WorldWideScience

Sample records for inhibitors reduce excess

  1. Investigation to identify the inhibitors and facilitators of excessive absenteeism in a mining environment / Dianne Williamson

    OpenAIRE

    Williamson, Dianne

    2013-01-01

    The objective of the study was to identify the facilitators and inhibitors of excessive absenteeism in a mining environment. Absenteeism can be one of the most important human resource issues in any organisation. Absenteeism can be really difficult, but with good understanding of what causes absenteeism and how to reduce it, organisations can limit the negative side effects of employee attendance issues. Absenteeism is not only a behaviour caused by an individual's character...

  2. Intermittent Ozonation to Reduce Excess Biological Sludge in SBR

    Directory of Open Access Journals (Sweden)

    Afshin Takdastan

    2009-09-01

    Full Text Available A combination of ozonation and an aerobic biological process such as the activated sludge has been recently developed as an alternative solution for sludge reduction with the objective of minimizing the excess biological sludge production. In this study, two SBR reactors each with a capacity of 20 liters and controlled by an on-line system are used. Once the steady state conditions were set in the reactors, sampling and testing of such parameters as COD, MLSS, MLVSS, DO, SOUR, SVI, residual ozone, and Y coefficient were performed over the 8 months of research. Results showed that during the solid retention time of 10 days, the kinetic coefficients of Y and Kd were 0.58 mg biomass/mg COD and 0.058 1/day, respectively. In the next stage of the study, different concentrations of ozone in the reactor were intermittently used to reduce the excess biological sludge production. The results showed that 22 mg of ozone per 1 gram of MLSS in the reactor was able to reduce the yield coefficient Y from 0.58 to 0.23 mg Biomass/mg COD. In other words, the excess biological sludge reduced by 60% but the soluble COD increased slightly in the effluent and the removal percentage decreased from 92 in the blank reactor to 76 in the test reactor. While the amount of SVI and SOUR for this level of ozone concentration reached 6 mgO2/h.gVSS and 27 ml/g, respectively. No excess sludge was observed in the reactor for an ozone concentration of 27 mg per 1 gram of MLSS.

  3. A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

    Science.gov (United States)

    Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

    2016-08-01

    Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

  4. Excessive sulfur supply reduces cadmium accumulation in brown rice (Oryza sativa L.)

    International Nuclear Information System (INIS)

    Fan Jianling; Hu Zhengyi; Ziadi, Noura; Xia Xu; Wu Congyanghui

    2010-01-01

    Human activities have resulted in cadmium (Cd) and sulfur (S) accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of excessive S supply on iron plaque formation and Cd accumulation in rice plants, using two Cd levels (0, 1.5 mg kg -1 ) combined with three S concentrations (0, 60, 120 mg kg -1 ). The results showed that excessive S supply significantly decreased Cd accumulation in brown rice due to the decrease of Cd availability and the increase of glutathione in rice leaves. But excessive S supply obviously increased Cd accumulation in roots due to the decrease of iron plaque formation on the root surface of rice. Therefore, excessive S supply may result in loss of rice yield, but it could effectively reduce Cd accumulation in brown rice exposed to Cd contaminated soils. - Excessive sulfur reduces cadmium accumulation in brown rice.

  5. Excess electrons in reduced rutile and anatase TiO2

    Science.gov (United States)

    Yin, Wen-Jin; Wen, Bo; Zhou, Chuanyao; Selloni, Annabella; Liu, Li-Min

    2018-05-01

    As a prototypical photocatalyst, TiO2 is a material of scientific and technological interest. In photocatalysis and other applications, TiO2 is often reduced, behaving as an n-type semiconductor with unique physico-chemical properties. In this review, we summarize recent advances in the understanding of the fundamental properties and applications of excess electrons in reduced, undoped TiO2. We discuss the characteristics of excess electrons in the bulk and at the surface of rutile and anatase TiO2 focusing on their localization, spatial distribution, energy levels, and dynamical properties. We examine specific features of the electronic states for photoexcited TiO2, for intrinsic oxygen vacancy and Ti interstitial defects, and for surface hydroxyls. We discuss similarities and differences in the behaviors of excess electrons in the rutile and anatase phases. Finally, we consider the effect of excess electrons on the reactivity, focusing on the interaction between excess electrons and adsorbates.

  6. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    OpenAIRE

    Atar Herziger; Amel Benzerga; Jana Berkessel; Niken L. Dinartika; Matija Franklin; Kamilla K. Steinnes; Felicia Sundström

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing soc...

  7. Excessive sulfur supply reduces cadmium accumulation in brown rice (Oryza sativa L.).

    Science.gov (United States)

    Fan, Jian-Ling; Hu, Zheng-Yi; Ziadi, Noura; Xia, Xu; Wu, Cong-Yang-Hui

    2010-02-01

    Human activities have resulted in cadmium (Cd) and sulfur (S) accumulation in paddy soils in parts of southern China. A combined soil-sand pot experiment was conducted to investigate the influence of excessive S supply on iron plaque formation and Cd accumulation in rice plants, using two Cd levels (0, 1.5 mg kg(-1)) combined with three S concentrations (0, 60, 120 mg kg(-1)). The results showed that excessive S supply significantly decreased Cd accumulation in brown rice due to the decrease of Cd availability and the increase of glutathione in rice leaves. But excessive S supply obviously increased Cd accumulation in roots due to the decrease of iron plaque formation on the root surface of rice. Therefore, excessive S supply may result in loss of rice yield, but it could effectively reduce Cd accumulation in brown rice exposed to Cd contaminated soils. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  8. Study on the Effectiveness of Infiltration Wells to Reduce Excess Surface Run Off In ITB

    Directory of Open Access Journals (Sweden)

    Mardiah Afifah Muhsinatu

    2018-01-01

    Full Text Available Institut Teknologi Bandung (ITB, Ganesha Campus, Indonesia, has an area of 28.86 hectares. The campus is located in Bandung. Starting from 2012, new buildings were constructed within the area, reducing the area of permeable surface significantly. In the past few years, there were several excess run off incidents in the campus. The insufficient area of permeable surface as well as the inadequate capacity of the drainage system contributes to the excess surface run off. The drainage system has only two outlets. Moreover, in some areas, the drainage systems are disconnected. Thus, most the surface run off are stored within the drainage system. The purpose of this study is to evaluate the effectiveness of infiltration wells for reducing the local excess run off in ITB. Precipitation data and drained service area are used to estimate the design discharge from each building in ITB. In order to avoid the excess surface run off of certain locations in ITB, then the infiltration wells are proposed to balance the area of impermeable surface. The effectiveness of the infiltration wells are evaluated by assessing their number to their contribution in reducing the excess surface runs off.

  9. Cooking rice in excess water reduces both arsenic and enriched vitamins in the cooked grain.

    Science.gov (United States)

    Gray, Patrick J; Conklin, Sean D; Todorov, Todor I; Kasko, Sasha M

    2016-01-01

    This paper reports the effects of rinsing rice and cooking it in variable amounts of water on total arsenic, inorganic arsenic, iron, cadmium, manganese, folate, thiamin and niacin in the cooked grain. We prepared multiple rice varietals both rinsed and unrinsed and with varying amounts of cooking water. Rinsing rice before cooking has a minimal effect on the arsenic (As) content of the cooked grain, but washes enriched iron, folate, thiamin and niacin from polished and parboiled rice. Cooking rice in excess water efficiently reduces the amount of As in the cooked grain. Excess water cooking reduces average inorganic As by 40% from long grain polished, 60% from parboiled and 50% from brown rice. Iron, folate, niacin and thiamin are reduced by 50-70% for enriched polished and parboiled rice, but significantly less so for brown rice, which is not enriched.

  10. Reducing the stoichiometric excess of HF in the hydrofluorination of UO2

    International Nuclear Information System (INIS)

    Zhao Jun; Qiu Lufu; Zhong Xing; Xu Heqing

    1989-11-01

    In a fluidized bed, UO 2 obtained from the decomposition-reduction of AUC (Ammonium Uranyl Carbonate) was fed to absorb HF remaining in the exhaust gas of UF 4 production process. In the case of 60% conversion of UO 2 and the reaction temperature in the region of 300 deg C, HF remaining in the exhaust gas in absorbing fluidized bed was less than 7 ∼ 8% (w/w), i.e. apparent stoichiometric excess of HF had reduced to 0% more or less. Hence, with the high hydrofluorination reactivity of UO 2 obtained from the decomposition-reduction of AUC, it is possible to reduce evidently the stoichiometric excess of HF in the hydrofluorination process by two fluidized beds in series in which solids move against the gas flow

  11. The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.

    Science.gov (United States)

    Elder, Randy W; Lawrence, Briana; Ferguson, Aneeqah; Naimi, Timothy S; Brewer, Robert D; Chattopadhyay, Sajal K; Toomey, Traci L; Fielding, Jonathan E

    2010-02-01

    A systematic review of the literature to assess the effectiveness of alcohol tax policy interventions for reducing excessive alcohol consumption and related harms was conducted for the Guide to Community Preventive Services (Community Guide). Seventy-two papers or technical reports, which were published prior to July 2005, met specified quality criteria, and included evaluation outcomes relevant to public health (e.g., binge drinking, alcohol-related crash fatalities), were included in the final review. Nearly all studies, including those with different study designs, found that there was an inverse relationship between the tax or price of alcohol and indices of excessive drinking or alcohol-related health outcomes. Among studies restricted to underage populations, most found that increased taxes were also significantly associated with reduced consumption and alcohol-related harms. According to Community Guide rules of evidence, these results constitute strong evidence that raising alcohol excise taxes is an effective strategy for reducing excessive alcohol consumption and related harms. The impact of a potential tax increase is expected to be proportional to its magnitude and to be modified by such factors as disposable income and the demand elasticity for alcohol among various population groups. Published by Elsevier Inc.

