cell line K-562 we found characteristic changes of cell morphology and cell surface markers suggesting differentiation and expression of a megacaryocytic lineage (Leukemia Research 1991;15:129-136). A summary of the current state of research is given. (authors)

  17. Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

    Energy Technology Data Exchange (ETDEWEB)

    Poorvu, Philip D. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Sadow, Cheryl A. [Department of Radiology, Brigham and Women' s Hospital, and Harvard Medical School, Boston, Massachusetts (United States); Townamchai, Kanokpis; Damato, Antonio L. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

    2013-04-01

    Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.

  18. Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

    International Nuclear Information System (INIS)

    Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis; Damato, Antonio L.; Viswanathan, Akila N.

    2013-01-01

    Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy

  19. Patterns of Failure and Toxicity after Intensity-Modulated Radiotherapy for Head and Neck Cancer

    International Nuclear Information System (INIS)

    Schoenfeld, Gordon O.; Amdur, Robert J.; Morris, Christopher G.; Li, Jonathan G.; Hinerman, Russell W.; Mendenhall, William M.

    2008-01-01

    Purpose: To determine the outcome of patients treated with intensity-modulated radiotherapy (IMRT) for head and neck cancer. Methods and Materials: We reviewed the charts of 100 consecutive patients treated with IMRT for squamous cell carcinoma of the oropharynx (64%), nasopharynx (16%), hypopharynx (14%), and larynx (6%). Most patients were treated with a concomitant boost schedule to 72 Gy. Of the 100 patients, 54 (54%) received adjuvant chemotherapy, mostly concurrent cisplatin. The dosimetry plans for patients with either locoregional failure or Grade 4-5 complications were reviewed and fused over the computed tomography images corresponding with the location of the event. Marginal failures were defined as those that occurred at a region of high-dose falloff, where conventional fields would have provided better coverage. Results: The median follow-up of living patients was 3.1 years (range, 1-5.2 years). The 3-year rate of local control, locoregional control, freedom from relapse, cause-specific survival, and overall survival for all patients was 89%, 87%, 72%, 78%, and 71%, respectively. The 3-year rate of freedom from relapse, cause-specific survival, and overall survival for the 64 oropharynx patients was 86%, 92%, and 84%, respectively. Of the 10 local failures, 2 occurred at the margin of the high-dose planning target volume. Both regional failures occurred within the planning target volume. No locoregional failures occurred outside the planning target volume. Of the 100 patients, 8 and 5 had Grade 4 and 5 complications from treatment, respectively. All patients with Grade 5 complications had received adjuvant chemotherapy. No attempt was made to discriminate between the complications from IMRT and other aspects of the patients' treatment. Conclusion: Intensity-modulated radiotherapy did not compromise the outcome compared with what we have achieved with conventional techniques. The 2 cases of recurrence in the high-dose gradient region highlight the

  20. A plant-wide aqueous phase chemistry module describing pH variations and ion speciation/pairing in wastewater treatment process models.

    Science.gov (United States)

    Flores-Alsina, Xavier; Kazadi Mbamba, Christian; Solon, Kimberly; Vrecko, Darko; Tait, Stephan; Batstone, Damien J; Jeppsson, Ulf; Gernaey, Krist V

    2015-11-15

    There is a growing interest within the Wastewater Treatment Plant (WWTP) modelling community to correctly describe physico-chemical processes after many years of mainly focusing on biokinetics. Indeed, future modelling needs, such as a plant-wide phosphorus (P) description, require a major, but unavoidable, additional degree of complexity when representing cationic/anionic behaviour in Activated Sludge (AS)/Anaerobic Digestion (AD) systems. In this paper, a plant-wide aqueous phase chemistry module describing pH variations plus ion speciation/pairing is presented and interfaced with industry standard models. The module accounts for extensive consideration of non-ideality, including ion activities instead of molar concentrations and complex ion pairing. The general equilibria are formulated as a set of Differential Algebraic Equations (DAEs) instead of Ordinary Differential Equations (ODEs) in order to reduce the overall stiffness of the system, thereby enhancing simulation speed. Additionally, a multi-dimensional version of the Newton-Raphson algorithm is applied to handle the existing multiple algebraic inter-dependencies. The latter is reinforced with the Simulated Annealing method to increase the robustness of the solver making the system not so dependent of the initial conditions. Simulation results show pH predictions when describing Biological Nutrient Removal (BNR) by the activated sludge models (ASM) 1, 2d and 3 comparing the performance of a nitrogen removal (WWTP1) and a combined nitrogen and phosphorus removal (WWTP2) treatment plant configuration under different anaerobic/anoxic/aerobic conditions. The same framework is implemented in the Benchmark Simulation Model No. 2 (BSM2) version of the Anaerobic Digestion Model No. 1 (ADM1) (WWTP3) as well, predicting pH values at different cationic/anionic loads. In this way, the general applicability/flexibility of the proposed approach is demonstrated, by implementing the aqueous phase chemistry module in some

  1. Calcium availability but not its content modulates metal toxicity in Scenedesmus quadricauda.

    Science.gov (United States)

    Kováčik, Jozef; Dresler, Sławomir

    2018-01-01

    Impact of calcium nutrition (pre-culture on solid medium with standard or elevated Ca dose, i. e. 0.17 and 4.40mM marked as low and high Ca) on acute metal toxicity (Cd, Mn and Pb, 24h of exposure to 10µM) in freshwater green alga Scenedesmus quadricauda was studied. Surprisingly, Ca content differed only slightly between low and high Ca samples and applied metals rather suppressed its amount. Na content was higher in metal-exposed high Ca samples, indicating that Ca/Na ratio may affect accumulation of metals. Content of heavy metals increased in order Cd < Mn < Pb and high Ca samples contained less metal than low Ca samples at least in absorbed fraction. Accumulation of ascorbic acid and thiols (GSH - glutathione and PC2 - phytochelatin 2) was affected mainly by Cd, GSH also by Mn and PC2 by Pb with often significant differences between low Ca and high Ca samples. Calcium nutrition also affected responses of algae to metals at the level of antioxidative enzyme activities (SOD, APX, and CAT) and elevated values were typically found in high Ca samples while ROS (hydrogen peroxide and superoxide radical) were mainly depleted in Mn treatment. These data confirm that Ca nutrition affects accumulation of metals in algae and metabolic parameters as observed in vascular plants but, unlike them, rather Ca/Na ratio than absolute Ca content seems to regulate the uptake of metals. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS iv: magnesium modulation at pH 7.20

    Directory of Open Access Journals (Sweden)

    Ali Akbar Moosavi-Movahedi

    2016-03-01

    Full Text Available We investigate the interaction of Mg2+ (0–2.30 mM and sodium n-dodecyl sulfate (SDS with hemoglobins (Hbs A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS and proteases (5.0 mM SDS. Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show that Mg2+ interaction with the proteins lowered the HbS oxygen affinity in comparison with the HbA. Additionally, [SDS]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg2+] introduction to the [SDS]-protein mixture, however decreased the concentration of denatured protein species. The [Mg2+]-[SDS]-protein interactions suggest that while ionic or coulomb interactions for the HbA, in the presence of the surfactants, are [Mg2+] dependent, those of the HbS are not. Furthermore, hydrophobicity is a crucial force for the HbS interaction at neutral pH and is little-masked by ionic, electrostatic or coulombic interactions. In conclusion, at physiological pH, the Mg-SDS interaction decreased the HbS denaturation in comparison to the HbA.

  3. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

    International Nuclear Information System (INIS)

    Lips, Irene M; Dehnad, Homan; Gils, Carla H van; Boeken Kruger, Arto E; Heide, Uulke A van der; Vulpen, Marco van

    2008-01-01

    We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used

  4. High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

    Directory of Open Access Journals (Sweden)

    Boeken Kruger Arto E

    2008-05-01

    Full Text Available Abstract We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment and weekly during treatment (acute toxicity were scored using the Common Toxicity Criteria (CTC. The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU complaints and 2% experienced grade 2 gastrointestinal (GI complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4. In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

  5. Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS) iv: magnesium modulation at pH 7.20

    OpenAIRE

    Ali Akbar Moosavi-Movahedi; Ferdinand C. Chilaka; Charles O. Nwamba

    2016-01-01

    We investigate the interaction of Mg2+ (0–2.30 mM) and sodium n-dodecyl sulfate (SDS) with hemoglobins (Hbs) A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS) and proteases (5.0 mM SDS). Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s) in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show ...

  6. Community production modulates coral reef pH and the sensitivity of ecosystem calcification to ocean acidification

    Science.gov (United States)

    DeCarlo, Thomas M.; Cohen, Anne L.; Wong, George T. F.; Shiah, Fuh-Kwo; Lentz, Steven J.; Davis, Kristen A.; Shamberger, Kathryn E. F.; Lohmann, Pat

    2017-01-01

    Coral reefs are built of calcium carbonate (CaCO3) produced biogenically by a diversity of calcifying plants, animals, and microbes. As the ocean warms and acidifies, there is mounting concern that declining calcification rates could shift coral reef CaCO3 budgets from net accretion to net dissolution. We quantified net ecosystem calcification (NEC) and production (NEP) on Dongsha Atoll, northern South China Sea, over a 2 week period that included a transient bleaching event. Peak daytime pH on the wide, shallow reef flat during the nonbleaching period was ˜8.5, significantly elevated above that of the surrounding open ocean (˜8.0-8.1) as a consequence of daytime NEP (up to 112 mmol C m-2 h-1). Diurnal-averaged NEC was 390 ± 90 mmol CaCO3 m-2 d-1, higher than any other coral reef studied to date despite comparable calcifier cover (25%) and relatively high fleshy algal cover (19%). Coral bleaching linked to elevated temperatures significantly reduced daytime NEP by 29 mmol C m-2 h-1. pH on the reef flat declined by 0.2 units, causing a 40% reduction in NEC in the absence of pH changes in the surrounding open ocean. Our findings highlight the interactive relationship between carbonate chemistry of coral reef ecosystems and ecosystem production and calcification rates, which are in turn impacted by ocean warming. As open-ocean waters bathing coral reefs warm and acidify over the 21st century, the health and composition of reef benthic communities will play a major role in determining on-reef conditions that will in turn dictate the ecosystem response to climate change.

  7. Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

    International Nuclear Information System (INIS)

    Deville, Curtiland; Both, Stefan; Bui, Viet; Hwang, Wei-Ting; Tan, Kay-See; Schaer, Mattia; Tochner, Zelig; Vapiwala, Neha

    2012-01-01

    Our purpose was to report acute gastrointestinal (GI) and genitourinary (GU) toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT) with a daily endorectal water-filled balloon (ERB H2O ), and assess associations with planning parameters and pretreatment clinical characteristics. The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERB H2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0) were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Mean age was 68 (range 51–88). Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV) rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps < 0.05). Maximum acute GU toxicity was grade 0, 1, and 2 for 17%, 41%, and 42% of patients, respectively. Infield bladder V20 (P = 0.03) and pretreatment International Prostate Symptom Scale (IPSS) (P = 0.003) were associated with grade 2 GU toxicity. Prostate IG-IMRT using a daily ERB H2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities

  8. Toxic essential oils. Part V: Behaviour modulating and toxic properties of thujones and thujone-containing essential oils of Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis L. and Tanacetum vulgare L.

    Science.gov (United States)

    Radulović, Niko S; Genčić, Marija S; Stojanović, Nikola M; Randjelović, Pavle J; Stojanović-Radić, Zorica Z; Stojiljković, Nenad I

    2017-07-01

    Neurotoxic thujones (α- and β-diastereoisomers) are common constituents of plant essential oils. In this study, we employed a statistical approach to determine the contribution of thujones to the overall observed behaviour-modulating and toxic effects of essential oils (Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis L. and Tanacetum vulgare L.) containing these monoterpene ketones. The data from three in vivo neuropharmacological tests on rats (open field, light-dark, and diazepam-induced sleep), and toxicity assays (brine shrimp, and antimicrobial activity against a panel of microorganisms), together with the data from detailed chemical analyses, were subjected to a multivariate statistical treatment to reveal the possible correlation(s) between the content of essential-oil constituents and the observed effects. The results strongly imply that the toxic and behaviour-modulating activity of the oils (hundreds of constituents) should not be associated exclusively with thujones. The statistical analyses pinpointed to a number of essential-oil constituents other than thujones that demonstrated a clear correlation with either the toxicity, antimicrobial effect or the activity on CNS. Thus, in addition to the thujone content, the amount and toxicity of other constituents should be taken into consideration when making risk assessment and determining the regulatory status of plants in food and medicines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

    Science.gov (United States)

    Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

    2015-09-01

    The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

  10. The MDT-15 subunit of mediator interacts with dietary restriction to modulate longevity and fluoranthene toxicity in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jennifer Schleit

    Full Text Available Dietary restriction (DR, the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA. FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS, which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway.

  11. The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

    International Nuclear Information System (INIS)

    Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

    2011-01-01

    Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm 3 , respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm 3 ) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm 3 increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

  12. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    International Nuclear Information System (INIS)

    Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2012-01-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I–III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V 45 ) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60–399) and 0.31 (95% CI 0.04–0.63), respectively. On multivariable logistic regression, increased V 45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04–4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  13. Late toxicity and quality of life after definitive treatment of prostate cancer: redefining optimal rectal sparing constraints for intensity-modulated radiation therapy

    International Nuclear Information System (INIS)

    Chennupati, Sravana K; Pelizzari, Charles A; Kunnavakkam, Rangesh; Liauw, Stanley L

    2014-01-01

    The objective of this study was to assess late toxicity and quality of life (QOL) for patients receiving definitive intensity-modulated radiotherapy (IMRT) and image-guided radiation therapy (IGRT) with regard to normal tissue sparing objectives. Three hundred and seventy-two consecutive men treated with definitive IMRT for prostate adenocarcinoma. Toxicity was graded by CTC v3.0 genitourinary (GU) and gastrointestinal (GI) toxicity at each follow-up visit. Patient-reported QOL (EPIC-26) was prospectively collected for a subset of men. Dosimetric data for bladder and rectum were compared to toxicity and QOL global domain scores, specifically analyzing outcomes for men who met ideal rectal constraints (V70 <10%, V65 <20%, V40 <40%). The median age and prescription dose was 69 years and 76 Gy, respectively. Median follow-up was 47 months. At 4 years, freedom from Grade 2 (FFG2) GI toxicity was 92% and FFG2 GU toxicity was 76%. On univariate analysis, current smoking, larger bladder volume, and higher RT dose were associated with decreased FFG2 GU toxicity, while use of anticoagulation, increasing age, and not meeting ideal rectal constraints were associated with decreased FFG2 GI toxicity (all P ≤ 0.05). Bowel QOL remained stable over the 2-year follow-up period and was higher for patients who met ideal rectal constraints (P = 0.05). IMRT with IGRT is associated with low rates of severe toxicity and a high GI and GU QOL. The use of strict rectal constraints can further improve GI QOL and reduce GI toxicity

  14. Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Deville, Curtiland, E-mail: deville@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Lin Haibo; Bar Ad, Voichita; Tochner, Zelig; Both, Stefan [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2012-03-15

    Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluated uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.

  15. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    International Nuclear Information System (INIS)

    Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-01-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

  16. The effect of pH on the uptake and toxicity of the bivalent weak base chloroquine tested on Salix viminalis and Daphnia magna

    DEFF Research Database (Denmark)

    Rendal, Cecilie; Kusk, Kresten Ole; Trapp, Stefan

    2011-01-01

    , and therefore a higher toxicity can be expected. The current study examines the pHdependent toxicity and bioaccumulation of the bivalent weak base chloroquine (pKa: 10.47 and 6.33, log KOW 4.67) tested on Salix viminalis (basket willow) and Daphnia magna (water flea). The transpiration rates of hydroponically...

  17. Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

    Directory of Open Access Journals (Sweden)

    Deville Curtiland

    2012-05-01

    Full Text Available Abstract Background Our purpose was to report acute gastrointestinal (GI and genitourinary (GU toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT with a daily endorectal water-filled balloon (ERBH2O, and assess associations with planning parameters and pretreatment clinical characteristics. Methods The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERBH2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0 were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Results Mean age was 68 (range 51–88. Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps  Conclusion Prostate IG-IMRT using a daily ERBH2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities.

  18. Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein.

    Directory of Open Access Journals (Sweden)

    Ken-ichiro Nakajima

    Full Text Available Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS and a neoculin basic subunit (NBS. Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular.

  19. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  20. Dosimetric Predictors of Duodenal Toxicity After Intensity Modulated Radiation Therapy for Treatment of the Para-aortic Nodes in Gynecologic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Jonathan [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Sulman, Erik P.; Jhingran, Anuja [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rauch, Gaiane M. [Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eifel, Patricia J. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Klopp, Ann H., E-mail: aklopp@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-02-01

    Purpose: To determine the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) for treatment of para-aortic nodes and to identify dosimetric parameters predictive of late duodenal toxicity. Methods and Materials: We identified 105 eligible patients with gynecologic malignancies who were treated with IMRT for gross metastatic disease in the para-aortic nodes from January 1, 2005, through December 31, 2009. Patients were treated to a nodal clinical target volume to 45 to 50.4 Gy with a boost to 60 to 66 Gy. The duodenum was contoured, and dosimetric data were exported for analysis. Duodenal toxicity was scored according to Radiation Therapy Oncology Group criteria. Univariate Cox proportional hazards analysis and recursive partitioning analysis were used to determine associations between dosimetric variables and time to toxicity and to identify the optimal threshold that separated patients according to risk of toxicity. Results: Nine of the 105 patients experienced grade 2 to grade 5 duodenal toxicity, confirmed by endoscopy in all cases. The 3-year actuarial rate of any duodenal toxicity was 11.7%. A larger volume of the duodenum receiving 55 Gy (V55) was associated with higher rates of duodenal toxicity. The 3-year actuarial rates of duodenal toxicity with V55 above and below 15 cm{sup 3} were 48.6% and 7.4%, respectively (P<.01). In Cox univariate analysis of dosimetric variables, V55 was associated with duodenal toxicity (P=.029). In recursive partitioning analysis, V55 less than 13.94% segregated all patients with duodenal toxicity. Conclusions: Dose-escalated IMRT can safely and effectively treat para-aortic nodal disease in gynecologic malignancies, provided that care is taken to limit the dose to the duodenum to reduce the risk of late duodenal toxicity. Limiting V55 to below 15 cm{sup 3} may reduce the risk of duodenal complications. In cases where the treatment cannot be delivered within these constraints

  1. Efficacy and Toxicity of Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Unknown Primary of Head and Neck

    International Nuclear Information System (INIS)

    Sher, David J.; Balboni, Tracy A.; Haddad, Robert I.; Norris, Charles M.; Posner, Marshall R.; Wirth, Lori J.; Goguen, Laura A.; Annino, Donald; Tishler, Roy B.

    2011-01-01

    Purpose: No single standard treatment paradigm is available for head-and-neck squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck radiotherapy with mucosal axis irradiation is widely used, with or without chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT) is a highly conformal method for delivering radiation that is becoming the standard of care and might reduce the long-term treatment-related sequelae. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for HNCUP. Patients and Materials: A retrospective study of all patients treated at the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and January 2009. The primary endpoint was overall survival; the secondary endpoints were locoregional and distant control, and acute and chronic toxicity. Results: A total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2 disease or greater. All patients underwent neck computed tomography, positron emission tomography-computed tomography, and examination under anesthesia with directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7 (29%) also underwent induction chemotherapy. The median involved nodal dose was 70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1 years, the 2-year actuarial overall survival and locoregional control rate was 92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia, although 11 patients (46%) required esophageal dilation for stricture. Conclusion: In a single-institution series, IMRT-based chemoradiotherapy for HNCUP was associated with superb overall survival and locoregional control. The xerostomia rates were promising, but the aggressive therapy was associated with significant rates of esophageal stenosis.

  2. Intensity-Modulated Radiotherapy Results in Significant Decrease in Clinical Toxicities Compared With Conventional Wedge-Based Breast Radiotherapy

    International Nuclear Information System (INIS)

    Harsolia, Asif; Kestin, Larry; Grills, Inga; Wallace, Michelle; Jolly, Shruti; Jones, Cortney; Lala, Moinaktar; Martinez, Alvaro; Schell, Scott; Vicini, Frank A.

    2007-01-01

    Purpose: We have previously demonstrated that intensity-modulated radiotherapy (IMRT) with a static multileaf collimator process results in a more homogenous dose distribution compared with conventional wedge-based whole breast irradiation (WBI). In the present analysis, we reviewed the acute and chronic toxicity of this IMRT approach compared with conventional wedge-based treatment. Methods and Materials: A total of 172 patients with Stage 0-IIB breast cancer were treated with lumpectomy followed by WBI. All patients underwent treatment planning computed tomography and received WBI (median dose, 45 Gy) followed by a boost to 61 Gy. Of the 172 patients, 93 (54%) were treated with IMRT, and the 79 patients (46%) treated with wedge-based RT in a consecutive fashion immediately before this cohort served as the control group. The median follow-up was 4.7 years. Results: A significant reduction in acute Grade 2 or worse dermatitis, edema, and hyperpigmentation was seen with IMRT compared with wedges. A trend was found toward reduced acute Grade 3 or greater dermatitis (6% vs. 1%, p = 0.09) in favor of IMRT. Chronic Grade 2 or worse breast edema was significantly reduced with IMRT compared with conventional wedges. No difference was found in cosmesis scores between the two groups. In patients with larger breasts (≥1,600 cm 3 , n = 64), IMRT resulted in reduced acute (Grade 2 or greater) breast edema (0% vs. 36%, p <0.001) and hyperpigmentation (3% vs. 41%, p 0.001) and chronic (Grade 2 or greater) long-term edema (3% vs. 30%, p 0.007). Conclusion: The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based RT

  3. Rectal toxicity after intensity modulated radiotherapy for prostate cancer: Which rectal dose volume constraints should we use?

    International Nuclear Information System (INIS)

    Fonteyne, Valérie; Ost, Piet; Vanpachtenbeke, Frank; Colman, Roos; Sadeghi, Simin; Villeirs, Geert; Decaestecker, Karel; De Meerleer, Gert

    2014-01-01

    Background: To define rectal dose volume constraints (DVC) to prevent ⩾grade2 late rectal toxicity (LRT) after intensity modulated radiotherapy (IMRT) for prostate cancer (PC). Material and methods: Six hundred thirty-seven PC patients were treated with primary (prostate median dose: 78 Gy) or postoperative (prostatic bed median dose: 74 Gy (adjuvant)–76 Gy (salvage)) IMRT while restricting the rectal dose to 76 Gy, 72 Gy and 74 Gy respectively. The impact of patient characteristics and rectal volume parameters on ⩾grade2 LRT was determined. DVC were defined to estimate the 5% and 10% risk of developing ⩾grade2 LRT. Results: The 5-year probability of being free from ⩾grade2 LRT, non-rectal blood loss and persisting symptoms is 88.8% (95% CI: 85.8–91.1%), 93.4% (95% CI: 91.0–95.1%) and 94.3% (95% CI: 92.0–95.9%) respectively. There was no correlation with patient characteristics. All volume parameters, except rectal volume receiving ⩾70 Gy (R70), were significantly correlated with ⩾grade2 LRT. To avoid 10% and 5% risk of ⩾grade2 LRT following DVC were derived: R40, R50, R60 and R65 <64–35%, 52–22%, 38–14% and 5% respectively. Conclusion: Applying existing rectal volume constraints resulted in a 5-year estimated risk of developing late ⩾grade2 LRT of 11.2%. New rectal DVC for primary and postoperative IMRT planning of PC patients are proposed. A prospective evaluation is needed

  4. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-04-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  5. Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

    International Nuclear Information System (INIS)

    Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

    2014-01-01

    Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

  6. Late toxicity after conformal and intensity-modulated radiation therapy for prostate cancer. Impact of previous surgery for benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Odrazka, K.; Dolezel, M.; Vanasek, J.

    2010-01-01

    The objective of this study was to retrospectively compare late toxicity of conventional-dose three-dimensional conformal radiation therapy (3D-CRT) and high-dose intensity-modulated radiation therapy (IMRT) for prostate cancer. A total of 340 patients with T1-3 prostate cancer were treated with 3D-CRT (n=228) and IMRT (n=112). The median follow-up time was 5.9 years and 3.0 years, respectively. The prescription dose was 70 Gy for 3D-CRT and 78 Gy for IMRT. Late gastrointestinal (GI) and genitourinary (GU) toxicities were graded according to the Fox Chase modification of the Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. There was no difference between 3D-CRT and IMRT in the incidence of GI and GU toxicity at 3 years. On multivariate analysis, transurethral resection of prostate/open transvesical prostatectomy (TURP/TVPE) for benign prostatic hyperplasia, carried out before radiotherapy, significantly increased the risk of Grade ≥2 GU toxicity (risk ratio 1.88). Among patients who experienced TURP/TVPE, the 5-year actuarial likelihood of Grade 2-3 urinary incontinence was 23%, compared with 9% for those without prostate surgery (P=0.01). Tolerance of 3D-CRT and IMRT was similar, despite the use of high radiation dose with IMRT. Previous TURP/TVPE increased the risk of GU toxicity. (author)

  7. Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome

    Energy Technology Data Exchange (ETDEWEB)

    Vandecasteele, K.; Eijkeren, M. van; Meerleer, G. de [Ghent University Hospital (Belgium). Dept. of Radiotherapy; Makar, A.; Broecke, R. van den; Tummers, P. [Ghent University Hospital (Belgium). Dept. of Gynecology; Delrue, L. [Ghent University Hospital (Belgium). Dept. of Radiology; Denys, H. [Ghent University Hospital (Belgium). Dept. of Medical Oncology; Lambein, K. [Ghent University Hospital (Belgium). Dept. of Pathology; Lambert, B. [Ghent University Hospital (Belgium). Dept. of Nuclear Medicine

    2012-07-15

    Purpose: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy {+-} cisplatin (IMAT {+-} C) followed by hysterectomy for locally advanced cervical cancer. Patients and methods: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT {+-} C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. Results: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. Conclusion: Surgery after IMAT {+-} C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising. (orig.)

  8. Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates

    Directory of Open Access Journals (Sweden)

    Sharoar Md

    2012-12-01

    Full Text Available Abstract Background Aggregation of soluble, monomeric β- amyloid (Aβ to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD. Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh, was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh. Results K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization. Conclusion K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.

  9. Intensity-modulated radiotherapy vs. parotid-sparing 3D conformal radiotherapy. Effect on outcome and toxicity in locally advanced head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lambrecht, M.; Nevens, D.; Nuyts, S. [University Hospitals Leuven (Belgium). Dept. of Radiation Oncology

    2013-03-15

    Background and purpose: Intensity-modulated radiotherapy (IMRT) has rapidly become standard of care in the management of locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, our aim was to retrospectively investigate the effect of the introducing IMRT on outcome and treatment-related toxicity compared to parotid-sparing 3D conformal radiotherapy (3DCRT). Material and methods: A total of 245 patients with stage III and IV HNSCC treated with primary radiotherapy between January 2003 and December 2010 were included in this analysis: 135 patients were treated with 3DCRT, 110 patients with IMRT. Groups were compared for acute and late toxicity, locoregional control (LRC), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analysis and compared using a log-rank test. Acute toxicity was analyzed according to the Common Terminology Criteria for Adverse Events v3.0 and late toxicity was scored using the RTOG/EORTC late toxicity scoring system. Results: Median follow-up was 35 months in the IMRT group and 68 months in the 3DCRT group. No significant differences were found in 3-year LRC and OS rates between the IMRT group and 3DCRT group. Significantly less acute mucositis {>=} grade 3 was observed in the IMRT group (32% vs. 44%, p = 0.03). There was significantly less late xerostomia {>=} grade 2 in the IMRT group than in the 3DCRT group (23% vs. 68%, p < 0.001). After 24 months, there was less dysphagia {>=} grade 2 in the IMRT group although differences failed to reach statistical significance. Conclusion: The introduction of IMRT in the radiotherapeutic management of locally advanced head and neck cancer significantly improved late toxicity without compromising tumor control compared to a parotid-sparing 3D conformal radiotherapy technique. (orig.)

  10. Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: Report on late toxicity and outcome

    International Nuclear Information System (INIS)

    Engels, Benedikt; Platteaux, Nele; Van den Begin, Robbe; Gevaert, Thierry; Sermeus, Alexandra; Storme, Guy; Verellen, Dirk; De Ridder, Mark

    2014-01-01

    Background and purpose: The addition of chemotherapy to preoperative radiotherapy has been established as the standard of care for patients with cT3-4 rectal cancer. As an alternative strategy, we explored intensity-modulated and image-guided radiotherapy (IMRT–IGRT) with a simultaneous integrated boost (SIB) in a prospective phase II study. Here, we report outcome and late toxicity after a median follow-up of 54 months. Methods and materials: A total of 108 patients were treated preoperatively with IMRT–IGRT, delivering a dose of 46 Gy in fractions of 2 Gy. Patients (n = 57) displaying an anticipated circumferential resection margin (CRM) of less than 2 mm based on magnetic resonance imaging received a SIB to the tumor up to a total dose of 55.2 Gy. Results: The absolute incidence of grade ⩾3 late gastrointestinal and urinary toxicity was 9% and 4%, respectively, with a 13% rate of any grade ⩾3 late toxicity. The actuarial 5-year local control (LC), progression-free survival (PFS) and overall survival (OS) were 97%, 57%, and 68%. On multivariate analysis, R1 resection and pN2 disease were associated with significantly impaired OS. Conclusions: The use of preoperative IMRT–IGRT with a SIB resulted in a high 5-year LC rate and non-negligible late toxicity

  11. Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

    International Nuclear Information System (INIS)

    Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

    2007-01-01

    Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

  12. Analyzing the capacity of the Daphnia magna and Pseudokirchneriella subcapitata bioavailability models to predict chronic zinc toxicity at high pH and low calcium concentrations and formulation of a generalized bioavailability model for D. magna.

    Science.gov (United States)

    Van Regenmortel, Tina; Berteloot, Olivier; Janssen, Colin R; De Schamphelaere, Karel A C

    2017-10-01

    Risk assessment in the European Union implements Zn bioavailability models to derive predicted-no-effect concentrations for Zn. These models are validated within certain boundaries (i.e., pH ≤ 8 and Ca concentrations ≥ 5mg/L), but a substantial fraction of the European surface waters falls outside these boundaries. Therefore, we evaluated whether the chronic Zn biotic ligand model (BLM) for Daphnia magna and the chronic bioavailability model for Pseudokirchneriella subcapitata could be extrapolated to pH > 8 and Ca concentrations model can accurately predict Zn toxicity for Ca concentrations down to 0.8 mg/L and pH values up to 8.5. Because the chronic Zn BLM for D. magna could not be extrapolated beyond its validity boundaries for pH, a generalized bioavailability model (gBAM) was developed. Of 4 gBAMs developed, we recommend the use of gBAM-D, which combines a log-linear relation between the 21-d median effective concentrations (expressed as free Zn 2+ ion activity) and pH, with more conventional BLM-type competition constants for Na, Ca, and Mg. This model is a first step in further improving the accuracy of chronic toxicity predictions of Zn as a function of water chemistry, which can decrease the uncertainty in implementing the bioavailability-based predicted-no-effect concentration in the risk assessment of high-pH and low-Ca concentration regions in Europe. Environ Toxicol Chem 2017;36:2781-2798. © 2017 SETAC. © 2017 SETAC.

  13. Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Tao HM

    2016-03-01

    Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity-modulated

  14. Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

    Energy Technology Data Exchange (ETDEWEB)

    Gandhi, Ajeet Kumar, E-mail: ajeetgandhi23@gmail.com [Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi (India); Sharma, Daya Nand; Rath, Goura Kisor; Julka, Pramod Kumar; Subramani, Vellaiyan; Sharma, Seema; Manigandan, Durai; Laviraj, M.A. [Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi (India); Kumar, Sunesh [Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi (India); Thulkar, Sanjay [Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi (India)

    2013-11-01

    Purpose: To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). Methods and Materials: Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m{sup 2}. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. Results: Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). Conclusion: WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify

  15. Reduced Toxicity With Intensity Modulated Radiation Therapy (IMRT) for Desmoplastic Small Round Cell Tumor (DSRCT): An Update on the Whole Abdominopelvic Radiation Therapy (WAP-RT) Experience

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Neil B. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Stein, Nicholas F. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kushner, Brian H.; Modak, Shakeel; Magnan, Heather M. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-01-01

    Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and Materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximal surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves

  16. Image-guided intensity-modulated radiotherapy of prostate cancer. Analysis of interfractional errors and acute toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Rudat, Volker; Nour, A.; Hammoud, M.; Alaradi, A.; Mohammed, A. [Saad Specialist Hospital, Department of Radiation Oncology, Al Khobar (Saudi Arabia)

    2016-02-15

    The aim of the study was to estimate interfractional deviations in patient and prostate position, the impact of the frequency of online verification on the treatment margins, and to assess acute radiation reactions of high-dose external beam image-guided intensity-modulated radiotherapy (IG-IMRT) of localized prostate cancer. IG-IMRT was performed by daily online verification of implanted fiducial prostate markers using a megavoltage electronic portal imaging device (EPID). A total of 1011 image-guided treatment fractions from 23 consecutive unselected prostate cancer patients were analyzed. The median total dose was 79.2 Gy (range 77.4-81.0 Gy). Acute radiation reactions were assessed weekly during radiotherapy using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.03. A relevant combined patient set-up and prostate motion population random error of 4-5 mm was observed. Compared to daily IGRT, image guidance every other day required an expansion of the CTV-PTV (clinical target volume-planning target volume) margin of 8.1, 6.6, and 4.1 mm in the longitudinal, vertical, and lateral directions, thereby, increasing the PTV by approximately 30-40 %. No grade 3 or 4 acute radiation reactions were observed with daily IG-IMRT. A high dose with surprisingly low acute toxicity can be applied with daily IG-IMRT using implanted fiducial prostate markers. Daily image guidance is clearly superior to image guidance every other fraction concerning adequate target coverage with minimal margins. (orig.) [German] Ziel der Studie war es, die interfraktionelle Variabilitaet der Patientenlagerung und Prostataposition, den Einfluss der Bildgebungsfrequenz und die akuten Strahlenreaktionen bei einer hochdosierten bildgesteuerten intensitaetsmodulierten Strahlentherapie (IG-IMRT) des Prostatakarzinoms zu untersuchen. IG-IMRT wurde durch taegliche Verifikation von implantierten roentgendichten Prostatamarkern mittels Megavolt-Bildgebung (''electronic portal imaging

  17. Toxicity of fatty acid 18:5n3 from Gymnodinium cf. mikimotoi: II. Intracellular pH and K+ uptake in isolated trout hepatocytes.

    Science.gov (United States)

    Fossat, B; Porthé-Nibelle, J; Sola, F; Masoni, A; Gentien, P; Bodennec, G

    1999-01-01

    Effects of octadecapentaenoic acid 18:5n3 and other related polyunsaturated fatty acids present in gymnodinium cf. mikimotoi were tested in isolated trout hepatocytes. These exotoxins decreased intracellular pH followed by a slow recovery to initial value and alkalinization of acidic compartments, suggesting an inhibition of vacuolar H(+)-ATPases. Moreover, addition of 18:5n3 to the extracellular medium induced a decrease of K+ uptake into hepatocytes as a result of Na,K-ATPase inhibition. However, high concentrations (10(-5)-10(-3) M) are necessary to induce these effects.

