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Sample records for acceptable toxicity profile

  1. [Validation and regulatory acceptance of alternative methods for toxicity evaluation].

    PubMed

    Ohno, Yasuo

    2004-01-01

    For regulatory acceptance of alternative methods (AMs) to animal toxicity tests, their reproducibility and relevance should be determined by intra- and inter-laboratory validation. Appropriate procedures of the validation and regulatory acceptance of AMs were recommended by OECD in 1996. According to those principles, several in vitro methods like skin corrosivity tests and phototoxicity tests were evaluated and accepted by ECVAM (European Center for the Validation of Alternative Methods), ICCVAM (The Interagency Coordinating Committee on the Validation of Alternative Methods), and OECD. Because of the difficulties in conducting inter-laboratory validation and relatively short period remained until EU's ban of animal experiments for safety evaluation of cosmetics, ECVAM and ICCVAM have recently started cooperation in validation and evaluation of AMs. It is also necessary to establish JaCVAM (Japanese Center for the Validation of AM) to contribute the issue and for the evaluation of new toxicity tests originated in Japan.

  2. Consumer acceptance and sensory profiling of reengineered kitoza products.

    PubMed

    Pintado, Ana I E; Monteiro, Maria J P; Talon, Régine; Leroy, Sabine; Scislowski, Valérie; Fliedel, Geneviève; Rakoto, Danielle; Maraval, Isabelle; Costa, Ana I A; Silva, Ana P; Pallet, Dominique; Tomlins, Keith; Pintado, Manuela M E

    2016-05-01

    Kitoza refers to a traditional way of preparing beef and pork in Madagascar. However, in order to improve some drawbacks previous identified, the product was submitted to a reengineering process. The acceptance and sensory profiling of improved Kitoza products among Portuguese consumers was investigated. A local smoked loin sausage was selected as basis for comparison. Firstly, a Focus Group study was performed to identify sensory descriptors for Kitoza products and explore product perception. Subsequently, a Flash Profile and a consumer sensory acceptance study were conducted. Flash Profile's results showed that beef- and pork-based Kitoza products investigated differed considerably in all sensory dimensions. The Portuguese sausage was characterized as having a more intense and lasting after taste, as well as displaying a higher degree of (meat) doneness. The acceptance study yielded higher overall liking ratings for pork- than for beef-based Kitoza, although the Portuguese sausage remained the most appreciated product.

  3. Preclinical toxicity profile of oral bilastine.

    PubMed

    Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

    2012-06-01

    As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

  4. GENE EXPRESSION PROFILING TO IDENTIFY BIOMARKERS OF REPRODUCTIVE TOXICITY

    EPA Science Inventory

    SOT 2005 SESSION ABSTRACT

    GENE EXPRESSION PROFILING TO IDENTIFY BIOMARKERS OF REPRODUCTIVE TOXICITY

    David J. Dix. National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle...

  5. Pathway Profiling and Tissue Modeling of Developmental Toxicity

    EPA Science Inventory

    High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

  6. GENE EXPRESSION PROFILING TO IDENTIFY MECHANISMS OF MALE REPRODUCTIVE TOXICITY

    EPA Science Inventory

    Gene Expression Profiling to Identify Mechanisms of Male Reproductive Toxicity
    David J. Dix
    National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
    Ab...

  7. A Review on Renal Toxicity Profile of Common Abusive Drugs

    PubMed Central

    Singh, Varun Parkash; Singh, Nirmal

    2013-01-01

    Drug abuse has become a major social problem of the modern world and majority of these abusive drugs or their metabolites are excreted through the kidneys and, thus, the renal complications of these drugs are very common. Morphine, heroin, cocaine, nicotine and alcohol are the most commonly abused drugs, and their use is associated with various types of renal toxicity. The renal complications include a wide range of glomerular, interstitial and vascular diseases leading to acute or chronic renal failure. The present review discusses the renal toxicity profile and possible mechanisms of commonly abused drugs including morphine, heroin, cocaine, nicotine, caffeine and alcohol. PMID:23946695

  8. Two age-related accumulation profiles of toxic metals.

    PubMed

    Yasuda, Hiroshi; Yoshida, Kazuya; Yasuda, Yuichi; Tsutsui, Toyoharu

    2012-07-01

    In order to investigate the body burden levels of toxic metals in Japanese, five toxic metal concentrations in scalp hair samples from 28,424 subjects from infant to elderly were determined with inductively coupled plasma mass spectrometry (ICP-MS). The geometric mean of hair mercury concentrations showed a high-significant age-correlated increase (r = 0.341, p < 0.0001) with a peak at the 6th decade of life and then decreased with further aging in both sexes. The mean mercury concentrations in male adults were significantly higher than those in female (p < 0.001), indicating the gender difference (male > female) in mercury accumulation. Arsenic also showed a similar accumulation profile with age dependency and gender difference in adult subjects. In contrast, cadmium, lead and aluminium exhibited another type of accumulation profile: the highest burden level was observed in infants aged 0-3 years old for every element in both sexes. In addition, cadmium was found to have a character accumulating in aged females, with significant age-dependency (r = 0.134, p < 0.0001) and gender difference (female > male). These findings suggest that toxic metals are classified into two families on the basis of their accumulation profiles, and that the three elements of mercury, arsenic and cadmium which accumulate age-dependently in adults, may play a role in aging process and higher burden with them may lead to acceleration of aging.

  9. Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance.

    PubMed

    Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

    2015-03-01

    This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice.

  10. Passion fruit juice with different sweeteners: sensory profile by descriptive analysis and acceptance

    PubMed Central

    Rocha, Izabela Furtado de Oliveira; Bolini, Helena Maria André

    2015-01-01

    This study evaluated the effect of different sweeteners on the sensory profile, acceptance, and drivers of preference of passion fruit juice samples sweetened with sucrose, aspartame, sucralose, stevia, cyclamate/saccharin blend 2:1, and neotame. Sensory profiling was performed by 12 trained assessors using quantitative descriptive analysis (QDA). Acceptance tests (appearance, aroma, flavor, texture and overall impression) were performed with 124 consumers of tropical fruit juice. Samples with sucrose, aspartame and sucralose showed similar sensory profile (P < 0.05), without bitter taste, bitter aftertaste, and metallic taste, and samples with sucrose and sucralose did not differ from each other for the attribute sweet aftertaste. Passion fruit flavor affected positively and sweet aftertaste affected negatively the acceptance of the samples. Samples sweetened with aspartame, sucralose, and sucrose presented higher acceptance scores for the attributes flavor, texture, and overall impression, with no significant (P < 0.05) differences between them. Aspartame and sucralose can be good substitutes for sucrose in passion fruit juice. PMID:25838891

  11. Toxicity profiles and solvent-toxicant interference in the planarian Schmidtea mediterranea after dimethylsulfoxide (DMSO) exposure.

    PubMed

    Stevens, An-Sofie; Pirotte, Nicky; Plusquin, Michelle; Willems, Maxime; Neyens, Thomas; Artois, Tom; Smeets, Karen

    2015-03-01

    To investigate hydrophobic test compounds in toxicological studies, solvents like dimethylsulfoxide (DMSO) are inevitable. However, using these solvents, the interpretation of test compound-induced responses can be biased. DMSO concentration guidelines are available, but are mostly based on acute exposures involving one specific toxicity endpoint. Hence, to avoid solvent-toxicant interference, we use multiple chronic test endpoints for additional interpretation of DMSO concentrations and propose a statistical model to assess possible synergistic, antagonistic or additive effects of test compounds and their solvents. In this study, the effects of both short- (1 day) and long-term (2 weeks) exposures to low DMSO concentrations (up to 1000 µl l(-1) ) were studied in the planarian Schmidtea mediterranea. We measured different biological levels in both fully developed and developing animals. In a long-term exposure set-up, a concentration of 500 µl l(-1) DMSO interfered with processes on different biological levels, e.g. behaviour, stem cell proliferation and gene expression profiles. After short exposure times, 500 µl l(-1) DMSO only affected motility, whereas the most significant changes on different parameters were observed at a concentration of 1000 µl l(-1) DMSO. As small sensitivity differences exist between biological levels and developmental stages, we advise the use of this solvent in concentrations below 500 µl l(-1) in this organism. In the second part of our study, we propose a statistical approach to account for solvent-toxicant interactions and discuss full-scale solvent toxicity studies. In conclusion, we reassessed DMSO concentration limits for different experimental endpoints in the planarian S. mediterranea.

  12. Evaluation of three soil toxicity tests used to monitor acceptable endpoints

    SciTech Connect

    Brinkmann, M.; Stroo, H.; Leuschner, A.; Leuteritz, D.; Stromberg, M.; Brourman, M.

    1995-12-31

    Three terrestrial toxicity tests were used to evaluate the efficacy of biological treatment of creosote and pentachlorophenol impacted soils at a Superfund site. Microtox, 5-day lettuce seed, and 14-day earthworm toxicity tests were performed on 10 soil samples at the beginning and end of 3 months of land treatment. Secondary endpoints of root length and earthworm weight loss were also evaluated. EC50 and LC50 values were calculated using a Trimmed Logit Statistical Program and compared to toxicity of 10 background samples collected from the site. Results for initial soils demonstrated toxicity with three of the five endpoints. End treatment results showed no measurable toxicity using all endpoints. Toxicity testing results are critical for obtaining regulatory approval for the full-scale treatment system. Post treatment closure requirements for the site will be based on bioassay results. Evaluation of the three tests used showed the Microtox test to be the most sensitive to this type of toxicity. Lettuce seed germination results were the least sensitive of the three primary endpoints chosen. Of the secondary endpoint criteria, root length demonstrated reliable EC50 values and showed toxicity trends similar to Microtox and earthworm tests. The earthworm weight loss endpoint was not a useful toxicity measurement at 14 days.

  13. Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.

    PubMed

    Mizotani, Yuji; Itoh, Shun; Hotta, Kohji; Tashiro, Etsu; Oka, Kotaro; Imoto, Masaya

    2015-08-07

    In vivo toxicity evaluation using model organisms is an important step for the development of new drugs. Here, we report that Ciona intestinalis, a chordate invertebrate, is beneficial to drug toxicity evaluation for the following reasons: rapid embryonic and larval development, resemblance to vertebrates, ease of management, low cost, transparent body, and low risk of ethical issues. The dynamic phenotypic change of Ciona larvae during metamorphosis prompted us to examine the effect of cytotoxic drugs on its development by quantifying six toxicity endpoints: degenerated tail size, ampulla length, rotation of body axis, stomach size, heart rate, and body size. As a result, mitochondrial respiratory inhibitors, tubulin polymerization/depolymerization inhibitors, or DNA/RNA synthesis inhibitors showed distinct toxicity profiles against these six endpoints, but drugs with the same targets showed a similar toxicity profile in Ciona. Our results suggest Ciona is an effective animal model for profiling drug toxicity and exploring the mechanisms of drugs with unknown targets.

  14. Profiling animal toxicants by automatically mining public bioassay data: a big data approach for computational toxicology.

    PubMed

    Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

    2014-01-01

    In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities.

  15. In vitro toxicity profiling of ultrapure non-dioxin-like polychlorinated biphenyl congeners and their relative toxic contribution to PCB mixtures in humans.

    PubMed

    Hamers, Timo; Kamstra, Jorke H; Cenijn, Peter H; Pencikova, Katerina; Palkova, Lenka; Simeckova, Pavlina; Vondracek, Jan; Andersson, Patrik L; Stenberg, Mia; Machala, Miroslav

    2011-05-01

    The toxic equivalency concept used for the risk assessment of polychlorinated biphenyls (PCBs) is based on the aryl hydrocarbon receptor (AhR)-mediated toxicity of coplanar dioxin-like (DL) PCBs. Most PCBs in the environment, however, are non-dioxin-like (NDL) PCBs that cannot adopt a coplanar structure required for AhR activation. For NDL-PCBs, no generally accepted risk concept is available because their toxicity is insufficiently characterized. Here, we systematically determined in vitro toxicity profiles for 24 PCBs regarding 10 different mechanisms of action. Prior to testing, NDL-PCB standards were purified to remove traces of DL compounds. All NDL-PCBs antagonized androgen receptor activation and inhibited gap junctional intercellular communication (GJIC). Lower chlorinated NDL-PCBs were weak estrogen receptor (ER) agonists, whereas higher chlorinated NDL-PCBs were weak ER antagonists. Several NDL-PCBs inhibited estradiol-sulfotransferase activity and bound to transthyretin (TTR) but with much weaker potencies than reported for hydroxylated PCB metabolites. AhR-mediated expression of uridine-glucuronyl transferase isozyme UGT1A6 was induced by DL-PCBs only. Hierarchical cluster analysis of the toxicity profiles yielded three separate clusters of NDL-PCBs and a fourth cluster of reference DL-PCBs. Due to small differences in relative potency among congeners, the highly abundant indicator PCBs 28, 52, 101, 118, 138, 153, and 180 also contributed most to the antiandrogenic, (anti)estrogenic, antithyroidal, tumor-promoting, and neurotoxic potencies calculated for PCB mixtures reported in human samples, whereas the most potent AhR-activating DL-PCB-126 contributed at maximum 0.2% to any of these calculated potencies. PCB-168 is recommended as an additional indicator congener, given its relatively high abundance and antiandrogenic, TTR-binding, and GJIC-inhibiting potencies.

  16. KSC 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT) Report

    NASA Technical Reports Server (NTRS)

    Barbre, Robert E.

    2015-01-01

    This report documents analysis results of the Kennedy Space Center updated 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT). This test was designed to demonstrate that the new DRWP operates in a similar manner to the previous DRWP for use as a situational awareness asset for mission operations at the Eastern Range to identify rapid changes in the wind environment that weather balloons cannot depict. Data examination and two analyses showed that the updated DRWP meets the specifications in the OAT test plan and performs at least as well as the previous DRWP. Data examination verified that the DRWP provides complete profiles every five minutes from 1.8-19.5 km in vertical increments of 150 m. Analysis of 5,426 wind component reports from 49 concurrent DRWP and balloon profiles presented root mean square (RMS) wind component differences around 2.0 m/s. The DRWP's effective vertical resolution (EVR) was found to be 300 m for both the westerly and southerly wind component, which the best EVR possible given the DRWP's vertical sampling interval. A third analysis quantified the sensitivity to rejecting data that do not have adequate signal by assessing the number of first-guess propagations at each altitude. This report documents the data, quality control procedures, methodology, and results of each analysis. It also shows that analysis of the updated DRWP produced results that were at least as good as the previous DRWP with proper rationale. The report recommends acceptance of the updated DRWP for situational awareness usage as per the OAT's intent.

  17. Profiling the reproductive toxicity of chemicals from multigeneration studies in the toxicity reference database

    EPA Science Inventory

    Multigeneration reproduction studies are used to characterize parental and offspring systemic toxicity, as well as reproductive toxicity of pesticides, industrial chemicals and pharmaceuticals. Results from 329 multigeneration studies on 316 chemicals have been digitized into sta...

  18. Results of the NASA Kennedy Space Center 50-MHz Doppler Radar Wind Profiler Operational Acceptance Test

    NASA Technical Reports Server (NTRS)

    Barbre', Robert E., Jr.; Decker, Ryan K.; Leahy, Frank B.; Huddleston, Lisa

    2016-01-01

    This paper presents results of the new Kennedy Space Center (KSC) 50-MHz Doppler Radar Wind Profiler (DRWP) Operational Acceptance Test (OAT). The goal of the OAT was to verify the data quality of the new DRWP against the performance of the previous DRWP in order to use wind data derived by the new DRWP for space launch vehicle operations support at the Eastern Range. The previous DRWP was used as a situational awareness asset for mission operations to identify rapid changes in the wind environment that weather balloons cannot depict. The Marshall Space Flight Center's Natural Environments Branch assessed data from the new DRWP collected during Jan-Feb 2015 against a specified set of test criteria. Data examination verified that the DRWP provides complete profiles every five minutes from 1.8-19.5 km in vertical increments of 150 m. Analysis of 49 concurrent DRWP and balloon profiles presented root mean square wind component differences around 2.0 m/s. Evaluation of the DRWP's coherence between five-minute wind pairs found the effective vertical resolution to be Nyquist-limited at 300 m for both wind components. In addition, the sensitivity to rejecting data that do not have adequate signal was quantified. This paper documents the data, quality control procedures, methodology, and results of each analysis.

  19. Validation, acceptance, and extension of a predictive model of reproductive toxicity using ToxCast data

    EPA Science Inventory

    The EPA ToxCast research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I tested 309 well-characterized chemicals (mostly pesticides) in over 500 assays of different molecular targets, cellular responses an...

  20. Gaining Acceptance for the use of in vitro Toxicity Assays and QIVIVE in Regulatory Risk Assessment

    EPA Science Inventory

    Testing strategies are anticipated to increasingly rely on in vitro data as a basis to characterize early steps or key events in toxicity at relevant dose levels in human tissues. This requires quantitative in vitro to in vivo extrapolation to characterize dose-response as a bas...

  1. Elucidation of Adverse Bioactivity Profiles as Predictors of Toxicity Potential

    EPA Science Inventory

    Toxicity testing in vitro remains a formidable challenge due to lack of understanding of key molecular targets and pathways underlying many pathological events. The combination of genome sequencing and widespread application of high-throughput screening tools have provided the me...

  2. Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity

    PubMed Central

    von Klot-Heydenfeldt, F.; Jabar, S.; Ranft, A.; Rossig, C.; Dirksen, U.; Van den Brande, J.; D'Incalci, M.; von Luettichau, I.; Grohar, P. J.; Berdel, W. E.; Burdach, St.

    2016-01-01

    Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial. PMID:27843394

  3. Toxic chemical hazard classification and risk acceptance guidelines for use in DOE facilities. Revision 2

    SciTech Connect

    Craig, D.K.; Davis, J.S.; Prowse, J.; Hoffman, P.W.

    1995-03-24

    The concentration-limit guidelines presented in this document apply to airborne releases of chemicals evaluated with respect to human health effects for the purposes of hazard classification and categorization, risk assessment and safety analysis. They apply to all DOE facilities and operations involving the use of potentially hazardous chemicals. The guidelines do not address other nonradiological hazards such as fire, pressure releases (including explosions), and chemical reactivity, but the guidelines are applicable to hazardous chemical releases resulting from these events. This report presents the subcommittee`s evaluation and recommendations regarding analyses of accidentally released toxic chemicals. The premise upon which these recommendations are based is that the mechanism of action of toxic chemicals is fundamentally different from that associated with radionuclides, with the exception of carcinogens. The recommendations reported herein are restricted to the airborne pathway because in an accident scenario this typically represents the most immediately significant route of public exposure. However, the subcommittee recognizes that exposure to chemicals through other pathways, in particular waterborne, can have significant impacts on human health and the environment. Although there are a number of chemicals for which absorption through the skin can contribute measurably to the total dose in chronic (e.g., occupational) exposure situations, this pathway has not been considered for the acute exposure scenarios considered in this report. Later studies. will address these issues if it appears desirable.

  4. Toxicity profile of commercially produced indigenous banana beer.

    PubMed

    Shale, K; Mukamugema, J; Lues, R J; Venter, P

    2012-08-01

    Mycotoxins, together with endotoxins, represent important classes of naturally occurring contaminants in food products, posing significant health risks to consumers. The aim of this study is to investigate the occurrence of both Fusarium mycotoxins and endotoxins in commercially produced traditional banana beer. Two brands of commercially produced traditional banana beer were collected from a local retail market in Kigali, Rwanda. Beer samples were analysed for the presence of deoxynivalenol (DON), fumonisin B₁ and zearalenone (ZEA), using an enzyme-linked immuno-sorbent assay (ELISA) method. The quantification of bacterial endotoxin using Limulus amoeboecyte lysate (LAL) assay was also conducted. The contamination levels were 20 and 6.7 µg kg⁻¹ for DON; 34 and 31.3 µg kg⁻¹ for FB₁; 0.66 and 2.2 µg kg⁻¹ for ZEA in brands A and B of the beers, respectively. Results indicate that the levels of Fusarium toxins and bacterial endotoxin reported in this study did not pose adverse human health effects as a result of drinking/consuming banana beer. However, exposure to low/sub-threshold doses or non-toxic levels of endotoxins magnifies the toxic effect of xenobiotic agents (e.g. fungal toxins) on liver and other target organs. Considering Fusarium toxins and/or endotoxin contamination levels in other agricultural commodities intended for human consumption, health risks might be high and the condition is aggravated when beer is contaminated by mixtures of the mycotoxins, as indicated in this study.

  5. Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea.

    PubMed

    Bae, So Hyun; Park, Min-Jung; Lee, Min Mi; Kim, Tae Min; Lee, Se-Hoon; Cho, Sung Yun; Kim, Young-Hoon; Kim, Yu Jung; Park, Chul-Kee; Kim, Chae-Yong

    2014-07-01

    This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.

  6. Sensory Profile and Consumer Acceptability of Prebiotic White Chocolate with Sucrose Substitutes and the Addition of Goji Berry (Lycium barbarum).

    PubMed

    Morais Ferreira, Janaína Madruga; Azevedo, Bruna Marcacini; Luccas, Valdecir; Bolini, Helena Maria André

    2017-03-01

    Functional food is a product containing nutrients that provide health benefits beyond basic nutrition. The objective of the present study was to evaluate the descriptive sensory profile and consumers' acceptance of functional (prebiotic) white chocolates with and without the addition of an antioxidant source (goji berry [GB]) and sucrose replacement. The descriptive sensory profile was determined by quantitative descriptive analysis (QDA) with trained assessors (n = 12), and the acceptance test was performed with 120 consumers. The correlation of descriptive and hedonic data was determined by partial least squares (PLS). The results of QDA indicated that GB reduces the perception of most aroma and flavor attributes, and enhances the bitter taste, bitter aftertaste, astringency, and most of the texture attributes. The consumers' acceptance of the chocolates was positive for all sensory characteristics, with acceptance scores above 6 on a 9-point scale. According to the PLS regression analysis, the descriptors cream color and cocoa butter flavor contributed positively to the acceptance of functional white chocolates. Therefore, prebiotic white chocolate with or without the addition of GB is innovative and can attract consumers, due to its functional properties, being a promising alternative for the food industry.

  7. Lipophilic toxin profile in Galicia (Spain): 2005 toxic episode.

    PubMed

    Villar-González, A; Rodríguez-Velasco, M L; Ben-Gigirey, B; Botana, L M

    2007-06-15

    By the end of 2005, a toxic episode of phytoplankton origin in bivalve shellfish led to the closing down of several shellfish production areas in Galicia (northwestern region of Spain). During this time, different kinds of shellfish were collected and analysed by LC-MS/MS to search for the following lipophilic toxins: okadaic acid (OA), dinophysistoxins (DTXs), pectenotoxins (PTXs), azaspiracids (AZAs) and spirolides. Samples were analysed before alkaline hydrolysis in order to investigate the presence of free OA and DTXs, AZAs, PTXs and spirolides, and after alkaline hydrolysis to detect OA and DTXs esters. All of the samples were found to be contaminated with OA and/or DTX-2, as well as esterified forms of these diarrhetic shellfish poison (DSP) toxins, at levels around and above European regulatory limit (160 microg of okadaic acid equivalents/kg). The analyses of mussels and razor clam also revealed the presence of 13-desmethyl spirolide C (SPX-1) at levels below 31 microg/kg. Likewise, in many of the samples different levels of pectenotoxin-2 secoacid (PTX-2sa) were detected. DSP toxin esters represent practically the 100% of the total OA equivalents for scallops, clams, razor clams and cockles.

  8. Desalinated versus recycled water: public perceptions and profiles of the accepters.

    PubMed

    Dolnicar, Sara; Schäfer, Andrea I

    2009-02-01

    Many countries' water resources are limited in both quantity and quality. While engineering solutions can now safely produce recycled and desalinated water from non-potable sources at a relatively low cost, the general public is sceptical about adopting these alternative water sources. Social scientists, policy makers and technical experts need to better understand what is causing this lack of acceptance by the general population and how acceptance levels for recycled and desalinated water can be increased. This study is the first to conduct a comparative analysis of knowledge, perceptions, and acceptability, and determine segments of residents who are more open-minded than the general population toward the use of recycled and desalinated water. The Australian population once perceived desalinated water as environmentally unfriendly, and recycled water as a public health hazard. The general level of knowledge about these two concepts as potential water sources has historically been low. After nearly five years of serious drought, accompanied by severe water restrictions across most of the country, and subsequent media attention on solutions to water scarcity, Australians now show more acceptance of desalinated water for close-to-body uses, and less resistance to recycled water for garden watering and cleaning uses. The types of people likely to be strong accepters of the two alternative water sources are distinctly different groups, and can be reached through different media mixes. This finding has significant implications for policy makers and water practitioners.

  9. Behavioural toxicity assessment of silver ions and nanoparticles on zebrafish using a locomotion profiling approach.

    PubMed

    Ašmonaitė, Giedrė; Boyer, Scott; Souza, Karine Bresolin de; Wassmur, Britt; Sturve, Joachim

    2016-04-01

    Zebrafish (Danio rerio) is not only a widely used species in the Fish Embryo Toxicity (FET) test but also an emerging model in behavioural ecotoxicology. By using automatic behaviour tracking technology, locomotion of developing zebrafish (ZF) larvae can be accurately recorded and potentially used in an ecotoxicological context to detect toxicant-induced behavioural alterations. In this study, we explored if and how quantitative locomotion data can be used for sub-lethal toxicity testing within the FET framework. We exposed ZF embryos to silver ions and nanoparticles, which previously have been reported to cause neurodevelopmental toxicity and behavioural retardation in early-life stages of ZF. Exposure to a broad range of silver (Ag(+) and AgNPs) concentrations was conducted, and developmental toxicity was assessed using FET criteria. For behavioural toxicity assessment, locomotion of exposed ZF eleutheroembryos (120hpf) was quantified according to a customised behavioural assay in an automatic video tracking system. A set of repeated episodes of dark/light stimulation were used to artificially stress ZF and evoke photo-motor responses, which were consequently utilized for locomotion profiling. Our locomotion-based behaviour profiling approach consisted of (1) dose-response ranking for multiple and single locomotion variables; (2) quantitative assessment of locomotion structure; and (3) analysis of ZF responsiveness to darkness stimulation. We documented that both silver forms caused adverse effects on development and inhibited hatchability and, most importantly, altered locomotion. High Ag(+) and AgNPs exposures significantly suppressed locomotion and a clear shift in locomotion towards inactivity was reported. Additionally, we noted that low, environmentally relevant Ag(+) concentrations may cause subordinate locomotive changes (hyperactivity) in developing fish. Overall, it was concluded that our locomotion-based behaviour-testing scheme can be used jointly

  10. Toxicity profile of lutein and lutein ester isolated from marigold flowers (Tagetes erecta).

    PubMed

    Harikumar, Kuzhuvelil Bhaskarannair; Nimita, Chittikappil Venugopal; Preethi, Korengath Chandran; Kuttan, Ramadasan; Shankaranarayana, Madapura Lingappiah; Deshpande, Jayant

    2008-01-01

    Lutein is a carotenoid with antioxidant properties and is commonly present in many fruits, vegetables, and egg yolk. Lutein affords protection against the development of the two common eye diseases of aging: cataract and macular degeneration. As the dietary lutein concentration is much lower compared to the actual requirement to reduce macular degeneration, supplementation of lutein is under consideration. There are very few data on the toxicity of lutein. In the present study, the authors have evaluated the short-term and long-term toxicity profile of lutein and its esterified form isolated from marigold flowers (Tagetes erecta) in young adult male and female Wistar rats. Lutein and its ester form administered orally at doses of 4, 40, and 400 mg/kg body weight for 4 weeks for short-term toxicity study and 13 weeks for a subchronic toxicity study did not produced any mortality, change in body weight, food consumption pattern, organ weight, and other adverse side reactions. Administration of lutein and ester form did not alter the hepatic and renal function, and did not produce any change in the hematological parameters and in lipid profile. Histopathological analysis of the organs supported the nontoxicity of lutein and its ester form.

  11. Detrimental effects of chemotherapeutics and other drugs on the endothelium: A call for endothelial toxicity profiling.

    PubMed

    Wojcik, Tomasz; Szczesny, Ewa; Chlopicki, Stefan

    2015-08-01

    The vascular endothelium is a real "maestro of circulation", and endothelial dysfunction leads to atherothrombosis, its cardiovascular complications, as well as to many other diseases. It is surprising that quite a large number of drugs seem to hamper the vasoprotective mechanisms of the endothelium, possibly promoting the development of cardiovascular diseases in patients initially treated for non-cardiological conditions. Toxicity profiling (including cardiac and liver toxicity assessment) is a routine procedure performed during pre-clinical drug development. Unfortunately, endothelium-dependent side effects are not taken into account in standard toxicity profiling protocols, as the "endothelial safety" of drugs is not required in order to enter the clinical phase of drug development. Presumably, this might be one of the reasons why several efficient therapeutics, including rofecoxib (COX-2 inhibitor), torcetrapib (CETP-inhibitor), and bardoxolone (Nrf2 activator), have unexpectedly displayed clinically significant cardiovascular hazard, resulting in their withdrawal from the market or alarming comments, respectively. In this review, we will briefly characterize the endothelial activity profiles of chemotherapeutics, antidepressants and antipsychotics-all drugs prescribed for severe, life-threatening and/or life-long diseases-and will show that at least some of them may display clinically relevant detrimental effects on endothelial function.

  12. Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

    SciTech Connect

    Ohashi, Toshio; Yorozu, Atsunori; Saito, Shiro; Tanaka, Nobumichi; Katayama, Norihisa; Kojima, Shinsuke; Maruo, Shinichiro; Kikuchi, Takashi; Dokiya, Takushi; Fukushima, Masanori; Yamanaka, Hidetoshi

    2015-09-01

    Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.

  13. Toxicity of copper intake: lipid profile, oxidative stress and susceptibility to renal dysfunction.

    PubMed

    Galhardi, Cristiano M; Diniz, Yeda S; Faine, Luciane A; Rodrigues, Hosana G; Burneiko, Regina C M; Ribas, Bartolome O; Novelli, Ethel L B

    2004-12-01

    The present study was carried out to investigate the effects of copper (Cu) intake on lipid profile, oxidative stress and tissue damage in normal and in diabetic condition. Since diabetes mellitus is a situation of high-risk susceptibility to toxic compounds, we examined potential early markers of Cu excess in diabetic animals. Male Wistar rats, at 60-days-old were divided into six groups of eight rats each. The control(C) received saline from gastric tube, the no-diabetic(Cu-10), treated with 10 mg/kg of Cu(Cu(++)-CuSO4, gastric tube), no-diabetic with Cu-60 mg/kg(Cu-60), diabetic(D), diabetic low-Cu(DCu-10) and diabetic high-Cu(DCu-60). Diabetes was induced by an ip injection of streptozotocin (60 mg/kg). After 30 days of treatments, no changes were observed in serum lactate dehydrogenase, alanine transaminase and alkaline phosphatase, indicating no adverse effects on cardiac and hepatic tissues. D-rats had glucose intolerance and dyslipidemic profile. Cholesterol and LDL-cholesterol were higher in Cu-60 and DCu-60 than in C, Cu-10 and D and DCu-10 groups respectively. Cu-60 rats had higher lipid hydroperoxide (HP) and lower superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) serum activities than C and Cu-10 rats. LH was increased and GSH-Px was decreased, while no alterations were observed in SOD and catalase in serum of DCu-60 animals. DCu-60 rats had increased urinary glucose, creatinine and albumin. In conclusion, Cu intake at high concentration induced adverse effects on lipid profile, associated with oxidative stress and diminished activities of antioxidant enzymes. Diabetic animals were more susceptible to copper toxicity. High Cu intake induced dyslipidemic profile, oxidative stress and kidney dysfunction in diabetic condition. Copper renal toxicity was associated with oxidative stress and reduction at least, one of the antioxidant enzymes.

  14. Profile of stress and toxicity gene expression in human hepatic cells treated with Efavirenz.

    PubMed

    Gomez-Sucerquia, Leysa J; Blas-Garcia, Ana; Marti-Cabrera, Miguel; Esplugues, Juan V; Apostolova, Nadezda

    2012-06-01

    Hepatic toxicity and metabolic disorders are major adverse effects elicited during the pharmacological treatment of the human immunodeficiency virus (HIV) infection. Efavirenz (EFV), the most widely used non-nucleoside reverse transcriptase inhibitor (NNRTI), has been associated with these events, with recent studies implicating it in stress responses involving mitochondrial dysfunction and oxidative stress in human hepatic cells. To expand these findings, we analyzed the influence of EFV on the expression profile of selected stress and toxicity genes in these cells. Significant up-regulation was observed with Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), which indicated metabolic stress. Several genes directly related to oxidative stress and damage exhibited increased expression, including Methalothionein 2A (MT2A), Heat shock 70kDa protein 6 (HSPA6), Growth differentiation factor 15 (GDF15) and DNA-damage-inducible transcript 3 (DDIT3). In addition, Early growth response protein 1 (EGR1) was enhanced, whereas mRNA levels of the inflammatory genes Chemokine (C-X-C motif) ligand 10 (CXCL10) and Serpin peptidase inhibitor (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1) decreased and increased, respectively. This profile of gene expression supports previous data demonstrating altered mitochondrial function and presence of oxidative stress/damage in EFV-treated hepatic cells, and may be of relevance in the search for molecular targets with therapeutic potential to be employed in the prevention, diagnosis and treatment of the hepatic toxicity associated with HIV therapy.

  15. Estimating toxic damage to soil ecosystems from soil organic matter profiles

    USGS Publications Warehouse

    Beyer, W.N.

    2001-01-01

    Concentrations of particulate and total organic matter were measured in upper soil profiles at 26 sites as a potential means to identify toxic damage to soil ecosystems. Because soil organic matter plays a role in cycling nutrients, aerating soil, retaining water, and maintaining tilth, a significant reduction in organic matter content in a soil profile is not just evidence of a change in ecosystem function, but of damage to that soil ecosystem. Reference sites were selected for comparison to contaminated sites, and additional sites were selected to illustrate how variables other than environmental contaminants might affect the Soil organic matter profile. The survey was undertaken on the supposition that environmental contaminants and other stressors reduce the activity of earthworms and other macrofauna, inhibiting the incorporation of organic matter into the soil profile. The profiles of the unstressed soils showed a continuous decrease in organic matter content from the uppermost mineral soil layer (0-2.5 cm) down to 15 cm. Stressed soils showed an abrupt decrease in soil organic matter content below a depth of 2.5 cm. The 2.5-5.0 cm layer of stressed soils--such as found in a pine barren, an orchard, sites contaminated with zinc, and a site with compacted soil--had less than 4% total organic matter and less than 1% particulate organic matter. However, damaged soil ecosystems were best identified by comparison of their profiles to the profiles of closely matched reference soils, rather than by comparison to these absolute values. The presence or absence of earthworms offered a partial explanation of observed differences in soil organic matter profiles.

  16. Results of the Updated NASA Kennedy Space Center 50-MHz Doppler Radar Wind Profiler Operational Acceptance Test

    NASA Technical Reports Server (NTRS)

    Barbre', Robert E., Jr.; Deker, Ryan K.; Leahy, Frank B.; Huddleston, Lisa

    2016-01-01

    We present here the methodology and results of the Operational Acceptance Test (OAT) performed on the new Kennedy Space Center (KSC) 50-MHz Doppler Radar Wind Profiler (DRWP). On day-of-launch (DOL), space launch vehicle operators have used data from the DRWP to invalidate winds in prelaunch loads and trajectory assessments due to the DRWP's capability to quickly identify changes in the wind profile within a rapidly-changing wind environment. The previous DRWP has been replaced with a completely new system, which needs to undergo certification testing before being accepted for use in range operations. The new DRWP replaces the previous three-beam system made of coaxial cables and a copper wire ground plane with a four-beam system that uses Yagi antennae with enhanced beam steering capability. In addition, the new system contains updated user interface software while maintaining the same general capability as the previous system. The new DRWP continues to use the Median Filter First Guess (MFFG) algorithm to generate a wind profile from Doppler spectra at each range gate. DeTect (2015) contains further details on the upgrade. The OAT is a short-term test designed so that end users can utilize the new DRWP in a similar manner to the previous DRWP during mission operations at the Eastern Range in the midst of a long-term certification process. This paper describes the Marshall Space Flight Center Natural Environments Branch's (MSFC NE's) analyses to verify the quality and accuracy of the DRWP's meteorological data output as compared to the previous DRWP. Ultimately, each launch vehicle program has the responsibility to certify the system for their own use.

  17. Toxicity Profile of a Nutraceutical Formulation Derived from Green Mussel Perna viridis

    PubMed Central

    Joseph, Deepu; Chakkalakal, Selsa J.

    2014-01-01

    The short-term (acute) and long-term (subchronic) toxicity profile, mean lethal dose 50 (LD50), and no-observed-adverse-effect level (NOAEL) of a nutraceutical formulation developed from green mussel Perna viridis, which showed in vitro and in vivo anti-inflammatory properties, were evaluated in the present study. The formulation was administered to the male and female Wistar rats at graded doses (0.5, 1.0, and 2.5 g/kg body weight) for two weeks of acute toxicity study and 0.5, 1.0, and 2.0 g/kg body weight for 90 days in subchronic toxicity study. The LD50, variations in clinical signs, changes in body weight, body weight, food/water consumption, organ weight (liver, kidney, spleen, and brain), hematology, serum chemistry, and histopathological changes were evaluated. The LD50 of the formulation was 5,000 mg/kg BW. No test article related mortalities as well as change in body weight, and food and water consumption were observed. No toxicity related significant changes were noted in renal/hepatic function, hematological indices, and serum biochemical parameters between the control and treated groups. Histopathological alterations were not observed in the vital organs of rats. The subchronic NOAEL for the formulation in rats is greater than 2000 mg/kg. This study demonstrated that the green mussel formulation is safe to consume without any adverse effects in the body. PMID:24995298

  18. Toxicity and biocompatibility profile of 3D bone scaffold developed by Universitas Indonesia: A preliminary study

    NASA Astrophysics Data System (ADS)

    Rahyussalim A., J.; Kurniawati, T.; Aprilya, D.; Anggraini, R.; Ramahdita, Ghiska; Whulanza, Yudan

    2017-02-01

    Scaffold as a biomaterial must fulfill some requirements to be safely implanted to the human body. Toxicity and biocompatibility test are needed to evaluate scaffold material in mediating cell proliferation and differentiation, secreting extracelullar matrix and carrying biomolecular signals for cell communication. An in vitro study with mesenchymal stem cells consisted of direct contact test and indirect contact test using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay was conducted on 4 scaffolds made of poly-L-lactic acid (PLA), polyvinyl alcohol (PVA), and hydroxyapatite-poly (vinyl alcohol) composite. There were cells-substrate adhesion impairment, morphological changes, cell death and reduction in cell proliferation seen at 2nd and 6th day in most tested scaffold. Cell count result at day-6 showed proliferation inhibition of more than 50% cell death (inhibition value >50) in all tested scaffold. In MTT assay, two scaffolds were proven non-toxic. In conclusion, various scaffold materials showed different toxicity effect. The toxicity and biocompatibility profile in this study is a preliminary data for further research aiming to use those local-made scaffolds to fill human bone defect in various needs.

  19. Consumer acceptability and sensory profile of cooked broccoli with mustard seeds added to improve chemoprotective properties.

    PubMed

    Ghawi, Sameer Khalil; Shen, Yuchi; Niranjan, Keshavan; Methven, Lisa

    2014-09-01

    Broccoli, a rich source of glucosinolates, is a commonly consumed vegetable of the Brassica family. Hydrolysis products of glucosinolates, isothiocyanates, have been associated with health benefits and contribute to the flavor of Brassica. However, boiling broccoli causes the myrosinase enzyme needed for hydrolysis to denature. In order to ensure hydrolysis, broccoli must either be mildly cooked or active sources of myrosinase, such as mustard seed powder, can be added postcooking. In this study, samples of broccoli were prepared in 6 different ways; standard boiling, standard boiling followed by the addition of mustard seeds, sous vide cooking at low temperature (70 °C) and sous vide cooking at higher temperature (100 °C) and sous vide cooking at higher temperature followed by the addition of mustard seeds at 2 different concentrations. The majority of consumers disliked the mildly cooked broccoli samples (70 °C, 12 min, sous vide) which had a hard and stringy texture. The highest mean consumer liking was for standard boiled samples (100 °C, 7 min). Addition of 1% mustard seed powder developed sensory attributes, such as pungency, burning sensation, mustard odor, and flavor. One cluster of consumers (32%) found mustard seeds to be a good complement to cooked broccoli; however, the majority disliked the mustard-derived sensory attributes. Where the mustard seeds were partially processed, doubling the addition to 2% led to only the same level of mustard and pungent flavors as 1% unprocessed seeds, and mean consumer liking remained unaltered. This suggests that optimization of the addition level of partially processed mustard seeds may be a route to enhance bioactivity of cooked broccoli without compromising consumer acceptability.

  20. In Vitro and In Vivo Toxicity Profiling of Ammonium-Based Deep Eutectic Solvents

    PubMed Central

    Hayyan, Maan; Looi, Chung Yeng; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd Ali

    2015-01-01

    The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes. PMID:25679975

  1. Influence of the sample toxic profile on the suitability of a high performance liquid chromatography method for official paralytic shellfish toxins control.

    PubMed

    Ben-Gigirey, B; Rodríguez-Velasco, M L; Villar-González, A; Botana, L M

    2007-01-26

    An HPLC-FLD method, involving pre-chromatographic oxidation of the PSP toxins with hydrogen peroxide and periodate, has been AOAC validated through a collaborative trial and adopted as AOAC Official Method. This method could be a candidate for replacing the mouse bioassay (MBA) for the Official Control of PSP toxins at European level, once accepted by the legislation. An interlaboratory exercise has been organized by the CRLMB to evaluate its "fitness for purpose" for the Official Control of PSP toxins in the EU laboratories. Eighteen EU laboratories took part in the study and had to analyze six bivalve mollusc samples with several PSP toxic profiles. The performance of the participant laboratories in the application of this method was compared with that obtained at the collaborative trial. Information on problems/drawbacks encountered by participants in the application of this method was also sought. The HPLC validated method is only applicable for Official PSP Control for certain samples. This depends on sample PSP toxic profile. Results obtained for samples where only GTX2,3 and STX were present were satisfactory and in agreement with MBA results. Results obtained for a sample with a toxic profile dominated by GTX6 and suspected to contain also C1,2 and C3,4 were not satisfactory. GTX5 and dc-STX could be quantified, although the results achieved (total toxicity) were lower than those obtained by MBA. It can be also useful as a screening method, complementary to MBA, helping in the reduction of the animals used. However, the lack of several PSP standards, the fact that the method is not validated for all the PSP toxins, and several drawbacks found in its application are a handicap to fully implement it for Official PSP Control as a viable replacement for bioassay.

  2. Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

    PubMed

    Sengupta, Pinaki; Das, Arindam; Ibrahim, Fuzianna; Mandal, Uttam Kumar; Chatterjee, Bappaditya; Mahmood, Syed; Das, Sreemoy Kanti; Kifayatullah, Muhammad

    2016-11-01

    It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

  3. Toxicity Profile of the Aqueous Ethanol Root Extract of Corrigiola telephiifolia Pourr. (Caryophyllaceae) in Rodents

    PubMed Central

    Lakmichi, Hind; Bakhtaoui, Fatima Zahra; Gadhi, Chemseddoha A.; Ezoubeiri, Aicha; El Jahiri, Younes; El Mansouri, Abdellah; Zrara, Ibtissam; Loutfi, Kenza

    2011-01-01

    Corrigiola telephiifolia Pourr. (Caryophyllaceae) is a Moroccan medicinal plant. Despite its popular usage, no study has been published concerning its toxicological profile. The acute toxicity of C. telephiifolia root extract was evaluated by giving it orally to mice at single doses of 5000, 10000, and 14000 mg/kg bodyweight. The extract was also administered at doses of 5, 70, and 2000 mg/kg bodyweight per day to rats for a forty-day toxicity study. No mortality or signs of toxicity were observed in the acute study. In the forty-day study in rats, the extract at 5 mg/kg/day showed no toxicological effects in either sex. At 70 mg/kg/day, the treated group differed from the control only by a significant decrease in serum concentrations of sodium and chloride ions (P < .05). At the dose of 2000 mg/kg/day, the extract significantly increased the serum concentrations of creatinine, alkaline phosphatase, gamma-glutamyltransferase and phosphorus (P < .05) all suggestive of functional nephrotoxicity and hepatotoxicity. The relative bodyweight of both sexes decreased at the dose of 2000 mg/kg/day, with a fast recovery for males. Histological examination did not reveal any treatment-related effects. In conclusion, Corrigiola extract appears safe at the doses used ethno-medicinally. Much higher doses pose toxicological risks. PMID:20953424

  4. Toxicity profile of choline chloride-based deep eutectic solvents for fungi and Cyprinus carpio fish.

    PubMed

    Juneidi, Ibrahim; Hayyan, Maan; Mohd Ali, Ozair

    2016-04-01

    An investigation on the toxicological assessment of 10 choline chloride (ChCl)-based deep eutectic solvents (DESs) towards four fungi strains and Cyprinus carpio fish was conducted. ChCl was combined with materials from different chemical groups such as alcohols, sugars, acids and others to form DESs. The study was carried out on the individual DES components, their aqueous mixture before DES formation and their formed DESs. The agar disc diffusion method was followed to investigate their toxicity on four fungi strains selected as a model of eukaryotic microorganisms (Phanerochaete chrysosporium, Aspergillus niger, Lentinus tigrinus and Candida cylindracea). Among these DESs, ChCl:ZnCl2 exhibited the highest inhibition zone diameter towards the tested fungi growth in vitro, followed by the acidic group (malonic acid and p-toluenesulfonic acid). Another study was conducted to test the acute toxicity and determine the lethal concentration at 50 % (LC50) of the same DESs on C. carpio fish. The inhibition range and LC50 of DESs were found to be different from their individual components. DESs were found to be less toxic than their mixture or individual components. The LC50 of ChCl:MADES is much higher than that of ChCl:MAMix. Moreover, the DESs acidic group showed a lower inhibition zone on fungi growth. Thus, DESs should be considered as new components with different physicochemical properties and toxicological profiles, and not merely compositions of compounds.