  12. Hsp90 inhibitors reduce influenza virus replication in cell culture

    International Nuclear Information System (INIS)

    Chase, Geoffrey; Deng, Tao; Fodor, Ervin; Leung, B.W.; Mayer, Daniel; Schwemmle, Martin; Brownlee, George

    2008-01-01

    The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses

  13. Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial

    DEFF Research Database (Denmark)

    Gullestad, Lars; Iversen, Martin; Mortensen, Svend-Aage

    2010-01-01

    The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking.......The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking....

  14. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    Directory of Open Access Journals (Sweden)

    Atar Herziger

    2017-06-01

    Full Text Available Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism in an empirical research design. The project will test (a whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b whether self-transcendence (i.e., biospheric and self-enhancement (i.e., egoistic and hedonic values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating, while priming the relevant values and goals (self-transcendence or self-enhancement. These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions.

  15. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    Science.gov (United States)

    Herziger, Atar; Benzerga, Amel; Berkessel, Jana; Dinartika, Niken L.; Franklin, Matija; Steinnes, Kamilla K.; Sundström, Felicia

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism) in an empirical research design. The project will test (a) whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b) whether self-transcendence (i.e., biospheric) and self-enhancement (i.e., egoistic and hedonic) values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating), while priming the relevant values and goals (self-transcendence or self-enhancement). These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions. PMID:28649220

  16. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption.

    Science.gov (United States)

    Herziger, Atar; Benzerga, Amel; Berkessel, Jana; Dinartika, Niken L; Franklin, Matija; Steinnes, Kamilla K; Sundström, Felicia

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism) in an empirical research design. The project will test (a) whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b) whether self-transcendence (i.e., biospheric) and self-enhancement (i.e., egoistic and hedonic) values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating), while priming the relevant values and goals (self-transcendence or self-enhancement). These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions.

  17. You Have to Be Prepared to Drink: Students' Views about Reducing Excessive Alcohol Consumption at University

    Science.gov (United States)

    Davies, Emma L.; Law, Cara; Hennelly, Sarah E.

    2018-01-01

    Purpose: Many existing interventions to reduce excessive drinking in university students attempt to target individual cognitions, which ignore the wider contextual features that drive excessive drinking and mark this as an important aspect of university life. The purpose of this paper is to explore students' views about preventing excessive…

  18. Dietary copper in excess of nutritional requirement reduces plasma and breast muscle cholesterol of chickens.

    Science.gov (United States)

    Bakalli, R I; Pesti, G M; Ragland, W L; Konjufca, V

    1995-02-01

    Male commercial broiler strain chickens were fed from hatching to 42 d of age either a control diet (based on corn and soybean meal) or the control diet supplemented with 250 mg copper/kg diet from cupric sulfate pentahydrate (for 35 or 42 d). Hypocholesterolemia (11.8% reduction) and decreased breast muscle cholesterol (20.4% reduction) were observed in copper-supplemented birds. There was a slight increase (P > .05) in breast muscle copper (14.5%), and all levels were very low (copper for 42 vs 35 d resulted in lower levels of cholesterol in the plasma (12.9 vs 10.8% reduction) and breast muscle (24.6 vs 16.2% reduction). Very similar results were found in two additional experiments in which hypocholesterolemia and reduced breast muscle cholesterol were associated with reduced plasma triglycerides and blood reduced glutathione. It is well known that hypercholesterolemia is a symptom of dietary copper deficiency. The data presented here indicate that blood and breast muscle cholesterol are inversely related to dietary copper in excess of the dietary requirement for maximal growth. The cholesterol content of the edible muscle tissue of broiler chickens can be reduced by approximately 25% after feeding a supranormal level of copper for 42 d without altering the growth of the chickens or substantially increasing the copper content of the edible meat.

  19. Development and evaluation of a theory- and evidence-based smartphone app to help reduce excessive alcohol consumption

    OpenAIRE

    Garnett, C. V.

    2017-01-01

    This PhD research programme aimed to develop and evaluate a smartphone app to reduce excessive alcohol consumption and used the theoretical framework of the Behaviour Change Wheel to guide its development and evaluation. There are many different factors influencing alcohol consumption that can be targeted in an intervention to reduce excessive alcohol consumption. This thesis focuses on the cognitive and motivational factors affecting alcohol consumption. The thesis involves three stages: ...

  20. Behaviour change techniques used in digital interventions to reduce excessive alcohol consumption

    Directory of Open Access Journals (Sweden)

    David Crane

    2015-10-01

    Full Text Available Background: Excessive alcohol consumption is a leading contributor to the global burden of disease. A large number of digital interventions have been developed to help people reduce their consumption. Coding interventions to assess the behaviour change techniques (BCTs they contain may advance understanding of the active ingredients that contribute to intervention effectiveness. Aim: To assess the extent to which BCTs are included in digital interventions to reduce alcohol consumption. Methods: A search of databases including MEDLINE, PsycINFO and the Cochrane Library identified 53 interventions to reduce alcohol consumption evaluated in RCTs. Intervention content was coded for BCTs according to the BCT Taxonomy (v1 using an established method. Results: There were 72 experimental arms in the 53 included studies. The most frequently used BCTs were: ‘Feedback on behaviour’ (70.8%, n=51, ‘Social comparison’ (68.1%, n=49, ‘Feedback on outcomes of behaviour (52.8%, n=38, ‘Social support’ (52.8%, n=38, and ‘Information about social and environmental consequences’ (50.0%, n=36. Of the ninety-three possible BCTs that could have been used, 15 were used in more than 20% of arms, 53 were used at least once and 40 were never used. The mean number of BCTs used was 7.8 (SD=5.6. Conclusions: Digital alcohol interventions have used a broad range of BCTs. However, many BCTs were used infrequently and the evaluations have not been set up to evaluate the effectiveness of individual BCTs or clusters of BCTs.

  1. Study of Using Excess Stock to Reduce Naval Aviation Depot-Level Repairable Piece Part Backorders

    Science.gov (United States)

    2016-12-01

    used to develop and run the comparison of the backorders and excess stock records. Python is chosen because of its ease of learning and use...sustainable source of bit-piece parts for future requisitions. 14. SUBJECT TERMS naval aviation AVDLRs, backorder, excess, DLA, WSS, FRC, Python ...SCHOOL December 2016 Approved by: Geraldo Ferrer Eddine Dahel Peter Ward Bryan Hudgens Academic Associate

  2. Increased onset of vergence adaptation reduces excessive accommodation during the orthoptic treatment of convergence insufficiency.

    Science.gov (United States)

    Sreenivasan, Vidhyapriya; Bobier, William R

    2015-06-01

    This research tested the hypothesis that the successful treatment of convergence insufficiency (CI) with vision-training (VT) procedures, leads to an increased capacity of vergence adaptation (VAdapt) allowing a more rapid downward adjustment of the convergence accommodation cross-link. Nine subjects with CI were recruited from a clinical population, based upon reduced fusional vergence amplitudes, receded near point of convergence or symptomology. VAdapt and the resulting changes to convergence accommodation (CA) were measured at specific intervals over 15 min (pre-training). Separate clinical measures of the accommodative convergence cross link, horizontal fusion limits and near point of convergence were taken and a symptomology questionnaire completed. Subjects then participated in a VT program composed of 2.5h at home and 1h in-office weekly for 12-14 weeks. Clinical testing was done weekly. VAdapt and CA measures were retaken once clinical measures normalized for 2 weeks (mid-training) and then again when symptoms had cleared (post-training). VAdapt and CA responses as well as the clinical measures were taken on a control group showing normal clinical findings. Six subjects provided complete data sets. CI clinical findings reached normal levels between 4 and 7 weeks of training but symptoms, VAdapt, and CA output remained significantly different from the controls until 12-14 weeks. The hypothesis was retained. The reduced VAdapt and excessive CA found in CI were normalized through orthoptic treatment. This time course was underestimated by clinical findings but matched symptom amelioration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Small-molecule aggregation inhibitors reduce excess amyloid in a trisomy 16 mouse cortical cell line

    Directory of Open Access Journals (Sweden)

    ANDRÉA C PAULA LIMA

    2008-01-01

    Full Text Available We have previously characterized a number of small molecule organic compounds that prevent the aggregation of the β-amyloid peptide and its neurotoxicity in hippocampal neuronal cultures. We have now evaluated the effects of such compounds on amyloid precursor protein (APP accumulation in the CTb immortalized cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down's syndrome. Compared to a non-trisomic cortical cell line (CNh, CTb cells overexpress APP and exhibit slightly elevated resting intracellular Ca2+ levéis ([Ca2+]¡. Here, we show that the compounds 2,4-dinitrophenol, 3-nitrophenol and 4-anisidine decreased intracellular accumulation of APP in CTb cells. Those compounds were non-toxic to the cells, and slightly increased the basal [Ca2+]¡. Results indícate that the compounds tested can be leads for the development of drugs to decrease intracellular vesicular accumulation of APP in trisomic cells.

  4. Use of selective serotonin reuptake inhibitors reduces fertility in men

    DEFF Research Database (Denmark)

    Nørr, L; Bennedsen, Birgit; Fedder, Jens

    2016-01-01

    Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included...

  5. Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial

    OpenAIRE

    Garnett, Claire; Crane, David; Michie, Susan; West, Robert; Brown, Jamie

    2016-01-01

    Background Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that cou...

  6. Does physical exercise reduce excessive daytime sleepiness by improving inflammatory profiles in obstructive sleep apnea patients?