  18. Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

    Science.gov (United States)

    Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

    2016-01-01

    The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

    Directory of Open Access Journals (Sweden)

    David Thomson

    2012-01-01

    Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

  20. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Wortel, Ruud C.; Incrocci, Luca [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Heemsbergen, Wilma D., E-mail: w.heemsbergen@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands)

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  1. Toxicity and dosimetric analysis of non-small cell lung cancer patients undergoing radiotherapy with 4DCT and image-guided intensity modulated radiotherapy: a regional centre's experience.

    Science.gov (United States)

    Livingston, Gareth C; Last, Andrew J; Shakespeare, Thomas P; Dwyer, Patrick M; Westhuyzen, Justin; McKay, Michael J; Connors, Lisa; Leader, Stephanie; Greenham, Stuart

    2016-09-01

    For patients receiving radiotherapy for locally advance non-small cell lung cancer (NSCLC), the probability of experiencing severe radiation pneumonitis (RP) appears to rise with an increase in radiation received by the lungs. Intensity modulated radiotherapy (IMRT) provides the ability to reduce planned doses to healthy organs at risk (OAR) and can potentially reduce treatment-related side effects. This study reports toxicity outcomes and provides a dosimetric comparison with three-dimensional conformal radiotherapy (3DCRT). Thirty curative NSCLC patients received radiotherapy using four-dimensional computed tomography and five-field IMRT. All were assessed for early and late toxicity using common terminology criteria for adverse events. All plans were subsequently re-planned using 3DCRT to the same standard as the clinical plans. Dosimetric parameters for lungs, oesophagus, heart and conformity were recorded for comparison between the two techniques. IMRT plans achieved improved high-dose conformity and reduced OAR doses including lung volumes irradiated to 5-20 Gy. One case each of oesophagitis and erythema (3%) were the only Grade 3 toxicities. Rates of Grade 2 oesophagitis were 40%. No cases of Grade 3 RP were recorded and Grade 2 RP rates were as low as 3%. IMRT provides a dosimetric benefit when compared to 3DCRT. While the clinical benefit appears to increase with increasing target size and increasing complexity, IMRT appears preferential to 3DCRT in the treatment of NSCLC.

  2. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

    Directory of Open Access Journals (Sweden)

    Rui Guo

    Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

  3. A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Sayan, Mutlay; Nelson, Carl; Gagne, Havaleh; Rubin, Deborah; Heimann, Ruth [Dept. of Radiation Oncology, University of Vermont Medical Center, Burlington (United States); Wilson, Karen [University of Vermont Cancer Center, Burlington (United States)

    2017-03-15

    Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

  4. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.

    Science.gov (United States)

    Sveistrup, Joen; af Rosenschöld, Per Munck; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

    2014-02-04

    Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

  5. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Detailed Conceptual Diagram

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  6. CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Simple Conceptual Diagram

    Science.gov (United States)

    Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

  7. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    International Nuclear Information System (INIS)

    Sveistrup, Joen; Rosenschöld, Per Munck af; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

    2014-01-01

    Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction

  8. Modulating and Measuring Intracellular H2O2 Using Genetically Encoded Tools to Study Its Toxicity to Human Cells.

    Science.gov (United States)

    Huang, Beijing K; Stein, Kassi T; Sikes, Hadley D

    2016-12-16

    Reactive oxygen species (ROS) such as H 2 O 2 play paradoxical roles in mammalian physiology. It is hypothesized that low, baseline levels of H 2 O 2 are necessary for growth and differentiation, while increased intracellular H 2 O 2 concentrations are associated with pathological phenotypes and genetic instability, eventually reaching a toxic threshold that causes cell death. However, the quantities of intracellular H 2 O 2 that lead to these different responses remain an unanswered question in the field. To address this question, we used genetically encoded constructs that both generate and quantify H 2 O 2 in a dose-response study of H 2 O 2 -mediated toxicity. We found that, rather than a simple concentration-response relationship, a combination of intracellular concentration and the cumulative metric of H 2 O 2 concentration multiplied by time (i.e., the area under the curve) determined the occurrence and level of cell death. Establishing the quantitative relationship between H 2 O 2 and cell toxicity promotes a deeper understanding of the intracellular effects of H 2 O 2 specifically as an individual reactive oxygen species, and it contributes to an understanding of its role in various redox-related diseases.

  9. PH sensor

    OpenAIRE

    Artero, C.; Nogueras Cervera, Marc; Manuel Lázaro, Antonio

    2012-01-01

    This paper presents a design of a marine instrument for the measurement of pH in seawater. The measurement system consists of a pH electrode connected to the underwater observatory OBSEA. The extracted data are useful for scientists researching ocean acidification. Peer Reviewed

  10. Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Chance, William W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rice, David C. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsao, Anne S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fontanilla, Hiral P. [Princeton Radiation Oncology, Monroe Township, New Jersey (United States); Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza J. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-01-01

    Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

  11. Modulation of protein fermentation does not affect fecal water toxicity: a randomized cross-over study in healthy subjects.

    Directory of Open Access Journals (Sweden)

    Karen Windey

    Full Text Available Protein fermentation results in production of metabolites such as ammonia, amines and indolic, phenolic and sulfur-containing compounds. In vitro studies suggest that these metabolites might be toxic. However, human and animal studies do not consistently support these findings. We modified protein fermentation in healthy subjects to assess the effects on colonic metabolism and parameters of gut health, and to identify metabolites associated with toxicity.After a 2-week run-in period with normal protein intake (NP, 20 healthy subjects followed an isocaloric high protein (HP and low protein (LP diet for 2 weeks in a cross-over design. Protein fermentation was estimated from urinary p-cresol excretion. Fecal metabolite profiles were analyzed using GC-MS and compared using cluster analysis. DGGE was used to analyze microbiota composition. Fecal water genotoxicity and cytotoxicity were determined using the Comet assay and the WST-1-assay, respectively, and were related to the metabolite profiles.Dietary protein intake was significantly higher during the HP diet compared to the NP and LP diet. Urinary p-cresol excretion correlated positively with protein intake. Fecal water cytotoxicity correlated negatively with protein fermentation, while fecal water genotoxicity was not correlated with protein fermentation. Heptanal, 3-methyl-2-butanone, dimethyl disulfide and 2-propenyl ester of acetic acid are associated with genotoxicity and indole, 1-octanol, heptanal, 2,4-dithiapentane, allyl-isothiocyanate, 1-methyl-4-(1-methylethenyl-benzene, propionic acid, octanoic acid, nonanoic acid and decanoic acid with cytotoxicity.This study does not support a role of protein fermentation in gut toxicity. The identified metabolites can provide new insight into colonic health.ClinicalTrial.gov NCT01280513.

  12. Intensity-Modulated Radiotherapy (IMRT) vs Helical Tomotherapy (HT) in Concurrent Chemoradiotherapy (CRT) for Patients with Anal Canal Carcinoma (ACC): an analysis of dose distribution and toxicities

    International Nuclear Information System (INIS)

    Yeung, Rosanna; McConnell, Yarrow; Warkentin, Heather; Graham, Darren; Warkentin, Brad; Joseph, Kurian; Doll, Corinne M

    2015-01-01

    Intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) have been adopted for radiotherapy treatment of anal canal carcinoma (ACC) due to better conformality, dose homogeneity and normal-tissue sparing compared to 3D-CRT. To date, only one published study compares dosimetric parameters of IMRT vs HT in ACC, but there are no published data comparing toxicities. Our objectives were to compare dosimetry and toxicities between these modalities. This is a retrospective study of 35 ACC patients treated with radical chemoradiotherapy at two tertiary cancer institutions from 2008–2010. The use of IMRT vs HT was primarily based on center availability. The majority of patients received fluorouracil (5-FU) and 1–2 cycles of mitomycin C (MMC); 2 received 5-FU and cisplatin. Primary tumor and elective nodes were prescribed to ≥54Gy and ≥45Gy, respectively. Patients were grouped into two cohorts: IMRT vs HT. The primary endpoint was a dosimetric comparison between the cohorts; the secondary endpoint was comparison of toxicities. 18 patients were treated with IMRT and 17 with HT. Most IMRT patients received 5-FU and 1 MMC cycle, while most HT patients received 2 MMC cycles (p < 0.01), based on center policy. HT achieved more homogenous coverage of the primary tumor (HT homogeneity and uniformity index 0.14 and 1.02 vs 0.29 and 1.06 for IMRT, p = 0.01 and p < 0.01). Elective nodal coverage did not differ. IMRT achieved better bladder, femoral head and peritoneal space sparing (V30 and V40, p ≤ 0.01), and lower mean skin dose (p < 0.01). HT delivered lower bone marrow (V10, p < 0.01) and external genitalia dose (V20 and V30, p < 0.01). Grade 2+ hematological and non-hematological toxicities were similar. Febrile neutropenia and unscheduled treatment breaks did not differ (both p = 0.13), nor did 3-year overall and disease-free survival (p = 0.13, p = 0.68). Chemoradiotherapy treatment of ACC using IMRT vs HT results in differences in dose homogenity and

  13. Long-term disease control and toxicity outcomes following surgery and intensity modulated radiation therapy (IMRT) in pediatric craniopharyngioma.

    Science.gov (United States)

    Greenfield, Brad J; Okcu, Mehmet F; Baxter, Patricia A; Chintagumpala, Murali; Teh, Bin S; Dauser, Robert C; Su, Jack; Desai, Snehal S; Paulino, Arnold C

    2015-02-01

    To report long-term progression-free survival (PFS) and late-toxicity outcomes in pediatric craniopharyngioma patients treated with IMRT. Twenty-four children were treated with IMRT to a median dose of 50.4Gy (range, 49.8-54Gy). The clinical target volume (CTV) was the gross tumor volume (GTV) with a 1cm margin. The planning target volume (PTV) was the CTV with a 3-5mm margin. Median follow-up was 107.3months. The 5- and 10-year PFS rates were 65.8% and 60.7%. The 5- and 10-year cystic PFS rates were 70.2% and 65.2% while the 5- and 10-year solid PFS were the same at 90.7%. Endocrinopathy was seen in 42% at initial diagnosis and in 74% after surgical intervention, prior to IMRT. Hypothalamic dysfunction and visual deficits were associated with increasing PTV and number of surgical interventions. IMRT is a viable treatment option for pediatric craniopharyngioma. Despite the use of IMRT, majority of the craniopharyngioma patients experienced long-term toxicity, many of which present prior to radiotherapy. Limitations of retrospective analyses on small patient cohort elicit the need for a prospective multi-institutional study to determine the absolute benefit of IMRT in pediatric craniopharyngioma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Long-term disease control and toxicity outcomes following surgery and intensity modulated radiation therapy (IMRT) in pediatric craniopharyngioma

    International Nuclear Information System (INIS)

    Greenfield, Brad J.; Okcu, Mehmet F.; Baxter, Patricia A.; Chintagumpala, Murali; Teh, Bin S.; Dauser, Robert C.; Su, Jack; Desai, Snehal S.; Paulino, Arnold C.

    2015-01-01

    Purpose: To report long-term progression-free survival (PFS) and late-toxicity outcomes in pediatric craniopharyngioma patients treated with IMRT. Patients and methods: Twenty-four children were treated with IMRT to a median dose of 50.4 Gy (range, 49.8–54 Gy). The clinical target volume (CTV) was the gross tumor volume (GTV) with a 1 cm margin. The planning target volume (PTV) was the CTV with a 3–5 mm margin. Median follow-up was 107.3 months. Results: The 5- and 10-year PFS rates were 65.8% and 60.7%. The 5- and 10-year cystic PFS rates were 70.2% and 65.2% while the 5- and 10-year solid PFS were the same at 90.7%. Endocrinopathy was seen in 42% at initial diagnosis and in 74% after surgical intervention, prior to IMRT. Hypothalamic dysfunction and visual deficits were associated with increasing PTV and number of surgical interventions. Conclusions: IMRT is a viable treatment option for pediatric craniopharyngioma. Despite the use of IMRT, majority of the craniopharyngioma patients experienced long-term toxicity, many of which present prior to radiotherapy. Limitations of retrospective analyses on small patient cohort elicit the need for a prospective multi-institutional study to determine the absolute benefit of IMRT in pediatric craniopharyngioma

  15. The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

    Science.gov (United States)

    Tian, Yun-Ming; Huang, Wei-Zeng; Yuan, Xia; Bai, Li; Zhao, Chong; Han, Fei

    2017-06-27

    Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

  16. Modulation of physiological responses with TiO2 nano-particle in Azolla pinnata R.Br. under 2,4-D toxicity.

    Science.gov (United States)

    De, Arnab Kumar; Ghosh, Arijit; Debnath, Subhas Chandra; Sarkar, Bipul; Saha, Indraneel; Adak, Malay Kumar

    2018-06-05

    The present work is emphasised with the herbicidal tolerance of Azolla pinnata R.Br. and its modulation with TiO 2 nano-particle. Both carbohydrate and nitrogen metabolism were effected with 2,4-D as herbicide and in few cases TiO 2 -NP had recovered few detrimental effects. From the nutrient status in Azolla it recorded the recovery of nitrogen as well as potassium by TiO 2 -NP but not in case of phosphorus. However, a conversion of nitrate to ammonium was more induced by TiO 2 -NP under herbicidal toxicity. Similar results were obtained for inter-conversion of amino acid-nitrate pool, but no changes with glutamine synthase activity with TiO 2 -NP. Initially, the effects of 2,4-D was monitored with changes of chlorophyll content but had not been recovered with nanoparticle. Photosynthetic reserves expressed as both total and reducing sugar were insensitive to TiO 2 -NP interference but activity of soluble and wall bound invertase was in reverse trend as compared to control. The 2,4-D mediated changes of redox and its oxidative stress was ameliorated in plants with over expressed ADH activity. As a whole the Azolla bio system with TiO 2 supplementation may be useful in sustenance against 2,4-D toxicity through recovery of nitrogen metabolism. Thus, Azolla-TiO 2 -NP bio system would be realised to monitor the herbicidal toxicity in soil and its possible bioremediation.

  17. Silymarin protects PBMC against B(a)P induced toxicity by replenishing redox status and modulating glutathione metabolizing enzymes-An in vitro study

    International Nuclear Information System (INIS)

    Kiruthiga, P.V.; Pandian, S. Karutha; Devi, K. Pandima

    2010-01-01

    PAHs are a ubiquitous class of environmental contaminants that have a large number of hazardous consequences on human health. An important prototype of PAHs, B(a)P, is notable for being the first chemical carcinogen to be discovered and the one classified by EPA as a probable human carcinogen. It undergoes metabolic activation to QD, which generate ROS by redox cycling system in the body and oxidatively damage the macromolecules. Hence, a variety of antioxidants have been tested as possible protectors against B(a)P toxicity. Silymarin is one such compound, which has high human acceptance, used clinically and consumed as dietary supplement around the world for its strong anti-oxidant efficacy. Silymarin was employed as an alternative approach for treating B(a)P induced damage and oxidative stress in PBMC, with an emphasis to provide the molecular basis for the effect of silymarin against B(a)P induced toxicity. PBMC cells exposed to either benzopyrene (1 μM) or silymarin (2.4 mg/ml) or both was monitored for toxicity by assessing LPO, PO, redox status (GSH/GSSG ratio), glutathione metabolizing enzymes GR and GPx and antioxidant enzymes CAT and SOD. This study also investigated the protective effect of silymarin against B(a)P induced biochemical alteration at the molecular level by FT-IR spectroscopy. Our findings were quite striking that silymarin possesses substantial protective effect against B(a)P induced oxidative stress and biochemical changes by restoring redox status, modulating glutathione metabolizing enzymes, hindering the formation of protein oxidation products, inhibiting LPO and further reducing ROS mediated damages by changing the level of antioxidant enzymes. The results suggest that silymarin exhibits multiple protections and it should be considered as a potential protective agent for environmental contaminant induced immunotoxicity.

  18. Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy

    International Nuclear Information System (INIS)

    McDonald, Mark W.; Liu, Yuan; Moore, Michael G.; Johnstone, Peter A. S.

    2016-01-01

    To evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT). Forty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation. In a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus. Proton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life

  19. Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12

    Directory of Open Access Journals (Sweden)

    Radmacher Michael D

    2006-10-01

    Full Text Available Abstract Background In Escherichia coli, pH regulates genes for amino-acid and sugar catabolism, electron transport, oxidative stress, periplasmic and envelope proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the overall intersection of pH stress and oxygen limitation has not been investigated. Results The pH dependence of gene expression was analyzed in oxygen-limited cultures of E. coli K-12 strain W3110. E. coli K-12 strain W3110 was cultured in closed tubes containing LBK broth buffered at pH 5.7, pH 7.0, and pH 8.5. Affymetrix array hybridization revealed pH-dependent expression of 1,384 genes and 610 intergenic regions. A core group of 251 genes showed pH responses similar to those in a previous study of cultures grown with aeration. The highly acid-induced gene yagU was shown to be required for extreme-acid resistance (survival at pH 2. Acid also up-regulated fimbriae (fimAC, periplasmic chaperones (hdeAB, cyclopropane fatty acid synthase (cfa, and the "constitutive" Na+/H+ antiporter (nhaB. Base up-regulated core genes for maltodextrin transport (lamB, mal, ATP synthase (atp, and DNA repair (recA, mutL. Other genes showed opposite pH responses with or without aeration, for example ETS components (cyo,nuo, sdh and hydrogenases (hya, hyb, hyc, hyf, hyp. A hypF strain lacking all hydrogenase activity showed loss of extreme-acid resistance. Under oxygen limitation only, acid down-regulated ribosome synthesis (rpl,rpm, rps. Acid up-regulated the catabolism of sugar derivatives whose fermentation minimized acid production (gnd, gnt, srl, and also a cluster of 13 genes in the gadA region. Acid up-regulated drug transporters (mdtEF, mdtL, but down-regulated penicillin-binding proteins (dacACD, mreBC. Intergenic regions containing regulatory sRNAs were up-regulated by acid (ryeA, csrB, gadY, rybC. Conclusion pH regulates a core set of genes independently of oxygen, including yagU, fimbriae, periplasmic chaperones, and nha

  20. A comparative study of pH modulation and trace elements of various fruit juices on enamel erosion: An in vitro study

    Directory of Open Access Journals (Sweden)

    S.V.S.G Nirmala

    2011-01-01

    Full Text Available Fruit juices are popular worldwide with children of all ages as they are sweet and perceived to be healthful. This in vitro study was sought to measure pH of 10 different fruit juices, to find out possible erosive effects on human dental enamel of 40 extracted sound premolars and also to measure fluoride and trace elements of these juices. The estimation of pH of fruit juices was done by using Systronic upH 362 pH meter. The erosive effects of fruit juices were tested by using polarized light microscope. Orion electrode was used to measure fluoride. The trace elements were estimated by using Atomic Absorption Spectrophotometer No. 6501F. The pH values in different juices were observed at different levels, and pH values of these juices were more acidic than baseline after 24 hours. As the time increased, the erosion effect became more in pineapple; grape and sugarcane juices, and they had more cariogenic trace elements like selenium, iron and manganese. So, these juices were found to be cariogenic. To conclude, orange, mousambi, mango, pomegranate, apple, chikku and watermelon juices had no erosive effect on the human enamel, with the presence of highest amount of trace elements like fluoride and phosphorous which are considered as strongly cariostatic.

  1. The Protective Role of Starch on Modulating Toxic Effects of Citrullus Colocynthis on Rat Liver and Intestine

    Directory of Open Access Journals (Sweden)

    Neda Eskandarzade

    2018-01-01

    Full Text Available Background: Despite using Citrullus colocynthis on treatment of various diseases, serious gastrointestinal disorders like bleeding are reported. In Traditional Iranian Medicine (TIM, administering equal weights of starch with this plant is suggested to produce more tolerable preparations from it. Hence, we assessed histopathological changes in rat liver and intestine after using starch as corrective agent. Methods: We designed three experiments in Veterinary Medicine School of Shahid Bahonar University in Kerman, Iran in 2016. The procedure was applied in 2016 for 15 days. In the first experiment, group No. 2 and 3 received single daily dose of alcoholic pulp extract of C. colocynthis at 300 and 600 mg/kg extract consecutively. In the second experiment, group No. 4 and 5 received 300 and 600 mg/kg extract plus the same amount of starch consecutively. In the third experiment, group No. 6 and 7 received extract at 300 and 600 mg/kg plus the three times weight of starch consecutively. The live rats were euthanized and their liver and intestine were removed for histopathology examination. The samples were stained with hematoxyline-eosin (H&E. Results: Rats in all of the groups died from bleeding and diarrhea except for group No.6 that showed no symptoms seen in other rats. Microscopic examination of their intestine showed no histopathological lesions or other degenerative changes of the epithelium. Conclusion: Clearly further works in modern phytotherapy will be required to delineate the role of starch in reducing C. colocynthis toxicity. Consumption of adequate weight of starch with the toxic dose of C. colocynthis make it safe for digestive system but could not prevent necrotic changes in the liver.

  2. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

    International Nuclear Information System (INIS)

    Lefever, Daniel E.; Xu, Joella; Chen, Yingjia; Huang, Guannan; Tamas, Nagy; Guo, Tai L.

    2016-01-01

    An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6 μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4 × 50 mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3 + NK + T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure. - Highlights: • TCDD promoted wasting syndrome. • TCDD decreased hyperglycemia. • TCDD exposure caused

  3. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lefever, Daniel E.; Xu, Joella; Chen, Yingjia [Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA 30602-7382 (United States); Huang, Guannan [Department of Environmental Health Sciences, University of Georgia, Athens, GA 30602-7382 (United States); Tamas, Nagy [Department of Veterinary Pathology, University of Georgia, Athens, GA 30602-7382 (United States); Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA 30602-7382 (United States)

    2016-08-01

    An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6 μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4 × 50 mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3{sup +} NK{sup +} T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure. - Highlights: • TCDD promoted wasting syndrome. • TCDD decreased hyperglycemia. • TCDD exposure

  4. pH modulates transport rates of manganese and cadmium in the green alga Chlamydomonas reinhardtii through non-competitive interactions: Implications for an algal BLM

    International Nuclear Information System (INIS)

    Francois, Laura; Fortin, Claude; Campbell, Peter G.C.

    2007-01-01

    The influence of pH on short-term uptake of manganese and cadmium by the green alga Chlamydomonas reinhardtii was studied to better understand the nature of proton interactions with metal membrane transporters. Manganese and cadmium internalization fluxes (J int ) were measured over a wide range of free metal ion concentrations from 1 x 10 -10 to 4 x 10 -4 M at several pH values (Mn: 5.0, 6.5 and 8.0; Cd: 5.0 and 6.5). For both metals, first-order biological internalization kinetics were observed but the maximum transport flux (J max ) decreased when pH decreased, in contradiction with the Biotic Ligand Model (BLM). This result suggested a non-competitive inhibition of metal uptake by the H + -ion. A Michaelis-Menten type inhibition model considering proton and calcium competition was tested. The metal biotic ligand stability constants and the stability constants for competitive binding of Ca 2+ and H + with the metal transporters were calculated: for manganese, K Mn = 10 4.20 and K Ca = 10 3.71 ; for cadmium, K Cd = 10 4.19 and K Ca = 10 4.76 ; for both metal transport systems, K H was not a significant parameter. Furthermore, metal uptake was not significantly influenced by the pH of the antecedent growth medium, suggesting that increases in metal fluxes as the pH is raised are caused by conformational changes of the surface transport proteins rather than by the synthesis of additional transport sites. Our results demonstrate that the BLM in its present state does not properly describe the true influence of pH on manganese and cadmium uptake by algae and that a non-competitive inhibition component must be integrated

  5. A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia

    Science.gov (United States)

    The basic helix-loop-helix (bHLH) transcription factors (TFs) play important roles in regulating multiple biological processes in plants. However, there are few reports about the function of bHLHs in flower senescence. In this study, a bHLH TF, PhFBH4, was found to be dramatically upregulated during...

  6. Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

    Energy Technology Data Exchange (ETDEWEB)

    Michalski, Jeff M., E-mail: jmichalski@radonc.wustl.edu [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Yan, Yan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Watkins-Bruner, Deborah [Emory University School of Nursing, Atlanta, Georgia (United States); Bosch, Walter R. [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Galvin, James M. [Department of Radiation Oncology Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Department of Radiation Oncology Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, QC (Canada); Morton, Gerard C. [Department of Radiation Oncology Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON (Canada); Parliament, Matthew B. [Department of Oncology Cross Cancer Institute, Edmonton, AB (Canada); Sandler, Howard M. [Department of Radiation Oncology Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California (United States)

    2013-12-01

    Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

  7. Reproductive toxicity of bisphenol A and cadmium in Potamopyrgus antipodarum and modulation of bisphenol A effects by different test temperature

    International Nuclear Information System (INIS)

    Sieratowicz, Agnes; Stange, Daniela; Schulte-Oehlmann, Ulrike; Oehlmann, Joerg

    2011-01-01

    An OECD initiative for the development of mollusc-based toxicity tests for endocrine disrupters and other chemicals has recommended three test species with respective test designs for further standardisation. Preparing a subsequent pre-validation study we performed a reproduction test with Potamopyrgus antipodarum, determining the concentration range of the selected test substances, bisphenol A (BPA) and cadmium (Cd). At 16 deg. C, the recommended test temperature, the number of embryos in the brood pouch was increased by BPA and decreased by Cd (NOEC: 20 μg BPA/L and 1 μg Cd/L). Coinstantaneous BPA tests at 7 deg. C and 25 deg. C demonstrated a temperature dependency of the response, resulting in lower NOECs (5 μg/L respectively). As expected, reproduction in control groups significantly varied depending on temperature. Additional observations of the brood stock showed seasonal fluctuations in reproduction under constant laboratory conditions. The recommended temperature range and test conditions have to be further investigated. - Highlights: → We performed a reproduction test with the mollusc Potamopyrgus antipodarum. → We defined the test substance concentration range for a pre-validation study. → The bisphenol A effect (increased reproduction) depends on the test temperature. → Reproduction of control groups significantly varies depending on temperature. → The brood stock shows seasonal fluctuations in reproduction at constant conditions. - A reproduction test with Potamopyrgus antipodarum with 2 substances for subsequent pre-validation is presented and bisphenol A effects show a temperature dependency.

  8. Heteroagglomeration of zinc oxide nanoparticles with clay mineral modulates the bioavailability and toxicity of nanoparticle in Tetrahymena pyriformis.

    Science.gov (United States)

    Gupta, Govind Sharan; Senapati, Violet Aileen; Dhawan, Alok; Shanker, Rishi

    2017-06-01

    The extensive use of zinc oxide nanoparticles (ZnO NPs) in cosmetics, sunscreens and healthcare products increases their release in the aquatic environment. The present study explored the possible interaction of ZnO NPs with montmorillonite clay minerals in aqueous conditions. An addition of ZnO NPs on clay suspension significantly (pclay particles from 1652±90nm to 2158±13nm due to heteroagglomeration. The electrokinetic measurements showed a significant (pclay association (-1.37±0.03μmcm/Vs) that results to the electrostatic interaction between ZnO NPs and clay particles. The attenuated total reflectance Fourier transform infrared spectroscopy analysis of ZnO NPs-clay association demonstrated the binding of ZnO NPs with the Si-O-Al region on the edges of clay particles. The increase in size of ZnO NPs-clay heteroagglomerates further leads to their sedimentation at 24h. Although, the stability of ZnO NPs in the clay suspension was decreased due to heteroagglomeration, but the bioavailability and toxicity of ZnO NPs-clay heteroagglomerates in Tetrahymena pyriformis was enhanced. These observations provide an evidence on possible mechanisms available in natural environment that can facilitate nanoparticles entry into the organisms present in lower trophic levels of the food web. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Endocrine modulation and toxic effects of two commonly used UV screens on the aquatic invertebrates Potamopyrgus antipodarum and Lumbriculus variegatus

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, Claudia [Johann Wolfgang Goethe-University, Department Aquatic Ecotoxicology, Siesmayerstrasse 70, 60323 Frankfurt (Germany)], E-mail: claudia.schmitt@ua.ac.be; Oetken, Matthias; Dittberner, Olaf; Wagner, Martin; Oehlmann, Joerg [Johann Wolfgang Goethe-University, Department Aquatic Ecotoxicology, Siesmayerstrasse 70, 60323 Frankfurt (Germany)

    2008-03-15

    The two UV screens 3-benzylidene-camphor (3-BC) and 3-(4'-methylbenzylidene)-camphor (4-MBC) were tested regarding their toxicity and estrogenic activity. The Yeast Estrogen Screen (YES) and two sediment assays with the freshwater invertebrates Lumbriculus variegatus and Potamopyrgus antipodarum were performed. In the YES, both substances activated the human estrogen receptor {alpha} with EC{sub 50} values of 44.2 {mu}M for 3-BC and 44.3 {mu}M for 4-MBC, whereby 4-MBC attained only 8% of the maximal response of 17{beta}-estradiol. For P. antipodarum embryo production increased after exposure to both substances (EC{sub 50} of 4.60 {mu}M 4-MBC = 1.17 mg kg{sup -1} dw) while mortality increased at high concentrations. The reproduction of L. variegatus was decreased by 3-BC with an EC{sub 50} of 5.95 {mu}M (=1.43 mg kg{sup -1} dw) and also by 4-MBC, where no EC{sub 50} could be calculated. While reproduction decreased, the worms' weight increased after exposure to 3-BC with an EC{sub 50} of 26.9 {mu}M (= 6.46 mg kg{sup -1} dw), hence the total biomass remained unaffected. - UV screens can have a significant impact on reproduction and development of aquatic invertebrates.

  10. Modulation of toxicity following external beam irradiation preceded by high-dose rate brachytherapy in inoperable oesophageal cancer

    International Nuclear Information System (INIS)

    Taal, B.G.; Aleman, B.M.P.; Koning, C.C.E.; Boot, H.

    1996-01-01

    To induce fast relief of dysphagia in inoperable oesephageal cancer, we applied high-dose rate (HDR) intraluminal irradiation followed by external irradiation (EBRT) in a phase II study. 15 patients (group A: n = 15; 10 men, 5 women; median age 66 years) were treated with 10 Gy HDR brachytherapy plus 40 Gy EBRT (15 fractions of 2.67 Gy). Severe side-effects were encountered in 60% of patients: 3 late ulceration, 2 pending fistula and 2 patients with fatal haemorrhage after an interval of 6 months. Overall response was excellent: 9 complete remissions (60%) and 6 partial responses (40%). Because of the high toxicity rate, in a subsequent study (group B: n = 30; 23 mean, 7 women; median age 66 years) the EBRT scheme was changed using smaller fractions (2.0 Gy) to reach the same total dose of 40 Gy. The complication rate (17%) was significantly reduced, while the overall response remained excellent (83%): 17 complete and 8 partial responses. The impressive change in complication rate of HDR brachytherapy and EBRT stresses the impact of the fraction per dose and illustrates the small therapeutic margins. (author)

  11. Modulation of toxicity following external beam irradiation preceded by high-dose rate brachytherapy in inoperable oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Taal, B.G.; Aleman, B.M.P.; Koning, C.C.E.; Boot, H. [Nederlands Kanker Inst. `Antoni van Leeuwenhoekhuis`, Amsterdam (Netherlands)

    1996-09-01

    To induce fast relief of dysphagia in inoperable oesephageal cancer, we applied high-dose rate (HDR) intraluminal irradiation followed by external irradiation (EBRT) in a phase II study. 15 patients (group A: n = 15; 10 men, 5 women; median age 66 years) were treated with 10 Gy HDR brachytherapy plus 40 Gy EBRT (15 fractions of 2.67 Gy). Severe side-effects were encountered in 60% of patients: 3 late ulceration, 2 pending fistula and 2 patients with fatal haemorrhage after an interval of 6 months. Overall response was excellent: 9 complete remissions (60%) and 6 partial responses (40%). Because of the high toxicity rate, in a subsequent study (group B: n = 30; 23 mean, 7 women; median age 66 years) the EBRT scheme was changed using smaller fractions (2.0 Gy) to reach the same total dose of 40 Gy. The complication rate (17%) was significantly reduced, while the overall response remained excellent (83%): 17 complete and 8 partial responses. The impressive change in complication rate of HDR brachytherapy and EBRT stresses the impact of the fraction per dose and illustrates the small therapeutic margins. (author).

  12. Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells

    Science.gov (United States)

    Coccia, Andrea; Mosca, Luciana; Puca, Rosa; Mangino, Giorgio; Rossi, Alessandro; Lendaro, Eugenio

    2016-01-01

    Epidemiological data indicate that the daily consumption of extra-virgin olive oil (EVOO), a common dietary habit of the Mediterranean area, lowers the incidence of certain types of cancer, in particular bladder neoplasm. The aim of the present study was to evaluate the antiproliferative activity of polyphenols extracted from EVOO on bladder cancer (BCa), and to clarify the biological mechanisms that trigger cell death. Furthermore, we also evaluated the ability of low doses of extra-virgin olive oil extract (EVOOE) to modulate the in vitro activity of paclitaxel or mitomycin, two antineoplastic drugs used in the management of different types of cancer. Our results showed that EVOOE significantly inhibited the proliferation and clonogenic ability of T24 and 5637 BCa cells in a dose-dependent manner. Furthermore, cell cycle analysis after EVOOE treatment showed a marked growth arrest prior to mitosis in the G2/M phase for both cell lines, with the subsequent induction of apoptosis only in the T24 cells. Notably, simultaneous treatment of mitomycin C and EVOOE reduced the drug cytotoxicity due to inhibition of ROS production. Conversely, the co-treatment of T24 cells with paclitaxel and the polyphenol extract strongly increased the apoptotic cell death at each tested concentration compared to paclitaxel alone. Our results support the epidemiological evidence indicating that olive oil consumption exerts health benefits and may represent a starting point for the development of new anticancer strategies. PMID:27748855

  13. Selenite modulates the level of phenolics and nutrient element to alleviate the toxicity of arsenite in rice (Oryza sativa L.).