  5. Molecular Characterization of Thyroid Toxicity: Anchoring Gene Expression Profiles to Biochemical and Pathologic End Points

    PubMed Central

    Glatt, Christine M.; Ouyang, Ming; Welsh, William; Green, John W.; Connor, John O; Frame, Steven R.; Everds, Nancy E.; Poindexter, Greg; Snajdr, Suzanne; Delker, Don A.

    2005-01-01

    Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PB-and PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5′-deiodinase I (5′-DI) activity to < 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein–coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress–related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression. PMID:16203246

  6. 3D printed polymers toxicity profiling: a caution for biodevice applications

    NASA Astrophysics Data System (ADS)

    Zhu, Feng; Skommer, Joanna; Friedrich, Timo; Kaslin, Jan; Wlodkowic, Donald

    2015-12-01

    A recent revolution in additive manufacturing technologies and access to 3D Computer Assisted Design (CAD) software has spurred an explosive growth of new technologies in biomedical engineering. This includes biomodels for diagnosis, surgical training, hard and soft tissue replacement, biodevices and tissue engineering. Moreover, recent developments in high-definition additive manufacturing systems such as Multi-Jet Modelling (MJM) and Stereolithography (SLA), capable of reproducing feature sizes close to 100 μm, promise brand new capabilities in fabrication of optical-grade biomicrofluidic Lab-on-a-Chip and MEMS devices. Compared with other rapid prototyping technologies such as soft lithography and infrared laser micromachining in PMMA, SLA and MJM systems can enable user-friendly production of prototypes, superior feature reproduction quality and comparable levels of optical transparency. Prospectively they can revolutionize fabrication of microfluidic devices with complex geometric features and eliminate the need to use clean room environment and conventional microfabrication techniques. In this work we demonstrate preliminary data on toxicity profiling of a panel of common polymers used in 3D printing applications. The main motivation of our work was to evaluate toxicity profiles of most commonly used polymers using standardized biotests according to OECD guidelines for testing of chemic risk assessment. Our work for the first time provides a multispecies view of potential dangers and limitation for building biocompatible devices using FDM, SLA and MJM additive manufacturing systems. Our work shows that additive manufacturing holds significant promise for fabricating LOC and MEMS but requires caution when selecting systems and polymers due to toxicity exhibited by some 3D printing polymers.

  7. Profiling Developmental Toxicity of 387 Environmental Chemicals using EPA’s Toxicity Reference Database (ToxRefDB)

    EPA Science Inventory

    EPA's Toxicity Reference Databases (ToxRefDB) was developed by the National Center for Computational Toxicology in partnership with EPA's Office of Pesticide Programs, to store data derived from in vivo animal toxicity studies [www.epa.gov/ncct/toxrefdb/]. The initial build of To...

  8. Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides

    SciTech Connect

    Tully, Douglas B.; Bao Wenjun; Goetz, Amber K.; Blystone, Chad R.; Ren, Hongzu; Schmid, Judith E.; Strader, Lillian F.; Wood, Carmen R.; Best, Deborah S.; Narotsky, Michael G.; Wolf, Douglas C.; Rockett, John C.; Dix, David J. . E-mail: dix.david@epa.gov

    2006-09-15

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

  9. TOXICITY PROFILING OF ENGINEERED NANOMATERIALS VIA MULTIVARIATE DOSE-RESPONSE SURFACE MODELING

    PubMed Central

    Patel, Trina; Telesca, Donatello; George, Saji; Nel, André E.

    2014-01-01

    New generation in vitro high-throughput screening (HTS) assays for the assessment of engineered nanomaterials provide an opportunity to learn how these particles interact at the cellular level, particularly in relation to injury pathways. These types of assays are often characterized by small sample sizes, high measurement error and high dimensionality, as multiple cytotoxicity outcomes are measured across an array of doses and durations of exposure. In this paper we propose a probability model for the toxicity profiling of engineered nanomaterials. A hierarchical structure is used to account for the multivariate nature of the data by modeling dependence between outcomes and thereby combining information across cytotoxicity pathways. In this framework we are able to provide a flexible surface-response model that provides inference and generalizations of various classical risk assessment parameters. We discuss applications of this model to data on eight nanoparticles evaluated in relation to four cytotoxicity parameters. PMID:25191531

  10. Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar Rats

    PubMed Central

    Sharwan, Gotmi; Jain, Parag; Pandey, Ravindra; Shukla, Shiv Shankar

    2016-01-01

    Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/ kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD – 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single- dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases. PMID:27695635

  11. Environmental Pollution, Toxicity Profile and Treatment Approaches for Tannery Wastewater and Its Chemical Pollutants.

    PubMed

    Saxena, Gaurav; Chandra, Ram; Bharagava, Ram Naresh

    Leather industries are key contributors in the economy of many developing countries, but unfortunately they are facing serious challenges from the public and governments due to the associated environmental pollution. There is a public outcry against the industry due to the discharge of potentially toxic wastewater having alkaline pH, dark brown colour, unpleasant odour, high biological and chemical oxygen demand, total dissolved solids and a mixture of organic and inorganic pollutants. Various environment protection agencies have prioritized several chemicals as hazardous and restricted their use in leather processing however; many of these chemicals are used and discharged in wastewater. Therefore, it is imperative to adequately treat/detoxify the tannery wastewater for environmental safety. This paper provides a detail review on the environmental pollution and toxicity profile of tannery wastewater and chemicals. Furthermore, the status and advances in the existing treatment approaches used for the treatment and/or detoxification of tannery wastewater at both laboratory and pilot/industrial scale have been reviewed. In addition, the emerging treatment approaches alone or in combination with biological treatment approaches have also been considered. Moreover, the limitations of existing and emerging treatment approaches have been summarized and potential areas for further investigations have been discussed. In addition, the clean technologies for waste minimization, control and management are also discussed. Finally, the international legislation scenario on discharge limits for tannery wastewater and chemicals has also been discussed country wise with discharge standards for pollution prevention due to tannery wastewater.

  12. Phenolic profile and antioxidant activity from non-toxic Mexican Jatropha curcas L. shell methanolic extracts.

    PubMed

    Perea-Domínguez, Xiomara Patricia; Espinosa-Alonso, Laura Gabriela; Hosseinian, Farah; HadiNezhad, Mehri; Valdez-Morales, Maribel; Medina-Godoy, Sergio

    2017-03-01

    Jatropha curcas seed shells are the by-product obtained during oil extraction process. Recently, its chemical composition has gained attention since its potential applications. The aim of this study was to identify phenolic compounds profile from a non-toxic J. curcas shell from Mexico, besides, evaluate J. curcas shell methanolic extract (JcSME) antioxidant activity. Free, conjugate and bound phenolics were fractionated and quantified (606.7, 193.32 and 909.59 μg/g shell, respectively) and 13 individual phenolic compounds were detected by HPLC. The radical-scavenging activity of JcSME was similar to Trolox and ascorbic acid by DPPH assay while by ABTS assay it was similar to BHT. Effective antioxidant capacity by ORAC was found (426.44 ± 53.39 μmol Trolox equivalents/g shell). The Mexican non-toxic J. curcas shell is rich in phenolic compounds with high antioxidant activity; hence, it could be considerate as a good source of natural antioxidants.

  13. Effects of Dietary Selenium Against Lead Toxicity Are Related to the Ion Profile in Chicken Muscle.

    PubMed

    Jin, Xi; Liu, Chun Peng; Teng, Xiao Hua; Fu, Jing

    2016-08-01

    Complex antagonistic interactions between Selenium (Se) and heavy metals have been reported in previous studies. However, little is known regarding the effects of Se on lead (Pb)-induced toxicity and the ion profile in the muscles of chickens. In this present study, we fed chickens either Se or Pb or both Se and Pb supplement and later analyzed the concentrations of 26 ions in chicken muscle tissues. We determined that a Se- and Pb-containing diets significantly affected microelements in chicken muscle. Treatment with Se increased the content of Se but resulted in a reduced concentration of Cu, As, Cd, Sn, Hg, and Ba. Treatment with Pb increased concentrations of Ni while reducing those of B, V, Cr, Fe, Co, Cu, Zn, and Mo. Moreover, Se also reduced the concentration of Pb, Zn, Co, Fe, V, and Cr, which in contrast were induced by Pb. Additionally, we also found that synergistic and antagonistic interactions existed between Se and Pb supplementation. Our findings suggested that Se can exert a negative effect on Pb in chicken muscle tissues and may be related to changes in ion profiles.

  14. Longitudinal Stability of Social Competence Indicators in a Portuguese Sample: Q-Sort Profiles of Social Competence, Measures of Social Engagement, and Peer Sociometric Acceptance

    ERIC Educational Resources Information Center

    Santos, António J.; Vaughn, Brian E.; Peceguina, Inês; Daniel, João R.

    2014-01-01

    This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple…

  15. Short communication: Influence of long-chain inulin and Lactobacillus paracasei subspecies paracasei on the sensory profile and acceptance of a traditional yogurt.

    PubMed

    Pimentel, T C; Cruz, A G; Prudencio, S H

    2013-10-01

    The objectives of this study were to evaluate the influence of the addition of long-chain inulin as a fat replacer and prebiotic agent (20g/L) and (or) probiotic Lactobacillus paracasei ssp. paracasei on the sensory profile and acceptance of yogurts, and to assess the influence of descriptive attributes on the sensory acceptance of the products. The addition of inulin to low-fat yogurt improved its brightness and firmness, which was similar to the full-fat yogurt. However, the use of long-chain inulin increased the separation of serum and no influence on creaminess was observed. Regarding the product's acceptability, the low-fat yogurt with added inulin presented similar acceptance compared with the full-fat yogurt. The addition of Lb. paracasei ssp. paracasei did not affect the sensory profile and acceptance of the low-fat yogurt. Using external preference mapping, it was possible to verify that the sensory acceptance was driven positively by the sweetness and creaminess and negatively driven by firmness (appearance and texture) and homogeneity (appearance). It was possible to formulate low-fat yogurts with added probiotics that presented similar sensory characteristics to those of full-fat yogurts, and this was due to the addition of the long-chain inulin as a fat replacer.

  16. GENE EXPRESSION PROFILING IN TESTIS AND LIVER OF MICE TO IDENTIFY MODES OF ACTION OF CONAZOLE TOXICITIES

    EPA Science Inventory

    Gene Expression Profiling in Testis and Liver of Mice to Identify MODES OF ACTION OF Conazole TOXICITies

    Amber K. Goetz1, Wenjun Bao2, Judith E. Schmid2, Carmen Wood2, Hongzu Ren2, Deborah S. Best2, Rachel N. Murrell1, John C. Rockett2, Michael G. Narotsky2, Douglas C. Wol...

  17. GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE

    EPA Science Inventory

    Gene Expression Profiling Of Accessible Surrogate Tissues To Monitor Molecular Changes In Inaccessible Target Tissues Following Toxicant Exposure
    John C. Rockett, Chad R. Blystone, Amber K. Goetz, Rachel N. Murrell, Judith E. Schmid and David J. Dix
    Reproductive Toxicology ...

  18. Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid carrier in BALB/c mice

    PubMed Central

    Ong, Yong Sze; Saiful Yazan, Latifah; Ng, Wei Keat; Noordin, Mustapha M; Sapuan, Sarah; Foo, Jhi Biau; Tor, Yin Sim

    2016-01-01

    Background Thymoquinone (TQ), the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ. Materials and methods The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed. Results In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes. Conclusion For long-term oral consumption, TQ and

  19. Profiling Chemicals Based on Chronic Toxicity Results from the U.S. EPA ToxRef Database

    PubMed Central

    Martin, Matthew T.; Judson, Richard S.; Reif, David M.; Kavlock, Robert J.; Dix, David J.

    2009-01-01

    Background Thirty years of pesticide registration toxicity data have been historically stored as hardcopy and scanned documents by the U.S. Environmental Protection Agency (EPA). A significant portion of these data have now been processed into standardized and structured toxicity data within the EPA’s Toxicity Reference Database (ToxRefDB), including chronic, cancer, developmental, and reproductive studies from laboratory animals. These data are now accessible and mineable within ToxRefDB and are serving as a primary source of validation for U.S. EPA’s ToxCast research program in predictive toxicology. Objectives We profiled in vivo toxicities across 310 chemicals as a model application of ToxRefDB, meeting the need for detailed anchoring end points for development of ToxCast predictive signatures. Methods Using query and structured data-mining approaches, we generated toxicity profiles from ToxRefDB based on long-term rodent bioassays. These chronic/cancer data were analyzed for suitability as anchoring end points based on incidence, target organ, severity, potency, and significance. Results Under conditions of the bioassays, we observed pathologies for 273 of 310 chemicals, with greater preponderance (> 90%) occurring in the liver, kidney, thyroid, lung, testis, and spleen. We observed proliferative lesions for 225 chemicals, and 167 chemicals caused progression to cancer-related pathologies. Conclusions Based on incidence, severity, and potency, we selected 26 primarily tissue-specific pathology end points to uniformly classify the 310 chemicals. The resulting toxicity profile classifications demonstrate the utility of structuring legacy toxicity information and facilitating the computation of these data within ToxRefDB for ToxCast and other applications. PMID:19337514

  20. Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and Acceptable Poisoning of Invasive Small Mammalian Pests

    PubMed Central

    Morgan, David; Warburton, Bruce; Nugent, Graham

    2015-01-01

    Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus spp.) are major vertebrate pests in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Aerial distribution of baits containing sodium fluoroacetate (1080) has been refined to maximise cost effectiveness and minimise environmental impact, but this method is strongly opposed by some as it is perceived as being indiscriminate. Although ground based control enables precise placement of baits, operations are often more than twice as costly as aerial control, mainly due to the high labour costs. We investigated a new approach to ground based control that combined aerial distribution of non-toxic ‘prefeed’ baits followed by sparse distribution of toxic baits at regular intervals along the GPS tracked prefeeding flight paths. This approach was tested in two field trials in which both 1080 baits and cholecalciferol baits were used in separate areas. Effectiveness of the approach, assessed primarily using ‘chewcards’, was compared with that of scheduled aerial 1080 operations that were conducted in outlying areas of both trials. Contractors carrying out ground based control were able to follow the GPS tracks of aerial prefeeding flight lines very accurately, and with 1080 baits achieved very high levels of kill of possums and rats similar to those achieved by aerial 1080 baiting. Cholecalciferol was less effective in the first trial, but by doubling the amount of cholecalciferol bait used in the second trial, few possums or rats survived. By measuring the time taken to complete ground baiting from GPS tracks, we predicted that the method (using 1080 baits) would be similarly cost effective to aerial 1080 operations for controlling possums and rats, and considerably less expensive than typical current costs of ground based control. The main limitations to the use of the method will be access to, and size of, the operational site

  1. Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and Acceptable Poisoning of Invasive Small Mammalian Pests.

    PubMed

    Morgan, David; Warburton, Bruce; Nugent, Graham

    2015-01-01

    Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus spp.) are major vertebrate pests in New Zealand, with impacts on conservation and agriculture being managed largely through poisoning operations. Aerial distribution of baits containing sodium fluoroacetate (1080) has been refined to maximise cost effectiveness and minimise environmental impact, but this method is strongly opposed by some as it is perceived as being indiscriminate. Although ground based control enables precise placement of baits, operations are often more than twice as costly as aerial control, mainly due to the high labour costs. We investigated a new approach to ground based control that combined aerial distribution of non-toxic 'prefeed' baits followed by sparse distribution of toxic baits at regular intervals along the GPS tracked prefeeding flight paths. This approach was tested in two field trials in which both 1080 baits and cholecalciferol baits were used in separate areas. Effectiveness of the approach, assessed primarily using 'chewcards', was compared with that of scheduled aerial 1080 operations that were conducted in outlying areas of both trials. Contractors carrying out ground based control were able to follow the GPS tracks of aerial prefeeding flight lines very accurately, and with 1080 baits achieved very high levels of kill of possums and rats similar to those achieved by aerial 1080 baiting. Cholecalciferol was less effective in the first trial, but by doubling the amount of cholecalciferol bait used in the second trial, few possums or rats survived. By measuring the time taken to complete ground baiting from GPS tracks, we predicted that the method (using 1080 baits) would be similarly cost effective to aerial 1080 operations for controlling possums and rats, and considerably less expensive than typical current costs of ground based control. The main limitations to the use of the method will be access to, and size of, the operational site, along with

  2. Comparative profiles of BRAF inhibitors: the paradox index as a predictor of clinical toxicity

    PubMed Central

    Adelmann, Charles H.; Ching, Grace; Du, Lili; Saporito, Rachael C.; Bansal, Varun; Pence, Lindy J.; Liang, Roger; Lee, Woojin; Tsai, Kenneth Y.

    2016-01-01

    BRAF inhibitor (BRAFi) therapy is associated with the induction of neoplasia, most commonly cutaneous squamous cell carcinoma (cuSCC). This toxicity is explained in part by “paradoxical ERK activation,” or the hyperactivation of ERK signaling by BRAFi in BRAF wild-type cells. However, the rate of cuSCC induction varies widely among BRAFi. To explore this mechanistically, we profiled paradoxical ERK activation by vemurafenib, dabrafenib, encorafenib (LGX818), and PLX8394, demonstrating that vemurafenib induces ERK activation the greatest, while dabrafenib and encorafenib have higher “paradox indices”, defined as the pERK activation EC80 divided by the IC80 against A375, corresponding to wider therapeutic windows for achieving tumor inhibition without paradoxical ERK activation. Our results identify differences in the paradox indices of these compounds as a potential mechanism for the differences in cuSCC induction rates and highlight the utility of using ERK activity as a biomarker for maximizing the clinical utility of BRAFi. PMID:27028853

  3. A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats

    PubMed Central

    Rodríguez, Sarai; Raurell, Imma; Torres-Arauz, Manuel; García-Lezana, Teresa; Genescà, Joan; Martell, María

    2017-01-01

    Statins present many beneficial effects in chronic liver disease, but concerns about safety exist. We evaluated the hepatic effects of a nitric oxide-releasing atorvastatin (NCX 6560) compared to conventional statins. Simvastatin, atorvastatin and NCX 6560 were evaluated in four-week bile duct-ligated rats (BDL) simulating decompensated cirrhosis and in thirteen-week carbon tetrachloride (CCl4) intoxicated rats, a model of early cirrhosis. In the BDL model, simvastatin treated rats showed high mortality and the remaining animals presented muscular and hepatic toxicity. At equivalent doses, NCX 6560 eliminated hepatic toxicity and reduced muscular toxicity (60–74%) caused by atorvastatin in the more advanced BDL model; toxicity was minimal in the CCl4 model. Atorvastatin and NCX 6560 similarly reduced portal pressure without changing systemic hemodynamics in both models. Atorvastatin and NCX 6560 caused a mild decrease in liver fibrosis and inflammation and a significant increase in intrahepatic cyclic guanosine monophosphate. NCX 6560 induced a higher intrahepatic vasoprotective profile (activated endothelial nitric oxide synthase and decreased platelet/endothelial cell adhesion molecule-1), especially in the CCl4 model, suggesting a higher benefit in early cirrhosis. In conclusion, NCX 6560 improves the liver profile and portal hypertension of cirrhotic rats similarly to conventional statins, but with a much better safety profile. PMID:28084470

  4. The Antagonistic Effect of Selenium on Lead Toxicity Is Related to the Ion Profile in Chicken Liver.

    PubMed

    Xu, Tong; Gao, Xuejiao; Liu, Guowen

    2016-02-01

    The interactions between the essential element selenium (Se) and the toxic element lead (Pb) have been reported extensively; however, limited data are available regarding the effects of Se on Pb and the ion profile in chicken liver. Whether the change in the ion profile was involved in the protective process of Se and the toxic effect of Pb is unknown. In the present study, we detected 26 ion profiles (including those of Na, Mg, K, Ca, B, Si, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, Sb, Ba, Tl, Li, Al, As, Cd, Sn, Hg, and Pb) in chicken liver following treatment with Se or Pb and with the compound treatment of Se and Pb. The results showed that Se supplementation decreased the content of B and Cr and increased that of Zn and Ba (P < 0.05); however, Pb exposure decreased Cr, Mn, Cu, Se, Mo, and Hg and increased V, Fe, Cd, and Sn (P < 0.05). The results showed that Se and Pb primarily influenced essential microelements and toxic microelements in the chicken liver. In this process, Se alleviated the increased Cd and Pb induced by Pb exposure but aggravated the decreased Cu and Mn. The results also indicated that there existed both synergistic and antagonistic interactions between different ions, further verifying the principal component analysis. Thus, the results showed that prolonged exposure to Se and Pb influences the ion profiles in chicken liver. The protective role of Se and toxic effect of Pb may be related to these changing ion profiles in chicken liver.

  5. Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex-pulicaria from whole-animal metabolic profiles.

    PubMed

    Taylor, Nadine S; Kirwan, Jennifer A; Johnson, Craig; Yan, Norman D; Viant, Mark R; Gunn, John M; McGeer, James C

    2016-05-01

    The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal-stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management.

  6. Offer/Acceptance Ratio.

    ERIC Educational Resources Information Center

    Collins, Mimi

    1997-01-01

    Explores how human resource professionals, with above average offer/acceptance ratios, streamline their recruitment efforts. Profiles company strategies with internships, internal promotion, cooperative education programs, and how to get candidates to accept offers. Also discusses how to use the offer/acceptance ratio as a measure of program…

  7. Strategies for integrating transcriptional profiling into high throughput toxicity testing (SOT Symposium Workshop presentation)

    EPA Science Inventory

    Presentation Description: The release of the National Research Council’s Report “Toxicity Testing in the 21st Century: A Vision and a Strategy” in 2007 initiated a broad-based movement in the toxicology community to re-think how toxicity testing and risk assessment are performed....

  8. Gene expression profile changes induced by acute toxicity of [C16 mim]Cl in loach (Paramisgurnus dabryanus).

    PubMed

    Nan, Ping; Yan, Shuaiguo; Wang, Yaxing; Du, Qiyan; Chang, Zhongjie

    2017-02-01

    Ionic liquids (ILs) are widely used as reaction media in various commercial applications. Many reports have indicated that most ILs are poorly decomposed by microorganisms and are toxic to aquatic organisms. In this study, differential gene expression profiling was conducted using a suppression subtraction hybridization cDNA library from hepatic tissue of the loach (Paramisgurnus dabryanus) after exposure to 1-hexadecyl-3-methylimidazolium chloride ([C16 mim]Cl), a representative IL. Two hundred and fifty-nine differentially expressed candidate genes, whose expression was altered by >2.0-fold by the [C16 mim]Cl treatment, were identified, including 127 upregulated genes and 132 downregulated genes. A gene ontology analysis of the known genes isolated in this study showed that [C16 mim]Cl-responsive genes were involved in cell cycle, stimulus response, defense response, DNA damage response, oxidative stress responses, and other biological responses. To identify candidate genes that may be involved in [C16 mim]Cl-induced toxicity, 259 clones were examined by Southern blot macroarray hybridization, and 20 genes were further characterized using quantitative real-time polymerase chain reaction. Finally, six candidate genes were selected, including three DNA damage response genes, two toxic substance metabolic genes, and one stress protein gene. Our results indicate that these changes in gene expression are associated with [C16 mim]Cl-induced toxicity, and that these six candidate genes can be promising biomarkers for detecting [C16 mim]Cl-induced toxicity. Therefore, this study demonstrates the use of a powerful assay to identify genes potentially involved in [C16 mim]Cl toxicity, and it provides a foundation for the further study of related genes and the molecular mechanism of [C16 mim]Cl toxicity. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 404-416, 2017.

  9. The affective profiles, psychological well-being, and harmony: environmental mastery and self-acceptance predict the sense of a harmonious life.

    PubMed

    Garcia, Danilo; Al Nima, Ali; Kjell, Oscar N E

    2014-01-01

    Background. An important outcome from the debate on whether wellness equals happiness, is the need of research focusing on how psychological well-being might influence humans' ability to adapt to the changing environment and live in harmony. To get a detailed picture of the influence of positive and negative affect, the current study employed the affective profiles model in which individuals are categorised into groups based on either high positive and low negative affect (self-fulfilling); high positive and high negative affect (high affective); low positive and low negative affect (low affective); and high negative and low positive affect (self-destructive). The aims were to (1) investigate differences between affective profiles in psychological well-being and harmony and (2) how psychological well-being and its dimensions relate to harmony within the four affective profiles. Method. 500 participants (mean age = 34.14 years, SD. = ±12.75 years; 187 males and 313 females) were recruited online and required to answer three self-report measures: The Positive Affect and Negative Affect Schedule; The Scales of Psychological Well-Being (short version) and The Harmony in Life Scale. We conducted a Multivariate Analysis of Variance where the affective profiles and gender were the independent factors and psychological well-being composite score, its six dimensions as well as the harmony in life score were the dependent factors. In addition, we conducted four multi-group (i.e., the four affective profiles) moderation analyses with the psychological well-being dimensions as predictors and harmony in life as the dependent variables. Results. Individuals categorised as self-fulfilling, as compared to the other profiles, tended to score higher on the psychological well-being dimensions: positive relations, environmental mastery, self-acceptance, autonomy, personal growth, and purpose in life. In addition, 47% to 66% of the variance of the harmony in life was explained by the

  10. The affective profiles, psychological well-being, and harmony: environmental mastery and self-acceptance predict the sense of a harmonious life

    PubMed Central

    Al Nima, Ali; Kjell, Oscar N.E.

    2014-01-01

    Background. An important outcome from the debate on whether wellness equals happiness, is the need of research focusing on how psychological well-being might influence humans’ ability to adapt to the changing environment and live in harmony. To get a detailed picture of the influence of positive and negative affect, the current study employed the affective profiles model in which individuals are categorised into groups based on either high positive and low negative affect (self-fulfilling); high positive and high negative affect (high affective); low positive and low negative affect (low affective); and high negative and low positive affect (self-destructive). The aims were to (1) investigate differences between affective profiles in psychological well-being and harmony and (2) how psychological well-being and its dimensions relate to harmony within the four affective profiles. Method. 500 participants (mean age = 34.14 years, SD. = ±12.75 years; 187 males and 313 females) were recruited online and required to answer three self-report measures: The Positive Affect and Negative Affect Schedule; The Scales of Psychological Well-Being (short version) and The Harmony in Life Scale. We conducted a Multivariate Analysis of Variance where the affective profiles and gender were the independent factors and psychological well-being composite score, its six dimensions as well as the harmony in life score were the dependent factors. In addition, we conducted four multi-group (i.e., the four affective profiles) moderation analyses with the psychological well-being dimensions as predictors and harmony in life as the dependent variables. Results. Individuals categorised as self-fulfilling, as compared to the other profiles, tended to score higher on the psychological well-being dimensions: positive relations, environmental mastery, self-acceptance, autonomy, personal growth, and purpose in life. In addition, 47% to 66% of the variance of the harmony in life was explained by

  11. Effect of Vitamin D3 Fortification and Saskatoon Berry Syrup Addition on the Flavor Profile, Acceptability, and Antioxidant Properties of Rooibos Tea (Aspalathus linearis).

    PubMed

    Grant, Jennifer; Ryland, Donna; Isaak, Cara K; Prashar, Suvira; Siow, Yaw L; Taylor, Carla G; Aliani, Michel

    2017-03-01

    The unique characteristics and healthful reputation of caffeine-free rooibos tea (RT) make it an ideal carrier for vitamin D3 supplementation, and a potential base for the addition of Saskatoon berry syrup (SBS), a natural flavor additive. The objective of this study was to determine the effect of vitamin D3 fortification and SBS addition on the flavor profile, consumer acceptability, and antioxidant properties of RT. Six formulations (RT, RT with SBS, RT with SBS and vitamin D3 , RT with vitamin D3 , green tea [GT], and GT with SBS) were evaluated by 12 trained panelists and 114 consumers. The formulations were also assessed for antioxidant capacity, physical characteristics, and untargeted phytochemical content. Sensory results revealed that the mean intensity values for berry and sweet attributes were significantly higher (P < 0.05) while bitter and astringent attributes were significantly lower when SBS was added to RT samples compared to those without syrup. Acceptability of flavor, aftertaste, and overall acceptability were also significantly higher for the RT with SBS. The addition of SBS to RT significantly increased the antioxidant capacities which may increase the related health benefits of RT. SBS contributed several polyphenols, particularly flavonoids, to the tea. Vitamin D3 added to RT formulations did not significantly affect the sensory attributes, acceptability, or antioxidant content. For the development of a functional vitamin D3 fortified iced-tea beverage that can be consumed as part of the daily diet, SBS could be a favorable flavoring additive that may provide additional health benefits.

  12. "Would you accept having your DNA profile inserted in the National Forensic DNA database? Why?" Results of a questionnaire applied in Portugal.

    PubMed

    Machado, Helena; Silva, Susana

    2014-01-01

    The creation and expansion of forensic DNA databases might involve potential threats to the protection of a range of human rights. At the same time, such databases have social benefits. Based on data collected through an online questionnaire applied to 628 individuals in Portugal, this paper aims to analyze the citizens' willingness to donate voluntarily a sample for profiling and inclusion in the National Forensic DNA Database and the views underpinning such a decision. Nearly one-quarter of the respondents would indicate 'no', and this negative response increased significantly with age and education. The overriding willingness to accept the inclusion of the individual genetic profile indicates an acknowledgement of the investigative potential of forensic DNA technologies and a relegation of civil liberties and human rights to the background, owing to the perceived benefits of protecting both society and the individual from crime. This rationale is mostly expressed by the idea that all citizens should contribute to the expansion of the National Forensic DNA Database for reasons that range from the more abstract assumption that donating a sample for profiling would be helpful in fighting crime to the more concrete suggestion that everyone (criminals and non-criminals) should be in the database. The concerns with the risks of accepting the donation of a sample for genetic profiling and inclusion in the National Forensic DNA Database are mostly related to lack of control and insufficient or unclear regulations concerning safeguarding individuals' data and supervising the access and uses of genetic data. By providing an empirically-grounded understanding of the attitudes regarding willingness to donate voluntary a sample for profiling and inclusion in a National Forensic DNA Database, this study also considers the citizens' perceived benefits and risks of operating forensic DNA databases. These collective views might be useful for the formation of international common

  13. Application of ultraperformance liquid chromatography/mass spectrometry-based metabonomic techniques to analyze the joint toxic action of long-term low-level exposure to a mixture of organophosphate pesticides on rat urine profile.

    PubMed

    Du, Longfei; Wang, Hong; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhang, Yuqiu; Zhao, Xiujuan; Sun, Changhao

    2013-07-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL). Results show that a single pesticide elicits no toxic response. This study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology. Pesticides were administered daily to rats through drinking water for 24 weeks. The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide. The metabonomic profiles of rats urine were analyzed by ultraperformance liquid chromatography/mass spectrometry. The 16 metabolites statistically significantly changed in all treated groups compared with the control group. Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides. Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine, and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid, and citric acid. The results indicated that a mixture of OP pesticides induced DNA damage and oxidative stress, disturbed the metabolism of lipids, and interfered with the tricarboxylic acid cycle. Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake but also the joint toxic action.

  14. Substituent Effects on Desferrithiocin and Desferrithiocin Analogue Iron Clearing and Toxicity Profiles

    PubMed Central

    Bergeron, Raymond J.; Wiegand, Jan; Bharti, Neelam; McManis, James S.

    2012-01-01

    Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to determine if a comparable reduction in renal toxicity could be achieved by performing the same structural manipulations on 1 itself. Accordingly, three DFT analogues were synthesized. Iron clearing efficiency and ferrokinetics were evaluated in rats and primates; toxicity assessments were carried out in rodents. The resulting DFT ligands demonstrated a reduction in toxicity that was equivalent to that of the DADFT analogues and presented with excellent iron clearing properties. PMID:22889170

  15. Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol.

    PubMed

    Cordeiro, Rui Martins; Stirling, Soren; Fahy, Gregory M; de Magalhães, João Pedro

    2015-12-01

    Cryopreservation consists of preserving living cells or tissues generally at -80 °C or below and has many current applications in cell and tissue banking, and future potential for organ banking. Cryoprotective agents such as ethylene glycol (EG) are required for successful cryopreservation of most living systems, but have toxic side effects whose mechanisms remain largely unknown. In this work, we investigated the mechanisms of toxicity of ethylene glycol in human umbilical vein endothelial cells (HUVECs) as a model of the vascular endothelium in perfused organs. Exposing cells to 60% v/v EG for 2 h at 4 °C resulted in only a slight decrease in subsequent cell growth, suggesting only modest toxicity of EG for this cell type. Gene expression analysis with whole genome microarrays revealed signatures indicative of a generalized stress response at 24 h after EG exposure and a trend toward partial recovery at 72 h. The observed changes involved signalling pathways, glycoproteins, and genes involved in extracellular and transmembrane functions, the latter suggesting potential effects of ethylene glycol on membranes. These results continue to develop a new paradigm for understanding cryoprotectant toxicity and reveal molecular signatures helpful for future experiments in more completely elucidating the toxic effects of ethylene glycol in vascular endothelial cells and other cell types.

  16. Toxicity and binding profile of lectins from the Genus canavalia on brine shrimp.

    PubMed

    Arruda, Francisco Vassiliepe Sousa; Melo, Arthur Alves; Vasconcelos, Mayron Alves; Carneiro, Romulo Farias; Barroso-Neto, Ito Liberato; Silva, Suzete Roberta; Pereira-Junior, Francisco Nascimento; Nagano, Celso Shiniti; Nascimento, Kyria Santiago; Teixeira, Edson Holanda; Saker-Sampaio, Silvana; Sousa Cavada, Benildo; Sampaio, Alexandre Holanda

    2013-01-01

    Lectins are sugar-binding proteins widely distributed in nature with many biological functions. Although many lectins have a remarkable biotechnological potential, some of them can be cytotoxic. Thus, the aim of this study was to assess the toxicity of five lectins, purified from seeds of different species of Canavalia genus. In order to determine the toxicity, assays with Artemia nauplii were performed. In addition, a fluorescence assay was carried out to evaluate the binding of lectins to Artemia nauplii. In order to verify the relationship between the structure of lectins and their cytotoxic effect, structural analysis was carried out to evaluate the volume of the carbohydrate recognition domain (CRD) of each lectin. The results showed that all lectins exhibited different toxicities and bound to a similar area in the digestive tract of Artemia nauplii. Concerning the structural analysis, differences in spatial arrangement and volume of CRD may explain the variation of the toxicity exhibited by each lectin. To this date, this is the first study that establishes a link between toxicity and structure of CRD from Diocleinae lectins.

  17. Predictive Signatures of Developmental Toxicity Modeled with HTS Data from ToxCast™ Bioactivity Profiles

    EPA Science Inventory

    The EPA ToxCast™ research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I contains 309 well-characterized chemicals which are mostly pesticides tested in over 600 assays of different molecular targets, cel...

  18. High Throughput Prioritization for Integrated Toxicity Testing Based on ToxCast Chemical Profiling

    EPA Science Inventory

    The rational prioritization of chemicals for integrated toxicity testing is a central goal of the U.S. EPA’s ToxCast™ program (http://epa.gov/ncct/toxcast/). ToxCast includes a wide-ranging battery of over 500 in vitro high-throughput screening assays which in Phase I was used to...

  19. Using in vitro Dose-Response Profiles to Enhance QSAR Modeling of in vivo Toxicity

    EPA Science Inventory

    To develop effective means for rapid toxicity evaluation of environmental chemicals, the Tox21 partnership among the National Toxicology Program (NTP), NIH Chemical Genomics Center, and National Center for Computational Toxicology (NCCT) at the US EPA are conducting a number of ...

  20. Speciation Profiles and Toxic Emission Factors for Nonroad Engines: DRAFT REPORT

    EPA Science Inventory

    This document details the research and development behind how MOVES2014a estimates air toxic emissions for nonroad engines and equipment run on conventional gasoline without ethanol (E0) and gasoline blended with 10% ethanol (E10) as well as diesel fuel, compressed natural gas (C...

  1. Toxicity Profile of IMRT Vs. 3D-CRT in Head and Neck Cancer: A Retrospective Study

    PubMed Central

    Tallari, Ramanjis; Malviya, Anupam

    2016-01-01

    Introduction Role of radiotherapy in comprehensive management of head and neck cancer for achieving tumour control and organ preservation is now well established and radiotherapy is routinely used in adjuvant setting after surgery, concurrently with chemotherapy or targeted agents and for palliation. Development of linear accelerator with Multileaf Collimator (MLC) have revolutionized radiation delivery techniques, allowing conformal and Intensity Modulated Radiotherapy (IMRT) to deliver highly conformal sculpted radiation dose to a very complex structure with improved sparing of adjoining critical structures like salivary glands, spinal cord, eyes, brainstem and larynx amounting to better therapeutic gain. Aim This retrospective study was to compare toxicity profile of IMRT with Three Dimensional Conformal Radiotherapy (3D CRT) in head and neck cancer. Materials and Methods Total of 80 patients from January 2013 to July 2015 with proven head and neck cancer who underwent radiotherapy on linac 2300 C/D machine were included in the study, IMRT group and 3D-CRT group comprised of 40 patients each. We have searched patient’s radiotherapy details in record section of our institute and observations were noted down. Patients received 70Gy/35 fractions, Monday to Friday as radical treatment and 60 Gy/30 fractions as adjuvant treatment were included. Results The 3D-CRT group demonstrated significantly more acute toxic effects compared with the IMRT group in our analysis. Acute Grade 3 or greater toxic effects to the skin occurred in 5 of 40 (12.5%), patients in the 3D-CRT group compared with 3 of 40 (7.5%) patients in the IMRT group. Acute Grade 3 or greater toxic effects to the mucous membranes occurred in 23 of 40 (57.5%) patients in the 3D-CRT group and only 16 of 40 (40%) patients in the IMRT group. Statistically significant dysphagia developed in 34 of 40 (85%), patients in 3D-CRT group compared with 23 of 40 (57.5%) patients in IMRT group, while statistically

  2. Plasma Lipid Profiling of Patients with Chronic Ocular Complications Caused by Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

    PubMed Central

    Maekawa, Keiko; Sotozono, Chie; Kinoshita, Shigeru; Saito, Yoshiro

    2016-01-01

    Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs. PMID:27898730

  3. Gene expression profiling to characterize sediment toxicity – a pilot study using Caenorhabditis elegans whole genome microarrays

    PubMed Central

    Menzel, Ralph; Swain, Suresh C; Hoess, Sebastian; Claus, Evelyn; Menzel, Stefanie; Steinberg, Christian EW; Reifferscheid, Georg; Stürzenbaum, Stephen R

    2009-01-01

    Background Traditionally, toxicity of river sediments is assessed using whole sediment tests with benthic organisms. The challenge, however, is the differentiation between multiple effects caused by complex contaminant mixtures and the unspecific toxicity endpoints such as survival, growth or reproduction. The use of gene expression profiling facilitates the identification of transcriptional changes at the molecular level that are specific to the bio-available fraction of pollutants. Results In this pilot study, we exposed the nematode Caenorhabditis elegans to three sediments of German rivers with varying (low, medium and high) levels of heavy metal and organic contamination. Beside chemical analysis, three standard bioassays were performed: reproduction of C. elegans, genotoxicity (Comet assay) and endocrine disruption (YES test). Gene expression was profiled using a whole genome DNA-microarray approach to identify overrepresented functional gene categories and derived cellular processes. Disaccharide and glycogen metabolism were found to be affected, whereas further functional pathways, such as oxidative phosphorylation, ribosome biogenesis, metabolism of xenobiotics, aging and several developmental processes were found to be differentially regulated only in response to the most contaminated sediment. Conclusion This study demonstrates how ecotoxicogenomics can identify transcriptional responses in complex mixture scenarios to distinguish different samples of river sediments. PMID:19366437

  4. Investigating the chemical profile of regenerated scorpion (Parabuthus transvaalicus) venom in relation to metabolic cost and toxicity.

    PubMed

    Nisani, Zia; Boskovic, Danilo S; Dunbar, Stephen G; Kelln, Wayne; Hayes, William K

    2012-09-01

    We investigated the biochemical profile of regenerated venom of the scorpion Parabuthus transvaalicus in relation to its metabolic cost and toxicity. Using a closed-system respirometer, we compared oxygen consumption between milked and unmilked scorpions to determine the metabolic costs associated with the first 192 h of subsequent venom synthesis. Milked scorpions had a substantially (21%) higher mean metabolic rate than unmilked scorpions, with the largest increases in oxygen consumption occurring at approximately 120 h, 162 h, and 186 h post-milking. Lethality tests in crickets indicated that toxicity of the regenerated venom returned to normal levels within 4 d after milking. However, the chemical profile of the regenerated venom, as evaluated by FPLC and MALDI-TOF mass spectrometry, suggested that regeneration of different venom components was asynchronous. Some peptides regenerated quickly, particularly those associated with the scorpion's "prevenom," whereas others required much or all of this time period for regeneration. This asynchrony could explain the different spikes detected in oxygen consumption of milked scorpions as various peptides and other venom components were resynthesized. These observations confirm the relatively high metabolic cost of venom regeneration and suggest that greater venom complexity can be associated with higher costs of venom production.

  5. Gene expression profiling of candidate genes in peripheral blood mononuclear cells for predicting toxicity of diesel exhaust particles.

    PubMed

    Srivastava, Ankita; Sharma, Amit; Yadav, Sanjay; Flora, Swaran J S; Dwivedi, Uppendra N; Parmar, Devendra

    2014-02-01

    To validate gene expression profiling of peripheral blood mononuclear cells (PBMCs) as a surrogate for monitoring tissue expression, this study using RT-PCR-based TaqMan low-density array (TLDA) was initiated to investigate similarities in the mRNA expression of target genes altered by exposure to diesel exhaust particles (DEPs) in freshly prepared PBMCs and in lungs. Adult Wistar rats were treated transtracheally with a single dose of 7.5 or 15 or 30mg/kg DEPs and sacrificed 24h later. Blood and lungs were immediately taken out and processed for RT-PCR. DEP treatment induced similar patterns of increase in the expression of polycyclic aromatic hydrocarbon-responsive cytochrome P450s, the phase II enzymes, and their associated transcription factors in both lungs and PBMCs, at all doses. Similar to that seen in lungs, a dose-dependent increase was observed in the expression of genes involved in inflammation, such as cytokines, chemokines, and adhesion molecules, in PBMCs. The expression of various genes involved in DNA repair and apoptosis was also increased in a dose-dependent manner in PBMCs and lungs. The present TLDA data indicating similarities in the responsiveness of candidate genes involved in the toxicity of DEPs between PBMCs and lungs after exposure to DEPs demonstrate that expression profiles of genes in PBMCs could be used as a surrogate for monitoring the acute toxicity of fine and ultrafine particulate matter present in vehicular emissions.

  6. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

    NASA Astrophysics Data System (ADS)

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals.

  7. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

    PubMed Central

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals. PMID:26786678

  8. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

    EPA Science Inventory

    Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

  9. Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the Spanish toxic oil syndrome.

    PubMed Central

    Ladona, M G; Izquierdo-Martinez, M; Posada de la Paz, M P; de la Torre, R; Ampurdanés, C; Segura, J; Sanz, E J

    2001-01-01

    In 1981, the Spanish toxic oil syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the toxicant(s) leading to a low detoxification or accumulation of toxic metabolites contributing to the disease. We conducted a matched case-control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compared with the unrelated controls (70 pairs) showed an increase in NAT2 defective alleles [OR = 6.96, 95% confidence interval (CI), 1.46-33.20] adjusted by age and sex. Glutathione transferase genetic polymorphisms (GSTM1, GSTT1) showed no association with cases compared with their siblings or unrelated controls. These findings suggest a possible role of impaired acetylation mediating susceptibility in TOS. PMID:11335185

  10. Functional Toxicogenomic Profiling Expands Insight into Modulators of Formaldehyde Toxicity in Yeast

    PubMed Central

    North, Matthew; Gaytán, Brandon D.; Romero, Carlos; De La Rosa, Vanessa Y.; Loguinov, Alex; Smith, Martyn T.; Zhang, Luoping; Vulpe, Chris D.

    2016-01-01

    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. PMID:27909446

  11. Occurrence, profiles, and toxic equivalents of chlorinated and brominated polycyclic aromatic hydrocarbons in E-waste open burning soils.

    PubMed

    Nishimura, Chiya; Horii, Yuichi; Tanaka, Shuhei; Asante, Kwadwo Ansong; Ballesteros, Florencio; Viet, Pham Hung; Itai, Takaaki; Takigami, Hidetaka; Tanabe, Shinsuke; Fujimori, Takashi

    2017-03-23

    We conducted this study to assess the occurrence, profiles, and toxicity of chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) and brominated polycyclic aromatic hydrocarbons (Br-PAHs) in e-waste open burning soils (EOBS). In this study, concentrations of 15 PAHs, 26 Cl-PAHs and 14 Br-PAHs were analyzed in EOBS samples. We found that e-waste open burning is an important emission source of Cl-PAHs and Br-PAHs as well as PAHs. Concentrations of total Cl-PAHs and Br-PAHs in e-waste open burning soil samples ranged from 21 to 2800 ng/g and from 5.8 to 520 ng/g, respectively. Compared with previous studies, the mean of total Cl-PAH concentrations of the EOBS samples in this study was higher than that of electronic shredder waste, that of bottom ash, and comparable to fly ash from waste incinerators in Korea and Japan. The mean of total Br-PAH concentrations of the EOBS samples was generally three to four orders of magnitude higher than those in incinerator bottom ash and comparable to incinerator fly ash, although the number of Br-PAH congeners measured differed among studies. We also found that the Cl-PAH and Br-PAH profiles were similar among all e-waste open burning soil samples but differed from those in waste incinerator fly ash. The profiles and principal component analysis results suggested a unique mechanism of Cl-PAH and Br-PAH formation in EOBS. In addition, the Cl-PAHs and Br-PAHs showed high toxicities equivalent to PCDD/Fs measured in same EOBS samples when calculated based on their relative potencies to benzo[a]pyrene. Along with chlorinated and brominated dioxins and PAHs, Cl-PAHs and Br-PAHs are important environmental pollutants to investigate in EOBS.