    Science.gov (United States)

    Alves, Eduardo da Silva; Ackel-D'Elia, Carolina; Luz, Gabriela Pontes; Cunha, Thays Crosara Abrahão; Carneiro, Gláucia; Tufik, Sergio; Bittencourt, Lia Rita Azeredo; de Mello, Marco Tulio

    2013-05-01

    Obstructive sleep apnea syndrome (OSAS) is associated with a variety of long-term consequences such as high rates of morbidity and mortality, due to excessive diurnal somnolence as well as cardiovascular and metabolic diseases. Obesity, recurrent episodes of upper airway obstruction, progressive hypoxemia, and sleep fragmentation during sleep cause neural, cardiovascular, and metabolic changes. These changes include activation of peripheral sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, insulin sensitivity, and inflammatory cytokines alterations, which predispose an individual to vascular damage. Previous studies proposed that OSAS modulated the expression and secretion of inflammatory cytokines from fat and other tissues. Independent of obesity, patients with OSAS exhibited elevated levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, which are associated with sleepiness, fatigue, and the development of a variety of metabolic and cardiovascular diseases. OSAS and obesity are strongly associated with each other and share many common pathways that induce chronic inflammation. Previous studies suggested that the protective effect of exercise may be partially attributed to the anti-inflammatory effect of regular exercise, and this effect was observed in obese patients. Although some studies assessed the effects of physical exercise on objective and subjective sleep parameters, the quality of life, and mood in patients with OSAS, no study has evaluated the effects of this treatment on inflammatory profiles. In this review, we cited some studies that directed our opinion to believe that since OSAS causes increased inflammation and has excessive daytime sleepiness as a symptom and being that physical exercise improves inflammatory profiles and possibly OSAS symptoms, it must be that physical exercise improves excessive daytime sleepiness due to its improvement in inflammatory profiles.

  7. Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial

    Directory of Open Access Journals (Sweden)

    Claire Garnett

    2016-07-01

    Full Text Available Abstract Background Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. Methods A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (25 experimental conditions after downloading the ‘Drink Less’ app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between-subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. Discussion This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and

  8. Evaluating the effectiveness of a smartphone app to reduce excessive alcohol consumption: protocol for a factorial randomised control trial.

    Science.gov (United States)

    Garnett, Claire; Crane, David; Michie, Susan; West, Robert; Brown, Jamie

    2016-07-08

    Excessive alcohol consumption is a leading cause of death and morbidity worldwide and interventions to help people reduce their consumption are needed. Interventions delivered by smartphone apps have the potential to help harmful and hazardous drinkers reduce their consumption of alcohol. However, there has been little evaluation of the effectiveness of existing smartphone interventions. A systematic review, amongst other methodologies, identified promising modular content that could be delivered by an app: self-monitoring and feedback; action planning; normative feedback; cognitive bias re-training; and identity change. This protocol reports a factorial randomised controlled trial to assess the comparative potential of these five intervention modules to reduce excessive alcohol consumption. A between-subject factorial randomised controlled trial. Hazardous and harmful drinkers aged 18 or over who are making a serious attempt to reduce their drinking will be randomised to one of 32 (2(5)) experimental conditions after downloading the 'Drink Less' app. Participants complete baseline measures on downloading the app and are contacted after 1-month with a follow-up questionnaire. The primary outcome measure is change in past week consumption of alcohol. Secondary outcome measures are change in AUDIT score, app usage data and usability ratings for the app. A factorial between-subjects ANOVA will be conducted to assess main and interactive effects of the five intervention modules for the primary and secondary outcome measures. This study will establish the extent to which the five intervention modules offered in this app can help reduce hazardous and harmful drinking. This is the first step in optimising and understanding what component parts of an app could help to reduce excessive alcohol consumption. The findings from this study will be used to inform the content of a future integrated treatment app and evaluated against a minimal control in a definitive randomised

  9. Royal Jelly Inhibits Pseudomonas aeruginosa Adherence and Reduces Excessive Inflammatory Responses in Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Heni Susilowati

    2017-01-01

    Full Text Available Pseudomonas aeruginosa is a Gram-negative bacterium and causes respiratory infection especially in elderly patients. Royal jelly has been used worldwide as a traditional remedy and as a nutrient; however, the effect against P. aeruginosa is unclear. The aim of this study was to analyze antibacterial, antiadherent, and anti-inflammatory effects of royal jelly against P. aeruginosa. Wild-type strain PAO1 and clinical isolates of P. aeruginosa were used for antibacterial assay and antiadherent assay to abiotic surface and epithelial cells, which are pharynx (Detroit 562 and lung (NCI-H292 epithelial cells. In anti-inflammatory assay, epithelial cells were pretreated with royal jelly before bacterial exposure to investigate its inhibitory effect on interleukin (IL-8 and macrophage inflammatory protein-3α/CCL20 overproduction. Although royal jelly did not have antibacterial activity at concentration of 50% w/v, antiadherent activity was confirmed on the abiotic surface and epithelial cells under concentration of 25%. Pretreatment with royal jelly significantly inhibited overproduction of IL-8 and CCL20 from both cells. These results demonstrated that royal jelly inhibits P. aeruginosa adherence and protects epithelial cells from excessive inflammatory responses against P. aeruginosa infection. Our findings suggested that royal jelly may be a useful supplement as complementary and alternative medicine for preventing respiratory infection caused by P. aeruginosa.

  10. Inhibitors

    Science.gov (United States)

    ... JM, and the Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor ... webinars on blood disorders Language: English (US) Español (Spanish) File Formats Help: How do I view different ...

  11. A new insight into resource recovery of excess sewage sludge: Feasibility of extracting mixed amino acids as an environment-friendly corrosion inhibitor for industrial pickling

    Energy Technology Data Exchange (ETDEWEB)

    Su, Wen; Tang, Bing, E-mail: renytang@163.com; Fu, Fenglian; Huang, Shaosong; Zhao, Shiyuan; Bin, Liying; Ding, Jiewei; Chen, Cuiqun

    2014-08-30

    Graphical abstract: - Highlights: • A value-added product was extracted from the municipal excess sludge. • The effective components contained in the product were mixed amino acids. • The product could provide a reliable protection to the steel from the acid medium. • A new insight into the resource recovery of excess sewage sludge was provided. - Abstract: The work mainly presented a laboratory-scale investigation on an effective process to extract a value-added product from municipal excess sludge. The functional groups in the hydrolysate were characterized with Fourier transform infrared spectrum, and the contained amino acids were measured by means of an automatic amino acid analyzer. The corrosion-inhibition characteristics of the hydrolysate were determined with weight-loss measurement, electrochemical polarization and scanning electron microscopy. Results indicated that the hydrolysate contained 15 kinds of amino acid, and their adsorption on the surface could effectively inhibit the corrosion reaction of the steel from the acid medium. Polarization curves indicated that the obtained hydrolysate was a mixed-type inhibitor, but mainly restricted metal dissolution on the anode. The adsorption accorded well with the Langmuir adsorption isotherm, involved an increase in entropy, and was a spontaneous, exothermic process.

  12. A new insight into resource recovery of excess sewage sludge: Feasibility of extracting mixed amino acids as an environment-friendly corrosion inhibitor for industrial pickling

    International Nuclear Information System (INIS)

    Su, Wen; Tang, Bing; Fu, Fenglian; Huang, Shaosong; Zhao, Shiyuan; Bin, Liying; Ding, Jiewei; Chen, Cuiqun

    2014-01-01

    Graphical abstract: - Highlights: • A value-added product was extracted from the municipal excess sludge. • The effective components contained in the product were mixed amino acids. • The product could provide a reliable protection to the steel from the acid medium. • A new insight into the resource recovery of excess sewage sludge was provided. - Abstract: The work mainly presented a laboratory-scale investigation on an effective process to extract a value-added product from municipal excess sludge. The functional groups in the hydrolysate were characterized with Fourier transform infrared spectrum, and the contained amino acids were measured by means of an automatic amino acid analyzer. The corrosion-inhibition characteristics of the hydrolysate were determined with weight-loss measurement, electrochemical polarization and scanning electron microscopy. Results indicated that the hydrolysate contained 15 kinds of amino acid, and their adsorption on the surface could effectively inhibit the corrosion reaction of the steel from the acid medium. Polarization curves indicated that the obtained hydrolysate was a mixed-type inhibitor, but mainly restricted metal dissolution on the anode. The adsorption accorded well with the Langmuir adsorption isotherm, involved an increase in entropy, and was a spontaneous, exothermic process

  13. [Assessment of realization of a reducing diet by obese women during treatment of excessive body mass].

    Science.gov (United States)

    Ostrowska, Lucyna; Stefańska, Ewa; Czapska, Danuta; Karczewski, Jan

    2008-01-01

    The study objective was to evaluate the realization of the reducing diet recommended in the treatment of overweight or obesity (1500 kcal) with regard to the caloric value and the content of basic nutrients, vitamins and bioelements. The study was conducted on a group of 48 women. Daily food rations were evaluated based on a week's dietary register. Results were averaged in each patient and compared to the norms worked out by the Institute of Food and Feeding in Warsaw for subjects with low physical activity. The mean energetic value of the diets was found to meet the requirements. Approximately 50% of the obese women consumed high-protein, low-fat and low-carbohydrate food rations. The analysis of vitamin content in daily food rations showed insufficient intake of vitamin E (in 89.6% of women), thiamin (83.3%), riboflavin (93.7%), niacin (60.4%), vitamin B6 (87.5%), folic acid (89.6%) and vitamin C (72.9%). Vitamin A intake was higher than the recommended norm in 47.9% of women. The lowest realization was noted in the case of potassium (64.6% of rations below the norm), calcium (100% below the norm), magnesium (64.6% below the norm). However, dietary sodium and phosphate content in most obese women exceeded the norms. The intake was too low in the case of iron (in 91.7%), zinc (in 97.9%) and copper (in 100%). It seems that long-term compliance with such a diet requires additional individual supplementation.

  14. Fibromodulin reduces scar size and increases scar tensile strength in normal and excessive-mechanical-loading porcine cutaneous wounds.