    Science.gov (United States)

    Chauhan, Reshu; Awasthi, Surabhi; Tripathi, Preeti; Mishra, Seema; Dwivedi, Sanjay; Niranjan, Abhishek; Mallick, Shekhar; Tripathi, Pratibha; Pande, Veena; Tripathi, Rudra Deo

    2017-04-01

    Arsenic (As) contamination of paddy rice is a serious threat all over the world particularly in South East Asia. Selenium (Se) plays important role in protection of plants against various abiotic stresses including heavy metals. Moreover, arsenite (AsIII) and selenite (SeIV) can be biologically antagonistic due to similar electronic configuration and sharing the common transporter for their uptake in plant. In the present study, the response of oxidative stress, phenolic compounds and nutrient elements was analyzed to investigate Se mediated As tolerance in rice seedlings during AsIII and SeIV exposure in hydroponics. Selenite (25µM) significantly decreased As accumulation in plant than As (25µM) alone treated plants. Level of oxidative stress related parameters viz., reactive oxygen species (ROS), lipid peroxidation, electrical conductivity, nitric oxide and pro-oxidant enzyme (NADPH oxidase), were in the order of As>As+Se>control>Se. Selenium ameliorated As phytotoxicity by increased level of phenolic compounds particularly gallic acid, protocatechuic acid, ferulic acid and rutin and thiol metabolism related enzymes viz., serine acetyl transferase (SAT) and cysteine synthase (CS). Selenium supplementation enhanced the uptake of nutrient elements viz., Fe, Mn, Co, Cu, Zn, Mo, and improved plant growth. The results concluded that Se addition in As contaminated environment might be an important strategy to reduce As uptake and associated phytotoxicity in rice plant by modulation of phenolic compounds and increased uptake of nutrient elements. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cellulosimicrobium funkei-like enhances the growth of Phaseolus vulgaris by modulating oxidative damage under Chromium(VI toxicity

    Directory of Open Access Journals (Sweden)

    Chinnannan Karthik

    2016-11-01

    Full Text Available Contamination of agriculture land by heavy metals is a worldwide risk that has sped up noticeably since the beginning of the industrial revolution. Hence, there arise the demands of heavy metal tolerant plant growth promoting bacterial strains for specific metal contaminated agricultural sites restoration. In this study, 36 bacterial isolates were screened out from the rhizospheric soil of Phaseolus vulgaris. Among these, two bacterial strains AR6 and AR8 were selected based on their higher Cr(VI tolerance (1200 and 1100 μg/mL, respectively and the maximum production of plant growth promoting substances. In the molecular characterization study, both the bacterial strains showed 99% homology with Cellulosimicrobium funkei KM032184. In greenhouse experiments, the exposure of Cr(VI to P.vulgaris inhibited the growth and photosynthetic pigments and increased the enzymatic and non-enzymatic antioxidant expressions. However, rhizosphere bacterial inoculations alleviated the negative effect of Cr(VI and enhanced the seed germination rate (89.54%, shoot (74.50%,root length (60%, total biomass (52.53%, chlorophyll a (15.91%, chlorophyll b (17.97%, total chlorophyll (16.58% and carotenoid content (3.59%. Moreover, bacterial inoculations stabilized and modulated the antioxidant system of P. vulgaris by reducing the accumulation of Cr in plant tissues. The present finding shows the Cr(VI tolerance and plant growth promoting properties of the rhizosphere bacterial strains which might make them eligible as biofertilizer of metal-contaminated soils.

  15. The KCNQ5 potassium channel from mouse: a broadly expressed M-current like potassium channel modulated by zinc, pH, and volume changes

    DEFF Research Database (Denmark)

    Jensen, Henrik Sindal; Callø, Kirstine; Jespersen, Thomas

    2005-01-01

    H-dependent potentiation by Zn2+ (EC50 = 21.8 microM at pH 7.4), inhibition by acidification (IC50 = 0.75 microM; pKa = 6.1), and regulation by small changes in cell volume. Furthermore, the channels are activated by the anti-convulsant drug retigabine (EC50 = 2.0 microM) and inhibited by the M-current blockers...... and hippocampus. This study shows that murine KCNQ5 channels, in addition to sharing biophysical and pharmacological characteristics with the human ortholog, are tightly regulated by physiological stimuli such as changes in extracellular Zn2+, pH, and tonicity, thus adding to the complex regulation...

  16. Modulation of microenvironmental pH for dual release and reduced in vivo gastrointestinal bleeding of aceclofenac using hydroxypropyl methylcellulose-based bilayered matrix tablet.

    Science.gov (United States)

    Kang, Won-Ho; Nguyen, Hien Van; Park, Chulhun; Choi, Youn-Woong; Lee, Beom-Jin

    2017-05-01

    This study was designed to develop a once-daily controlled-release matrix tablet of aceclofenac 200mg (AFC-CR) with dual release characteristics and to investigate the role of an alkalizer in enhancing drug solubility and reducing the occurrence of gastroduodenal mucosal lesions. Two formulation approaches were employed, namely a monolithic matrix tablet and a bilayered tablet. In vitro dissolution studies of AFC-CR tablets were carried out in simulated intestinal fluid (pH6.8 buffer). The in vivo pharmacokinetic studies and drug safety of the immediate-release reference tablet Airtal® 100mg (Daewoong Co., Korea) and the optimized AFC-CR tablet were compared in beagle dogs under fasted condition. The optimally selected AFC-CR formulation displayed the desired dual release characteristics in simulated intestinal fluid with satisfactory micromeritic properties. The swelling action of the optimal matrix tablet, which was visualized by near-infrared (NIR) chemical imaging, occurred rapidly following hydration. Incorporation of sodium carbonate (Na 2 CO 3 ) was found to enhance the release rate of the AFC-CR bilayered tablets at early stages and increase the microenvironmental pH (pH M ). A pharmacokinetic study in beagle dogs indicated a higher drug plasma concentration and a sustained-release pattern for the AFC-CR tablet compared to the Airtal® tablet. AFC-CR was also superior to Airtal® in terms of in vivo drug safety, since no beagle dog receiving AFC-CR experienced gastrointestinal bleeding. The significant enhancement of drug safety was attributed to the size reduction and the increase of pH M of drug particles by means of incorporation of the alkalizer. These findings provide a scientific rationale for developing a novel controlled-release matrix tablet with enhanced patient compliance and better pain control. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Standardized extracts of Bacopa monniera protect against MPP+- and paraquat-induced toxicity by modulating mitochondrial activities, proteasomal functions, and redox pathways.

    Science.gov (United States)

    Singh, Manjeet; Murthy, Ven; Ramassamy, Charles

    2012-01-01

    Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases and affects millions of people worldwide. Strong evidence supports the role of free radicals, oxidative stress, mitochondrial, and proteasomal dysfunctions underlying neuronal death in PD. Environmental factors, especially pesticides, represent one of the primary classes of neurotoxic agents associated with PD, and several epidemiological studies have identified the exposure of the herbicide paraquat (PQ) as a potential risk factor for the onset of PD. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of Bacopa monniera (BM) against PQ-induced and 1-methyl-4-phenyl-pyridinium iodide (MPP(+))-induced toxicities and to elucidate the mechanisms underlying this protection. Our results show that a pretreatment with the BM extract from 50 μg/ml protected the dopaminergic SK-N-SH cell line against MPP(+)- and PQ-induced toxicities in various cell survival assays. We demonstrate that BM pretreatment prevented the depletion of glutathione (GSH) besides preserving the mitochondrial membrane potential and maintaining the mitochondrial complex I activity. BM pretreatment from 10.0 μg/ml also prevented the generation of intracellular reactive oxygen species and decreased the mitochondrial superoxide level. BM treatment activated the nuclear factor erythroid 2-related factor 2 pathway by modulating the expression of Keap1, thereby upregulating the endogenous GSH synthesis. The effect of BM on the phosphorylation of Akt further strengthens its role in the promotion of cell survival. By preserving the cellular redox homeostasis and mitochondrial activities and by promoting cell survival pathways, BM extract may have therapeutic uses in various age-related neurodegenerative diseases such as PD.

  18. A retrospective comparison of outcome and toxicity of preoperative image-guided intensity-modulated radiotherapy versus conventional pelvic radiotherapy for locally advanced rectal carcinoma

    International Nuclear Information System (INIS)

    Huang, Chun-Ming; Huang, Ming-Yii; Tsai, Hsiang-Lin; Huang, Ching-Wen; Ma, Cheng-Jen; Lin, Chih-Hung; Huang, Chih-Jen; Wang, Jaw-Yuan

    2017-01-01

    The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II–III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those in the 3DCRT group (66.7% vs 43.5%, P = 0.071). The median follow-up was 53 months (range, 18–95 months) in the 3DCRT group and 43 months (range, 17–69 months) in the IG-IMRT group. Four-year overall, disease-free, and local failure–free survival rates of the IG-IMRT and 3DCRT groups were 81.6% and 67.9% (P = 0.12), 53.8% and 51.8% (P = 0.51), and 88% and 75.1% (P = 0.031), respectively. LARC patients treated with preoperative IG-IMRT achieved lower acute gastrointestinal adverse effects and a higher local control rate than those treated with 3DCRT, but there was no prominent difference in distant metastasis rate and overall survival between two treatment modalities.

  19. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

    Science.gov (United States)

    Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

    2010-11-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

  20. Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

    International Nuclear Information System (INIS)

    Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

    2010-01-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

  1. An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Shuangmei; Pan, Luqing, E-mail: panlq@ouc.edu.cn; Sun, Xiaohua

    2013-11-15

    Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

  2. Jasmonic acid Modulates the Physio-Biochemical Attributes, Antioxidant Enzyme Activity and Gene Expression in Glycine max under Nickel Toxicity

    Directory of Open Access Journals (Sweden)

    Geetika eSirhindi

    2016-05-01

    Full Text Available In present study, we evaluated the effects of Jasmonic acid (JA on physio-biochemical attributes, antioxidant enzyme activity and gene expression in soybean (Glycine max L. plants subjected to nickel (Ni stress. Ni stress decreases the shoot and root length and chlorophyll content by 37.23%, 38.31% and 39.21% respectively over the control. However, application of JA was found to improve the chlorophyll content and growth of Ni-stressed seedlings in terms of root and shoot length. Plants supplemented with Jasmonate restores the chlorophyll fluorescence, which was disturbed by Ni stress. The present study demonstrated increase in proline, glycinebetaine, total protein and total soluble sugar (TSS by 33.09%, 51.26%, 22.58% and 49.15% respectively under Ni toxicity as compared to control. Supplementation of JA to Ni stressed plants further enhanced the above parameters. Ni stress increases hydrogen peroxide (H2O2 by 68.49%, lipid peroxidation (MDA by 50.57% and NADPH oxidase by 50.92% over the control. Supplementation of JA minimizes the accumulation of H2O2, MDA and NADPH oxidase, which helps in stabilization of biomolecules. The activities of superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and ascorbate peroxidase (APX increases by 40.04%, 28.22%, 48.53% and 56.79% respectively over the control in Ni treated seedlings and further enhancement in the antioxidant activity was observed by the application of JA. Ni treated soybean seedlings showed increase in expression of Fe-SOD by 77.62%, CAT by 15.25%, POD by 58.33% and APX by 80.58% over the control. Nevertheless, application of JA further enhanced the expression of the above genes in the present study. Our results signified that Ni stress caused negative impacts on soybean seedlings, but, co-application of JA facilitate the seedlings to combat the detrimental effects of Ni through enhanced osmolytes and osmoprotectants, antioxidant enzyme activity and gene expression.

  3. An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

    International Nuclear Information System (INIS)

    Tian, Shuangmei; Pan, Luqing; Sun, Xiaohua

    2013-01-01

    Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

  4. Short-term nutritional strategies before slaughter are effective in modulating the final pH and color of broiler breast meat.

    Science.gov (United States)

    Guardia, Sarah; Lessire, Michel; Corniaux, Alain; Métayer-Coustard, Sonia; Mercerand, Frédéric; Tesseraud, Sophie; Bouvarel, Isabelle; Berri, Cécile

    2014-07-01

    The poultry meat industry is faced with various quality issues related to variations in the ultimate pH of breast meat. The aim of this study was to evaluate the possibility to control breast ultimate pH by distributing finishing diets varying in amino acid (AA) and energy content for a short period before slaughter. Experimental diets were distributed to PM3 broilers on the last 3 d before slaughter (36 d of age). They consisted of a control (C) diet (3,150 kcal/kg; 200 g/kg of CP; 10.0 g/kg of true digestible Lys) with adequate amounts of AA other than Lys, 6 diets isocaloric to the control diet including 3 Lys-deficient (8.0 g/kg) diets with an adequate (Lys-/AA), low (Lys-/AA-), or high (Lys-/AA+) amount of other essential AA calculated in relation to Lys, and 3 Lys-rich (12.0 g/kg) diets with an adequate (Lys+/AA), low (Lys+/AA-), or high (Lys+/AA+) amount of other essential AA calculated in relation to Lys, and 2 diets isoproteic to C with a high (3,300 kcal/kg, E+) or low (3,000 kcal/kg, E-) energy content. Broiler feed consumption and growth performance were slightly affected by AA and energy content during the finishing period. Feed intake (33-36 d) was lower with the Lys+/AA+ and E+, and FCR between 24 and 36 d was higher with the Lys-/AA- and E- than with the C diet. Body weight at d 36 was lower in Lys-/AA-, Lys+/AA+, and E+ than in C, whereas the breast meat yield and abdominal fatness were not affected by diet. Lower pH values were observed in broilers fed Lys-deficient diets containing a high amount of other AA (Lys-/AA+) than in broilers fed diets containing low (AA-) or adequate (AA) amounts of other AA. This study shows that it is possible to alter the pH of breast meat by changing AA profile over a short period before slaughter, with limited impact on broiler growth and carcass composition. © 2014 Poultry Science Association Inc.

  5. Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

    International Nuclear Information System (INIS)

    González-Ruiz, Víctor; González-Cuevas, Yamisley; Arunachalam, Sankaralingam; Martín, M. Antonia; Olives, Ana I.; Ribelles, Pascual; Ramos, M. Teresa; Menéndez, J. Carlos

    2012-01-01

    Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5–7.2) the neutral form of the luotonin derivatives emit in the region of 410–450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pK a ⁎ values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pK a ⁎ values and the chemical structure was found. The protonation of luotonin A was also studied by 1 H-NMR and 13 C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features. - Highlights: ► This is the first study on the fluorescence properties of luotonin A analogues. ► Fluorescence and NMR experiments

  6. Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Ruiz, Victor; Gonzalez-Cuevas, Yamisley; Arunachalam, Sankaralingam [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Martin, M. Antonia, E-mail: mantonia@farm.ucm.es [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Olives, Ana I. [S. D. Quimica Analitica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain); Ribelles, Pascual; Ramos, M. Teresa; Menendez, J. Carlos [D. Quimica Organica y Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid (Spain)

    2012-09-15

    Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5-7.2) the neutral form of the luotonin derivatives emit in the region of 410-450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pK{sub a}{sup Low-Asterisk} values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pK{sub a}{sup Low-Asterisk} values and the chemical structure was found. The protonation of luotonin A was also studied by {sup 1}H-NMR and {sup 13}C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features. - Highlights: Black-Right-Pointing-Pointer This is the first study on the fluorescence

  7. Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking

    International Nuclear Information System (INIS)

    Lee, Jae-Rin; Hahn, Hwa-Sun; Kim, Young-Hoon; Nguyen, Hong-Hoa; Yang, Jun-Mo; Kang, Jong-Sun; Hahn, Myong-Joon

    2011-01-01

    Highlights: ► APPL1 regulates the protein level of EGFR in response to EGF stimulation. ► Depletion of APPL1 accelerates the movement of EGF/EGFR from the cell surface to the perinuclear region in response to EGF. ► Knockdown of APPL1 enhances the activity of Rab5. -- Abstract: The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5.

  8. Mechanisms of Phosphine Toxicity

    Directory of Open Access Journals (Sweden)

    Nisa S. Nath

    2011-01-01

    Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

  9. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail: dtchang@stanford.edu

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0

  10. The pH Stability of Foot-and-Mouth Disease Virus Particles Is Modulated by Residues Located at the Pentameric Interface and in the N Terminus of VP1.

    Science.gov (United States)

    Caridi, Flavia; Vázquez-Calvo, Angela; Sobrino, Francisco; Martín-Acebes, Miguel A

    2015-05-01

    The picornavirus foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. The FMDV capsid is highly acid labile, and viral particles lose infectivity due to their disassembly at pH values slightly below neutrality. This acid sensitivity is related to the mechanism of viral uncoating and genome penetration from endosomes. In this study, we have analyzed the molecular basis of FMDV acid-induced disassembly by isolating and characterizing a panel of novel FMDV mutants differing in acid sensitivity. Amino acid replacements altering virion stability were preferentially distributed in two different regions of the capsid: the N terminus of VP1 and the pentameric interface. Even more, the acid labile phenotype induced by a mutation located at the pentameric interface in VP3 could be compensated by introduction of an amino acid substitution in the N terminus of VP1. These results indicate that the acid sensitivity of FMDV can be considered a multifactorial trait and that virion stability is the fine-tuned product of the interaction between residues from different capsid proteins, in particular those located within the N terminus of VP1 or close to the pentameric interface. The viral capsid protects the viral genome from environmental factors and contributes to virus dissemination and infection. Thus, understanding of the molecular mechanisms that modulate capsid stability is of interest for the basic knowledge of the biology of viruses and as a tool to improve the stability of conventional vaccines based on inactivated virions or empty capsids. Using foot-and-mouth disease virus (FMDV), which displays a capsid with extreme acid sensitivity, we have performed a genetic study to identify the molecular determinants involved in capsid stability. A panel of FMDV mutants with differential sensitivity to acidic pH was generated and characterized, and the results showed that two different regions of FMDV

  11. Toxic Hazards Research Unit Annual Report: 1986

    Science.gov (United States)

    1987-04-01

    mediated hemolysis by mercapto compounds. Journal of Applied Toxicology, Volume 6, Number 5, pages 336-370, 1986. Hydrophobic tributyltin ( TBT ...7 ~OF~ AAMRL-TR-87-020 NMRI-87-2 ’~LRES 4 Iq 1986 TOXIC HAZARDS RESEARCH UNIT ANNUAL REPORT WILLIAM E. HOUSTON, Ph.D. RAYMOND S. KUTZMAN, Ph.D...and is approved for publication. FOR THE COMMANDElRi BRUCE 0. STUART, Ph.D. Director, Toxic Hazards Division Harry G. Armstrong Aerospace Medical

  12. SU-D-204-03: Comparison of Patient Positioning Methods Through Modeling of Acute Rectal Toxicity in Intensity Modulated Radiation Therapy for Prostate Cancer. Does Quality of Data Matter More Than the Quantity?

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X; Fatyga, M; Vora, S; Wong, W; Schild, S; Schild, M [Mayo Clinic Arizona, Phoenix, AZ (United States); Herman, M [Mayo Clinic, Rochester, MN (United States); Li, J; Wu, T [Arizona State University, Tempe, AZ (United States)

    2016-06-15

    Purpose: To determine if differences in patient positioning methods have an impact on the incidence and modeling of grade >=2 acute rectal toxicity in prostate cancer patients who were treated with Intensity Modulated Radiation Therapy (IMRT). Methods: We compared two databases of patients treated with radiation therapy for prostate cancer: a database of 79 patients who were treated with 7 field IMRT and daily image guided positioning based on implanted gold markers (IGRTdb), and a database of 302 patients who were treated with 5 field IMRT and daily positioning using a trans-abdominal ultrasound system (USdb). Complete planning dosimetry was available for IGRTdb patients while limited planning dosimetry, recorded at the time of planning, was available for USdb patients. We fit Lyman-Kutcher-Burman (LKB) model to IGRTdb only, and Univariate Logistic Regression (ULR) NTCP model to both databases. We perform Receiver Operating Characteristics analysis to determine the predictive power of NTCP models. Results: The incidence of grade >= 2 acute rectal toxicity in IGRTdb was 20%, while the incidence in USdb was 54%. Fits of both LKB and ULR models yielded predictive NTCP models for IGRTdb patients with Area Under the Curve (AUC) in the 0.63 – 0.67 range. Extrapolation of the ULR model from IGRTdb to planning dosimetry in USdb predicts that the incidence of acute rectal toxicity in USdb should not exceed 40%. Fits of the ULR model to the USdb do not yield predictive NTCP models and their AUC is consistent with AUC = 0.5. Conclusion: Accuracy of a patient positioning system affects clinically observed toxicity rates and the quality of NTCP models that can be derived from toxicity data. Poor correlation between planned and clinically delivered dosimetry may lead to erroneous or poorly performing NTCP models, even if the number of patients in a database is large.

  13. PhEDEx Data Service

    International Nuclear Information System (INIS)

    Egeland, Ricky; Wildish, Tony; Huang, Chih-Hao

    2010-01-01

    The PhEDEx Data Service provides access to information from the central PhEDEx database, as well as certificate-authenticated managerial operations such as requesting the transfer or deletion of data. The Data Service is integrated with the 'SiteDB' service for fine-grained access control, providing a safe and secure environment for operations. A plug-in architecture allows server-side modules to be developed rapidly and easily by anyone familiar with the schema, and can automatically return the data in a variety of formats for use by different client technologies. Using HTTP access via the Data Service instead of direct database connections makes it possible to build monitoring web-pages with complex drill-down operations, suitable for debugging or presentation from many aspects. This will form the basis of the new PhEDEx website in the near future, as well as providing access to PhEDEx information and certificate-authenticated services for other CMS dataflow and workflow management tools such as CRAB, WMCore, DBS and the dashboard. A PhEDEx command-line client tool provides one-stop access to all the functions of the PhEDEx Data Service interactively, for use in simple scripts that do not access the service directly. The client tool provides certificate-authenticated access to managerial functions, so all the functions of the PhEDEx Data Service are available to it. The tool can be expanded by plug-ins which can combine or extend the client-side manipulation of data from the Data Service, providing a powerful environment for manipulating data within PhEDEx.

  14. The toxicity of zinc oxide nanoparticles to Lemna minor (L.) is predominantly caused by dissolved Zn.

    Science.gov (United States)

    Chen, Xiaolin; O'Halloran, John; Jansen, Marcel A K

    2016-05-01

    Nano-ZnO particles have been reported to be toxic to many aquatic organisms, although it is debated whether this is caused by nanoparticles per sé, or rather dissolved Zn. This study investigated the role of dissolved Zn in nano-ZnO toxicity to Lemna minor. The technical approach was based on modulating nano-ZnO dissolution by either modifying the pH of the growth medium and/or surface coating of nano-ZnO, and measuring resulting impacts on L. minor growth and physiology. Results show rapid and total dissolution of nano-ZnO in the medium (pH 4.5). Quantitatively similar toxic effects were found when L. minor was exposed to nano-ZnO or the "dissolved Zn equivalent of dissolved nano-ZnO". The conclusion that nano-ZnO toxicity is primarily caused by dissolved Zn was further supported by the observation that phytotoxicity was absent on medium with higher pH-values (>7), where dissolution of nano-ZnO almost ceased. Similarly, the reduced toxicity of coated nano-ZnO, which displays a slower Zn dissolution, is also consistent with a major role for dissolved Zn in nano-ZnO toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Ph3CCOOSnPh3.Ph3PO AND Ph3CCOOSnPh3.Ph3AsO: SYNTHESIS AND INFRARED STUDY

    Directory of Open Access Journals (Sweden)

    ABDOU MBAYE

    2014-08-01

    Full Text Available The mixture of ethanolic solutions of Ph3CCOOSnPh3 and Ph3PO or Ph3AsO gives Ph3CCOOSnPh3.Ph3PO and Ph3CCOOSnPh3.Ph3AsO adducts which have been characterized by infrared spectroscopy. A discrete structure is suggested for both, the environment around the tin centre being trigonal bipyramidal, the triphenylacetate anion behaving as a mondentate ligand.

  16. Introducing Toxics

    OpenAIRE

    David C. Bellinger

    2013-01-01

    With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present ...

  17. Melatonin and resveratrol reverse the toxic effect of high boron (B) and modulate biochemical parameters in pepper plants (Capsicum annuum L.).

    Science.gov (United States)

    Sarafi, Eleana; Tsouvaltzis, Pavlos; Chatzissavvidis, Christos; Siomos, Anastasios; Therios, Ioannis

    2017-03-01

    The objectives of this research were to test a possible involvement of melatonin (MEL) and resveratrol (RES) in restoring growth and to control boron (B) toxicity in peppers. The plants were subjected to four different nutrient solution treatments as following: 1) half-strength Hoagland's nutrient solution (Control), 2) half-strength Hoagland's nutrient solution+100 μM B (100 μMB), 3) half-strength Hoagland's nutrient solution+100 μM boron+100 μMresveratrol (100 μMRES), and 4) half-strength Hoagland's nutrient solution+100 μM B+1 μMmelatonin (1 μM MEL). Pepper plants subjected to B excess (100 μM) for 68 days (d) exhibited visible B toxicity symptoms, reduced rate of photosynthesis (Pn) and reduced dry weight (DW), while their leaf and fruit had the greatest increase of B concentration. The reduction of photosynthesis was restored, the reduction of DW was prevented, while the B leaf and fruit accumulation was moderated with the application of both 100 μMresveratrol (RES) and 1 μMmelatonin (MEL). Moreover, plants exposed to MEL and/or RES displayed no visible B toxicity symptoms. The present study revealed a novel role of MEL and/or RES in the adaptation of pepper plants to B excess based on plant growth, physiological and biochemical criteria. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Multifactorial Biological Modulation of Warm Ischemia Reperfusion Injury in Liver Transplantation From Non-Heart-Beating Donors Eliminates Primary Nonfunction and Reduces Bile Salt Toxicity

    NARCIS (Netherlands)

    Monbaliu, Diethard; Vekemans, Katrien; Hoekstra, Harm; Vaahtera, Lauri; Libbrecht, Louis; Derveaux, Katelijne; Parkkinen, Jaakko; Liu, Qiang; Heedfeld, Veerle; Wylin, Tine; Deckx, Hugo; Zeegers, Marcel; Balligand, Erika; Buurman, Wim; van Pelt, Jos; Porte, Robert J.; Pirenne, Jacques

    Objective: To design a multifactorial biological modulation approach targeting ischemia reperfusion injury to augment viability of porcine liver grafts from non-heart-beating donors (NHBD). Background Data: Liver Transplantation (LTx) from NHBD is associated with an increased risk of primary

  19. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    NARCIS (Netherlands)

    Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; van der Heide, Uulke A.; van Herk, Marcel; Heemsbergen, Wilma D.

    2015-01-01

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions

  20. Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

    2014-11-15

    Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

  1. Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

    International Nuclear Information System (INIS)

    Kachnic, Lisa A.; Tsai, Henry K.; Coen, John J.; Blaszkowsky, Lawrence S.; Hartshorn, Kevan; Kwak, Eunice L.; Willins, John D.; Ryan, David P.; Hong, Theodore S.

    2012-01-01

    Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs ≤3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6–43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2–24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.

  2. Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org [Department of Radiation Oncology, Boston Medical Center, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Tsai, Henry K. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA (United States); Coen, John J. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Blaszkowsky, Lawrence S. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Hartshorn, Kevan [Department of Medicine, Boston Medical Center, Boston, MA (United States); Kwak, Eunice L. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Willins, John D. [Department of Radiation Oncology, Boston Medical Center, Boston, MA (United States); Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Ryan, David P. [Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Hong, Theodore S. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2012-01-01

    Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to the anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs {<=}3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.

  3. An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

    NARCIS (Netherlands)

    Schutte, M.E.; Freidig, A.P.; Sandt, J.J.M. van de; Alink, G.M.; Rietjens, I.M.C.M.; Groten, J.P.

    2006-01-01

    The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated

  4. Identification of causes of oil sands coke leachate toxicity

    International Nuclear Information System (INIS)

    Puttaswamy, N.; Liber, K.

    2010-01-01

    The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

  5. Impact of post operative intensity modulated radiotherapy on acute gastro-intestinal toxicity for patients with endometrial cancer: Results of the phase II RTCMIENDOMETRE French multicentre trial

    International Nuclear Information System (INIS)

    Barillot, Isabelle; Tavernier, Elsa; Peignaux, Karine; Williaume, Danièle; Nickers, Philippe; Leblanc-Onfroy, Magali; Lerouge, Delphine

    2014-01-01

    Purpose/objective: Whole “conventional” pelvic irradiation (up to 45–50 Gy) following hysterectomy is associated with a high rate of adverse gastro-intestinal (GI) adverse events, of which around 60% correspond to acute grade 2 toxicity. The phase II RTCMIENDOMETRE trial was designed to test the hypothesis that IMRT could reduce the incidence of grade 2 or more acute GI toxicity to less than 30% in patients irradiated post-operatively for an endometrial cancer. Materials/methods: Patients with post-operative stage Ib G3, Ic or II endometrial carcinomas with no history of chronic inflammatory bowel disease were eligible. Guidelines for volume delineation and dose prescription were detailed in the protocol. The investigators were advised to use a web-based atlas developed for the RTOG 0418 study. The dose of the vaginal and nodal PTV was 45 Gy in 25 fractions. To assess the ability of the participating centres to comply with the protocol guidelines, they were requested to complete a dummy run procedure before inclusion of their 1st patient. GI and genito-urinary (GU) toxicity were graded according to the CTCAE V 3.0 classification and were prospectively recorded every week during irradiation, as well as at time of brachytherapy insertions and during the follow-up visit at week 15 (W15). Special attention was given to note any changes to the grade of adverse events between W5 and W15. Results: From May 2008 to April 2010, 49 patients from 6 centres were recruited for the trial. One patient could not be treated, one patient died of vascular stroke at W3 without toxicity, and 1 patient refused to be followed-up after treatment. Thus, 46 cases were available for analysis at W15. The distribution by stage was as follows: Ib 16.3%, Ic 64.2%, II 20.4%. Thirty six patients (75%) received an additional vaginal vault boost of 6–10 Gy delivered by HDR brachytherapy in 1 or 2 fractions. Among the 47 patients who completed IMRT, 27% (95% CI 14.5–39.7%) developed at

  6. The technical feasibility of an image-guided intensity-modulated radiotherapy (IG-IMRT) to perform a hypofractionated schedule in terms of toxicity and local control for patients with locally advanced or recurrent pancreatic cancer

    International Nuclear Information System (INIS)

    Son, Seok Hyun; Song, Jin Ho; Choi, Byung Ock; Kang, Young-nam; Lee, Myung Ah; Kang, Ki Mun; Jang, Hong Seok

    2012-01-01

    The purpose of this study was to evaluate the technical feasibility of an image-guided intensity modulated radiotherapy (IG-IMRT) using involved-field technique to perform a hypofractionated schedule for patients with locally advanced or recurrent pancreatic cancer. From May 2009 to November 2011, 12 patients with locally advanced or locally recurrent pancreatic cancer received hypofractionated CCRT using TomoTherapy Hi-Art with concurrent and sequential chemotherapy at Seoul St. Mary’s Hospital, the Catholic University of Korea. The total dose delivered was 45 Gy in 15 fractions or 50 Gy in 20 fractions. The target volume did not include the uninvolved regional lymph nodes. Treatment planning and delivery were performed using the IG-IMRT technique. The follow-up duration was a median of 31.1 months (range: 5.7-36.3 months). Grade 2 or worse acute toxicities developed in 7 patients (58%). Grade 3 or worse gastrointestinal and hematologic toxicity occurred in 0% and 17% of patients, respectively. In the response evaluation, the rates of partial response and stable disease were 58% and 42%, respectively. The rate of local failure was 8% and no regional failure was observed. Distant failure was the main cause of treatment failure. The progression-free survival and overall survival durations were 7.6 and 12.1 months, respectively. The involved-field technique and IG-IMRT delivered via a hypofractionated schedule are feasible for patients with locally advanced or recurrent pancreatic cancer

  7. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors to h...

  8. Transperineal Injection of Hyaluronic Acid in Anterior Perirectal Fat to Decrease Rectal Toxicity From Radiation Delivered With Intensity Modulated Brachytherapy or EBRT for Prostate Cancer Patients

    International Nuclear Information System (INIS)

    Prada, Pedro J.; Fernandez, Jose; Martinez, Alvaro A.; Rua, Angeles de la; Gonzalez, Jose M.; Fernandez, Jose M.; Juan, German

    2007-01-01

    Purpose: Rectal toxicity remains a serious complication affecting quality of life for prostate cancer patients treated with radiotherapy. We began an investigational trial injecting hyaluronic acid (HA) in the perirectal fat to increase the distance between the prostate and the anterior rectal wall. This is the first report using HA injection in oncology. Methods and Materials: This is a trial of external beam radiation therapy with HDR brachytherapy boosts in prostate cancer. During the two high-dose-rate (HDR) fractions, thermoluminescent dosimeter dosimeters were placed in the urethra and in the rectum. Before the second HDR fraction, 3-7 mL (mean, 6 mL) of HA was injected under transrectal ultrasound guidance in the perirectal fat to systematically create a 1.5-cm space. Urethral and rectal HDR doses were calculated and measured. Computed tomography and magnetic resonance imaging were used to assess the stability of the new space. Results: Twenty-seven patients enrolled in the study. No toxicity was produced from the HA or the injection. In follow-up computed tomography and magnetic resonance imaging, the HA injection did not migrate or change in mass/shape for close to 1 year. The mean distance between rectum and prostate was 2.0 cm along the entire length of the prostate. The median measured rectal dose, when normalized to the median urethral dose, demonstrated a decrease in dose from 47.1% to 39.2% (p < 0.001) with or without injection. For an HDR boost dose of 1150 cGy, the rectum mean Dmax reduction was from 708 cGy to 507 cGy, p < 0.001, and the rectum mean Dmean drop was from 608 to 442 cGy, p < 0.001 post-HA injection. Conclusion: The new 2-cm distance derived from the HA injection significantly decreased rectal dose in HDR brachytherapy. Because of the several-month duration of stability, the same distance was maintained during the course of external beam radiation therapy

  9. Development of pyridine-containing macrocyclic copper(II) complexes: potential role in the redox modulation of oxaliplatin toxicity in human breast cells.

    Science.gov (United States)

    Fernandes, Ana S; Costa, Judite; Gaspar, Jorge; Rueff, José; Cabral, M Fátima; Cipriano, Madalena; Castro, Matilde; Oliveira, Nuno G

    2012-09-01

    The unique redox and catalytic chemistry of Cu has justified the development of novel Cu complexes for different therapeutic uses including cancer therapy. In this work, four pyridine-containing aza-macrocyclic copper(II) complexes were prepared (CuL1-CuL4) varying in ring size and/or substituents and their superoxide scavenging activity evaluated. CuL3, the most active superoxide scavenger, was further studied as a modulator of the cytotoxicity of oxaliplatin in epithelial breast MCF10A cells and in MCF7 breast cancer cells. Our results show that CuL3 enhances the therapeutic window of oxaliplatin, by both protecting non-tumour cells and increasing its cytotoxic effect in breast carcinoma cells. CuL3 is thus a promising complex to be further studied and to be used as a lead compound for the optimization of novel chemotherapy sensitizers.

  10. An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

    International Nuclear Information System (INIS)

    Schutte, Maaike E.; Freidig, Andreas P.; Sandt, Johannes J.M. van de; Alink, Gerrit M.; Rietjens, Ivonne M.C.M.; Groten, John P.

    2006-01-01

    The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using the in silico model for flavone, kaempferol and chrysoeriol, the apparent Ki value for inhibition of the active transport to the apical side was estimated to be below 53 μM and for morin, robinetin and taxifolin between 164 and 268 μM. For myricetin, luteolin, naringenin and quercetin, the apparent Ki values were determined more accurately and amounted to 37.3, 12.2, 11.7 and 5.6 μM respectively. Additional experiments revealed that the apical to basolateral PhIP transport was also increased in the presence of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as those of the flavonoids. This observation together with the fact that flavonoids are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of these apical membrane transporters is involved in the flavonoid-mediated increased apical to basolateral PhIP transport. Based on the apparent Ki values obtained, it is concluded that the flavonols, at the levels present in the regular Western diet, are capable of stimulating the transport of PhIP through Caco-2 monolayers from the apical to the basolateral compartment. This points to flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a possible adverse effect of these supposed beneficial food ingredients

  11. Introducing Toxics

    Directory of Open Access Journals (Sweden)

    David C. Bellinger

    2013-04-01

    Full Text Available With this inaugural issue, Toxics begins its life as a peer-reviewed, open access journal focusing on all aspects of toxic chemicals. We are interested in publishing papers that present a wide range of perspectives on toxicants and naturally occurring toxins, including exposure, biomarkers, kinetics, biological effects, fate and transport, treatment, and remediation. Toxics differs from many other journals in the absence of a page or word limit on contributions, permitting authors to present their work in as much detail as they wish. Toxics will publish original research papers, conventional reviews, meta-analyses, short communications, theoretical papers, case reports, commentaries and policy perspectives, and book reviews (Book reviews will be solicited and should not be submitted without invitation. Toxins and toxicants concern individuals from a wide range of disciplines, and Toxics is interested in receiving papers that represent the full range of approaches applied to their study, including in vitro studies, studies that use experimental animal or non-animal models, studies of humans or other biological populations, and mathematical modeling. We are excited to get underway and look forward to working with authors in the scientific and medical communities and providing them with a novel venue for sharing their work. [...