  12. A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma

    PubMed Central

    Pillai, Pradeep Sadasivan; Jayakumar, Krishnan Nair Lalithamma

    2015-01-01

    Introduction A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. Aim To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. Materials and Methods A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. Statistical Analysis Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. Results Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. Conclusion FAC and AT regimens are equally efficacious but have different

  13. Towards Profiles of Resistance Development and Toxicity for the Small Cationic Hexapeptide RWRWRW-NH2

    PubMed Central

    Wenzel, Michaela; Prochnow, Pascal; Mowbray, Catherine; Vuong, Cuong; Höxtermann, Stefan; Stepanek, Jennifer J.; Albada, H. Bauke; Hall, Judith; Metzler-Nolte, Nils; Bandow, Julia E.

    2016-01-01

    RWRWRW-NH2 (MP196) is an amphipathic hexapeptide that targets the bacterial cytoplasmic membrane and inhibits cellular respiration and cell wall synthesis. In previous studies it showed promising activity against Gram-positive bacteria and no significant cytotoxicity or hemolysis. MP196 is therefore used as lead structure for developing more potent antibiotic derivatives. Here we present a more comprehensive study on the parent peptide MP196 with regard to clinically relevant parameters. We found that MP196 acts rapidly bactericidal killing 97% of initial CFU within 10 min at two times MIC. We were unable to detect resistance in standard 24 and 48 h resistance frequency assays. However, MP196 was effective against some but not all MRSA and VISA strains. Serum binding of MP196 was intermediate and we confirmed its low toxicity against mammalian cell lines. MP196 did neither induce NFκB activation nor cause an increase in IL8 levels at 250 μg/mL, and no IgE-dependent activation of basophil granulocytes was detected at 500 μg/mL. Yet, MP196 demonstrated acute toxicity in mice upon injection into the blood stream. Phase contrast microscopy of mouse blood treated with MP196 revealed a shrinking of erythrocytes at 250 μg/mL and severe morphological changes and lysis of erythrocytes at 500 μg/mL. These data suggest that MP196 derivatization directed at further lowering hemolysis could be instrumental in overcoming acute toxicity. The assessment of hemolysis is a critical step in the evaluation of the clinical potential of promising antimicrobial peptides and should be accompanied by microscopy-based morphological analysis of blood cells. PMID:27617260

  14. Longitudinal stability of social competence indicators in a Portuguese sample: Q-sort profiles of social competence, measures of social engagement, and peer sociometric acceptance.

    PubMed

    Santos, António J; Vaughn, Brian E; Peceguina, Inês; Daniel, João R

    2014-03-01

    This study examines the temporal stability (over 3 years) of individual differences in 3 domains relevant to preschool children's social competence: social engagement/motivation, profiles of behavior and personality attributes characteristic of socially competent young children, and peer acceptance. Each domain was measured with multiple indicators. Sociometric status categories (Asher & Dodge, 1986) and reciprocated friendships were derived from sociometric data. Composites for social competence domains were significantly associated across all time points. Within age-periods, social competence domains were associated with both sociometric and friendship status categories; however, neither sociometric status nor reciprocated friendships were stable over time. Nevertheless, analyses examining the social competence antecedents to reciprocated friendship at age-4 and age-5 suggested that more socially competent children in the prior year were more likely to have a reciprocated friendship in the current year. Popular and rejected sociometric status categories were also associated with social competence indicators in prior years, but this was most clearly seen at age-5.

  15. Potentially-toxic and essential elements profile of AH1N1 patients in Mexico City

    PubMed Central

    Moya, Mireya; Bautista, Edgar G.; Velázquez-González, Antonio; Vázquez-Gutiérrez, Felipe; Tzintzun, Guadalupe; García-Arreola, María Elena; Castillejos, Manuel; Hernández, Andrés

    2013-01-01

    During spring of 2009, a new influenza virus AH1N1 spread in the world causing acute respiratory illness and death, resulting in the first influenza pandemic since 1968. Blood levels of potentially-toxic and essential elements of 40 pneumonia and confirmed AH1N1 were evaluated against two different groups of controls, both not infected with the pandemic strain. Significant concentrations of potentially-toxic elements (lead, mercury, cadmium, chromium, arsenic) along with deficiency of selenium or increased Zn/Cu ratios characterized AH1N1 cases under study when evaluated versus controlled cases. Deficiency of selenium is progressively observed from controls I (influenza like illness) through controls II (pneumonia) and finally pneumonia -AH1N1 infected patients. Cases with blood Se levels greater than the recommended for an optimal cut-off to activate glutathione peroxidase (12.5 μg/dL) recovered from illness and survived. Evaluation of this essential element in critical pneumonia patients at the National Institutes is under evaluation as a clinical trial. PMID:23422930

  16. Peer consultation on relationship between PAC profile and toxicity of petroleum substances.

    PubMed

    Patterson, Jacqueline; Maier, Andrew; Kohrman-Vincent, Melissa; Dourson, Michael L

    2013-11-01

    An expert peer consultation panel reviewed a report by the PAC Analysis Task Group, which hypothesized that systemic, developmental, and reproductive toxicity observed in repeated-dose dermal toxicity studies was related to polycyclic aromatic compound (PAC) content. Peer consultations seek to solicit scientific and technical input from experts on the scientific basis and merits of the subject report. This peer consultation panel included nine scientists with expertise in petroleum chemistry, biostatistics, toxicology, risk assessment, structure activity, and reproductive and developmental toxicology. The panel evaluated the technical quality of the PAC report and provided recommendations for improving the statistical and biological approaches. The PAC report authors revised their methods and documentation, which are published elsewhere in this supplement. A review of the post peer consultation manuscripts confirmed that many of the key suggestions from expert panel members were considered and incorporated. In cases where the PAC report authors did not fully incorporate panel suggestions from the peer consultation, they have provided an explanation and support for their decision. This peer consultation demonstrates the value of formal engagement of peers in development of new scientific methods and approaches.

  17. Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Wolf, Douglas C; Allen, James W; George, Michael H; Hester, Susan D; Sun, Guobin; Moore, Tanya; Thai, Sheau-Fung; Delker, Don; Winkfield, Ernest; Leavitt, Sharon; Nelson, Gail; Roop, Barbara C; Jones, Carlton; Thibodeaux, Julie; Nesnow, Stephen

    2006-01-01

    Conazoles are a class of azole based fungicides used in agriculture and as pharmaceutical products. They have a common mode of antifungal action through inhibition of ergosterol biosynthesis. Some members of this class have been shown to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. The particular mode of toxic and tumorigenic action for these compounds is not known, however it has been proposed that triadimefon-induced rat thyroid tumors arise through the specific mechanism of increased TSH. The present study was designed to identify commonalities of effects across the different conazoles and to determine unique features of the tissue responses that suggest a toxicity pathway and a mode of action for the observed thyroid response for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500, 1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000 ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs, body and liver weight, histopathology of thyroid and liver, hepatic metabolizing enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose-dependent increase in liver weight but not body weight for all treatments. The indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD) activity, had a dose-related increase at all time points for all conazoles. Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme measured as glucuronidation of 1-naphthol, was induced to the same extent after 30 and 90 days for all three conazoles. Livers from all high dose treated rats had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid follicular cell hypertrophy, increased follicular cell proliferation, and colloid depletion were

  18. An Unusual Case of Central Retinal Vein Occlusion and Review of the Toxicity Profile of Regorafenib in GIST Patients.

    PubMed

    Schvartsman, Gustavo; Wagner, Michael J; Zobniw, Chrystia M; Trinh, Van Anh; Patel, Shreyaskumar; Somaiah, Neeta

    2016-08-01

    Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract with around 5000 new cases per year. Outcomes for patients with GIST dramatically improved after the development of tyrosine kinase inhibitors targeted against the aberrant signaling pathways that drive GIST oncogenesis. Majority of patients derive benefit from first-line imatinib, and the type of driver mutation is predictive of response. However, almost half of the patients eventually develop resistance to initial targeted therapy and further lines of treatment do not have the same impact. Regorafenib is an oral multi-kinase inhibitor approved as a third-line therapy for advanced GIST and though its efficacy is limited in comparison to imatinib, it has activity across the various driver mutation categories in GIST even in the setting of imatinib resistance. Herein, we describe a case of central retinal vein occlusion (CRVO) secondary to regorafenib and review regorafenib's efficacy and toxicity profile.

  19. Transcriptome profiling of genes and pathways associated with arsenic toxicity and tolerance in Arabidopsis

    PubMed Central

    2014-01-01

    Background Arsenic (As) is a toxic metalloid found ubiquitously in the environment and widely considered an acute poison and carcinogen. However, the molecular mechanisms of the plant response to As and ensuing tolerance have not been extensively characterized. Here, we report on transcriptional changes with As treatment in two Arabidopsis accessions, Col-0 and Ws-2. Results The root elongation rate was greater for Col-0 than Ws-2 with As exposure. Accumulation of As was lower in the more tolerant accession Col-0 than in Ws-2. We compared the effect of As exposure on genome-wide gene expression in the two accessions by comparative microarray assay. The genes related to heat response and oxidative stresses were common to both accessions, which indicates conserved As stress-associated responses for the two accessions. Most of the specific response genes encoded heat shock proteins, heat shock factors, ubiquitin and aquaporin transporters. Genes coding for ethylene-signalling components were enriched in As-tolerant Col-0 with As exposure. A tolerance-associated gene candidate encoding Leucine-Rich Repeat receptor-like kinase VIII (LRR-RLK VIII) was selected for functional characterization. Genetic loss-of-function analysis of the LRR-RLK VIII gene revealed altered As sensitivity and the metal accumulation in roots. Conclusions Thus, ethylene-related pathways, maintenance of protein structure and LRR-RLK VIII-mediated signalling may be important mechanisms for toxicity and tolerance to As in the species. Here, we provide a comprehensive survey of global transcriptional regulation for As and identify stress- and tolerance-associated genes responding to As. PMID:24734953

  20. The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

    PubMed Central

    Liang, Jinyan; Dai, Xiaomeng; Wan, Chao; Hong, Xiaohua; Zhang, Kai; Liu, Li

    2017-01-01

    Purpose The current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC). Method Electronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model. Results This meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4–41.5) and 55.6% (95% CI 49.2–61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3–64.9), 70.3% (95% CI 62.6–76.9), and 40.0% (95% CI 30.6–50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1–39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070). Conclusions Metronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence. PMID:28296916

  1. Toxicity profile of ethanolic extract of Azadirachta indica stem bark in male Wistar rats

    PubMed Central

    Ashafa, Anofi Omotayo Tom; Orekoya, Latifat Olubukola; Yakubu, Musa Toyin

    2012-01-01

    Objective To investigate the toxic implications of ethanolic stem bark extract of Azadirachta indica (A. indica) at 50, 100, 200 and 300 mg/kg body weight in Wistar rats. Methods Fifty male rats of Wistar strains were randomly grouped into five (A-E) of ten animals each. Animals in Group A (control) were orally administered 1 mL of distilled water on daily basis for 21 days while those in Groups B-E received same volume of the extract corresponding to 50, 100, 200 and 300 mg/kg body weight. Results The extract did not significantly (P>0.05) alter the levels of albumin, total protein, red blood cells and factors relating to it whereas the white blood cell, platelets, serum triacylglycerol and high-density lipoprotein cholesterol decreased significantly (P<0.05). In contrast, the final body weights, absolute weights of the liver, kidney, lungs and heart as well as their organ-body weight ratios, serum globulins, total and conjugated bilirubin, serum cholesterol, low-density lipoprotein cholesterol and computed atherogenic index increased significantly. The spleen-body weight ratio, alkaline phosphatase, alanine and aspartate transaminases, sodium, potassium, calcium, feed and water intake were altered at specific doses. Conclusions Overall, the alterations in the biochemical parameters of toxicity have consequential effects on the normal functioning of the organs of the animals. Therefore, the ethanolic extract of A. indica stem bark at the doses of 50, 100, 200 and 300 mg/kg body weight may not be completely safe as an oral remedy and should be taken with caution if absolutely necessary. PMID:23569852

  2. Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

    PubMed

    Vliegenthart, A D B; Shaffer, J M; Clarke, J I; Peeters, L E J; Caporali, A; Bateman, D N; Wood, D M; Dargan, P I; Craig, D G; Moore, J K; Thompson, A I; Henderson, N C; Webb, D J; Sharkey, J; Antoine, D J; Park, B K; Bailey, M A; Lader, E; Simpson, K J; Dear, J W

    2015-10-22

    Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.

  3. Use of Zebrafish Larvae as a Multi-Endpoint Platform to Characterize the Toxicity Profile of Silica Nanoparticles

    PubMed Central

    Pham, Duc-Hung; De Roo, Bert; Nguyen, Xuan-Bac; Vervaele, Mattias; Kecskés, Angela; Ny, Annelii; Copmans, Daniëlle; Vriens, Hanne; Locquet, Jean-Pierre; Hoet, Peter; de Witte, Peter A. M.

    2016-01-01

    Nanomaterials are being extensively produced and applied in society. Human and environmental exposures are, therefore, inevitable and so increased attention is being given to nanotoxicity. While silica nanoparticles (NP) are one of the top five nanomaterials found in consumer and biomedical products, their toxicity profile is poorly characterized. In this study, we investigated the toxicity of silica nanoparticles with diameters 20, 50 and 80 nm using an in vivo zebrafish platform that analyzes multiple endpoints related to developmental, cardio-, hepato-, and neurotoxicity. Results show that except for an acceleration in hatching time and alterations in the behavior of zebrafish embryos/larvae, silica NPs did not elicit any developmental defects, nor any cardio- and hepatotoxicity. The behavioral alterations were consistent for both embryonic photomotor and larval locomotor response and were dependent on the concentration and the size of silica NPs. As embryos and larvae exhibited a normal touch response and early hatching did not affect larval locomotor response, the behavior changes observed are most likely the consequence of modified neuroactivity. Overall, our results suggest that silica NPs do not cause any developmental, cardio- or hepatotoxicity, but they pose a potential risk for the neurobehavioral system. PMID:27872490

  4. Metabolic profiling in Caenorhabditis elegans provides an unbiased approach to investigations of dosage dependent lead toxicity.

    PubMed

    Sudama, Gita; Zhang, John; Isbister, Jenefir; Willett, James D

    2013-02-01

    The nematode, Caenorhabditis elegans (CE), serves as a model system in which to explore the impact of particularly low-levels of lead [250, 500, 1000 and 2000 parts per million (ppm) (1.4 × 10(-6) M to 1.1 × 10(-5) M/nematode)] on specific metabolic pathways and processes. Chromatographic profiles of redox active metabolites are captured through application of high performance liquid chromatography coupled to electrochemical detection (Coularray/HPLC). Principal Component Analysis (PCA: unbiased cluster analysis) and the application of a slicing program, located significant areas of difference occurring within the 2.8-4.58 min section of the chromatograms. It is within this region of the data profiles that known components of the purine pathway reside. Two analytes of unknown structure were detected at 3.5 and 4 min respectively. Alterations in levels of the purine, tryptophan and tyrosine pathway intermediates measured in response to differing concentrations of lead acetate indicate that the effect of lead on these pathways is not linear, yet the ratio of the pathway precursors, tryptophan and tyrosine remains relatively constant. The application of the above combined analytical approaches enhances the value of data generated. Exposure of CE to very low levels of lead produced significant alterations in profiles of electrochemically active compounds. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-012-0438-0) contains supplementary material, which is available to authorized users.

  5. Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

    EPA Science Inventory

    Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

  6. Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

    EPA Science Inventory

    Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

  7. Safety profile of Hoodia gordonii extract: rabbit prenatal developmental toxicity study.

    PubMed

    Dent, M P; Wolterbeek, A P M; Russell, P J; Bradford, R

    2012-01-01

    Hoodia gordonii extract was orally administered by gavage to groups of 22 female New Zealand white rabbits from day 3-28 after mating at doses of 0 (control), 3, 6 or 12 mg/kg bodyweight/day. These doses were reached by a dose escalation phase between days 3 and 7 after mating. As well as a vehicle control group, a control group pair-fed to the high dose was also included. On day 29 after mating the females were euthanized and examined. Treatment at 6 or 12 mg/kg/day was associated with a dose-related reduction in feed intake and bodyweight gain. Feed consumption and bodyweight gain was unaffected at 3mg/kg/day. In spite of marked maternal effects at 12 mg/kg/day, reproductive indices were unaffected at all doses and there were no effects on fetal or placental weights and no morphological changes in the fetuses. The no-observed-effect level (NOEL) for developmental effects was therefore 12 mg/kg/day, and the maternal NOEL was 3mg/kg/day. At doses that caused marked maternal effects, H. gordonii extract did not affect embryonic or fetal development in a species that is considered predictive of developmental toxicity in man.

  8. Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort.

    PubMed

    Morris, Katrina A; Golding, John F; Blesing, Claire; Evans, D Gareth; Ferner, Rosalie E; Foweraker, Karen; Halliday, Dorothy; Jena, Raj; McBain, Catherine; McCabe, Martin G; Swampillai, Angela; Warner, Nicola; Wilson, Shaun; Parry, Allyson; Afridi, Shazia K

    2017-01-01

    Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis type 2 (NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event (CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32 female), median age 24.5 years (range 11-66 years), were followed for a median of 32.7 months (range 12.0-60.2 months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24 %) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5 %) had proteinuria. Of 36 patients followed for 36 months, 78 % were free from hypertension and 86 % were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be independent predictors of development of hypertension with dose of 7.5 mg/kg 3 weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

  9. Effects of High Toxic Boron Concentration on Protein Profiles in Roots of Two Citrus Species Differing in Boron-Tolerance Revealed by a 2-DE Based MS Approach

    PubMed Central

    Sang, Wen; Huang, Zeng-Rong; Yang, Lin-Tong; Guo, Peng; Ye, Xin; Chen, Li-Song

    2017-01-01

    Citrus are sensitive to boron (B)-toxicity. In China, B-toxicity occurs in some citrus orchards. So far, limited data are available on B-toxicity-responsive proteins in higher plants. Thirteen-week-old seedlings of “Sour pummelo” (Citrus grandis) and “Xuegan” (Citrus sinensis) was fertilized every other day until dripping with nutrient solution containing 10 μM (control) or 400 μM (B-toxicity) H3BO3 for 15 weeks. The typical B-toxic symptom only occurred in 400 μM B-treated C. grandis leaves, and that B-toxicity decreased root dry weight more in C. grandis seedlings than in C. sinensis ones, demonstrating that C. sinensis was more tolerant to B-toxicity than C. grandis. Using a 2-dimensional electrophoresis (2-DE) based MS approach, we identified 27 up- and four down-accumulated, and 28 up- and 13 down-accumulated proteins in B-toxic C. sinensis and C. grandis roots, respectively. Most of these proteins were isolated only from B-toxic C. sinensis or C. grandis roots, only nine B-toxicity-responsive proteins were shared by the two citrus species. Great differences existed in B-toxicity-induced alterations of protein profiles between C. sinensis and C. grandis roots. More proteins related to detoxification were up-accumulated in B-toxic C. grandis roots than in B-toxic C. sinensis roots to meet the increased requirement for the detoxification of the more reactive oxygen species and other toxic compounds such as aldehydes in the former. For the first time, we demonstrated that the active methyl cycle was induced and repressed in B-toxic C. sinensis and C. grandis roots, respectively, and that C. sinensis roots had a better capacity to keep cell wall and cytoskeleton integrity than C. grandis roots in response to B-toxicity, which might be responsible for the higher B-tolerance of C. sinensis. In addition, proteins involved in nucleic acid metabolism, biological regulation and signal transduction might play a role in the higher B-tolerance of C. sinensis

  10. PROFILING GENE EXPRESSION IN HUMAN H295R ADRENOCORTICAL CARCINOMA CELLS AND RAT TESTES TO IDENTIFY PATHWAYS OF TOXICITY FOR CONAZOLE FUNGICIDES

    EPA Science Inventory

    Profiling Gene Expression in Human H295R Adrenocortical Carcinoma Cells and Rat Testes to Identify Pathways of Toxicity for Conazole Fungicides
    Ren1, H., Schmid1, J., Retief2, J., Turpaz2, Y.,Zhang3, X.,Jones3, P., Newsted3, J.,Giesy3, J., Wolf1, D.,Wood1, C., Bao1, W., Dix1, ...

  11. Evaluation of the toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. in rodents.

    PubMed

    Adeneye, A A; Adeyemi, O O; Agbaje, E O; Banjo, A A F

    2010-01-01

    Hunteria umbellata (K. Schum.) Hallier f. (family: Apocynaceae) is reputed for the folkloric management of labour, pain and swellings, stomach ulcers, diabetes, obesity, and anaemia, with no scientific report of its toxicity and reversibility profile. The present study was, therefore, aimed at investigating the in vivo toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (HU). The acute oral and intraperitoneal toxicity studies of HU were determined in Swiss albino mice while its 90-day oral toxicity and toxicity reversibility profile on anthropometric, biochemical, haematological and histopathological parameters were also assessed using standard procedures. Results showed that the LD50 values for the acute oral and intraperitoneal toxicity studies for HU were estimated to be 1000 mg/kg and 459.3 mg/kg, respectively. Visible signs of immediate and delayed toxicities including starry hair coat, respiratory distress, and dyskinesia were observed. For the chronic oral toxicity study, HU administered for 90 days produced significant (p < 0.001) reductions in the weight gain pattern and significant (p < 0.001) and dose related increases in the relative weights of liver, stomach, spleen, testis, lungs and heart, at the 100 and 500 mg/kg of HU. Chronic HU treatment also produced significant (p < 0.05, p < 0.001) dose related reductions in the serum levels of fasting blood glucose, bicarbonate, urea and creatinine while causing non-significant (p > 0.05) alterations in the serum levels of sodium, potassium, alaninine transaminase, aspartate transaminase, alkaline phosphatase, total and conjugated bilirubin, total protein and albumin. Also, chronic oral treatment with HU produced significant (p < 0.05, p < 0.01, p < 0.001) and dose-related increases in the red cell count, packed cell volume, haemoglobin concentration, platelet count, total leucocyte count and lymphocyte differential while producing significant (p < 0.05) reductions in

  12. Antidiabetic, antidyslipidemic and toxicity profile of ENV-2: A potent pyrazole derivative against diabetes and related diseases.

    PubMed

    Hernández-Vázquez, Eduardo; Ocampo-Montalban, Hugo; Cerón-Romero, Litzia; Cruz, Miguel; Gómez-Zamudio, Jaime; Hiriart-Valencia, Guadalupe; Villalobos-Molina, Rafael; Flores-Flores, Angelica; Estrada-Soto, Samuel

    2017-03-18

    Diabetes is a major health problem and a predisposition factor for further degenerative complications and, therefore, novel therapies are urgently needed. Currently, cannabinoid receptor 1 (CB1 receptor) antagonists have been considered as promissory entities for metabolic disorders treatment. Accordingly, the purpose of this work was the evaluation of the sub-acute antidiabetic, anti-hyperglycemic, antidyslipidemic and toxicological profile of ENV-2, a potent hypoglycemic and antioxidant CB1 receptor antagonist. In this study, ENV-2 showed a pronounced anti-hyperglycemic effect even at a dose of 5mg/kg (P<0.05) in a glucose tolerance test on normoglycemic rats. Moreover, after administration of ENV-2 (16mg/kg) to diabetic rats, a prominent antidiabetic activity was observed (P<0.05), which was higher than glibenclamide. Sub-acute treatment (10 days) of ENV-2 resulted in a significant reduction of plasma glucose (P<0.05). Also, the levels of peripheral lipids were improved; blood triacylglycerols (TG) and cholesterol (CHOL) were diminished (P<0.05). In addition, it was found that ENV-2 reduced IL-1β and IL-18 mRNA expression in adipose tissue (P<0.05). Due to the satisfactory outcomes, we were interested in evaluating the toxicity of ENV-2 in both acute and sub-chronic approaches. Regarding the acute administration, the compound resulted to be non-toxic and was grouped in category 5 according to OECD. It was also found that sub-chronic administration did not increase the size of the studied organs, while no structural damage was observed in heart, lung, liver and kidney tissues. Finally, neither AST nor ALT damage hepatic markers were augmented.

  13. Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure.

    PubMed

    Korashy, Hesham M; Attafi, Ibraheem M; Famulski, Konrad S; Bakheet, Saleh A; Hafez, Mohammed M; Alsaad, Abdulaziz M S; Al-Ghadeer, Abdul Rahman M

    2017-02-01

    Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these

  14. Profiles of paralytic shellfish toxins in bivalves of low and elevated toxicities following exposure to Gymnodinium catenatum blooms in Portuguese estuarine and coastal waters.

    PubMed

    Botelho, Maria João; Vale, Carlos; Ferreira, João Gomes

    2015-11-01

    Profiles of paralytic shellfish toxins (PSTs) were examined in 405 composite samples of Mytilus spp., Cerastoderma edule, Donax trunculus and Spisula solida collected between 2007 and 2012 from natural production areas in two estuaries (Aveiro and Mondego), two coastal lagoons (Óbidos and Formosa), and three open coastal areas (Aguda, Comporta and Culatra). Toxin concentrations were obtained from the biotoxin monitoring programme database. Episodes of PST toxicity in Portugal have been associated with Gymnodinium catenatum blooms. Toxin profiles for each species showed no trend over the surveyed years. In general, profiles differ only slightly among areas, except for Óbidos. However, toxin profiles in bivalves varied between low and elevated toxicities, corresponding to below and above the PST regulatory limit, respectively. The ratio R1=(C1+2):B1, which were the main toxins produced by G. catenatum cells, decreased considerably between elevated and low toxicity cockles, indicating the elimination of C1+2 or conversion of compounds into B1. R2=[(dcSTX)+(dcGTX2+3)]:[(C1+2)+(B1)], which represents the ratio of minor to major toxins in G. catenatum cells, increased substantially in wedge clams (D. trunculus) of low toxicity and less markedly in cockles (C. edule) and mussels (Mytilus spp.). These differences are interpreted as the predominance of a biotransformation phase after exposure to the algal bloom. The toxin profile of surf clams (S. solida) was dominated by decarbamoyl compounds, reflecting intense biotransformation during exposure to blooms. The higher ratio R2 in low toxicity samples suggests that elimination of the produced decarbamoyl toxins was slower than biotransformation.

  15. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study.

    PubMed

    Gyan, Emmanuel; Damotte, Diane; Courby, Stéphane; Sénécal, Delphine; Quittet, Philippe; Schmidt-Tanguy, Aline; Banos, Anne; Le Gouill, Steven; Lamy, Thierry; Fontan, Jean; Maisonneuve, Hervé; Alexis, Magda; Dreyfus, Francois; Tournilhac, Olivier; Laribi, Kamel; Solal-Céligny, Philippe; Arakelyan, Nina; Cartron, Guillaume; Gressin, Remy

    2013-07-01

    The optimal management of relapsed diffuse large B-cell lymphoma (DLBCL) is not standardized. The Groupe Ouest Est des Leucémies et aAutres Maladies du Sang developed a combination of vinorelbine, ifosfamide, mitoxantrone and prednisone (NIMP) for the treatment of relapsed DLBCL, and assessed its efficacy and safety in association with rituximab (R). This multicentric phase II study included 50 patients with DLBCL in first relapse, aged 18-75 years. Patients received rituximab 375 mg/m² day 1, ifosfamide 1000 mg/m² days 1-5, vinorelbine 25 mg/m² days 1 and 15, mitoxantrone 10 mg/m² day 1, and prednisone 1 mg/kg days 1-5, every 28 days for three cycles. Responding patients underwent autologous transplantation or received three additional R-NIMP cycles. All patients were evaluable for toxicity and 49 for response. Centralized pathology review confirmed DLBCL in all cases. Toxicities were mainly haematological with infectious events needing hospitalization in nine cases. Two toxic deaths were observed. After three cycles, 22 patients (44%) achieved complete response/unconfirmed complete response, 11 achieved partial response (24%), 2 had stable disease and 13 progressed. The non-germinal centre B immunophenotype was associated with shorter progression-free survival. in conclusion, the R-NIMP regimen displayed significant activity in relapsed DLBCL, with acceptable toxicity and should be considered a candidate for combination with new agents.

  16. Carbonyl emission and toxicity profile of diesel blends with an animal-fat biodiesel and a tire pyrolysis liquid fuel.

    PubMed

    Ballesteros, R; Guillén-Flores, J; Martínez, J D

    2014-02-01

    In this paper, two diesel fuels, an animal-fat biodiesel and two diesel blends with the animal-fat biodiesel (50vol.%) and with a tire pyrolysis liquid (TPL) fuel (5vol.%) have been tested in a 4-cylinder, 4-stroke, turbocharged, intercooled, 2.0L Nissan diesel automotive engine (model M1D) with common-rail injection system and diesel oxidation catalyst (DOC). Carbonyl emissions have been analyzed both before and after DOC and specific reactivity of carbonyl profile has been calculated. Carbonyl sampling was carried out by means of a heated line, trapping the gas in 2,4-DNPH cartridges. The eluted content was then analyzed in an HPLC system, with UV-VIS detection. Results showed, on the one hand, an increase in carbonyl emissions with the biodiesel fraction in the fuel. On the other hand, the addition of TPL to diesel also increased carbonyl emissions. These trends were occasionally different if the emissions were studied after the DOC, as it seems to be selectivity during the oxidation process. The specific reactivity was also studied, finding a decrease with the oxygen content within the fuel molecule, although the equivalent ozone emissions slightly increased with the oxygen content. Finally, the emissions toxicity was also studied, comparing them to different parameters defined by different organizations. Depending on the point of study, emissions were above or below the established limits, although acrolein exceeded them as it has the least permissive values.

  17. Gene expression profiling in common cormorant liver with an oligo array: assessing the potential toxic effects of environmental contaminants.

    PubMed

    Nakayama, Kei; Iwata, Hisato; Kim, Eun-Young; Tashiro, Kosuke; Tanabe, Shinsuke

    2006-02-01

    To establish a monitoring system for gene expression profiles related to chemical contamination in wild common cormorants (Phalacrocorax carbo), the present study constructed an oligo array designed from expressed sequence tag (EST) sequences of the cormorant liver, where 1061 unique oligonucleotides were spotted. Common cormorants were collected from Lake Biwa, Japan in May 2001 and 2002. With the use of this oligo array, gene expression profiles in the liver of individual specimens were evaluated. To determine the expression patterns of genes altered by environmental contaminants, relationships between concentrations of persistent organochlorines including polychlorinated dibenzo-p-dioxins, furans, polychlorinated biphenyls, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), butyltins, and bisphenol A (BPA) and expression levels of each gene in the cormorant liver were examined using stepwise multiple regression analysis. The reliability of data obtained by the oligo array was further confirmed by quantifying the expression levels of certain genes using real-time RT-PCR. The 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalent (TEQ) level was positively correlated with both cytochrome P4501A4 and 1A5 gene expression. In addition, the mRNA level of an antioxidant enzyme, Cu/Zn superoxide dismutase, was negatively correlated with hepatic total TEQ. Other antioxidant enzymes, glutathione peroxidase 3 and glutathione S-transferase class mu, were negatively correlated with HCHs and BPA levels, respectively. The mRNA expression level of a nonenzymatic antioxidant, haptoglobin, was negatively but not significantly correlated with CHLs. These results led to a hypothesis that wild cormorant population may suffer from oxidative stress due to chemically induced formation of reactive oxygen species and subsequent reduction of antioxidant resistance. Thus, the cormorant oligo array may be

  18. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  19. Profiling Chemicals Based on Chronic Toxicity Results from the U.S. EPA ToxRef Database

    EPA Science Inventory

    Thirty years of pesticide registration toxicity data have been historically stored as hardcopy and scanned documents by the U.S. Environmental Protection Agency (EPA) . A significant portion of these data have now been processed into standardized and structured toxicity data with...

  20. Toxicity profiling of marine surface sediments: A case study using rapid screening bioassays of exhaustive total extracts, elutriates and passive sampler extracts.

    PubMed

    Vethaak, A Dick; Hamers, Timo; Martínez-Gómez, Concepción; Kamstra, Jorke H; de Weert, Jasperien; Leonards, Pim E G; Smedes, Foppe

    2017-03-01

    This study was carried out in the framework of the ICON project (Integrated Assessment of Contaminant Impacts on the North Sea) (Hylland et al., 2015) and aimed (1) to evaluate the toxicity of marine sediments using a battery of rapid toxicity bioassays, and; (2) to explore the applicability and data interpretation of in vitro toxicity profiling of sediment extracts obtained from ex situ passive sampling. Sediment samples were collected at 12 selected (estuarine, coastal, offshore) sites in the North Sea, Icelandic waters (as reference sites), south-western Baltic Sea and western Mediterranean during autumn 2008. Organic extracts using a mild non-destructive clean-up procedure were prepared from total sediment and silicone passive samplers and tested with five in vitro bioassays: DR-Luc bioassay, ER-Luc bioassay, AR-EcoScreen bioassay, transthyretin (TTR) binding assay, and Vibrio fischeri bioluminescence bioassay. In vitro toxicity profiling of total sediment and silicone passive sampler extracts showed the presence of multiple organic contaminations by arylhydrocarbon receptor agonists (e.g. polycyclic aromatic hydrocarbons) and endocrine-active compounds, as well as non-specific toxicity caused by organic contaminants, at virtually all sampling sites. In vitro responses to total sediment extracts from coastal/estuarine sites were significantly different from those in offshore sites (p < 0.05). Several bioassays of passive sampler extracts showed highest activity in some offshore sediment samples. Impact on embryogenesis success and larval growth in undiluted sediment elutriates was shown at some sites using the in vivo sea urchin embryo test. The observed toxicity profiles could only partially be explained by the chemical target analysis, indicating the presence of unknown or unanalysed biologically-active compounds in the sediments. In vitro bioassay testing with silicone passive sampler extracts of sediments is a promising tool to assess the toxic

  1. A patient-specific therapeutic approach for tumour cell population extinction and drug toxicity reduction using control systems-based dose-profile design

    PubMed Central

    2013-01-01

    Background When anti-tumour therapy is administered to a tumour-host environment, an asymptotic tapering extremity of the tumour cell distribution is noticed. This extremity harbors a small number of residual tumour cells that later lead to secondary malignances. Thus, a method is needed that would enable the malignant population to be completely eliminated within a desired time-frame, negating the possibility of recurrence and drug-induced toxicity. Methods In this study, we delineate a computational procedure using the inverse input-reconstruction approach to calculate the unknown drug stimulus input, when one desires a known output tissue-response (full tumour cell elimination, no excess toxicity). The asymptotic extremity is taken care of using a bias shift of tumour-cell distribution and guided control of drug administration, with toxicity limits enforced, during mutually-synchronized chemotherapy (as Temozolomide) and immunotherapy (Interleukin-2 and Cytotoxic T-lymphocyte). Results Quantitative modeling is done using representative characteristics of rapidly and slowly-growing tumours. Both were fully eliminated within 2 months with checks for recurrence and toxicity over a two-year time-line. The dose-time profile of the therapeutic agents has similar features across tumours: biphasic (lymphocytes), monophasic (chemotherapy) and stationary (interleukin), with terminal pulses of the three agents together ensuring elimination of all malignant cells. The model is then justified with clinical case studies and animal models of different neurooncological tumours like glioma, meningioma and glioblastoma. Conclusion The conflicting oncological objectives of tumour-cell extinction and host protection can be simultaneously accommodated using the techniques of drug input reconstruction by enforcing a bias shift and guided control over the drug dose-time profile. For translational applicability, the procedure can be adapted to accommodate varying patient parameters

  2. Toxic substances handbook

    NASA Technical Reports Server (NTRS)

    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.

  3. PROFILE OF TOXIC RESPONSE TO SEDIMENTS USING WHOLE-ANIMAL AND IN VITRO SUBMITOCHONDRIAL PARTICLE (SMP) ASSAYS

    EPA Science Inventory

    A rapid bioassy for monitoring acute toxicity of wastewater, ground water, and soil and sediment extracts using submitochondrial particles (SMP) has been developed. The assay utilizes the mitochondrial electron transfer enzyme complex present in all eukaryotic cells. Prior develo...

  4. Systematic review of vismodegib toxicity profile in the treatment of advanced basal cell carcinomas compared to other systemic therapies in dermatology.

    PubMed

    Juhasz, Margit L W; Marmur, Ellen S

    2014-06-01

    Vismodegib is a first-in-class, hedgehog-signal inhibitor that is FDA-approved for use with advanced basal cell carcinomas (BCCs) that cannot be removed by either surgical resection or treated with radiation. Release of the drug was fast-tracked because of need for this type of drug, and its overall efficacy in clinical trial by producing either regression or even resolution of advanced BCCs. Compared to placebo, patients using vismodegib have arrested BCC progression, reduced size of BCC, and decreased recurrence of BCC. Unfortunately, vismodegib has notable adverse effects (especially those of alopecia, gastrointestinal, muscle spasms, and dysguesia) that make dermatologists reluctant to prescribe the drug and patients unwilling to undergo therapy. In this article, we tackle this dilemma by comparing the toxicity profile of vismodegib to the adverse effect profiles of other dermatologic chemotherapeutics, immunomodulators, retinoids, and biologics. Considering that many of these drugs carry their own risks and those drugs used to treat advanced melanoma have similar toxicity profiles to that of vismodegib, we hope dermatologists and patients alike will be more willing to try vismodegib as a treatment option for advanced BCCs in the future.

  5. Correlation among the toxicity profiling (28-days repeated oral dose toxicity), toxicokinetics and tissue distribution data of ulifloxacin, the active metabolite of prulifloxacin in Wistar albino rats.

    PubMed

    Nandi, Utpal; Roy, Bikash; Das, Anjan Kumar; Pal, Tapan Kumar

    2012-09-01

    This experiment was designed to investigate correlation among 28-days repeated oral dose toxicity, toxicokinetics and tissue distribution data of ulifloxacin (active metabolite of prulifloxacin) in Wistar albino rats. Prulifloxacin was administered for 28-days in rats at 0, 100, 200, 400mg/kg/day followed by 14-days recovery period. Simultaneously different toxicokinetic parameters and tissue distributions of ulifloxacin was examined by LC-MS/MS method. Plasma levels and tissue concentrations of ulifloxacin were increased with dose-related manner. Ulifloxacin was also distributed to many tissues, and concentration in lungs nearly equivalent to the plasma concentration. Based on these results it was concluded that long-term repeated dose of prulifloxacin may produce different blood parameters abnormality, liver damage, stomach ulcer, joint damage and dysfunction of lungs in rats which relates to high tissue distribution and accumulation of ulifloxacin in these tissues. These findings help in management of prulifloxacin induced adverse effects by appropriate dose selection in clinical practice.

  6. Distribution, diffusive fluxes, and toxicity of heavy metals and PAHs in pore water profiles from the northern bays of Taihu Lake.

    PubMed

    Lei, Pei; Zhang, Hong; Shan, Baoqing; Zhang, Bozheng

    2016-11-01

    Pore water plays a more significant role than do sediments in pollutant cycling dynamics. Also, concentrations of pollutants in pore water provide important information about their bioavailability or eco-toxicity; however, very few studies have focused on this topic. In this study, four duplicate sediment cores from three typical northern bays as well as the central part of Taihu Lake were collected to investigate the distribution, diffusive fluxes, and toxicity of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in pore water profiles, which will be good in understanding the mobility and toxicity of these toxic pollutants and achieving better environmental management. The diffusive fluxes of heavy metals across the sediment-water interface was estimated through Fick's First Law, and the toxicity of heavy metals and PAHs in pore water was assessed by applying a water quality index (interstitial water toxicity criteria unit, IWCTU) and a hazard index (HI), respectively. The average concentrations of Cr, Cu, Ni, Pb, and Zn in surface pore water were 18.8, 23.4, 12.0, 13.5, and 42.5 μg L(-1), respectively. Also, concentrations of the selected heavy metals in both overlying water and pore water from Taihu Lake were all lower than the standard values of the environmental quality standards for surface water. The concentrations as the pore water depth increased, and the highest detected concentrations of heavy metals were recorded between 3 and 5 cm below the sediment surface. The average diffusive fluxes of these metals were 27.3, 24.8, 7.03, 7.81, and -3.32 μg (m(2) day)(-1), respectively, indicating export from sediment into overlying water, with the exception of Zn. There was a potential risk of toxicity, mainly from Pb and Cu, indicating that heavy metals in pore water had slight to moderate impact on sediment-dwelling organisms by values of the IWCTU and the Nemeraw index. The total PAH concentrations in pore water were higher than those in overlying

  7. Profile of toxic response to sediments using whole-animal and in vitro submitochondrial particle (SMP) assays

    SciTech Connect

    Bettermann, A.D.; Dorofi, J.C.; Lazorchak, J.M.

    1996-03-01

    A rapid bioassay for monitoring acute toxicity of wastewater, ground water, and soil and sediment extracts using submitochondrial particles (SMP) has been developed. The assay utilizes the mitochondrial electron transfer enzyme complex, present in all eukaryotic cells. Prior developmental work with pure chemicals chosen from the US Environmental Protection Agency`s (EPA) priority pollutant list documented order-of-magnitude predictability between the bioassay response and whole-organism tests (e.g., fathead minnow). Recent work has adapted the assay for analysis of uncharacterized environmental samples, including stormwater runoff, landfill leachate, and soil and sediment extracts. A feasibility study was performed to determine whether the SMP assay could detect toxicity in samples previously assessed for toxicity to amphipods. Acute toxicity tests using Hyalella azteca were performed on 30 sediment samples from Colorado`s Arkansas River, Eagle River, and Chalk Creek watersheds, all of which have been directly or indirectly affected by heavy metal mine tailings and drainage. In parallel, two SMP assay protocols designed to differentiate between modes of toxicity were performed on elutriate samples from 23 of the above sites. The results from analysis of the sediments differed widely in the nature and degree of test responses. Significant correlation was found between the responses of the SMP electron transfer protocol and the whole-organisms assay, and between the responses of the SMP electron transfer protocol and levels of zinc and sulfur, as determined by inductively coupled plasma spectroscopy.

  8. Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline*

    PubMed Central

    Ranninger, Christina; Rurik, Marc; Limonciel, Alice; Ruzek, Silke; Reischl, Roland; Wilmes, Anja; Jennings, Paul; Hewitt, Philip; Dekant, Wolfgang; Kohlbacher, Oliver; Huber, Christian G.

    2015-01-01

    Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter−1 of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter−1 for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways. PMID:26055719

  9. Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline.

    PubMed

    Ranninger, Christina; Rurik, Marc; Limonciel, Alice; Ruzek, Silke; Reischl, Roland; Wilmes, Anja; Jennings, Paul; Hewitt, Philip; Dekant, Wolfgang; Kohlbacher, Oliver; Huber, Christian G

    2015-07-31

    Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter(-1) of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter(-1) for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways.

  10. Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

    PubMed Central

    Zuhl, Andrea M.; Nolan, Charles E.; Brodney, Michael A.; Niessen, Sherry; Atchison, Kevin; Houle, Christopher; Karanian, David A.; Ambroise, Claude; Brulet, Jeffrey W.; Beck, Elizabeth M.; Doran, Shawn D.; O'Neill, Brian T.; am Ende, Christopher W.; Chang, Cheng; Geoghegan, Kieran F.; West, Graham M.; Judkins, Joshua C.; Hou, Xinjun; Riddell, David R.; Johnson, Douglas S.

    2016-01-01

    Inhibition of β-secretase BACE1 is considered one of the most promising approaches for treating Alzheimer's disease. Several structurally distinct BACE1 inhibitors have been withdrawn from development after inducing ocular toxicity in animal models, but the target mediating this toxicity has not been identified. Here we use a clickable photoaffinity probe to identify cathepsin D (CatD) as a principal off-target of BACE1 inhibitors in human cells. We find that several BACE1 inhibitors blocked CatD activity in cells with much greater potency than that displayed in cell-free assays with purified protein. Through a series of exploratory toxicology studies, we show that quantifying CatD target engagement in cells with the probe is predictive of ocular toxicity in vivo. Taken together, our findings designate off-target inhibition of CatD as a principal driver of ocular toxicity for BACE1 inhibitors and more generally underscore the power of chemical proteomics for discerning mechanisms of drug action. PMID:27727204

  11. Toxicity of nickel ions and comprehensive analysis of nickel ion-associated gene expression profiles in THP-1 cells.

    PubMed

    Zhang, Ying; Zhang, Zhi-Wei; Xie, Yu-Mei; Wang, Shu-Shui; Qiu, Qing-Huan; Zhou, Ying-Ling; Zeng, Guo-Hong

    2015-09-01

    The aim of the present study was to explore the toxic effects and underlying mechanisms of nickel ions during therapeutic nickel‑based alloy‑treatment in congenital heart disease by investigating the metal‑induced cytotoxicity to the human monocyte‑derived macrophage cell line THP‑1. THP‑1 cells were treated with NiCl2·6H2O (25, 50, 100, 200, 400 and 800 µM) for 24, 48 and 72 h, respectively. MTT was applied to detect THP‑1 cell proliferation following NiCl2 treatment. Apoptosis of THP‑1 cells was quantified using flow cytometry. Illumina sequencing was used for screening the associated genes, whose mRNA expression levels were further confirmed by quantitative real‑time polymerase chain reaction. High concentrations of nickel ions had a significant suppressive effect on cell proliferation at the three concentrations investigated (200, 400 and 800 µM). Treatment with nickel ions (25‑400 µM) for 48 h reduced cell viability in a dose‑dependent manner. The mRNA expression levels of RELB, FIGF, SPI‑1, CXCL16 and CRLF2 were significantly increased following nickel treatment. The results of the present study suggested that nickel ions exert toxic effects on THP‑1 cell growth, which may indicate toxicity of the nickel ion during treatment of congenital heart disease. The identification of genes modified by the toxic effects of nickel on THP‑1 cells (EPOR, RELB, FIGF, SPI‑1, TGF‑β1, CXCL16 and CRLF2) may aid in the development of interventional measures for the treatment/prevention of nickel ion‑associated toxic effects during the treatment of congenital heart disease.