    Science.gov (United States)

    Jiang, Wenlu; Ting, Kang; Lee, Soonchul; Zara, Janette N; Song, Richard; Li, Chenshuang; Chen, Eric; Zhang, Xinli; Zhao, Zhihe; Soo, Chia; Zheng, Zhong

    2018-04-01

    Hypertrophic scarring is a major postoperative complication which leads to severe disfigurement and dysfunction in patients and usually requires multiple surgical revisions due to its high recurrence rates. Excessive-mechanical-loading across wounds is an important initiator of hypertrophic scarring formation. In this study, we demonstrate that intradermal administration of a single extracellular matrix (ECM) molecule-fibromodulin (FMOD) protein-can significantly reduce scar size, increase tensile strength, and improve dermal collagen architecture organization in the normal and even excessive-mechanical-loading red Duroc pig wound models. Since pig skin is recognized by the Food and Drug Administration as the closest animal equivalent to human skin, and because red Duroc pigs show scarring that closely resembles human proliferative scarring and hypertrophic scarring, FMOD-based technologies hold high translational potential and applicability to human patients suffering from scarring-especially hypertrophic scarring. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. A Single Day of Excessive Dietary Fat Intake Reduces Whole-Body Insulin Sensitivity: The Metabolic Consequence of Binge Eating

    Directory of Open Access Journals (Sweden)

    Siôn A. Parry

    2017-07-01

    Full Text Available Consuming excessive amounts of energy as dietary fat for several days or weeks can impair glycemic control and reduce insulin sensitivity in healthy adults. However, individuals who demonstrate binge eating behavior overconsume for much shorter periods of time; the metabolic consequences of such behavior remain unknown. The aim of this study was to determine the effect of a single day of high-fat overfeeding on whole-body insulin sensitivity. Fifteen young, healthy adults underwent an oral glucose tolerance test before and after consuming a high-fat (68% of total energy, high-energy (78% greater than daily requirements diet for one day. Fasting and postprandial plasma concentrations of glucose, insulin, non-esterified fatty acids, and triglyceride were measured and the Matsuda insulin sensitivity index was calculated. One day of high-fat overfeeding increased postprandial glucose area under the curve (AUC by 17.1% (p < 0.0001 and insulin AUC by 16.4% (p = 0.007. Whole-body insulin sensitivity decreased by 28% (p = 0.001. In conclusion, a single day of high-fat, overfeeding impaired whole-body insulin sensitivity in young, healthy adults. This highlights the rapidity with which excessive consumption of calories through high-fat food can impair glucose metabolism, and suggests that acute binge eating may have immediate metabolic health consequences for the individual.

  16. Effect of ionizing radiation on reducing the several inhibitors in codling moth Cydia pomonella (L.) medium

    International Nuclear Information System (INIS)

    Mohamad, F. A.

    2008-01-01

    The medium for Codling moth, Cydia pomonella (L) was sterilized using ionizing radiation (0, 5, 15 and 25 KGy) or heat (cooking for 40 minutes.). inhibitors were also added either on the top of the diet or by mixing it with the diet. The results showed that all Codling moth larvae in the ionizing radiation sterilized diet died before reaching the 4th larval instar. Results of using both radiation and cooking for sterilizing the diet gave variable results; those treated with 15 KGy gave significantly more moths with higher weight and more fecundity. The results also showed that increasing the amount of microbial inhibitors in diet negatively affected the number of produced moth and their biological characteristics. Consequently irradiation could be a mean for reducing the amount of chemical inhibitors added to the diet. (author)

  17. Enhancing the Capacity of School Nurses to Reduce Excessive Anxiety in Children: Development of the CALM Intervention.

    Science.gov (United States)

    Drake, Kelly L; Stewart, Catherine E; Muggeo, Michela A; Ginsburg, Golda S

    2015-08-01

    Excessive anxiety is among the most common psychiatric problems facing youth. Because anxious youth tend to have somatic complaints, many seek help from the school nurse. Thus, school nurses are in an ideal position to provide early intervention. This study addresses this problem and describes the plans to develop and test a new intervention (Child Anxiety Learning Modules; CALM), delivered by school nurses, to reduce child anxiety and improve academic functioning. An iterative development process including consultation with an expert panel, two open trials, and a pilot randomized controlled study comparing CALM to usual care is proposed. Feedback will be solicited from all participants during each phase and data on outcome measures will be provided by children, parents, teachers, and independent evaluators. Data will be collected on intervention satisfaction and feasibility. Primary outcomes that include child anxiety symptoms, classroom behavior, and school performance (e.g., attendance, grades, standardized test scores) will be collected at pre- and post-interventions and at a 3-month follow-up evaluation. Pediatric anxiety is a common problem that school nurses frequently encounter. Consequently, they are well positioned to play a key role in enhancing access to behavioral health interventions to reduce anxiety and may therefore make a significant positive public health impact. © 2015 Wiley Periodicals, Inc.

  18. Reduced ovarian glyoxalase-I activity by dietary glycotoxins and androgen excess: a causative link to polycystic ovarian syndrome.

    Science.gov (United States)

    Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

    2012-10-24

    Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s) = 0.533, p androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS.

  19. Proteasome inhibitors induce apoptosis and reduce viral replication in primary effusion lymphoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Saji, Chiaki [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812 (Japan); Higashi, Chizuka; Niinaka, Yasufumi [Faculty of Medicine, University of Yamanashi, Chuoh-shi 409-3898 (Japan); Yamada, Koji [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812 (Japan); Noguchi, Kohji [Faculty of Pharmacy, Keio University, 1-5-30 Shiba-koen, Minato-ku, Tokyo 105-8512 (Japan); Fujimuro, Masahiro, E-mail: fuji2@mb.kyoto-phu.ac.jp [Department of Cell Biology, Kyoto Pharmaceutical University, Misasagi-Shichonocho 1, Yamashinaku, Kyoto 607-8412 (Japan)

    2011-12-02

    Highlights: Black-Right-Pointing-Pointer Constitutive NF-{kappa}B signaling is essential for the survival and growth of PEL cells. Black-Right-Pointing-Pointer NF-{kappa}B signaling is upregulated by the proteasome-dependent degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer Proteasome inhibitors suppress NF-{kappa}B signaling and induce apoptosis in PEL cells through stabilization of I{kappa}B{alpha}. Black-Right-Pointing-Pointer Proteasome inhibitors suppress viral replication in PEL cells during lytic KSHV infection. -- Abstract: Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV). This study provides evidence that proteasomal activity is required for both survival of PEL cells stably harboring the KSHV genome and viral replication of KSHV. We evaluated the cytotoxic effects of proteasome inhibitors on PEL cells. The proteasome inhibitors MG132, lactacystin, and proteasome inhibitor I dramatically inhibited cell proliferation and induced apoptosis of PEL cells through the accumulation of p21 and p27. Furthermore, proteasome inhibitors induced the stabilization of NF-{kappa}B inhibitory molecule (I{kappa}B{alpha}) and suppressed the transcriptional activity of NF-{kappa}B in PEL cells. The NF-{kappa}B specific inhibitor BAY11-7082 also induced apoptosis in PEL cells. The constitutive activation of NF-{kappa}B signaling is essential for the survival and growth of B cell lymphoma cells, including PEL cells. NF-{kappa}B signaling is upregulated by proteasome-dependent degradation of I{kappa}B{alpha}. The suppression of NF-{kappa}B signaling by proteasome inhibitors may contribute to the induction of apoptosis in PEL cells. In addition, proteasome activity is required for KSHV replication in KSHV latently infected PEL cells. MG132 reduced the production of progeny virus from PEL cells at low concentrations, which do not affect PEL cell growth. These findings suggest that proteasome

  20. Carotenoid inhibitors reduce strigolactone production and Striga hermonthica infection in rice.

    Science.gov (United States)

    Jamil, Muhammad; Charnikhova, Tatsiana; Verstappen, Francel; Bouwmeester, Harro

    2010-12-01

    The strigolactones are internal and rhizosphere signalling molecules in plants that are biosynthesised through carotenoid cleavage. They are secreted by host roots into the rhizosphere where they signal host-presence to the symbiotic arbuscular mycrorrhizal (AM) fungi and the parasitic plants of the Orobanche, Phelipanche and Striga genera. The seeds of these parasitic plants germinate after perceiving these signalling molecules. After attachment to the host root, the parasite negatively affects the host plant by withdrawing water, nutrients and assimilates through a direct connection with the host xylem. In many areas of the world these parasites are a threat to agriculture but so far very limited success has been achieved to minimize losses due to these parasitic weeds. Considering the carotenoid origin of the strigolactones, in the present study we investigated the possibilities to reduce strigolactone production in the roots of plants by blocking carotenoid biosynthesis using carotenoid inhibitors. Hereto the carotenoid inhibitors fluridone, norflurazon, clomazone and amitrole were applied to rice either through irrigation or through foliar spray. Irrigation application of all carotenoid inhibitors and spray application of amitrole significantly decreased strigolactone production, Striga hermonthica germination and Striga infection, also in concentrations too low to affect growth and development of the host plant. Hence, we demonstrate that the application of carotenoid inhibitors to plants can affect S. hermonthica germination and attachment indirectly by reducing the strigolactone concentration in the rhizosphere. This finding is useful for further studies on the relevance of the strigolactones in rhizosphere signalling. Since these inhibitors are available and accessible, they may represent an efficient technology for farmers, including poor subsistence farmers in the African continent, to control these harmful parasitic weeds. Copyright © 2010 Elsevier Inc

  1. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    Science.gov (United States)

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-07-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

  2. Randomized controlled clinical trial of behavioral lifestyle intervention with partial meal replacement to reduce excessive gestational weight gain.