  12. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Jennifer L., E-mail: peterson.jennifer2@mayo.edu [Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL (United States); Buskirk, Steven J. [Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL (United States); Heckman, Michael G.; Diehl, Nancy N. [Section of Biostatistics, Mayo Clinic Florida, Jacksonville, FL (United States); Bernard, Johnny R. [Section of Biostatistics, Mayo Clinic Florida, Jacksonville, FL (United States); Department of Radiation Oncology, Southern Ohio Medical Center, Portsmouth, OH (United States); Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J. [Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL (United States)

    2014-04-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm{sup 3} of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications.

  13. Image-guided intensity-modulated radiotherapy for prostate cancer: Dose constraints for the anterior rectal wall to minimize rectal toxicity

    International Nuclear Information System (INIS)

    Peterson, Jennifer L.; Buskirk, Steven J.; Heckman, Michael G.; Diehl, Nancy N.; Bernard, Johnny R.; Tzou, Katherine S.; Casale, Henry E.; Bellefontaine, Louis P.; Serago, Christopher; Kim, Siyong; Vallow, Laura A.; Daugherty, Larry C.; Ko, Stephen J.

    2014-01-01

    Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT) treatment for prostate cancer. The anterior rectal wall is at the greatest risk of injury as it lies closest to the target volume and receives the highest dose of RT. This study evaluated the absolute volume of anterior rectal wall receiving a high dose to identify potential ideal dose constraints that can minimize rectal AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate cancer who underwent image-guided intensity-modulated RT at our institution were included. AEs were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to 80 Gy in 2.5-Gy increments was determined. Multivariable Cox regression models were used to identify cut points in these volumes that led to an increased risk of early and late rectal AEs. Early AEs occurred in most patients (88%); however, relatively few of them (13%) were grade ≥2. At 5 years, the cumulative incidence of late rectal AEs was 37%, with only 5% being grade ≥2. For almost all RT doses, we identified a threshold of irradiated absolute volume of anterior rectal wall above which there was at least a trend toward a significantly higher rate of AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45 cm 3 of anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5 Gy, respectively, had a significantly increased risk of late AEs (relative risks [RR]: 2.18 to 2.72; p ≤ 0.041) and of grade ≥ 2 early AEs (RR: 6.36 to 6.48; p = 0.004). Our study provides evidence that definitive image-guided intensity-modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also identifies dose thresholds for the absolute volume of anterior rectal wall above which patients are at greater risk of early and late complications

  14. Antimony Toxicity

    Directory of Open Access Journals (Sweden)

    Shyam Sundar

    2010-12-01

    Full Text Available Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically.

  15. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    But-Hadzic, Jasna, E-mail: jbut@onko-i.si [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Anderluh, Franc [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Brecelj, Erik; Edhemovic, Ibrahim [Division of Surgery, Institute of Oncology, Ljubljana (Slovenia); Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Kozelj, Miran; Krebs, Bojan [Division of Surgery, University Medical Centre Maribor, Maribor (Slovenia); Oblak, Irena [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Omejc, Mirko [Division of Surgery, University Medical Centre Lubljana, Ljubljana (Slovenia); Vogrin, Andrej [Division of Diagnostics, Institute of Oncology, Ljubljana (Slovenia); Velenik, Vaneja [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia)

    2016-12-01

    Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

  16. Antimony Toxicity

    OpenAIRE

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The...

  17. Oxygen toxicity

    Directory of Open Access Journals (Sweden)

    C. A. van der Westhuizen

    1990-07-01

    Full Text Available Oxygen has been discovered about 200 years ago. Since then the vital physiological involvement of oxygen in various biologi­cal processes, mainly energy production, has been established. However, in the body molecular oxygen can be converted to toxic oxygen metabolites such as superoxide anion, hydrogen peroxide, the hydroxyl radical and singlet oxygen. These toxic metabolites are produced mainly in the mitochondria, plasma membranes and endoplasmic reticulum.

  18. Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

    International Nuclear Information System (INIS)

    Olsen, Jeffrey R.; Moughan, Jennifer; Myerson, Robert; Abitbol, Andre; Doncals, Desiree E.; Johnson, Douglas; Schefter, Tracey E.; Chen, Yuhchyau; Fisher, Barbara; Michalski, Jeff; Narayan, Samir; Chang, Albert; Crane, Christopher H.; Kachnic, Lisa

    2017-01-01

    Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P 4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.

  19. Hematologic Toxicity in Patients Treated With Postprostatectomy Whole-Pelvis Irradiation With Different Intensity Modulated Radiation Therapy Techniques Is Not Negligible and Is Prolonged: Preliminary Results of a Longitudinal, Observational Study

    Energy Technology Data Exchange (ETDEWEB)

    Cozzarini, Cesare, E-mail: cozzarini.cesare@hsr.it [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy); Chiorda, Barbara Noris [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy); Sini, Carla; Fiorino, Claudio [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Briganti, Alberto; Montorsi, Francesco [Department of Urology, Vita-Salute University, Milan (Italy); Di Muzio, Nadia [Department of Radiotherapy, San Raffaele Scientific Institute, Milan (Italy)

    2016-06-01

    Purpose: To address the thus-far poorly investigated severity and duration of hematologic toxicity from whole-pelvis radiation therapy (WPRT) in a cohort of chemo-naïve patients treated with postprostatectomy radiation therapy including WPRT with different intensity modulated radiation therapy (IMRT) techniques, doses, and fractionations. Methods and Materials: This analysis pertains to 125 patients (70 from a pilot study and 55 from an observational protocol) for whom 1 baseline and at least 3 subsequent blood samples (median 6), obtained at irradiation midpoint and end, and thereafter at 3, 6, and 12 months, were available. Patients were treated with adjuvant (n=73) or salvage intent; static-field IMRT (n=19); volumetric modulated arc therapy (n=60) or helical Tomotherapy (n=46); and conventional (n=39) or moderately hypofractionated (median 2.35 Gy per fraction, n=86) regimens. The median 2-Gy equivalent dose (EQD2) to the prostatic bed was 70.4 Gy with a lymph-nodal planning target volume of 50.2 Gy. Clinical and dosimetric data were collected. Results: Both leukopenia and thrombocytopenia were significant (median nadir count 65% and 67% of baseline, respectively), with leukopenia also persisting (1-year median count 75% of baseline). Lymphopenia was the major contributor to the severity and 1-year persistence of leukopenia; all patients developed acute grade ≥1 lymphopenia (61% and 26% grade 2 and ≥3, respectively), whereas 1-year grade ≥2 lymphopenia was still present in 16%. In addition to an independent predictive role of corresponding baseline values, multivariable analyses highlighted that higher EQD2 doses to lymph nodal planning target volume increased risk of acute neutropenia and hypofractionation for acute thrombocytopenia. Of note, patients of older age were at higher risk for acute grade 2 lymphopenia, and interestingly, increased risk of grade >2 lymphopenia for those who smoked at least one year. No role for different IMRT techniques

  20. Hematologic Toxicity in Patients Treated With Postprostatectomy Whole-Pelvis Irradiation With Different Intensity Modulated Radiation Therapy Techniques Is Not Negligible and Is Prolonged: Preliminary Results of a Longitudinal, Observational Study

    International Nuclear Information System (INIS)

    Cozzarini, Cesare; Chiorda, Barbara Noris; Sini, Carla; Fiorino, Claudio; Briganti, Alberto; Montorsi, Francesco; Di Muzio, Nadia

    2016-01-01

    Purpose: To address the thus-far poorly investigated severity and duration of hematologic toxicity from whole-pelvis radiation therapy (WPRT) in a cohort of chemo-naïve patients treated with postprostatectomy radiation therapy including WPRT with different intensity modulated radiation therapy (IMRT) techniques, doses, and fractionations. Methods and Materials: This analysis pertains to 125 patients (70 from a pilot study and 55 from an observational protocol) for whom 1 baseline and at least 3 subsequent blood samples (median 6), obtained at irradiation midpoint and end, and thereafter at 3, 6, and 12 months, were available. Patients were treated with adjuvant (n=73) or salvage intent; static-field IMRT (n=19); volumetric modulated arc therapy (n=60) or helical Tomotherapy (n=46); and conventional (n=39) or moderately hypofractionated (median 2.35 Gy per fraction, n=86) regimens. The median 2-Gy equivalent dose (EQD2) to the prostatic bed was 70.4 Gy with a lymph-nodal planning target volume of 50.2 Gy. Clinical and dosimetric data were collected. Results: Both leukopenia and thrombocytopenia were significant (median nadir count 65% and 67% of baseline, respectively), with leukopenia also persisting (1-year median count 75% of baseline). Lymphopenia was the major contributor to the severity and 1-year persistence of leukopenia; all patients developed acute grade ≥1 lymphopenia (61% and 26% grade 2 and ≥3, respectively), whereas 1-year grade ≥2 lymphopenia was still present in 16%. In addition to an independent predictive role of corresponding baseline values, multivariable analyses highlighted that higher EQD2 doses to lymph nodal planning target volume increased risk of acute neutropenia and hypofractionation for acute thrombocytopenia. Of note, patients of older age were at higher risk for acute grade 2 lymphopenia, and interestingly, increased risk of grade >2 lymphopenia for those who smoked at least one year. No role for different IMRT techniques

  1. Acidic pH and short-chain fatty acids activate Na+ transport but differentially modulate expression of Na+/H+ exchanger isoforms 1, 2, and 3 in omasal epithelium.

    Science.gov (United States)

    Lu, Zhongyan; Yao, Lei; Jiang, Zhengqian; Aschenbach, Jörg R; Martens, Holger; Shen, Zanming

    2016-01-01

    Low sodium content in feed and large amounts of salivary sodium secretion are essential requirements to efficient sodium reabsorption in the dairy cow. It is already known that Na(+)/H(+) exchange (NHE) of the ruminal epithelium plays a key role in Na(+) absorption, and its function is influenced by the presence of short-chain fatty acids (SCFA) and mucosal pH. By contrast, the functional role and regulation of NHE in omasal epithelium have not been completely understood. In the present study, we used model studies in small ruminants (sheep and goats) to investigate NHE-mediated Na(+) transport and the effects of pH and SCFA on NHE activity in omasal epithelium and on the expression of NHE isoform in omasal epithelial cells. Conventional Ussing chamber technique, primary cell culture, quantitative PCR, and Western blot were used. In native omasal epithelium of sheep, the Na(+) transport was electroneutral, and it was inhibited by the specific NHE3 inhibitor 3-[2-(3-guanidino-2-methyl-3-oxo-propenyl)-5-methyl-phenyl]-N-isopropylidene-2-methyl-acrylamide dihydrochloride, which decreased mucosal-to-serosal, serosal-to-mucosal, and net flux rates of Na(+) by 80% each. The application of low mucosal pH (6.4 or 5.8) in the presence of SCFA activated the Na(+) transport across omasal epithelium of sheep compared with that at pH 7.4. In cultured omasal epithelial cells of goats, mRNA and protein of NHE1, NHE2, and NHE3 were detected. The application of SCFA increased NHE1 mRNA and protein expression, which was most prominent when the culture medium pH decreased from 7.4 to 6.8. At variance, the mRNA and protein expression of NHE2 and NHE3 were decreased with low pH and SCFA, which was contrary to the published data from ruminal epithelial studies. In conclusion, this paper shows that (1) NHE1, NHE2, and NHE3 are expressed in omasal epithelium; (2) NHE3 mediates the major portion of transepithelial Na(+) transport in omasal epithelium; and (3) SCFA and acidic pH acutely

  2. Predictors of Radiation Therapy–Related Gastrointestinal Toxicity From Anal Cancer Dose-Painted Intensity Modulated Radiation Therapy: Secondary Analysis of NRG Oncology RTOG 0529

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Jeffrey R., E-mail: Jeffrey.R.Olsen@ucdenver.edu [University of Colorado Denver, Aurora, Colorado (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Myerson, Robert [Washington University, St. Louis, Missouri (United States); Abitbol, Andre [Baptist Hospital of Miami, Miami, Florida (United States); Doncals, Desiree E. [Summa Akron City Hospital accruals for Akron City Hospital, Akron, Ohio (United States); Johnson, Douglas [Florida Radiation Oncology Group–Baptist Regional, Jacksonville, Florida (United States); Schefter, Tracey E. [University of Colorado Denver, Aurora, Colorado (United States); Chen, Yuhchyau [University of Rochester Medical Center, Rochester, New York (United States); Fisher, Barbara [London Regional Cancer Program—University of Western Ontario, London, Ontario (Canada); Michalski, Jeff [Washington University, St. Louis, Missouri (United States); Narayan, Samir [Michigan Cancer Research Consortium CCOP, Ann Arbor, Michigan (United States); Chang, Albert [University of California San Francisco, San Francisco, California (United States); Crane, Christopher H. [Memorial Sloan Kettering Cancer Center, New York, New York (United States); Kachnic, Lisa [Vanderbilt University Medical Center, Nashville, Tennessee (United States)

    2017-06-01

    Purpose: NRG Oncology RTOG 0529 assessed the feasibility of dose-painted intensity modulated radiation therapy (DP-IMRT) to reduce the acute morbidity of chemoradiation with 5-fluorouracil (5FU) and mitomycin-C (MMC) for T2-4N0-3M0 anal cancer. This secondary analysis was performed to identify patient and treatment factors associated with acute and late gastrointestinal (GI) adverse events (AEs). Methods and Materials: NRG Oncology RTOG 0529 treatment plans were reviewed to extract dose-volume data for tightly contoured small bowel, loosely contoured anterior pelvic contents (APC), and uninvolved colon outside the target volume (UC). Univariate logistic regression was performed to evaluate association between volumes of each structure receiving doses ≥5 to 60 Gy (V5-V60) in 5-Gy increments between patients with and without grade ≥2 acute and late GI AEs, and grade ≥3 acute GI AEs. Additional patient and treatment factors were evaluated in multivariate logistic regression (acute AEs) or Cox proportional hazards models (late AEs). Results: Among 52 evaluable patients, grade ≥2 acute, grade ≥2 late, and grade ≥3 acute GI AEs were observed in 35, 17, and 10 patients, respectively. Trends (P<.05) toward statistically significant associations were observed between grade ≥2 acute GI AEs and small bowel dose (V20-V40), grade ≥2 late GI AEs and APC dose (V60), grade ≥3 acute GI AEs and APC dose (V5-V25), increasing age, tumor size >4 cm, and worse Zubrod performance status. Small bowel volumes of 186.0 cc, 155.0 cc, 41.0 cc, and 30.4 cc receiving doses greater than 25, 30, 35, and 40 Gy, respectively, correlated with increased risk of acute grade ≥2 GI AEs. Conclusions: Acute and late GI AEs from 5FU/MMC chemoradiation using DP-IMRT correlate with radiation dose to the small bowel and APC. Such associations will be incorporated in the dose-volume normal tissue constraint design for future NRG oncology anal cancer studies.

  3. Radionuclide toxicity

    International Nuclear Information System (INIS)

    Galle, P.

    1982-01-01

    The aim of this symposium was to review the radionuclide toxicity problems. Five topics were discussed: (1) natural and artificial radionuclides (origin, presence or emission in the environment, human irradiation); (2) environmental behaviour of radionuclides and transfer to man; (3) metabolism and toxicity of radionuclides (radioiodine, strontium, rare gas released from nuclear power plants, ruthenium-activation metals, rare earths, tritium, carbon 14, plutonium, americium, curium and einsteinium, neptunium, californium, uranium) cancerogenous effects of radon 222 and of its danghter products; (4) comparison of the hazards of various types of energy; (5) human epidemiology of radionuclide toxicity (bone cancer induction by radium, lung cancer induction by radon daughter products, liver cancer and leukaemia following the use of Thorotrast, thyroid cancer; other site of cancer induction by radionuclides) [fr

  4. PH og modernismen

    DEFF Research Database (Denmark)

    Ahnfeldt-Mollerup, Merete

    2012-01-01

    Artiklen kaster et kritisk blik på Poul Henningsens samfundsanalyse og dennes sammenhæng med hans design. PH ses i en bredere national og international sammenhæng. Diskussion af designmetoder, æstetik og Bauhaus.......Artiklen kaster et kritisk blik på Poul Henningsens samfundsanalyse og dennes sammenhæng med hans design. PH ses i en bredere national og international sammenhæng. Diskussion af designmetoder, æstetik og Bauhaus....

  5. Phénomènes dépendants du spin dans des structures à un puits quantique CdMnTe à modulation de dopage de type-n

    OpenAIRE

    Teran , Francisco Jose

    2001-01-01

    The study of the electronic and magnetic properties of n-type modulation doped CdMnTe quantum well structures has allowed to investigate the sp-d exchange interaction between 2D electrons and localized magnetic moments of Mn2+ ions. Such exchange interaction realigns the electronic spin states leading to a giant Zeeman splitting which deeply modifies the optical and electronic properties of the semiconductor host. At low magnetic fields, the sp-d exchange interaction term can be successfully ...

  6. PhD on Track – designing learning for PhD students

    Directory of Open Access Journals (Sweden)

    Gunhild Austrheim

    2013-12-01

    Full Text Available Three years ago we started the project "Information Management for Knowledge Creation". The project was initiated to create online information literacy modules for PhD students. The result of our endeavours, PhD on Track, will be launched in May 2013. The initial stage of the project was mapping out the information behaviour of PhD students, as well as what services they require from the library through a literature review and a focus group study. The findings of these inquiries formed the knowledge base from which we developed our information literacy modules. Our paper will focus on the interaction between content production and user testing when creating PhD on Track. Methods: User testing has been employed throughout the production stage. We have tested navigation and organisation of the web site, content and usability. The project team have conducted expert testing. Analysis: The results from our user testing have played an important part in decisions concerning content production. Our working hypothesis was that the PhD students would want an encyclopaedic website, a place to quickly find answers. However, the user tests revealed that PhD students understood and expected the website to be learning modules. Conclusions: The PhD students in the tests agreed that a site such as this would be useful, especially to new PhD students. They also liked the design, but had some qualms with the level of information. They preferred shorter text, but with more depth. The students would likewise have preferred more practical examples, more illustrations and more discipline specific information. The current content of PhD on Track reflects the feedback from the user testing. We have retained initial ideas such as one section for reviewing and discovering research literature and one section for publishing PhD research work. In addition, we have included more practical examples to indicate efficient workflows or relevant actions in context. Illustrations

  7. Toxicity identification evaluation methods for identification of toxicants in refinery effluents

    International Nuclear Information System (INIS)

    Barten, K.A.; Mount, D.R.; Hackett, J.R.

    1993-01-01

    During the last five years, the authors have used Toxicity Identification Evaluation (TIE) methods to characterize and identify the source(s) of toxicity in effluents from dozens of municipal and industrial facilities. In most cases, specific chemicals responsible for toxicity have been identified. Although generally successful, the initial experience was that for several refinery effluents, they were able only to qualitatively characterize the presence of organic toxicants; standard toxicant identification procedures were not able to isolate specific organic chemicals. They believe that organic toxicity in these refinery effluents is caused by multiple organic compounds rather than by just a few; evidence for this includes an inability to isolate toxicity in a small number of fractions using liquid chromatography and the presence of very large numbers of compounds in isolated fractions. There is also evidence that the toxicant(s) may be ionic, in that the toxicity of whole effluent and isolated fractions often show increasing toxicity with decreasing pH. Finally, positive-pressure filtration has also reduced toxicity in some samples. In this presentation the authors summarize their experiences with refinery effluents, focusing on typical patterns they have observed and alternative procedures they have used to better understand the nature of these toxicants

  8. Plant Habitat (PH)

    Science.gov (United States)

    Onate, Bryan

    2016-01-01

    The International Space Station (ISS) will soon have a platform for conducting fundamental research of Large Plants. Plant Habitat (PH) is designed to be a fully controllable environment for high-quality plant physiological research. PH will control light quality, level, and timing, temperature, CO2, relative humidity, and irrigation, while scrubbing ethylene. Additional capabilities include leaf temperature and root zone moisture and oxygen sensing. The light cap will have red (630 nm), blue (450 nm), green (525 nm), far red (730 nm) and broad spectrum white LEDs. There will be several internal cameras (visible and IR) to monitor and record plant growth and operations.

  9. Aluminium Toxicity Targets in Plants

    Directory of Open Access Journals (Sweden)

    Sónia Silva

    2012-01-01

    Full Text Available Aluminium (Al is the third most abundant metallic element in soil but becomes available to plants only when the soil pH drops below 5.5. At those conditions, plants present several signals of Al toxicity. As reported by literature, major consequences of Al exposure are the decrease of plant production and the inhibition of root growth. The root growth inhibition may be directly/indirectly responsible for the loss of plant production. In this paper the most remarkable symptoms of Al toxicity in plants and the latest findings in this area are addressed. Root growth inhibition, ROS production, alterations on root cell wall and plasma membrane, nutrient unbalances, callose accumulation, and disturbance of cytoplasmic Ca2+ homeostasis, among other signals of Al toxicity are discussed, and, when possible, the behavior of Al-tolerant versus Al-sensitive genotypes under Al is compared.

  10. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  11. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    all chemicals and impact pathways characterizes the contribution of each factor to the total variation of 10–12 orders of magnitude in impacts per kg across all chemicals. This large variation between characterisation factors for different chemicals as well as the 3 orders of magnitude uncertainty....... As a whole, the assessment of toxicity in LCA has progressed on a very sharp learning curve during the past 20 years. This rapid progression is expected to continue in the coming years, focusing more on direct exposure of workers to chemicals during manufacturing and of consumers during product use...

  12. Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.

    Science.gov (United States)

    Callaghan, Paul S; Siriwardana, Amila; Hassett, Matthew R; Roepe, Paul D

    2016-03-31

    Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transport of chloroquine (CQ) via the transporter. During analysis of all 53 known naturally occurring PfCRT isoforms, two isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even in the absence of CQ. Additional analysis of six very recently identified PfCRT isoforms from Malaysia also showed some toxicity. In this paper the nature of this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of PfCRT transport CQ with an efficiency intermediate to that catalyzed by previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is found to perturb vacuolar physiology, suggesting a fitness cost to position 160 amino acid substitutions. These data further define the wide range of activities that exist for PfCRT isoforms found in P. falciparum isolates from around the globe.

  13. Interactive effects of pH and metals on mitochondrial functions of intertidal bivalves Crassostrea virginica and Mercenaria mercenaria

    International Nuclear Information System (INIS)

    Ivanina, Anna V.; Sokolova, Inna M.

    2013-01-01

    Highlights: •Interactive effects of trace metals Cd and Cu and pH were studied in mitochondria of clams and oysters. •Mitochondrial respiration and membrane potential of bivalves were robust to pH variation (6.6–7.8). •Elevated levels of Cd and Cu inhibited mitochondrial respiration in the pH-dependent manner but did not affect the membrane potential. •Negative effects of Cd and Cd on mitochondrial respiration were alleviated at low pH (7.0 and below). •Moderate acidosis may protect molluscan mitochondria from metal toxicity. -- Abstract: Intertidal bivalves experience broad fluctuations of environmental temperature, pH and oxygen content which could change their intracellular pH. They are also exposed to trace metals such as cadmium (Cd) and copper (Cu) that accumulate in their tissues and may negatively affect mitochondrial functions and bioenergetics. We determined the interactive effects of pH and trace metals (25 μM Cd or Cu) on mitochondrial functions (including respiration and membrane potentials in both ADP-stimulated (state 3) and resting (state 4) states) of two common marine bivalves, the hard clams (Mercenaria mercenaria) and eastern oysters (Crassostrea virginica). In the absence of the trace metals, mitochondrial functions of C. virginica and M. mercenaria were insensitive to pH in a broad physiologically relevant range (6.6–7.8). Mitochondrial respiration was generally suppressed by 25 μM Cd or Cu (with the stronger effects observed for ADP-stimulated compared to the resting respiration) while the mitochondrial membrane potential was unaffected. pH modulated the effects of Cu and Cd on mitochondrial respiration of the bivalves. In oysters, Cu suppressed ADP-stimulated mitochondrial respiration at high and low pH values (6.6 and 7.8, respectively), but had no effect in the intermediate pH range (7.0–7.4). In clams, the negative effect of Cu on ADP-stimulated respiration was only observed at extremely high pH (7.8). A decrease in pH

  14. Interactive effects of pH and metals on mitochondrial functions of intertidal bivalves Crassostrea virginica and Mercenaria mercenaria

    Energy Technology Data Exchange (ETDEWEB)

    Ivanina, Anna V.; Sokolova, Inna M., E-mail: isokolov@uncc.edu

    2013-11-15

    Highlights: •Interactive effects of trace metals Cd and Cu and pH were studied in mitochondria of clams and oysters. •Mitochondrial respiration and membrane potential of bivalves were robust to pH variation (6.6–7.8). •Elevated levels of Cd and Cu inhibited mitochondrial respiration in the pH-dependent manner but did not affect the membrane potential. •Negative effects of Cd and Cd on mitochondrial respiration were alleviated at low pH (7.0 and below). •Moderate acidosis may protect molluscan mitochondria from metal toxicity. -- Abstract: Intertidal bivalves experience broad fluctuations of environmental temperature, pH and oxygen content which could change their intracellular pH. They are also exposed to trace metals such as cadmium (Cd) and copper (Cu) that accumulate in their tissues and may negatively affect mitochondrial functions and bioenergetics. We determined the interactive effects of pH and trace metals (25 μM Cd or Cu) on mitochondrial functions (including respiration and membrane potentials in both ADP-stimulated (state 3) and resting (state 4) states) of two common marine bivalves, the hard clams (Mercenaria mercenaria) and eastern oysters (Crassostrea virginica). In the absence of the trace metals, mitochondrial functions of C. virginica and M. mercenaria were insensitive to pH in a broad physiologically relevant range (6.6–7.8). Mitochondrial respiration was generally suppressed by 25 μM Cd or Cu (with the stronger effects observed for ADP-stimulated compared to the resting respiration) while the mitochondrial membrane potential was unaffected. pH modulated the effects of Cu and Cd on mitochondrial respiration of the bivalves. In oysters, Cu suppressed ADP-stimulated mitochondrial respiration at high and low pH values (6.6 and 7.8, respectively), but had no effect in the intermediate pH range (7.0–7.4). In clams, the negative effect of Cu on ADP-stimulated respiration was only observed at extremely high pH (7.8). A decrease in pH

  15. Regulation of pH During Amelogenesis.

    Science.gov (United States)

    Lacruz, Rodrigo S; Nanci, Antonio; Kurtz, Ira; Wright, J Timothy; Paine, Michael L

    2010-02-01

    During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation.

  16. Toxicity of oils and petroleum hydrocarbons to estuarine crustaceans

    Energy Technology Data Exchange (ETDEWEB)

    Tatem, H.E. (Army Engineer Waterways Experiment Station, Vicksburg, MS); Cox, B.A.; Anderson, J.W.

    1978-04-01

    Bioassay experiments with various life stages of three estuarine shrimp and soluble petroleum hydrocarbons (PH) revealed residual Bunker C oil and refined No. 2 fuel oil to be more toxic than two crude oils tested. Larvae of Palaemonetes pugio were slightly more sensitive to the PH than adults, while young penaeid shrimp were shown to be more resistant than older, larger individuals. Shrimp exposed to PH in conjunction with temperature and salinity changes were more susceptible to the PH. Some common aromatic and diaromatic PH, including three naphthalene compounds, were utilized in bioassays. Naphthalenes were highly toxic. The toxicity of petroleum products is closely related to aromatic hydrocarbon content, especially the naphthalenes and related hydrocarbons.

  17. Sulfate Reduction at Low Ph To Remediate Acid Mine Drainage

    NARCIS (Netherlands)

    Sánchez-Andrea, I.; Sanz, J.L.; Bijmans, M.F.M.; Stams, A.J.M.

    2014-01-01

    Industrial activities and the natural oxidation of metallic sulfide-ores produce sulfate-rich waters with low pH and high heavy metals content, generally termed acid mine drainage (AMD). This is of great environmental concern as some heavy metals are highly toxic. Within a number of possibilities,

  18. PhD Dissertations

    OpenAIRE

    Redazione Reti Medievali (a cura di)

    2010-01-01

    Report of PhD Dissertations.Anna Airò La scrittura delle regole. Politica e istituzioni a Taranto nel Quattrocento, Tesi di dottorato di ricerca in Storia medievale, Università degli studi di Firenze, 2005 Pasquale Arfé La Clavis Physicae II (316-529) di Honorius Augustodunensis. Studio ed edizione critica, Tesi di dottorato in Storia della filosofia medievale, Università degli Studi di Napoli "L'Orientale", 2005 Alessandro Azzimonti Scrittura agiografica e strutture di potere nell'Italia c...

  19. Investigating copper toxicity in the tropical fish cardinal tetra (Paracheirodon axelrodi) in natural Amazonian waters: Measurements, modeling, and reality

    International Nuclear Information System (INIS)

    Crémazy, Anne; Wood, Chris M.; Smith, D. Scott; Ferreira, Márcio S.; Johannsson, Ora E.; Giacomin, Marina; Val, Adalberto L.

    2016-01-01

    Highlights: • Copper toxicity to a tropical fish varied greatly in different Amazonian waters. • The biotic ligand model could not capture this variability. • Possible physiological protection was offered by natural organic matter. • Care must be used in applying BLM to fish in tropical waters. - Abstract: Copper at high concentrations is an ionoregulatory toxicant in fish and its toxicity is known to be strongly modulated by the water chemistry. The toxicity of Cu to the tropical fish cardinal tetra (Paracheirodon axelrodi) was investigated in waters from two major rivers of the Amazon watershed: the Rio Negro (filtered <0.45 μm, pH 5.6, DOC = 8.4 mg L"−"1, Na = 33 μM, Ca = 8 μM) and the Rio Solimões (filtered <0.45 μm, pH 6.7, DOC = 2.8 mg L"−"1, Na = 185 μM, Ca = 340 μM), as well as in a natural “reference water” (groundwater) which was almost DOC-free (pH 6.0, DOC = 0.34 mg L"−"1, Na = 53 μM, Ca = 5 μM). Acute 96-h mortality, Cu bioaccumulation and net flux rates of Na"+, Cl"−, K"+ and total ammonia were determined in P. axelrodi exposed in each water. Copper speciation in each water was determined by two thermodynamic models and by potentiometry, and its toxicity was predicted based on the biotic ligand model (BLM) framework. Our results indicate that high Na"+ loss is the main mode of toxic action of Cu in P. axelrodi, in accordance with general theory. Cardinal tetra showed a particularly high ability to tolerate Cu and to maintain Na"+ balance, similar to the ability of this and other endemic Rio Negro species to tolerate low pH and ion-poor conditions. Cu toxicity was lower in Rio Negro than in the other two waters tested, and the free [Cu"2"+] at the LC50, as determined by any of the three speciation methods tested, was approximately 10-fold higher. This variation could not be captured by a realistic set of BLM parameters. At least in part, this observation may be due to gill physiological alterations induced by the abundant

  20. Investigating copper toxicity in the tropical fish cardinal tetra (Paracheirodon axelrodi) in natural Amazonian waters: Measurements, modeling, and reality

    Energy Technology Data Exchange (ETDEWEB)

    Crémazy, Anne, E-mail: acremazy@zoology.ubc.ca [Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); Wood, Chris M. [Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); Smith, D. Scott [Department of Chemistry and Biochemistry, Wilfrid Laurier University, Waterloo, ON N2L 3C5 (Canada); Ferreira, Márcio S. [Laboratory of Ecophysiology and Molecular Evolution, National Institute for Amazonian Research, Manaus, AM (Brazil); Johannsson, Ora E.; Giacomin, Marina [Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); Val, Adalberto L. [Laboratory of Ecophysiology and Molecular Evolution, National Institute for Amazonian Research, Manaus, AM (Brazil)

    2016-11-15

    Highlights: • Copper toxicity to a tropical fish varied greatly in different Amazonian waters. • The biotic ligand model could not capture this variability. • Possible physiological protection was offered by natural organic matter. • Care must be used in applying BLM to fish in tropical waters. - Abstract: Copper at high concentrations is an ionoregulatory toxicant in fish and its toxicity is known to be strongly modulated by the water chemistry. The toxicity of Cu to the tropical fish cardinal tetra (Paracheirodon axelrodi) was investigated in waters from two major rivers of the Amazon watershed: the Rio Negro (filtered <0.45 μm, pH 5.6, DOC = 8.4 mg L{sup −1}, Na = 33 μM, Ca = 8 μM) and the Rio Solimões (filtered <0.45 μm, pH 6.7, DOC = 2.8 mg L{sup −1}, Na = 185 μM, Ca = 340 μM), as well as in a natural “reference water” (groundwater) which was almost DOC-free (pH 6.0, DOC = 0.34 mg L{sup −1}, Na = 53 μM, Ca = 5 μM). Acute 96-h mortality, Cu bioaccumulation and net flux rates of Na{sup +}, Cl{sup −}, K{sup +} and total ammonia were determined in P. axelrodi exposed in each water. Copper speciation in each water was determined by two thermodynamic models and by potentiometry, and its toxicity was predicted based on the biotic ligand model (BLM) framework. Our results indicate that high Na{sup +} loss is the main mode of toxic action of Cu in P. axelrodi, in accordance with general theory. Cardinal tetra showed a particularly high ability to tolerate Cu and to maintain Na{sup +} balance, similar to the ability of this and other endemic Rio Negro species to tolerate low pH and ion-poor conditions. Cu toxicity was lower in Rio Negro than in the other two waters tested, and the free [Cu{sup 2+}] at the LC50, as determined by any of the three speciation methods tested, was approximately 10-fold higher. This variation could not be captured by a realistic set of BLM parameters. At least in part, this observation may be due to gill

  1. Esophageal pH monitoring

    Science.gov (United States)

    pH monitoring - esophageal; Esophageal acidity test ... Esophageal pH monitoring is used to check how much stomach acid is entering the esophagus. It also checks how well the acid is cleared downward into the ...

  2. Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis.

    Science.gov (United States)

    Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

    2016-03-10

    The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5'-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis.

  3. Toxic Anterior Segment Syndrome (TASS

    Directory of Open Access Journals (Sweden)

    Özlem Öner

    2011-12-01

    Full Text Available Toxic anterior segment syndrome (TASS is a sterile intraocular inflammation caused by noninfectious substances, resulting in extensive toxic damage to the intraocular tissues. Possible etiologic factors of TASS include surgical trauma, bacterial endotoxin, intraocular solutions with inappropriate pH and osmolality, preservatives, denatured ophthalmic viscosurgical devices (OVD, inadequate sterilization, cleaning and rinsing of surgical devices, intraocular lenses, polishing and sterilizing compounds which are related to intraocular lenses. The characteristic signs and symptoms such as blurred vision, corneal edema, hypopyon and nonreactive pupil usually occur 24 hours after the cataract surgery. The differential diagnosis of TASS from infectious endophthalmitis is important. The main treatment for TASS formation is prevention. TASS is a cataract surgery complication that is more commonly seen nowadays. In this article, the possible underlying causes as well as treatment and prevention methods of TASS are summarized. (Turk J Oph thal mol 2011; 41: 407-13

  4. Modulation of the partition coefficient between octanol and buffer at pH 7.4 and pKa to achieve the optimum balance of blood clearance and volume of distribution for a series of tetrahydropyran histamine type 3 receptor antagonists.