  12. Subchronic oral toxicity and metabolite profiling of the p53 stabilizing agent, CP-31398, in rats and dogs.

    PubMed

    Johnson, William D; Muzzio, Miguel; Detrisac, Carol J; Kapetanovic, Izet M; Kopelovich, Levy; McCormick, David L

    2011-11-18

    CP-31398 (N'-[2-[2-(4-methoxyphenyl)ethenyl]-4-quinazolinyl]-N,N-dimethyl-1,3-propanediamine dihydrochloride) is a styrylquinazoline that stabilizes the DNA binding conformation of p53, thereby maintaining the activity of p53 as a transcription factor and tumor suppressor. In consideration of the potential use of p53 stabilizers for cancer prevention and therapy, 28-day studies (with recovery) were performed to characterize the toxicity of CP-31398 in rats and dogs. In the rat study, groups of 15 CD rats/sex received daily gavage exposure to CP-31398 at 0, 40, 80, or 160mg/kg/day (0, 240, 480, or 960mg/m(2)/day). In the dog study, groups of five beagle dogs received daily gavage exposure to CP-31398 at 0, 10, 20, or 40mg/kg/day (0, 200, 400, or 800mg/m(2)/day). The high dose of CP-31398 induced mortality in both species: seven male rats and four female rats died as a result of hepatic infarcts, and two female dogs died as a result of hepatic necrosis without evidence of thrombosis. No deaths were seen in the mid- or low-dose groups in either species. In dogs, sporadic emesis was seen in the high dose and mid dose groups, and reductions in body weight gain were observed in all drug-exposed groups. CP-31398 induced mild anemia in both species; clinical pathology data also demonstrated hepatic toxicity, renal toxicity, inflammatory reactions, and coagulopathies in rats in the high dose and mid dose groups. Treatment-related microscopic changes in high dose and mid dose rats were identified in the liver, kidney, heart, bone marrow, lung, adrenals, spleen, thymus, skeletal muscle, and ovary; microscopic changes in the liver, heart, lung, and adrenals persisted through the recovery period. In dogs, microscopic changes were identified in the central nervous system, lung, and liver; changes in all tissues remained at the end of the recovery period. The liver is the primary site of limiting toxicity for CP-31398 in rats, and is also a key site of toxicity in dogs. The

  13. Heavy metals pollution in soil profiles from seasonal-flooding riparian wetlands in a Chinese delta: Levels, distributions and toxic risks

    NASA Astrophysics Data System (ADS)

    Zhang, Guangliang; Bai, Junhong; Zhao, Qingqing; Jia, Jia; Wen, Xiaojun

    2017-02-01

    Soil profile samples were collected in seasonal-flooding riparian wetlands in the Yellow River Delta (YRD) of China in autumn and spring to investigate the levels, distributions and toxic risks of heavy metals in soil profiles. Total elemental contents of Al, As, Cd, Cr, Cu, Ni, Pb and Zn were determined using inductively coupled plasma atomic absorption spectrometry (ICP-AAS). Results indicated that the contents of determined heavy metals showed non-negligible depth variations (coefficient of variation > 10%), and their distribution patterns were irregular. Compared with other heavy metals, both As and Cd presented higher enrichment factors (EF) based on the classification of EF values (moderate enrichment for As while significant enrichment for Cd). Cluster analysis (CA) and principal components analysis (PCA) revealed that Cr, Cu, Ni, Pb and Zn might derive from the common source, while As and Cd shared another similar source. The toxic unit (TU) values of these heavy metals did not exceed probable effect levels (PEL) except for Ni. Both As and Ni showed higher contributions to the sum of TU (∑TUs), which indicated they were the primary concerns of heavy metals pollution. Generally, As, Cd and Ni should be paid more attention for wetlands managers and policy makers to avoid potential ecotoxicity in the study area. The findings of this study could contribute to the prevention and control of heavy metals pollution in estuarine wetlands.

  14. Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

    SciTech Connect

    Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; Ende, Piet van den; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.

    2012-02-01

    Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.

  15. Purification, characterization and toxic profile of two toxins isolated from puffer fish Tetraodon patoca, available in Bangladesh.

    PubMed

    Hasan, Sohel; Rahman, M M; Hossain, T; Mosaddik, A; Khatun, S; Absar, N

    2007-03-01

    Among the marine toxins related to human intoxication, tetrodotoxin has been known as one of the most prejudicial. Two tetrodotoxins, namely PFT-1 and PFT-2 were isolated and purified from liver of puffer fish by thin layer chromatography. The structure of both the toxins was elucidated by means of IR, 1H-NMR and 13C-NMR and mass spectroscopy. Sub acute toxicity study showed that both the toxins had pronounced effects on total RBC, WBC, platelet and ESR. Further serum levels of SGPT, SGOT, SALP, bilirubin, creatinine and urea are also affected by the toxins. The histopathological examinations showed that all the tissues such as liver, lung, heart and kidney of rat were severely changed after treatment with the toxins. The toxicity of the purified compounds, PFT-1 and PFT-2 were also performed by brine shrimp lethality bioassay.

  16. Short-term repeated-dose toxicity profile of archaeosomes administered to mice via intravenous and oral routes.

    PubMed

    Omri, Abdelwahab; Agnew, Brian J; Patel, Girishchandra B

    2003-01-01

    Archaeosomes, liposomes made from polar ether lipids of archaea, show promise for vaccine and drug delivery applications. The potential toxicity of intravenously (14, 70, or 140 mg/kg/day for 5 consecutive days) and orally (gavaged at 55, 275, or 550 mg/kg/day for 10 consecutive days) administered unilamellar archaeosomes, prepared from the total polar lipids (TPLs) extracted from several species of archaea, was assessed in female BALB/c mice. Liposomes prepared from an ester phospholipid composition were included for comparative purposes. Control groups of mice were administered 0.1 ml phosphate-buffered saline (PBS) by either route. Animals were monitored at least once daily for temperature, body weight, and clinical signs of adverse reactions. One day after the last dose, the mice were sacrificed. Blood was collected for selected biochemical/enzyme analyses, and the major organs (heart, lungs, liver, spleen, kidneys) were weighed and examined macroscopically. In addition, the spleens were examined histologically. At the two lower dosages of intravenously administered vesicles, there were no significant indications of toxicity, as compared with the PBS-administered control group. At the highest intravenous dose of 140 mg/kg/day, archaeosomes prepared from the TPL of the extreme halophiles, Halobacterium salinarum and Natronobacterium magadii, indicated potential toxicity, as evidenced by clinical signs (hyperactivity and/or piloerection), drop in body temperature, and loss in body weight. Spleens from mice administered some archaeosomes types, primarily at the highest intravenous dose tested, were enlarged, had increased organ weight, and microscopic examination revealed mild to moderate expansion of the red pulp with increased numbers of hematopoietic cells, but no changes in the white pulp. There were similar clinical signs at one or more of the higher oral doses of the ester liposomes and some of the archaeosome types; however, no other apparent toxicity was

  17. Building America Top Innovations 2014 Profile: ASHRAE Standard 62.2. Ventilation and Acceptable Indoor Air Quality in Low-Rise Residential Buildings

    SciTech Connect

    none,

    2014-11-01

    This 2014 Top Innovations profile describes Building America research and support in developing and gaining adoption of ASHRAE 62.2, a residential ventilation standard that is critical to transforming the U.S. housing industry to high-performance homes.

  18. Vertical profile, source apportionment, and toxicity of PAHs in sediment cores of a wharf near the coal-based steel refining industrial zone in Kaohsiung, Taiwan.

    PubMed

    Chen, Chih-Feng; Chen, Chiu-Wen; Ju, Yun-Ru; Dong, Cheng-Di

    2016-03-01

    Three sediment cores were collected from a wharf near a coal-based steel refining industrial zone in Kaohsiung, Taiwan. Analyses for 16 polycyclic aromatic hydrocarbons (PAHs) of the US Environmental Protection Agency priority list in the core sediment samples were conducted using gas chromatography-mass spectrometry. The vertical profiles of PAHs in the core sediments were assessed, possible sources and apportionment were identified, and the toxicity risk of the core sediments was determined. The results from the sediment analyses showed that total concentrations of the 16 PAHs varied from 11774 ± 4244 to 16755 ± 4593 ng/g dry weight (dw). Generally, the vertical profiles of the PAHs in the sediment cores exhibited a decreasing trend from the top to the lower levels of the S1 core and an increasing trend of PAHs from the top to the lower levels of the S2 and S3 cores. Among the core sediment samples, the five- and six-ring PAHs were predominantly in the S1 core, ranging from 42 to 54 %, whereas the composition of the PAHs in the S2 and S3 cores were distributed equally across three groups: two- and three-ring, four-ring, and five- and six-ring PAHs. The results indicated that PAH contamination at the site of the S1 core had a different source. The molecular indices and principal component analyses with multivariate linear regression were used to determine the source contributions, with the results showing that the contributions of coal, oil-related, and vehicle sources were 38.6, 35.9, and 25.5 %, respectively. A PAH toxicity assessment using the mean effect range-median quotient (m-ERM-q, 0.59-0.79), benzo[a]pyrene toxicity equivalent (TEQ(carc), 1466-1954 ng TEQ/g dw), and dioxin toxicity equivalent (TEQ(fish), 3036-4174 pg TEQ/g dw) identified the wharf as the most affected area. The results can be used for regular monitoring, and future pollution prevention and management should target the coal-based industries in this region for pollution reduction.

  19. Acceptance speech.

    PubMed

    Yusuf, C K

    1994-01-01

    I am proud and honored to accept this award on behalf of the Government of Bangladesh, and the millions of Bangladeshi children saved by oral rehydration solution. The Government of Bangladesh is grateful for this recognition of its commitment to international health and population research and cost-effective health care for all. The Government of Bangladesh has already made remarkable strides forward in the health and population sector, and this was recognized in UNICEF's 1993 "State of the World's Children". The national contraceptive prevalence rate, at 40%, is higher than that of many developed countries. It is appropriate that Bangladesh, where ORS was discovered, has the largest ORS production capacity in the world. It was remarkable that after the devastating cyclone in 1991, the country was able to produce enough ORS to meet the needs and remain self-sufficient. Similarly, Bangladesh has one of the most effective, flexible and efficient control of diarrheal disease and epidemic response program in the world. Through the country, doctors have been trained in diarrheal disease management, and stores of ORS are maintained ready for any outbreak. Despite grim predictions after the 1991 cyclone and the 1993 floods, relatively few people died from diarrheal disease. This is indicative of the strength of the national program. I want to take this opportunity to acknowledge the contribution of ICDDR, B and the important role it plays in supporting the Government's efforts in the health and population sector. The partnership between the Government of Bangladesh and ICDDR, B has already borne great fruit, and I hope and believe that it will continue to do so for many years in the future. Thank you.

  20. Toxicity profiling of water contextual zinc oxide, silver, and titanium dioxide nanoparticles in human oral and gastrointestinal cell systems.

    PubMed

    Giovanni, Marcella; Tay, Chor Yong; Setyawati, Magdiel Inggrid; Xie, Jianping; Ong, Choon Nam; Fan, Rongli; Yue, Junqi; Zhang, Lifeng; Leong, David Tai

    2015-12-01

    Engineered nanoparticles (ENPs) are increasingly detected in water supply due to environmental release of ENPs as the by-products contained within the effluent of domestic and industrial run-off. The partial recycling of water laden with ENPs, albeit at ultra-low concentrations, may pose an uncharacterized threat to human health. In this study, we investigated the toxicity of three prevalent ENPs: zinc oxide, silver, and titanium dioxide over a wide range of concentrations that encompasses drinking water-relevant concentrations, to cellular systems representing oral and gastrointestinal tissues. Based on published in silico-predicted water-relevant ENPs concentration range from 100 pg/L to 100 µg/L, we detected no cytotoxicity to all the cellular systems. Significant cytotoxicity due to the NPs set in around 100 mg/L with decreasing extent of toxicity from zinc oxide to silver to titanium dioxide NPs. We also found that noncytotoxic zinc oxide NPs level of 10 mg/L could elevate the intracellular oxidative stress. The threshold concentrations of NPs that induced cytotoxic effect are at least two to five orders of magnitude higher than the permissible concentrations of the respective metals and metal oxides in drinking water. Based on these findings, the current estimated levels of NPs in potable water pose little cytotoxic threat to the human oral and gastrointestinal systems within our experimental boundaries.

  1. Release behavior and toxicity profiles towards A549 cell lines of ciprofloxacin from its layered zinc hydroxide intercalation compound

    PubMed Central

    2013-01-01

    Background Layered hydroxides salts (LHS), a layered inorganic compound is gaining attention in a wide range of applications, particularly due to its unique anion exchange properties. In this work, layered zinc hydroxide nitrate (LZH), a family member of LHS was intercalated with anionic ciprofloxacin (CFX), a broad spectrum antibiotic via ion exchange in a mixture solution of water:ethanol. Results Powder x-ray diffraction (XRD), Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) confirmed the drug anions were successfully intercalated in the interlayer space of LZH. Specific surface area of the obtained compound was increased compared to that of the host due to the different pore textures between the two materials. CFX anions were slowly released over 80 hours in phosphate-buffered saline (PBS) solution due to strong interactions that occurred between the intercalated anions and the host lattices. The intercalation compound demonstrated enhanced antiproliferative effects towards A549 cancer cells compared to the toxicity of CFX alone. Conclusions Strong host-guest interactions between the LZH lattice and the CFX anion give rise to a new intercalation compound that demonstrates sustained release mode and enhanced toxicity effects towards A549 cell lines. These findings should serve as foundations towards further developments of the brucite-like host material in drug delivery systems. PMID:23849189

  2. MicroRNA expression profile in common bean (Phaseolus vulgaris) under nutrient deficiency stresses and manganese toxicity.

    PubMed

    Valdés-López, Oswaldo; Yang, S Samuel; Aparicio-Fabre, Rosaura; Graham, Peter H; Reyes, José Luis; Vance, Carroll P; Hernández, Georgina

    2010-08-01

    *MicroRNAs (miRNAs) play a pivotal role in post-transcriptional regulation of gene expression in plants. Information on miRNAs in legumes is as yet scarce. This work investigates miRNAs in an agronomically important legume, common bean (Phaseolus vulgaris). *A hybridization approach employing miRNA macroarrays - printed with oligonucleotides complementary to 68 known miRNAs - was used to detect miRNAs in the leaves, roots and nodules of control and nutrient-stressed (phosphorus, nitrogen, or iron deficiency; acidic pH; and manganese toxicity) common bean plants. *Thirty-three miRNAs were expressed in control plants and another five were only expressed under stress conditions. The miRNA expression ratios (stress:control) were evaluated using principal component and hierarchical cluster analyses. A group of miRNAs responded to nearly all stresses in the three organs analyzed. Other miRNAs showed organ-specific responses. Most of the nodule-responsive miRNAs showed up-regulation. miRNA blot expression analysis confirmed the macroarray results. Novel miRNA target genes were proposed for common bean and the expression of selected targets was evaluated by quantitative reverse transcriptase-polymerase chain reaction. *In addition to the detection of previously reported stress-responsive miRNAs, we discovered novel common bean stress-responsive miRNAs, for manganese toxicity. Our data provide a foundation for evaluating the individual roles of miRNAs in common bean.

  3. In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components.

    PubMed

    Verma, Ranjana; Xu, Xiufen; Jaiswal, Manoj K; Olsen, Cara; Mears, David; Caretti, Giuseppina; Galdzicki, Zygmunt

    2011-06-15

    Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma (SKNMC), and mouse myoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50-200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calcium channel blockers/chelators to the metal solutions. Tungsten and its alloy showed cytotoxicity at concentrations > 50 μg/ml, while we found significant toxicity with cobalt and nickel for most tested concentrations. Diverse cell-specific toxic effects were observed, with C2C12 being relatively resistant to tungsten-alloy mediated toxic impact. Tungsten-alloy, but not tungsten, caused almost complete dephosphorylation of H3-Ser10 in C2C12 and hippocampal primary neuronal cultures with H3-hypoacetylation in C2C12. Dramatic H3-Ser10 dephosphorylation was found in all cobalt treated cultures with a decrease in H3 pan-acetylation in C2C12, SKNMC and HEK293. Trimethylation of H3-K4 was not affected. Both tungsten-alloy and cobalt mediated H3-Ser10 dephosphorylation were reversed with BAPTA-AM, highlighting the role of intracellular calcium, confirmed with 2-photon calcium imaging. In summary, our results for the first time reveal epigenetic modifications triggered by tungsten-alloy exposure in C2C12 and hippocampal primary neuronal cultures suggesting the underlying synergistic effects of tungsten, nickel and cobalt mediated by changes in intracellular calcium homeostasis and

  4. In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components

    SciTech Connect

    Verma, Ranjana; Xu, Xiufen; Jaiswal, Manoj K.; Olsen, Cara; Mears, David; Caretti, Giuseppina; Galdzicki, Zygmunt

    2011-06-15

    Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma (SKNMC), and mouse myoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50-200 {mu}g/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calcium channel blockers/chelators to the metal solutions. Tungsten and its alloy showed cytotoxicity at concentrations > 50 {mu}g/ml, while we found significant toxicity with cobalt and nickel for most tested concentrations. Diverse cell-specific toxic effects were observed, with C2C12 being relatively resistant to tungsten-alloy mediated toxic impact. Tungsten-alloy, but not tungsten, caused almost complete dephosphorylation of H3-Ser10 in C2C12 and hippocampal primary neuronal cultures with H3-hypoacetylation in C2C12. Dramatic H3-Ser10 dephosphorylation was found in all cobalt treated cultures with a decrease in H3 pan-acetylation in C2C12, SKNMC and HEK293. Trimethylation of H3-K4 was not affected. Both tungsten-alloy and cobalt mediated H3-Ser10 dephosphorylation were reversed with BAPTA-AM, highlighting the role of intracellular calcium, confirmed with 2-photon calcium imaging. In summary, our results for the first time reveal epigenetic modifications triggered by tungsten-alloy exposure in C2C12 and hippocampal primary neuronal cultures suggesting the underlying synergistic effects of tungsten, nickel and cobalt mediated by changes in intracellular calcium homeostasis

  5. In Vitro Immune Toxicity of Depleted Uranium: Effects on Murine Macrophages, CD4+ T Cells, and Gene Expression Profiles

    PubMed Central

    Wan, Bin; Fleming, James T.; Schultz, Terry W.; Sayler, Gary S.

    2006-01-01

    Depleted uranium (DU) is a by-product of the uranium enrichment process and shares chemical properties with natural and enriched uranium. To investigate the toxic effects of environmental DU exposure on the immune system, we examined the influences of DU (in the form of uranyl nitrate) on viability and immune function as well as cytokine gene expression in murine peritoneal macrophages and splenic CD4+ T cells. Macrophages and CD4+ T cells were exposed to various concentrations of DU, and cell death via apoptosis and necrosis was analyzed using annexin-V/propidium iodide assay. DU cytotoxicity in both cell types was concentration dependent, with macrophage apoptosis and necrosis occurring within 24 hr at 100 μM DU exposure, whereas CD4+ T cells underwent cell death at 500 μM DU exposure. Noncytotoxic concentrations for macrophages and CD4+ T cells were determined as 50 and 100 μM, respectively. Lymphoproliferation analysis indicated that macrophage accessory cell function was altered with 200 μM DU after exposure times as short as 2 hr. Microarray and real-time reverse-transcriptase polymerase chain reaction analyses revealed that DU alters gene expression patterns in both cell types. The most differentially expressed genes were related to signal transduction, such as c-jun, NF-κ Bp65, neurotrophic factors (e.g., Mdk), chemokine and chemokine receptors (e.g., TECK/CCL25), and interleukins such as IL-10 and IL-5, indicating a possible involvement of DU in cancer development, autoimmune diseases, and T helper 2 polarization of T cells. The results are a first step in identifying molecular targets for the toxicity of DU and the elucidation of the molecular mechanisms for the immune modulation ability of DU. PMID:16393663

  6. Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers

    PubMed Central

    Salvador, F.; Sánchez-Montalvá, A.; Treviño, B.; Serre, N.; Sao Avilés, A.; Almirante, B.

    2015-01-01

    Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals. PMID:26195525

  7. Liver and kidney damage induced by 4-aminopyridine in a repeated dose (28 days) oral toxicity study in rats: gene expression profile of hybrid cell death.

    PubMed

    Frejo, María Teresa; Del Pino, Javier; Lobo, Margarita; García, Jimena; Capo, Miguel Andrés; Díaz, María Jesús

    2014-03-03

    4-Aminopyridine (4-AP) is an orphan drug indicated for the treatment of neuromuscular disorders. There is a great controversy around the use of this drug because of its narrow safety index and because a large number of adverse effects have been reported. Moreover, it was shown to induce cell death in different cell lines, being reported mainly apoptosis and necrosis as the principal pathways of cell death mediated by blockage of K channels or the Na, K-ATPase, but until now it was not described in vivo cell death induced by 4-aminipyridine. To provide new subchronic toxicity data and specifically, evaluate if 4-AP is able to induce in vivo cell death process and the main pathways related to it, a repeated dose (28 days) oral toxicity study, at therapeutic range of doses, was conducted in rats. The anatomical pathology, the biochemical and hematological parameters were analyzed and a real-time PCR array analysis was developed with an Ingenuity Pathway Analysis (IPA). The leucocytes number, the lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) enzymatic activity were increased at all dose but the erythrocytes number, the hemoglobin concentration, the alkaline phosphatase (FAL) and alanine aminotransferase (ALT) enzymatic activity were increased only at highest dose studied. However, glucose levels decreased at all doses. The biochemical results are indicative of hepatic damage. The anatomy pathology studies showed cell death only on liver and kidney, and the real-time PCR array on liver tissue expressed a gene expression profile of necrotic and apoptotic induced cell death. The present work shows for the first time in vivo cell death on liver and kidney with features of apoptosis and necrosis induced by 4-AP and the gene expression profile shows that the cell death is mediated by necrotic and apoptotic pathways that support this finding.

  8. Gene transcription, metabolite and lipid profiling in eco-indicator daphnia magna indicate diverse mechanisms of toxicity by legacy and emerging flame-retardants.

    PubMed

    Scanlan, Leona D; Loguinov, Alexandre V; Teng, Quincy; Antczak, Philipp; Dailey, Kathleen P; Nowinski, Daniel T; Kornbluh, Jonah; Lin, Xin Xin; Lachenauer, Erica; Arai, Audrey; Douglas, Nora K; Falciani, Francesco; Stapleton, Heather M; Vulpe, Chris D

    2015-06-16

    The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity of seven FR chemicals and formulations was assessed on the freshwater crustacean Daphnia magna. Acute 48-h nominal LC50 values for penta- and octabromodiphenyl ether (pentaBDE, octaBDE), Firemaster 550 (FM550), Firemaster BZ-54 (BZ54), bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP), triphenyl phosphate (TPhP), and nonbrominated BEH-TEBP analog bis(2-ethylhexyl) phthalate (BEHP) ranged from 0.058 mg/L (pentaBDE) to 3.96 mg/L (octaBDE). mRNA expression, (1)H NMR-based metabolomic and lipidomic profiling at 1/10 LC50 revealed distinct patterns of molecular response for each exposure, suggesting pentaPBDE affects transcription and translation, octaBDE and BEH-TEBP affect glycosphingolipid biosynthesis and BZ54 affects Wnt and Hedgehog signal pathways as well as glycosaminoglycan degradation. Brominated components of FM550 (i.e., BZ54) were significantly higher in Daphnia after 48 h following 1/10 LC50 exposure. FM550 elicited significant mRNA changes at five concentrations across a range from 1/10(6) LC50 to 1/2 LC50. Analyses suggest FM550 impairs nutrient utilization or uptake in Daphnia.

  9. Hepatic transcriptomic profiles of European flounder (Platichthys flesus) from field sites and computational approaches to predict site from stress gene responses following exposure to model toxicants.

    PubMed

    Falciani, F; Diab, A M; Sabine, V; Williams, T D; Ortega, F; George, S G; Chipman, J K

    2008-11-11

    Genomic technologies offer opportunities to gain a more global assessment of the health status of an organism through an understanding of the functional pathways that are responding to pollutant exposure. We have developed a 13,000 clone cDNA toxicogenomics microarray for Platichthys flesus, the European flounder (EU-GENIPOL Project). We aimed to distinguish the origins of flounder taken from six sampling sites of different pollution status in Northern Europe according to their hepatic gene expression profile using bioinformatic approaches. To determine which gene expression differences may relate to pollutant impact, we have completed complementary laboratory exposures of flounder to selected toxicants and determined the associated gene expression profiles. Using multivariate variable selection coupled with a statistical modelling procedure (GALGO) we can predict geographical site but the accuracy is limited to specific sites. The search space for a combination of genes that effectively predicts class membership is very large, however, by combining the signatures derived from acute laboratory exposure to individual chemicals to limit the search space, a very accurate model for classification of all the different environmental sites was achieved. The final model utilised the expression profiles of 16 clones and validation with a qPCR array comprising these genes correctly assigned the site of origin for fish obtained from three of the sites in an independent sampling. These data would imply that the gene expression fingerprints obtained with these arrays are primarily attributable to variations in chemical pollutant responses at the different sites, indicating their potential utility in environmental impact assessment.

  10. Profile of the capsaicin 8% patch for the management of neuropathic pain associated with postherpetic neuralgia: safety, efficacy, and patient acceptability

    PubMed Central

    Laklouk, Muhammad; Baranidharan, Ganesan

    2016-01-01

    Capsaicin is a naturally occurring irritant active ingredient found in hot peppers. It is a ligand for transient receptor potential channel vanilloid receptors, which are found in nociceptive nerve terminals in the skin. Initial exposure to topical capsaicin leads to excitation of these receptors, release of vasoactive mediators, erythema, intense burning, pain, and thereafter desensitization of sensory neurons resulting in inhibition of pain transmission. Capsaicin 8% has been licensed for the treatment of postherpetic neuralgia pain in recent years. A single application of high-concentration capsaicin for 60 minutes for postherpetic neuralgia has been robustly evaluated. Capsaicin 8% patches are applied to the most painful areas of healthy skin and allowed to remain for 60 minutes. Treatment can be repeated every 90 days if the pain persists or returns. The patches are usually applied in specialist pain clinics where patients can be pretreated and monitored. Health care staff need to take certain precautions before administering these patches to avoid unintentional contact. Common adverse effects of the capsaicin 8% patch are transient mild-to-moderate self-limiting application-site burning, pain, erythema, pruritus, papules, swelling, dryness, and hypertension. To manage local pain from capsaicin application, the skin is pretreated with a local anesthetic such as topical lidocaine or an oral analgesic such as oxycodone for up to 5 days. A transient increase in pain is usually seen within 48 hours of patch application before the pain-relieving effect starts. Systemic absorption is minimal and clinically insignificant. The nature of administration and relatively high cost of capsaicin patches can significantly limit their use to a small number of patients with severe refractory symptoms. This review highlights recent evidence related to the use and effectiveness of the 8% capsaicin patch for Postherpetic Neuralgia and discusses its safety and side-effect profiles

  11. Profile of the capsaicin 8% patch for the management of neuropathic pain associated with postherpetic neuralgia: safety, efficacy, and patient acceptability.

    PubMed

    Laklouk, Muhammad; Baranidharan, Ganesan

    2016-01-01

    Capsaicin is a naturally occurring irritant active ingredient found in hot peppers. It is a ligand for transient receptor potential channel vanilloid receptors, which are found in nociceptive nerve terminals in the skin. Initial exposure to topical capsaicin leads to excitation of these receptors, release of vasoactive mediators, erythema, intense burning, pain, and thereafter desensitization of sensory neurons resulting in inhibition of pain transmission. Capsaicin 8% has been licensed for the treatment of postherpetic neuralgia pain in recent years. A single application of high-concentration capsaicin for 60 minutes for postherpetic neuralgia has been robustly evaluated. Capsaicin 8% patches are applied to the most painful areas of healthy skin and allowed to remain for 60 minutes. Treatment can be repeated every 90 days if the pain persists or returns. The patches are usually applied in specialist pain clinics where patients can be pretreated and monitored. Health care staff need to take certain precautions before administering these patches to avoid unintentional contact. Common adverse effects of the capsaicin 8% patch are transient mild-to-moderate self-limiting application-site burning, pain, erythema, pruritus, papules, swelling, dryness, and hypertension. To manage local pain from capsaicin application, the skin is pretreated with a local anesthetic such as topical lidocaine or an oral analgesic such as oxycodone for up to 5 days. A transient increase in pain is usually seen within 48 hours of patch application before the pain-relieving effect starts. Systemic absorption is minimal and clinically insignificant. The nature of administration and relatively high cost of capsaicin patches can significantly limit their use to a small number of patients with severe refractory symptoms. This review highlights recent evidence related to the use and effectiveness of the 8% capsaicin patch for Postherpetic Neuralgia and discusses its safety and side-effect profiles.

  12. A comprehensive insight into functional profiles of free-living microbial community responses to a toxic Akashiwo sanguinea bloom

    NASA Astrophysics Data System (ADS)

    Yang, Caiyun; Li, Yi; Zhou, Yanyan; Lei, Xueqian; Zheng, Wei; Tian, Yun; van Nostrand, Joy D.; He, Zhili; Wu, Liyou; Zhou, Jizhong; Zheng, Tianling

    2016-10-01

    Phytoplankton blooms are a worldwide problem and can greatly affect ecological processes in aquatic systems, but its impacts on the functional potential of microbial communities are limited. In this study, a high-throughput microarray-based technology (GeoChip) was used to profile the functional potential of free-living microbes from the Xiamen Sea Area in response to a 2011 Akashiwo sanguinea bloom. The bloom altered the overall community functional structure. Genes that were significantly (p < 0.05) increased during the bloom included carbon degradation genes and genes involved in nitrogen (N) and/or phosphorus (P) limitation stress. Such significantly changed genes were well explained by chosen environmental factors (COD, nitrite-N, nitrate-N, dissolved inorganic phosphorus, chlorophyll-a and algal density). Overall results suggested that this bloom might enhance the microbial converting of nitrate to N2 and ammonia nitrogen, decrease P removal from seawater, activate the glyoxylate cycle, and reduce infection activity of bacteriophage. This study presents new information on the relationship of algae to other microbes in aquatic systems, and provides new insights into our understanding of ecological impacts of phytoplankton blooms.

  13. A comprehensive insight into functional profiles of free-living microbial community responses to a toxic Akashiwo sanguinea bloom

    PubMed Central

    Yang, Caiyun; Li, Yi; Zhou, Yanyan; Lei, Xueqian; Zheng, Wei; Tian, Yun; Van Nostrand, Joy D.; He, Zhili; Wu, Liyou; Zhou, Jizhong; Zheng, Tianling

    2016-01-01

    Phytoplankton blooms are a worldwide problem and can greatly affect ecological processes in aquatic systems, but its impacts on the functional potential of microbial communities are limited. In this study, a high-throughput microarray-based technology (GeoChip) was used to profile the functional potential of free-living microbes from the Xiamen Sea Area in response to a 2011 Akashiwo sanguinea bloom. The bloom altered the overall community functional structure. Genes that were significantly (p < 0.05) increased during the bloom included carbon degradation genes and genes involved in nitrogen (N) and/or phosphorus (P) limitation stress. Such significantly changed genes were well explained by chosen environmental factors (COD, nitrite-N, nitrate-N, dissolved inorganic phosphorus, chlorophyll-a and algal density). Overall results suggested that this bloom might enhance the microbial converting of nitrate to N2 and ammonia nitrogen, decrease P removal from seawater, activate the glyoxylate cycle, and reduce infection activity of bacteriophage. This study presents new information on the relationship of algae to other microbes in aquatic systems, and provides new insights into our understanding of ecological impacts of phytoplankton blooms. PMID:27703234

  14. Permeability Profiles and Intestinal Toxicity Assessment of Hydrochlorothiazide and Its Inclusion Complex with β-Cyclodextrin Loaded into Chitosan Nanoparticles.

    PubMed

    Onnainty, R; Schenfeld, E M; Petiti, J P; Longhi, M R; Torres, A; Quevedo, M A; Granero, G E

    2016-11-07

    Here, a novel drug delivery system was developed for the hydrochlorothiazide (HCT):β-cyclodextrin (βCD) inclusion complex loaded into chitosan (CS) nanoparticles (NPs) [CS/HCT:βCD NPs]. It was found, for the first time, that exposure of the intestinal mucosa to free HCT resulted in an increased and abnormal intestinal permeability associated with several injuries to the intestinal epithelium. Nevertheless, the HCT delivery system obtained ameliorated the damage of the intestinal epithelium induced by HCT. Furthermore, we found that the corresponding permeability profiles for both the free HCT and the CS/HCT:βCD NPs were exponential and lineal, respectively. We propose that the increased intestinal uptake and severe tissue injury of HCT to the intestinal epithelium could be directly related to possible effects of this drug on the ionoregulatory Na(+/)K(+)-ATPase channel. Thus, it is postulated that the CS/HCT:βCD NPs may increase the gastrointestinal retention of the HCT, which would provide increased adherence to the mucus barrier that lines the intestinal epithelium; consequently, this would act as a slow HCT release delivery system and maintain lower drug levels of luminal gut in comparison with the administration of free HCT, leading to less severe local injury.

  15. 454 pyrosequencing-based analysis of gene expression profiles in the amphipod Melita plumulosa: transcriptome assembly and toxicant induced changes.

    PubMed

    Hook, Sharon E; Twine, Natalie A; Simpson, Stuart L; Spadaro, David A; Moncuquet, Philippe; Wilkins, Marc R

    2014-08-01

    Next generation sequencing using Roche's 454 pyrosequencing platform can be used to generate genomic information for non-model organisms, although there are bioinformatic challenges associated with these studies. These challenges are compounded by a lack of a standardized protocol to either assemble data or to evaluate the quality of a de novo transcriptome. This study presents an assembly of the control and toxicant responsive transcriptome of Melita plumulosa, an Australian amphipod commonly used in ecotoxicological studies. RNA was harvested from control amphipods, juvenile amphipods, and from amphipods exposed to either metal or diesel contaminated sediments. This RNA was used as the basis for a 454 based transcriptome sequencing effort. Sequencing generated 1.3 million reads from control, juvenile, metal-exposed and diesel-exposed amphipods. Different read filtering and assembly protocols were evaluated to generate an assembly that (i) had an optimal number of contigs; (ii) had long contigs; (iii) contained a suitable representation of conserved genes; and (iv) had long ortholog alignment lengths relative to the length of each contig. A final assembly, generated using fixed-length trimming based on the sequence quality scores, followed by assembly using the MIRA algorithm, produced the best results. The 26,625 contigs generated via this approach were annotated using Blast2GO, and the differential expression between treatments and control was determined by mapping with BWA followed by DESeq. Although the mapping generated low coverage, many differentially expressed contigs, including some with known developmental or toxicological function, were identified. This study demonstrated that 454 pyrosequencing is an effective means of generating reference transcriptome information for organisms, such as the amphipod M. plumulosa, that have no genomic information available in databases or in closely related sequenced species. It also demonstrated how optimization of

  16. Toxicity profiles in mice treated with hepatotumorigenic and non-hepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.

    PubMed

    Allen, James W; Wolf, Douglas C; George, Michael H; Hester, Susan D; Sun, Guobin; Thai, Sheau-Fung; Delker, Don A; Moore, Tanya; Jones, Carlton; Nelson, Gail; Roop, Barbara C; Leavitt, Sharon; Winkfield, Ernest; Ward, William O; Nesnow, Stephen

    2006-01-01

    , propiconazole, and triadimefon, from the nontumorigenic myclobutanil. These findings serve to anchor other transcriptional profiling studies aimed at probing differences in key events and modes of action for tumorigenic and nontumorigenic conazoles.

  17. Profile and outcome of patients with acute toxicity admitted in intensive care unit: Experiences from a major corporate hospital in urban India

    PubMed Central

    Singh, Omender; Javeri, Yash; Juneja, Deven; Gupta, Manish; Singh, Gurpreet; Dang, Rohit

    2011-01-01

    Background and Aim: There is scarcity of data from the Indian subcontinent regarding the profile and outcome of patients presenting with acute poisoning admitted to intensive care units (ICU). We undertook this retrospective analysis to assess the course and outcome of such patients admitted in an ICU of a tertiary care private hospital. Methods: We analyzed data from 138 patients admitted to ICU with acute poisoning between July 2006 and March 2009. Data regarding type of poisoning, time of presentation, reason for ICU admission, ICU course and outcome were obtained. Results: Seventy (50.7%) patients were males and majority (47.8%) of admissions were from age group 21 to 30 years. The most common agents were benzodiazepines, 41/138 (29.7%), followed by alcohol, 34/138 (24.63%) and opioids, 10/138 (7.2%). Thirty-two (23%) consumed two or more agents. Commonest mode of toxicity was suicidal (78.3%) and the route of exposure was mainly oral (97.8%). The highest incidence of toxicity was due to drugs (46.3%) followed by household agents (13%). Organ failure was present in 67 patients (48.5%). During their ICU course, dialysis was required in four, inotropic support in 14 and ventilator support in 13 patients. ICU mortality was 3/138 (2.8%). All deaths were due to aluminium phosphide poisoning. Conclusions: The present data give an insight into epidemiology of poisoning and represents a trend in urban India. The spectrum differs as we cater to urban middle and upper class. There is an increasing variety and complexity of toxins, with substance abuse attributing to significant number of cases. PMID:22013253

  18. Profiling the culprit in Alzheimer's disease (AD): bacterial toxic proteins - Will they be significant for the aetio-pathogenesis of AD and the transmissible spongiform encephalopathies?

    PubMed

    Schmitt, H Peter

    2007-01-01

    The aetiology of Alzheimer's disease (AD) and the transmissible spongiform encephalopathies (tSEs) is still elusive. The concept that prion protein (PrP(Sc)) is the aetiological agent (infectious protein) in the tSEs has recently been questioned. In AD, the cause of the aberrant cleavage of the beta-amyloid precursor protein (APP), resulting in the production of amyloidogenic Abeta fragments, has yet remained obscure. Moreover, the amyloid hypothesis of AD has been seriously challenged. In both AD and the tSEs, pathogens of various nature, including bacteria, have been discussed as possible causal factors. However, aetiological considerations have completely neglected microbial products such as the bacterial toxic proteins (BTPs). The present paper is aimed at drawing a "culprit profile" of these toxic molecules that can exert, at low-dosage, neuro-degeneration through various effects. Clearly, BTPs may affect cell-surface receptors including modulatory amine transmitter receptor expression, block neuro-transmitter release, increase intra-cellular Ca(2+) levels, affect intra-cellular signal transduction, change cyto-skeletal processing, alter synaptic transmission, influence APP proteolysis, interact with cell surface proteins like PrP(C) or their GPI anchors, act as chaperones inducing conformational change in proteins (e.g., PrP(C) to PrP(Sc)), alter lipid membrane integrity by affecting phospholipases or forming pores and channels, induce vacuolar (spongiform) change and elicit inflammatory reactions with cytokine production including cytokines that were demonstrated in the AD brain. Like PrP(Sc), BTPs can be heat-stable and acid-resistant. BTPs can meet the key-proteins of AD and tSEs in the lipid-rich domains of the plasma membrane called rafts. Basically, this might enable them to initiate a large variety of unfavourable molecular events, eventually resulting in pathogenetic cascades as in AD and the tSEs. All in all, their profile lends support to the

  19. Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

    SciTech Connect

    Chen, Yuhchyau Pandya, Kishan J.; Feins, Richard; Johnstone, David W.; Watson, Thomas; Smudzin, Therese; Keng, Peter C.

    2008-06-01

    Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3 pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.

  20. Gene expression profiling of the hippocampal dentate gyrus in an adult toxicity study captures a variety of neurodevelopmental dysfunctions in rat models of hypothyroidism.

    PubMed

    Shiraki, Ayako; Saito, Fumiyo; Akane, Hirotoshi; Akahori, Yumi; Imatanaka, Nobuya; Itahashi, Megu; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    We previously found that developmental hypothyroidism changed the expression of genes in the rat hippocampal dentate gyrus, a brain region where adult neurogenesis is known to occur. In the present study, we performed brain region-specific global gene expression profiling in an adult rat hypothyroidism model to see if it reflected the developmental neurotoxicity we saw in the developmental hypothyroidism model. Starting when male rats were 5 weeks old, we administered 6-propyl-2-thiouracil at a doses of 0, 0.1 and 10 mg kg(-1) body weight by gavage for 28 days. We selected four brain regions to represent both cerebral and cerebellar tissues: hippocampal dentate gyrus, cerebral cortex, corpus callosum and cerebellar vermis. We observed significant alterations in the expression of genes related to neural development (Eph family genes and Robo3) in the cerebral cortex and hippocampal dentate gyrus and in the expression of genes related to myelination (Plp1 and Mbp) in the hippocampal dentate gyrus. We observed only minor changes in the expression of these genes in the corpus callosum and cerebellar vermis. We used real-time reverse-transcription polymerase chain reaction to confirm Chrdl1, Hes5, Mbp, Plp1, Slit1, Robo3 and the Eph family transcript expression changes. The most significant changes in gene expression were found in the dentate gyrus. Considering that the gene expression profile of the adult dentate gyrus closely related to neurogenesis, 28-day toxicity studies looking at gene expression changes in adult hippocampal dentate gyrus may also detect possible developmental neurotoxic effects.

  1. Toxic megacolon

    MedlinePlus

    ... disease - toxic megacolon; Crohn disease - toxic megacolon; Ulcerative colitis - toxic megacolon ... people with an inflamed colon due to: Ulcerative colitis , or Crohn disease that is not well controlled ...

  2. Toxic Synovitis

    MedlinePlus

    ... Feeding Your 1- to 2-Year-Old Toxic Synovitis KidsHealth > For Parents > Toxic Synovitis A A A ... and causes no long-term problems. About Toxic Synovitis Toxic synovitis (also known as transient synovitis ) is ...

  3. Gene Transcription, Metabolite and Lipid Profiling in Eco-Indicator Daphnia magna Indicate Diverse Mechanisms of Toxicity by Legacy and Emerging Flame-Retardants

    EPA Science Inventory

    The use of chemical flame-retardants (FR) in consumer products has steadily increased over the last 30 years. Toxicity data exist for legacy FRs such as pentabromodiphenyl ether (pentaBDE), but less is known about effects of new formulations. To address this issue, the toxicity o...

  4. Toxic substances alert program

    NASA Technical Reports Server (NTRS)

    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.

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

    SciTech Connect

    Deville, Curtiland; Vapiwala, Neha; Hwang, Wei-Ting; Lin Haibo; Bar Ad, Voichita; Tochner, Zelig; Both, Stefan

    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.

  6. Profiling and Racial Profiling: An Interactive Exercise

    ERIC Educational Resources Information Center

    Semple, Philip

    2013-01-01

    Racial Profiling has been recognized as a serious problem that affects many segments of our society and is especially notable in law enforcement. Governments and police services have pronounced that racial profiling is not acceptable and will not be tolerated. They have gone to great lengths in trying to eradicate racial profiling through…

  7. Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA’s ToxRefDB

    EPA Science Inventory

    As the primary source for regulatory developmental toxicity information, prenatal studies characterize maternal effects and fetal endpoints including malformations, resorptions, and fetal weight reduction. Results from 383 rat and 368 rabbit prenatal studies on 387 chemicals, mo...

  8. Toxic Hepatitis

    MedlinePlus

    Toxic hepatitis Overview By Mayo Clinic Staff Toxic hepatitis is an inflammation of your liver in reaction to certain substances to which you're exposed. Toxic hepatitis can be caused by alcohol, chemicals, drugs or ...

  9. Social Acceptance of Wind: A Brief Overview (Presentation)

    SciTech Connect

    Lantz, E.

    2015-01-01

    This presentation discusses concepts and trends in social acceptance of wind energy, profiles recent research findings, and discussions mitigation strategies intended to resolve wind power social acceptance challenges as informed by published research and the experiences of individuals participating in the International Energy Agencies Working Group on Social Acceptance of Wind Energy

  10. Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

    PubMed Central

    O’Connor, Sean Timothy Francis; Lan, Jiaqi; North, Matthew; Loguinov, Alexandre; Zhang, Luoping; Smith, Martyn T.; Gu, April Z.; Vulpe, Chris

    2012-01-01

    Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems. PMID:23403841

  11. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia.

    PubMed

    Aldoss, Ibrahim; Douer, Dan; Behrendt, Carolyn E; Chaudhary, Preeti; Mohrbacher, Ann; Vrona, Janice; Pullarkat, Vinod

    2016-04-01

    Despite having been long regarded as too toxic for adult patients, pediatric-like regimens containing L-asparaginase have resulted in improved outcomes for adults with acute lymphoblastic leukemia (ALL). To characterize the spectrum of toxicity of repeated doses of polyethylene glycolated-asparaginase (PEG-asp) in adults, we reviewed all doses (2000 IU/m(2) ) administered as part of a pediatric-inspired regimen in adult ALL at our center. Subjects aged 18-60 yr with ALL (n = 152, 69.1% male) contributed 522 dose cycles to the study. Hepatotoxicity was the most common adverse event: grades 3-4 transaminitis and hyperbilirubinemia occurred in 53.9% and 23.7% of subjects, respectively. Hepatotoxicity was reversible; no cases of fulminate hepatic failure were observed. Other toxicities affecting at least 5% of subjects were grades 3-4 triglyceridemia in 50.9%, hypofibrinogenemia (<100 mg/dL) in 47.9%, clinical pancreatitis in 12.6%, venous thromboembolism in 11.2%, allergic reaction in 7.2%, and any grade bleeding in 5.3%. PEG-asp was always discontinued after grades 3-4 pancreatitis or allergic reaction. Otherwise, toxicities did not preclude administration of additional cycles of the drug. Our results suggest that repeated PEG-asp dosing is safe in adults aged 18-60 yr, even after occurrence of a drug-related toxicity.

  12. LIMS user acceptance testing.

    PubMed

    Klein, Corbett S

    2003-01-01

    Laboratory Information Management Systems (LIMS) play a key role in the pharmaceutical industry. Thorough and accurate validation of such systems is critical and is a regulatory requirement. LIMS user acceptance testing is one aspect of this testing and enables the user to make a decision to accept or reject implementation of the system. This paper discusses key elements in facilitating the development and execution of a LIMS User Acceptance Test Plan (UATP).

  13. Intra-articular administration of lidocaine plus adrenaline in dogs: Pharmacokinetic profile and evaluation of toxicity in vivo and in vitro.