    Science.gov (United States)

    Phelan, Suzanne; Wing, Rena R; Brannen, Anna; McHugh, Angelica; Hagobian, Todd A; Schaffner, Andrew; Jelalian, Elissa; Hart, Chantelle N; Scholl, Theresa O; Munoz-Christian, Karen; Yin, Elaine; Phipps, Maureen G; Keadle, Sarah; Abrams, Barbara

    2018-02-01

    Behavioral lifestyle interventions during pregnancy can prevent excessive gestational weight gain (GWG) in women with normal weight; however, effective interventions to reduce GWG in ethnically diverse women with obesity are lacking. A randomized controlled trial was conducted to test whether a behavioral lifestyle intervention with partial meal replacement reduces GWG rate in Hispanic and non-Hispanic women with overweight or obesity relative to enhanced usual care. Participants (n = 257) were recruited in San Luis Obispo, California, and Providence, Rhode Island, between November 2012 and May 2016. Participants were pregnant (mean ± SD: 13.6 ± 1.8 wk of gestation) with overweight or obesity and had a mean age of 30.3 y; 41.6% of participants were Hispanic. Women were randomly assigned within site and by ethnicity to enhanced usual care (n = 128) or to a behavioral lifestyle intervention with partial meal replacement (n = 129). The primary outcome was GWG per week of observation. Secondary outcomes were proportions exceeding Institute of Medicine (IOM) guidelines for total GWG, changes in weight-control behaviors and cardiovascular disease risk factors, and incidence of pregnancy complications. Study retention was 99.6% (256 of 257). The intervention compared with usual care resulted in less mean ± SD weekly GWG (0.33 ± 0.25 compared with 0.39 ± 0.23 kg/wk; P = 0.02) and total GWG (9.4 ± 6.9 compared with 11.2 ± 7.0 kg; P = 0.03) and reduced the proportion of women who exceeded IOM guidelines for total GWG (41.1% compared with 53.9%; P = 0.03). No significant group × time × demographic subgroup (ethnicity, BMI, age, parity, and income) interactions were observed. Among intervention participants, greater meal replacement intake was related to reduced GWG rate (β = -0.07; 95% CI:-0.12, -0.03; P = 0.002). The intervention compared with usual care increased weight-control strategies (P meal replacement significantly reduced GWG in Hispanic

  3. Meclofenamic Acid Reduces Reactive Oxygen Species Accumulation and Apoptosis, Inhibits Excessive Autophagy, and Protects Hair Cell-Like HEI-OC1 Cells From Cisplatin-Induced Damage

    Directory of Open Access Journals (Sweden)

    He Li

    2018-05-01

    Full Text Available Hearing loss is the most common sensory disorder in humans, and a significant number of cases is due to the ototoxicity of drugs such as cisplatin that cause hair cell (HC damage. Thus, there is great interest in finding agents and mechanisms that protect HCs from ototoxic drug damage. It has been proposed that epigenetic modifications are related to inner ear development and play a significant role in HC protection and HC regeneration; however, whether the m6A modification and the ethyl ester form of meclofenamic acid (MA2, which is a highly selective inhibitor of FTO (fatmass and obesity-associated enzyme, one of the primary human demethylases, can affect the process of HC apoptosis induced by ototoxic drugs remains largely unexplored. In this study, we took advantage of the HEI-OC1 cell line, which is a cochlear HC-like cell line, to investigate the role of epigenetic modifications in cisplatin-induced cell death. We found that cisplatin injury caused reactive oxygen species accumulation and increased apoptosis in HEI-OC1 cells, and the cisplatin injury was reduced by co-treatment with MA2 compared to the cisplatin-only group. Further investigation showed that MA2 attenuated cisplatin-induced oxidative stress and apoptosis in HEI-OC1 cells. We next found that the cisplatin-induced upregulation of autophagy was significantly inhibited after MA2 treatment, indicating that MA2 inhibited the cisplatin-induced excessive autophagy. Our findings show that MA2 has a protective effect and improves the viability of HEI-OC1 cells after cisplatin treatment, and they provide new insights into potential therapeutic targets for the amelioration of cisplatin-induced ototoxicity.

  4. An assessment of nitrification inhibitors to reduce nitrous oxide emissions from UK agriculture

    International Nuclear Information System (INIS)

    Misselbrook, T H; Cardenas, L M; Camp, V; Thorman, R E; Williams, J R; Rollett, A J; Chambers, B J

    2014-01-01

    A trial was conducted consisting of 14 experiments across sites in England of contrasting soil type and annual rainfall to assess the effectiveness of nitrification inhibitors (predominantly dicyandiamide (DCD) but limited assessment also of 3, 4-dimethylpyrazole phosphate (DMPP) and a commercial product containing two pyrazole derivatives) in reducing direct nitrous oxide (N 2 O) emissions from fertilizer nitrogen (N), cattle urine and cattle slurry applications to land. Measurements were also made of the impact on ammonia (NH 3 ) volatilization, nitrate (NO 3 − ) leaching, crop yield and crop N offtake. DCD proved to be very effective in reducing direct N 2 O emissions following fertilizer and cattle urine applications, with mean reduction efficiencies of 39, 69 and 70% for ammonium nitrate, urea and cattle urine, respectively. When included with cattle slurry a mean, non-significant reduction of 56% was observed. There were no N 2 O emission reductions observed from the limited assessments of the other nitrification inhibitors. Generally, there were no impacts of the nitrification inhibitors on NH 3 volatilization, NO 3 − leaching, crop yield or crop N offtake. Use of DCD could give up to 20% reduction in N 2 O emissions from UK agriculture, but cost-effective delivery mechanisms are required to encourage adoption by the sector. Direct N 2 O emissions from the studied sources were substantially lower than IPCC default values and development of UK country-specific emission factors for use in inventory compilation is warranted. (paper)

  5. A new synthetic matrix metalloproteinase inhibitor reduces human mesenchymal stem cell adipogenesis.

    Directory of Open Access Journals (Sweden)

    Dale B Bosco

    Full Text Available Development of adipose tissue requires the differentiation of less specialized cells, such as human mesenchymal stem cells (hMSCs, into adipocytes. Since matrix metalloproteinases (MMPs play critical roles in the cell differentiation process, we conducted investigations to determine if a novel mercaptosulfonamide-based MMP inhibitor (MMPI, YHJ-7-52, could affect hMSC adipogenic differentiation and lipid accumulation. Enzyme inhibition assays, adipogenic differentiation experiments, and quantitative PCR methods were employed to characterize this inhibitor and determine its effect upon adipogenesis. YHJ-7-52 reduced lipid accumulation in differentiated cells by comparable amounts as a potent hydroxamate MMPI, GM6001. However, YHJ-7-82, a non-inhibitory structural analog of YHJ-7-52, in which the zinc-binding thiol group is replaced by a hydroxyl group, had no effect on adipogenesis. The two MMPIs (YHJ-7-52 and GM6001 were also as effective in reducing lipid accumulation in differentiated cells as T0070907, an antagonist of peroxisome-proliferator activated receptor gamma (PPAR-gamma, at a similar concentration. PPAR-gamma is a typical adipogenic marker and a key regulatory protein for the transition of preadiopocyte to adipocyte. Moreover, MMP inhibition was able to suppress lipid accumulation in cells co-treated with Troglitazone, a PPAR-gamma agonist. Our results indicate that MMP inhibitors may be used as molecular tools for adipogenesis and obesity treatment research.

  6. Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Shelly A Cruz

    2018-01-01

    Full Text Available Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK associated with the tumor necrosis factor-alpha (TNF-α/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-α. However, subsequent lower doses (5 mg/kg/day failed to sustain this neuroprotective effect after 4 days. Dabrafenib blocked lipopolysaccharides-induced activation of TNF-α in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-α-induced necroptotic pathway after ischemic brain injury. Since Dabrafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

  7. Enhancing the Capacity of School Nurses to Reduce Excessive Anxiety in Children: Development of the CALM Intervention

    Science.gov (United States)

    Drake, Kelly L.; Stewart, Catherine E.; Muggeo, Michela A.; Ginsburg, Golda S.

    2015-01-01

    Problem: Excessive anxiety is among the most common psychiatric problems facing youth. Because anxious youth tend to have somatic complaints, many seek help from the school nurse. Thus, school nurses are in an ideal position to provide early intervention. This study addresses this problem and describes the plans to develop and test a new…

  8. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

    Science.gov (United States)

    Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

    2017-09-01

    S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

  9. Reduced storage and balancing needs in a fully renewable European power system with excess wind and solar power generation

    DEFF Research Database (Denmark)

    Heide, Dominik; Greiner, Martin; von Bremen, Lüder

    The storage and balancing needs of a simplified European power system, which is based on wind and solar power generation only, are derived from an extensive weather-driven modeling of hourly power mismatches between generation and load. The storage energy capacity, the annual balancing energy...... and the balancing power are found to depend significantly on the mixing ratio between wind and solar power generation. They decrease strongly with the overall excess generation. At 50% excess generation the required long-term storage energy capacity and annual balancing energy amount to 1% of the annual consumption....... The required balancing power turns out to be 25% of the average hourly load. These numbers are in agreement with current hydro storage lakes in Scandinavia and the Alps, as well as with potential hydrogen storage in mostly North-German salt caverns....

  10. Reduced storage and balancing needs in a fully renewable European power system with excess wind and solar power generation

    DEFF Research Database (Denmark)

    Heide, Dominik; Greiner, Martin; von Bremen, Lüder

    2011-01-01

    The storage and balancing needs of a simplified European power system, which is based on wind and solar power generation only, are derived from an extensive weather-driven modeling of hourly power mismatches between generation and load. The storage energy capacity, the annual balancing energy...... and the balancing power are found to depend significantly on the mixing ratio between wind and solar power generation. They decrease strongly with the overall excess generation. At 50% excess generation the required long-term storage energy capacity and annual balancing energy amount to 1% of the annual consumption....... The required balancing power turns out to be 25% of the average hourly load. These numbers are in agreement with current hydro storage lakes in Scandinavia and the Alps, as well as with potential hydrogen storage in mostly North-German salt caverns....

  11. Review of interventions to reduce ultraviolet tanning: Need for treatments targeting excessive tanning, an emerging addictive behavior.