    Science.gov (United States)

    Hay, Tanya; Jones, Rhys; Beaumont, Kevin; Kemp, Mark

    2009-09-01

    The relationship between rat pharmacokinetics and physicochemical parameters [the partition coefficient between octanol and buffer at pH 7.4 (log D((7.4))) and pK(a)] was studied for a series of tetrahydropyran compounds. Sixteen compounds ranging in log D((7.4)) 0.1 to 1.8 were administered intravenously to rats, and the pharmacokinetic parameters were determined from blood concentration time curves. Across the series, a weak correlation was observed between log D((7.4)) and blood clearance, suggesting that log D((7.4)) values less than 0.5 were required to prevent clearance at hepatic blood flow. In terms of the volume of distribution (V(d)), the compounds fell into three distinct subseries characterized by the number of basic centers and differences in ionization of each basic center at physiological pH. These were referred to as the monobasic, weak second base, and strong second base subseries. All the compounds exhibited V(d) greater than body water, as would be expected from their lipophilic and basic nature. For a given clog P, the strong second base subseries showed higher V(d) than the weak second base subseries, which in turn exhibited higher values than the monobasic subseries. In addition, for the weak second base subseries, V(d) could be tuned by modulating the pK(a) of the second basic center. This relationship was rationalized in respect to the interactions of the ionizable centers with phospholipid heads in the cell membrane and/or lysosomal trapping. Compounds in the weak second base subseries showed optimal V(d), and when combined with a log D((7.4)) of 0.1, driving to moderate blood clearance, one compound showed the optimal pharmacokinetic profile.

  5. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  6. Toxicity identification evaluations of produced-water effluents

    International Nuclear Information System (INIS)

    Sauer, T.C.; Costa, H.J.; Brown, J.S.; Ward, T.J.

    1997-01-01

    Toxicity identification evaluations (TIEs) were performed on 14 produced-water (PW) samples of various salinities from inland and offshore oil- and gas-production facilities operated by different companies in Wyoming, Texas, California, and Louisiana (USA) to evaluate the efficacy of TIE procedures in determining potential toxicants in PW effluents. The research involved acute (24- and 48-h) freshwater and marine toxicity tests on whole PW and PW fractions generated by standard US Environmental Protection Agency and PW-specific fractionation schemes. Factors influencing PW TIEs were investigated, such as the effect of salinity in selecting fractionation manipulations, the effect of toxicity test replication (i.e., reproducibility) in distinguishing changes in toxicities between whole PW and its fractions, and the suitability of different test species in PW TIEs. The results obtained and lessons learned from conducting these PW TIEs are presented in this article. Components, or fractions, contributing to toxicity differed for each PW with no specific fraction being consistently toxic. For most PW samples, toxicity attributed to any one fraction represented only part of the toxicity of the whole sample. However, no more than two fraction types were identified as potential toxicants in any sample. Potential toxicants identified during this study, besides salinity, included acidic and basic organic compound class fractions, particulates removed by filtration at pH 11, ammonia, hydrocarbons, hydrogen sulfide, material removed by pH change, and volatile compounds

  7. Astrocyte-neuron interaction in diphenyl ditelluride toxicity directed to the cytoskeleton

    International Nuclear Information System (INIS)

    Heimfarth, Luana; Silva Ferreira, Fernanda da; Pierozan, Paula; Mingori, Moara Rodrigues; Moreira, José Cláudio Fonseca; Batista Teixeira da Rocha, João; Pessoa-Pureur, Regina

    2017-01-01

    Highlights: • Diphenyl ditelluride is toxic to the cytoskeleton of neural cells in vitro. • Hypophosphorylation disrupts cytoskeletal homeostasis and causes cell dysfunction. • Calcium signaling underlies hypophosphorylation of intermediate filaments. • Actin disorganization causes altered astrocyte morphology. • Astrocyte cytoskeleton is more susceptible than neuronal cytoskeleton. - Abstract: Diphenylditelluride (PhTe) 2 is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe) 2 caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-D-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors. Upregulated Ca 2+ influx downstream of NMDA receptors activated Ca 2+ -dependent protein phosphatase 2B (PP2B) causing hypophosphorylation of astrocyte and neuron IFs. Immunocytochemistry showed that hypophosphorylated intermediate filaments (IF) failed to disrupt their organization into the cytoskeleton. However, phalloidin-actin-FITC stained cytoskeleton evidenced misregulation of actin distribution, cell spreading and increased stress fibers in astrocytes. βIII tubulin staining showed that neurite meshworks are not altered by (PhTe) 2 , suggesting greater susceptibility of astrocytes than neurons to (PheTe) 2 toxicity. These findings indicate that signals leading to IF hypophosphorylation fail to disrupt the cytoskeletal IF meshwork of interacting astrocytes and neurons in vitro however astrocyte actin network seems more susceptible. Our findings support that intracellular Ca 2+ is one of the crucial signals that modulate the action of (PhTe) 2 in co-cultured astrocytes and neurons and highlights the cytoskeleton

  8. PhD Dissertations

    Directory of Open Access Journals (Sweden)

    Redazione Reti Medievali (a cura di

    2004-06-01

    Full Text Available Report of PhD Dissertations. Francesco Barone Istituzioni, società ed economia a Catania nel tardo medioevo (XIV-XV secolo, Tesi di dottorato in Storia medievale (XVI ciclo, Università degli Studi di Firenze, 2004   Laura Berti Ceroni Il territorio e le strutture di Cesarea e Classe tra tarda antichità e alto medioevo in rapporto con Ravenna, Tesi di dottorato di ricerca in Storia e Informatica, Università degli studi di Bologna, 2002-2003.   Marco Bicchierai Poppi dalla signoria dei conti Guidi al vicariato del Casentino (1360-1480, Tesi di dottorato in Storia medievale (XIV ciclo, Università degli Studi di Firenze, 2004   Emanuela Garimberti Spatiosa ad habitandum loca. Luoghi e identità nella Historia Langobardorum di Paolo Diacono, Tesi di dottorato in Storia medievale (XV ciclo, Università degli Studi di Bologna, 2004   Lorenzo Tanzini Sistemi normativi e pratiche istituzionali a Firenze dalla fine del XIII all’inizio del XV secolo, Tesi di dottorato di ricerca in Storia medievale (XVI ciclo, Università degli Studi di Firenze, 2004   Stefania Tarquini Pellegrinaggio e asseto urbano di Roma, Tesi di dottorato di ricerca in Storia dei centri, delle vie e della cultura dei pellegrinaggi nel Medioevo euro mediterraneo (XV ciclo, Università degli studi di Lecce, 2003

  9. PhD Dissertations

    Directory of Open Access Journals (Sweden)

    Redazione Reti Medievali (a cura di

    2010-06-01

    Full Text Available Report of PhD dissertations. Andrea Brugnoli Una storia locale: l’organizzazione del territorio veronese nel medioevo: trasformazioni della realtà e schemi notarili (IX-metà XII secolo, Tesi di dottorato di ricerca in Scienze Storiche e Antropologiche (XXII ciclo, Università degli Studi di Verona, 2010   Luca Filangieri Famiglie e gruppi dirigenti a Genova (secoli XII-metà XIII, Tesi di dottorato di ricerca in Storia medievale (XXII ciclo, Università degli Studi di Firenze, 2010   Jakub Kujawi ski Wernakularna kolekcja historiograficzna z rękopisu francuskiego nr 688 z Biblioteki Narodowej w Paryżu. Studium źródłoznawcze (La raccolta dei volgarizzamenti delle opere storiografiche nel manoscritto francese 688 della Biblioteca Nazionale di Parigi, Tesi di dottorato, Università “Adam Mickiewicz”, Facoltà di Storia, Pozna, a.a. 2009/2010   Marta Longhi I signori “de Radicata”. Strategie di affermazione familiare e patrimoniale nel Piemonte dei secoli XII-XIV, Tesi di dottorato di ricerca in Istituzioni, Società, Religioni dal Tardo Antico alla fine del Medioevo (XX ciclo, Università di Torino, 2008

  10. PhD Dissertations

    Directory of Open Access Journals (Sweden)

    Redazione Reti Medievali (a cura di

    2003-06-01

    Full Text Available Reporto of PhD Dissertations.   Mario Dalle Carbonare Società, potere e clientele nell’Irlanda altomedievale (secoli V-IX, Tesi di dottorato di ricerca in Storia sociale europea, Università "Ca' Foscari" di Venezia, 2003 Vieri Mazzoni La legislazione antighibellina e la politica oligarchica della Parte Guelfa di Firenze nel secondo Trecento (1347-1378, Tesi di dottorato di ricerca in Storia Medievale (ciclo XII, Università degli Studi di Firenze   Alma Poloni Pisa dalle origini del movimento popolare alla discesa di Ludovico il Bavaro. I gruppi dirigenti cittadini tra continuità e trasformazione, Tesi di dottorato di ricerca in Storia dell'Europa nel medioevo, Università degli studi di Pisa, 2003   Andrea Puglia Potere marchionale, amministrazione del territorio, società locali dalla morte di Ugo di Tuscia a Guelfo VI di Baviera (1001-1160, Tesi di dottorato di ricerca in Storia medievale, Università degli studi di Milano, 2003

  11. Do diosgenin ameliorate urinary bladder toxic effect of ...

    African Journals Online (AJOL)

    SWEET

    2012-01-26

    Jan 26, 2012 ... experimental animal models? ... BSO doses using a Swiss albino mouse model. Toxicity modulation ... bladder inflammation induced by CP in rats and mice .... 0.1 ml NADPH (nicotinamide adenine dinucleotide phosphate.

  12. Intracellular pH gradients in migrating cells

    DEFF Research Database (Denmark)

    Martin, Christine; Pedersen, Stine Helene Falsig; Schwab, Albrecht

    2011-01-01

    might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of p...

  13. Label-Free Carbon-Dots-Based Ratiometric Fluorescence pH Nanoprobes for Intracellular pH Sensing.

    Science.gov (United States)

    Shangguan, Jingfang; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Xu, Fengzhou; Liu, Jinquan; Tang, Jinlu; Yang, Xue; Huang, Jin

    2016-08-02

    Measuring pH in living cells is of great importance for better understanding cellular functions as well as providing pivotal assistance for early diagnosis of diseases. In this work, we report the first use of a novel kind of label-free carbon dots for intracellular ratiometric fluorescence pH sensing. By simple one-pot hydrothermal treatment of citric acid and basic fuchsin, the carbon dots showing dual emission bands at 475 and 545 nm under single-wavelength excitation were synthesized. It is demonstrated that the fluorescence intensities of the as-synthesized carbon dots at the two emissions are pH-sensitive simultaneously. The intensity ratio (I475 nm/I545 nm) is linear against pH values from 5.2 to 8.8 in buffer solution, affording the capability as ratiometric probes for intracellular pH sensing. It also displays that the carbon dots show excellent reversibility and photostability in pH measurements. With this nanoprobe, quantitative fluorescence imaging using the ratio of two emissions (I475 nm/I545 nm) for the detection of intracellular pH were successfully applied in HeLa cells. In contrast to most of the reported nanomaterials-based ratiometric pH sensors which rely on the attachment of additional dyes, these carbon-dots-based ratiometric probes are low in toxicity, easy to synthesize, and free from labels.

  14. Studying the effect of CO2-induced acidification on sediment toxicity using acute amphipod toxicity test.

    Science.gov (United States)

    Basallote, M Dolores; De Orte, Manoela R; DelValls, T Ángel; Riba, Inmaculada

    2014-01-01

    Carbon capture and storage is increasingly being considered one of the most efficient approaches to mitigate the increase of CO2 in the atmosphere associated with anthropogenic emissions. However, the environmental effects of potential CO2 leaks remain largely unknown. The amphipod Ampelisca brevicornis was exposed to environmental sediments collected in different areas of the Gulf of Cádiz and subjected to several pH treatments to study the effects of CO2-induced acidification on sediment toxicity. After 10 days of exposure, the results obtained indicated that high lethal effects were associated with the lowest pH treatments, except for the Ría of Huelva sediment test. The mobility of metals from sediment to the overlying seawater was correlated to a pH decrease. The data obtained revealed that CO2-related acidification would lead to lethal effects on amphipods as well as the mobility of metals, which could increase sediment toxicity.

  15. A PhD is a PhD is a PhD

    OpenAIRE

    Ostrow, Deborah Anne

    2017-01-01

    A PhD is a PhD is a PhD is a practice-based project that interrogates the process of an artist undertaking PhD research under established criteria. It consists of an exegesis, an original screenplay, and a digital film made for online viewing, with images drawn from a range of documentaries and films found on YouTube. They have been dissected, re-assembled and then re-embedded to YouTube. The source material covers topics such as medicalization of madness, the conspicuous appropriation of uni...

  16. The pH Game.

    Science.gov (United States)

    Chemecology, 1996

    1996-01-01

    Describes a game that can be used to teach students about the acidity of liquids and substances around their school and enable them to understand what pH levels tell us about the environment. Students collect samples and measure the pH of water, soil, plants, and other natural material. (DDR)

  17. Use of zeolite for removing ammonia and ammonia-caused toxicity in marine toxicity identification evaluations.

    Science.gov (United States)

    Burgess, R M; Perron, M M; Cantwell, M G; Ho, K T; Serbst, J R; Pelletier, M C

    2004-11-01

    Ammonia occurs in marine waters including effluents, receiving waters, and sediment interstitial waters. At sufficiently high concentrations, ammonia can be toxic to aquatic species. Toxicity identification evaluation (TIE) methods provide researchers with tools for identifying aquatic toxicants. For identifying ammonia toxicity, there are several possible methods including pH alteration and volatilization, Ulva lactuca addition, microbial degradation, and zeolite addition. Zeolite addition has been used successfully in freshwater systems to decrease ammonia concentrations and toxicity for several decades. However, zeolite in marine systems has been used less because ions in the seawater interfere with zeolite's ability to adsorb ammonia. The objective of this study was to develop a zeolite method for removing ammonia from marine waters. To accomplish this objective, we performed a series of zeolite slurry and column chromatography studies to determine uptake rate and capacity and to evaluate the effects of salinity and pH on ammonia removal. We also assessed the interaction of zeolite with several toxic metals. Success of the methods was also evaluated by measuring toxicity to two marine species: the mysid Americamysis bahia and the amphipod Ampelisca abdita. Column chromatography proved to be effective at removing a wide range of ammonia concentrations under several experimental conditions. Conversely, the slurry method was inconsistent and variable in its overall performance in removing ammonia and cannot be recommended. The metals copper, lead, and zinc were removed by zeolite in both the slurry and column treatments. The zeolite column was successful in removing ammonia toxicity for both the mysid and the amphipod, whereas the slurry was less effective. This study demonstrated that zeolite column chromatography is a useful tool for conducting marine water TIEs to decrease ammonia concentrations and characterize toxicity.

  18. Toxicity alarm: Case history

    International Nuclear Information System (INIS)

    Hogan, D.; Retallack, J.

    1993-01-01

    In late fall 1991, the Novacor petrochemical plant near Joffre, Alberta experienced a toxicity alarm, the first since its startup 14 years ago. Fish exposed to a normal toxicity test were stressed within 2 h and showed 100% mortality after 24 h. A history of the events leading up to, during, and after the toxicity alarm is presented. The major effluent sources were three cooling water systems. Although these sources are well characterized, the event causes were not immediately clear. Initial toxic screening indicated that one was very toxic, another moderately toxic, and the third not toxic at all. All three systems utilized the same chemical treatment program to avoid fouling: stabilized phosphates with minor variants. The most toxic of the cooling systems operated at 10-12 cycles, had three chemicals for biocide control, and had three makeup streams. Toxic and nontoxic system characteristics were compared. An in-depth modified toxicity identification and evaluation program was then performed to identify and evaluate the cause of the toxicity alarm for future prevention. The most probable causes of toxicity were identified by elimination. The combination of high numbers of cycles, hydrocarbons in the makeup water, and bromine added as an antifoulant resulted in formation of aromatic bromamines which are capable of causing the toxic condition experienced. 2 tabs

  19. Human vaginal pH and microbiota: an update.

    Science.gov (United States)

    Godha, Keshav; Tucker, Kelly M; Biehl, Colton; Archer, David F; Mirkin, Sebastian

    2018-06-01

    A woman's vaginal pH has many implications on her health and it can be a useful tool in disease diagnosis and prevention. For that reason, the further examination of the relationship between the human vaginal pH and microbiota is imperative. In the past several decades, much has been learned about the physiological mechanisms modulating the vaginal pH, and exogenous/genetic factors that may influence it. A unified, coherent understanding of these concepts is presented to comprehend their interrelationships and their cumulative effect on a woman's health. In this review, we explore research on vaginal pH and microbiota throughout a woman's life, vaginal intermediate cell anaerobic metabolism and net proton secretion by the vaginal epithelial, and the way these factors interact to acidify the vaginal pH. This review provides foundational information about what a microbiota is and its relationship with human physiology and vaginal pH. We then evaluate the influence of physiological mechanisms, demographic factors, and propose ideas for the mechanisms behind their action on the vaginal pH.

  20. Toxic substances handbook

    Science.gov (United States)

    Junod, T. L.

    1979-01-01

    Handbook, published in conjunction with Toxic Substances Alert Program at NASA Lewis Research Center, profiles 187 toxic chemicals in their relatively pure states and include 27 known or suspected carcinogens.

  1. Larval gut pH profile in pestiferous .i.Chironomus crassicaudatus./i. and .i.Glyptotendipes paripes./i. (Chironomidae: Diptera) in reference to the toxicity potential of .i.Bacillus thuringiensis./i. serovar .i.israelensis./i

    Czech Academy of Sciences Publication Activity Database

    Frouz, Jan; Lobinske, R.J.; Yaqub, A.; Ali, A.

    2007-01-01

    Roč. 23, č. 3 (2007), s. 355-358 ISSN 8756-971X Institutional research plan: CEZ:AV0Z60660521 Keywords : chironomidae larvae * gut pH * Bacillus thuringiensis serovar israelensis Subject RIV: EH - Ecology, Behaviour Impact factor: 0.706, year: 2007

  2. Effect of pH on Pulp Potential and Sulphide Mineral Flotation

    OpenAIRE

    GÖKTEPE, Ferihan

    2014-01-01

    Control of pH is one of the most widely applied methods for the modulation of mineral flotation. In this study the effect of pH on potential in solution and sulphur minerals flotation is discussed with various electrodes. The electrodes were platinum, gold, chalcopyrite, pyrite and galena. In solution, potentials were linearly dependent on pH with a different slope for each electrode. Chalcopyrite, pyrite, sphalerite and galena minerals flotation tests were performed in a microflot...

  3. Urine pH test

    Science.gov (United States)

    ... urine test Male urinary tract References Bose A, Monk RD, Bushinsky DA. Kidney stones. In: Melmed S, Polonsky ... and its influence on urine pH. J Am Diet Assoc . 1995;95(7):791-797. PMID: 7797810 ...

  4. Exercise and Pulmonary Hypertension (PH)

    Science.gov (United States)

    ... Situations Find a Doctor PH Care Centers PHA Classroom PHA Registry Insurance Guide Specialty Pharmacy Other Resources ... no published data in the medical literature regarding routine exercise in patients with PAH. However, there are ...

  5. Programmable pH buffers

    Science.gov (United States)

    Gough, Dara Van; Huber, Dale L.; Bunker, Bruce C.; Roberts, Mark E.

    2017-01-24

    A programmable pH buffer comprises a copolymer that changes pK.sub.a at a lower critical solution temperature (LCST) in water. The copolymer comprises a thermally programmable polymer that undergoes a hydrophobic-to-hydrophilic phase change at the LCST and an electrolytic polymer that exhibits acid-base properties that are responsive to the phase change. The programmable pH buffer can be used to sequester CO.sub.2 into water.

  6. On the Toxicity of the Aromatic Diamines and their Tetramethylcarboxylic Acid Derivatives

    OpenAIRE

    Gili, Pedro; Mederos, Alfredo

    2000-01-01

    The use of the theoretical PALLAS 3.0 program, to study the toxic behaviour of tetramethylcarboxylic acids, potential pharmaceuticals derived from o-phenylenediamines, indicates that o-phenylenediamines are highly toxic (level 1), while the tetramethycarboxylic acid derivatives (o-PhDTA and 3,4-TDTA) are slightly toxic, similar to EDTA (level 3). Therefore these ligands o-PhDTA and 3,4-TDTA, similar to EDTA, can be used as sequestering agents of toxic metals and overload of essential metals i...

  7. A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

    Science.gov (United States)

    Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

    2017-11-01

    Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Identification of a molecular pH sensor in coral.

    Science.gov (United States)

    Barott, Katie L; Barron, Megan E; Tresguerres, Martin

    2017-11-15

    Maintaining stable intracellular pH (pHi) is essential for homeostasis, and requires the ability to both sense pH changes that may result from internal and external sources, and to regulate downstream compensatory pH pathways. Here we identified the cAMP-producing enzyme soluble adenylyl cyclase (sAC) as the first molecular pH sensor in corals. sAC protein was detected throughout coral tissues, including those involved in symbiosis and calcification. Application of a sAC-specific inhibitor caused significant and reversible pHi acidosis in isolated coral cells under both dark and light conditions, indicating sAC is essential for sensing and regulating pHi perturbations caused by respiration and photosynthesis. Furthermore, pHi regulation during external acidification was also dependent on sAC activity. Thus, sAC is a sensor and regulator of pH disturbances from both metabolic and external origin in corals. Since sAC is present in all coral cell types, and the cAMP pathway can regulate virtually every aspect of cell physiology through post-translational modifications of proteins, sAC is likely to trigger multiple homeostatic mechanisms in response to pH disturbances. This is also the first evidence that sAC modulates pHi in any non-mammalian animal. Since corals are basal metazoans, our results indicate this function is evolutionarily conserved across animals. © 2017 The Author(s).

  9. Economical wireless optical ratiometric pH sensor

    International Nuclear Information System (INIS)

    Vuppu, Sandeep; Kostov, Yordan; Rao, Govind

    2009-01-01

    The development and application of a portable, wireless fluorescence-based optical pH sensor is presented. The design incorporates the MSP430 microcontroller as the control unit, an RF transceiver for wireless communication, digital filters and amplifiers and a USB-based communication module for data transmission. The pH sensor is based on ratiometric fluorescence detection from pH sensitive dye incorporated in a peel-and-stick patch. The ability of the instrument to detect the pH of the solution with contact only between the sensor patch and the solution makes it partially non-invasive. The instrument also has the ability to transmit data wirelessly, enabling its use in processes that entail stringent temperature control and sterility. The use of the microcontroller makes it a reliable, low-cost and low-power device. The luminous intensity of the light source can be digitally controlled to maximize the sensitivity of the instrument. It has a resolution of 0.05 pH. The sensor is accurate and reversible over the pH range of 6.5–9

  10. Data collection and analysis strategies for phMRI.

    Science.gov (United States)

    Mandeville, Joseph B; Liu, Christina H; Vanduffel, Wim; Marota, John J A; Jenkins, Bruce G

    2014-09-01

    Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed "phMRI". The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Tomotherapy for prostate adenocarcinoma: A report on acute toxicity

    International Nuclear Information System (INIS)

    Keiler, Louis; Dobbins, Donald; Kulasekere, Ravi; Einstein, Douglas

    2007-01-01

    Background and purpose: To analyze the impact of Tomotherapy (TOMO) intensity modulated radiotherapy (IMRT) on acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer. Materials and methods: The records of 55 consecutively treated TOMO patients were reviewed. Additionally a well-matched group of 43 patients treated with LINAC-based step and shoot IMRT (LINAC) was identified. Acute toxicity was scored according to Radiation Therapy Oncology Group acute toxicity criterion. Results: The grade 2-3 acute GU toxicity rates for the TOMO vs. LINAC groups were 51% vs. 28% (p = 0.001). Acute grade 2 GI toxicity was 25% vs. 40% (p = 0.024), with no grade 3 GI toxicity in either group. In univariate analysis, androgen deprivation, prostate volume, pre-treatment urinary toxicity, and prostate dose homogeneity correlated with acute GI and GU toxicity. With multivariate analysis use of Tomotherapy, median bladder dose and bladder dose homogeneity remained significantly correlated with GU toxicity. Conclusions: Acute GI toxicity for prostate cancer is improved with Tomotherapy at a cost of increased acute GU toxicity possibly due to differences in bladder and prostate dose distribution

  12. Polyaluminium chloride (PAX-18) - acute toxicity and toxicity for early development stages of common carp (Cyprinus carpio)

    Czech Academy of Sciences Publication Activity Database

    Mácová, S.; Máchová, J.; Prokeš, Miroslav; Plhalová, L.; Široká, Z.; Dlesková, K.; Doleželová, P.; Svobodová, Z.

    2009-01-01

    Roč. 30, Suppl. 1 (2009), s. 192-198 ISSN 0172-780X. [Interdisciplinary Czech-Slovak Toxicological Conference /14./. Brno, 01.06.2009-03.06.2009] R&D Projects: GA MZe QH71305 Institutional research plan: CEZ:AV0Z60930519 Keywords : fish * acute toxicity test * embryo-larval toxicity test * pH Subject RIV: GL - Fishing Impact factor: 1.047, year: 2009 http://node.nel.edu/?node_id=9497

  13. Narrow pH Range of Surface Water Bodies Receiving Pesticide Input in Europe.

    Science.gov (United States)

    Bundschuh, Mirco; Weyers, Arnd; Ebeling, Markus; Elsaesser, David; Schulz, Ralf

    2016-01-01

    Fate and toxicity of the active ingredients (AI's) of plant protection products in surface waters is often influenced by pH. Although a general range of pH values is reported in literature, an evaluation targeting aquatic ecosystems with documented AI inputs is lacking at the larger scale. Results show 95% of European surface waters (n = 3075) with a documented history of AI exposure fall within a rather narrow pH range, between 7.0 and 8.5. Spatial and temporal variability in the data may at least be partly explained by the calcareous characteristics of parental rock material, the affiliation of the sampling site to a freshwater ecoregion, and the photosynthetic activity of macrophytes (i.e., higher pH values with photosynthesis). Nonetheless, the documented pH range fits well with the standard pH of most ecotoxicological test guidelines, confirming the fate and ecotoxicity of AIs are usually adequately addressed.

  14. Toxic substances alert program

    Science.gov (United States)

    Junod, T. L.

    1978-01-01

    A toxicity profile is provided, of 187 toxic substances procured by NASA Lewis Research Center during a 3 1/2 year period, including 27 known or suspected carcinogens. The goal of the program is to assure that the center's health and safety personnel are aware of the procurement and use of toxic substances and to alert and inform the users of these materials as to the toxic characteristics and the control measures needed to ensure their safe use. The program also provides a continuing record of the toxic substances procured, who procured them, what other toxic substances the user has obtained in the past, and where similar materials have been used elsewhere at the center.

  15. Astrocyte-neuron interaction in diphenyl ditelluride toxicity directed to the cytoskeleton.

    Science.gov (United States)

    Heimfarth, Luana; da Silva Ferreira, Fernanda; Pierozan, Paula; Mingori, Moara Rodrigues; Moreira, José Cláudio Fonseca; da Rocha, João Batista Teixeira; Pessoa-Pureur, Regina

    2017-03-15

    Diphenylditelluride (PhTe) 2 is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe) 2 caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors. Upregulated Ca 2+ influx downstream of NMDA receptors activated Ca 2+ -dependent protein phosphatase 2B (PP2B) causing hypophosphorylation of astrocyte and neuron IFs. Immunocytochemistry showed that hypophosphorylated intermediate filaments (IF) failed to disrupt their organization into the cytoskeleton. However, phalloidin-actin-FITC stained cytoskeleton evidenced misregulation of actin distribution, cell spreading and increased stress fibers in astrocytes. βIII tubulin staining showed that neurite meshworks are not altered by (PhTe) 2 , suggesting greater susceptibility of astrocytes than neurons to (PheTe) 2 toxicity. These findings indicate that signals leading to IF hypophosphorylation fail to disrupt the cytoskeletal IF meshwork of interacting astrocytes and neurons in vitro however astrocyte actin network seems more susceptible. Our findings support that intracellular Ca 2+ is one of the crucial signals that modulate the action of (PhTe) 2 in co-cultured astrocytes and neurons and highlights the cytoskeleton as an end-point of the neurotoxicity of this compound. Cytoskeletal misregulation is associated with cell dysfunction, therefore, the understanding of the molecular mechanisms mediating the neurotoxicity of this compound is a matter of increasing interest since tellurium compounds are increasingly released in the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Electrochemical oxidation of selective estrogen receptor modulator raloxifene

    International Nuclear Information System (INIS)

    Li, Xi-Qian; He, Jian-Bo; Liu, Lu; Cui, Ting

    2013-01-01

    Highlights: ► Application and analysis of in situ thin-layer spectroelectrochemistry. ► Cyclic voltabsorptometry used for a drug study. ► Highly pH-dependent oxidative metabolism of raloxifene. ► A complex parallel-consecutive mechanism proposed for oxidation of raloxifene. -- Abstract: Raloxifene is a selective estrogen receptor modulator that may produce toxic oxidative species in metabolism. The oxidation mechanism of raloxifene with different pH values was studied by cyclic voltammetry, X-ray photoelectron spectroscopy (XPS), in situ UV–vis spectral analysis and cyclic voltabsorptometry based on a long optical-path thin-layer electrochemical cell. Time-derivative cyclic voltabsorptograms were obtained for comparative discussion with the corresponding cyclic voltammograms. Raloxifene was initially oxidized to reactive phenoxyl radicals, followed by a series of transformation steps leading to different final products in different pH media. A parallel-consecutive reaction mechanism was proposed for the pH-dependent formation of 7-hydroxyraloxifene, raloxifene 6,7-o-quinone and two raloxifene dimers, each pathway following a complex electrochemical-chemical mechanism. Both raloxifene diquinone methide and its N-oxides were not detected by in situ UV–vis spectroscopy and XPS analysis. This work provides an electrochemical viewpoint and comparable information for better understanding of the oxidative metabolism and chemical toxicology of raloxifene under physiological conditions in vivo or in vitro

  17. Effects of pH on uranium uptake and oxidative stress responses induced in Arabidopsis thaliana

    OpenAIRE

    Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; Van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

    2013-01-01

    Uranium (U) causes oxidative stress in Arabidopsis thaliana plants grown at pH 5.5. However, U speciation and its toxicity strongly depend on environmental parameters, for example pH. It is unknown how different U species determine U uptake and translocation within plants and how they might affect the oxidative defense mechanisms of these plants. The present study analyzed U uptake and oxidative stress-related responses in A. thaliana (Columbia ecotype) under contrasted U chemical speciation ...

  18. Optical coherence tomography findings in methanol toxicity.

    Science.gov (United States)

    Klein, Kendra A; Warren, Alexis K; Baumal, Caroline R; Hedges, Thomas R

    2017-01-01

    Methanol toxicity poses a significant public health problem in developing countries, and in Southeast Asia, where the most common source of poisoning is via adulterated liquor in local drinks. Methanol toxicity can have devastating visual consequences and retinal specialists should be aware of the features of this toxic optic neuropathy. The authors report a case of severe systemic methanol toxicity and relatively mild optic neuropathy demonstrating unique retinal changes on optical coherence tomography (OCT). A previously healthy student developed ataxia, difficulty breathing and loss of consciousness hours after drinking homemade alcohol while traveling in Indonesia. She was found to have a serum pH of 6.79 and elevated methanol levels. She was treated with intravenous ethanol, methylprednisolone and sodium bicarbonate. When she awoke she had bilateral central scotomas. At presentation, she had central depression on visual field testing. OCT of the retinal nerve fiber layer (RNFL) was normal but ganglion cell layer analysis (GCL) showed highly selective loss of the nasal fibers in both eyes. Further, OCT of the macula demonstrated inner nuclear layer (INL) microcysts in the corresponding area of selective GCL loss in both eyes. The selective involvement of the papillomacular bundle fibers is common in toxic optic neuropathies and represents damage to the small caliber axons rich in mitochondria. Despite severe systemic toxicity, the relative sparing of the optic nerve in this case enabled characterization of the evolution of methanol toxicity with segmental GCL involvement and preservation of the RNFL, corresponding to the papillomacular bundle. This is the first reported case of INL microcysts in methanol optic neuropathy and supports that they are a non-specific finding, and may represent preferential damage to the papillomacular bundle.

  19. Paulette Gray, Ph.D.

    Science.gov (United States)

    Paulette S. Gray, Ph.D. is the Director for the Division of Extramural Activities (DEA). As the director of the division, she is responsible for the overall scientific, fiscal, and administrative management of the division, including broad strategic planning, development, implementation, and evaluation.

  20. pH in Action

    NARCIS (Netherlands)

    Tijskens, L.M.M.; Biekman, E.S.A.

    2001-01-01

    Based on fundamental chemical relations, well-established in chemical engineering and chemical technology over almost a century, the effects of pH in food and agricultural products will be deduced for different situations and processes. Based on simple equilibria and dissociation of water, salts,

  1. Neuronal pH regulation

    DEFF Research Database (Denmark)

    Vorstrup, S; Jensen, K E; Thomsen, C

    1989-01-01

    The intracellular pH in the brain was studied in six healthy volunteers before and immediately after the administration of 2 g of acetazolamide. Phosphorus-31 nuclear magnetic resonance spectroscopy by a 1.5 tesla whole-body scanner was used. The chemical shift between the inorganic phosphate...

  2. Females and Toxic Leadership

    Science.gov (United States)

    2012-12-14

    labeled as toxic, can he or she be rehabilitated?; Are there leadership styles that can be promoted to combat toxic leadership?; and Are the senior...examines leadership styles that are favorable for female leaders, and offers Transformational/Adaptive leadership as a style promising rehabilitative tools

  3. The Role of the Plasma Membrane H+-ATPase in Plant Responses to Aluminum Toxicity

    Directory of Open Access Journals (Sweden)

    Jiarong Zhang

    2017-10-01

    Full Text Available Aluminum (Al toxicity is a key factor limiting plant growth and crop production on acid soils. Increasing the plant Al-detoxification capacity and/or breeding Al-resistant cultivars are a cost-effective strategy to support crop growth on acidic soils. The plasma membrane H+-ATPase plays a central role in all plant physiological processes. Changes in the activity of the plasma membrane H+-ATPase through regulating the expression and phosphorylation of this enzyme are also involved in many plant responses to Al toxicity. The plasma membrane H+-ATPase mediated H+ influx may be associated with the maintenance of cytosolic pH and the plasma membrane gradients as well as Al-induced citrate efflux mediated by a H+-ATPase-coupled MATE co-transport system. In particular, modulating the activity of plasma membrane H+-ATPase through application of its activators (e.g., magnesium or IAA or using transgenics has effectively enhanced plant resistance to Al stress in several species. In this review, we critically assess the available knowledge on the role of the plasma membrane H+-ATPase in plant responses to Al stress, incorporating physiological and molecular aspects.

  4. Industrial PhD report: Sustainable Innovation

    DEFF Research Database (Denmark)

    Olesen, Gitte Gylling Hammershøj

    2011-01-01

    Erhvervs PhD rapport udarbejdet i tilknytning til Erhvervs PhD kurset der er obligatorisk for Erhvervs PhD studerende. Rapporten omhandler relationer melllem den akademiske verden og industrien i sammenhæng med PhD projektet, betragtet og analyseret gennem teori om bæredygtig innovation....