    PubMed

    Di Salvo, A; Chiaradia, E; della Rocca, G; Mancini, F; Galarini, R; Giusepponi, D; De Monte, V; Cagnardi, P; Marenzoni, M L; Bufalari, A

    2016-02-01

    The aim of this study was to evaluate the safety of intra-articular (IA) lidocaine plus adrenaline for improving peri-operative analgesia in anaesthetized dogs undergoing arthroscopy of the elbow. A solution of lidocaine (L) 1.98% plus adrenaline 1:100.000 was administered via the IA route and its safety evaluated in terms of cardio-, neuro-, and chondro-toxicity. No bradycardia or hypotension was recorded from induction to the last observational time point. Signs of toxicity of the nervous system could have been masked by the general anaesthesia but lidocaine concentrations detected in the blood were lower than those thought to be capable of producing toxicity. The assessment of in vitro chondrotoxicity showed a dose- and time-dependent effect of lidocaine on the viability of articular cells. Adrenaline appeared to reduce the chondrotoxicity of 1% lidocaine, following an exposure of up to 30 min.

  14. On Maximum FODO Acceptance

    SciTech Connect

    Batygin, Yuri Konstantinovich

    2014-12-24

    This note illustrates maximum acceptance of FODO quadrupole focusing channel. Acceptance is the largest Floquet ellipse of a matched beam: A = $\\frac{a^2}{β}$$_{max}$ where a is the aperture of the channel and βmax is the largest value of beta-function in the channel. If aperture of the channel is restricted by a circle of radius a, the s-s acceptance is available for particles oscillating at median plane, y=0. Particles outside median plane will occupy smaller phase space area. In x-y plane, cross section of the accepted beam has a shape of ellipse with truncated boundaries.

  15. Cytochrome P450 Expression Profile of the PICM-19H Pig Liver Cell Line: Potential Application to Rapid Liver Toxicity Assays.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In vitro models of the liver are needed to replace animal models for the rapid assessment of drug biotransformation and toxicity. One hepatocellular model, the PICM-19 pig liver stem cell line, may fulfill this need since these cells have many activities associated with xenobiotic phase I and phas...

  16. Regioselective synthesis and biological profiling of butyric and phenylalkylcarboxylic esters derivated from D-mannose and xylitol: influence of alkyl chain length on acute toxicity.

    PubMed

    Pouillart, P; Douillet, O; Scappini, B; Gozzini, A; Santini, V; Grossi, A; Pagliai, G; Strippoli, P; Rigacci, L; Ronco, G; Villa, P

    1999-01-01

    Regiospecific synthesis of 12 novel n-butyric and phenylalkylcarboxylic monoesters of mannose and xylitol was achieved. The strategy adopted, avoided a tedious intramolecular transesterification step, previously described for the synthesis of analogous compounds and permitted the facile synthesis of a new generation of stable derivatives. The general tolerance of the drugs has been assayed after intravenous administration of a bolus dose into mice. Monobutyric esters showed a low toxicity commensurate with the requirements for future development. A relationship was observed between chain length and toxicity. In contrast, phenylacetic, 3-phenylpropionic and 4-phenylbutyric esters were found to be toxic. Phenylbutyric esters induced marked and specific neuromuscular damage. Preliminary biological investigations of the new series of monobutyric esters showed them to retain the benificial biological properties of butyric acid whilst remaining relatively non toxic. They induced an inhibition of in vitro proliferation of 10 human cases of de novo acute myeloid leukemia (AML) primary cultures and AML established cell lines. AML blasts growth appeared to be blocked and cell differentiation was established. Transcription and expression of maturation markers and finally apoptosis were observed. Moreover, human gamma-chain hemoglobin (HbF) synthesis in erythroleukemia cells was stimulated by monobutyric esters. Mannose and xylitol butyric derivatives would appear to have exciting potential in treatment of beta-Hemoglobinopathies, sickle cell anemia and cancer.

  17. Survey of receiving-water environmental impacts associated with discharges from pulp mills; 1: Mill characteristics, receiving-water chemical profiles and lab toxicity tests

    SciTech Connect

    Robinson, R.D. . Dept. of Environmental Biology); Carey, J.H. . Rivers Research Branch); Solomon, K.R. ); Smith, I.R. . Water Resources Branch); Servos, M.R.; Munkittrick, K.R. . Great Lakes Lab. for Fisheries and Aquatic Sciences)

    1994-07-01

    This survey examined the relationship between environmental responses at pulp mill sites and the pulping process, effluent treatment, and bleaching technology used by pulp mills. This manuscript is the first in a series of four; it reviews the location and operating characteristics of mills included in the survey and provides background information on water chemistry that is relevant to the other components of the survey. In addition, lab 7-d toxicity tests of receiving water were conducted using fathead minnows (Pimephales promelas) and the cladoceran Ceriodaphnia dubia with water samples collected upstream and downstream of effluent discharges at 11 Canadian pulp and paper mills; these samples were collected at the same time as fish surveys were conducted. Survival of fathead minnow larvae was significantly reduced at four of the 11 downstream sites. Ceriodaphnia reproduction was significantly higher at six of the 11 downstream sites and significantly lower at two downstream sites. There were no significant effects on fathead minnow larva growth or adult Ceriodaphnia survival at any of the examined downstream sites. Negative effects in the toxicity tests were generally associated with the low dilution discharge of primary treated effluent with a previous history of acute toxicity. Fathead minnow and Ceriodaphnia tests were generally correlated with historical data on benthic macroinvertebrate community responses. Neither toxicity test predicted the physiological changes in wild fish that are presented in accompanying papers.

  18. Development of safety profile evaluating pharmacokinetics, pharmacodynamics and toxicity of a combination of pioglitazone and olmesartan medoxomil in Wistar albino rats.

    PubMed

    Sengupta, Pinaki; Nandi, Utpal; Pal, Tapan Kumar

    2012-02-01

    Pioglitazone (PIO), an antidiabetic drug and olmesartan medoxomil (OLM), an antihypertensive drug were administered orally alone and in combination to Wistar albino rats for evaluation of pharmacokinetics, pharmacodynamics and repeated dose 28-day oral toxicity of individual drugs and their combination. Pharmacokinetic study was performed by orally administering PIO and OLM at single dose of 3 and 2mg/kg, respectively alone and in combination analyzing the plasma samples using LC-MS/MS. Antidiabetic activity evaluation was done in type-2 diabetes mellitus induced animals at same dose level as in pharmacokinetic study daily for 30 days. PIO and/or OLM were administered orally to animals at daily doses of 50, 100 and 150 mg/kg for 28 days for toxicity study. There was no significant alteration in the pharmacokinetic parameters of either drug indicating absence of any pharmacokinetic interaction when co-administered. Positive pharmacodynamic interaction between PIO and OLM was established in this study. Two drugs in combination showed no evidence of potentiation of 28-day repeated dose toxicity in animals. Again, drugs, alone and in combination, caused only minor changes in clinical-laboratory tests and histopathological change was not found in the experiment performed. In conclusion, PIO and OLM combination can primarily be stated as safe in terms of present toxicity and pharmacokinetics findings.

  19. Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats.

    PubMed

    Ateba, Sylvin Benjamin; Simo, Rudy Valdès; Mbanya, Jean Claude; Krenn, Liselotte; Njamen, Dieudonné

    2014-03-01

    Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL.

  20. Fatty Acid-Derived Pro-Toxicants of the Rat Selective Toxicant Norbormide.

    PubMed

    Choi, Hans; Conole, Daniel; Atkinson, Darcy J; Laita, Olivia; Jay-Smith, Morgan; Pagano, Mario Angelo; Ribaudo, Giovanni; Cavalli, Maurizio; Bova, Sergio; Hopkins, Brian; Brimble, Margaret A; Rennison, David

    2016-06-01

    Norbormide [5-(α-hydroxy-α-2-pyridylbenzyl)-7-(α-2-pyridylbenzylidene)-5-norbornene-2,3-dicarboximide] (NRB), an existing but infrequently used rodenticide, is known to be uniquely toxic to rats but relatively harmless to other rodents and mammals. However, as an acute vasoactive, NRB has a rapid onset of action which makes it relatively unpalatable to rats, often leading to sublethal uptake and accompanying bait shyness. A series of NRB-derived pro-toxicants (3a - i, 4a - i, and 5a - i) were prepared in an effort to 'mask' this acute response and improve both palatability and efficacy. Their synthesis, in vitro biological evaluation (vasocontractile response in rat vasculature, stability in selected rat media) and palatability/efficacy in Sprague-Dawley, wild Norway, and wild ship rats is described. Most notably, pro-toxicant 3d was revealed to be free of all pre-cleavage vasoconstrictory activity in rat caudal artery and was subsequently demonstrated to release NRB in the presence of rat blood, liver, and pancreatic enzymes. Moreover, it consistently displayed a high level of acceptance by rats in a two-choice bait-palatability and efficacy trial, with accompanying high mortality. On this evidence, fatty acid ester prodrugs would appear to offer a promising platform for the further development of NRB-derived toxicants with enhanced palatability and efficacy profiles.

  1. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group.

    PubMed

    Hayakawa, F; Sakura, T; Yujiri, T; Kondo, E; Fujimaki, K; Sasaki, O; Miyatake, J; Handa, H; Ueda, Y; Aoyama, Y; Takada, S; Tanaka, Y; Usui, N; Miyawaki, S; Suenobu, S; Horibe, K; Kiyoi, H; Ohnishi, K; Miyazaki, Y; Ohtake, S; Kobayashi, Y; Matsuo, K; Naoe, T

    2014-10-17

    The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR-ABL-negative ALL. Patients aged 15-24 years (n=139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58-75%) and 73% (95% CI 64-80%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, P<0.001). These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR-ABL-negative ALL.

  2. Laser ablation ICP-MS profiling and semiquantitative determination of trace element concentrations in desert tortoise shells: Documenting the uptake of elemental toxicants

    USGS Publications Warehouse

    Seltzer, M.D.; Berry, K.H.

    2005-01-01

    The outer keratin layer (scute) of desert tortoise shells consists of incrementally grown laminae in which various bioaccumulated trace elements are sequestered during scute deposition. Laser ablation ICP-MS examination of laminae in scutes of dead tortoises revealed patterns of trace elemental distribution from which the chronology of elemental uptake can be inferred. These patterns may be of pathologic significance in the case of elemental toxicants such as arsenic, which has been linked to both shell and respiratory diseases. Laser ablation transects, performed along the lateral surfaces of sectioned scutes, offered the most successful means of avoiding exogenous contamination that was present on the scute exterior. Semiquantitative determination of elemental concentrations was achieved using sulfur, a keratin matrix element, as an internal standard. The results presented here highlight the potential of laser ablation ICP-MS as a diagnostic tool for investigating toxic element uptake as it pertains to tortoise morbidity and mortality.

  3. Comparative In Vitro Toxicity Profile of Electronic and Tobacco Cigarettes, Smokeless Tobacco and Nicotine Replacement Therapy Products: E-Liquids, Extracts and Collected Aerosols

    PubMed Central

    Misra, Manoj; Leverette, Robert D.; Cooper, Bethany T.; Bennett, Melanee B.; Brown, Steven E.

    2014-01-01

    The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic. PMID:25361047

  4. Adaptive Estimation of Personalized Maximum Tolerated Dose in Cancer Phase I Clinical Trials Based on All Toxicities and Individual Genomic Profile

    PubMed Central

    Chen, Zhengjia; Li, Zheng; Zhuang, Run; Yuan, Ying; Kutner, Michael; Owonikoko, Taofeek; Curran, Walter J.; Kowalski, Jeanne

    2017-01-01

    Background Many biomarkers have been shown to be associated with the efficacy of cancer therapy. Estimation of personalized maximum tolerated doses (pMTDs) is a critical step toward personalized medicine, which aims to maximize the therapeutic effect of a treatment for individual patients. In this study, we have established a Bayesian adaptive Phase I design which can estimate pMTDs by utilizing patient biomarkers that can predict susceptibility to specific adverse events and response as covariates. Methods Based on a cutting-edge cancer Phase I clinical trial design called escalation with overdose control using normalized equivalent toxicity score (EWOC-NETS), which fully utilizes all toxicities, we propose new models to incorporate patient biomarker information in the estimation of pMTDs for novel cancer therapeutic agents. The methodology is fully elaborated and the design operating characteristics are evaluated with extensive simulations. Results Simulation studies demonstrate that the utilization of biomarkers in EWOC-NETS can estimate pMTDs while maintaining the original merits of this Phase I trial design, such as ethical constraint of overdose control and full utilization of all toxicity information, to improve the accuracy and efficiency of the pMTD estimation. Conclusions Our novel cancer Phase I designs with inclusion of covariate(s) in the EWOC-NETS model are useful to estimate a personalized MTD and have substantial potential to improve the therapeutic effect of drug treatment. PMID:28125617

  5. Comparative in vitro toxicity profile of electronic and tobacco cigarettes, smokeless tobacco and nicotine replacement therapy products: e-liquids, extracts and collected aerosols.

    PubMed

    Misra, Manoj; Leverette, Robert D; Cooper, Bethany T; Bennett, Melanee B; Brown, Steven E

    2014-10-30

    The use of electronic cigarettes (e-cigs) continues to increase worldwide in parallel with accumulating information on their potential toxicity and safety. In this study, an in vitro battery of established assays was used to examine the cytotoxicity, mutagenicity, genotoxicity and inflammatory responses of certain commercial e-cigs and compared to tobacco burning cigarettes, smokeless tobacco (SLT) products and a nicotine replacement therapy (NRT) product. The toxicity evaluation was performed on e-liquids and pad-collected aerosols of e-cigs, pad-collected smoke condensates of tobacco cigarettes and extracts of SLT and NRT products. In all assays, exposures with e-cig liquids and collected aerosols, at the doses tested, showed no significant activity when compared to tobacco burning cigarettes. Results for the e-cigs, with and without nicotine in two evaluated flavor variants, were very similar in all assays, indicating that the presence of nicotine and flavors, at the levels tested, did not induce any cytotoxic, genotoxic or inflammatory effects. The present findings indicate that neither the e-cig liquids and collected aerosols, nor the extracts of the SLT and NRT products produce any meaningful toxic effects in four widely-applied in vitro test systems, in which the conventional cigarette smoke preparations, at comparable exposures, are markedly cytotoxic and genotoxic.

  6. Developmental Toxicity

    EPA Science Inventory

    This chapter provides an overview the developmental toxicity resulting from exposure to perfluorinated alkyl acids (PFAAs). The majority of studies of PFAA-induced developmental toxicity have examined effects of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA) a...

  7. Newbery Medal Acceptance.

    ERIC Educational Resources Information Center

    Freedman, Russell

    1988-01-01

    Presents the Newbery Medal acceptance speech of Russell Freedman, writer of children's nonfiction. Discusses the place of nonfiction in the world of children's literature, the evolution of children's biographies, and the author's work on "Lincoln." (ARH)

  8. Use of Bevacizumab in Community Settings: Toxicity Profile and Risk of Hospitalization in Patients With Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Carroll, Nikki M.; Delate, Thomas; Menter, Alex; Hornbrook, Mark C.; Kushi, Lawrence; Aiello Bowles, Erin J.; Loggers, Elizabeth T.; Ritzwoller, Debra P.

    2015-01-01

    Purpose: Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non–small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy. Methods: Patients with stages IIIB-IV NSCLC age ≥ 21 years diagnosed between 2005 and 2010 who received first-line CP or CPB were identified at four health maintenance organizations (N = 1,109). Using patient and tumor characteristics and hospital and ambulatory encounters from automated data in the 180 days after chemotherapy initiation, the association between CP and CPB and toxicities and hospitalizations were evaluated with χ2 tests and propensity score–adjusted regression models. Results: Patients who received CPB were significantly younger and had significantly more bleeding, proteinuria, and GI perforation events (all P < .05). For these patients, the unadjusted odds ratio associated with the likelihood of having a hospitalization was 0.46 (95% CI, 0.32 to 0.67). As shown by multivariable and propensity score–adjusted models, patients who received CPB were less likely to have been hospitalized (odds ratio, 0.48; 95% CI, 0.32 to 0.71) and had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47 to 0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47 to 0.60) than patients who received CP. Conclusion: Consistent with earlier randomized clinical trials, significantly more toxicity events were identified in patients treated with CPB. However, both unadjusted and adjusted models showed that patients who received CPB were less likely than patients who received CP to experience a hospital-related event after the initiation of chemotherapy. Findings here confirm the need for adherence to clinical recommendations for judicious use of CPB, but provide reassurance regarding the relative risk for hospitalizations. PMID:26060223

  9. Vertical distribution, composition profiles, sources and toxicity assessment of PAH residues in the reclaimed mudflat sediments from the adjacent Thane Creek of Mumbai.

    PubMed

    Basavaiah, N; Mohite, R D; Singare, P U; Reddy, A V R; Singhal, R K; Blaha, U

    2017-02-23

    A study on vertical distribution of magnetic susceptibility, carcinogenic and endocrine disrupting PAHs was performed in the reclaimed mudflat sediments adjacent to the Thane Creek of Mumbai. The 5-rings PAHs and ΣC-PAHs were more dominant at 120cm depth contributing 52.23% and 60.19% respectively to ∑PAHs. The average ratio values of LMW/HMW PAHs (0.58); Fla/(Fla+Pyr) (0.50); Ant/(Ant+Phe) (0.50); BaA/(Chry+BaA) (0.48); BaP/BghiP (2.06), Phe/Ant (1.03) and BaA/Chr (0.93) indicate that the PAH contamination might have raised due to inefficient combustion and pyrogenic emissions during the open burning of solid waste in the vicinity. This was further supported by the anthropogenic ferri(o)magnetic loading over the last 100years influencing the Creek sediments. The PAHs toxicity estimation was performed by calculating the toxic equivalent quantity (TEQ) value of 8.62ng TEQ/g which was below the safe level (600ng TEQ/g) suggested by the Canadian risk-based soil criterion for protection of human health.

  10. Acute and sub-chronic oral toxicity profiles of lipopeptides from Bacillus mojavensis A21 and evaluation of their in vitro anticoagulant activity.

    PubMed

    Ben Ayed, Hanen; Nasri, Rim; Jemil, Nawel; Ben Amor, Ikram; Gargouri, Jalel; Hmidet, Noomen; Nasri, Moncef

    2015-07-05

    The aim of the present study was to evaluate the acute and sub-chronic toxicity of lipopeptides mixture produced by Bacillus mojavensis A21 as well as their in vitro anticoagulant activity. A21 lipopeptides was given to mice at single dose from 75 mg to 1000 mg/kg body weight (bw). The median lethal dose (LD50) of A21 lipopeptides was about 550 mg/kg bw. Sub-chronic toxicity study for 28 days was done by daily oral administration of A21 lipopeptides at doses of 40 and 400 mg/kg bw in rats. Results showed that A21 lipopeptides did not cause any change in body weights and they did not produce any marked alterations in the hematological blood parameters including hematocrit concentration, hemoglobin level, white and red cells count. However, the platelets level decreased significantly compared to control value. Moreover, no significant differences in the serum biochemical characteristics were observed for rats treated by the lowest dose. In contrast, a little enhancement of alanine-aminotransferase (ALT) activity and decrease in total cholesterol were observed with the highest dose. A21 lipopeptides were also found to cause a prolongation of the thrombin time (TT), the prothrombin time (PT) and the activated partial thromboplastin time (APTT). Overall, A21 lipopeptides may be very promising compounds for therapeutic purposes.

  11. Accepting space radiation risks.

    PubMed

    Schimmerling, Walter

    2010-08-01

    The human exploration of space inevitably involves exposure to radiation. Associated with this exposure are multiple risks, i.e., probabilities that certain aspects of an astronaut's health or performance will be degraded. The management of these risks requires that such probabilities be accurately predicted, that the actual exposures be verified, and that comprehensive records be maintained. Implicit in these actions is the fact that, at some point, a decision has been made to accept a certain level of risk. This paper examines ethical and practical considerations involved in arriving at a determination that risks are acceptable, roles that the parties involved may play, and obligations arising out of reliance on the informed consent paradigm seen as the basis for ethical radiation risk acceptance in space.

  12. Toxicity of a Novel Herbomineral Preparation Las01 on Human Cancer Cell Lines and Its Safety Profile in Humans and Animals

    PubMed Central

    Sheikh, Saba; Srivastava, Ashok; Tripathi, Rajesh; Tripathi, Shalini; Trivedi, V. P.; Saxena, R. C.

    2012-01-01

    Polyhedral formulations based on Rasayana therapy described in Charaka Samhita showed remarkable improvement in quality of life of various cancer patients who have been found to be refractory or poor responders to modern chemotherapy and radiation treatment. One of the most recent novel herbomineral preparation, Las01 prepared absolutely as per the instruction given in the ancient Ayurvedic literature has been found to be effective as a potent anticancer drug in the human cell lines, the MCF-7 and Hela cancer cell lines. This novel preparation of Las01 is also found to be devoid of toxicity both in animals as well as in human subjects, which is the main drawback of chemotherapeutic agents used in modern system of medicine. Our results warrant multicentric clinical trials on a large scale which seems to be a future promising drug to cure incurables cancer patients. PMID:22969832

  13. Toxic responses in rat embryonic cells to silver nanoparticles and released silver ions as analyzed via gene expression profiles and transmission electron microscopy.

    PubMed

    Xu, Liming; Shi, Chang; Shao, Anliang; Li, Xuefei; Cheng, Xiang; Ding, Rigao; Wu, Gang; Chou, Laisheng Lee

    2015-05-01

    After exposing rat embryonic cells to 20 μg/mL of silver nanoparticle (NP) suspension and their released ions for different time periods, silver nanoparticles were found in cellular nuclei, mitochondria, cytoplasm and lysosomes by transmission electron microscopy (TEM). We also observed mitochondrial destruction, distension of endoplasmic reticulum and apoptotic bodies. Global gene expression analysis showed a total of 279 genes that were up-regulated and 389 genes that were down-regulated in the silver-NP suspension exposure group, while 3 genes were up-regulated and 41 genes were down-regulated in the silver ion exposure group. Further, the GO pathway analysis suggested that these differentially expressed genes are involved in several biological processes, such as energy metabolism, oxygen transport, enzyme activities, molecular binding, etc. It is possible that inhibition of oxygen transport is mediated by the significant down-regulation of genes of the globin family, which might play an important role in silver ion-induced toxicity. KEGG pathway analysis showed that there were 23 signal pathways that were affected in the cells after exposure to silver-NP suspension, but not silver ion alone. The most significant change concerned inflammatory signal pathways, which were only found in silver-NP suspension exposed cells, indicating that inflammatory response might play an important role in the mechanism(s) of silver-NP-induced toxicity. The significant up-regulation of matrix metalloproteinases 3 and 9 suggests that silver NPs could induce extracellular matrix degradation via an inflammatory signaling pathway. The significant up-regulation of secretory leukocyte peptidase inhibitor and serine protease inhibitor 2c was considered to be an embryonic cellular defense mechanism in response to silver-NP-induced inflammation.

  14. Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity

    PubMed Central

    Davis, Myrtle; Li, Jianying; Knight, Elaine; Eldridge, Sandy R.; Daniels, Kellye K.; Bushel, Pierre R.

    2015-01-01

    Combinations of anticancer agents may have synergistic anti-tumor effects, but enhanced hematological toxicity often limit their clinical use. We examined whether “microarray profiles” could be used to compare early molecular responses following a single dose of agents administered individually with that of the agents administered in a combination. We compared the mRNA responses within bone marrow of Sprague-Dawley rats after a single 30 min treatment with topotecan at 4.7 mg/kg or oxaliplatin at 15 mg/kg alone to that of sequentially administered combination therapy or vehicle control for 1, 6, and 24 h. We also examined the histopathology of the bone marrow following all treatments. Drug-related histopathological lesions were limited to bone marrow hypocellularity for animals dosed with either agent alone or in combination. Lesions had an earlier onset and higher incidence for animals given topotecan alone or in combination with oxaliplatin. Severity increased from mild to moderate when topotecan was administered prior to oxaliplatin compared with administering oxaliplatin first. Notably, six patterns of co-expressed genes were detected at the 1 h time point that indicate regulatory expression of genes that are dependent on the order of the administration. These results suggest alterations in histone biology, chromatin remodeling, DNA repair, bone regeneration, and respiratory and oxidative phosphorylation are among the prominent pathways modulated in bone marrow from animals treated with an oxaliplatin/topotecan combination. These data also demonstrate the potential for early mRNA patterns derived from target organs of toxicity to inform toxicological risk and molecular mechanisms for agents given in combination. PMID:25729387

  15. Identification and confirmation of ammonia toxicity in contaminated sediments using a modified toxicity identification evaluation approach

    SciTech Connect

    Sprang, P.A. Van; Janssen, C.R.

    1997-12-01

    Toxicity identification of sediment pore waters from four sites in the Upper Scheldt (Belgium) was assessed using a simplified and discriminative toxicity identification evaluation procedure. The samples from all locations exhibited acute toxicity toward the freshwater crustacean Thamnocephalus platyurus. Toxicity was removed or considerably reduced by the cation exchange resins and air stripping at pH 11. In addition, the toxicity of the pore waters was found to be highly pH dependent. Increased toxicity was observed at higher pH levels, whereas reduced toxicity was found at lower pH levels. Based on these results, ammonia was suggested as the main toxic agent. The presence of ammonia concentrations exceeding the 24-h median lethal concentration and comparison of the toxicity characterization profiles of the pore waters with those of the suspected toxicant supported this hypothesis. Furthermore, a significant positive correlation between the observed toxicity of the pore waters and the expected toxicity (due to the presence of the suspected toxicant) confirmed ammonia as the true toxic agent. Finally, the ratio between the expected ammonia toxicity and the observed toxicity from the characterization tests was approx. 1, meaning that all or most of the observed toxicity was caused by the presence of one toxicant (i.e., ammonia). The developed toxicity identification evaluation procedure is suggested as a useful tool for the identification and confirmation of toxicants in contaminated sediments.

  16. Why was Relativity Accepted?

    NASA Astrophysics Data System (ADS)

    Brush, S. G.

    Historians of science have published many studies of the reception of Einstein's special and general theories of relativity. Based on a review of these studies, and my own research on the role of the light-bending prediction in the reception of general relativity, I discuss the role of three kinds of reasons for accepting relativity (1) empirical predictions and explanations; (2) social-psychological factors; and (3) aesthetic-mathematical factors. According to the historical studies, acceptance was a three-stage process. First, a few leading scientists adopted the special theory for aesthetic-mathematical reasons. In the second stage, their enthusiastic advocacy persuaded other scientists to work on the theory and apply it to problems currently of interest in atomic physics. The special theory was accepted by many German physicists by 1910 and had begun to attract some interest in other countries. In the third stage, the confirmation of Einstein's light-bending prediction attracted much public attention and forced all physicists to take the general theory of relativity seriously. In addition to light-bending, the explanation of the advance of Mercury's perihelion was considered strong evidence by theoretical physicists. The American astronomers who conducted successful tests of general relativity became defenders of the theory. There is little evidence that relativity was `socially constructed' but its initial acceptance was facilitated by the prestige and resources of its advocates.

  17. UGV acceptance testing

    NASA Astrophysics Data System (ADS)

    Kramer, Jeffrey A.; Murphy, Robin R.

    2006-05-01

    With over 100 models of unmanned vehicles now available for military and civilian safety, security or rescue applications, it is important to for agencies to establish acceptance testing. However, there appears to be no general guidelines for what constitutes a reasonable acceptance test. This paper describes i) a preliminary method for acceptance testing by a customer of the mechanical and electrical components of an unmanned ground vehicle system, ii) how it has been applied to a man-packable micro-robot, and iii) discusses the value of testing both to ensure that the customer has a workable system and to improve design. The test method automated the operation of the robot to repeatedly exercise all aspects and combinations of components on the robot for 6 hours. The acceptance testing process uncovered many failures consistent with those shown to occur in the field, showing that testing by the user does predict failures. The process also demonstrated that the testing by the manufacturer can provide important design data that can be used to identify, diagnose, and prevent long-term problems. Also, the structured testing environment showed that sensor systems can be used to predict errors and changes in performance, as well as uncovering unmodeled behavior in subsystems.

  18. Approaches to acceptable risk

    SciTech Connect

    Whipple, C.

    1997-04-30

    Several alternative approaches to address the question {open_quotes}How safe is safe enough?{close_quotes} are reviewed and an attempt is made to apply the reasoning behind these approaches to the issue of acceptability of radiation exposures received in space. The approaches to the issue of the acceptability of technological risk described here are primarily analytical, and are drawn from examples in the management of environmental health risks. These include risk-based approaches, in which specific quantitative risk targets determine the acceptability of an activity, and cost-benefit and decision analysis, which generally focus on the estimation and evaluation of risks, benefits and costs, in a framework that balances these factors against each other. These analytical methods tend by their quantitative nature to emphasize the magnitude of risks, costs and alternatives, and to downplay other factors, especially those that are not easily expressed in quantitative terms, that affect acceptance or rejection of risk. Such other factors include the issues of risk perceptions and how and by whom risk decisions are made.

  19. Aminophylline toxicity.

    PubMed

    Albert, S

    1987-02-01

    Aminophylline therapy has undergone change in the past decade. With the changes in usage and dosage forms, the frequency of toxicity in the pediatric population, especially in adolescents, has increased dramatically. Two distinct patterns, chronic and acute, have been recognized and treatment methods for both are changing. Table 4 summarizes the emerging state-of-the-art therapy for aminophylline toxicity. Judging from the activity seen in the literature, investigation into aminophylline toxicity will continue to be a priority. We will see a greater understanding of the disease process and a refining of the therapeutic process. The ultimate goal is the elimination of mortality and the minimization of morbidity from aminophylline toxicity.

  20. Lidocaine toxicity.

    PubMed

    Mehra, P; Caiazzo, A; Maloney, P

    1998-01-01

    Local anesthetics are the most commonly used drugs in dentistry. The number of adverse reactions reported, particularly toxic reactions, are extraordinarily negligible. This article reports a case of lidocaine toxicity with its typical manifestation in a 37-yr-old healthy male. The toxic reaction followed transoral/transpharyngeal topical spraying of lidocaine preoperatively during preparation for general anesthesia. A review of dosages of the most commonly used local anesthetic drugs in dentistry and the management of a toxic reaction is presented. Clinicians need to be in a position to recognize and successfully manage this potential adverse reaction.

  1. Optimization of 4-aminoquinoline/clotrimazole-based hybrid antimalarials: further structure-activity relationships, in vivo studies, and preliminary toxicity profiling.

    PubMed

    Gemma, Sandra; Camodeca, Caterina; Sanna Coccone, Salvatore; Joshi, Bhupendra P; Bernetti, Matteo; Moretti, Vittoria; Brogi, Simone; Bonache de Marcos, Maria Cruz; Savini, Luisa; Taramelli, Donatella; Basilico, Nicoletta; Parapini, Silvia; Rottmann, Matthias; Brun, Reto; Lamponi, Stefania; Caccia, Silvio; Guiso, Giovanna; Summers, Robert L; Martin, Rowena E; Saponara, Simona; Gorelli, Beatrice; Novellino, Ettore; Campiani, Giuseppe; Butini, Stefania

    2012-08-09

    Despite recent progress in the fight against malaria, the emergence and spread of drug-resistant parasites remains a serious obstacle to the treatment of infections. We recently reported the development of a novel antimalarial drug that combines the 4-aminoquinoline pharmacophore of chloroquine with that of clotrimazole-based antimalarials. Here we describe the optimization of this class of hybrid drug through in-depth structure-activity relationship studies. Antiplasmodial properties and mode of action were characterized in vitro and in vivo, and interactions with the parasite's 'chloroquine resistance transporter' were investigated in a Xenopus laevis oocyte expression system. These tests indicated that piperazine derivatives 4b and 4d may be suitable for coadministration with chloroquine against chloroquine-resistant parasites. The potential for metabolism of the drugs by cytochrome P450 was determined in silico, and the lead compounds were tested for toxicity and mutagenicity. A preliminary pharmacokinetic analysis undertaken in mice indicated that compound 4b has an optimal half-life.

  2. 1H NMR-based lipidomics of rodent fur: species-specific lipid profiles and SCD1 inhibitor-related dermal toxicity.

    PubMed

    Khandelwal, Purnima; Stryker, Steven; Chao, Hannguang; Aranibar, Nelly; Lawrence, R Michael; Madireddi, Malavi; Zhao, Wenjun; Chen, Luping; Reily, Michael D

    2014-07-01

    A method is described that allows noninvasive identification and quantitative assessment of lipid classes present in sebaceous excretions in rodents. The method relies on direct high-field proton NMR analysis of common group lipid protons in deuterated organic solvent extracts of fur. Extracts from as little as 15 mg of fur from rat, mouse, and hamster provided acceptable results on a 600 MHz NMR equipped with a cryogenically cooled proton-observe probe. In rats, sex- and age-related differences in lipid composition are larger than differences in fur collected from various body regions within an individual and much larger than interanimal differences in age- and sex-matched specimens. The utility of this method to noninvasively monitor drug-induced sebaceous gland atrophy in rodents is demonstrated in rats dosed with a stearoyl-CoA desaturase 1 (SCD1) inhibitor. In this model, a 35% reduction in sebum lipids, extracted from fur, was observed. Finally, structural elucidation of cholesta-7,24-dien-3β-ol ester as the most prominent, previously unidentified sebum sterol ester in male Syrian hamsters is described. The utility of this method for drug and cosmetic safety and efficacy assessment is discussed.

  3. Toxic Encephalopathy

    PubMed Central

    Kim, Jae Woo

    2012-01-01

    This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

  4. Tungsten toxicity.

    PubMed

    Witten, Mark L; Sheppard, Paul R; Witten, Brandon L

    2012-04-05

    There is emerging evidence that tungsten has toxic health effects. We summarize the recent tungsten toxicity research in this short review. Tungsten is widely used in many commercial and military applications because it has the second highest melting temperature of any element. Consequently, it is important to elucidate the potential health effects of tungsten.

  5. Borocaptate sodium (BSH) toxicity issues

    SciTech Connect

    LaHann, T.

    1995-11-01

    ISU`s Center for Toxicology Research has been conducting toxicity testing of borocaptate sodium (BSH) to aid in assessing if proposed human studies of BSH are likely to be acceptably safe. This report describes BSH interactions with other biological agents.

  6. Acceptability of human risk.

    PubMed

    Kasperson, R E

    1983-10-01

    This paper has three objectives: to explore the nature of the problem implicit in the term "risk acceptability," to examine the possible contributions of scientific information to risk standard-setting, and to argue that societal response is best guided by considerations of process rather than formal methods of analysis. Most technological risks are not accepted but are imposed. There is also little reason to expect consensus among individuals on their tolerance of risk. Moreover, debates about risk levels are often at base debates over the adequacy of the institutions which manage the risks. Scientific information can contribute three broad types of analyses to risk-setting deliberations: contextual analysis, equity assessment, and public preference analysis. More effective risk-setting decisions will involve attention to the process used, particularly in regard to the requirements of procedural justice and democratic responsibility.

  7. Acceptability of human risk.

    PubMed Central

    Kasperson, R E

    1983-01-01

    This paper has three objectives: to explore the nature of the problem implicit in the term "risk acceptability," to examine the possible contributions of scientific information to risk standard-setting, and to argue that societal response is best guided by considerations of process rather than formal methods of analysis. Most technological risks are not accepted but are imposed. There is also little reason to expect consensus among individuals on their tolerance of risk. Moreover, debates about risk levels are often at base debates over the adequacy of the institutions which manage the risks. Scientific information can contribute three broad types of analyses to risk-setting deliberations: contextual analysis, equity assessment, and public preference analysis. More effective risk-setting decisions will involve attention to the process used, particularly in regard to the requirements of procedural justice and democratic responsibility. PMID:6418541

  8. Acceptance Test Plan.

    DTIC Science & Technology

    2014-09-26

    7 RD-Ai507 154 CCEPTANCE TEST PLN(U) WESTINGHOUSE DEFENSE ND i/i ELECTRO ICS CENTER BALTIMORE MD DEVELOPMENT AND OPERATIONS DIY D C KRRiJS 28 JUN...Ln ACCEPTANCE TEST PLAN FOR SPECIAL RELIABILITY TESTS FOR BROADBAND MICROWAVE AMPLIFIER PANEL David C. Kraus, Reliability Engineer WESTINGHOUSE ...ORGANIZATION b. OFFICE SYMBOL 7g& NAME OF MONITORING ORGANIZATION tIf appdeg ble) WESTINGHOUSE ELECTRIC CORP. - NAVAL RESEARCH LABORATORY e. AOORES$ (Ci7t

  9. Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.

    PubMed

    Mangiacavalli, Silvia; Pochintesta, Lara; Pascutto, Cristiana; Cocito, Federica; Pompa, Alessandra; Cazzola, Mario; Corso, Alessandro

    2013-02-01

    Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase.

  10. Ecdysone-Related Biomarkers of Toxicity in the Model Organism Chironomus riparius: Stage and Sex-Dependent Variations in Gene Expression Profiles

    PubMed Central

    Gómez-Sande, Pablo; Ozáez, Irene; Cobo, Fernando; Servia, María J.

    2015-01-01

    Despite being considered a model organism in toxicity studies, particularly in assessing the environmental impact of endocrine disrupting compounds (EDCs) and other chemicals, the molecular basis of development is largely unknown in Chironomus riparius. We have characterized the expression patterns of important genes involved in the ecdysone pathway from embryos to pupa, but specially during the different phases of C. riparius fourth larval instar, according to the development of genital and thoracic imaginal discs. Real-Time PCR was used to analyze: EcR and usp, two genes encoding the two dimerizing partners of the functional ecdysone receptor; E74, an early response gene induced by ecdysteroids; vg (vitellogenin), an effector gene; hsp70 and hsc70, two heat-shock genes involved in the correct folding of the ecdysone receptor; and rpL13, as a part of the ribosomal machinery. Our results show for the first time stage and sex-dependent variations in ecdysone-responsive genes, specially during the late larval stage of C. riparius. The induction in the expression of EcR and usp during the VII-VIII phase of the fourth instar is concomitant with a coordinated response in the activity of the other genes analyzed, suggesting the moment where larvae prepare for pupation. This work is particularly relevant given that most of the analyzed genes have been proposed previously in this species as sensitive biomarkers for the toxicological evaluation of aquatic ecosystems. Identifying the natural regulation of these molecular endpoints throughout the Chironomus development will contribute to a more in-depth and accurate evaluation of the disrupting effects of EDCs in ecotoxicological studies. PMID:26448051

  11. Ecdysone-Related Biomarkers of Toxicity in the Model Organism Chironomus riparius: Stage and Sex-Dependent Variations in Gene Expression Profiles.

    PubMed

    Planelló, Rosario; Herrero, Óscar; Gómez-Sande, Pablo; Ozáez, Irene; Cobo, Fernando; Servia, María J

    2015-01-01

    Despite being considered a model organism in toxicity studies, particularly in assessing the environmental impact of endocrine disrupting compounds (EDCs) and other chemicals, the molecular basis of development is largely unknown in Chironomus riparius. We have characterized the expression patterns of important genes involved in the ecdysone pathway from embryos to pupa, but specially during the different phases of C. riparius fourth larval instar, according to the development of genital and thoracic imaginal discs. Real-Time PCR was used to analyze: EcR and usp, two genes encoding the two dimerizing partners of the functional ecdysone receptor; E74, an early response gene induced by ecdysteroids; vg (vitellogenin), an effector gene; hsp70 and hsc70, two heat-shock genes involved in the correct folding of the ecdysone receptor; and rpL13, as a part of the ribosomal machinery. Our results show for the first time stage and sex-dependent variations in ecdysone-responsive genes, specially during the late larval stage of C. riparius. The induction in the expression of EcR and usp during the VII-VIII phase of the fourth instar is concomitant with a coordinated response in the activity of the other genes analyzed, suggesting the moment where larvae prepare for pupation. This work is particularly relevant given that most of the analyzed genes have been proposed previously in this species as sensitive biomarkers for the toxicological evaluation of aquatic ecosystems. Identifying the natural regulation of these molecular endpoints throughout the Chironomus development will contribute to a more in-depth and accurate evaluation of the disrupting effects of EDCs in ecotoxicological studies.

  12. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

    PubMed

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites

  13. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    PubMed Central

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of

  14. Age and Acceptance of Euthanasia.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1980-01-01

    Study explores relationship between age (and sex and race) and acceptance of euthanasia. Women and non-Whites were less accepting because of religiosity. Among older people less acceptance was attributable to their lesser education and greater religiosity. Results suggest that quality of life in old age affects acceptability of euthanasia. (Author)

  15. Venom of the Coral Snake Micrurus clarki: Proteomic Profile, Toxicity, Immunological Cross-Neutralization, and Characterization of a Three-Finger Toxin

    PubMed Central

    Lomonte, Bruno; Sasa, Mahmood; Rey-Suárez, Paola; Bryan, Wendy; Gutiérrez, José María

    2016-01-01

    Micrurus clarki is an uncommon coral snake distributed from the Southeastern Pacific of Costa Rica to Western Colombia, for which no information on its venom could be found in the literature. Using a ‘venomics’ approach, proteins of at least nine families were identified, with a moderate predominance of three-finger toxins (3FTx; 48.2%) over phospholipase A2 (PLA2; 36.5%). Comparison of this venom profile with those of other Micrurus species suggests that it may represent a more balanced, ‘intermediate’ type within the dichotomy between 3FTx- and PLA2-predominant venoms. M. clarki venom was strongly cross-recognized and, accordingly, efficiently neutralized by an equine therapeutic antivenom against M. nigrocinctus, revealing their high antigenic similarity. Lethal activity for mice could be reproduced by a PLA2 venom fraction, but, unexpectedly, not by fractions corresponding to 3FTxs. The most abundant venom component, hereby named clarkitoxin-I, was identified as a short-chain (type I) 3FTx, devoid of lethal effect in mice, whose target remains to be defined. Its amino acid sequence of 66 residues shows high similarity with predicted sequences of venom gland transcripts described for M. fulvius, M. browni, and M. diastema. PMID:27164141

  16. High acceptance recoil polarimeter

    SciTech Connect

    The HARP Collaboration

    1992-12-05

    In order to detect neutrons and protons in the 50 to 600 MeV energy range and measure their polarization, an efficient, low-noise, self-calibrating device is being designed. This detector, known as the High Acceptance Recoil Polarimeter (HARP), is based on the recoil principle of proton detection from np[r arrow]n[prime]p[prime] or pp[r arrow]p[prime]p[prime] scattering (detected particles are underlined) which intrinsically yields polarization information on the incoming particle. HARP will be commissioned to carry out experiments in 1994.

  17. Baby-Crying Acceptance

    NASA Astrophysics Data System (ADS)

    Martins, Tiago; de Magalhães, Sérgio Tenreiro

    The baby's crying is his most important mean of communication. The crying monitoring performed by devices that have been developed doesn't ensure the complete safety of the child. It is necessary to join, to these technological resources, means of communicating the results to the responsible, which would involve the digital processing of information available from crying. The survey carried out, enabled to understand the level of adoption, in the continental territory of Portugal, of a technology that will be able to do such a digital processing. It was used the TAM as the theoretical referential. The statistical analysis showed that there is a good probability of acceptance of such a system.

  18. Digitalis toxicity

    MedlinePlus

    ... may be rapid, or slow and irregular. An ECG is done to check for irregular heartbeats. Blood ... A. Digitalis toxicity. In: Goldberger AL, ed. Clinical Electrocardiography : A Simplified Approach, 8th ed. Philadelphia, PA: Elsevier ...

  19. Beryllium Toxicity

    MedlinePlus

    ... Digg Facebook Google Bookmarks Yahoo MyWeb Beryllium Toxicity Patient Education Care Instruction Sheet Course : WB 1095 CE Original ... of Contents Introduction Printer-Friendly version of the Patient Education Sheet [PDF - 48 KB] What Is Beryllium? Beryllium ...

  20. Toxic'' terminology

    SciTech Connect

    Powers, J.

    1991-01-01

    A number of terms (e.g., toxic chemicals,'' toxic pollutants,'' toxic waste,'' and similar nomenclature) refer to substances that are subject to regulation under one or more federal environmental laws. State laws and regulations also provide additional, similar, or identical terminology that may be confused with the federally defined terms. Many of these terms appear synonymous, and it is easy to use them interchangeably. However, in a regulatory context, inappropriate use of narrowly defined terms can lead to confusion about the substances referred to, the statutory provisions that may apply, and the regulatory requirements for compliance under the applicable federal statues. This information Brief provides regulatory definitions, a brief discussion of compliance requirements, and reference for the precise terminology that should be used when referring to toxic'' substances regulated under federal environmental laws. A companion CERCLA Information Brief (EH-231-003/0191) addresses hazardous'' nomenclature.

  1. Antimony Toxicity

    PubMed Central

    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 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. PMID:21318007

  2. An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix™ hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children.

    PubMed

    Knuf, Markus; Pantazi-Chatzikonstantinou, Anna; Pfletschinger, Ulrich; Tichmann-Schumann, Irmingard; Maurer, Hartwig; Maurer, Lothar; Fischbach, Thomas; Zinke, Henrike; Pankow-Culot, Heidemarie; Papaevangelou, Vassiliki; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

    2011-06-06

    Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ≥ 97.3% of ACWY-TT vaccinees had rSBA titres ≥ 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ≥ 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.

  3. 21 CFR 801.415 - Maximum acceptable level of ozone.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Maximum acceptable level of ozone. 801.415 Section... level of ozone. (a) Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in...

  4. 21 CFR 801.415 - Maximum acceptable level of ozone.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Maximum acceptable level of ozone. 801.415 Section... level of ozone. (a) Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in...

  5. 21 CFR 801.415 - Maximum acceptable level of ozone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Maximum acceptable level of ozone. 801.415 Section... level of ozone. (a) Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in...

  6. 21 CFR 801.415 - Maximum acceptable level of ozone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Maximum acceptable level of ozone. 801.415 Section... level of ozone. (a) Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in...

  7. 21 CFR 801.415 - Maximum acceptable level of ozone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Maximum acceptable level of ozone. 801.415 Section... level of ozone. (a) Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in...