    Science.gov (United States)

    Stapleton, Jerod L; Hillhouse, Joel; Levonyan-Radloff, Kristine; Manne, Sharon L

    2017-12-01

    Millions of Americans engage in tanning each year, defined as intentional ultraviolet radiation (UVR) exposure in the form of sunbathing or the use of indoor tanning beds. An emerging body of research suggests that UVR has addictive properties and some tanners engage in excessive tanning. This article provides an overview of the evidence of tanning addiction and a systematic review of existing tanning interventions with the goal of evaluating their potential to impact addicted tanners. Our search identified 24 intervention studies that were summarized and discussed according to 3 primary themes. First, there is a dearth of tanning interventions that target excessive tanning or are designed as treatments for tanning addiction. Second, tanning interventions are primarily educational interventions designed to increase knowledge of the risks of tanning. Third, there are notable aspects of existing tanning interventions that are relevant to addiction science, including the use of brief motivational and cognitive-behavioral-based interventions. Future directions are considered including recommendations for utilizing the existing evidence base to formulate interventions targeting excessive tanners. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Reducing conditions are the key for efficient production of active ribonuclease inhibitor in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Neubauer Peter

    2011-05-01

    Full Text Available Abstract Background The eukaryotic RNase ribonuclease/angiogenin inhibitors (RI are a protein group distinguished by a unique structure - they are composed of hydrophobic leucine-rich repeat motifs (LRR and contain a high amount of reduced cysteine residues. The members of this group are difficult to produce in E. coli and other recombinant hosts due to their high aggregation tendency. Results In this work dithiothreitol (DTT was successfully applied for improving the yield of correctly folded ribonuclease/angiogenin inhibitor in E. coli K12 periplasmic and cytoplasmic compartments. The feasibility of the in vivo folding concepts for cytoplasmic and periplasmic production were demonstrated at batch and fed-batch cultivation modes in shake flasks and at the bioreactor scale. Firstly, the best secretion conditions of RI in the periplasmic space were evaluated by using a high throughput multifactorial screening approach of a vector library, directly with the Enbase fed-batch production mode in 96-well plates. Secondly, the effect of the redox environment was evaluated in isogenic dsbA+ and dsbA- strains at the various cultivation conditions with reducing agents in the cultivation medium. Despite the fusion to the signal peptide, highest activities were found in the cytoplasmic fraction. Thus by removing the signal peptide the positive effect of the reducing agent DTT was clearly proven also for the cytoplasmic compartment. Finally, optimal periplasmic and cytoplasmic RI fed-batch production processes involving externally added DTT were developed in shake flasks and scaled up to the bioreactor scale. Conclusions DTT highly improved both, periplasmic and cytoplasmic accumulation and activity of RI at low synthesis rate, i.e. in constructs harbouring weak recombinant synthesis rate stipulating genetic elements together with cultivation at low temperature. In a stirred bioreactor environment RI folding was strongly improved by repeated pulse addition

  13. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

    Science.gov (United States)

    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  14. A selective phosphodiesterase 10A inhibitor reduces l-dopa-induced dyskinesias in parkinsonian monkeys.

    Science.gov (United States)

    Beck, Goichi; Maehara, Shunsuke; Chang, Phat Ly; Papa, Stella M

    2018-03-06

    Phosphodiesterase 10A is a member of the phosphodiesterase family whose brain expression is restricted to the striatum. Phosphodiesterase 10A regulates cyclic adenosine monophosphate and cyclic guanosine monophosphate, which mediate responses to dopamine receptor activation, and the levels of these cyclic nucleotides are decreased in experimental models of l-dopa-induced dyskinesia. The elevation of cyclic adenosine monophosphate/cyclic guanosine monophosphate levels by phosphodiesterase 10A inhibition may thus be targeted to reduce l-dopa-induced dyskinesia. The present study was aimed at determining the potential antidyskinetic effects of phosphodiesterase 10A inhibitors in a primate model of Parkinson's disease (PD). The experiments performed in this model were also intended to provide translational data for the design of future clinical trials. Five MPTP-treated macaques with advanced parkinsonism and reproducible l-dopa-induced dyskinesia were used. MR1916, a selective phosphodiesterase 10A inhibitor, at doses 0.0015 to 0.05 mg/kg, subcutaneously, or its vehicle (control test) was coadministered with l-dopa methyl ester acutely (predetermined optimal and suboptimal subcutaneous doses) and oral l-dopa chronically as daily treatment for 5 weeks. Standardized scales were used to assess motor disability and l-dopa-induced dyskinesia by blinded examiners. Pharmacokinetics was also examined. MR1916 consistently reduced l-dopa-induced dyskinesia in acute tests of l-dopa optimal and suboptimal doses. Significant effects were present with every MR1916 dose tested, but the most effective was 0.015 mg/kg. None of the MR1916 doses tested affected the antiparkinsonian action of l-dopa at the optimal dose. The anti-l-dopa-induced dyskinesia effect of MR1916 (0.015 mg/kg, subcutaneously) was sustained with chronic administration, indicating that tolerance did not develop over the 5-week treatment. No adverse effects were observed after MR1916 administration acutely or

  15. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

    OpenAIRE

    Suhana Samat; Francis Kanyan Enchang; Fuzina Nor Hussein; Wan Iryani Wan Ismail

    2017-01-01

    Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using h...

  16. Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT)

    OpenAIRE

    Allmark, Peter; Tod, Angela

    2013-01-01

    Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess wint...

  17. A Novel Ras Inhibitor (MDC-1016 Reduces Human Pancreatic Tumor Growth in Mice

    Directory of Open Access Journals (Sweden)

    Gerardo G Mackenzie

    2013-10-01

    Full Text Available Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its persistent resistance to chemotherapy. The currently limited treatment options for pancreatic cancer underscore the need for more efficient agents. Because activating Kras mutations initiate and maintain pancreatic cancer, inhibition of this pathway should have a major therapeutic impact. We synthesized phospho-farnesylthiosalicylic acid (PFTS; MDC-1016 and evaluated its efficacy, safety, and metabolism in preclinical models of pancreatic cancer. PFTS inhibited the growth of human pancreatic cancer cells in culture in a concentration- and time-dependent manner. In an MIA PaCa-2 xenograft mouse model, PFTS at a dose of 50 and 100 mg/kg significantly reduced tumor growth by 62% and 65% (P < .05 vs vehicle control. Furthermore, PFTS prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. PFTS appeared to be safe, with the animals showing no signs of toxicity during treatment. Following oral administration, PFTS was rapidly absorbed, metabolized to FTS and FTS glucuronide, and distributed through the blood to body organs. Mechanistically, PFTS inhibited Ras-GTP, the active form of Ras, both in vitro and in vivo, leading to the inhibition of downstream effector pathways c-RAF/mitogen-activated protein-extracellular signal-regulated kinase (ERK kinase (MEK/ERK1/2 kinase and phosphatidylinositol 3-kinase/AKT. In addition, PFTS proved to be a strong combination partner with phospho-valproic acid, a novel signal transducer and activator of transcription 3 (STAT3 inhibitor, displaying synergy in the inhibition of pancreatic cancer growth. In conclusion, PFTS, a direct Ras inhibitor, is an efficacious agent for the treatment of pancreatic cancer in preclinical models, deserving further evaluation.

  18. Atomoxetine, a norepinephrine reuptake inhibitor, reduces seizure-induced respiratory arrest.

    Science.gov (United States)

    Zhang, Honghai; Zhao, Haiting; Feng, Hua-Jun

    2017-08-01

    Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication, and no effective preventive strategies are currently available for this fatal disorder. Clinical and animal studies of SUDEP demonstrate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death after generalized seizures in many cases. Enhancing brain levels of serotonin reduces S-IRA in animal models relevant to SUDEP, including the DBA/1 mouse. Given that serotonin in the brain plays an important role in modulating respiration and arousal, these findings suggest that deficits in respiration and/or arousal may contribute to S-IRA. It is well known that norepinephrine is an important neurotransmitter that modulates respiration and arousal in the brain as well. Therefore, we hypothesized that enhancing noradrenergic neurotransmission suppresses S-IRA. To test this hypothesis, we examined the effect of atomoxetine, a norepinephrine reuptake inhibitor (NRI), on S-IRA evoked by either acoustic stimulation or pentylenetetrazole in DBA/1 mice. We report the original observation that atomoxetine specifically suppresses S-IRA without altering the susceptibility to seizures evoked by acoustic stimulation, and atomoxetine also reduces S-IRA evoked by pentylenetetrazole in DBA/1 mice. Our data suggest that the noradrenergic signaling is importantly involved in S-IRA, and that atomoxetine, a medication widely used to treat attention deficit hyperactivity disorder (ADHD), is potentially useful to prevent SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Pectinesterase inhibitor from jelly-fig (Ficus awkeotsang Makino) achenes reduces methanol content in carambola wine.

    Science.gov (United States)

    Wu, James Swi-Bea; Wu, Ming-Chang; Jiang, Chii-Ming; Hwang, Ya-Ping; Shen, Szu-Chuan; Chang, Hung-Min

    2005-11-30

    Crude pectinesterase (PE) inhibitor (PEI) extracted from jelly-fig achenes (JFA) (Ficus awakeosang Makino) was added to carambola (Averrhoa carambola L.) puree to determine the change in methanol production during fermentation. Addition of pectin or microbial pectic enzyme to puree increased dose-dependently the methanol content in fermented products. Decreasing ratio (from 1:0 to 1:19, v:v) of pectic enzyme to diluted crude PEI solution in the puree-enzyme mixture decreased the PE activity remarkably. Except for transmittance (%T), addition of crude PEI to puree did not affect apparently the physical and chemical properties of wine; however, it reduced methanol content in the control from 256 to 58 ppm. The degree of esterification (DE) of pectin in starting puree was approximately 70%. It decreased to approximately 27% in the control group and reduced slightly to approximately 67% in fermented puree with crude PEI added after 14 days of fermentation. This reveals that crude PEI solution was potent in inhibiting intrinsic carambola PE activity and appeared to be a potential alternative for methanol reduction in wines.

  20. Method for reducing excess heat supply experienced in typical Chinese district heating systems by achieving hydraulic balance and improving indoor air temperature control at the building level

    International Nuclear Information System (INIS)

    Zhang, Lipeng; Gudmundsson, Oddgeir; Thorsen, Jan Eric; Li, Hongwei; Li, Xiaopeng; Svendsen, Svend

    2016-01-01

    A common problem with Chinese district heating systems is that they supply more heat than the actual heat demand. The reason for this excess heat supply is the general failure to use control devices to adjust the indoor temperature and flow in the building heating systems in accordance with the actual heat demand. This results in 15–30% of the total supplied heat being lost. This paper proposes an integrated approach that aims to reduce the excess heat loss by introducing pre-set thermostatic radiator valves combined with automatic balancing valves. Those devices establish hydraulic balance, and stabilize indoor temperatures. The feasibility and the energy consumption reduction of this approach were verified by means of simulation and a field test. By moving the system from centrally planned heat delivery to demand-driven heat delivery, excess heat loss can be significantly reduced. Results show that once the hydraulic balance is achieved and indoor temperatures are controlled with this integrated approach, 17% heat savings and 42.8% pump electricity savings can be achieved. The energy savings will also have a positive environmental effect with seasonal reductions of 11 kg CO_2, 0.1 kg SO_2, and 0.03 kg NO_x per heating square meter for a typical case in Harbin. - Highlights: • Two real cases reflect the temperature and flow control situation of heating systems in China. • Pre-set radiator valves with automatic balancing valves create dynamic hydraulic balance. • IDA-ICE simulation shows 17% heat saving and 48% pump electricity saving. • This approach can improve the comfort level of multi-storey/high-rise residential buildings. • This approach can reduce excess heat supply and bring out positive environmental impacts.