  5. A ph sensor based on a flexible substrate

    Science.gov (United States)

    Huang, Wen-Ding

    implanted inside the esophagus. Our pH electrode can monitor the pH changes of gastric juice in real time when the reflux happening in the esophagus. Our micro flexible pH sensor performed clear responses in each distinct pH reflux episode quickly and accurately comparing with the other commercial pH monitoring system. For the food freshness monitoring applications, we used the flexible pH sensor as a freshness indicator to monitor the pH changing profile during the food spoilage procedure. The sensor was then embedded with radio frequency identification (RFID) based passive telemetry enabling remote monitoring of food freshness. In the result, our pH-wireless RFID system presented 633Hz/pH of the sensitivity in the frequency calibration. The calibration of stability and dynamical response of the RFID system were also demonstrated before the test on food freshness monitoring. Finally, a white fish meat for long term spoilage procedure monitoring was applied and tested by using our wireless IrOx pH sensing system. Our RFID pH sensing module is able to monitor, collect and transmit the pH information continuously for 18 hours during the food spoilage procedure. In this dissertation, a micro size of IrOx/AgCl pH sensor was fabricated on a flexible substrate. The physical properties of the IrO x thin film was verified in the work. The different sensing capability such as the sensitivity, stability, reversibility, response time, repeatability, selectivity, and temperature dependence was then demonstrated in this work. After the different in-vitro tests, the pH sensor were embedded with our passive RFID circuitry for the in-vivo GERD diagnosis and food freshness monitoring application. Our wireless pH sensing system was able to deliver the accurate and quick pH sensing data wirelessly. In conclusion, our deformable IrOx pH electrodes have been demonstrated with the advantages of accommodating and conforming sensors in small spaces or curved surfaces. This miniature IrOx pH sensor

  6. The neutral species of the weak base trimethoprim is more toxic to willow trees (Salix viminalis) than the cation

    DEFF Research Database (Denmark)

    Mikes, O.; Trapp, Stefan

    2011-01-01

    The acute toxicity of the veterinary antibiotic trimethoprim (TMP) to willow trees was tested at three different pH levels in hydroponic solutions with TMP concentrations of 1, 10, 100 or 1000 mg/L. The pH variation was achieved by using ammonium (pH 4.3, low) or nitrate (pH 6.4, medium) as nitro......The acute toxicity of the veterinary antibiotic trimethoprim (TMP) to willow trees was tested at three different pH levels in hydroponic solutions with TMP concentrations of 1, 10, 100 or 1000 mg/L. The pH variation was achieved by using ammonium (pH 4.3, low) or nitrate (pH 6.4, medium...

  7. Molecular mechanisms of fluoride toxicity.

    Science.gov (United States)

    Barbier, Olivier; Arreola-Mendoza, Laura; Del Razo, Luz María

    2010-11-05

    Halfway through the twentieth century, fluoride piqued the interest of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and in in vivo experimental models. Until the 1990s, the toxicity of fluoride was largely ignored due to its "good reputation" for preventing caries via topical application and in dental toothpastes. However, in the last decade, interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. In recent years, several investigations demonstrated that fluoride can induce oxidative stress and modulate intracellular redox homeostasis, lipid peroxidation and protein carbonyl content, as well as alter gene expression and cause apoptosis. Genes modulated by fluoride include those related to the stress response, metabolic enzymes, the cell cycle, cell-cell communications and signal transduction. The primary purpose of this review is to examine recent findings from our group and others that focus on the molecular mechanisms of the action of inorganic fluoride in several cellular processes with respect to potential physiological and toxicological implications. This review presents an overview of the current research on the molecular aspects of fluoride exposure with emphasis on biological targets and their possible mechanisms of involvement in fluoride cytotoxicity. The goal of this review is to enhance understanding of the mechanisms by which fluoride affects cells, with an emphasis on tissue-specific events in humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Pediatric Toxic Shock Syndrome

    Directory of Open Access Journals (Sweden)

    Jennifer Yee

    2017-09-01

    Full Text Available Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of a pediatric patient with toxic shock syndrome. The case is also appropriate for teaching of medical students and advanced practice providers, as well as a review of the principles of crisis resource management, teamwork, and communication. Introduction: Toxic shock syndrome is a low-frequency, high-acuity scenario requiring timely identification and aggressive management. If patients suffering from this condition are managed incorrectly, they may progress into multi-organ dysfunction and potentially death. Toxic shock syndrome has been associated with Streptococcus and Staphylococcus aureus (Staph. Approximately half of Staph cases are associated with menstruation, which was first described in the 1970s-1980s and was associated with the use of absorbent tampons.1 Group A Streptococcus may cause complications such as necrotizing fasciitis and gangrenous myositis.2 Pediatric patients may present critically ill from toxic shock syndrome. Providers need to perform a thorough history and physical exam to discern the source of infection. Management requires aggressive care with antibiotics and IV fluids. Objectives: By the end of this simulation session, the learner will be able to: 1 Recognize toxic shock syndrome. 2 Review the importance of a thorough physical exam. 3 Discuss management of toxic shock syndrome, including supportive care and the difference in antibiotic choices for streptococcal and staphylococcal toxic shock syndrome. 4 Appropriately disposition a patient suffering from toxic shock syndrome. 5 Communicate effectively with team members and nursing staff during a resuscitation of a critically ill patient. Method: This session was conducted using high-fidelity simulation, followed by a debriefing session and lecture on toxic shock syndrome.

  9. Mercury and other element exposure in tree swallows nesting at low pH and neutral pH lakes in northern Wisconsin USA

    International Nuclear Information System (INIS)

    Custer, Thomas W.; Custer, Christine M.; Thogmartin, Wayne E.; Dummer, Paul M.; Rossmann, Ronald; Kenow, Kevin P.; Meyer, Michael W.

    2012-01-01

    The primary objective of this study was to determine whether tree swallows (Tachycineta bicolor) demonstrate similar responses to lake pH and mercury (Hg) contamination in northern Wisconsin as do common loons (Gavia immer). Similar to common loons, Hg concentrations in the blood of tree swallow nestlings were higher, Hg concentrations in eggs tended to be higher, and egg size tended to be smaller at low (<6.2) pH lakes. In contrast to common loons, tree swallow nestling production was not lower at low pH lakes. Based on modeling associations, Hg concentrations in tree swallow eggs and nestling blood can be used to predict Hg concentrations in common loons without the invasive or destructive sampling of loons. Mean concentrations of cadmium, manganese, and mercury in nestling livers were higher at low pH lakes than neutral pH lakes. Concentrations of cadmium, chromium, mercury, selenium, and zinc were not at toxic levels. - Highlights: ► Mercury concentrations in tree swallow nestling livers were higher in low than neutral pH lakes. ► Tree swallow eggs were smaller at low than neutral pH lakes. ► Tree swallow hatching success was not correlated with mercury concentrations in eggs. ► Mercury concentrations in tree swallows can be used to predict common loon exposure. - Mercury concentrations in tree swallows were higher at low pH lakes.

  10. Comparison of mucous and cutaneous toxicity of IMRT and of conventional radiotherapy associated with cetuximab

    International Nuclear Information System (INIS)

    Kreps, S.; Tamby, E.; Dessard Diana, B.; Berges, O.; Botti, M.; Deberne, M.; Henni, M.; Durdux, C.; Housset, M.; Giraud, P.

    2011-01-01

    The authors report a retrospective assessment of acute, cutaneous and mucous toxicity resulting from an association of cetuximab and conventional conformational radiotherapy, and from an intensity-modulated conformational radiotherapy (IMRT). Seven patients presenting nasopharyngeal, oropharyngeal or hypopharyngeal tumours have been irradiated with intensity modulation, and seven without. It appears that the association of cetuximab and radiotherapy is not well tolerated and requires a close monitoring. Intensity-modulated radiotherapy allows a significant reduction of dose and of toxicity. However, mucous toxicity remains significant. Short communication

  11. Acute toxicity of copper oxide nanoparticles to Daphnia magna under different test conditions

    DEFF Research Database (Denmark)

    Thit, Amalie; Huggins, Krista; Selck, Henriette

    2017-01-01

    suspensions changed in a way similar to what is known for dissolved Cu: first in ISO standard test conditions (pH 7.8), second with slight acidity (pH 6.5), third in the presence of citric acid, and fourth in the presence of humic acid. For all four exposure conditions, the toxicity of Cu employed...... in the three forms followed the same sequence, i.e., CuSO4 > monodispersed 6 nm CuO ≫ poly-dispersed CuO. The toxicity of all Cu forms decreased from pH 6.5, ≫ pH 7.8, > pH 7.8 + citric acid, to ≫ pH 7.8 + humic acid. This pattern is in agreement with concentrations of Cu2+ calculated using the equilibrium...

  12. Electronic Cigarette Toxicity.

    Science.gov (United States)

    Payne, J Drew; Michaels, David; Orellana-Barrios, Menfil; Nugent, Kenneth

    2017-04-01

    Electronic cigarettes (e-cigarettes) are often advertised as a healthier product when compared with traditional cigarettes. Currently, there are limited data to support this and only a threat of federal regulation from the US Food and Drug Administration. Calls to poison control centers about e-cigarette toxicity, especially in children, and case reports of toxic exposures have increased over the past 3 years. This research letter reports the frequency of hazardous exposures to e-cigarettes and characterizes the reported adverse health effects associated with e-cigarette toxicity.

  13. Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

    Directory of Open Access Journals (Sweden)

    Čolović Mirjana B.

    2013-01-01

    Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

  14. Toxicity Estimation Software Tool (TEST)

    Science.gov (United States)

    The Toxicity Estimation Software Tool (TEST) was developed to allow users to easily estimate the toxicity of chemicals using Quantitative Structure Activity Relationships (QSARs) methodologies. QSARs are mathematical models used to predict measures of toxicity from the physical c...

  15. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual 3.2

    Science.gov (United States)

    The Web-ICE Endangered Species module simultaneously estimates toxicity to taxa representing threatened or endangered species using up to 25 surrogates. This module batch processes toxicity values for endangered species from all species, genus, and family level models available f...

  16. Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

    Directory of Open Access Journals (Sweden)

    Richard Sauerheber

    2013-01-01

    Full Text Available The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

  17. Physiologic conditions affect toxicity of ingested industrial fluoride.

    Science.gov (United States)

    Sauerheber, Richard

    2013-01-01

    The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

  18. Predicting molybdenum toxicity to higher plants: Influence of soil properties

    Energy Technology Data Exchange (ETDEWEB)

    McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Functions, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C. [Soil Science Department, Centre for Soils and Ecosystems Functions, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Curdy, R. [Laboratory for Environmental Biotechnology (LBE), Swiss Federal Institute of Technology Lausanne (EPFL) Station 6 CH, 1015 Lausanne (Switzerland); Zhao, F.J. [Soil Science Department, Centre for Soils and Ecosystems Functions, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom)

    2010-10-15

    The effect of soil properties on the toxicity of molybdenum (Mo) to four plant species was investigated. Soil organic carbon or ammonium-oxalate extractable Fe oxides were found to be the best predictors of the 50% effective dose (ED{sub 50}) of Mo in different soils, explaining > 65% of the variance in ED{sub 50} for four species except for ryegrass (26-38%). Molybdenum concentrations in soil solution and consequently plant uptake were increased when soil pH was artificially raised because sorption of Mo to amorphous oxides is greatly reduced at high pH. The addition of sulphate significantly decreased Mo uptake by oilseed rape. For risk assessment, we suggest that Mo toxicity values for plants should be normalised using soil amorphous iron oxide concentrations. - Amorphous iron oxides or organic carbon were found to be the best predictors of the toxicity threshold values of Mo to higher plants on different soils.

  19. Predicting molybdenum toxicity to higher plants: Influence of soil properties

    International Nuclear Information System (INIS)

    McGrath, S.P.; Mico, C.; Curdy, R.; Zhao, F.J.

    2010-01-01

    The effect of soil properties on the toxicity of molybdenum (Mo) to four plant species was investigated. Soil organic carbon or ammonium-oxalate extractable Fe oxides were found to be the best predictors of the 50% effective dose (ED 50 ) of Mo in different soils, explaining > 65% of the variance in ED 50 for four species except for ryegrass (26-38%). Molybdenum concentrations in soil solution and consequently plant uptake were increased when soil pH was artificially raised because sorption of Mo to amorphous oxides is greatly reduced at high pH. The addition of sulphate significantly decreased Mo uptake by oilseed rape. For risk assessment, we suggest that Mo toxicity values for plants should be normalised using soil amorphous iron oxide concentrations. - Amorphous iron oxides or organic carbon were found to be the best predictors of the toxicity threshold values of Mo to higher plants on different soils.

  20. Dredged Material Evaluations: Review of Zooplankton Toxicity Test Methods for Marine Water Quality Evaluations

    Science.gov (United States)

    2016-09-01

    term impacts of the DM while settling through the water column (elutriate toxicity tests), and long-term toxicity (whole sediment toxicity tests) and...elutriates are prepared according to guidance (USEPA/USACE 1991; 1998) by mixing sediment and site water and allowing settling for prescribed periods...of water and waste water . 17th ed. Washington, DC: APHA. Arnold, W. R., R. L. Diamond, and D. S. Smith. 2010a. The effects of salinity, pH, and

  1. pH and the cytotoxicity of fluoride in an animal cell culture system

    International Nuclear Information System (INIS)

    Helgeland, K.; Leirskar, J.

    1976-01-01

    To investigate the mechanism for the toxicity of silicate cement as observed in a cell culture system, the effects of pH and fluoride were tested on human epithelial cells (NCTC 2544). At pH 7.3, fluoride concentrations from 15 to 25 μg/ml (0.79 to 1.3 mM) had a growth inhibitory effect. When the pH of the incubation medium was lowered to the range 7.0 to 6.4, an enhanced cytotoxic effect of fluoride was found, and even at 5 to 10 μg/ml growth inhibition occurred. Concomitant with the enhanced cytotoxicity of fluoride at low pH, there was an increased utilization of glucose and formation of lactate. Upon lowering the pH of the incubation medium from 7.4 to 6.7, a twofold increase in the intracellular concentration of fluoride was found. (author)

  2. Irreducible Specht modules are signed Young modules

    OpenAIRE

    Hemmer, David J.

    2005-01-01

    Recently Donkin defined signed Young modules as a simultaneous generalization of Young and twisted Young modules for the symmetric group. We show that in odd characteristic, if a Specht module $S^\\lambda$ is irreducible, then $S^\\lambda$ is a signed Young module. Thus the set of irreducible Specht modules coincides with the set of irreducible signed Young modules. This provides evidence for our conjecture that the signed Young modules are precisely the class of indecomposable self-dual module...

  3. ELEMENTAL ANALYSIS OF RESPIRABLE TIRE PARTICLES AND ASSESSMENT OF CARDIO-PULMONARY TOXICITY IN RATS

    Science.gov (United States)

    Elemental Analysis of Respirable Tire Particles and Assessment of Cardio-pulmonary Toxicity in RatsR.R. Gottipolu, PhD1, E. Landa, PhD2, J.K. McGee, MS1, M.C. Schladweiler, BS1, J.G. Wallenborn, MS3, A.D. Ledbetter, BS1, J.E. Richards, MS1 and U.P. Kodavanti, PhD1. 1NHEER...

  4. Toxicity Reference Database

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

  5. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  6. Potential enzyme toxicity of oxytetracycline to catalase

    International Nuclear Information System (INIS)

    Chi Zhenxing; Liu Rutao; Zhang Hao

    2010-01-01

    Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of OTC in the environment is potentially harmful. In the present work, the non-covalent toxic interaction of OTC with catalase was investigated by the fluorescence spectroscopy, UV-vis absorption and circular dichroism (CD) spectroscopy at physiological pH 7.4. OTC can interact with catalase to form a complex mainly by van der Waals' interactions and hydrogen bonds with one binding site. The association constants K were determined to be K 293K = 7.09 x 10 4 L mol -1 and K 311K = 3.31 x 10 4 L mol -1 . The thermodynamic parameters (ΔH o , ΔG o and ΔS o ) of the interaction were calculated. Based on the Foerster theory of non-radiative energy transfer, the distance between bound OTC and the tryptophan residues of catalase was determined to be 6.48 nm. The binding of OTC can result in change of the micro-environment of the tryptophan residues and the secondary structure of catalase. The activity of catalase was also inhibited for the bound OTC. This work establishes a new strategy to probe the enzyme toxicity of veterinary drug residues and is helpful for clarifying the molecular toxic mechanism of OTC in vivo. The established strategy can be used to investigate the potential enzyme toxicity of other small organic pollutants and drugs.

  7. The role of pH in heavy metal detoxification by biosorption from ...

    African Journals Online (AJOL)

    The high level of toxic metal pollution in the environment is a result of increased human activities. The hydrogen ion concentration of solutions has been known to affect reactions in solutions. The role of pH in As(V), Pb(II) and Hg(II) ions detoxification by bio-sorption from aqueous solutions using coconut fiber and sawdust ...

  8. Alkaline pH sensor molecules.

    Science.gov (United States)

    Murayama, Takashi; Maruyama, Ichiro N

    2015-11-01

    Animals can survive only within a narrow pH range. This requires continual monitoring of environmental and body-fluid pH. Although a variety of acidic pH sensor molecules have been reported, alkaline pH sensor function is not well understood. This Review describes neuronal alkaline pH sensors, grouped according to whether they monitor extracellular or intracellular alkaline pH. Extracellular sensors include the receptor-type guanylyl cyclase, the insulin receptor-related receptor, ligand-gated Cl- channels, connexin hemichannels, two-pore-domain K+ channels, and transient receptor potential (TRP) channels. Intracellular sensors include TRP channels and gap junction channels. Identification of molecular mechanisms underlying alkaline pH sensing is crucial for understanding how animals respond to environmental alkaline pH and how body-fluid pH is maintained within a narrow range. © 2015 Wiley Periodicals, Inc.

  9. Low pH Cements

    International Nuclear Information System (INIS)

    Savage, David; Benbow, Steven

    2007-05-01

    The development of low-pH cements for use in geological repositories for radioactive waste stems from concerns over the potential for deleterious effects upon the host rock and other EBS materials (notably bentonite) under the hyperalkaline conditions (pH > 12) of cement pore fluids. Low pH cement (also known as low heat cement) was developed by the cement industry for use where large masses of cement (e.g. dams) could cause problems regarding heat generated during curing. In low pH cements, the amount of cement is reduced by substitution of materials such as fly ash, blast furnace slag, silica fume, and/or non-pozzolanic silica flour. SKB and Posiva have ruled out the use of blast furnace slag and fly-ash and are focusing on silica fume as a blending agent. Currently, no preferred composition has been identified by these agencies. SKB and Posiva have defined a pH limit ≤ 11 for cement grout leachates. To attain this pH, blending agents must comprise at least 50 wt % of dry materials. Because low pH cement has little, or no free portlandite, the cement consists predominantly of calcium silicate hydrate (CSH) gel with a Ca/Si ratio ≤ 0.8. Although there are potential implications for the performance of the spent fuel and cladding due to the presence of hyperalkaline fluids from cement, the principal focus for safety assessment lies with the behaviour of bentonite. There are a number of potential constraints on the interaction of hyperalkaline cement pore fluids with bentonite, including mass balance, thermodynamic issues, mass transport, and kinetics, but none of these is likely to be limiting if conventional OPC cements are employed in repository construction. Nevertheless: Low-pH cements may supply approximately 50 % less hydroxyl ions than conventional OPC for a given volume of cement, but mass balance constraints are complicated by the uncertainty concerning the type of secondary minerals produced during cement-bentonite interaction. The change of aqueous

  10. Low pH Cements

    Energy Technology Data Exchange (ETDEWEB)

    Savage, David; Benbow, Steven [Quintessa Ltd., Henley-on-Thames (United Kingdom)

    2007-05-15

    The development of low-pH cements for use in geological repositories for radioactive waste stems from concerns over the potential for deleterious effects upon the host rock and other EBS materials (notably bentonite) under the hyperalkaline conditions (pH > 12) of cement pore fluids. Low pH cement (also known as low heat cement) was developed by the cement industry for use where large masses of cement (e.g. dams) could cause problems regarding heat generated during curing. In low pH cements, the amount of cement is reduced by substitution of materials such as fly ash, blast furnace slag, silica fume, and/or non-pozzolanic silica flour. SKB and Posiva have ruled out the use of blast furnace slag and fly-ash and are focusing on silica fume as a blending agent. Currently, no preferred composition has been identified by these agencies. SKB and Posiva have defined a pH limit {<=} 11 for cement grout leachates. To attain this pH, blending agents must comprise at least 50 wt % of dry materials. Because low pH cement has little, or no free portlandite, the cement consists predominantly of calcium silicate hydrate (CSH) gel with a Ca/Si ratio {<=} 0.8. Although there are potential implications for the performance of the spent fuel and cladding due to the presence of hyperalkaline fluids from cement, the principal focus for safety assessment lies with the behaviour of bentonite. There are a number of potential constraints on the interaction of hyperalkaline cement pore fluids with bentonite, including mass balance, thermodynamic issues, mass transport, and kinetics, but none of these is likely to be limiting if conventional OPC cements are employed in repository construction. Nevertheless: Low-pH cements may supply approximately 50 % less hydroxyl ions than conventional OPC for a given volume of cement, but mass balance constraints are complicated by the uncertainty concerning the type of secondary minerals produced during cement-bentonite interaction. The change of aqueous

  11. pH-dependent toxicity of sulphur mustard in vitro

    International Nuclear Information System (INIS)

    Sawyer, Thomas W.; Vair, Cory; Nelson, Peggy; Shei Yimin; Bjarnason, Stephen; Tenn, Catherine; McWilliams, Michael; Villanueva, Mercy; Burczyk, Andrew

    2007-01-01

    The dependence of sulphur mustard (HD) toxicity on intracellular (pH i ) and extracellular pH was examined in CHO-K1 cells. HD produced an immediate and significant concentration-dependent decline in cytosolic pH, and also inhibited the mechanisms responsible for restoring pH i to physiological values. The concentration-response of HD-induced cytosolic acidification, closely paralleled the acidification of the extracellular buffer through HD hydrolysis. A viability study was carried out in order to assess the importance of HD-induced cytosolic acidification. Cultures were exposed to HD for 1 h in media that were adjusted through a pH range (pH 5.0-10), and the 24 h LC 50 values were assessed using the viability indicator dye alamarBlue TM . The toxicity of HD was found to be dependent on extracellular pH, with a greater than eight-fold increase in LD 50 obtained in cultures treated with HD at pH 9.5, compared to those treated at pH 5.0. Assays of apoptotic cell death, including morphology, soluble DNA, caspase-3 activity and TUNEL also showed that as pH was increased, much greater HD concentrations were required to cause cell death. The modest decline in HD half-life measured in buffers of increasing pH, did not account for the protective effects of basic pH. The early event(s) that HD initiates to eventually culminate in cell death are not known. However, based on the data obtained in this study, we propose that HD causes an extracellular acidification through chemical hydrolysis and that this, in both a concentration and temporally related fashion, results in cytosolic acidification. Furthermore, HD also acts to poison the antiporter systems responsible for maintaining physiological pH i , so that the cells are unable to recover from this insult. It is this irreversible decline in pH i that initiates the cascade of events that results in HD-induced cell death

  12. Differential gene expression in tomato fruit and Colletotrichum gloeosporioides during colonization of the RNAi-SlPH tomato line with reduced fruit acidity and higher pH.

    Science.gov (United States)

    Barad, Shiri; Sela, Noa; Dubey, Amit K; Kumar, Dilip; Luria, Neta; Ment, Dana; Cohen, Shahar; Schaffer, Arthur A; Prusky, Dov

    2017-08-04

    The destructive phytopathogen Colletotrichum gloeosporioides causes anthracnose disease in fruit. During host colonization, it secretes ammonia, which modulates environmental pH and regulates gene expression, contributing to pathogenicity. However, the effect of host pH environment on pathogen colonization has never been evaluated. Development of an isogenic tomato line with reduced expression of the gene for acidity, SlPH (Solyc10g074790.1.1), enabled this analysis. Total RNA from C. gloeosporioides colonizing wild-type (WT) and RNAi-SlPH tomato lines was sequenced and gene-expression patterns were compared. C. gloeosporioides inoculation of the RNAi-SlPH line with pH 5.96 compared to the WT line with pH 4.2 showed 30% higher colonization and reduced ammonia accumulation. Large-scale comparative transcriptome analysis of the colonized RNAi-SlPH and WT lines revealed their different mechanisms of colonization-pattern activation: whereas the WT tomato upregulated 13-LOX (lipoxygenase), jasmonic acid and glutamate biosynthesis pathways, it downregulated processes related to chlorogenic acid biosynthesis II, phenylpropanoid biosynthesis and hydroxycinnamic acid tyramine amide biosynthesis; the RNAi-SlPH line upregulated UDP-D-galacturonate biosynthesis I and free phenylpropanoid acid biosynthesis, but mainly downregulated pathways related to sugar metabolism, such as the glyoxylate cycle and L-arabinose degradation II. Comparison of C. gloeosporioides gene expression during colonization of the WT and RNAi-SlPH lines showed that the fungus upregulates ammonia and nitrogen transport and the gamma-aminobutyric acid metabolic process during colonization of the WT, while on the RNAi-SlPH tomato, it mainly upregulates the nitrate metabolic process. Modulation of tomato acidity and pH had significant phenotypic effects on C. gloeosporioides development. The fungus showed increased colonization on the neutral RNAi-SlPH fruit, and limited colonization on the WT acidic fruit

  13. Histone deacetylase-mediated regulation of endolysosomal pH.

    Science.gov (United States)

    Prasad, Hari; Rao, Rajini

    2018-05-04

    The pH of the endolysosomal system is tightly regulated by a balance of proton pump and leak mechanisms that are critical for storage, recycling, turnover, and signaling functions in the cell. Dysregulation of endolysosomal pH has been linked to aging, amyloidogenesis, synaptic dysfunction, and various neurodegenerative disorders, including Alzheimer's disease. Therefore, understanding the mechanisms that regulate luminal pH may be key to identifying new targets for managing these disorders. Meta-analysis of yeast microarray databases revealed that nutrient-limiting conditions inhibited the histone deacetylase (HDAC) Rpd3 and thereby up-regulated transcription of the endosomal Na + /H + exchanger Nhx1, resulting in vacuolar alkalinization. Consistent with these findings, Rpd3 inhibition by the HDAC inhibitor and antifungal drug trichostatin A induced Nhx1 expression and vacuolar alkalinization. Bioinformatics analysis of Drosophila and mouse databases revealed that caloric control of the Nhx1 orthologs DmNHE3 and NHE6, respectively, is also mediated by HDACs. We show that NHE6 is a target of the transcription factor cAMP-response element-binding protein (CREB), a known regulator of cellular responses to low-nutrient conditions, providing a molecular mechanism for nutrient- and HDAC-dependent regulation of endosomal pH. Of note, pharmacological targeting of the CREB pathway to increase NHE6 expression helped regulate endosomal pH and correct defective clearance of amyloid Aβ in an apoE4 astrocyte model of Alzheimer's disease. These observations from yeast, fly, mouse, and cell culture models point to an evolutionarily conserved mechanism for HDAC-mediated regulation of endosomal NHE expression. Our insights offer new therapeutic strategies for modulation of endolysosomal pH in fungal infection and human disease. © 2018 Prasad and Rao.

  14. Signed Young Modules and Simple Specht Modules

    OpenAIRE

    Danz, Susanne; Lim, Kay Jin

    2015-01-01

    By a result of Hemmer, every simple Specht module of a finite symmetric group over a field of odd characteristic is a signed Young module. While Specht modules are parametrized by partitions, indecomposable signed Young modules are parametrized by certain pairs of partitions. The main result of this article establishes the signed Young module labels of simple Specht modules. Along the way we prove a number of results concerning indecomposable signed Young modules that are of independent inter...

  15. Fetal scalp pH testing

    Science.gov (United States)

    Fetal scalp blood; Scalp pH testing; Fetal blood testing - scalp; Fetal distress - fetal scalp testing; Labor - fetal scalp testing ... a baby. In these cases, testing the scalp pH can help the doctor decide whether the fetus ...

  16. Acid loading test (pH)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003615.htm Acid loading test (pH) To use the sharing features on this page, please enable JavaScript. The acid loading test (pH) measures the ability of the ...

  17. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

  18. Memory Modulation

    NARCIS (Netherlands)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive

  19. Module descriptor

    DEFF Research Database (Denmark)

    Vincenti, Gordon; Klausen, Bodil; Kjær Jensen, Jesper

    2016-01-01

    The Module Descriptor including a Teacher’s Guide explains and describes how to work innovatively and co-creatively with wicked problems and young people. The descriptor shows how interested educators and lecturers in Europe can copy the lessons of the Erasmus+ project HIP when teaching their own...

  20. Biona-C Cell Culture pH Monitoring System

    Science.gov (United States)

    Friedericks, C.

    1999-01-01

    Sensors 2000! is developing a system to demonstrate the ability to perform accurate, real-time measurements of pH and CO2 in a cell culture media in Space. The BIONA-C Cell Culture pH Monitoring System consists of S2K! developed ion selective sensors and control electronics integrated with the fluidics of a cell culture system. The integrated system comprises a "rail" in the Cell Culture Module (CCM) of WRAIR (Space Biosciences of Walter Read Army Institute of Research). The CCM is a Space Shuttle mid-deck locker experiment payload. The BIONA-C is displayed along with associated graphics and text explanations. The presentation will stimulate interest in development of sensor technology for real-time cell culture measurements. The transfer of this technology to other applications will also be of interest. Additional information is contained in the original document.

  1. pH sensor calibration procedure

    OpenAIRE

    Artero Delgado, Carola; Nogueras Cervera, Marc; Manuel Lázaro, Antonio; Prat Tasias, Jordi; Prat Farran, Joana d'Arc

    2013-01-01

    This paper describes the calibration of pH sensor located at the OBSEA marine Observatory. This instrument is based on an industrial pH electrode that is connected to a CTD instrument (Conductivity, Temperature, and Depth ). The calibration of the pH sensor has been done using a high precision spectrophotometer pH meter from Institute of Marine Sciences (ICM), and in this way it has been obtained a numerical function for the p H sensor propor...

  2. PhD students and integrative research

    NARCIS (Netherlands)

    Fry, G.; Tress, B.; Tress, G.

    2006-01-01

    The training of PhD students is currently very dynamic and varies widely from place to place. We present some examples of this variation and comment on how it may affect the way PhD students cope with integrative studies. Our focus is on the training needs of PhD students studying integrative

  3. The toxicity of plutonium

    International Nuclear Information System (INIS)

    Crouse, P.L.

    1994-01-01

    Shipments of plutonium occasionally pass around the Cape coastal waters on its way to Japan from Europe. This invariably leads to a great deal of speculation of the dangers involved and of the extreme toxicity of plutonium, with the media and environmental groups claiming that (a) plutonium is the most toxic substance known to man, and that (b) a few kilograms of plutonium ground finely and dispersed in the atmosphere could kill every human being on earth. Comparisons with other poisons are drawn, e.g. common inorganic chemicals and biological agents. The original scare around the extraordinary toxicity of Pu seems to have started in 1974 with the claims of Tamplin and Cochran's hot particle theory about plutonium lodging in the sensitive portions of the lungs in small concentrated aggregates where they are much more effective in producing cancers. This theory, however, is regarded as thoroughly discredited by the experts in the field of radiotoxicity. 8 refs

  4. Iron metabolism and toxicity

    International Nuclear Information System (INIS)

    Papanikolaou, G.; Pantopoulos, K.

    2005-01-01

    Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

  5. Seasonal variability in irradiance affects herbicide toxicity to the marine flagellate Dunaliella tertiolecta

    NARCIS (Netherlands)

    Sjollema, S.B.; Vavourakis, C.D.; van der Geest, H.G.; Vethaak, A.D.; Admiraal, W.

    2014-01-01

    Photosynthetically Active Radiation (PAR) and Ultraviolet Radiation (UVR) of the solar spectrum affect microalgae directly and modify the toxicity of phytotoxic compounds present in water. As a consequence seasonal variable PAR and UVR levels are likely to modulate the toxic pressure of contaminants

  6. Role of soil properties in sewage sludge toxicity to soil collembolans

    OpenAIRE

    Domene, X.

    2010-01-01

    Soil properties are one of the most important factors explaining the different toxicity results found in different soils. Although there is knowledge about the role of soil properties on the toxicity of individual chemicals, not much is known about its relevance for sewage sludge amendments. In particular little is known about the effect of soil properties on the toxicity modulation of these complex wastes. In addition, in most studies on sewage sludges the identity of the main substances lin...

  7. Catalytic Ozonation of Phenolic Wastewater: Identification and Toxicity of Intermediates

    Directory of Open Access Journals (Sweden)

    Mahdi Farzadkia

    2014-01-01

    Full Text Available A new strategy in catalytic ozonation removal method for degradation and detoxification of phenol from industrial wastewater was investigated. Magnetic carbon nanocomposite, as a novel catalyst, was synthesized and then used in the catalytic ozonation process (COP and the effects of operational conditions such as initial pH, reaction time, and initial concentration of phenol on the degradation efficiency and the toxicity assay have been investigated. The results showed that the highest catalytic potential was achieved at optimal neutral pH and the removal efficiency of phenol and COD is 98.5% and 69.8%, respectively. First-order modeling demonstrated that the reactions were dependent on the initial concentration of phenol, with kinetic constants varying from 0.038 min−1  ([phenol]o = 1500 mg/L to 1.273 min−1 ([phenol]o = 50 mg/L. Bioassay analysis showed that phenol was highly toxic to Daphnia magna (LC50 96 h=5.6 mg/L. Comparison of toxicity units (TU of row wastewater (36.01 and the treated effluent showed that TU value, after slightly increasing in the first steps of ozonation for construction of more toxic intermediates, severely reduced at the end of reaction (2.23. Thus, COP was able to effectively remove the toxicity of intermediates which were formed during the chemical oxidation of phenolic wastewaters.

  8. Modulation of biochemical stress initiated by toxicants in diet ...

    African Journals Online (AJOL)

    sunny t

    2016-07-27

    Jul 27, 2016 ... meat in some parts of Nigeria, such as Owerri in Imo state (Ujowundu et al., ..... containing bromocresol green (BCG) was added to the tubes mixed ...... Xin Z, Waterman DF, Henken RM, Harman RJ (1991) Effects of copper.

  9. External radiation toxicity

    International Nuclear Information System (INIS)

    Fritz, T.E.

    1979-01-01

    The section contains summaries of research on neutron and gamma-ray toxicity in rodents, late effects of low-dose rate, whole-body, protracted exposure to 60 Co gamma rays on young adult beagles, and the effects of protracted, low-dose rate exposure to 60 Co gamma rays on preclinical leukemic phase-related changes in the granulopoietic system of beagles

  10. Local anaesthetic toxicity

    African Journals Online (AJOL)

    Local anaesthetic toxicity has been known since the introduction of local anaesthetic drugs into anaesthetic practice more than a hundred ... was the first to think of cocaine as a narcotic. ..... anaesthetics act as Na+ channel-blocking agents, they slow down .... all neurons, leading to global CNS depression, slowing and.