  8. Continuation rates, bleeding profile acceptability, and satisfaction of women using an oral contraceptive pill containing estradiol valerate and dienogest versus a progestogen-only pill after switching from an ethinylestradiol-containing pill in a real-life setting: results of the CONTENT study

    PubMed Central

    Briggs, Paula; Serrani, Marco; Vogtländer, Kai; Parke, Susanne

    2016-01-01

    Background Oral contraceptives are still associated with high discontinuation rates, despite their efficacy. There is a wide choice of oral contraceptives available, and the aim of this study was to assess continuation rates, bleeding profile acceptability, and the satisfaction of women in the first year of using a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) versus a progestogen-only pill (POP) in a real-life setting after discontinuing an ethinylestradiol-containing pill. Methods and results In this prospective, noninterventional, observational study, 3,152 patients were included for the efficacy analyses (n=2,558 women in the E2V/DNG group and n=592 in the POP group (two patients fulfilled the criteria of the efficacy population, but the used product was not known). Women had been taking an ethinylestradiol-containing pill ≥3 months before deciding to switch to the E2V/DNG pill or a POP. Overall, 19.8% (n=506) of E2V/DNG users and 25.8% (n=153) of POP users discontinued their prescribed pill. The median time to discontinuation was 157.0 days and 127.5 days, respectively. Time to discontinuation due to bleeding (P<0.0001) or other reasons (P=0.022) was significantly longer in the E2V/DNG group versus the POP group. The E2V/DNG pill was also associated with shorter (48.7% vs 44.1%), lighter (54% vs 46.1%), and less painful bleeding (91.1% vs 73.7%) and greater user satisfaction (80.7% vs 64.6%) than POP use, within 3–5 months after switch. Conclusion The E2V/DNG pill was associated with higher rates of continuation, bleeding profile acceptability, and user satisfaction than POP use and may be an alternative option for women who are dissatisfied with their current pill. PMID:27695365

  9. Toxic Myopathies

    PubMed Central

    Pasnoor, Mamatha; Barohn, Richard J.; Dimachkie, Mazen M.

    2014-01-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, as they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features and possible underlying cellular mechanisms. PMID:25037083

  10. Understanding Genetic Toxicity Through Data Mining: The ...

    EPA Pesticide Factsheets

    This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies. This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies.

  11. Sonic boom acceptability studies

    NASA Technical Reports Server (NTRS)

    Shepherd, Kevin P.; Sullivan, Brenda M.; Leatherwood, Jack D.; Mccurdy, David A.

    1992-01-01

    The determination of the magnitude of sonic boom exposure which would be acceptable to the general population requires, as a starting point, a method to assess and compare individual sonic booms. There is no consensus within the scientific and regulatory communities regarding an appropriate sonic boom assessment metric. Loudness, being a fundamental and well-understood attribute of human hearing was chosen as a means of comparing sonic booms of differing shapes and amplitudes. The figure illustrates the basic steps which yield a calculated value of loudness. Based upon the aircraft configuration and its operating conditions, the sonic boom pressure signature which reaches the ground is calculated. This pressure-time history is transformed to the frequency domain and converted into a one-third octave band spectrum. The essence of the loudness method is to account for the frequency response and integration characteristics of the auditory system. The result of the calculation procedure is a numerical description (perceived level, dB) which represents the loudness of the sonic boom waveform.

  12. Toxic remediation

    DOEpatents

    Matthews, Stephen M.; Schonberg, Russell G.; Fadness, David R.

    1994-01-01

    What is disclosed is a novel toxic waste remediation system designed to provide on-site destruction of a wide variety of hazardous organic volatile hydrocarbons, including but not limited to halogenated and aromatic hydrocarbons in the vapor phase. This invention utilizes a detoxification plenum and radiation treatment which transforms hazardous organic compounds into non-hazardous substances.

  13. Cadmium toxicity

    PubMed Central

    Wan, Lichuan; Zhang, Haiyan

    2012-01-01

    Cadmium is a well-known environmental pollutant with distinctly toxic effects on plants. It can displace certain essential metals from a wealth of metalloproteins, and thus disturb many normal physiological processes and cause severe developmental aberrant. The harmful effects of cadmium stress include, but are not limited to: reactive oxygen species overproduction, higher lipid hydroperoxide contents, and chloroplast structure change, which may lead to cell death. Plants have developed diverse mechanisms to alleviate environmental cadmium stress, e.g., cadmium pump and transporting cadmium into the leaf vacuoles. This mini-review focuses on the current research into understanding the cellular mechanisms of cadmium toxicity on cytoskeleton, vesicular trafficking and cell wall formation in plants. PMID:22499203

  14. Toxic gases.

    PubMed Central

    Matthews, G.

    1989-01-01

    An overview of the widespread use of gases and some volatile solvents in modern society is given. The usual circumstances in which undue exposure may occur are described. The most prominent symptoms and general principles of diagnosis and treatment are given and are followed by more specific information on the commoner, more toxic materials. While acute poisonings constitute the greater part of the paper, some indication of chronic disorders arising from repeated or prolonged exposure is also given. PMID:2687827

  15. Studying toxicity

    USGS Publications Warehouse

    Elkus, A.; LeBlanc, L.; Kim, C.; Van Beneden, R.; Mayer, G.

    2006-01-01

    With funding from the George Mitchell Center for the Environment at the University of Maine, a team of scientists used a simple laboratory-based sediment resuspension design, and two well-established aquatic toxicology models, fathead minnows (Pimephales promelas) and zebrafish (Danio rerio), to evaluate if resuspension of Penobscot river sediment significantly elevates the toxicity of river water and to provide preliminary information on the types of chemicals likely to desorb during resuspension. The group collected sediments from two sites with known chemical contamination downstream of the Great Works and Veazie dams. The sediments were examined to determine the dynamics of PAH desorption and degradation under different resuspension frequencies. The scientists used clarified water from resuspension experiments for toxicity tests with the water-flea Ceriodaphnia dubia, and other aquatic test organisms to infer toxicity from sediments from northern California rivers. Data from the study will help ascertain whether metals and/or xenoestrogens are present in the desorption water and give insight into possible avenues of sediment remediation.

  16. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    PubMed Central

    Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

  17. Major pesticides are more toxic to human cells than their declared active principles.

    PubMed

    Mesnage, Robin; Defarge, Nicolas; Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300-600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

  18. Acceptance of tinnitus: validation of the tinnitus acceptance questionnaire.

    PubMed

    Weise, Cornelia; Kleinstäuber, Maria; Hesser, Hugo; Westin, Vendela Zetterqvist; Andersson, Gerhard

    2013-01-01

    The concept of acceptance has recently received growing attention within tinnitus research due to the fact that tinnitus acceptance is one of the major targets of psychotherapeutic treatments. Accordingly, acceptance-based treatments will most likely be increasingly offered to tinnitus patients and assessments of acceptance-related behaviours will thus be needed. The current study investigated the factorial structure of the Tinnitus Acceptance Questionnaire (TAQ) and the role of tinnitus acceptance as mediating link between sound perception (i.e. subjective loudness of tinnitus) and tinnitus distress. In total, 424 patients with chronic tinnitus completed the TAQ and validated measures of tinnitus distress, anxiety, and depression online. Confirmatory factor analysis provided support to a good fit of the data to the hypothesised bifactor model (root-mean-square-error of approximation = .065; Comparative Fit Index = .974; Tucker-Lewis Index = .958; standardised root mean square residual = .032). In addition, mediation analysis, using a non-parametric joint coefficient approach, revealed that tinnitus-specific acceptance partially mediated the relation between subjective tinnitus loudness and tinnitus distress (path ab = 5.96; 95% CI: 4.49, 7.69). In a multiple mediator model, tinnitus acceptance had a significantly stronger indirect effect than anxiety. The results confirm the factorial structure of the TAQ and suggest the importance of a general acceptance factor that contributes important unique variance beyond that of the first-order factors activity engagement and tinnitus suppression. Tinnitus acceptance as measured with the TAQ is proposed to be a key construct in tinnitus research and should be further implemented into treatment concepts to reduce tinnitus distress.

  19. Risk assessment for neurobehavioral toxicity

    SciTech Connect

    McMillan, D.E.

    1987-12-01

    A study of the National Academy of Sciences/National Research Council (NAS/NRC) found neurobehavioral toxicity to be one of the areas where almost no data are available for the assessment of toxicity. Using the NAS/NRC report and a data base from the American Conference of Government Industrial Hygienists (ACGIH), an estimate of the number of neurobehavioral toxins in commercial chemicals can be made. Although the assumption made in making such a calculation may be invalid, the exercise suggests that the number of neurobehavioral toxins may be quite large. There does seem to be general agreement as to what type of neurobehavioral test procedures are appropriate for regulatory purposes. Select committees have consistently recommended the use of test batteries that include schedule-controlled behavior, motor activity, and neuropathological examination following in vivo perfusion, for regulatory purposes. Alkyltin data developed from such a battery were applied to the risk assessment model employed by the United States Environmental Protection Agency (EPA) in their calculations of acceptable daily intake. Using this test battery and the EPA risk assessment model, the acceptable daily intake calculated is of the same order of magnitude as the total limit values established by the ACGIH. A number of special issues in neurobehavioral toxicity also are discussed, including the definition of adverse neurobehavioral toxic effect, species extrapolation, correlation of behavior and neuropathology, alternative methods, and quality of life issues.

  20. Cone penetrometer acceptance test report

    SciTech Connect

    Boechler, G.N.

    1996-09-19

    This Acceptance Test Report (ATR) documents the results of acceptance test procedure WHC-SD-WM-ATR-151. Included in this report is a summary of the tests, the results and issues, the signature and sign- off ATP pages, and a summarized table of the specification vs. ATP section that satisfied the specification.

  1. Thermal Stress and Toxicity

    EPA Science Inventory

    Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral te...

  2. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  3. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  4. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  5. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  6. 40 CFR 799.9110 - TSCA acute oral toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of Prevention, Pesticides, and Toxic Substances (OPPTS) harmonized test guideline 870.1100 (August... of test substance per unit weight of test animal (milligrams per kilogram). (d) Alternative.... EPA will accept three alternative Organization for Economic Cooperation and Development (OECD)...

  7. Extending the Technology Acceptance Model: Policy Acceptance Model (PAM)

    NASA Astrophysics Data System (ADS)

    Pierce, Tamra

    There has been extensive research on how new ideas and technologies are accepted in society. This has resulted in the creation of many models that are used to discover and assess the contributing factors. The Technology Acceptance Model (TAM) is one that is a widely accepted model. This model examines people's acceptance of new technologies based on variables that directly correlate to how the end user views the product. This paper introduces the Policy Acceptance Model (PAM), an expansion of TAM, which is designed for the analysis and evaluation of acceptance of new policy implementation. PAM includes the traditional constructs of TAM and adds the variables of age, ethnicity, and family. The model is demonstrated using a survey of people's attitude toward the upcoming healthcare reform in the United States (US) from 72 survey respondents. The aim is that the theory behind this model can be used as a framework that will be applicable to studies looking at the introduction of any new or modified policies.

  8. The "Barnum Effect" and Acceptance of Negative Personal Evaluation

    ERIC Educational Resources Information Center

    Dmitruk, Victor M.; And Others

    1973-01-01

    Rokeach's value survey and Maxhover's Figure Drawing Tests were administered to two groups of college students. Subjects were then given bogus personality profiles. They were equally likely to accept positive and negative personal evaluations irrespective of whether the tests on which they were purportedly based were scored and interpreted'' by a…

  9. Toxic terror

    SciTech Connect

    Whelan, E.M.

    1985-01-01

    A review of toxic materials in the environment explores the evolution of public awareness of the problem, public and governmental reaction, the effort to establish standards of safe levels and danger thresholds, and the struggle to implement and enforce environmental policy. Separate chapters deal with environmental premises and scientific realities, the DDT debate and birth of environmentalism, the disaster of Love Canal, pesticides, PCBs, PBBs, formaldehyde, dioxin, air pollution, water pollution, nuclear energy and radioactive materials, acid rain, and the status of American health. The book concludes with a chapter on the need for scientific research and hard evidence to either prove or disprove the pessimism of those who warn of a threat to human health and survival.

  10. Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

    SciTech Connect

    Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

    2011-07-15

    Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

  11. Market Acceptance of Smart Growth

    EPA Pesticide Factsheets

    This report finds that smart growth developments enjoy market acceptance because of stability in prices over time. Housing resales in smart growth developments often have greater appreciation than their conventional suburban counterparts.

  12. L-286 Acceptance Test Record

    SciTech Connect

    HARMON, B.C.

    2000-01-14

    This document provides a detailed account of how the acceptance testing was conducted for Project L-286, ''200E Area Sanitary Water Plant Effluent Stream Reduction''. The testing of the L-286 instrumentation system was conducted under the direct supervision

  13. Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules.

    PubMed

    Nobre, Lígia S; Jeremias, Hélia; Romão, Carlos C; Saraiva, Lígia M

    2016-01-28

    can show opposite toxicity profiles towards bacteria and eukaryotic cells; (ii) their activity can be modulated through manipulation of the ancillary ligands, as shown with the three {Ru(CO)3}(2+) and two zerovalent Mo based CORMs; and (iii) their toxicity to eukaryotic cells can be made acceptably low. With this new approach, this work contributes to the understanding of the roots of the bactericidal action of CORMs and helps in establishing strategies for their development into a new class of antibiotics.

  14. Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities.

    PubMed

    Kollmannsberger, Christian; Bjarnason, Georg; Burnett, Patrick; Creel, Patricia; Davis, Mellar; Dawson, Nancy; Feldman, Darren; George, Suzanne; Hershman, Jerome; Lechner, Thomas; Potter, Amy; Raymond, Eric; Treister, Nathaniel; Wood, Laura; Wu, Shenhong; Bukowski, Ronald

    2011-01-01

    The multitargeted tyrosine-kinase inhibitor sunitinib has emerged as one of the standards of care for good- and intermediate-risk metastatic renal cell carcinoma. Although generally associated with acceptable toxicity, sunitinib exhibits a novel and distinct toxicity profile that requires monitoring and management. Fatigue, diarrhea, anorexia, oral changes, hand-foot syndrome and other skin toxicity, thyroid dysfunction, myelotoxicity, and hypertension seem to be the most common and clinically relevant toxicities of sunitinib. Drug dosing and treatment duration are correlated with response to treatment and survival. Treatment recommendations for hypertension have been published but, currently, no standard guidelines exist for the management of noncardiovascular side effects. To discuss the optimal management of noncardiovascular side effects, an international, interdisciplinary panel of experts gathered in November 2009. Existing literature on incidence, severity, and underlying mechanisms of side effects as well as on potential treatment options were carefully reviewed and discussed. On the basis of these proceedings and the thorough review of the existing literature, recommendations were made for the monitoring, prevention, and treatment of the most common noncardiovascular side effects and are summarized in this review. The proactive assessment and consistent and timely management of sunitinib-related side effects are critical to ensure optimal treatment benefit by allowing appropriate drug dosing and prolonged treatment periods.

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26962011

  17. Chronic toxicity of biphenyl to Daphnia magna Straus

    SciTech Connect

    Gersich, F.M.; Bartlett, E.A.; Murphy, P.G.; Milazzo, D.P. )

    1989-09-01

    The US Environmental Protection Agency (EPA) issued a final test rule (1985) for biphenyl on the authority of Section 4(a) of the Toxic Substances Control Act (TSCA). Contained within this rule was the requirement for generating chronic daphnid toxicity data for biphenyl. Biphenyl is used primarily to produce dye carriers, heat-transfer fluids and alkylated biphenyls. The acute toxicity of biphenyl to Daphnia magna has been reported. The 48-hr LC50 values were 4.7 and 2.1 mg/L, respectively. To date, the chronic toxicity of biphenyl to fish and aquatic invertebrates has not been investigated. The objective of this study was to determine the chronic toxicity of biphenyl to D. magna. The daphnid chronic toxicity test is designed to estimate the maximum acceptable toxicant concentration (MATC). The MATC is defined as the concentration falling between the highest concentration showing no effect and the next higher concentration showing a toxic effect when compared to the controls.

  18. From requirements to acceptance tests

    NASA Technical Reports Server (NTRS)

    Baize, Lionel; Pasquier, Helene

    1993-01-01

    From user requirements definition to accepted software system, the software project management wants to be sure that the system will meet the requirements. For the development of a telecommunication satellites Control Centre, C.N.E.S. has used new rules to make the use of tracing matrix easier. From Requirements to Acceptance Tests, each item of a document must have an identifier. A unique matrix traces the system and allows the tracking of the consequences of a change in the requirements. A tool has been developed, to import documents into a relational data base. Each record of the data base corresponds to an item of a document, the access key is the item identifier. Tracing matrix is also processed, providing automatically links between the different documents. It enables the reading on the same screen of traced items. For example one can read simultaneously the User Requirements items, the corresponding Software Requirements items and the Acceptance Tests.

  19. Defining acceptable conditions in wilderness

    NASA Astrophysics Data System (ADS)

    Roggenbuck, J. W.; Williams, D. R.; Watson, A. E.

    1993-03-01

    The limits of acceptable change (LAC) planning framework recognizes that forest managers must decide what indicators of wilderness conditions best represent resource naturalness and high-quality visitor experiences and how much change from the pristine is acceptable for each indicator. Visitor opinions on the aspects of the wilderness that have great impact on their experience can provide valuable input to selection of indicators. Cohutta, Georgia; Caney Creek, Arkansas; Upland Island, Texas; and Rattlesnake, Montana, wilderness visitors have high shared agreement that littering and damage to trees in campsites, noise, and seeing wildlife are very important influences on wilderness experiences. Camping within sight or sound of other people influences experience quality more than do encounters on the trails. Visitors’ standards of acceptable conditions within wilderness vary considerably, suggesting a potential need to manage different zones within wilderness for different clientele groups and experiences. Standards across wildernesses, however, are remarkably similar.

  20. Sediment Toxicity Identification Evaluation

    EPA Science Inventory

    Approach combining chemical manipulations and aquatic toxicity testing, generally with whole organisms, to systematically characterize, identify and confirm toxic substances causing toxicity in whole sediments and sediment interstitial waters. The approach is divided into thre...

  1. Idaho CERCLA Disposal Facility Complex Waste Acceptance Criteria

    SciTech Connect

    W. Mahlon Heileson

    2006-10-01

    The Idaho Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Disposal Facility (ICDF) has been designed to accept CERCLA waste generated within the Idaho National Laboratory. Hazardous, mixed, low-level, and Toxic Substance Control Act waste will be accepted for disposal at the ICDF. The purpose of this document is to provide criteria for the quantities of radioactive and/or hazardous constituents allowable in waste streams designated for disposal at ICDF. This ICDF Complex Waste Acceptance Criteria is divided into four section: (1) ICDF Complex; (2) Landfill; (3) Evaporation Pond: and (4) Staging, Storage, Sizing, and Treatment Facility (SSSTF). The ICDF Complex section contains the compliance details, which are the same for all areas of the ICDF. Corresponding sections contain details specific to the landfill, evaporation pond, and the SSSTF. This document specifies chemical and radiological constituent acceptance criteria for waste that will be disposed of at ICDF. Compliance with the requirements of this document ensures protection of human health and the environment, including the Snake River Plain Aquifer. Waste placed in the ICDF landfill and evaporation pond must not cause groundwater in the Snake River Plain Aquifer to exceed maximum contaminant levels, a hazard index of 1, or 10-4 cumulative risk levels. The defined waste acceptance criteria concentrations are compared to the design inventory concentrations. The purpose of this comparison is to show that there is an acceptable uncertainty margin based on the actual constituent concentrations anticipated for disposal at the ICDF. Implementation of this Waste Acceptance Criteria document will ensure compliance with the Final Report of Decision for the Idaho Nuclear Technology and Engineering Center, Operable Unit 3-13. For waste to be received, it must meet the waste acceptance criteria for the specific disposal/treatment unit (on-Site or off-Site) for which it is destined.

  2. Further Conceptualization of Treatment Acceptability

    ERIC Educational Resources Information Center

    Carter, Stacy L.

    2008-01-01

    A review and extension of previous conceptualizations of treatment acceptability is provided in light of progress within the area of behavior treatment development and implementation. Factors including legislation, advances in research, and service delivery models are examined as to their relationship with a comprehensive conceptualization of…

  3. Acceptance and Commitment Therapy: Introduction

    ERIC Educational Resources Information Center

    Twohig, Michael P.

    2012-01-01

    This is the introductory article to a special series in Cognitive and Behavioral Practice on Acceptance and Commitment Therapy (ACT). Instead of each article herein reviewing the basics of ACT, this article contains that review. This article provides a description of where ACT fits within the larger category of cognitive behavior therapy (CBT):…

  4. Nitrogen trailer acceptance test report

    SciTech Connect

    Kostelnik, A.J.

    1996-02-12

    This Acceptance Test Report documents compliance with the requirements of specification WHC-S-0249. The equipment was tested according to WHC-SD-WM-ATP-108 Rev.0. The equipment being tested is a portable contained nitrogen supply. The test was conducted at Norco`s facility.

  5. Imaginary Companions and Peer Acceptance

    ERIC Educational Resources Information Center

    Gleason, Tracy R.

    2004-01-01

    Early research on imaginary companions suggests that children who create them do so to compensate for poor social relationships. Consequently, the peer acceptance of children with imaginary companions was compared to that of their peers. Sociometrics were conducted on 88 preschool-aged children; 11 had invisible companions, 16 had personified…

  6. Euthanasia Acceptance: An Attitudinal Inquiry.

    ERIC Educational Resources Information Center

    Klopfer, Fredrick J.; Price, William F.

    The study presented was conducted to examine potential relationships between attitudes regarding the dying process, including acceptance of euthanasia, and other attitudinal or demographic attributes. The data of the survey was comprised of responses given by 331 respondents to a door-to-door interview. Results are discussed in terms of preferred…

  7. Helping Our Children Accept Themselves.

    ERIC Educational Resources Information Center

    Gamble, Mae

    1984-01-01

    Parents of a child with muscular dystrophy recount their reactions to learning of the diagnosis, their gradual acceptance, and their son's resistance, which was gradually lessened when he was provided with more information and treated more normally as a member of the family. (CL)

  8. Toxic Shock Syndrome

    MedlinePlus

    ... burn to avoid getting a staph infection. Toxic shock syndrome treatment Because toxic shock syndrome gets worse quickly, you may be seriously ... toxic shock syndrome in a wound? Resources Toxic Shock Syndrome ... treatment, women's health Family Health, Women January 2017 Copyright © ...

  9. Health and Environmental Effects Profile for ethyl methacrylate

    SciTech Connect

    Not Available

    1986-06-01

    The Health and Environmental Effects Profile for ethyl methacrylate was prepared to support listings of hazardous constituents of a wide range of waste streams under Section 3001 of the Resource Conservation and Recovery Act (RCRA) and to provide health-related limits for emergency actions under Section 101 of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). Both published literature and information obtained from Agency program office files were evaluated as they pertained to potential human health, aquatic life and environmental effects. Quantitative estimates are presented provided sufficient data are available. Ethyl methacrylate has been determined to be a systemic toxicant. An acceptable daily intake (ADI) for ethyl methacrylate is 0.086 mg/kg/day for oral exposure.

  10. Acceptability of reactors in space

    SciTech Connect

    Buden, D.

    1981-01-01

    Reactors are the key to our future expansion into space. However, there has been some confusion in the public as to whether they are a safe and acceptable technology for use in space. The answer to these questions is explored. The US position is that when reactors are the preferred technical choice, that they can be used safely. In fact, it does not appear that reactors add measurably to the risk associated with the Space Transportation System.

  11. Acceptability of reactors in space

    SciTech Connect

    Buden, D.

    1981-04-01

    Reactors are the key to our future expansion into space. However, there has been some confusion in the public as to whether they are a safe and acceptable technology for use in space. The answer to these questions is explored. The US position is that when reactors are the preferred technical choice, that they can be used safely. In fact, it dies not appear that reactors add measurably to the risk associated with the Space Transportation System.

  12. Assessing aquatic terrestrial toxicity

    SciTech Connect

    Hall, W.S.; Mirenda, R.J.

    1993-06-01

    it is recognized that the toxic effects of environmental samples cannot be predicted based on chemical concentration data alone. The EPA recommends an integrated approach that uses both chemical specific and whole effluent toxicity testing methods to control effluent toxicity. Toxicity tests allow for the consideration of site-specific factors that may increase or decrease the toxicity of a chemical in a given medium.

  13. Consumer studies on sensory acceptability of boar taint: a review.

    PubMed

    Font-i-Furnols, Maria

    2012-12-01

    Boar taint can be found in meat from boars and affects consumer acceptability of pork. The aim of this review is: (1) to describe different aspects of the existing methodologies used in consumer studies when evaluating boar taint from a sensory point of view, (2) to draw conclusions on different studies regarding the acceptability of meat from entire males, and (3) to discuss a possible harmonization of the different aspects to be considered when performing consumer studies on boar taint. This paper focuses on different aspects of studies previously carried out such as the country of assessment, the location of the test, the cooking procedure, the type of meat samples evaluated, the attributes and scales used, consumer profile, the results obtained, and the effect of androstenone sensitivity of the consumers on boar meat acceptability. A discussion on the possibility of a harmonization of the different aspects is also performed and final remarks and considerations have been drawn.

  14. Toxicity and repellency to rats of actidione

    USGS Publications Warehouse

    Traub, R.; DeWitt, J.B.; Welch, J.F.; Newman, D.

    1950-01-01

    The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards. Rats refused to accept food or water containing this material even under conditions of acute starvation and died of starvation and thirst,rather than accept water containing l.0 mg. of actidione per liter. The compound is highly toxic to .rats with the minimum .lethal dose by oral administration being approximately l.0 mg./Kg body weight. Paperboard treated with the compound resisted gnawing attacks by specially trained and motivated rats for periods of two hundred hours, although similar .untreated boards were pierced within thirty-to sixty minutes.

  15. Practical Differential Profiling

    SciTech Connect

    Schulz, M; De Supinski, B R

    2007-02-04

    Comparing performance profiles from two runs is an essential performance analysis step that users routinely perform. In this work we present eGprof, a tool that facilitates these comparisons through differential profiling inside gprof. We chose this approach, rather than designing a new tool, since gprof is one of the few performance analysis tools accepted and used by a large community of users. eGprof allows users to 'subtract' two performance profiles directly. It also includes callgraph visualization to highlight the differences in graphical form. Along with the design of this tool, we present several case studies that show how eGprof can be used to find and to study the differences of two application executions quickly and hence can aid the user in this most common step in performance analysis. We do this without requiring major changes on the side of the user, the most important factor in guaranteeing the adoption of our tool by code teams.

  16. Virtual Embryo: Systems Modeling in Developmental Toxicity

    EPA Science Inventory

    High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

  17. Axelrod model: accepting or discussing

    NASA Astrophysics Data System (ADS)

    Dybiec, Bartlomiej; Mitarai, Namiko; Sneppen, Kim

    2012-10-01

    Agents building social systems are characterized by complex states, and interactions among individuals can align their opinions. The Axelrod model describes how local interactions can result in emergence of cultural domains. We propose two variants of the Axelrod model where local consensus is reached either by listening and accepting one of neighbors' opinion or two agents discuss their opinion and achieve an agreement with mixed opinions. We show that the local agreement rule affects the character of the transition between the single culture and the multiculture regimes.

  18. 76 FR 23600 - Availability of Draft Toxicological Profile

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Availability of Draft Toxicological Profile AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), Department of Health and Human... Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, Mailstop F- 62,...

  19. 75 FR 71132 - Availability of Draft Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Availability of Draft Toxicological Profiles AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), Department of Health and Human... Medicine, Agency for Toxic Substances and Disease Registry, Mailstop F-62, 1600 Clifton Road, NE.,...

  20. Automated Test Systems for Toxic Vapor Detectors

    NASA Technical Reports Server (NTRS)

    Mattson, C. B.; Hammond, T. A.; Schwindt, C. J.

    1997-01-01

    The NASA Toxic Vapor Detection Laboratory (TVDL) at the Kennedy Space Center (KSC), Florida, has been using Personal Computer based Data Acquisition and Control Systems (PCDAS) for about nine years. These systems control the generation of toxic vapors of known concentrations under controlled conditions of temperature and humidity. The PCDAS also logs the test conditions and the test article responses in data files for analysis by standard spreadsheets or custom programs. The PCDAS was originally developed to perform standardized qualification and acceptance tests in a search for a commercial off-the-shelf (COTS) toxic vapor detector to replace the hydrazine detectors for the Space Shuttle launch pad. It has since become standard test equipment for the TVDL and is indispensable in producing calibration standards for the new hydrazine monitors at the 10 part per billion (ppb) level. The standard TVDL PCDAS can control two toxic vapor generators (TVG's) with three channels each and two flow/temperature/humidity (FIFH) controllers and it can record data from up to six toxic vapor detectors (TVD's) under test and can deliver flows from 5 to 50 liters per minute (L/m) at temperatures from near zero to 50 degrees Celsius (C) using an environmental chamber to maintain the sample temperature. The concentration range for toxic vapors depends on the permeation source installed in the TVG. The PCDAS can provide closed loop control of temperature and humidity to two sample vessels, typically one for zero gas and one for the standard gas. This is required at very low toxic vapor concentrations to minimize the time required to passivate the sample delivery system. Recently, there have been several requests for information about the PCDAS by other laboratories with similar needs, both on and off KSC. The purpose of this paper is to inform the toxic vapor detection community of the current status and planned upgrades to the automated testing of toxic vapor detectors at the Kennedy

  1. Learning Style Profile: Examiner's Manual.

    ERIC Educational Resources Information Center

    Keefe, James W.; Monk, John S.

    This examiner's manual accompanies the Learning Style Profile (LSP), which measures cognitive skills as well as affective and environmental preferences. Charles Letteri's General Operations Model was accepted as the prototype for relating learning styles to cognitive information processing. The LSP was developed from 1983 to 1986; several versions…

  2. Toxic Shock Syndrome

    MedlinePlus

    ... toxic shock syndrome results from toxins produced by Staphylococcus aureus (staph) bacteria, but the condition may also ... a skin or wound infection. Bacteria, most commonly Staphylococcus aureus (staph), causes toxic shock syndrome. It can ...

  3. Sediment Toxicity Testing

    EPA Science Inventory

    Sediment toxicity testing has become a fundamental component of regulatory frameworks for assessing the risks posed by contaminated sediments and for development of chemical sediment quality guidelines. Over the past two decades, sediment toxicity testing methods have advanced co...

  4. Whole Effluent Toxicity (WET)

    EPA Pesticide Factsheets

    Whole Effluent Toxicity (WET) describes the aggregate toxic effect of an aqueous sample (e.g., whole effluent wastewater discharge) as measured by an organism's response upon exposure to the sample (e.g., lethality, impaired growth, or reproduction).

  5. State Profiles.

    ERIC Educational Resources Information Center

    State-Federal Information Clearinghouse for Exceptional Children, Reston, VA.

    State-by-state public policy profiles are provided by the Council for Exceptional Children's State-Federal Information Clearinghouse. These profiles summarize the present legal base for the delivery of educational services to handicapped children in the United States. Included in each profile is information from various avenues used to establish…

  6. Toxic gases from fires.

    PubMed

    Terrill, J B; Montgomery, R R; Reinhardt, C F

    1978-06-23

    The major lethal factors in uncontrolled fires are toxic gases, heat, and oxygen deficiency. The predominant toxic gas is carbon monoxide, which is readily generated from the combusion of wood and other cellulosic materials. Increasing use of a variety of synthetic polymers has stimulated interest in screening tests to evaluated the toxicity of polymeric materials when thermally decomposed. As yet, this country lacks a standardized fire toxicity test protocol.

  7. How Toxic Is It?

    ERIC Educational Resources Information Center

    Crellin, John R.

    1989-01-01

    Discusses the relative danger from toxicity of some typical chemicals. Notes that some materials in solutions have low toxicity, but in dust form have high toxicity. Suggests that more chemical compounds should be treated as the dangerous compounds they are. Lists common compounds found in the lab. (MVL)

  8. Studying Student Teachers' Acceptance of Role Responsibility.

    ERIC Educational Resources Information Center

    Davis, Michael D.; Davis, Concetta M.

    1980-01-01

    There is variance in the way in which student teachers accept responsibility for the teaching act. This study explains why some variables may affect student teachers' acceptance of role responsibilities. (CM)

  9. [Subjective well-being and self acceptance].

    PubMed

    Makino, Y; Tagami, F

    1998-06-01

    The purpose of the present study was to examine the relationship between subjective well-being and self acceptance, and to design a happiness self-writing program to increase self acceptance and subjective well-being of adolescents. In study 1, we examined the relationship between social interaction and self acceptance. In study 2, we created a happiness self-writing program in cognitive behavioral approach, and examined whether the program promoted self acceptance and subjective well-being. Results indicated that acceptance of self-openness, an aspect of self acceptance, was related to subjective well-being. The happiness self-writing program increased subjective well-being, but it was not found to have increased self acceptance. It was discussed why the program could promote subjective well-being, but not self acceptance.

  10. 78 FR 43205 - Proposed Substances To Be Evaluated for Set 27 Toxicological Profiles

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ... HUMAN SERVICES Agency for Toxic Substances and Disease Registry Proposed Substances To Be Evaluated for Set 27 Toxicological Profiles AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR... evaluated for Set 27 toxicological profiles. SUMMARY: The Agency for Toxic Substances and Disease...

  11. Relative toxicity of materials in fire situations

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Cumming, H. J.; Casey, C. J.

    1978-01-01

    The results of toxicity testing of additional materials is presented. Relative toxicity data on polymers by generic type are presented and include wood, polyurethane flexible foam, polyvinyl chloride (PVC), acrylonitrile/butadiene/styrene (ABS), and polyisoprene (natural rubber). A second table gives relative toxicity data on fibers and fabrics including wool, nylon, rayon, polyester, and aromatic polyamide. Sulfur-containing materials seemed to exhibit the shortest times to death of laboratory animals. Some chlorine-containing polymers tended to exhibit shortest time to death also while some halogen-containing polymers gave the shortest time to incapacitation. Among fibers and fabrics, wool, silk, and polyester exhibited the shortest times to incapacitation and times to death. Difficulty in restricting generally accepted materials is discussed and attention is given to other factors important in comparing materials, such as backcoatings and relative weights.

  12. Death Attitudes Across the Life-Span: The Development and Validation of the Death Attitude Profile (DAP).

    ERIC Educational Resources Information Center

    Gesser, Gina; And Others

    1988-01-01

    The Death Attitude Profile was developed and four orthogonal factors were identified: Fear of Death/Dying, Approach-Oriented Death Acceptance, Escape-Oriented Death Acceptance, and Neutral Death Acceptance. An elderly sample (N=50) showed less fear of death and more acceptance (all three kinds of acceptance) than did middle aged (N=50) and young…

  13. Decision support tools for proton therapy ePR: intelligent treatment planning navigator and radiation toxicity tool for evaluating of prostate cancer treatment

    NASA Astrophysics Data System (ADS)

    Le, Anh H.; Deshpande, Ruchi; Liu, Brent J.

    2010-03-01

    The electronic patient record (ePR) has been developed for prostate cancer patients treated with proton therapy. The ePR has functionality to accept digital input from patient data, perform outcome analysis and patient and physician profiling, provide clinical decision support and suggest courses of treatment, and distribute information across different platforms and health information systems. In previous years, we have presented the infrastructure of a medical imaging informatics based ePR for PT with functionality to accept digital patient information and distribute this information across geographical location using Internet protocol. In this paper, we present the ePR decision support tools which utilize the imaging processing tools and data collected in the ePR. The two decision support tools including the treatment plan navigator and radiation toxicity tool are presented to evaluate prostate cancer treatment to improve proton therapy operation and improve treatment outcomes analysis.

  14. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  15. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  16. Older Adults' Acceptance of Information Technology

    ERIC Educational Resources Information Center

    Wang, Lin; Rau, Pei-Luen Patrick; Salvendy, Gavriel

    2011-01-01

    This study investigated variables contributing to older adults' information technology acceptance through a survey, which was used to find factors explaining and predicting older adults' information technology acceptance behaviors. Four factors, including needs satisfaction, perceived usability, support availability, and public acceptance, were…

  17. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  18. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  19. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  20. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  1. 46 CFR 28.73 - Accepted organizations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Accepted organizations. 28.73 Section 28.73 Shipping... INDUSTRY VESSELS General Provisions § 28.73 Accepted organizations. An organization desiring to be designated by the Commandant as an accepted organization must request such designation in writing. As...

  2. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... offered have either achieved commercial market acceptance or been satisfactorily supplied to an agency... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance....

  3. 21 CFR 820.86 - Acceptance status.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Acceptance status. 820.86 Section 820.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Acceptance Activities § 820.86 Acceptance status. Each manufacturer...

  4. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  5. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) 41 U.S...) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an agency under current...

  6. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Market acceptance. 2911.103... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  7. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... either— (i) Achieved commercial market acceptance; or (ii) Been satisfactorily supplied to an...

  8. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  9. 48 CFR 2911.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Market acceptance. 2911... DESCRIBING AGENCY NEEDS Selecting And Developing Requirements Documents 2911.103 Market acceptance. The... offered have either achieved commercial market acceptance or been satisfactorily supplied to an...

  10. Toxic Hazards Research Unit

    NASA Technical Reports Server (NTRS)

    Macewen, J. D.; Vernot, E. H.

    1971-01-01

    The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

  11. Propylene Glycol Toxicity in Adolescent with Refractory Myoclonic Status Epilepticus

    PubMed Central

    Cannon, Bryan C.; Ritter, Matthew J.; Schueler, Kerry E.

    2017-01-01

    Propylene glycol (PG) is a solvent commonly used in medications that, while benign at low doses, may cause toxicity in adults and children at high doses. We describe a case and the physiologic sequelae of propylene glycol toxicity manifested in a critically ill adolescent male with refractory myoclonic status epilepticus aggressively treated with multiple PG-containing medications (lorazepam, phenobarbital, and pentobarbital)—all within accepted dosing guidelines and a total daily PG exposure previously recognized to be safe. Hemodynamic measurements by bedside echocardiography during clinical toxicity are also reported. Clinicians should have a high index of suspicion for propylene glycol toxicity in patients treated with PG-containing medications even when the total PG exposure is lower than currently accepted limits. PMID:28331645

  12. The relation between remembered parental acceptance in childhood and self-acceptance among young Turkish adults.

    PubMed

    Kuyumcu, Behire; Rohner, Ronald P

    2016-05-11

    This study examined the relation between young adults' age and remembrances of parental acceptance in childhood, and their current self-acceptance. The study was based on a sample of 236 young adults in Turkey (139 women and 97 men). The adult version of the Parental Acceptance-Rejection/Control Questionnaire for mothers and fathers along with the Self-Acceptance subscale of the Psychological Well-Being Scale, and the Personal Information Form were used as measures. Results showed that both men and women tended to remember having been accepted in childhood by both their mothers and fathers. Women, however, reported more maternal and paternal acceptance in childhood than did men. Similarly, the level of self-acceptance was high among both men and women. However, women's self-acceptance was higher than men's. Correlational analyses showed that self-acceptance was positively related to remembrances of maternal and paternal acceptance among both women and men. Results indicated that age and remembered paternal acceptance significantly predicted women's self-acceptance. Age and remembered maternal acceptance made significant and independent contributions to men's self-acceptance. Men's remembrances of paternal acceptance in childhood did not make significant contribution to their self-acceptance. Finally, the relation between women's age and self-acceptance was significantly moderated by remembrances of paternal acceptance in childhood.

  13. Mitochondrial toxicity: myths and facts.

    PubMed

    Moyle, Graeme

    2004-05-01

    Nucleoside analogue reverse transcriptase inhibitors (NRTIs) represent key components of the antiretroviral combinations used to manage HIV infection. A range of nucleoside analogues are currently available which differ in their convenience of administration, frequency of dosing, resistance profile and frequency and severity of adverse effects. Many of the important and treatment limiting side-effects of nucleoside analogues have been suggested to be related to the impact of these agents on mitochondrial DNA polymerase gamma. Depletion of mitochondrial DNA or impacts of these agents on mitochondrial enzymes during chronic nucleoside analogue therapy may lead to cellular respiratory dysfunction and both generalised and tissue specific toxicities. In particular, fatal lactic acidosis represents a rare but clinically important manifestation of nucleoside analogue induced mitochondrial dysfunction. Other potentially severe toxicities which are well-characterised include peripheral neuropathy (PN) and myopathy. Management of potentially mitochondrial toxicity during nucleoside analogue therapy remains a challenge. A range of nutritional supplements, both as treatments and prophylaxes have been proposed and some investigated in vitro but not as yet in vivo. At present, therefore, interruption of nucleoside analogue therapy, or substitution of the probable causative agent with nucleoside analogues which appear better tolerated represent the mainstay of management.

  14. Big Data in Chemical Toxicity Research: The Use of High-Throughput Screening Assays To Identify Potential Toxicants

    PubMed Central

    2015-01-01

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound’s ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described. PMID:25195622

  15. Big data in chemical toxicity research: the use of high-throughput screening assays to identify potential toxicants.

    PubMed

    Zhu, Hao; Zhang, Jun; Kim, Marlene T; Boison, Abena; Sedykh, Alexander; Moran, Kimberlee

    2014-10-20

    High-throughput screening (HTS) assays that measure the in vitro toxicity of environmental compounds have been widely applied as an alternative to in vivo animal tests of chemical toxicity. Current HTS studies provide the community with rich toxicology information that has the potential to be integrated into toxicity research. The available in vitro toxicity data is updated daily in structured formats (e.g., deposited into PubChem and other data-sharing web portals) or in an unstructured way (papers, laboratory reports, toxicity Web site updates, etc.). The information derived from the current toxicity data is so large and complex that it becomes difficult to process using available database management tools or traditional data processing applications. For this reason, it is necessary to develop a big data approach when conducting modern chemical toxicity research. In vitro data for a compound, obtained from meaningful bioassays, can be viewed as a response profile that gives detailed information about the compound's ability to affect relevant biological proteins/receptors. This information is critical for the evaluation of complex bioactivities (e.g., animal toxicities) and grows rapidly as big data in toxicology communities. This review focuses mainly on the existing structured in vitro data (e.g., PubChem data sets) as response profiles for compounds of environmental interest (e.g., potential human/animal toxicants). Potential modeling and mining tools to use the current big data pool in chemical toxicity research are also described.

  16. VIRTUAL EMBRYO: SYSTEMS MODELING IN DEVELOPMENTAL TOXICITY - Symposium: SOT 2012

    EPA Science Inventory

    High-throughput screening (HTS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. Chemical profiling in ToxCast covered 965 drugs-chemicals in over 500 diverse assays testing...

  17. Acceptability of GM foods among Pakistani consumers.

    PubMed

    Ali, Akhter; Rahut, Dil Bahadur; Imtiaz, Muhammad

    2016-04-02

    In Pakistan majority of the consumers do not have information about genetically modified (GM) foods. In developing countries particularly in Pakistan few studies have focused on consumers' acceptability about GM foods. Using comprehensive primary dataset collected from 320 consumers in 2013 from Pakistan, this study analyzes the determinants of consumers' acceptability of GM foods. The data was analyzed by employing the bivariate probit model and censored least absolute deviation (CLAD) models. The empirical results indicated that urban consumers are more aware of GM foods compared to rural consumers. The acceptance of GM foods was more among females' consumers as compared to male consumers. In addition, the older consumers were more willing to accept GM food compared to young consumers. The acceptability of GM foods was also higher among wealthier households. Low price is the key factor leading to the acceptability of GM foods. The acceptability of the GM foods also reduces the risks among Pakistani consumers.

  18. Consumer Acceptability of Intramuscular Fat

    PubMed Central

    Frank, Damian; Joo, Seon-Tea

    2016-01-01

    Fat in meat greatly improves eating quality, yet many consumers avoid visible fat, mainly because of health concerns. Generations of consumers, especially in the English-speaking world, have been convinced by health authorities that animal fat, particularly saturated or solid fat, should be reduced or avoided to maintain a healthy diet. Decades of negative messages regarding animal fats has resulted in general avoidance of fatty cuts of meat. Paradoxically, low fat or lean meat tends to have poor eating quality and flavor and low consumer acceptability. The failure of low-fat high-carbohydrate diets to curb “globesity” has prompted many experts to re-evaluate of the place of fat in human diets, including animal fat. Attitudes towards fat vary dramatically between and within cultures. Previous generations of humans sought out fatty cuts of meat for their superior sensory properties. Many consumers in East and Southeast Asia have traditionally valued more fatty meat cuts. As nutritional messages around dietary fat change, there is evidence that attitudes towards animal fat are changing and many consumers are rediscovering and embracing fattier cuts of meat, including marbled beef. The present work provides a short overview of the unique sensory characteristics of marbled beef and changing consumer preferences for fat in meat in general. PMID:28115880

  19. Understanding Genetic Toxicity Through Data Mining: The Process of Building Knowledge by Integrating Multiple Genetic Toxicity Databases

    EPA Science Inventory

    This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in...

  20. Interspecies quantitative structure-toxicity-toxicity (QSTTR) relationship modeling of ionic liquids. Toxicity of ionic liquids to V. fischeri, D. magna and S. vacuolatus.

    PubMed

    Das, Rudra Narayan; Roy, Kunal; Popelier, Paul L A

    2015-12-01

    Considering the increasing uses of ionic liquids (ILs) in various industrial processes and chemical engineering operations, a complete assessment of their hazardous profile is essential. In the absence of adequate experimental data, in silico modeling might be helpful in filling data gaps for the toxicity of ILs towards various ecological indicator organisms. Using the rationale of taxonomic relatedness, the development of predictive quantitative structure-toxicity-toxicity relationship (QSTTR) models allows predicting the toxicity of ILs to a particular species using available experimental toxicity data towards a different species. Such studies may employ, along with the available experimental toxicity data to a species, molecular structure features and physicochemical properties of chemicals as independent variables for prediction of the toxicity profile against another closely related species. A few such interspecies toxicity correlation models have been reported in the literature for diverse chemicals in general, but this approach has been rarely applied to the class of ionic liquids. The present study involves the use of IL toxicity data towards the bacteria Vibrio fischeri along with molecular structure derived information or computational descriptors like extended topochemical atom (ETA) indices, quantum topological molecular similarity (QTMS) descriptors and computed lipophilicity measure (logk0) for the interspecies exploration of the toxicity data towards green algae S. vacuolatus and crustacea Daphnia magna, separately. This modeling study has been performed in accordance with the OECD guidelines. Finally, predictions for a true external set have been performed to fill the data gap of toxicity towards daphnids and algae using the Vibrio toxicity data and molecular structure attributes.