  1. Fermentable sugars and microbial inhibitors formation from two ...

    African Journals Online (AJOL)

    ... under low severity factor and its enzymatic degradability was investigated in this ... The highest glucan conversion and recovery at the optimum conditions were ... reduce microbial inhibitors formation and excessive biomass processing cost.

  2. A controlled intervention to promote a healthy body image, reduce eating disorder risk and prevent excessive exercise among trainee health education and physical education teachers.

    Science.gov (United States)

    Yager, Zali; O'Dea, Jennifer

    2010-10-01

    This study examined the impact of two interventions on body image, eating disorder risk and excessive exercise among 170 (65% female) trainee health education and physical education (HE&PE) teachers of mean (standard deviation) age 21.6 (2.3) who were considered an 'at-risk' population for poor body image and eating disorders. In the first year of the study, the control group cohort (n = 49 females, 20 males) received the regular didactic health education curriculum; in the second year of the study, the Intervention 1 cohort (n = 31 females, 21 males) received a self-esteem and media literacy health education program and in the third year of the study, the Intervention 2 cohort (n = 30 females, 19 males) received a combined self-esteem, media literacy and dissonance program using online and computer-based activities. Intervention 2 produced the best results, with males improving significantly in self-esteem, body image and drive for muscularity. Intervention 2 females improved significantly on Eating Disorders Inventory Drive for Thinness, Eating Disorder Examination and excessive exercise. The improvements were consistent at 6-month follow-up for females. It is feasible to promote body image, reduce body dissatisfaction and reduce excessive exercise among trainee HE&PE teachers via a health education curriculum.

  3. Sodium-glucose co-transporter type 2 inhibitors reduce evening home blood pressure in type 2 diabetes with nephropathy.

    Science.gov (United States)

    Takenaka, Tsuneo; Kishimoto, Miyako; Ohta, Mari; Tomonaga, Osamu; Suzuki, Hiromichi

    2017-05-01

    The effects of sodium-glucose co-transporter type 2 inhibitors on home blood pressure were examined in type 2 diabetes with nephropathy. The patients with diabetic nephropathy were screened from medical records in our hospitals. Among them, 52 patients who measured home blood pressure and started to take sodium-glucose co-transporter type 2 inhibitors were selected. Clinical parameters including estimated glomerular filtration rate, albuminuria and home blood pressure for 6 months were analysed. Sodium-glucose co-transporter type 2 inhibitors (luseogliflozin 5 mg/day or canagliflozin 100 mg/day) reduced body weight, HbA1c, albuminuria, estimated glomerular filtration rate and office blood pressure. Although sodium-glucose co-transporter type 2 inhibitors did not alter morning blood pressure, it reduced evening systolic blood pressure. Regression analyses revealed that decreases in evening blood pressure predicted decrements in albuminuria. The present data suggest that sodium-glucose co-transporter type 2 inhibitors suppress sodium overload during daytime to reduce evening blood pressure and albuminuria.

  4. A reduced-amide inhibitor of Pin1 binds in a conformation resembling a twisted-amide transition state.

    Science.gov (United States)

    Xu, Guoyan G; Zhang, Yan; Mercedes-Camacho, Ana Y; Etzkorn, Felicia A

    2011-11-08

    The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R-pSer-Ψ[CH(2)N]-Pro-2-(indol-3-yl)ethylamine, 1 [R = fluorenylmethoxycarbonyl (Fmoc)] and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC(50) value of 6.3 μM, which is 4.5-fold better for Pin1 than our comparable ground-state analogue, a cis-amide alkene isostere-containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination and resulted in an IC(50) value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1.

  5. Reduced-Amide Inhibitor of Pin1 Binds in a Conformation Resembling a Twisted-Amide Transition State†

    Science.gov (United States)

    Xu, Guoyan G.; Zhang, Yan; Mercedes-Camacho, Ana Y.; Etzkorn, Felicia A.

    2011-01-01

    The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R–pSer–Ψ[CH2N]–Pro–2-(indol-3-yl)-ethylamine, 1 (R = fluorenylmethoxycarbonyl, Fmoc), and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC50 value of 6.3 μM, which is 4.5-fold better inhibition for Pin1 than our comparable ground state analogue, a cis-amide alkene isostere containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination, and resulted in an IC50 value of 12 μM. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser, and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1. PMID:21980916

  6. Fetal programming: excess prenatal testosterone reduces postnatal luteinizing hormone, but not follicle-stimulating hormone responsiveness, to estradiol negative feedback in the female.

    Science.gov (United States)

    Sarma, Hirendra N; Manikkam, Mohan; Herkimer, Carol; Dell'Orco, James; Welch, Kathleen B; Foster, Douglas L; Padmanabhan, Vasantha

    2005-10-01

    Exposure of female sheep fetuses to excess testosterone (T) during early to midgestation produces postnatal hypergonadotropism manifest as a selective increase in LH. This hypergonadotropism may result from reduced sensitivity to estradiol (E2) negative feedback and/or increased pituitary sensitivity to GnRH. We tested the hypothesis that excess T before birth reduces responsiveness of LH and FSH to E2 negative feedback after birth. Pregnant ewes were treated with T propionate (100 mg/kg in cotton seed oil) or vehicle twice weekly from d 30-90 gestation. Responsiveness to E2 negative feedback was assessed at 12 and 24 wk of age in the ovary-intact female offspring. Our experimental strategy was first to arrest follicular growth and reduce endogenous E2 by administering the GnRH antagonist (GnRH-A), Nal-Glu (50 microg/kg sc every 12 h for 72 h), and then provide a fixed amount of exogenous E2 via an implant. Blood samples were obtained every 20 min at 12 wk and every 10 min at 24 wk before treatment, during and after GnRH-A treatment both before and after E2 implant. GnRH-A ablated LH pulsatility, reduced FSH by approximately 25%, and E2 production diminished to near detection limit of assay at both ages in both groups. Prenatal T treatment produced a precocious and selective reduction in responsiveness of LH but not FSH to E2 negative feedback, which was manifest mainly at the level of LH/GnRH pulse frequency. Collectively, these findings support the hypothesis that prenatal exposure to excess T decreases postnatal responsiveness to E2 inhibitory feedback of LH/GnRH secretion to contribute to the development of hypergonadotropism.

  7. Biochar-enhanced composts reduce the potential leaching of nutrients and heavy metals and suppress plant-parasitic nematodes in excessively fertilized cucumber soils.

    Science.gov (United States)

    Cao, Yune; Gao, Yanming; Qi, Yanbin; Li, Jianshe

    2018-03-01

    Excessive fertilization is a common agricultural practice that has largely reduced soil nutrient retention capacity and led to nutrient leaching in China. To reduce nutrient leaching, in this study, we evaluated the application of biochar, compost, and biochar-compost on soil properties, leaching water quality, and cucumber plant growth in soils with different nutrient levels. In general, the concentrations of nutrients and heavy metals in leaching water were higher under high-nutrient conditions than under low-nutrient conditions. Both biochar and compost efficiently enhanced soil cation exchange capacity (CEC), water holding capacity (WHC), and microbial biomass carbon (MBC), nitrogen (MBN), and phosphorus (MBP), reduced the potential leaching of nutrients and heavy metals, and improved plant growth. The efficiency of biochar and compost in soil CEC, WHC, MBC, MBN, and MBP and plant growth was enhanced when applied jointly. In addition, biochar and biochar-enhanced compost efficiently suppressed plant-parasitic nematode infestation in a soil with high levels of both N and P. Our results suggest that biochar-enhanced compost can reduce the potential environmental risks in excessively fertilized vegetable soils.

  8. Dietary low or excess levels of lipids reduced growth performance, and impaired immune function and structure of head kidney, spleen and skin in young grass carp (Ctenopharyngodon idella) under the infection of Aeromonas hydrophila.