  11. Toxicity of lunar dust

    NARCIS (Netherlands)

    Linnarsson, D.; Carpenter, J.; Fubini, B.; Gerde, P.; Loftus, D.; Prisk, K.; Staufer, U.; Tranfield, E.; van Westrenen, W.

    2012-01-01

    The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of

  12. Uranium: biokinetics and toxicity

    International Nuclear Information System (INIS)

    Menetrier, F.; Renaud-Salis, V.; Flury-Herard, A.

    2000-01-01

    This report was achieved as a part of a collaboration with the Fuel Cycle Direction. Its aim was to give the state of the art about: the behaviour of uranium in the human organism (biokinetics) after ingestion, its toxicity (mainly renal) and the current regulation about its incorporation. Both in the upstream and in the downstream of the fuel cycle, uranium remains, quantitatively, the first element in the cycle which is, at the present time, temporarily disposed or recycled. Such a considerable quantity of uranium sets the problem of its risk on the health. In the long term, the biosphere may be affected and consequently the public may ingest water or food contaminated with uranium. In this way, radiological and chemical toxicity risk may be activated. This report emphasizes: the necessity of confirming some experimental and epidemiological biokinetic data used or not in the ICRP models. Unsolved questions remain about the gastrointestinal absorption according to chemical form (valency state, mixtures...), mass and individual variations (age, disease) further a chronic ingestion of uranium. It is well established that uranium is mainly deposited in the skeleton and the kidney. But the skeleton kinetics following a chronic ingestion and especially in some diseases has to be more elucidated; the necessity of taking into account uranium at first as a chemical toxic, essentially in the kidney and determining the threshold of functional lesion. In this way, it is important to look for some specific markers; the problem of not considering chemical toxicity of uranium in the texts regulating its incorporation

  13. How toxic is ibogaine?

    NARCIS (Netherlands)

    Litjens, Ruud P. W.; Brunt, Tibor M.

    2016-01-01

    Ibogaine is a psychoactive indole alkaloid found in the African rainforest shrub Tabernanthe Iboga. It is unlicensed but used in the treatment of drug and alcohol addiction. However, reports of ibogaine's toxicity are cause for concern. To review ibogaine's pharmacokinetics and pharmacodynamics,

  14. Monosodium Glutamate Toxicity

    African Journals Online (AJOL)

    Dr Olaleye

    The brain is reportedly sensitive to monosodium glutamate (MSG) toxicity via oxidative stress. Sida acuta leaf ethanolic .... wherein the right hemisphere, was preserved for histology and fixed in 10% ... Biochemical Assays: The left hemisphere of the brain samples was ...... development in male and female rats. Exp Physiol.

  15. Nanomaterials and Retinal Toxicity

    Science.gov (United States)

    The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

  16. Toxic Hazards in Aviation.

    Science.gov (United States)

    1981-04-01

    Pasteur, Lillm,FRANCE. (2) CONISH H.H., EARTH M.L.& IANNi F.L, "Comparative Toxicology of Platics during Thar-modecoqiorition Intsw-re8posium on...Pyrolysnis and Combustion of Materials" Firm and Materials (1976).1, 29-35 (8) ALAAIE Y."Toxicity of Platic dacomposition ProductsŖd Annu~al Progress

  17. Dynamic regulation of gastric surface pH by luminal pH

    OpenAIRE

    Chu, Shaoyou; Tanaka, Shin; Kaunitz, Jonathan D.; Montrose, Marshall H.

    1999-01-01

    In vivo confocal imaging of the mucosal surface of rat stomach was used to measure pH noninvasively under the mucus gel layer while simultaneously imaging mucus gel thickness and tissue architecture. When tissue was superfused at pH 3, the 25 μm adjacent to the epithelial surface was relatively alkaline (pH 4.1 ± 0.1), and surface alkalinity was enhanced by topical dimethyl prostaglandin E2 (pH 4.8 ± 0.2). Luminal pH was changed from pH 3 to pH 5 to mimic the fasted-to-fed transition in intra...

  18. Enhancement of Radiotherapeutic Efficacy by Paclitaxel-Loaded ph-Sensitive Block Copolymer Micelles

    International Nuclear Information System (INIS)

    Jinhyang, C.; Jaesook, P.; Dong-Hoon, J.

    2012-01-01

    Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nano materials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nano materials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into ph-sensitive block copolymer micelle (psm-PTX), polyethylene glycol-graft-poly(β-amino ester), and pre clinically evaluated for its effect on RT. The size of psm-PTX was 125. 4.4±nm at ph 7.4. psm-PTX released PTX rapidly in the acidic condition (ph 6.5), while it was reasonably stable in the physiologic condition (ph 7.4). The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemo radiotherapeutic efficacy.

  19. Estimation of toxicity using the Toxicity Estimation Software Tool (TEST)

    Science.gov (United States)

    Tens of thousands of chemicals are currently in commerce, and hundreds more are introduced every year. Since experimental measurements of toxicity are extremely time consuming and expensive, it is imperative that alternative methods to estimate toxicity are developed.

  20. Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

    OpenAIRE

    Md. Rajibur Rahaman Khan; Shin-Won Kang

    2016-01-01

    In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal?s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The...

  1. Novel functions of CCM1 delimit the relationship of PTB/PH domains.

    Science.gov (United States)

    Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

    2017-10-01

    Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and

  2. pH control structure design for a periodically operated membrane separation process

    DEFF Research Database (Denmark)

    Prado Rubio, Oscar Andres; Jørgensen, Sten Bay; Jonsson, Gunnar Eigil

    2012-01-01

    A bioreactor integrated with an electrically driven membrane separation process (Reverse Electro-Enhanced Dialysis – REED) is under investigation as potential technology for intensifying lactic acid bioproduction. In this contribution the pH regulation issue in the periodically operated REED module...

  3. Differential toxicity and influence of salinity on acute toxicity of ...

    African Journals Online (AJOL)

    Differential toxicity and influence of salinity on acute toxicity of copper sulphate and lead nitrate against Oreochromis niloticus. KA Bawa-Allah, F Osuala, J Effiong. Abstract. This study investigated the salinity-tolerance of Oreochromis niloticus and the influence of salinity changes on the acute toxicities of copper sulphate ...

  4. Long-term toxicity assessment of soils in a recovered area affected by a mining spill

    International Nuclear Information System (INIS)

    Romero-Freire, A.; García Fernández, I.; Simón Torres, M.; Martínez Garzón, F.J.; Martín Peinado, F.J.

    2016-01-01

    Residual pollution in the Guadiamar Green Corridor still remains after Aználcollar mine spill in 1998. The polluted areas are identified by the absence of vegetation, soil acidic pH and high concentrations of As, Pb, Zn and Cu. Soil toxicity was assessed by lettuce root elongation and induced soil respiration bioassays. In bare soils, total As and Pb concentrations and water-extractable levels for As, Zn and Cu exceeded the toxicity guidelines. Pollutants responsible for toxicity were different depending on the tested organism, with arsenic being most toxic for lettuce and the metal mixture to soil respiration. Soil properties, such as pH or organic carbon content, are key factors to control metal availability and toxicity in the area. According to our results, there is a risk of pollution to living organisms and the soil quality criteria established in the area should be revised to reduce the risk of toxicity. - Highlights: • 15 years after the Aznalcóllar mine spill residual pollution remains in some areas. • Toxic levels were exceeded for total As and Pb and for soluble As, Zn and Cu. • Metals responsible for soil toxicity are different depending on the tested organism. • pH and organic carbon content reduce metal availability and therefore soil toxicity. • Regulatory guidelines in the area should be revised to reduce the risk of toxicity. - Residual pollution in the Guadiamar Green Corridor remains in some areas after long-term stabilization, with some risk of pollution according to toxicity bioassays.

  5. Biological control of toxic cyanobacteri

    CSIR Research Space (South Africa)

    Ndlela, Luyanda L

    2017-05-01

    Full Text Available . Ecotoxicity studies: is toxicity reduced? (Testing on daphnids, fish and human cell lines) Resulting impacts on cyanotoxins (Toxin conformation changes, ELISA detection) Competition assays against toxic cyanobacteria (Can Bacillus etc. outcompete...

  6. Allegheny County Toxics Release Inventory

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  7. Measurements of spectral responses for developing fiber-optic pH sensor

    Science.gov (United States)

    Yoo, Wook Jae; Heo, Ji Yeon; Jang, Kyoung Won; Seo, Jeong Ki; Moon, Jin Soo; Park, Jang-Yeon; Park, Byung Gi; Cho, Seunghyun; Lee, Bongsoo

    2011-01-01

    In this study, we have fabricated a fiber-optic pH sensor, which is composed of a light source, a pH-sensing probe, plastic optical fibers and a spectrometer, for determining the degree of infection by Helicobacter pylori in the stomach. As pH indicators, phenol red and m-cresol purple are used, and pH liquid solutions are prepared by mixing phenol red or m-cresol purple solutions and various kinds of pH buffer solutions. The light emitted by a light source is guided by plastic optical fibers to the pH liquid solution, and the optical characteristic of a reflected light is changed according to the color variations of the pH indicator in the pH-sensing probe. Therefore, we have measured the intensities and wavelength shifts of the reflected lights, which change according to the color variations of indicators at different pH values, by using a spectrometer for spectral analysis. Also, the relationships between the pH values of liquid solutions and the optical properties of the modulated lights are obtained on the basis of the changes of the colors of indicators.

  8. Salivary pH as a marker of plasma adiponectin concentrations in Women.

    Science.gov (United States)

    Tremblay, Monique; Loucif, Yacine; Methot, Julie; Brisson, Diane; Gaudet, Daniel

    2012-02-03

    Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p salivary pH (R2) was 10.8% (p salivary pH quartiles (p = 0.005). These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.

  9. Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells

    International Nuclear Information System (INIS)

    Reid, I.R.; Civitelli, R.; Avioli, L.V.; Hruska, K.A.

    1988-01-01

    It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pH i ) and there is some evidence that this in turn may influence cell growth. The authors have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5,(6)-carboxyfluorescein indicated that these cells regulate pH i by means of an amiloride-inhibitable Na + -H + exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pH i with a half-maximal effect at 10 -11 M. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pH i and [ 3 H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [ 3 H]thymidine incorporation in the presence of amiloride, even though it did not affect pH i in these circumstances. It is concluded that PTH decreases pH i and growth in UMR 106 cells but that these changes can be dissociated. Depression of pH i may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment

  10. Toxic waste liquor disposal

    International Nuclear Information System (INIS)

    Burton, W.R.

    1985-01-01

    Toxic waste liquors, especially radio active liquors, are disposed in a sub-zone by feeding down a bore hole a first liquid, then a buffer liquid (e.g. water), then the toxic liquors. Pressure variations are applied to the sub-zone to mix the first liquid and liquors to form gels or solids which inhibit further mixing and form a barrier between the sub-zone and the natural waters in the environment of the sub-zone. In another example the location of the sub-zone is selected so that the environement reacts with the liquors to produce a barrier around the zone. Blind bore holes are used to monitor the sub-zone profile. Materials may be added to the liquor to enhance barrier formation. (author)

  11. Photosynthetic and cellular toxicity of cadmium in Chlorella vulgaris.

    Science.gov (United States)

    Ou-Yang, Hui-Ling; Kong, Xiang-Zhen; Lavoie, Michel; He, Wei; Qin, Ning; He, Qi-Shuang; Yang, Bin; Wang, Rong; Xu, Fu-Liu

    2013-12-01

    The toxic effects of cadmium (Cd) on the green alga Chlorella vulgaris were investigated by following the response to Cd of various toxicity endpoints (cell growth, cell size, photochemical efficiency of PSII in the light or Φ(PSII), maximal photochemical efficiency or Fv/Fm, chlorophyll a fluorescence, esterase activity, and cell viability). These toxicity endpoints were studied in laboratory batch cultures of C. vulgaris over a long-term 96-h exposure to different Cd concentrations using flow cytometry and pulse amplitude modulated fluorometry. The sequence of sensitivity of these toxicity endpoints was: cell yield > Φ(PSII) ≈ esterase activity > Fv/Fm > chlorophyll a fluorescence ≈ cell viability. It is shown that cell apoptosis or cell death only accounted for a minor part of the reduction in cell yield even at very high algistatic free Cd²⁺ concentrations, and other mechanisms such as blocked cell divisions are major contributors to cell yield inhibition. Furthermore, cadmium may affect both the electron donors and acceptors of the electron transport chain at high free Cd²⁺ concentration. Finally, the resistance of cells to cell death was size-dependent; medium-sized cells had the highest toxicity threshold. The present study brings new insights into the toxicity mechanisms of Cd in C. vulgaris and provides a detailed comparison of the sensitivity of various Cd toxicity endpoints. © 2013 SETAC.

  12. Modeling pH variation in reverse osmosis.

    Science.gov (United States)

    Nir, Oded; Bishop, Noga Fridman; Lahav, Ori; Freger, Viatcheslav

    2015-12-15

    The transport of hydronium and hydroxide ions through reverse osmosis membranes constitutes a unique case of ionic species characterized by uncommonly high permeabilities. Combined with electromigration, this leads to complex behavior of permeate pH, e.g., negative rejection, as often observed for monovalent ions in nanofiltration of salt mixtures. In this work we employed a rigorous phenomenological approach combined with chemical equilibrium to describe the trans-membrane transport of hydronium and hydroxide ions along with salt transport and calculate the resulting permeate pH. Starting from the Nernst-Planck equation, a full non-linear transport equation was derived, for which an approximate solution was proposed based on the analytical solution previously developed for trace ions in a dominant salt. Using the developed approximate equation, transport coefficients were deduced from experimental results obtained using a spiral wound reverse osmosis module operated under varying permeate flux (2-11 μm/s), NaCl feed concentrations (0.04-0.18 M) and feed pH values (5.5-9.0). The approximate equation agreed well with the experimental results, corroborating the finding that diffusion and electromigration, rather than a priori neglected convection, were the major contributors to the transport of hydronium and hydroxide. The approach presented here has the potential to improve the predictive capacity of reverse osmosis transport models for acid-base species, thereby improving process design/control. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Effect of long-term smoking on salivary flow rate and salivary pH

    Directory of Open Access Journals (Sweden)

    Mala Singh

    2015-01-01

    Full Text Available Introduction: Saliva is a complex and important body fluid which is very essential for oral health and it is the first biological fluid that is exposed to cigarette smoke, which contains numerous toxic compositions responsible for structural and functional changes in saliva. Aim: To evaluate the long-term effect of smoking on salivary flow rate (SFR and salivary pH. Materials and Methods: The subjects of the study were divided into smokers and nonsmokers. Each group comprised of 35 male adults. The saliva of each subject was collected under resting conditions. They were asked to spit in a graduated container at an interval of 60 s for 5 min. Salivary pH was measured immediately after measuring SFR using the (Indikrom Paper pH indicator and calibrated cylinder. Based on the color change of the indicator paper strip, the pH was assessed in comparison with a color chart. Data were analyzed by Student′s t-test using SPSS 15. Results: The mean (±standard deviation SFR and pH were 0.20 (±0.05 ml/min and 6.30 (±0.36 respectively in smokers while the mean SFR and pH were 0.36 (±0.06 ml/min and 7.10 (±0.24 in nonsmokers. The difference was statistically significant (P = 0.00. Conclusion: Long-term smoking significantly reduces the SFR and salivary pH.

  14. Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

    Science.gov (United States)

    Gatea, Florentina; Teodor, Eugenia Dumitra; Seciu, Ana-Maria; Covaci, Ovidiu Ilie; Mănoiu, Sorin; Lazăr, Veronica; Radu, Gabriel Lucian

    2015-07-01

    The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells.

  15. Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

    Energy Technology Data Exchange (ETDEWEB)

    Gatea, Florentina; Teodor, Eugenia Dumitra, E-mail: eu-teodor@yahoo.com [National Institute for Biological Sciences, Centre of Bioanalysis (Romania); Seciu, Ana-Maria [National Institute for Biological Sciences, Cellular and Molecular Biology Department (Romania); Covaci, Ovidiu Ilie [SARA Pharm Solutions (Romania); Mănoiu, Sorin [National Institute for Biological Sciences, Cellular and Molecular Biology Department (Romania); Lazăr, Veronica [University of Bucharest, Faculty of Biology (Romania); Radu, Gabriel Lucian [University “Politehnica” Bucharest, Faculty of Applied Chemistry and Materials Science (Romania)

    2015-07-15

    The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells.

  16. Portable, accurate toxicity testing

    International Nuclear Information System (INIS)

    Sabate, R.W.; Stiffey, A.V.; Dewailly, E.L.; Hinds, A.A.; Vieaux, G.J.

    1994-01-01

    Ever tightening environmental regulations, severe penalties for non-compliance, and expensive remediation costs have stimulated development of methods to detect and measure toxins. Most of these methods are bioassays that must be performed in the laboratory; none previously devised has been truly portable. The US Army, through the Small Business Innovative Research program, has developed a hand-held, field deployable unit for testing toxicity of battlefield water supplies. This patented system employs the measurable quenching, in the presence of toxins, of the natural bioluminescence produced by the marine dinoflagellate alga Pyrocystis lunula. The procedure's inventor used it for years to measure toxicity concentrations of chemical warfare agents actually, their simulants, primarily in the form of pesticides and herbicides plus assorted toxic reagents, waterbottom samples, drilling fluids, even blood. While the procedure is more precise, cheaper, and faster than most bioassays, until recently it was immobile. Now it is deployable in the field. The laboratory apparatus has been proven to be sensitive to toxins in concentrations as low as a few parts per billion, repeatable within a variation of 10% or less, and unlike some other bioassays effective in turbid or colored media. The laboratory apparatus and the hand-held tester have been calibrated with the EPA protocol that uses the shrimplike Mysidopsis bahia. The test organism tolerates transportation well, but must be rested a few hours at the test site for regeneration of its light-producing powers. Toxicity now can be measured confidently in soils, water columns, discharge points, and many other media in situ. Most significant to the oil industry is that drilling fluids can be monitored continuously on the rig

  17. Lead toxicity: current concerns.

    OpenAIRE

    Goyer, R A

    1993-01-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has be...

  18. Toxic Substances Control Act

    Energy Technology Data Exchange (ETDEWEB)

    1992-05-15

    This Reference Book contains a current copy of the Toxic Substances Control Act and those regulations that implement the statute and appear to be most relevant to DOE activities. The document is provided to DOE and contractor staff for informational purposes only and should not be interpreted as legal guidance. Questions concerning this Reference Book may be directed to Mark Petts, EH-231 (202/586-2609).

  19. Kombucha--toxicity alert.

    Science.gov (United States)

    The Kombucha mushroom, also known as Manchurian mushroom, is a mail-order product touted to lower blood pressure and raise T-cell counts. No controlled trials have been conducted to test these claims. Aspergillus, a mold that may grow on the Kombucha mushroom, attacks the brain and may be fatal to persons with weakened immune systems. Reported toxicity reactions have included stomach problems and yeast infections. Taking Kombucha in combination with other drugs may affect the drugs potency.

  20. Toxicity of nitrogen pentoxide

    Energy Technology Data Exchange (ETDEWEB)

    Diggle, W M; Gage, J C

    1954-01-01

    Two ppM N/sub 2/O/sub 5/ for 4 h or 1 ppM, 4 h/day for 12 days produced acute pulmonary edema in rats. Ten daily 4-h exposures to 0.5 ppM produced no edema but respiratory distress. NO/sub 2/ produced no edema (some hemorrhage) at 80 mg/m/sup 3/. Nitric acid vapor (63 mg/m/sup 3/) had no obvious toxic effect.

  1. Potential enzyme toxicity of oxytetracycline to catalase

    Energy Technology Data Exchange (ETDEWEB)

    Zhenxing, Chi; Rutao, Liu; Zhang Hao, E-mail: Trutaoliu@sdu.edu.cn [School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment and Health, Shandong Province, 27 Shanda South Road, Jinan 250100 (China)

    2010-10-15

    Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of OTC in the environment is potentially harmful. In the present work, the non-covalent toxic interaction of OTC with catalase was investigated by the fluorescence spectroscopy, UV-vis absorption and circular dichroism (CD) spectroscopy at physiological pH 7.4. OTC can interact with catalase to form a complex mainly by van der Waals' interactions and hydrogen bonds with one binding site. The association constants K were determined to be K{sub 293K} = 7.09 x 10{sup 4} L mol{sup -1} and K{sub 311K} = 3.31 x 10{sup 4} L mol{sup -1}. The thermodynamic parameters ({Delta}H{sup o}, {Delta}G{sup o} and {Delta}S{sup o}) of the interaction were calculated. Based on the Foerster theory of non-radiative energy transfer, the distance between bound OTC and the tryptophan residues of catalase was determined to be 6.48 nm. The binding of OTC can result in change of the micro-environment of the tryptophan residues and the secondary structure of catalase. The activity of catalase was also inhibited for the bound OTC. This work establishes a new strategy to probe the enzyme toxicity of veterinary drug residues and is helpful for clarifying the molecular toxic mechanism of OTC in vivo. The established strategy can be used to investigate the potential enzyme toxicity of other small organic pollutants and drugs.

  2. Toxicity and toxicokinetics of metformin in rats

    International Nuclear Information System (INIS)

    Quaile, Michael P.; Melich, David H.; Jordan, Holly L.; Nold, James B.; Chism, Jack P.; Polli, Joseph W.; Smith, Glenn A.; Rhodes, Melissa C.

    2010-01-01

    Metformin is a first-line drug for the treatment of type 2 diabetes (T2D) and is often prescribed in combination with other drugs to control a patient's blood glucose level and achieve their HbA1c goal. New treatment options for T2D will likely include fixed dose combinations with metformin, which may require preclinical combination toxicology studies. To date, there are few published reports evaluating the toxicity of metformin alone to aid in the design of these studies. Therefore, to understand the toxicity of metformin alone, Crl:CD(SD) rats were administered metformin at 0, 200, 600, 900 or 1200 mg/kg/day by oral gavage for 13 weeks. Administration of ≥ 900 mg/kg/day resulted in moribundity/mortality and clinical signs of toxicity. Other adverse findings included increased incidence of minimal necrosis with minimal to slight inflammation of the parotid salivary gland for males given 1200 mg/kg/day, body weight loss and clinical signs in rats given ≥ 600 mg/kg/day. Metformin was also associated with evidence of minimal metabolic acidosis (increased serum lactate and beta-hydroxybutyric acid and decreased serum bicarbonate and urine pH) at doses ≥ 600 mg/kg/day. There were no significant sex differences in mean AUC 0-24 or C max nor were there significant differences in mean AUC 0-24 or C max following repeated dosing compared to a single dose. The no observable adverse effect level (NOAEL) was 200 mg/kg/day (mean AUC 0-24 = 41.1 μg h/mL; mean C max = 10.3 μg/mL based on gender average week 13 values). These effects should be taken into consideration when assessing potential toxicities of metformin in fixed dose combinations.

  3. Resveratrol prevents ammonia toxicity in astroglial cells.

    Directory of Open Access Journals (Sweden)

    Larissa Daniele Bobermin

    Full Text Available Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS. Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS, GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA and extracellular signal-regulated kinase (ERK pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity.

  4. Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

    Science.gov (United States)

    Guerra, Maria Cristina; Leite, Marina Concli; Souza, Diogo Onofre; Gonçalves, Carlos-Alberto; Gottfried, Carmem

    2012-01-01

    Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO) production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS). Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS), GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB) are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox) were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity. PMID:23284918

  5. pH distribution in human tumors

    International Nuclear Information System (INIS)

    Thistlethwaite, A.J.; Leeper, D.B.; Moylan, D.J.; Nerlinger, R.E.

    1984-01-01

    pH distribution in human tumors is being determined to evaluate this parameter as a prognostic indicator of hyperthermia response. pH is measured by a modified glass pH electrode (21g, model MI 408, Microelectrodes, Inc., Londonderry, NH) inserted through an 18g open-ended Angiocath. Eight tumors have been evaluated to date; and of those, 3 were also assayed after the first heat treatment coincident with determination of blood flow. Tumors were between 2-5 cm, of various histologies, and of primary, recurrent, or metastatic origin. 2-4 measurements were made per tumor. Pretreatment readings were between 6.4 and 7.2 pH units. As tumor blood flow increased after 1 hr heating (41.5 - 43 0 ) pH rose 0.1 - 0.3 units. Normal rat muscle yields pH readings of 7.35 - 7.45. Although there was considerable heterogeneity of pH within tumors, accuracy and drift were not a problem. 5-15 min were required for pH stabilization after catheter insertion and <5 min after electrode insertion. A saline wheal was used for anesthesia to preclude modification of pH by anesthetics. Patient tolerance has not been a problems. This study suggests that human tumor tissue has a preponderance of areas more acidic than normal tissue. This may serve to sensitize tumor cells to hyperthermia and provide a prognostic indicator of tumor response

  6. Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

    OpenAIRE

    Richard Sauerheber

    2013-01-01

    The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity ...

  7. Separations chemistry of toxic metals

    International Nuclear Information System (INIS)

    Smith, P.; Barr, M.; Barrans, R.

    1996-01-01

    Sequestering and removing toxic metal ions from their surroundings is an increasingly active area of research and is gaining importance in light of current environmental contamination problems both within the DOE complex and externally. One method of separating metal ions is to complex them to a molecule (a ligand or chelator) which exhibits specific binding affinity for a toxic metal, even in the presence of other more benign metals. This approach makes use of the sometimes subtle differences between toxic and non-toxic metals resulting from variations in size, charge and shape. For example, toxic metals such as chromium, arsenic, and technetium exist in the environment as oxyanions, negatively charged species with a characteristic tetrahedral shape. Other toxic metals such as actinides and heavy metals are positively charged spheres with specific affinities for particular donor atoms such as oxygen (for actinides) and nitrogen (for heavy metals). In most cases the toxic metals are found in the presence of much larger quantities of less toxic metals such as sodium, calcium and iron. The selectivity of the chelators is critical to the goal of removing the toxic metals from their less toxic counterparts. The approach was to build a ligand framework that complements the unique characteristics of the toxic metal (size, charge and shape) while minimizing interactions with non-toxic metals. The authors have designed ligands exhibiting specificity for the target metals; they have synthesized, characterized and tested these ligands; and they have shown that they exhibit the proposed selectivity and cooperative binding effects

  8. Particles in swimming pool filters – Does pH determine the DBP formation?

    DEFF Research Database (Denmark)

    Hansen, Kamilla Marie Speht; Willach, Sarah; Mosbæk, Hans

    2012-01-01

    The formation was investigated for different groups of disinfection byproducts (DBPs) during chlorination of filter particles from swimming pools at different pH-values and the toxicity was estimated. Specifically, the formation of the DBP group trihalomethanes (THMs), which is regulated in many...... or initial free chlorine concentrations the particles were chlorinated at different pH-values in the relevant range for swimming pools. THM and HAA formations were reduced by decreasing pH while HAN formation increased with decreasing pH. Based on the organic content the relative DBP formation from...

  9. A new mechanism of macrophyte mitigation: how submerged plants reduce malathion's acute toxicity to aquatic animals.

    Science.gov (United States)

    Brogan, William R; Relyea, Rick A

    2014-08-01

    A growing body of evidence suggests that aquatic plants can mitigate the toxicity of insecticides to sensitive aquatic animals. The current paradigm is that this ability is driven primarily by insecticide sorption to plant tissues, especially for hydrophobic compounds. However, recent work shows that submerged plants can strongly mitigate the toxicity of the relatively hydrophilic insecticide malathion, despite the fact that this compound exhibits a slow sorption rate to plants. To examine this disparity, we tested the hypothesis that the mitigating effect of submerged plants on malathion's toxicity is driven primarily by the increased water pH from plant photosynthesis causing the hydrolysis of malathion, rather than by sorption. To do this, we compared zooplankton (Daphnia magna) survival across five environmentally relevant malathion concentrations (0, 1, 4, 6, or 36 μg L(-1)) in test containers where we chemically manipulated water pH in the absence of plants or added the submerged plant (Elodea canadensis) but manipulated plant photosynthetic activity via shading or no shading. We discovered that malathion was equally lethal to Daphnia at all concentrations tested when photosynthetically inactive (i.e. shaded) plants were present (pH at time of dosing=7.8) or when pH was chemically decreased (pH=7.7). In contrast, when photosynthetically active (i.e. unshaded) plants were present (pH=9.8) or when pH was chemically increased (pH=9.5), the effects of 4 and 6 μg L(-1) of malathion on Daphnia were mitigated strongly and to an equal degree. These results demonstrate that the mitigating effect of submerged plants on malathion's toxicity can be explained entirely by a mechanism of photosynthesizing plants causing an increase in water pH, resulting in rapid malathion hydrolysis. Our findings suggest that current ecotoxicological models and phytoremediation strategies may be overlooking a critical mechanism for mitigating pesticides. Copyright © 2014 Elsevier Ltd

  10. Modern toxic antipersonnel projectiles.

    Science.gov (United States)

    Gaillard, Yvan; Regenstreif, Philippe; Fanton, Laurent

    2014-12-01

    In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray

  11. Thyroid cancer in toxic and non-toxic multinodular goiter

    Directory of Open Access Journals (Sweden)

    Cerci C

    2007-01-01

    Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

  12. MEMORY MODULATION

    Science.gov (United States)

    Roozendaal, Benno; McGaugh, James L.

    2011-01-01

    Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

  13. PIXE analysis of mineral composition of alfalfa root-tip exposed to low pH or aluminum stress condition

    International Nuclear Information System (INIS)

    Yokota, Satoshi; Mae, Tadahiko; Ojima, Kunihiko; Ishii, Keizo.

    1994-01-01

    PIXE analysis was applied to study alteration of mineral composition (Al, P, K, and Cl) of alfalfa root-tip exposed to low pH or aluminum stress. These minerals were detectable using one or two pieces of root-tips. Short-term (within 4 h) decreases in K/P and Cl/P ratios were observed under low pH and aluminum stress conditions. However, degree of the decrease was not same. Differences in toxic effects of low pH and Al on the root-tip of alfalfa are discussed. (author)

  14. Relationships between soil properties and toxicity of copper and nickel to bok choy and tomato in Chinese soils.

    Science.gov (United States)

    Li, Bo; Zhang, Hongtao; Ma, Yibing; McLaughlin, Mike J

    2013-10-01

    The toxicity of copper (Cu) and nickel (Ni) to bok choy and tomato shoot growth was investigated in a wide range of Chinese soils with and without leaching with artificial rainwater. The results showed that the variations of Ni toxicity induced by soil properties were wider than those of Cu toxicity to both tomato and bok choy plant growth. Leaching generally decreased the toxicity of Cu and Ni added to soils, which also depended on soils, metals, and test plant species. Soil factors controlling metal phytotoxicity were found to be soil pH and soil organic carbon content for Cu, and soil pH for Ni. It was also found that soil pH had stronger effects on Ni toxicity than on Cu toxicity. Predictive toxicity models based on these soil factors were developed. These toxicity models for Cu and Ni toxicity to tomato plant growth were validated using an independent data set for European soils. These models could be applied to predict the Cu and Ni phytotoxicity in not only Chinese soils but also European soils. © 2013 SETAC.

  15. A microfabricated fringing field capacitive pH sensor with an integrated readout circuit

    Energy Technology Data Exchange (ETDEWEB)

    Arefin, Md Shamsul, E-mail: md.arefin@monash.edu; Redoute, Jean-Michel; Rasit Yuce, Mehmet [Electrical and Computer Systems Engineering, Monash University, Melbourne (Australia); Bulut Coskun, M.; Alan, Tuncay; Neild, Adrian [Mechanical and Aerospace Engineering, Monash University, Melbourne (Australia)

    2014-06-02

    This work presents a microfabricated fringe-field capacitive pH sensor using interdigitated electrodes and an integrated modulation-based readout circuit. The changes in capacitance of the sensor result from the permittivity changes due to pH variations and are converted to frequency shifts using a crossed-coupled voltage controlled oscillator readout circuit. The shift in resonant frequency of the readout circuit is 30.96 MHz for a change in pH of 1.0–5.0. The sensor can be used for the measurement of low pH levels, such as gastric acid, and can be integrated with electronic pills. The measurement results show high repeatability, low noise, and a stable output.

  16. A microfabricated fringing field capacitive pH sensor with an integrated readout circuit

    International Nuclear Information System (INIS)

    Arefin, Md Shamsul; Redoute, Jean-Michel; Rasit Yuce, Mehmet; Bulut Coskun, M.; Alan, Tuncay; Neild, Adrian

    2014-01-01

    This work presents a microfabricated fringe-field capacitive pH sensor using interdigitated electrodes and an integrated modulation-based readout circuit. The changes in capacitance of the sensor result from the permittivity changes due to pH variations and are converted to frequency shifts using a crossed-coupled voltage controlled oscillator readout circuit. The shift in resonant frequency of the readout circuit is 30.96 MHz for a change in pH of 1.0–5.0. The sensor can be used for the measurement of low pH levels, such as gastric acid, and can be integrated with electronic pills. The measurement results show high repeatability, low noise, and a stable output.

  17. Hydrogel-coated fiber Bragg grating sensor for pH monitoring

    Science.gov (United States)

    Pabbisetti, Vayu Nandana Kishore; Madhuvarasu, Sai Shankar

    2016-06-01

    We present a fiber-optic wavelength-modulated sensor for pH applications. Fiber Bragg grating (FBG) is functionalized with a stimulus-responsive hydrogel that induces a strain on FBG due to mechanical expansion of the gel in response to ambient pH changes. The gel is synthesized from the blends of poly (vinyl alcohol)/poly (acrylic acid). The induced strain results in a shift of FBG reflected peak that is monitored by an interrogator. The sensor system shows good linearity in the acidic pH range of 3 to 7 with a sensitivity of 12.16 pm/pH. In addition, it shows good repeatability and oscillator behavior, which proves it to be fit for pH sensing applications.

  18. [Toxicity and influencing factors of liquid chlorine on chironomid larvae].

    Science.gov (United States)

    Sun, Xing-Bin; Cui, Fu-Yi; Zhang, Jin-Song; Guo, Zhao-Hai; Xu, Feng; Liu, Li-Jun

    2005-09-01

    The excessive propagation of Chironomid larvae (red worm) in the sedimentation tanks is a difficult problem for the normal function of waterworks. The toxic effect of liquid chlorine on the different instar larvae of Chironomid was studied using distilled water as test sample. Furthermore, the effect of pH value, organic matter content, ammonia nitrogen, and algae content on toxicity of liquid chlorine was observed. The results show that the tolerance of Chironomid larvae to liquid chlorine is strengthened with the increase in instar. The 24h semi-lethal concentration (LC50) of liquid chlorine to the 4th instar larvae of Chironomid is 3.39 mg/L. Low pH value and high algae content are helpful to improve the toxic effect of liquid chlorine to Chironomid larvae. In neutral water body, the increase in organic matter content results in the decrease in the death rate of Chironomid larvae. The toxicity of liquid chlorine differs greatly in different concentrations of ammonia nitrogen. The death rate of the 4th instar larvae of Chironomid in raw water is higher by contrast with that in sedimentation tanks water for 24h disposal with various amount of liquid chlorine.

  19. Coaching af ph.d.-studerende

    DEFF Research Database (Denmark)

    Godskesen, Mirjam Irene

    Rapporten danner grundlag for at etablere et koncept for ph.d.-coaching. Erfaringerne fra et 2-årigt projekt om ph.d.-coaching i SCKK regi beskrives. De centrale temaer er tilrettelæggelse af den individuelle coaching, typiske temaer i coachingen og arbejdsdeling mellem coach og vejleder. Der er...