  1. Acceptance in Romantic Relationships: The Frequency and Acceptability of Partner Behavior Inventory

    ERIC Educational Resources Information Center

    Doss, Brian D.; Christensen, Andrew

    2006-01-01

    Despite the recent emphasis on acceptance in romantic relationships, no validated measure of relationship acceptance presently exists. To fill this gap, the 20-item Frequency and Acceptability of Partner Behavior Inventory (FAPBI; A. Christensen & N. S. Jacobson, 1997) was created to assess separately the acceptability and frequency of both…

  2. 24 CFR 203.202 - Plan acceptability and acceptance renewal criteria-general.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUD acceptance of such change or modification, except that changes mandated by other applicable laws... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Plan acceptability and acceptance... Underwriting Procedures Insured Ten-Year Protection Plans (plan) § 203.202 Plan acceptability and...

  3. Establishment of an equivalence acceptance criterion for accelerated stability studies.

    PubMed

    Burdick, Richard K; Sidor, Leslie

    2013-01-01

    In this article, the use of statistical equivalence testing for providing evidence of process comparability in an accelerated stability study is advocated over the use of a test of differences. The objective of such a study is to demonstrate comparability by showing that the stability profiles under nonrecommended storage conditions of two processes are equivalent. Because it is difficult at accelerated conditions to find a direct link to product specifications, and hence product safety and efficacy, an equivalence acceptance criterion is proposed that is based on the statistical concept of effect size. As with all statistical tests of equivalence, it is important to collect input from appropriate subject-matter experts when defining the acceptance criterion.

  4. Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies--changes in drug metabolizing genes and potential mechanisms linked to kava toxicity.

    PubMed

    Guo, Lei; Shi, Qiang; Dial, Stacey; Xia, Qingsu; Mei, Nan; Li, Quan-zhen; Chan, Po-Chuen; Fu, Peter

    2010-02-01

    The association of kava products with liver-related health risks has prompted regulatory action in many countries. We used a genome-wide gene expression approach to generate global gene expression profiles from the livers of male B6C3F1 mice administered kava extract by gavage for 14 weeks, and identified the differentially expressed drug metabolizing genes in response to kava treatments. Analyses of gene functions and pathways reveal that the levels of significant numbers of genes involving drug metabolism were changed and that the pathways involving xenobiotics metabolism, Nrf2-mediated oxidative stress response, mitochondrial functions and others, were altered. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, potentially leading to herb-drug interactions and hepatotoxicity.

  5. Review of Toxic Epidermal Necrolysis

    PubMed Central

    Harris, Victoria; Jackson, Christopher; Cooper, Alan

    2016-01-01

    Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation. There is uncertainty around the accepted management of TEN. The lack of definitive management guidelines for TEN is explained in part by the rarity of the disease and its high mortality rate, which makes it difficult to conduct randomised control trials on emerging therapies. Developments have been made in pharmacogenomics, with numerous HLA alleles identified; however, these have largely been ethnically specific. These associations have translated into screening recommendations for Han Chinese. PMID:27999358

  6. Toxicity of carbon nanotubes.

    PubMed

    Wang, Jing; Xu, Yuanzhi; Yang, Zhi; Huang, Renhuan; Chen, Jing; Wang, Raorao; Lin, Yunfeng

    2013-10-01

    Carbon nanotubes (CNTs) find their extensive application as a promising material in medicine due to unique characteristics. However, such materials have been accompanied with potentially hazardous effects on human health. The toxicity of CNTs may vary depending on their structural characteristics, surface properties and chemical composition. To gain insight into the toxicity of CNTs in vivo and in vitro, we summarize contributing factors for the toxic effects of CNTs in this review. In addition, we elaborate on the toxic effects and mechanisms in target sites at systemic, organic, cellular, and biomacromolecule levels. Various issues are reported to be effected when exposed to CNTs including (1) blood circulation, (2) lymph circulation, (3) lung, (4) heart, (5) kidney, (6) spleen, (7) bone marrow, and (8) blood brain barrier. Though there have been published reports on the toxic effects of CNTs to date, more studies will still be needed to gain full understanding of their potential toxicity and underlying mechanisms.

  7. Acute toxicity of arsenobetaine

    SciTech Connect

    Kaise, T.; Watanabe, S.; Itoh, K.

    1985-01-01

    The acute toxicity of arsenobetaine was studied in male mice. No deaths were observed with oral administration of 10 g/kg of arsenobetaine. Therefore the LD/sub 50/ value was higher than 10 g/kg. This compound was found in urine in the non-metabolized form. No particular toxic symptoms were observed following administration. These suggest that arsenobetaine has low toxicity and is not metabolized in mice.

  8. Clinical outcomes, toxicity, and cosmesis in breast cancer patients with close skin spacing treated with accelerated partial breast irradiation (APBI) using multi-lumen/catheter applicators

    PubMed Central

    Akhtari, Mani; Abboud, Mirna; Szeja, Sean; Pino, Ramiro; Lewis, Gary D.; Bass, Barbara L.; Miltenburg, Darlene M.; Butler, E. Brian

    2016-01-01

    Purpose Accelerated partial breast irradiation (APBI) using a single-lumen device is associated with better cosmetic outcomes if the spacing between the applicator and skin is > 7 mm. However, there are no reports addressing the late toxicity and clinical outcomes in patients treated with single-entry multi-lumen/catheter applicators who had close skin spacing (7 mm or less). We undertook this study to report clinical outcome, acute and late toxicity as well as cosmesis of early stage breast cancer patients with close skin spacing treated with APBI using multi-lumen or multi-catheter devices. Material and methods This is a retrospective study of all breast cancer patients who had undergone APBI using single-entry multi-lumen/catheter devices in a single institution between 2008 to 2012. The study was limited to those with ≤ 7 mm spacing between the device and skin. Results We identified 37 patients and 38 lesions with skin spacing of ≤ 7 mm. Seven lesions (18%) had spacing of ≤ 3 mm. Median follow-up was 47.5 months. There was one case of ipsilateral breast recurrence and one ipsilateral axillary recurrence. Based on RTOG criteria, 22 treated lesions experienced grade 1 and 9 lesions experienced grade 2 toxicity. Twenty-one lesions experienced late grade 1 toxicity. One patient had to undergo mastectomy due to mastitis. Twenty-four treated breasts showed excellent and 11 had good cosmetic outcome. Overall cosmesis trended towards a significant correlation with skin spacing. However, all patients with ≤ 3 mm skin spacing experienced acute and late toxicities. Conclusions Accelerated partial breast irradiation can be safely performed in patients with skin spacing of ≤ 7 mm using single-entry multi-lumen/catheter applicators with excellent cosmetic outcomes and an acceptable toxicity profile. However, skin spacing of ≤ 3 mm is associated with acute and late toxicity and should be avoided if possible. PMID:28115955

  9. Evaluation of multiple mechanism-based toxicity endpoints in primary cultured human hepatocytes for the identification of drugs with clinical hepatotoxicity: Results from 152 marketed drugs with known liver injury profiles.

    PubMed

    Zhang, Jie; Doshi, Utkarsh; Suzuki, Ayako; Chang, Ching-Wei; Borlak, Jürgen; Li, Albert P; Tong, Weida

    2016-08-05

    We report here the results of a collaborative research program to develop a robust and reliable in vitro system to allow an accurate definition of the drug-induced liver injury (DILI) potential of new drug entities during drug development. The in vitro hepatotoxic potential of 152 drugs with known DILI profiles were evaluated in primary cultured human hepatocytes with four mechanistically-relevant endpoints: cellular ATP depletion, reactive oxygen species (ROS), glutathione (GSH) depletion, and caspase activation for apoptosis. The drugs, 80 in the testing set and 72 in the validation set, were classified based on serious clinical/regulatory outcomes as defined by reported acute liver failure, black-box warning, and/or withdrawal. The drugs were further sub-categorized for dominant types of liver injury. Logistic regression models were performed to calculate the area under the receiver operating characteristics curve (AUROC) and to evaluate the prediction potential of the selected endpoints for serious clinical/regulatory outcomes. The ROS/ATP ratio was found to yield an excellent AUROC in both the testing (0.8989, P < 0.0001) and validation set (0.8545, P < 0.0001), and was found to distinguish drugs associated with severe from non-severe DILI cases (p < 0.0001). The results suggest that evaluation of drugs in primary human hepatocytes using the ROS/ATP ratio endpoint may aid the definition of their potential to cause severe DILI.

  10. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  11. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  12. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  13. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  14. 7 CFR 1207.323 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE POTATO RESEARCH AND PROMOTION PLAN Potato Research and Promotion Plan National Potato Promotion Board § 1207.323 Acceptance. Each...

  15. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  16. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  17. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  18. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  19. 7 CFR 932.32 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE OLIVES GROWN IN CALIFORNIA Order Regulating Handling Olive Administrative Committee § 932.32 Acceptance. Any person selected by the...

  20. Acceptance Criteria for Aerospace Structural Adhesives.

    DTIC Science & Technology

    ADHESIVES, *AIRFRAMES, PRIMERS, STRUCTURAL ENGINEERING, CHEMICAL COMPOSITION, MECHANICAL PROPERTIES, INDUSTRIAL PRODUCTION , DATA ACQUISITION , PARTICLE SIZE, ACCEPTANCE TESTS, ELASTOMERS, BONDING, QUALITY CONTROL, .

  1. 2013 SYR Accepted Poster Abstracts.

    PubMed

    2013-01-01

    SYR 2013 Accepted Poster abstracts: 1. Benefits of Yoga as a Wellness Practice in a Veterans Affairs (VA) Health Care Setting: If You Build It, Will They Come? 2. Yoga-based Psychotherapy Group With Urban Youth Exposed to Trauma. 3. Embodied Health: The Effects of a Mind�Body Course for Medical Students. 4. Interoceptive Awareness and Vegetable Intake After a Yoga and Stress Management Intervention. 5. Yoga Reduces Performance Anxiety in Adolescent Musicians. 6. Designing and Implementing a Therapeutic Yoga Program for Older Women With Knee Osteoarthritis. 7. Yoga and Life Skills Eating Disorder Prevention Among 5th Grade Females: A Controlled Trial. 8. A Randomized, Controlled Trial Comparing the Impact of Yoga and Physical Education on the Emotional and Behavioral Functioning of Middle School Children. 9. Feasibility of a Multisite, Community based Randomized Study of Yoga and Wellness Education for Women With Breast Cancer Undergoing Chemotherapy. 10. A Delphi Study for the Development of Protocol Guidelines for Yoga Interventions in Mental Health. 11. Impact Investigation of Breathwalk Daily Practice: Canada�India Collaborative Study. 12. Yoga Improves Distress, Fatigue, and Insomnia in Older Veteran Cancer Survivors: Results of a Pilot Study. 13. Assessment of Kundalini Mantra and Meditation as an Adjunctive Treatment With Mental Health Consumers. 14. Kundalini Yoga Therapy Versus Cognitive Behavior Therapy for Generalized Anxiety Disorder and Co-Occurring Mood Disorder. 15. Baseline Differences in Women Versus Men Initiating Yoga Programs to Aid Smoking Cessation: Quitting in Balance Versus QuitStrong. 16. Pranayam Practice: Impact on Focus and Everyday Life of Work and Relationships. 17. Participation in a Tailored Yoga Program is Associated With Improved Physical Health in Persons With Arthritis. 18. Effects of Yoga on Blood Pressure: Systematic Review and Meta-analysis. 19. A Quasi-experimental Trial of a Yoga based Intervention to Reduce Stress and

  2. Polymyxin E sulfate-loaded liposome for intravenous use: preparation, lyophilization, and toxicity assessment in vivo.

    PubMed

    Wang, Dongkai; Kong, Liwen; Wang, Jing; He, Xiaoling; Li, Xiang; Xiao, Yuting

    2009-01-01

    Polymyxin E sulfate, a hydrophilic drug with high tissue toxicity, was formulated into a stable liposome to reduce its in vivo toxicity. The liposome was prepared using both a reverse phase evaporation and freezing-thawing method. The encapsulation efficiency was determined by high-performance liquid chromatography. The influence of the freezing-thawing process on the liposome's stability was evaluated using a centrifugation test. The dialysis method was employed to investigate the in vitro release profile of the drug-loaded liposome. The toxicity of the polymyxin E sulfate-loaded liposome was compared with the polymyxin E sulfate solution in Kunming mice by intravenous administration. A freeze-drying (lyophilization) technique was utilized to prepare the proliposome. A cryoprotectant formulation was optimized by the evaluation of the particle diameter and encapsulation efficiency of the redispersed proliposomes, while the influence of the concentration and method of the addition of the cryoprotectant on the protective effect was investigated as well. It was found that the stability and encapsulation efficiency of the liposome could be improved by the freezing-thawing process. The delayed drug release profile of the drug-loaded liposome was observed in vitro, and a comparison with the polymyxin E sulfate solution revealed that the in vivo toxicity of the polymyxin E sulfate-loaded liposome was significantly reduced. Sucrose and mannitol at a weight ratio of 1:0.8:0.6 (phospholipids:mannitol:sucrose) added inside displayed the greatest protective effect on the polymyxin E sulfate liposome during freeze-drying. The rehydrated proliposomes with optimized cryoprotectants produced an acceptable particle diameter (204.1 nm) and a satisfactory encapsulation efficiency percentage (51.48%), thus demonstrating a practical method for preparation of polymyxin E sulfate-loaded proliposome. A combination of the reverse phase evaporation and freezing-thawing methods was found to

  3. In acceptance we trust? Conceptualising acceptance as a viable approach to NGO security management.

    PubMed

    Fast, Larissa A; Freeman, C Faith; O'Neill, Michael; Rowley, Elizabeth

    2013-04-01

    This paper documents current understanding of acceptance as a security management approach and explores issues and challenges non-governmental organisations (NGOs) confront when implementing an acceptance approach to security management. It argues that the failure of organisations to systematise and clearly articulate acceptance as a distinct security management approach and a lack of organisational policies and procedures concerning acceptance hinder its efficacy as a security management approach. The paper identifies key and cross-cutting components of acceptance that are critical to its effective implementation in order to advance a comprehensive and systematic concept of acceptance. The key components of acceptance illustrate how organisational and staff functions affect positively or negatively an organisation's acceptance, and include: an organisation's principles and mission, communications, negotiation, programming, relationships and networks, stakeholder and context analysis, staffing, and image. The paper contends that acceptance is linked not only to good programming, but also to overall organisational management and structures.

  4. Reproductive toxicity of brazilein in ICR mice.

    PubMed

    Yuan, Zhi-Yi; Lei, Fan; Chai, Yu-Shuang; Wu, Hao; Zhao, Shuang; Wang, Yu-Gang; Feng, Tian-Shi; Li, Hui-Ying; Li, Hui-Yu; Zhan, Hong-Lei; Xing, Dong-Ming; DU, Li-Jun

    2016-06-01

    Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.

  5. Toxic hazards research unit

    SciTech Connect

    Macewen, J.D.; Vernot, E.H.

    1980-08-01

    Chronic toxicity or oncogenic studies were carried out with methylcyclohexane, tricyclodecane, purified 1,1-dimethylhydrazine, and bicycloheptadiene. A subchronic inhalation study was conducted with shale derived JP-5 and DFM fuels. Acute toxicity studies were conducted on a variety of chemical agents used by the Air Force and Navy.

  6. Leadership Profiles.

    ERIC Educational Resources Information Center

    Teach, Beverly; And Others

    1994-01-01

    Presents profiles of two leaders in the field of educational media and technology: Carolyn Guss and Mendel Sherman, both retired professors from Indiana University's program in Information Systems Technology. (KRN)

  7. Leadership Profiles.

    ERIC Educational Resources Information Center

    Morgan, Robert M.; And Others

    1992-01-01

    Presents profiles of three leaders in the field of educational media and technology: Robert Mills Gagne, Florida State University; Robert Heinich, Indiana University; and Charles Francis Schuller, University of Georgia. (SLW)

  8. Biophysical Profile

    MedlinePlus

    ... is Rh positive Worrisome results from other prenatal tests Your health care provider might also recommend a biophysical profile if ... the test and at regular intervals during the test. Your health care provider or a member of your health care ...

  9. 40 CFR 372.85 - Toxic chemical release reporting form and instructions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS TOXIC CHEMICAL RELEASE REPORTING: COMMUNITY RIGHT-TO-KNOW Forms and Instructions § 372.85 Toxic chemical release reporting form and..., using the TRI online-reporting software provided by EPA. (1) EPA will no longer accept...

  10. 40 CFR 227.8 - Limitations on the disposal rates of toxic wastes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... toxic wastes. 227.8 Section 227.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Environmental Impact § 227.8 Limitations on the disposal rates of toxic wastes. No wastes will be deemed acceptable for ocean dumping unless such wastes can be dumped so as not to exceed the limiting...

  11. 40 CFR 227.8 - Limitations on the disposal rates of toxic wastes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... toxic wastes. 227.8 Section 227.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Environmental Impact § 227.8 Limitations on the disposal rates of toxic wastes. No wastes will be deemed acceptable for ocean dumping unless such wastes can be dumped so as not to exceed the limiting...

  12. 40 CFR 227.8 - Limitations on the disposal rates of toxic wastes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... toxic wastes. 227.8 Section 227.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Environmental Impact § 227.8 Limitations on the disposal rates of toxic wastes. No wastes will be deemed acceptable for ocean dumping unless such wastes can be dumped so as not to exceed the limiting...

  13. 40 CFR 227.8 - Limitations on the disposal rates of toxic wastes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... toxic wastes. 227.8 Section 227.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Environmental Impact § 227.8 Limitations on the disposal rates of toxic wastes. No wastes will be deemed acceptable for ocean dumping unless such wastes can be dumped so as not to exceed the limiting...

  14. 40 CFR 227.8 - Limitations on the disposal rates of toxic wastes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... toxic wastes. 227.8 Section 227.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Environmental Impact § 227.8 Limitations on the disposal rates of toxic wastes. No wastes will be deemed acceptable for ocean dumping unless such wastes can be dumped so as not to exceed the limiting...

  15. Heavy Metal, Religiosity, and Suicide Acceptability.

    ERIC Educational Resources Information Center

    Stack, Steven

    1998-01-01

    Reports on data taken from the General Social Survey that found a link between "heavy metal" rock fanship and suicide acceptability. Finds that relationship becomes nonsignificant once level of religiosity is controlled. Heavy metal fans are low in religiosity, which contributes to greater suicide acceptability. (Author/JDM)

  16. Hanford Site liquid waste acceptance criteria

    SciTech Connect

    LUECK, K.J.

    1999-09-11

    This document provides the waste acceptance criteria for liquid waste managed by Waste Management Federal Services of Hanford, Inc. (WMH). These waste acceptance criteria address the various requirements to operate a facility in compliance with applicable environmental, safety, and operational requirements. This document also addresses the sitewide miscellaneous streams program.

  17. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  18. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  19. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  20. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  1. Nevada Test Site Waste Acceptance Criteria (NTSWAC)

    SciTech Connect

    NNSA /NSO Waste Management Project

    2008-06-01

    This document establishes the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office, Nevada Test Site Waste Acceptance Criteria (NTSWAC). The NTSWAC provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive (LLW) and LLW Mixed Waste (MW) for disposal.

  2. Consumer acceptance of ginseng food products.

    PubMed

    Chung, Hee Sook; Lee, Young-Chul; Rhee, Young Kyung; Lee, Soo-Yeun

    2011-01-01

    Ginseng has been utilized less in food products than in dietary supplements in the United States. Sensory acceptance of ginseng food products by U.S. consumers has not been reported. The objectives of this study were to: (1) determine the sensory acceptance of commercial ginseng food products and (2) assess influence of the addition of sweeteners to ginseng tea and ginseng extract to chocolate on consumer acceptance. Total of 126 consumers participated in 3 sessions for (1) 7 commercial red ginseng food products, (2) 10 ginseng teas varying in levels of sugar or honey, and (3) 10 ginseng milk or dark chocolates varying in levels of ginseng extract. Ginseng candy with vitamin C and ginseng crunchy white chocolate were the most highly accepted, while sliced ginseng root product was the least accepted among the seven commercial products. Sensory acceptance increased in proportion to the content of sugar and honey in ginseng tea, whereas acceptance decreased with increasing content of ginseng extract in milk and dark chocolates. Findings demonstrate that ginseng food product types with which consumers have been already familiar, such as candy and chocolate, will have potential for success in the U.S. market. Chocolate could be suggested as a food matrix into which ginseng can be incorporated, as containing more bioactive compounds than ginseng tea at a similar acceptance level. Future research may include a descriptive analysis with ginseng-based products to identify the key drivers of liking and disliking for successful new product development.

  3. Genres Across Cultures: Types of Acceptability Variation

    ERIC Educational Resources Information Center

    Shaw, Philip; Gillaerts, Paul; Jacobs, Everett; Palermo, Ofelia; Shinohara, Midori; Verckens, J. Piet

    2004-01-01

    One can ask four questions about genre validity across cultures. Does a certain form or configuration occur in the culture in question? Is it acceptable? If acceptable, is it in practice preferred? Is it recommended by prescriptive authorities? This paper reports the results of an attempt to answer these questions empirically by testing the…

  4. 48 CFR 11.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Market acceptance. 11.103... DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 11.103 Market acceptance. (a) Section... may, under appropriate circumstances, require offerors to demonstrate that the items offered— (1)...

  5. 48 CFR 2811.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Market acceptance. 2811.103... Planning DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 2811.103 Market acceptance... offerors to demonstrate that the items offered meet the criteria set forth in FAR 11.103(a)....

  6. 5 CFR 1655.11 - Loan acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Loan acceptance. 1655.11 Section 1655.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD LOAN PROGRAM § 1655.11 Loan acceptance. The TSP record keeper will reject a loan application if: (a) The participant is not qualified to apply...

  7. 5 CFR 1655.11 - Loan acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Loan acceptance. 1655.11 Section 1655.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD LOAN PROGRAM § 1655.11 Loan acceptance. The TSP record keeper will reject a loan application if: (a) The participant is not qualified to apply...

  8. 5 CFR 1655.11 - Loan acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Loan acceptance. 1655.11 Section 1655.11 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD LOAN PROGRAM § 1655.11 Loan acceptance. The TSP record keeper will reject a loan application if: (a) The participant is not qualified to apply...

  9. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  10. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  11. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  12. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY... Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf of the head...

  13. 48 CFR 3011.103 - Market acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Market acceptance. 3011.103 Section 3011.103 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Developing Requirements Documents 3011.103 Market acceptance. (a) Contracting officers may act on behalf...

  14. 48 CFR 411.103 - Market acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Market acceptance. 411.103... ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 411.103 Market... accordance with FAR 11.103(a), the market acceptability of their items to be offered. (b) The...

  15. Understanding diversity: the importance of social acceptance.

    PubMed

    Chen, Jacqueline M; Hamilton, David L

    2015-04-01

    Two studies investigated how people define and perceive diversity in the historically majority-group dominated contexts of business and academia. We hypothesized that individuals construe diversity as both the numeric representation of racial minorities and the social acceptance of racial minorities within a group. In Study 1, undergraduates' (especially minorities') perceptions of campus diversity were predicted by perceived social acceptance on a college campus, above and beyond perceived minority representation. Study 2 showed that increases in a company's representation and social acceptance independently led to increases in perceived diversity of the company among Whites. Among non-Whites, representation and social acceptance only increased perceived diversity of the company when both qualities were high. Together these findings demonstrate the importance of both representation and social acceptance to the achievement of diversity in groups and that perceiver race influences the relative importance of these two components of diversity.

  16. Heavy metal, religiosity, and suicide acceptability.

    PubMed

    Stack, S

    1998-01-01

    There has been little work at the national level on the subject of musical subcultures and suicide acceptability. The present work explores the link between "heavy metal" rock fanship and suicide acceptability. Metal fanship is thought to elevate suicide acceptability through such means as exposure to a culture of personal and societal chaos marked by hopelessness, and through its associations with demographic risk factors such as gender, socioeconomic status, and education. Data are taken from the General Social Survey. A link between heavy metal fanship and suicide acceptability is found. However, this relationship becomes nonsignificant once level of religiosity is controlled. Metal fans are low in religiosity, which contributes, in turn, to greater suicide acceptability.

  17. Monte Carlo determination of Phoswich Array acceptance

    SciTech Connect

    Costales, J.B.; E859 Collaboration

    1992-07-01

    The purpose of this memo is to describe the means by which the acceptance of the E859 Phoswich Array is determined. By acceptance, two things are meant: first, the geometrical acceptance (the angular size of the modules); second, the detection acceptance (the probability that a particle of a given 4-momentum initially in the detector line-of-sight is detected as such). In particular, this memo will concentrate on those particles for which the energy of the particle can be sufficiently measured; that is to say, protons, deuterons and tritons. In principle, the phoswich array can measure the low end of the pion energy spectrum, but with a poor resolution. The detection acceptance of pions and baryon clusters heavier than tritons will be neglected in this memo.

  18. Modeling of the charge acceptance of lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Thele, M.; Schiffer, J.; Karden, E.; Surewaard, E.; Sauer, D. U.

    This paper presents a model for flooded and VRLA batteries that is parameterized by impedance spectroscopy and includes the overcharging effects to allow charge-acceptance simulations (e.g. for regenerative-braking drive-cycle profiles). The full dynamic behavior and the short-term charge/discharge history is taken into account. This is achieved by a detailed modeling of the sulfate crystal growth and modeling of the internal gas recombination cycle. The model is applicable in the full realistic temperature and current range of automotive applications. For model validation, several load profiles (covering the dynamics and the current range appearing in electrically assisted or hybrid cars) are examined and the charge-acceptance limiting effects are elaborately discussed. The validation measurements have been performed for different types of lead-acid batteries (flooded and VRLA). The model is therefore an important tool for the development of automotive power nets, but it also allows to analyze different charging strategies and energy gains which can be achieved during regenerative-braking.

  19. Toxicity Estimation Software Tool (TEST)

    EPA Science Inventory

    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...

  20. ENGINEERING BULLETIN: BIOLOGICAL TOXICITY TESTING

    EPA Science Inventory

    This Engineering Bulletin is intended to provide site managers with information on ecological assessment and biological toxicity testing, applicability of biological toxicity testing, planning effective biological toxicity assessments, descriptions of test methods, limitations, c...

  1. Digitalis toxicity: ECG vignette.

    PubMed

    Vyas, Aniruddha; Bachani, Neeta; Thakur, Hrishikesh; Lokhandwala, Yash

    2016-09-01

    "Digitalis toxicity, often candidly indexed as poisoning, has plagued the medical profession for over 200 years. The situation qualifies as a professional disgrace on the basis of three items: the situation persists, physicians are often slow to recognize it and, over the decades, writers have been harsh in their denunciation of fellow physicians when toxicity has occurred…." These are the opening remarks of an essay published in 1983 on the 2nd centenary of William Withering's 'magic potion from foxglove's extract for dropsy.' Even today, after many decades, these words appear relevant! We present and discuss an interesting ECG of digitalis toxicity.

  2. CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

    EPA Pesticide Factsheets

    Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

  3. A Positive View of Peer Acceptance in Aggressive Youth: Risk for Future Peer Acceptance.

    ERIC Educational Resources Information Center

    Hughes, Jan N.; Cavell, Timothy A.; Prasad-Gaur, Archna

    2001-01-01

    Uses longitudinal data to determine whether a positive view of perceived peer acceptance is a risk factor for continued aggression and social rejection for aggressive children. Results indicate that perceived peer acceptance did not predict aggression. However, children who reported higher levels of perceived peer acceptance received lower actual…

  4. Consumer Acceptance of Dry Dog Food Variations

    PubMed Central

    Donfrancesco, Brizio Di; Koppel, Kadri; Swaney-Stueve, Marianne; Chambers, Edgar

    2014-01-01

    Simple Summary The objectives of this study were to compare the acceptance of different dry dog food products by consumers, determine consumer clusters for acceptance, and identify the characteristics of dog food that drive consumer acceptance. Pet owners evaluated dry dog food samples available in the US market. The results indicated that appearance of the sample, especially the color, influenced pet owner’s overall liking more than the aroma of the product. Abstract The objectives of this study were to compare the acceptance of different dry dog food products by consumers, determine consumer clusters for acceptance, and identify the characteristics of dog food that drive consumer acceptance. Eight dry dog food samples available in the US market were evaluated by pet owners. In this study, consumers evaluated overall liking, aroma, and appearance liking of the products. Consumers were also asked to predict their purchase intent, their dog’s liking, and cost of the samples. The results indicated that appearance of the sample, especially the color, influenced pet owner’s overall liking more than the aroma of the product. Overall liking clusters were not related to income, age, gender, or education, indicating that general consumer demographics do not appear to play a main role in individual consumer acceptance of dog food products. PMID:26480043

  5. National Air Toxics Assessment

    EPA Pesticide Factsheets

    NATA is an ongoing comprehensive evaluation of air toxics in the U.S. As a screening tool, it helps air agencies prioritize pollutants, emission sources and locations of interest for further study to gain a better understanding of risks.

  6. Aspects of aluminum toxicity

    SciTech Connect

    Hewitt, C.D.; Savory, J.; Wills, M.R. )

    1990-06-01

    Aluminum is the most abundant metal in the earth's crust. The widespread occurrence of aluminum, both in the environment and in foodstuffs, makes it virtually impossible for man to avoid exposure to this metal ion. Attention was first drawn to the potential role of aluminum as a toxic metal over 50 years ago, but was dismissed as a toxic agent as recently as 15 years ago. The accumulation of aluminum, in some patients with chronic renal failure, is associated with the development of toxic phenomena; dialysis encephalopathy, osteomalacic dialysis osteodystrophy, and an anemia. Aluminum accumulation also occurs in patients who are not on dialysis, predominantly infants and children with immature or impaired renal function. Aluminum has also been implicated as a toxic agent in the etiology of Alzheimer's disease, Guamiam amyotrophic lateral sclerosis, and parkinsonism-dementia. 119 references.

  7. Toxic shock syndrome

    MedlinePlus

    ... by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock-like ... men. Risk factors include: Recent childbirth Infection with Staphylococcus aureus ( S aureus ), commonly called a Staph infection Foreign ...

  8. WASTE WATER TOXICITY IDENTIFCATIONS

    EPA Science Inventory

    Toxicity Identification Evaluation (TIE) technology has been used in the scientific and regulatory evaluation of wastewaters for approximately 20 years. This article provides a review of the general and regional considerations, data analysis, specific methods and improvements, m...

  9. BIOMARKERS OF REPRODUCTIVE TOXICITY

    EPA Science Inventory

    Identification and verification of anatomical, endocrine, cellular and molecular biomarkers is crucial for successful clinical diagnosis and treatment of toxicity and disease, as well as basic toxicological, epidemiological and other research. Various in situ biomarkers of repro...

  10. Approaches to acceptable risk: a critical guide

    SciTech Connect

    Fischhoff, B.; Lichtenstein, S.; Slovic, P.; Keeney, R.; Derby, S.

    1980-12-01

    Acceptable-risk decisions are an essential step in the management of technological hazards. In many situations, they constitute the weak (or missing) link in the management process. The absence of an adequate decision-making methodology often produces indecision, inconsistency, and dissatisfaction. The result is neither good for hazard management nor good for society. This report offers a critical analysis of the viability of various approaches as guides to acceptable-risk decisions. This report seeks to define acceptable-risk decisions and to examine some frequently proposed, but inappropriate, solutions. 255 refs., 22 figs., 25 tabs.

  11. Hanford Site Solid Waste Acceptance Criteria

    SciTech Connect

    Not Available

    1993-11-17

    This manual defines the Hanford Site radioactive, hazardous, and sanitary solid waste acceptance criteria. Criteria in the manual represent a guide for meeting state and federal regulations; DOE Orders; Hanford Site requirements; and other rules, regulations, guidelines, and standards as they apply to acceptance of radioactive and hazardous solid waste at the Hanford Site. It is not the intent of this manual to be all inclusive of the regulations; rather, it is intended that the manual provide the waste generator with only the requirements that waste must meet in order to be accepted at Hanford Site TSD facilities.

  12. Consumer acceptance of nutrigenomics-based personalised nutrition.

    PubMed

    Ronteltap, A; van Trijp, J C M; Renes, R J

    2009-01-01

    Nutrigenomics is a new and promising development in nutritional science which aims to understand the fundamental molecular processes affected by foods. Despite general agreement on its promise for better understanding diet-health relationships, less consensus exists among experts on the potential of spin-offs aimed at the consumer such as personalised nutrition. Research into consumer acceptance of such applications is scarce. The present study develops a set of key hypotheses on public acceptance of personalised nutrition and tests these in a representative sample of Dutch consumers. An innovative consumer research methodology is used in which consumers evaluate short films which are systematically varied scenarios for the future of personalised nutrition. Consumer evaluations of these films, which are pre-tested in a pilot study, allow a formal test of how consumer perceptions of personalised nutrition drive consumer acceptance and through which fundamental psychological processes these effects are mediated. Public acceptance is enhanced if consumers can make their genetic profile available free at their own choice, if the actual spin-off products provide a clearly recognisable advantage to the consumer, and are easy to implement into the daily routine. Consumers prefer communication on nutrigenomics and personalised nutrition by expert stakeholders to be univocal and aimed at building support with consumers and their direct environments for this intriguing new development. Additionally, an exploratory segmentation analysis indicated that people have different focal points in their preferences for alternative scenarios of personalised nutrition. The insights obtained from the present study provide guidance for the successful further development of nutrigenomics and its applications.

  13. Chinese Nurses' Acceptance of PDA: A Cross-Sectional Survey Using a Technology Acceptance Model.

    PubMed

    Wang, Yanling; Xiao, Qian; Sun, Liu; Wu, Ying

    2016-01-01

    This study explores Chinese nurses' acceptance of PDA, using a questionnaire based on the framework of Technology Acceptance Model (TAM). 357 nurses were involved in the study. The results reveal the scores of the nurses' acceptance of PDA were means 3.18~3.36 in four dimensions. The younger of nurses, the higher nurses' title, the longer previous usage time, the more experienced using PDA, and the more acceptance of PDA. Therefore, the hospital administrators may change strategies to enhance nurses' acceptance of PDA, and promote the wide application of PDA.

  14. Personality Factors Associated with the Decision to Accept or Reject Mobility Training.

    ERIC Educational Resources Information Center

    White, K.; And Others

    1990-01-01

    Adventitiously blind adults (n=79) who had accepted mobility training were compared to 60 subjects who had rejected training. Personality profiles varied significantly between groups on seven scales of the Minnesota Multiphasic Personality Inventory: psychasthenia; schizophrenia; psychopathic deviate; depression; hypomania; paranoia; and…

  15. Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake

    PubMed Central

    Edwards, James A.

    2016-01-01

    Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission. PMID:26885380

  16. PARTICLE SPECIATION AND EMISSION PROFILES OF SMALL 2-STROKE ENGINES

    EPA Science Inventory

    The Human Exposure and Atmospheric Sciences Division (HEASD) conducts studies designed to acquire information from emission sources for use in source apportionment studies. The objective of this work is to characterize a complete, speciated emission profile (PM and air toxics) ...

  17. What Are Acceptable Limits of Radiation?

    NASA Video Gallery

    Brad Gersey, lead research scientist at the Center for Radiation Engineering and Science for Space Exploration, or CRESSE, at Prairie View A&M University, describes the legal and acceptable limits ...

  18. Behavioral genetics: scientific and social acceptance.

    PubMed

    Lorenz, David R

    2003-01-01

    Human behavioral genetics can be broadly defined as the attempt to characterize and define the genetic or hereditary basis for human behavior. Examination of the history of these scientific enterprises reveals episodes of controversy, and an apparent distinction between scientific and social acceptance of the genetic nature of such complex behaviors. This essay will review the history and methodology of behavioral genetics research, including a more detailed look at case histories involving behavioral genetic research for aggressive behavior and alcoholism. It includes a discussion of the scientific versus social qualities of the acceptance of behavioral genetics research, as well as the development of a general model for scientific acceptance involving the researchers, the scientific literature, the scientific peer group, the mainstream media, and the public at large. From this model follows a discussion of the means and complications by which behavioral genetics research may be accepted by society, and an analysis of how future studies might be conducted.

  19. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as...

  20. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as...

  1. 7 CFR 1205.326 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE COTTON RESEARCH AND PROMOTION Cotton Research and Promotion Order Cotton Board § 1205.326 Acceptance. Any person selected by the Secretary as...

  2. Integrated Model for E-Learning Acceptance

    NASA Astrophysics Data System (ADS)

    Ramadiani; Rodziah, A.; Hasan, S. M.; Rusli, A.; Noraini, C.

    2016-01-01

    E-learning is not going to work if the system is not used in accordance with user needs. User Interface is very important to encourage using the application. Many theories had discuss about user interface usability evaluation and technology acceptance separately, actually why we do not make it correlation between interface usability evaluation and user acceptance to enhance e-learning process. Therefore, the evaluation model for e-learning interface acceptance is considered important to investigate. The aim of this study is to propose the integrated e-learning user interface acceptance evaluation model. This model was combined some theories of e-learning interface measurement such as, user learning style, usability evaluation, and the user benefit. We formulated in constructive questionnaires which were shared at 125 English Language School (ELS) students. This research statistics used Structural Equation Model using LISREL v8.80 and MANOVA analysis.

  3. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service any component until it passes all applicable inspections and tests prescribed by this subpart and...

  4. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service any component until it passes all applicable inspections and tests prescribed by this subpart and...

  5. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service any component until it passes all applicable inspections and tests prescribed by this subpart and...

  6. 49 CFR 193.2303 - Construction acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: FEDERAL SAFETY STANDARDS Construction § 193.2303 Construction acceptance. No person may place in service any component until it passes all applicable inspections and tests prescribed by this subpart and...

  7. Gas characterization system software acceptance test report

    SciTech Connect

    Vo, C.V.

    1996-03-28

    This document details the results of software acceptance testing of gas characterization systems. The gas characterization systems will be used to monitor the vapor spaces of waste tanks known to contain measurable concentrations of flammable gases.

  8. Nevada Test Site Waste Acceptance Criteria

    SciTech Connect

    U.S. Department of Energy, Nevada Operations Office, Waste Acceptance Criteria

    1999-05-01

    This document provides the requirements, terms, and conditions under which the Nevada Test Site will accept low-level radioactive and mixed waste for disposal; and transuranic and transuranic mixed waste for interim storage at the Nevada Test Site.

  9. Leadership Profiles.

    ERIC Educational Resources Information Center

    Orey, Michael; Moore, David M.; Reeves, Thomas

    2003-01-01

    Contains the following two leadership profiles of individuals who have made significant contributions to the field of instructional technology: "Francis M. Dwyer: Visual Researcher Extraordinaire" (David M. Moore); and "Tribute to John G. Hedberg: Professor of Education, University of Wollongong" (Thomas Reeves). (MES)

  10. Acceptance Test Plan for ANSYS Software

    SciTech Connect

    CREA, B.A.

    2000-10-25

    This plan governs the acceptance testing of the ANSYS software (Full Mechanical Release 5.5) for use on Project Word Management Contract (PHMC) computer systems (either UNIX or Microsoft Windows/NT). There are two phases to the acceptance testing covered by this test plan: program execution in accordance with the guidance provided in installation manuals; and ensuring results of the execution are consistent with the expected physical behavior of the system being modeled.

  11. The Effect of Toxic Leadership

    DTIC Science & Technology

    2012-03-15

    personal characteristics.12 Therefore, toxic leaders create toxic climates by changing the content of the culture.13 The resulting damage to the...resilient and resistant to change ; however, in a favorable climate , toxic subcultures not only form, but also thrive. How do organizations become a...emphasize the symptoms of toxicity (individual characteristics, traits) and not the disease (culture, climate , outcomes). Although characteristics

  12. Natural current profiles in a tokamak

    SciTech Connect

    Taylor, J.B.

    1990-08-01

    In this paper I show how one may arrive at a universal, or natural, family of Tokamak profiles using only accepted physical principles. These particular profiles are similar to ones proposed previously on the basis of ad hoc variational principles and the point of the present paper is to provide a justification for them. However in addition, the present work provides an interesting view of Tokamak fluctuations and leads to a new result -- a relationship between the inward particle pinch velocity, the diffusion coefficient and the current profile. The basic Tokamak model is described in this paper. Then an analogy is developed between Tokamak profiles and the equilibrium of a realisable dynamical system. Then the equations governing the natural Tokamak profiles are derived by applying standard statistical mechanics to this analog. The profiles themselves are calculated and some other results of the theory are described.

  13. PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 1. Toxin levels

    PubMed Central

    Deeds, Jonathan R.; Petitpas, Christian M.; Shue, Vangie; White, Kevin D.; Keafer, Bruce A.; McGillicuddy, Dennis J.; Milligan, Peter J.; Anderson, Donald M.; Turner, Jefferson T.

    2014-01-01

    As part of the NOAA ECOHAB funded Gulf of Maine Toxicity (GOMTOX)1 project, we determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP) toxin composition, and concentration in quantitatively-sampled size-fractionated (20–64, 64–100, 100–200, 200–500, and > 500 μm) particulate water samples, and the community composition of potential grazers of A. fundyense in these size fractions, at multiple depths (typically 1, 10, 20 m, and near-bottom) during 10 large-scale sampling cruises during the A. fundyense bloom season (May–August) in the coastal Gulf of Maine and on Georges Bank in 2007, 2008, and 2010. Our findings were as follows: (1) when all sampling stations and all depths were summed by year, the majority (94% ± 4%) of total PSP toxicity was contained in the 20–64 μm size fraction; (2) when further analyzed by depth, the 20–64 μm size fraction was the primary source of toxin for 97% of the stations and depths samples over three years; (3) overall PSP toxin profiles were fairly consistent during the three seasons of sampling with gonyautoxins (1, 2, 3, and 4) dominating (90.7% ± 5.5%), followed by the carbamate toxins saxitoxin (STX) and neosaxitoxin (NEO) (7.7% ± 4.5%), followed by n-sulfocarbamoyl toxins (C1 and 2, GTX5) (1.3% ± 0.6%), followed by all decarbamoyl toxins (dcSTX, dcNEO, dcGTX2&3) (< 1%), although differences were noted between PSP toxin compositions for nearshore coastal Gulf of Maine sampling stations compared to offshore Georges Bank sampling stations for 2 out of 3 years; (4) surface cell counts of A. fundyense were a fairly reliable predictor of the presence of toxins throughout the water column; and (5) nearshore surface cell counts of A. fundyense in the coastal Gulf of Maine were not a reliable predictor of A. fundyense populations offshore on Georges Bank for 2 out of the 3 years sampled. PMID:25076816

  14. PSP toxin levels and plankton community composition and abundance in size-fractionated vertical profiles during spring/summer blooms of the toxic dinoflagellate Alexandrium fundyense in the Gulf of Maine and on Georges Bank, 2007, 2008, and 2010: 1. Toxin levels.

    PubMed

    Deeds, Jonathan R; Petitpas, Christian M; Shue, Vangie; White, Kevin D; Keafer, Bruce A; McGillicuddy, Dennis J; Milligan, Peter J; Anderson, Donald M; Turner, Jefferson T

    2014-05-01

    As part of the NOAA ECOHAB funded Gulf of Maine Toxicity (GOMTOX) project, we determined Alexandrium fundyense abundance, paralytic shellfish poisoning (PSP) toxin composition, and concentration in quantitatively-sampled size-fractionated (20-64, 64-100, 100-200, 200-500, and > 500 μm) particulate water samples, and the community composition of potential grazers of A. fundyense in these size fractions, at multiple depths (typically 1, 10, 20 m, and near-bottom) during 10 large-scale sampling cruises during the A. fundyense bloom season (May-August) in the coastal Gulf of Maine and on Georges Bank in 2007, 2008, and 2010. Our findings were as follows: (1) when all sampling stations and all depths were summed by year, the majority (94% ± 4%) of total PSP toxicity was contained in the 20-64 μm size fraction; (2) when further analyzed by depth, the 20-64 μm size fraction was the primary source of toxin for 97% of the stations and depths samples over three years; (3) overall PSP toxin profiles were fairly consistent during the three seasons of sampling with gonyautoxins (1, 2, 3, and 4) dominating (90.7% ± 5.5%), followed by the carbamate toxins saxitoxin (STX) and neosaxitoxin (NEO) (7.7% ± 4.5%), followed by n-sulfocarbamoyl toxins (C1 and 2, GTX5) (1.3% ± 0.6%), followed by all decarbamoyl toxins (dcSTX, dcNEO, dcGTX2&3) (< 1%), although differences were noted between PSP toxin compositions for nearshore coastal Gulf of Maine sampling stations compared to offshore Georges Bank sampling stations for 2 out of 3 years; (4) surface cell counts of A. fundyense were a fairly reliable predictor of the presence of toxins throughout the water column; and (5) nearshore surface cell counts of A. fundyense in the coastal Gulf of Maine were not a reliable predictor of A. fundyense populations offshore on Georges Bank for 2 out of the 3 years sampled.

  15. Lead toxicity: a review.

    PubMed

    Wani, Ab Latif; Ara, Anjum; Usmani, Jawed Ahmad

    2015-06-01

    Lead toxicity is an important environmental disease and its effects on the human body are devastating. There is almost no function in the human body which is not affected by lead toxicity. Though in countries like US and Canada the use of lead has been controlled up to a certain extent, it is still used vehemently in the developing countries. This is primarily because lead bears unique physical and chemical properties that make it suitable for a large number of applications for which humans have exploited its benefits from historical times and thus it has become a common environmental pollutant. Lead is highly persistent in the environment and because of its continuous use its levels rise in almost every country, posing serious threats. This article reviews the works listed in the literature with recent updates regarding the toxicity of lead. Focus is also on toxic effects of lead on the renal, reproductive and nervous system. Finally the techniques available for treating lead toxicity are presented with some recent updates.