  20. Salivary pH: A diagnostic biomarker

    Directory of Open Access Journals (Sweden)

    Sharmila Baliga

    2013-01-01

    Full Text Available Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study Design: The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001 whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001. Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  1. Salivary pH: A diagnostic biomarker.

    Science.gov (United States)

    Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

    2013-07-01

    Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  2. Ph og børnenes rum

    DEFF Research Database (Denmark)

    de Coninck-Smith, Ning

    2008-01-01

    Arkiteten og kulturkritikeren PH tegnede to bygninger til børn, nemlig fabriksbørnehaven ved Dehns Vaskeri fra 1948 og det ombyggede børnehjem Mindet fra 1954. Bidraget diskuterer PH's særlige greb om arkitektur til børn og placerer det ind i samtidens diskussion om børn, deres udvikling og behov....

  3. PER PhDs & Bachelor's Degrees

    Science.gov (United States)

    White, Susan C.

    2017-01-01

    Recently, the editor remarked to me that physics departments that offered a PhD with a specialization in Physics Education Research (PER) seemed to graduate more bachelor's degree recipients than those physics PhD departments that did not have the specialization. I was not convinced. That led to quite a bit of discussion between us. He compiled a…

  4. Urbanism PhD Research 2008 - 2010

    NARCIS (Netherlands)

    Smit, M.; Van der Hoeven, F.D.; Brand, N.; Van der Burg, L.; Çal??kan, O.; Tan, E.R.; Wang, C.Y.; Zhou, J.

    2009-01-01

    To ensure the quality of the Ph.D. research the Department introduced a special procedure for periodic evaluation: after a period of nine months the potential Ph.D. candidates are asked to present their research design, theoretical framework and methodological approach to the members of the

  5. (ajst) the influence of ph and adsorbent

    African Journals Online (AJOL)

    goethite sorbed a little more metal ion than the natural goethite. This was attributed ... was greatly governed by pH with nearly 100% adsorption of Pb occurring at initial pH of 5. Generally, Pb was ... extensively study and applied for the removal of heavy .... Goethite has variable surface charge characteristics, which gave it a ...

  6. On Calibration of pH Meters

    Directory of Open Access Journals (Sweden)

    Da-Ming Zhu

    2005-04-01

    Full Text Available The calibration of pH meters including the pH glass electrode, ISE electrodes,buffers, and the general background for calibration are reviewed. Understanding of basicconcepts of pH, pOH, and electrode mechanism is emphasized. New concepts of pH, pOH,as well as critical examination of activity, and activity coefficients are given. Theemergence of new solid state pH electrodes and replacement of the salt bridge with aconducting wire have opened up a new horizon for pH measurements. A pH buffer solutionwith a conducting wire may be used as a stable reference electrode. The misleadingunlimited linear Nernstian slope should be discarded. Calibration curves with 3 nonlinearportions for the entire 0—14 pH range due to the isoelectric point change effect areexplained. The potential measurement with stirring or unstirring and effects by double layer(DL and triple layer (TL will be discussed.

  7. Spectroscopic determination of pH

    International Nuclear Information System (INIS)

    Faanu, A.; Glover, E.T.; Bailey, E.; Rochelle, C.

    2009-01-01

    A technique of measuring pH at temperature range of 20 - 70 0 C and high pressure conditions of 1 - 200 atmospheres has been developed by relating the ratio of absorbance peaks of indicator solutions (basic and acidic) as a function of pH, using ultraviolet-visible spectrophotometer. The pH values of the buffer solutions measured at 20 0 C and 70 0 C indicated slight temperature dependence, while the pressure had no effect. The pH of the buffer solutions increased with temperature with relative standard deviations in the range 0.4 - 0.5 % at 95 % confidence interval. The possible causes of the temperature dependence were attributed to changes in pH values as the temperature changed. (au)

  8. Determination Of Ph Including Hemoglobin Correction

    Science.gov (United States)

    Maynard, John D.; Hendee, Shonn P.; Rohrscheib, Mark R.; Nunez, David; Alam, M. Kathleen; Franke, James E.; Kemeny, Gabor J.

    2005-09-13

    Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

  9. Endoscopic sensing of alveolar pH.

    Science.gov (United States)

    Choudhury, D; Tanner, M G; McAughtrie, S; Yu, F; Mills, B; Choudhary, T R; Seth, S; Craven, T H; Stone, J M; Mati, I K; Campbell, C J; Bradley, M; Williams, C K I; Dhaliwal, K; Birks, T A; Thomson, R R

    2017-01-01

    Previously unobtainable measurements of alveolar pH were obtained using an endoscope-deployable optrode. The pH sensing was achieved using functionalized gold nanoshell sensors and surface enhanced Raman spectroscopy (SERS). The optrode consisted of an asymmetric dual-core optical fiber designed for spatially separating the optical pump delivery and signal collection, in order to circumvent the unwanted Raman signal generated within the fiber. Using this approach, we demonstrate a ~100-fold increase in SERS signal-to-fiber background ratio, and demonstrate multiple site pH sensing with a measurement accuracy of ± 0.07 pH units in the respiratory acini of an ex vivo ovine lung model. We also demonstrate that alveolar pH changes in response to ventilation.

  10. Toxicity of acid mine pit lake water remediated with limestone and phosphorus

    Energy Technology Data Exchange (ETDEWEB)

    Neil, L.L.; McCullough, C.D.; Lund, M.A.; Evans, L.H.; Tsvetnenko, Y. [Edith Cowan University, Joondalup, WA (Australia)

    2009-11-15

    Pit lakes are increasingly common worldwide and have potential to provide many benefits. However, lake water toxicity may require remediation before beneficial end uses can be realised. Three treatments to remediate AMD (pH similar to 4.8) pit lake water containing elevated concentrations of Al and Zn from Collie, Western Australia were tested in mesocosms. Treatments were: (a) limestone neutralisation (L), (b) phosphorus amendment (P), and c) combined limestone neutralisation and phosphorus amendment (L+P). Laboratory bioassays with Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila assessed remediation. Limestone neutralisation increased pH and reduced heavy metal concentrations by 98% (Al) to 14% (Mg), removing toxicity to the three test species within 2 months. Phosphorus amendment removed toxicity after 6 months of treatment. However, phosphorus amendment to prior limestone neutralisation failed to reduce toxicity more than limestone neutralisation alone. Low concentrations of both phosphorus and nitrogen appear to limit phytoplankton population growth in all treatments.

  11. Toxicity of acid mine pit lake water remediated with limestone and phosphorus.

    Science.gov (United States)

    Neil, Luke L; McCullough, Clint D; Lund, Mark A; Evans, Louis H; Tsvetnenko, Yuri

    2009-11-01

    Pit lakes are increasingly common worldwide and have potential to provide many benefits. However, lake water toxicity may require remediation before beneficial end uses can be realised. Three treatments to remediate AMD (pH approximately 4.8) pit lake water containing elevated concentrations of Al and Zn from Collie, Western Australia were tested in mesocosms. Treatments were: (a) limestone neutralisation (L), (b) phosphorus amendment (P), and (c) combined limestone neutralisation and phosphorus amendment (L+P). Laboratory bioassays with Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila assessed remediation. Limestone neutralisation increased pH and reduced heavy metal concentrations by 98% (Al) to 14% (Mg), removing toxicity to the three test species within 2 months. Phosphorus amendment removed toxicity after 6 months of treatment. However, phosphorus amendment to prior limestone neutralisation failed to reduce toxicity more than limestone neutralisation alone. Low concentrations of both phosphorus and nitrogen appear to limit phytoplankton population growth in all treatments.

  12. Is LSD toxic?

    Science.gov (United States)

    Nichols, David E; Grob, Charles S

    2018-03-01

    LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200μg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Toxic potential of palytoxin.

    Science.gov (United States)

    Patocka, Jiří; Gupta, Ramesh C; Wu, Qing-hua; Kuca, Kamil

    2015-10-01

    This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na(+)/K(+)-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.

  14. Development of Hybrid pH sensor for long-term seawater pH monitoring.

    Science.gov (United States)

    Nakano, Y.; Egashira, T.; Miwa, T.; Kimoto, H.

    2016-02-01

    We have been developing the in situ pH sensor (Hybrid pH sensor: HpHS) for the long-term seawater pH monitoring. We are planning to provide the HpHS for researchers and environmental consultants for observation of the CCS (Carbon dioxide Capture and Storage) monitoring system, the coastal environment monitoring system (e.g. Blue Carbon) and ocean acidification. The HpHS has two types of pH sensors (i.e. potentiometric pH sensor and spectrophotometric pH sensor). The spectrophotometric pH sensor can measure pH correctly and stably, however it needs large power consumption and a lot of reagents in a long period of observation. The pH sensor used m-cresol purple (mCP) as an indicator of pH (Clayton and Byrne, 1993 and Liu et al., 2011). We can choose both coefficients before deployment. On the other hand, although the potentiometric pH sensor is low power consumption and high-speed response (within 10 seconds), drifts in the pH of the potentiometric measurements may possibly occur for a long-term observation. The HpHS can measure in situ pH correctly and stably combining advantage of both pH sensors. The HpHS consists of an aluminum pressure housing with optical cell (main unit) and an aluminum silicon-oil filled, pressure-compensated vessel containing pumps and valves (diaphragm pump and valve unit) and pressure-compensated reagents bags (pH indicator, pure water and Tris buffer or certified reference material: CRM) with an ability to resist water pressure to 3000m depth. The main unit holds system control boards, pump drivers, data storage (micro SD card), LED right source, photodiode, optical cell and pressure proof windows. The HpHS also has an aluminum pressure housing that holds a rechargeable lithium-ion battery or a lithium battery for the power supply (DC 24 V). The HpHS is correcting the value of the potentiometric pH sensor (measuring frequently) by the value of the spectrophotometric pH sensor (measuring less frequently). It is possible to calibrate in

  15. Metal metabolism and toxicity

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Whelton, B.D.; Moretti, E.S.; Peterson, D.P.; Oldham, R.D.

    1985-01-01

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  16. Control of air toxics

    International Nuclear Information System (INIS)

    Livengood, C.D.

    1995-01-01

    For more than 10 years, Argonne National Laboratory has supported the US DOE's Flue Gas Cleanup Program objective by developing new or improved environmental controls for industries that use fossil fuels. Argonne's pollutant emissions research has ranged from experiments in the basic chemistry of pollution-control systems, through laboratory-scale process development and testing, to pilot-scale field tests of several technologies. The work on air toxics is currently divided into two components: Investigating measures to improve the removal of mercury in existing pollution-control systems applied to coal combustion; and, Developing sensors and control techniques for emissions found in the textile industry

  17. Effect of long-term smoking on salivary flow rate and salivary pH

    OpenAIRE

    Mala Singh; Navin Anand Ingle; Navpreet Kaur; Pramod Yadav; Ekta Ingle

    2015-01-01

    Introduction: Saliva is a complex and important body fluid which is very essential for oral health and it is the first biological fluid that is exposed to cigarette smoke, which contains numerous toxic compositions responsible for structural and functional changes in saliva. Aim: To evaluate the long-term effect of smoking on salivary flow rate (SFR) and salivary pH. Materials and Methods: The subjects of the study were divided into smokers and nonsmokers. Each group comprised of 35 male adul...

  18. Adsorption of diclofenac onto organoclays: Effects of surfactant and environmental (pH and temperature) conditions

    OpenAIRE

    De Oliveira , Tiago; Guégan , Régis; Thiebault , Thomas; Le Milbeau , Claude; Muller , Fabrice; Teixeira , Vinicius; Giovanela , Marcelo; Boussafir , Mohammed

    2017-01-01

    Accepted Manuscript; International audience; Among pharmaceutical products (PPs) recalcitrant to water treatments, diclofenac shows a high toxicity and remains at high concentration in natural aquatic environments. The aim of this study concerns the understanding of the adsorption mechanism of this anionic PP onto two organoclays prepared with two long-alkyl chains cationic surfactants showing different chemical nature for various experimental pH and temperature conditions. The experimental d...

  19. Effect of pH on the formation of disinfection byproducts in swimming pool water – Is less THM better?

    DEFF Research Database (Denmark)

    Hansen, Kamilla Marie Speht; Willach, Sarah; Antoniou, Maria

    2012-01-01

    This study investigated the formation and predicted toxicity of different groups of disinfection byproducts (DBPs) from human exudates in relation to chlorination of pool water at different pH values. Specifically, the formation of the DBP groups trihalomethanes (THMs), haloacetic acids (HAAs......), haloacetonitriles (HANs) and trichloramine (NCl3), resulting from the chlorination of body fluid analog, were investigated at 6.0 ≤ pH ≤ 8.0. Either the initial concentration of active chorine or free chlorine was kept constant in the tested pH range. THM formation was reduced by decreasing pH but HAN, and NCl3...... formation was investigated and found to follow the same pH dependency as without bromide present, with the overall DBP formation increasing, except for HAAs. Estimation of genotoxicity and cytotoxicity of the chlorinated human exudates showed that among the quantified DBP groups, HAN formation were...

  20. Ammonia toxicity: from head to toe?

    Science.gov (United States)

    Dasarathy, Srinivasan; Mookerjee, Rajeshwar P; Rackayova, Veronika; Rangroo Thrane, Vinita; Vairappan, Balasubramaniyan; Ott, Peter; Rose, Christopher F

    2017-04-01

    Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction.

  1. Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

    Science.gov (United States)

    Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

    2015-12-01

    Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

  2. pH gradients in the diffusive boundary layer of subarctic macrophytes

    KAUST Repository

    Hendriks, Iris E.; Duarte, Carlos M.; Marbà , Nú ria; Krause-Jensen, Dorte

    2017-01-01

    Highly productive macrophytes produce diurnal and seasonal cycles in CO concentrations modulated by metabolic activity, which cause discrepancies between pH in the bulk water and near seaweed blades, especially when entering the diffusion boundary layer (DBL). Calcifying epiphytic organisms living in this environment are therefore exposed to a different pH environment than that of the water column. To evaluate the actual pH environment on blade surfaces, we measured the thickness of the DBL and pH gradients within it for six subarctic macrophytes: Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, Zostera marina, Saccharina longicruris, and Agarum clathratum. We measured pH under laboratory conditions at ambient temperatures (2–3 °C) and slow, stable flow over the blade surface at five light intensities (dark, 30, 50, 100 and 200 µmol photons m s). Boundary layer thickness ranged between 511 and 1632 µm, while the maximum difference in pH (∆pH) between the blade surface and the water column ranged between 0.4 ± 0.14 (average ± SE; Zostera) and 1.2 ± 0.13 (average ± SE; Ulva) pH units. These differences in pH are larger than predictions for pH changes in the bulk water by the end of the century. A simple quadratic model best described the relationship between light intensity and maximum ∆pH, pointing at relatively low optimum PAR of between 28 and 139 µmol photons m s to reach maximum ∆pH. Elevated pH at the blade surface may provide chemical “refugia” for calcifying epiphytic organisms, especially during summer at higher latitudes where photoperiods are long.

  3. pH gradients in the diffusive boundary layer of subarctic macrophytes

    KAUST Repository

    Hendriks, Iris E.

    2017-06-20

    Highly productive macrophytes produce diurnal and seasonal cycles in CO concentrations modulated by metabolic activity, which cause discrepancies between pH in the bulk water and near seaweed blades, especially when entering the diffusion boundary layer (DBL). Calcifying epiphytic organisms living in this environment are therefore exposed to a different pH environment than that of the water column. To evaluate the actual pH environment on blade surfaces, we measured the thickness of the DBL and pH gradients within it for six subarctic macrophytes: Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, Zostera marina, Saccharina longicruris, and Agarum clathratum. We measured pH under laboratory conditions at ambient temperatures (2–3 °C) and slow, stable flow over the blade surface at five light intensities (dark, 30, 50, 100 and 200 µmol photons m s). Boundary layer thickness ranged between 511 and 1632 µm, while the maximum difference in pH (∆pH) between the blade surface and the water column ranged between 0.4 ± 0.14 (average ± SE; Zostera) and 1.2 ± 0.13 (average ± SE; Ulva) pH units. These differences in pH are larger than predictions for pH changes in the bulk water by the end of the century. A simple quadratic model best described the relationship between light intensity and maximum ∆pH, pointing at relatively low optimum PAR of between 28 and 139 µmol photons m s to reach maximum ∆pH. Elevated pH at the blade surface may provide chemical “refugia” for calcifying epiphytic organisms, especially during summer at higher latitudes where photoperiods are long.

  4. Effects of water chemistry on the dissolution of ZnO nanoparticles and their toxicity to Escherichia coli

    International Nuclear Information System (INIS)

    Li Mei; Lin Daohui; Zhu Lizhong

    2013-01-01

    The dissolution of ZnO nanoparticles (nano-ZnO) plays an important role in the toxicity of nano-ZnO to the aquatic organisms. The effects of water chemistry such as pH, ionic components, and dissolved organic matter (DOM) on the dissolution of nano-ZnO and its toxicity to Escherichia coli (E. coli) were investigated in synthetic and natural water samples. The results showed that the toxicity of nano-ZnO to E. coli depended on not only free Zn 2+ but also the coexisting cations which could reduce the toxicity of Zn 2+ . Increasing solution pH, HPO 4 2− , and DOM reduced the concentration of free Zn 2+ released from nano-ZnO, and thus lowered the toxicity of nano-ZnO. In addition, both Ca 2+ and Mg 2+ dramatically reduced the toxicity of Zn 2+ to E. coli. These results highlight the importance of water chemistry on the toxicity evaluation of nano-ZnO in natural waters. - Highlights: ► The effects of water chemistry on the toxicity of nano-ZnO were investigated. ► Increasing solution pH, HPO 4 2− , and DOM reduced nano-ZnO toxicity to E. coli. ► Ca 2+ and Mg 2+ could dramatically reduce the toxicity of nano-ZnO to E. coli. ► Free Zn 2+ ions and water hardness together controlled nano-ZnO toxicity in waters. - The toxicity of nano-ZnO to E. coli depended on not only free Zn 2+ but also Ca 2+ and Mg 2+ which could reduce the toxicity of Zn 2+ .

  5. Seasonal variability in irradiance affects herbicide toxicity to the marine flagellate Dunaliella tertiolecta

    Directory of Open Access Journals (Sweden)

    Sascha eSjollema

    2014-06-01

    Full Text Available Photosynthetically Active Radiation (PAR and Ultraviolet Radiation (UVR of the solar spectrum affect microalgae directly and modify the toxicity of phytotoxic compounds present in water. As a consequence seasonal variable PAR and UVR levels are likely to modulate the toxic pressure of contaminants in the field. Therefore the present study aimed to determine the toxicity of two model contaminants, the herbicides diuron and Irgarol®1051, under simulated irradiance conditions mimicking different seasons. Irradiance conditions of spring and autumn were simulated with a set of Light Emitting Diodes (LEDs. Toxicity of both herbicides was measured individually and in a mixture by determining the inhibition of photosystem II efficiency (ΦPSII of the marine flagellate Dunaliella teriolecta using Pulse Amplitude Modulation (PAM fluorometry. Toxicity of the single herbicides was higher under simulated spring irradiance than under autumn irradiance and this effect was also observed for mixtures of the herbicides. This irradiance dependent toxicity indicates that herbicide toxicity in the field is seasonally variable. Consequently toxicity tests under standard light conditions may overestimate or underestimate the toxic effect of phytotoxic compounds.

  6. Toxicity of tritium

    International Nuclear Information System (INIS)

    Dobson, R.L.

    1979-01-01

    Among radionuclides of importance in atomic energy, 3 H has relatively low toxicity. The main health and environmental worry is the possibility that significant biological effects may follow from protracted exposure to low concentrations in water. To examine this possible hazard and measure toxicity at low tritium concentrations, chronic exposure studies were done on mice and monkeys. During vulnerable developmental periods animals were exposed to 3 HOH, and mice were exposed also to 60 Co gamma irradiation and energy-related chemical agents. The biological endpoint measured was the irreversible loss of female germ cells. Effects from tritium were observed at surprisingly low concentrations where 3 H was found more damaging than previously thought. Comparisons between tritium and gamma radiation showed the relative biological effectiveness (RBE) to be greater than 1 and to reach approximately 3 at very low exposures. For perspective, other comparisons were made: between radiation and chemical agents, which revealed parallels in action on germ cells, and between pre- and postnatal exposure, which warn of possible special hazard to the fetus from both classes of energy-related byproducts

  7. Toxic compounds in honey.

    Science.gov (United States)

    Islam, Md Nazmul; Khalil, Md Ibrahim; Islam, Md Asiful; Gan, Siew Hua

    2014-07-01

    There is a wealth of information about the nutritional and medicinal properties of honey. However, honey may contain compounds that may lead to toxicity. A compound not naturally present in honey, named 5-hydroxymethylfurfural (HMF), may be formed during the heating or preservation processes of honey. HMF has gained much interest, as it is commonly detected in honey samples, especially samples that have been stored for a long time. HMF is a compound that may be mutagenic, carcinogenic and cytotoxic. It has also been reported that honey can be contaminated with heavy metals such as lead, arsenic, mercury and cadmium. Honey produced from the nectar of Rhododendron ponticum contains alkaloids that can be poisonous to humans, while honey collected from Andromeda flowers contains grayanotoxins, which can cause paralysis of limbs in humans and eventually leads to death. In addition, Melicope ternata and Coriaria arborea from New Zealand produce toxic honey that can be fatal. There are reports that honey is not safe to be consumed when it is collected from Datura plants (from Mexico and Hungary), belladonna flowers and Hyoscamus niger plants (from Hungary), Serjania lethalis (from Brazil), Gelsemium sempervirens (from the American Southwest), Kalmia latifolia, Tripetalia paniculata and Ledum palustre. Although the symptoms of poisoning due to honey consumption may differ depending on the source of toxins, most common symptoms generally include dizziness, nausea, vomiting, convulsions, headache, palpitations or even death. It has been suggested that honey should not be considered a completely safe food. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Thallium toxicity in humans.

    Science.gov (United States)

    Cvjetko, Petra; Cvjetko, Ivan; Pavlica, Mirjana

    2010-03-01

    Thallium is a naturally occurring trace element, widely distributed in the earth's crust, but at very low concentrations. It does not have a known biological use and does not appear to be an essential element for life. It has been considered one of the most toxic heavy metals.Occasionally, there are reports on thallium poisoning as results of suicide or murder attempt or accident. The main threat to humans is through occupational exposure, environmental contamination, and accumulation in food, mainly in vegetables grown on contaminated soil. Increasing use in emerging new technologies and demanding high-tech industry constantly raise concern about exposure risk to all living organisms. Thallium is considered a cumulative poison that can cause adverse health effects and degenerative changes in many organs. The effects are the most severe in the nervous system. The exact mechanism of thallium toxicity still remains unknown, although impaired glutathione metabolism, oxidative stress, and disruption of potassium-regulated homeostasis may play a role. The lack of data about mutagenic, carcinogenic, or teratogenic effects of thallium compounds in humans calls for further research.

  9. Molecular toxicity of nanomaterials.

    Science.gov (United States)

    Chang, Xue-Ling; Yang, Sheng-Tao; Xing, Gengmei

    2014-10-01

    With the rapid developments in the fields of nanoscience and nanotechnlogy, more and more nanomaterials and their based consumer products have been used into our daily life. The safety concerns of nanomaterials have been well recognized by the scientific community and the public. Molecular mechanism of interactions between nanomaterials and biosystems is the most essential topic and final core of the biosafety. In the last two decades, nanotoxicology developed very fast and toxicity phenomena of nanomaterials have been reported. To achieve better understanding and detoxication of nanomaterials, thorough studies of nanotoxicity at molecular level are important. The interactions between nanomaterials and biomolecules have been widely investigated as the first step toward the molecular nanotoxicology. The consequences of such interactions have been discussed in the literature. Besides this, the chemical mechanism of nanotoxicology is gaining more attention, which would lead to a better design of nontoxic nanomaterials. In this review, we focus on the molecular nanotoxicology and explore the toxicity of nanomaterials at molecular level. The molecular level studies of nanotoxicology are summarized and the published nanotoxicological data are revisited.

  10. Hybrid silica materials for detection of toxic species and clinical diagnosis

    OpenAIRE

    Pascual Vidal, Lluís

    2017-01-01

    The present PhD thesis entitled "Silica Hybrid Materials for detection of toxic species and clinical diagnosis" is focused on the design and synthesis of new hybrid materials, using different silica supports as inorganic scaffolds, with applications in recognition, sensing and diagnostic protocols. The first chapter of the PhD thesis is devoted to the definition and classification of hybrid materials, relying on concepts of Nanotechnology, Supramolecular and Materials Chemistry. State o...

  11. Dietary Chemoprevention of PhIP Induced Carcinogenesis in Male Fischer 344 Rats with Tomato and Broccoli

    Science.gov (United States)

    Canene-Adams, Kirstie; Sfanos, Karen S.; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G.; Brayton, Cory; De Marzo, Angelo M.

    2013-01-01

    The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers. PMID:24312188

  12. Catalases are NAD(PH-dependent tellurite reductases.

    Directory of Open Access Journals (Sweden)

    Iván L Calderón

    2006-12-01

    Full Text Available Reactive oxygen species damage intracellular targets and are implicated in cancer, genetic disease, mutagenesis, and aging. Catalases are among the key enzymatic defenses against one of the most physiologically abundant reactive oxygen species, hydrogen peroxide. The well-studied, heme-dependent catalases accelerate the rate of the dismutation of peroxide to molecular oxygen and water with near kinetic perfection. Many catalases also bind the cofactors NADPH and NADH tenaciously, but, surprisingly, NAD(PH is not required for their dismutase activity. Although NAD(PH protects bovine catalase against oxidative damage by its peroxide substrate, the catalytic role of the nicotinamide cofactor in the function of this enzyme has remained a biochemical mystery to date. Anions formed by heavy metal oxides are among the most highly reactive, natural oxidizing agents. Here, we show that a natural isolate of Staphylococcus epidermidis resistant to tellurite detoxifies this anion thanks to a novel activity of its catalase, and that a subset of both bacterial and mammalian catalases carry out the NAD(PH-dependent reduction of soluble tellurite ion (TeO(3(2- to the less toxic, insoluble metal, tellurium (Te(o, in vitro. An Escherichia coli mutant defective in the KatG catalase/peroxidase is sensitive to tellurite, and expression of the S. epidermidis catalase gene in a heterologous E. coli host confers increased resistance to tellurite as well as to hydrogen peroxide in vivo, arguing that S. epidermidis catalase provides a physiological line of defense against both of these strong oxidizing agents. Kinetic studies reveal that bovine catalase reduces tellurite with a low Michaelis-Menten constant, a result suggesting that tellurite is among the natural substrates of this enzyme. The reduction of tellurite by bovine catalase occurs at the expense of producing the highly reactive superoxide radical.

  13. Objective determination of pH thresholds in the analysis of 24 h ambulatory oesophageal pH monitoring

    NARCIS (Netherlands)

    Weusten, B. L.; Roelofs, J. M.; Akkermans, L. M.; vanBerge-Henegouwen, G. P.; Smout, A. J.

    1996-01-01

    In 24 h oesophageal pH monitoring, pH 4 is widely but arbitrarily used as the threshold between reflux and non-reflux pH values. The aim of the study was to define pH thresholds objectively, based on Gaussian curve fitting of pH frequency distributions. Single-channel 24 h oesophageal pH monitoring

  14. The pH sensitive properties of carboxymethyl chitosan nanoparticles cross-linked with calcium ions.

    Science.gov (United States)

    Kalliola, Simo; Repo, Eveliina; Srivastava, Varsha; Heiskanen, Juha P; Sirviö, Juho Antti; Liimatainen, Henrikki; Sillanpää, Mika

    2017-05-01

    In environmental applications the applied materials are required to be non-toxic and biodegradable. Carboxymethyl chitosan nanoparticles cross-linked with Ca 2+ ions (CMC-Ca) fulfill these requirements, and they are also renewable. These nanoparticles were applied to oil-spill treatment in our previous study and here we focused on enhancing their properties. It was found that while the divalent Ca 2+ ions are crucial for the formation of the CMC-Ca, the attractive interaction between NH 3 + and COO - groups contributed significantly to the formation and stability of the CMC-Ca. The stability decreased as a function of pH due to the deprotonation of the amino groups. Therefore, the nanoparticles were found to be fundamentally pH sensitive in solution, if the pH deviated from the pH (7-9) that was used in the synthesis of the nanoparticles. The pH sensitive CMC-Ca synthesized in pH 7 and 8 were most stable in the studied conditions and could find applications in oil-spill treatment or controlled-release of substances. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Stabilization of pH in solid-matrix hydroponic systems

    Science.gov (United States)

    Frick, J.; Mitchell, C. A.

    1993-01-01

    2-[N-morpholino]ethanesulfonic acid (MES) buffer or Amberlite DP-1 (cation-exchange resin beads) were used to stabilize substrate pH of passive-wicking, solid-matrix hydroponic systems in which small canopies of Brassica napus L. (CrGC 5-2, genome : ACaacc) were grown to maturity. Two concentrations of MES (5 or 10 mM) were included in Hoagland 1 nutrient solution. Alternatively, resin beads were incorporated into the 2 vermiculite : 1 perlite (v/v) growth medium at 6% or 12% of total substrate volume. Both strategies stabilized pH without toxic side effects on plants. Average seed yield rates for all four pH stabilization treatments (13.3 to 16.9 g m-2 day-1) were about double that of the control (8.2 g m-2 day-1), for which there was no attempt to buffer substrate pH. Both the highest canopy seed yield rate (16.9 g m-2 day-1) and the highest shoot harvest index (19.5%) occurred with the 6% resin bead treatment, even though the 10 mM MES and 12% bead treatments maintained pH within the narrowest limits. The pH stabilization methods tested did not significantly affect seed oil and protein contents.

  16. Fast Convolution Module (Fast Convolution Module)

    National Research Council Canada - National Science Library

    Bierens, L

    1997-01-01

    This report describes the design and realisation of a real-time range azimuth compression module, the so-called 'Fast Convolution Module', based on the fast convolution algorithm developed at TNO-FEL...

  17. Functional photoacoustic microscopy of pH.

    Science.gov (United States)

    Chatni, Muhammad Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin I; Wang, Lihong V

    2011-10-01

    pH is a tightly regulated indicator of metabolic activity. In mammalian systems, an imbalance of pH regulation may result from or result in serious illness. In this paper, we report photoacoustic microscopy (PAM) of a commercially available pH-sensitive fluorescent dye (SNARF-5F carboxylic acid) in tissue phantoms. We demonstrated that PAM is capable of pH imaging in absolute values at tissue depths of up to 2.0 mm, greater than possible with other forms of optical microscopy.

  18. Toxic industrial deposit remediation by ant activity

    Science.gov (United States)

    Jilkova, Veronika; Frouz, Jan

    2016-04-01

    Toxic industrial deposits are often contaminated by heavy metals and the substrates have low pH values. In such systems, soil development is thus slowed down by high toxicity and acidic conditions which are unfavourable to soil fauna. Ants (Hymenoptera, Formicidae) are considered tolerant to heavy metal pollution and are known to increase organic matter content and microbial activity in their nests. Here, we focused on soil remediation caused by three ant species (Formica sanguinea, Lasius niger, and Tetramorium sp.) in an ore-washery sedimentation basin near Chvaletice (Czech Republic). Soil samples were taken from the centre of ant nests and from the nest surroundings (>3 m from nests). Samples were then analyzed for microbial activity and biomass and contents of organic matter and nutrients. As a result, ant species that most influenced soil properties was F. sanguinea as there were higher microbial activity and total nitrogen and ammonia contents in ant nests than in the surrounding soil. We expected such a result because F. sanguinea builds conspicuous large nests and is a carnivorous species that brings substantial amounts of nitrogen in insect prey to their nests. Effects of the other two ant species might be lower because of smaller nests and different feeding habits as they rely mainly on honeydew from aphids or on plant seeds that do not contain much nutrients.

  19. The PhD by Publication

    Directory of Open Access Journals (Sweden)

    Susi Peacock

    2017-07-01

    Full Text Available Aim/Purpose: The purpose of this work is to develop more nuanced understandings of the PhD by publication, particularly raising awareness of the retrospective PhD by publication. The article aims to contribute to contemporary debates about the differing pathways to the attainment of doctoral study completion and the artifacts submitted for that purpose. It also seeks to support prospective graduate students and supervisors who are embarking upon alternative routes to doctoral accreditation. Background: The PhD is considered the pinnacle of academic study – highly cherished, and replete with deeply held beliefs. In response to changes in job markets, developments in the disciplines, and more varied student cohorts, diverse pathways to completion of this award have emerged, such as the PhD by publication (PhDP. A PhDP may either be prospective or retrospective. For the former, publications are planned and created with their contributions to the PhDP in mind. The retrospective PhD is assembled after some, or most, of the publications have been completed. The artifact submitted for examination in this case consists of a series of peer-reviewed academic papers, books, chapters, or equivalents that have been published or accepted for publication, accompanied by an over-arching narrative. The retrospective route is particularly attractive for professionals who are research-active but lack formal academic accreditation at the highest level. Methodology: This article calls upon a literature review pertaining to the award of PhDP combined with the work of authors who offer their personal experiences of the award. The author also refers to her candidature as a Scottish doctoral student whilst studying for the award of PhD by publication. Contribution: This work raises awareness of the PhDP as a credible and comparable pathway for graduate students. The article focuses upon the retrospective PhDP which, as with all routes to doctoral accreditation, has

  20. Wild lettuce (Lactuca virosa) toxicity

    OpenAIRE

    Besharat, Sima; Besharat, Mahsa; Jabbari, Ali

    2009-01-01

    Wild lettuce (Lactuca virosa) can cause toxic effects when eaten. Wild lettuce grows in the north of Iran and some natives consume it unaware of its adverse side effects. We describe eight patients with manifestations of wild lettuce toxicity, admitted to a general hospital affiliated to the Golestan University of Medical Sciences. All the patients recovered (although one had to spend 48 h in the intensive care unit) and no chronic complications were reported. A clinical suspicion of toxicity...

  1. Module theory, extending modules and generalizations

    CERN Document Server

    Tercan, Adnan

    2016-01-01

    The main focus of this monograph is to offer a comprehensive presentation of known and new results on various generalizations of CS-modules and CS-rings. Extending (or CS) modules are generalizations of injective (and also semisimple or uniform) modules. While the theory of CS-modules is well documented in monographs and textbooks, results on generalized forms of the CS property as well as dual notions are far less present in the literature. With their work the authors provide a solid background to module theory, accessible to anyone familiar with basic abstract algebra. The focus of the book is on direct sums of CS-modules and classes of modules related to CS-modules, such as relative (injective) ejective modules, (quasi) continuous modules, and lifting modules. In particular, matrix CS-rings are studied and clear proofs of fundamental decomposition results on CS-modules over commutative domains are given, thus complementing existing monographs in this area. Open problems round out the work and establish the...

  2. Cyclophosphamide-induced pulmonary toxicity

    International Nuclear Information System (INIS)

    Siemann, D.W.; Macler, L.; Penney, D.P.

    1986-01-01

    Unlike radiation effects, pulmonary toxicity following drug treatments may develop soon after exposure. The dose-response relationship between Cyclophosphamide and lung toxicity was investigated using increased breathing frequency assays used successfully for radiation induced injury. The data indicate that release of protein into the alveolus may play a significant role in Cy induced pulmonary toxicity. Although the mechanism responsible for the increased alveo