  16. Lead toxicity: a review

    PubMed Central

    Ara, Anjum; Usmani, Jawed Ahmad

    2015-01-01

    Lead toxicity is an important environmental disease and its effects on the human body are devastating. There is almost no function in the human body which is not affected by lead toxicity. Though in countries like US and Canada the use of lead has been controlled up to a certain extent, it is still used vehemently in the developing countries. This is primarily because lead bears unique physical and chemical properties that make it suitable for a large number of applications for which humans have exploited its benefits from historical times and thus it has become a common environmental pollutant. Lead is highly persistent in the environment and because of its continuous use its levels rise in almost every country, posing serious threats. This article reviews the works listed in the literature with recent updates regarding the toxicity of lead. Focus is also on toxic effects of lead on the renal, reproductive and nervous system. Finally the techniques available for treating lead toxicity are presented with some recent updates. PMID:27486361

  17. What Renders TAU Toxic

    PubMed Central

    Götz, Jürgen; Xia, Di; Leinenga, Gerhard; Chew, Yee Lian; Nicholas, Hannah R.

    2013-01-01

    TAU is a microtubule-associated protein that under pathological conditions such as Alzheimer’s disease (AD) forms insoluble, filamentous aggregates. When 20 years after TAU’s discovery the first TAU transgenic mouse models were established, one declared goal that was achieved was the modeling of authentic TAU aggregate formation in the form of neurofibrillary tangles. However, as we review here, it has become increasingly clear that TAU causes damage much before these filamentous aggregates develop. In fact, because TAU is a scaffolding protein, increased levels and an altered subcellular localization (due to an increased insolubility and impaired clearance) result in the interaction of TAU with cellular proteins with which it would otherwise either not interact or do so to a lesser degree, thereby impairing their physiological functions. We specifically discuss the non-axonal localization of TAU, the role phosphorylation has in TAU toxicity and how TAU impairs mitochondrial functions. A major emphasis is on what we have learned from the four available TAU knock-out models in mice, and the knock-out of the TAU/MAP2 homolog PTL-1 in worms. It has been proposed that in human pathological conditions such as AD, a rare toxic TAU species exists which needs to be specifically removed to abrogate TAU’s toxicity and restore neuronal functions. However, what is toxic in one context may not be in another, and simply reducing, but not fully abolishing TAU levels may be sufficient to abrogate TAU toxicity. PMID:23772223

  18. Metabolism and toxicity of arsenicals in mammals.

    PubMed

    Sattar, Adeel; Xie, Shuyu; Hafeez, Mian Abdul; Wang, Xu; Hussain, Hafiz Iftikhar; Iqbal, Zahid; Pan, Yuanhu; Iqbal, Mujahid; Shabbir, Muhammad Abubakr; Yuan, Zonghui

    2016-12-01

    Arsenic (As) is a metalloid usually found in organic and inorganic forms with different oxidation states, while inorganic form (arsenite As-III and arsenate As-v) is considered to be more hazardous as compared to organic form (methylarsonate and dimethylarsinate), with mild or no toxicity in mammals. Due to an increasing trend to using arsenicals as growth promoters or for treatment purposes, the understanding of metabolism and toxicity of As gets vital importance. Its toxicity is mainly depends on oxi-reduction states (As-III or As-v) and the level of methylation during the metabolism process. Currently, the exact metabolic pathways of As have yet to be confirmed in humans and food producing animals. Oxidative methylation and glutathione conjugation is believed to be major pathways of As metabolism. Oxidative methylation is based on conversion of Arsenite in to mono-methylarsonic acid and di-methylarsenic acid in mammals. It has been confirmed that As is only methylated in the presence of glutathione or thiol compounds, suggesting that As is being methylated in trivalent states. Subsequently, non-conjugated trivalent arsenicals are highly reactive with thiol which converts the trivalent arsenicals in to less toxic pentavalent forms. The glutathione conjugate stability of As is the most important factor for determining the toxicity. It can lead to DNA damage by alerting enzyme profile and production of reactive oxygen and nitrogen species which causes the oxidative stress. Moreover, As causes immune-dysfunction by hindering cellular and humeral immune response. The present review discussed different metabolic pathways and toxic outcomes of arsenicals in mammals which will be helpful in health risk assessment and its impact on biological world.

  19. The contribution of chronic illness to acceptance of death in hospitalized patients.

    PubMed

    Nichols, Joyce; Riegel, Barbara

    2002-02-01

    This pilot study explored acceptance of death in the chronically ill. It was hypothesized that chronic illness would be a positive predictor of premature acceptance of death. Acceptance of death, if premature, may lead to untimely acquiescence to death, making people less likely to seek medical care and practice preventive health behaviors. A correlational design was used to explore the relationship between chronic illness and acceptance of death, controlling for age. Data were collected on death acceptance using the revised version of the Life Attitude Profile. Number of chronic illnesses was obtained from self-report and a review of the medical record in a sample of 76 hospitalized individuals. The number of chronic illnesses was significantly and positively associated with death acceptance, but age was not. The model explained only 5.2% of the variance in death acceptance, however. Chronic illness is clearly only one of many factors stimulating individuals to ponder death earlier than expected. Nurses need to be alert to the possibility that individuals with multiple chronic illnesses may be prematurely acquiescing to death. If acquiescence causes failure to participate in care, it could potentially exacerbate chronic conditions unnecessarily.

  20. Self-acceptance, acceptance of others, and SYMLOG: equivalent measures of the two central interpersonal dimensions?

    PubMed

    Hurley, J R

    1991-07-01

    After 50 hours of small group participation during 9 weeks, 91 young adults rated each same-group member's conduct on SYMLOG's dimensions of dominance, friendliness, and task-orientedness. Earlier, they made similar ratings twice, several weeks apart, on separate measures of self-acceptance and acceptance of others. Individuals' mean SYMLOG dominance ratings by group peers correlated much more highly with aggregated ratings for self-acceptance (.83) than for other-acceptance (.02), while SYMLOG friendliness correlated more positively with acceptance of others (.85) than with self-acceptance (.05). Self-ratings yielded parallel, but weaker associations. After attenuation corrections, these divergent approaches to assessing the interpersonal domain's central dimensions yielded empirically equivalent results. Both methods provide measures relevant to small group processes.

  1. Toxicity of adipic acid.

    PubMed

    Kennedy, Gerald L

    2002-05-01

    Adipic acid has very low acute toxicity in rats with an LD50 > 5000 mg/kg. Adipic acid produced mild to no skin irritation on intact guinea pig skin as a 50% concentration in propylene glycol; it was not a skin sensitizer. Adipic acid caused mild conjunctival irritation in washed rabbit eyes; in unwashed rabbit eyes, there was mild conjunctival irritation, minimal iritis, but no corneal effects. Adipic acid dust may irritate the mucous membranes of the lungs and nose. In a 2-year feeding study, rats fed adipic acid at concentrations up to 5% in the diet exhibited only weight loss. Adipic acid is not genetically active in a wide variety of assay systems. Adipic acid caused no developmental toxicity in mice, rats, rabbits, or hamsters when administered orally. Adipic acid is partially metabolized in humans; the balance is eliminated unchanged in the urine. Adipic acid is slightly to moderately toxic to fish, daphnia, and algae in acute tests.

  2. Iron metabolism and toxicity

    SciTech Connect

    Papanikolaou, G.; Pantopoulos, K. . E-mail: kostas.pantopoulos@mcgill.ca

    2005-01-15

    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.

  3. Neuromuscular toxicity of therapy.

    PubMed

    Mollman, J E

    1992-06-01

    The peripheral nervous system is frequently impaired in patients who have cancer. This impairment often results from toxicity of treatment but may also be due to direct invasion by tumor or may be part of a paraneoplastic syndrome. This review summarizes the recent literature regarding peripheral neuropathies and myopathies that are seen in patients with cancer. Highlights include the neuromuscular toxicity of some of the newer chemotherapeutic agents and immune mediators such as taxol and interleukin-2; a discussion of some of the agents being investigated for chemoprotection and rescue; an assessment of the evidence supporting the concept of motor neuron disease as a paraneoplastic disorder; and an interesting case report of megakaryoblastic leukemia invading peripheral nerves. Also summarized are some nice reviews and prospective studies of the toxicity of more conventional treatments.

  4. FINAL DISPOSAL OF RADIOACTIVE WASTE IN GERMANY: PLAN APPROVAL PROCESS OF KONRAD MINE AND ACCEPTANCE REQUIREMENTS

    SciTech Connect

    Bandt, Gabriele; Posnatzki, Britta; Beckers, Klaus-Arno

    2003-02-27

    Currently no final repository for any type of radioactive waste is operated in Germany. Preliminary Final Storage Acceptance Requirements for radioactive waste packages were published in 1995. Up to now these are the basis for treatment of radioactive waste in Germany. After licensing of the final repository these preliminary waste acceptance requirements are completed with licensing conditions. Some of these conditions affect the preliminary waste acceptance requirements, e. g. behavior of chemo-toxic substances in case of accidents in the final repository or the allowed maximum concentration of fissile material. The presented examples of radioactive waste conditioning campaigns demonstrate that no difficulties are expected in management, characterization and quality assurance of radioactive wastes due to the licensing conditions.

  5. Aquatic toxicity of triclosan.

    PubMed

    Orvos, David R; Versteeg, Donald J; Inauen, Josef; Capdevielle, Marie; Rothenstein, Arthur; Cunningham, Virginia

    2002-07-01

    The aquatic toxicity of triclosan (TCS), a chlorinated biphenyl ether used as an antimicrobial in consumer products, was studied with activated-sludge microorganisms, algae, invertebrates, and fish. Triclosan, a compound used for inhibiting microbial growth, was not toxic to wastewater microorganisms at concentrations less than aqueous solubility. The 48-h Daphnia magna median effective concentration (EC50) was 390 microg/L and the 96-h median lethal concentration values for Pimephales promelas and Lepomis macrochirus were 260 and 370 microg/L, respectively. A no-observed-effect concentration (NOEC) and lowest-observed-effect concentration of 34.1 microg/L and 71.3 microg/L, respectively, were determined with an early life-stage toxicity test with Oncorhynchus mykiss. During a 96-h Scenedesmus study, the 96-h biomass EC50 was 1.4 microg/L and the 96-h NOEC was 0.69 microg/L. Other algae and Lemna also were investigated. Bioconcentration was assessed with Danio rerio. The average TCS accumulation factor over the five-week test period was 4,157 at 3 microg/L and 2,532 at 30 microg/L. Algae were determined to be the most susceptible organisms. Toxicity of a TCS-containing wastewater secondary effluent to P. promelas and Ceriodaphnia was evaluated and no observed differences in toxicity between control and TCS-treated laboratory units were detected. The neutral form of TCS was determined to be associated with toxic effects. Ionization and sorption will mitigate those effects in the aquatic compartment.

  6. Children acceptance of laser dental treatment

    NASA Astrophysics Data System (ADS)

    Lazea, Andreea; Todea, Carmen

    2016-03-01

    Objectives: To evaluate the dental anxiety level and the degree of acceptance of laser assisted pedodontic treatments from the children part. Also, we want to underline the advantages of laser use in pediatric dentistry, to make this technology widely used in treating dental problems of our children patients. Methods: Thirty pediatric dental patients presented in the Department of Pedodontics, University of Medicine and Pharmacy "Victor Babeş", Timişoara were evaluated using the Wong-Baker pain rating scale, wich was administered postoperatory to all patients, to assess their level of laser therapy acceptance. Results: Wong-Baker faces pain rating scale (WBFPS) has good validity and high specificity; generally it's easy for children to use, easy to compare and has good feasibility. Laser treatment has been accepted and tolerated by pediatric patients for its ability to reduce or eliminate pain. Around 70% of the total sample showed an excellent acceptance of laser dental treatment. Conclusions: Laser technology is useful and effective in many clinical situations encountered in pediatric dentistry and a good level of pacient acceptance is reported during all laser procedures on hard and soft tissues.

  7. Acceptance criteria for method equivalency assessments.

    PubMed

    Chatfield, Marion J; Borman, Phil J

    2009-12-15

    Quality by design (ICH-Topic Q8) requires that process control strategy requirements are met and maintained. The challenging task of setting appropriate acceptance criteria for assessment of method equivalence is a critical component of satisfying these requirements. The use of these criteria will support changes made to methods across the product lifecycle. A method equivalence assessment is required when a change is made to a method which may pose a risk to its ability to monitor the quality of the process. Establishing appropriate acceptance criteria are a vital, but not clearly understood, prerequisite to deciding the appropriate design/sample size of the equivalency study. A number of approaches are proposed in the literature for setting acceptance criteria for equivalence which address different purposes. This perspective discusses those purposes and then provides more details on setting acceptance criteria based on patient and producer risk, e.g., tolerance interval approach and the consideration of method or process capability. Applying these to a drug substance assay method for batch release illustrates that, for the equivalence assessment to be meaningful, a clear understanding and appraisal of the control requirements of the method is needed. Rather than a single exact algorithm, the analyst's judgment on a number of aspects is required in deciding the appropriate acceptance criteria.

  8. Physiologic correlates to background noise acceptance

    NASA Astrophysics Data System (ADS)

    Tampas, Joanna; Harkrider, Ashley; Nabelek, Anna

    2001-05-01

    Acceptance of background noise can be evaluated by having listeners indicate the highest background noise level (BNL) they are willing to accept while following the words of a story presented at their most comfortable listening level (MCL). The difference between the selected MCL and BNL is termed the acceptable noise level (ANL). One of the consistent findings in previous studies of ANL is large intersubject variability in acceptance of background noise. This variability is not related to age, gender, hearing sensitivity, personality, type of background noise, or speech perception in noise performance. The purpose of the current experiment was to determine if individual differences in physiological activity measured from the peripheral and central auditory systems of young female adults with normal hearing can account for the variability observed in ANL. Correlations between ANL and various physiological responses, including spontaneous, click-evoked, and distortion-product otoacoustic emissions, auditory brainstem and middle latency evoked potentials, and electroencephalography will be presented. Results may increase understanding of the regions of the auditory system that contribute to individual noise acceptance.

  9. Biomolecular Profiling of Jet Fuel Toxicity Using Proteomics

    DTIC Science & Technology

    2006-02-28

    at room temperature and 8 volumes (of wet tissue weight) of a lysis buffer containing 9 M urea (BDH Aristar), 4% Igepal CA- 630 (Sigma-Aldrich), 1...buffer containing 9 M urea, 4% Igepal CA-630 ([octylphenoxy] polyethoxyethanol), 1 % DTT and 2% carrier ampholytes (pH 8-10.5) were added directly to

  10. Toxic Hazards Research Unit

    DTIC Science & Technology

    1977-09-01

    showed that OMP-4 had produced eschar formation and destruction of the dermal layer down to the fascia, thus classifying it as a corrosive material. Both...dimethylamino Ethyl Corporationrial wer pr aredp- cresol with corn oil or pro- (solid) pylene glycol and ad- N,N’-disalicylidene-l,2- duPontpropane diamine...amino guanidine Rat >5000 5000(0) Below toxic 2,6,di-tert-butyl-di- Rata 1189(669-2111) 500(0),1000(3),2000(4) Toxic methylamino-p- cresol Mousea 307(190

  11. The toxicity of refrigerants

    SciTech Connect

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  12. 5 CFR 2601.204 - Conditions for acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Conditions for acceptance. 2601.204... IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts § 2601.204 Conditions for acceptance. (a) No gift may be accepted that: (1)...

  13. Recreating an esthetically and functionally acceptable dentition: a multidisciplinary approach.

    PubMed

    Goyal, Mukesh Kumar; Goyal, Shelly; Hegde, Veena; Balkrishana, Dhanasekar; Narayana, Aparna I

    2013-01-01

    Patients today demand a youthful, attractive smile with comfortable functional acceptance. The complete oral rehabilitation of patients with a functionally compromised dentition frequently involves a multidisciplinary approach and presents a considerable clinical challenge. To a great extent, proper patient selection and careful interdisciplinary treatment planning, including acknowledgment of the patient's perceived needs, reasons for seeking services, financial ability, and socioeconomic profile, can govern the predictability of successful restorations. This clinical report describes a successful interdisciplinary approach for the management of a severely worn dentition with reduced vertical dimension of occlusion. Treatment modalities included periodontal crown lengthening procedures, endodontic treatment followed by post and core restorations, and prosthetic rehabilitation for severe tooth surface loss and reduced vertical dimension of occlusion comprising metal-ceramic restorations in esthetic zones and full-metal restorations in posterior regions.

  14. Can YAG screen accept LEReC bunch train?

    SciTech Connect

    Seletskiy, S.; Thieberger, P.; Miller, T.

    2016-05-18

    LEReC RF diagnostic beamline is supposed to accept 250 us long pulse trains of 1.6 MeV – 2.6 MeV (kinetic energy) electrons. This beamline is equipped with YAG profile monitor. Since we are interested in observing only the last macro bunch in the train, one of the possibilities is to install a fast kicker and a dedicated dump upstream of the YAG screen (and related diagnostics equipment). This approach is expensive and challenging from engineering point of view. Another possibility is to send the whole pulse train to the YAG screen and to use a fast gated camera (such as Imperex B0610 with trigger jitter under 60ns) to observe the image from the last pulse only. In this paper we study the feasibility of the last approach.

  15. The use of IV lipid emulsion for lipophilic drug toxicities.

    PubMed

    Kaplan, Amy; Whelan, Megan

    2012-01-01

    IV lipid emulsion (ILE) therapy is emerging as a potential antidote for lipophilic drug toxicities in both human and veterinary medicine. ILE has already gained acceptance in human medicine as a treatment of local anesthetic systemic toxicity, but its mechanism of action, safety margins, and standardized dosing information remains undetermined at this time. Experimental and anecdotal use of ILE in the human and veterinary literature, theorized mechanisms of action, current dosing recommendations, potential adverse effects, and indications for use in human and veterinary emergency medicine are reviewed herein.

  16. When should conscientious objection be accepted?

    PubMed

    Magelssen, Morten

    2012-01-01

    This paper makes two main claims: first, that the need to protect health professionals' moral integrity is what grounds the right to conscientious objection in health care; and second, that for a given claim of conscientious objection to be acceptable to society, a certain set of criteria should be fulfilled. The importance of moral integrity for individuals and society, including its special role in health care, is advocated. Criteria for evaluating the acceptability of claims to conscientious objection are outlined. The precise content of the criteria is dictated by the two main interests that are at stake in the dilemma of conscientious objection: the patient's interests and the health professional's moral integrity. Alternative criteria proposed by other authors are challenged. The bold claim is made that conscientious objection should be recognised by society as acceptable whenever the five main criteria of the proposed set are met.

  17. STOL ride quality criteria - Passenger acceptance.

    NASA Technical Reports Server (NTRS)

    Jacobson, I. D.; Kuhlthau, A. R.

    1972-01-01

    The ability to mathematically model human reaction to variables involved in transportation systems offers a very desirable tool both for the prediction of passenger acceptance of proposed systems, and for establishing acceptance criteria for the system designer. As a first step in the development of a general model for STOL systems, a mathematical formulation is presented which accepts as inputs nine variables felt to be important in flight under STOL-type conditions and presents an index of human response as the output. The variables used are three linear motions, three angular motions, pressure, temperature and noise level. The results are used to establish specifications for stability augmentation systems to improve the ride quality of existing STOL aircraft.

  18. Acceptance Priority Ranking & Annual Capacity Report

    SciTech Connect

    2004-07-31

    The Nuclear Waste Policy Act of 1982, as amended (the Act), assigns the Federal Government the responsibility for the disposal of spent nuclear fuel and high-level waste. Section 302(a) of the Act authorizes the Secretary to enter into contracts with the owners and generators of commercial spent nuclear fuel and/or high-level waste. The Standard Contract for Disposal of Spent Nuclear Fuel and/or High-Level Radioactive Waste (Standard Contract) established the contractual mechanism for the Department's acceptance and disposal of spent nuclear fuel and high-level waste. It includes the requirements and operational responsibilities of the parties to the Standard Contract in the areas of administrative matters, fees, terms of payment, waste acceptance criteria, and waste acceptance procedures. The Standard Contract provides for the acquisition of title to the spent nuclear fuel and/or high-level waste by the Department, its transportation to Federal facilities, and its subsequent disposal.

  19. A survey of physicians' acceptance of telemedicine.

    PubMed

    Sheng, O R; Hu, P J; Chau, P Y; Hjelm, N M; Tam, K Y; Wei, C P; Tse, J

    1998-01-01

    Physicians' acceptance of telemedicine is an important managerial issue facing health-care organizations that have adopted, or are about to adopt, telemedicine. Most previous investigations of the acceptance of telemedicine have lacked theoretical foundation and been of limited scope. We examined technology acceptance and usage among physicians and specialists from 49 clinical departments at eight public tertiary hospitals in Hong Kong. Out of the 1021 questionnaires distributed, 310 were completed and returned, a 30% response rate. The preliminary findings suggested that use of telemedicine among clinicians in Hong Kong was moderate. While 18% of the respondents were using some form of telemedicine for patient care and management, it accounted for only 6.3% of the services provided. The intensity of their technology usage was also low, accounting for only 6.8% of a typical telemedicine-assisted service. These preliminary findings have managerial implications.

  20. Mercury toxicity and neurodegenerative effects.

    PubMed

    Carocci, Alessia; Rovito, Nicola; Sinicropi, Maria Stefania; Genchi, Giuseppe

    2014-01-01

    Mercury is among the most toxic heavy metals and has no known physiological role in humans. Three forms of mercury exist: elemental, inorganic and organic. Mercury has been used by man since ancient times. Among the earliest were the Chinese and Romans, who employed cinnabar (mercury sulfide) as a red dye in ink (Clarkson et al. 2007). Mercury has also been used to purify gold and silver minerals by forming amalgams. This is a hazardous practice, but is still widespread in Brazil's Amazon basin, in Laos and in Venezuela, where tens of thousands of miners are engaged in local mining activities to find and purify gold or silver. Mercury compounds were long used to treat syphilis and the element is still used as an antiseptic,as a medicinal preservative and as a fungicide. Dental amalgams, which contain about 50% mercury, have been used to repair dental caries in the U.S. since 1856.Mercury still exists in many common household products around the world.Examples are: thermometers, barometers, batteries, and light bulbs (Swain et al.2007). In small amounts, some organo mercury-compounds (e.g., ethylmercury tiosalicylate(thimerosal) and phenylmercury nitrate) are used as preservatives in some medicines and vaccines (Ballet al. 2001).Each mercury form has its own toxicity profile. Exposure to Hg0 vapor and MeHg produce symptoms in CNS, whereas, the kidney is the target organ when exposures to the mono- and di-valent salts of mercury (Hg+ and Hg++, respectively)occur. Chronic exposure to inorganic mercury produces stomatitis, erethism and tremors. Chronic MeHg exposure induced symptoms similar to those observed in ALS, such as the early onset of hind limb weakness (Johnson and Atchison 2009).Among the organic mercury compounds, MeHg is the most biologically available and toxic (Scheuhammer et a!. 2007). MeHg is neurotoxic, reaching high levels of accumulation in the CNS; it can impair physiological function by disrupting endocrine glands (Tan et a!. 2009).The most

  1. Assessing the potential toxicity of new pharmaceuticals.

    PubMed

    Johnson, D E; Wolfgang, G H

    2001-09-01

    Optimizing chemical structures to create potentially safe drugs during discovery and early development relies on a combination of predictive algorithms, screening, formal toxicology studies, and early clinical trials. Early in the process three critical questions emerge that must be answered by a detailed "profiling" approach. These questions are: 1) is there a correlation between the chemical structure and potential toxicity that can be used to optimize structures of lead compounds, 2) can specific markers of potential toxicity can be identified carly and used as mechanistic decision-making screens, and 3) will exposures (plasma levels) in animal studies correlate with exposures encountered in the clinic thereby providing "coverage" for safety? Depending on the therapeutic class of compounds being considered and the level of knowledge available, feedback loops of information can be established to guide the development process.

  2. The Third FRAME Toxicity Committee: working toward greater implementation of alternatives in toxicity testing.

    PubMed

    Combes, Robert D; Balls, Michael; Bansil, Lee; Barratt, Martin; Bell, David; Botham, Philip; Broadhead, Caren; Clothier, Richard; George, Elizabeth; Fentem, Julia; Jackson, Michael; Indans, Ian; Loizou, George; Navaratnam, Vyra; Pentreath, Victor; Phillips, Barry; Stemplewski, Henry; Stewart, Jane

    2004-06-01

    FRAME (the Fund for the Replacement of Animals in Medical Experiments; http://www. frame.org.uk) is a scientific charity, which has, for over 30 years, been advocating and conducting its own research on the application of the Three Rs (reduction, refinement and replacement) to animal experimentation. FRAME develops and validates scientifically based replacement alternative methods to facilitate their acceptance by scientists and regulators. As part of these activities, FRAME established a FRAME Toxicity Committee in 1979, and a report of its work was published in 1982, and discussed in the proceedings of a subsequent meeting, published in 1983. A Second Toxicity Committee formed in 1988, reported its work in 1990, which was discussed in the proceedings of a subsequent conference, published in 1991. The work of these committees was extremely successful and influential in laying the foundation for later activities in alternatives research. A Third FRAME Toxicity Committee was formed in 1999, since much progress had been achieved in the previous decade, especially with regard to the successful validation of several non-animal replacement methods and the start of their regulatory acceptance. Moreover, some new test methods are on the point of being validated, and many new techniques and discoveries are impacting on toxicity testing. Also, interest in reduction and refinement in toxicology has increased. However, there is considerable scope and need for the further implementation of the Three Rs in toxicity testing, especially due to recent plans for the large-scale testing of high-production volume, hormonally-active and existing chemicals, and the increasing use of transgenic animal models. The new committee comprises 18 experts from industry, academia, animal welfare, legislative and regulatory bodies, with one observer from the UK Government Home Office. The main objective is to review progress made in the application of the Three Rs in the development and safety

  3. Consumer Acceptance of a Polyphenolic Coffee Beverage.

    PubMed

    Nguyen, Thuy; Kuchera, Meredith; Smoot, Katie; Diako, Charles; Vixie, Beata; Ross, Carolyn F

    2016-10-05

    The objective of this study was to determine if Chardonnay grape seed pomace (GSP), a waste stream of wine production, could be used as a functional ingredient in brewed coffee. Two consumer panels were conducted to assess the acceptance of coffee at coffee replacement (w/w) values of 0% (control), 6.25%, 12.50%, 18.75%, or 25% GSP. The 1st consumer panel (n = 80) assessed the coffee samples served "black." The 2nd panel (n = 67) assessed the coffee samples with adjustment (that is, sweeteners, milk, and cream) options available. Consumer sensory evaluation involved evaluating the 5 treatments individually for acceptance of appearance, aroma, taste/flavor, and overall acceptance using a 9-point hedonic scale. A check-all-that-apply questionnaire surveyed the sensory attributes describing aroma, appearance, and taste/flavor of the samples. Oxygen radical absorbance capacity was used to measure the effects of antioxidant levels in GSP coffee samples. Results showed that GSP could be added at 6.25% replacement without significantly affecting the overall consumer acceptance of coffee compared to the control (0% GSP). Above 6.25% GSP supplementation, the coffee beverage was described as more tan, milky, watery/dilute, and mild, and was generally less accepted by the consumers. GSP also increased the antioxidant capacity of the coffee compared to the control (0% GSP), with no significant differences among replacement values. Therefore, 6.25% GSP replacement is recommended for creating coffee beverages acceptable to consumers. Further in vivo investigation may substantiate the free-radical scavenging capacity of GSP coffee and its potential health benefits.

  4. Hanford Site solid waste acceptance criteria

    SciTech Connect

    Ellefson, M.D.

    1998-07-01

    Order 5820.2A requires that each treatment, storage, and/or disposal facility (referred to in this document as TSD unit) that manages low-level or transuranic waste (including mixed waste and TSCA PCB waste) maintain waste acceptance criteria. These criteria must address the various requirements to operate the TSD unit in compliance with applicable safety and environmental requirements. This document sets forth the baseline criteria for acceptance of radioactive waste at TSD units operated by WMH. The criteria for each TSD unit have been established to ensure that waste accepted can be managed in a manner that is within the operating requirements of the unit, including environmental regulations, DOE Orders, permits, technical safety requirements, waste analysis plans, performance assessments, and other applicable requirements. Acceptance criteria apply to the following TSD units: the Low-Level Burial Grounds (LLBG) including both the nonregulated portions of the LLBG and trenches 31 and 34 of the 218-W-5 Burial Ground for mixed waste disposal; Central Waste Complex (CWC); Waste Receiving and Processing Facility (WRAP); and T Plant Complex. Waste from all generators, both from the Hanford Site and from offsite facilities, must comply with these criteria. Exceptions can be granted as provided in Section 1.6. Specific waste streams could have additional requirements based on the 1901 identified TSD pathway. These requirements are communicated in the Waste Specification Records (WSRds). The Hanford Site manages nonradioactive waste through direct shipments to offsite contractors. The waste acceptance requirements of the offsite TSD facility must be met for these nonradioactive wastes. This document does not address the acceptance requirements of these offsite facilities.

  5. ToxCast: Developing Predictive Signatures of Chemically Induced Toxicity (S)

    EPA Science Inventory

    ToxCast, the United States Environmental Protection Agency’s chemical prioritization research program, is developing methods for utilizing computational chemistry, bioactivity profiling and toxicogenomic data to predict potential for toxicity and prioritize limited testing resour...

  6. [Could infant euthanasia be ever acceptable?].

    PubMed

    Beca, J P; Leiva, A

    2014-10-01

    The recent enactment of a law that allows infant euthanasia in Belgium raises questions with varied answers. To contribute to a better understanding of the topic, euthanasia and legislation concepts are described. After a bioethical analysis, we propose as conclusion that children euthanasia could only be acceptable in very exceptional situations in which palliative measures have failed. The answer should be that it is not acceptable in our setting, not until we have public policies, protocols and palliative care services for terminally ill children.

  7. Nevada Test Site Waste Acceptance Criteria

    SciTech Connect

    U. S. Department of Energy, National Nuclear Security Administration Nevada Site Office

    2005-10-01

    This document establishes the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) waste acceptance criteria (WAC). The WAC provides the requirements, terms, and conditions under which the Nevada Test Site (NTS) will accept low-level radioactive (LLW) and mixed waste (MW) for disposal. It includes requirements for the generator waste certification program, characterization, traceability, waste form, packaging, and transfer. The criteria apply to radioactive waste received at the NTS Area 3 and Area 5 Radioactive Waste Management Complex (RWMC) for storage or disposal.

  8. Measuring Acceptance of Sleep Difficulties: The Development of the Sleep Problem Acceptance Questionnaire

    PubMed Central

    Bothelius, Kristoffer; Jernelöv, Susanna; Fredrikson, Mats; McCracken, Lance M.; Kaldo, Viktor

    2015-01-01

    Study Objectives: Acceptance may be an important therapeutic process in sleep medicine, but valid psychometric instruments measuring acceptance related to sleep difficulties are lacking. The purpose of this study was to develop a measure of acceptance in insomnia, and to examine its factor structure as well as construct validity. Design: In a cross-sectional design, a principal component analysis for item reduction was conducted on a first sample (A) and a confirmatory factor analysis on a second sample (B). Construct validity was tested on a combined sample (C). Setting: Questionnaire items were derived from a measure of acceptance in chronic pain, and data were gathered through screening or available from pretreatment assessments in four insomnia treatment trials, administered online, via bibliotherapy and in primary care. Participants: Adults with insomnia: 372 in sample A and 215 in sample B. Sample C (n = 820) included sample A and B with another 233 participants added. Measures: Construct validity was assessed through relations with established acceptance and sleep scales. Results: The principal component analysis presented a two-factor solution with eight items, explaining 65.9% of the total variance. The confirmatory factor analysis supported the solution. Acceptance of sleep problems was more closely related to subjective symptoms and consequences of insomnia than to diary description of sleep, or to acceptance of general private events. Conclusions: The Sleep Problem Acceptance Questionnaire (SPAQ), containing the subscales “Activity Engagement” and “Willingness”, is a valid tool to assess acceptance of insomnia. Citation: Bothelius K, Jernelöv S, Fredrikson M, McCracken LM, Kaldo V. Measuring acceptance of sleep difficulties: the development of the sleep problem acceptance questionnaire. SLEEP 2015;38(11):1815–1822. PMID:26085302

  9. Test systems to identify reproductive toxicants.

    PubMed

    Riecke, K; Stahlmann, R

    2000-09-01

    Experience with drugs and other xenobiotics indicates that both animal testing and epidemiological studies are necessary to provide adequate data for an estimation of risks that might be associated with exposure to a chemical substance. In this review, the pros and cons of test systems for reproductive toxicity are discussed. Usually, several studies are performed to cover the different phases of the reproductive cycle. In the preclinical development of drugs, the three so-called 'segment testing protocols' have been used for several decades now. More recently, new testing concepts have been accepted internationally which include more flexibility in implementation. Several examples of compounds with the potential for reproductive toxicity are presented in more detail in a discussion of some pitfalls of the tests for fertility (phthalates and fluoroquinolones), teratogenicity (acyclovir and protease inhibitors) and postnatal developmental toxicity (fluoroquinolones). In addition, important aspects of kinetics and metabolism as a prerequisite for a rational interpretation of results from toxicological studies are briefly discussed. In vitro assays are useful for supplementing the routinely used in vivo approaches or for studying an expected or defined effect, but they are not suitable for revealing an unknown effect of a chemical on the complex reproductive process.

  10. Fire toxicity scaling

    SciTech Connect

    Braun, E.; Levin, B.C.; Paabo, M.; Gurman, J.; Holt, T.

    1987-02-01

    The toxicity of the thermal-decomposition products from two flexible polyurethane foams (with and without a fire retardant) and a cotton upholstery fabric was evaluated by a series of small-scale and large-scale tests single mock-up upholstery chair tests during smoldering or flaming decomposition. In addition other fire property data such as rates of heat release, effective heats of combustion, specific gas species yields, and smoke obscuration were measured. The degree of toxicity observed during and following the flaming tests (both large-scale room burns and the NBS Toxicity Tests) could be explained by a 3-Gas Model which includes the combined toxicological effects of CO, CO/sub 2/, and HCN. Essentially, no animal deaths were noted during the thirty minute exposures to the non-flaming or smoldering combustion products produced in the NBS Toxicity Test Method or the large-scale room test. In the large-scale room tests, little toxicological difference was noted between decomposition products from the burn room and a second room 12 meters away.

  11. Quebec's Toxic Pollution Concern.

    ERIC Educational Resources Information Center

    Mingie, Walter

    The best solution to the problems of increased pollution of Quebec lakes and rivers with toxic wastes and increased incidence of pollution related diseases is to educate children, to make them aware of the environment and man's interrelationship with it. Attitudes of concern, based on knowledge, must be developed so that as adults, they will take…

  12. Nanomaterials and Retinal Toxicity

    EPA Science Inventory

    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...

  13. Respiratory Toxicity Biomarkers

    EPA Science Inventory

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  14. Iron toxicity screening.

    PubMed

    Cheng, C S; Sullivan, T D; Li, P K

    1979-06-01

    Fischer's method for rapid detection of acute iron toxicity is modified to suit pediatric cases. TPTZ (2,4,6-tripyridyl-s-triazine) is the chromogen of choice since in a small volume of serum slight to moderate hemolysis can cause a false positive result bathophenanthroline. Ordinary labware is amenable to this simplified procedure.

  15. MPI Profiling

    SciTech Connect

    Han, D K; Jones, T R

    2005-02-11

    The Message Passing Interface (MPI) is the de facto message-passing standard for massively parallel programs. It is often the case that application performance is a crucial factor, especially for solving grand challenge problems. While there have been many studies on the scalability of applications, there have not been many focusing on the specific types of MPI calls being made and their impact on application performance. Using a profiling tool called mpiP, a large spectrum of parallel scientific applications were surveyed and their performance results analyzed.

  16. Organic Matter Application Can Reduce Copper Toxicity in Tomato Plants

    ERIC Educational Resources Information Center

    Campbell, Brian

    2010-01-01

    Copper fungicides and bactericides are often used in tomato cultivation and can cause toxic Cu levels in soils. In order to combat this, organic matter can be applied to induce chelation reactions and form a soluble complex by which much of the Cu can leach out of the soil profile or be taken up safely by plants. Organic acids such as citric,…

  17. Toxic Substances Portal- Arsenic

    MedlinePlus

    ... Some PDF files may be electronic conversions from paper copy or other electronic ASCII text files. This ... format errors. Users are referred to the original paper copy of the toxicological profile for the official ...

  18. Comparing toxic air pollutant programs

    SciTech Connect

    Hawkins, S.C.

    1997-05-01

    This article compares state and federal toxic air pollutant programs. The Clean Air Act Ammendments created a program for the control of Hazardous Air Pollutants based on the establishment of control technology standards. State toxic programs can be classified into two categories: control technology-based and ambient concentration-based. Many states have opened to implement the MACT standards while enforcing their own state air toxics programs. Specific topics discussed include the following: the Federal air toxics program; existing state regulations; New Jersey Air Toxic Program; New York Toxics program.

  19. Measuring Technology Acceptance Level of Turkish Pre-Service English Teachers by Using Technology Acceptance Model

    ERIC Educational Resources Information Center

    Kirmizi, Özkan

    2014-01-01

    The aim of this study is to investigate technology acceptance of prospective English teachers by using Technology Acceptance Model (TAM) in Turkish context. The study is based on Structural Equation Model (SEM). The participants of the study from English Language Teaching Departments of Hacettepe, Gazi and Baskent Universities. The participants…

  20. Technology Acceptance in an Academic Context: Faculty Acceptance of Online Education

    ERIC Educational Resources Information Center

    Gibson, Shanan G.; Harris, Michael L.; Colaric, Susan M.

    2008-01-01

    The authors surveyed faculty from a college of business and a college of education regarding their attitudes toward online education. Results of the survey were examined to determine the degree to which the technology acceptance model was able to adequately explain faculty acceptance of online education. Results indicate that perceived usefulness…

  1. Estimation of toxicity using the Toxicity Estimation Software Tool (TEST)

    EPA Science Inventory

    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.

  2. Self-acceptance: a factor in the adoption process.

    PubMed

    DiGiulio, J F

    1988-01-01

    This study determined that high self-acceptance of adoptive parents influenced high parental acceptance of their adopted children. A case is made for emphasizing self-acceptance in adoption procedures.

  3. Environmentally Acceptable Medium Caliber Ammunition Percussion Primers

    DTIC Science & Technology

    2007-10-31

    typically contain lead styphnate and antimony sulfide along with other constituents. Although highly effective, these heavy metal compounds have been...contain barium nitrate. Although not negatively categorized by the EPA itself, barium compounds are generally regarded as toxic and likewise should...contains the lead styphnate based FA956 composition2 which is a typical formulation of conventional military ammunition percussion primers. The

  4. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data

    EPA Science Inventory

    EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

  5. 7 CFR 929.25 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Acceptance. 929.25 Section 929.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES...

  6. 7 CFR 929.25 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acceptance. 929.25 Section 929.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES...

  7. 7 CFR 929.25 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acceptance. 929.25 Section 929.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES...

  8. 7 CFR 929.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 929.25 Section 929.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES...

  9. 7 CFR 929.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 929.25 Section 929.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE CRANBERRIES GROWN IN STATES...

  10. The Acceptance of Global Education Scale.

    ERIC Educational Resources Information Center

    Bingham, Jane

    The Acceptance of Global Education Scale (AGES) measures the attitudes of secondary social studies teachers toward goal statements for the social studies curriculum that reflect a global perspective. AGES can be used in inservice and preservice teacher training programs to form guidelines for construction of a secondary global education…

  11. 37 CFR 1.803 - Acceptable depository.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Acceptable depository. 1.803 Section 1.803 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES Biotechnology Invention Disclosures Deposit...

  12. 37 CFR 1.803 - Acceptable depository.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Acceptable depository. 1.803 Section 1.803 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES Biotechnology Invention Disclosures Deposit...

  13. 37 CFR 1.803 - Acceptable depository.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Acceptable depository. 1.803 Section 1.803 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES Biotechnology Invention Disclosures Deposit...

  14. 37 CFR 1.803 - Acceptable depository.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Acceptable depository. 1.803 Section 1.803 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES Biotechnology Invention Disclosures Deposit...

  15. 37 CFR 1.803 - Acceptable depository.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Acceptable depository. 1.803 Section 1.803 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES Biotechnology Invention Disclosures Deposit...

  16. 7 CFR 1210.323 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Acceptance. 1210.323 Section 1210.323 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Watermelon Research and Promotion Plan National Watermelon Promotion Board § 1210.323...

  17. Acceptance of sugar reduction in flavored yogurt.

    PubMed

    Chollet, M; Gille, D; Schmid, A; Walther, B; Piccinali, P

    2013-09-01

    To investigate what level of sugar reduction is accepted in flavored yogurt, we conducted a hedonic test focusing on the degree of liking of the products and on optimal sweetness and aroma levels. For both flavorings (strawberry and coffee), consumers preferred yogurt containing 10% added sugar. However, yogurt containing 7% added sugar was also acceptable. On the just-about-right scale, yogurt containing 10% sugar was more often described as too sweet compared with yogurt containing 7% sugar. On the other hand, the sweetness and aroma intensity for yogurt containing 5% sugar was judged as too low. A second test was conducted to determine the effect of flavoring concentration on the acceptance of yogurt containing 7% sugar. Yogurts containing the highest concentrations of flavoring (11% strawberry, 0.75% coffee) were less appreciated. Additionally, the largest percentage of consumers perceived these yogurts as "not sweet enough." These results indicate that consumers would accept flavored yogurts with 7% added sugar instead of 10%, but 5% sugar would be too low. Additionally, an increase in flavor concentration is undesirable for yogurt containing 7% added sugar.

  18. 7 CFR 930.26 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 930.26 Section 930.26 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE TART CHERRIES GROWN IN THE STATES...

  19. 40 CFR 600.007 - Vehicle acceptability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... a different maximum value for electric vehicles, plug-in hybrid electric vehicles, and fuel cell... 600.007 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL... Administrator will judge the acceptability of a fuel economy data vehicle on the basis of the...

  20. 7 CFR 922.25 - Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acceptance. 922.25 Section 922.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED...

  1. 7 CFR 922.25 - Acceptance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acceptance. 922.25 Section 922.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED...

  2. 7 CFR 922.25 - Acceptance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acceptance. 922.25 Section 922.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED...

  3. 7 CFR 922.25 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Acceptance. 922.25 Section 922.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED...

  4. 7 CFR 922.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 922.25 Section 922.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE APRICOTS GROWN IN DESIGNATED...

  5. 7 CFR 945.27 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 945.27 Section 945.27 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE IRISH POTATOES GROWN IN...

  6. 48 CFR 611.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Market acceptance. 611.103 Section 611.103 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 611.103 Market...

  7. 48 CFR 1311.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Market acceptance. 1311.103 Section 1311.103 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 1311.103...

  8. 48 CFR 611.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Market acceptance. 611.103 Section 611.103 Federal Acquisition Regulations System DEPARTMENT OF STATE COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 611.103 Market...

  9. 48 CFR 1311.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Market acceptance. 1311.103 Section 1311.103 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 1311.103...

  10. 48 CFR 2811.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Market acceptance. 2811.103 Section 2811.103 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 2811.103...

  11. 48 CFR 811.103 - Market acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Market acceptance. 811.103 Section 811.103 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 811.103...

  12. 48 CFR 811.103 - Market acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Market acceptance. 811.103 Section 811.103 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 811.103...

  13. 48 CFR 1011.103 - Market Acceptance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Market Acceptance. 1011.103 Section 1011.103 Federal Acquisition Regulations System DEPARTMENT OF THE TREASURY COMPETITION AND ACQUISITION PLANNING DESCRIBING AGENCY NEEDS Selecting and Developing Requirements Documents 1011.103...

  14. 7 CFR 915.25 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 915.25 Section 915.25 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE AVOCADOS GROWN IN SOUTH FLORIDA...

  15. 7 CFR 989.32 - Acceptance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Acceptance. 989.32 Section 989.32 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  16. 7 CFR 989.32 - Acceptance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acceptance. 989.32 Section 989.32 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  17. School Choice Acceptance: An Exploratory Explication

    ERIC Educational Resources Information Center

    Koven, Steven G.; Khan, Mobin

    2014-01-01

    School choice is presented by some as a panacea to the challenges facing education in the United States. Acceptance of choice as a solution, however, is far from universal. This article examines two possible contributors to choice adoption: ideology and political culture. Political culture was found to better explain the complex phenomenon of…

  18. Void fraction instrument acceptance test procedure

    SciTech Connect

    Pearce, K.L.

    1994-09-15

    This acceptance test procedure (ATP) was written to test the void fraction instrument (VFI) and verify that the unit is ready for field service. The procedure verifies that the mechanical and electrical features (not specifically addressed in the software ATP) and software alarms are operating as designed.

  19. 24 CFR 7.34 - Acceptability.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., Color Religion, Sex, National Origin, Age, Disability or Reprisal Complaints § 7.34 Acceptability. (a...), the Department shall notify the Complainant in writing of its determination, the rationale for that determination and that those claims will not be investigated, and shall place a copy of the notice in...

  20. Nevada National Security Site Waste Acceptance Criteria

    SciTech Connect

    NSTec Environmental Management

    2012-02-28

    This document establishes the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO), Nevada National Security Site Waste Acceptance Criteria (NNSSWAC). The NNSSWAC provides the requirements, terms, and conditions under which the Nevada National Security Site (NNSS) will accept DOE non-radioactive classified waste, DOE non-radioactive hazardous classified waste, DOE low-level radioactive waste (LLW), DOE mixed low-level waste (MLLW), and U.S. Department of Defense (DOD) classified waste for permanent disposal. Classified waste is the only waste accepted for disposal that may be non-radioactive and will be required to meet the waste acceptance criteria for radioactive waste as specified in this document. The NNSA/NSO and support contractors are available to assist you in understanding or interpreting this document. For assistance, please call the NNSA/NSO Waste Management Project (WMP) at (702) 295-7063, and your call will be directed to the appropriate contact.