    Science.gov (United States)

    Ni, Pei-Jun; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-08-01

    Our study explored the effect of dietary lipids on growth and immunity and structure (head kidney, spleen and skin) of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp with an average initial weight of 261.41 ± 0.53 g were fed diets containing six graded levels of lipids at 5.9-80.1 g/kg diet for 8 weeks. After that, a challenge trial was conducted by injection of Aeromonas hydrophila over 2 weeks. The results indicated that compared with optimal lipids supplementation, low and excess levels of lipids down-regulated the mRNA levels of antimicrobial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα) and ribosomal p70S6 kinase (S6K1), and up-regulated pro-inflammatory cytokines, nuclear factor κB p65 (NF-κB p65), NF-κB c-Rel (not p52), IκB kinase α (IKKα), IKKβ, IKKγ, and eIF4E-binding protein (4EBP) mRNA levels in the head kidney and spleen of young grass carp (P lipids also increased reactive oxygen species (ROS) production and malondialdehyde (MDA) and protein carbonyl (PC) contents, reduced the activities of antioxidant enzymes (P lipids down-regulated the mRNA levels of B-cell lymphoma-2 (Bcl-2) and inhibitor of apoptosis protein (IAP) in the head kidney and spleen, whereas up-regulated the mRNA levels of apoptotic protease activating factor-1 (Apaf-1), caspase 3, 7, 8 and 9 mRNA levels in the head kidney and spleen and Fas ligand (FasL) mRNA levels in the spleen of young grass carp, suggesting that low or excess levels of lipids could decrease the head kidney and spleen immune function, induce oxidative damage and apoptosis and impair antioxidant system of young grass carp. At last, low or excess levels of lipids also impaired the immune function and structure in the skin of young grass carp. Based on the quadratic regression analysis for PWG, skin haemorrhage and lesions morbidity and IgM content, the dietary lipids requirements for young grass carp were estimated to be 43.7, 60.2, 55.0 and 52.1

  9. Proton Pump Inhibitor Use Is Associated With a Reduced Risk of Infection with Intestinal Protozoa.

    Science.gov (United States)

    Sheele, Johnathan M

    2017-12-01

    Proton pump inhibitors (PPIs) can kill some human protozoan parasites in cell culture better than the drug metronidazole. Clinical data showing an antiprotozoal effect for PPIs are lacking. The objective of the study is to determine if PPI use is associated with a reduced risk of having intestinal parasites. We obtained electronic medical record data for all persons who received a stool ova and parasite (O & P) examination at our tertiary care academic medical center in Cleveland, Ohio, between January 2000 and September 2014. We obtained the person's age, whether they were taking a PPI at the time of the O & P examination, and whether the pathology report indicated the presence of any parasites. χ 2 with Yates correction was used to determine if PPI use was associated with stool protozoa. Three intestinal protozoa were identified in 1199 patients taking a PPI (0.3%), and 551 intestinal parasites were identified in the 14,287 patients not taking a PPI (3.9%). There was a statistically significant lower likelihood of finding protozoa in the stool of a person taking a PPI compared with those not taking a PPI (P protozoa reported on stool O & P examination compared with those not taking a PPI. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  10. Economic Evaluation of PCSK9 Inhibitors in Reducing Cardiovascular Risk from Health System and Private Payer Perspectives.

    Directory of Open Access Journals (Sweden)

    Alejandro Arrieta

    Full Text Available The introduction of Proprotein covertase subtilisin/kexin type 9 (PCSK9 inhibitors has been heralded as a major advancement in reducing low-density lipoprotein cholesterol levels by nearly 50%. However, concerns have been raised on the added value to the health care system in terms of their costs and benefits. We assess the cost-effectiveness of PCSK9 inhibitors based on a decision-analytic model with existing clinical evidence. The model compares a lipid-lowering therapy based on statin plus PCSK9 inhibitor treatment with statin treatment only (standard therapy. From health system perspective, incremental cost per quality adjusted life years (QALYs gained are presented. From a private payer perspective, return-on-investment and net present values over patient lifespan are presented. At the current annual cost of $14,000 to $15,000, PCSK9 inhibitors are not cost-effective at an incremental cost of about $350,000 per QALY. Moreover, for every dollar invested in PCSK9 inhibitors, the private payer loses $1.98. Our study suggests that the annual treatment price should be set at $4,250 at a societal willingness-to-pay of $100,000 per QALY. However, we estimate the breakeven price for private payer is only $600 per annual treatment. At current prices, our study suggests that PCSK9 inhibitors do not add value to the U.S. health system and their provision is not profitable for private payers. To be the breakthrough drug in the fight against cardiovascular disease, the current price of PCSK9 inhibitors must be reduced by more than 70%.

  11. Radiation-induced G/sub 2/-arrest is reduced by inhibitors of poly(adenosine diphosphoribose) synthetase

    International Nuclear Information System (INIS)

    Rowley, R.

    1985-01-01

    Experiments are in progress to test whether poly(adenosine diphosphoribose) synthesis is required for the induction of G/sub 2/-arrest in growing mammalian cells following X-irradiation. A variety of poly(ADPR) synthetase inhibitors have been tested to determine: 1) whether addition of an inhibitor to X-irradiated CHO cells reduces G/sub 2/-arrest; 2) whether compounds structurally similar to poly-(ADPR) synthetase inhibitors but inactive against this enzyme affect radiation-induced G/sub 2/-arrest and 3) whether the concentration dependence for poly(ADPR) synthetase inhibition matches that for G/sub 2/-arrest reduction. G/sub 2/-arrest was measured in X-irradiated (1.5 Gy) CHO cells using the mitotic cell selection technique. Poly(ADPR) synthetase activity was measured in permeabilized cells by /sup 3/H-NAD incorporation. The synthetase inhibitors used were 3-aminobenzamide, benzamide, nicotinamide, 4-acetyl pyridine, caffeine and theophylline. The inactive compounds used were 3-aminobenzoic acid, benzoic acid, nicotinic acid, adenine, adenosine and 3'-deoxyadenosine. Inhibitors of poly(ADPR) synthetase reduced G/sub 2/-arrest while related compounds which produced no enzyme inhibition did not. The concentration dependencies for G/sub 2/-arrest reduction and enzyme inhibition were similar only for methyl xanthines. Further analysis awaits the determination of intracellular drug concentrations

  12. Urease inhibitor for reducing ammonia emissions from an open-lot beef cattle feedyard in the Texas High Plains

    Science.gov (United States)

    Reduction of ammonia (NH3) emissions from animal feeding operations is important from the perspective of environmental policy and its impact on agriculture. In laboratory studies, urease inhibitors have been effective in reducing NH3 emissions from beef cattle manure, however there has been little t...

  13. Method for reducing excess heat supply experienced in typical Chinese district heating systems by achieving hydraulic balance and improving indoor air temperature control at the building level

    DEFF Research Database (Denmark)

    Zhang, Lipeng; Gudmundsson, Oddgeir; Thorsen, Jan Eric

    2016-01-01

    A common problem with Chinese district heating systems is that they supply more heat than the actual heat demand. The reason for this excess heat supply is the general failure to use control devices to adjust the indoor temperature and flow in the building heating systems in accordance with the a......A common problem with Chinese district heating systems is that they supply more heat than the actual heat demand. The reason for this excess heat supply is the general failure to use control devices to adjust the indoor temperature and flow in the building heating systems in accordance...... with the actual heat demand. This results in 15-30% of the total supplied heat being lost. This paper proposes an integrated approach that aims to reduce the excess heat loss by introducing pre-set thermostatic radiator valves combined with automatic balancing valves. Those devices establish hydraulic balance...... that once the hydraulic balance is achieved and indoor temperatures are controlled with this integrated approach, 17% heat savings and 42.8% pump electricity savings can be achieved. The energy savings will also have a positive environmental effect with seasonal reductions of 11 kg CO2, 0.1 kg SO2, and 0...

  14. Reduced Airway Hyperresponsiveness by Phosphodiesterase 3 and 4 Inhibitors in Guinea-Pigs

    Directory of Open Access Journals (Sweden)

    Nöella Germain

    1999-01-01

    Full Text Available The aim of the present study was to compare the effects of selective phosphodiesterase (PDE 3, 4 and 5 inhibitors on antigen-induced airway hyperresponsiveness in sensitized guinea-pigs. When the sensitized guinea-pigs were orally pre-treated with the selective PDE4 inhibitor, Ro 20-1724 (30 mg/kg, and studied 48 h after OA, a significant reduction (p<0.01 of the leftward shift of the dose-response curve to ACh was noted, whereas it was ineffective at the lower dose (10 mg/kg. Administration of the selective PDE3 inhibitor, milrinone (30 mg/kg also elicited a significant reduction (p<0.01 of the airway hyperresponsiveness, whereas the PDE5 inhibitor zaprinast (30 mg/kg was ineffective. These results show that both PDE3 and PDE4 inhibitors are able to inhibit the antigen-induced airway hyperresponsiveness in sensitized guinea-pigs and support the potential utility of selective PDE inhibitors in the treatment of asthma.

  15. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach.

    Science.gov (United States)

    Rohof, Wout O; Bennink, Roelof J; Boeckxstaens, Guy E

    2014-07-01

    The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Reduced circulating stem cells associate with excess fasting and post-load NEFA exposure in healthy adults with normal glucose tolerance.

    Science.gov (United States)

    Fadini, Gian Paolo; Tura, Andrea; Pacini, Giovanni; Avogaro, Angelo; Vigili de Kreutzenberg, Saula

    2017-06-01

    Reduced levels of circulating stem cells (CSCs) predict cardiovascular events and death, but the factors underlying variability of CSCs in healthy adults are mostly unknown. Previous studies detected associations of CSCs with glucose tolerance or insulin resistance, while the role of fatty acids has been overlooked. We herein aimed to describe in better detail the metabolic abnormalities associated with a reduced CSC level. This was a cross-sectional study on 94 healthy male and female individuals with normal glucose tolerance, aged 18-65 years. All participants underwent an oral glucose tolerance test (OGTT) with blood samples collected at 0, 10, 20, 30, 60, 90 and 120 min. Mathematical models were applied to plasma glucose, insulin, C-peptide and non-esterified fatty acids (NEFA) concentrations. CSCs were defined as CD34 + or CD133 + . Participants (mean ± SEM age 43.8 ± 0.7; 41% males) were divided according to CSC levels below (low) or above (high) the median value and metabolic parameters were compared. There was no significant baseline difference between groups except for higher concentrations of fasting NEFA in subjects with low CSCs. Upon OGTT, individuals with low CSCs had higher area under curve (AUC) of NEFA (p glucose, insulin and C-peptide. Several insulin sensitivity and beta cell function indexes were not significantly different, except for a decrease in the disposition index (DI) in subjects with low CSCs. CSCs were associated with excess NEFA levels independently from age and DI. We show for the first time that, in healthy adults with normal glucose tolerance, low CSCs are strongly associated with excess NEFA exposure. The pathophysiological consequence of this association needs to be interpreted in view of the prognostic role of CSCs. Future studies should explore whether excess NEFA and low CSCs and are causally interconnected. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Suhana Samat

    2017-01-01

    Full Text Available Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

  18. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

    Science.gov (United States)

    Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

    2017-01-01

    Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

  19. Association of Proton Pump Inhibitors with Reduced Risk of Warfarin-related Serious Upper Gastrointestinal Bleeding

    Science.gov (United States)

    Ray, Wayne A.; Chung, Cecilia P.; Murray, Katherine T.; Smalley, Walter E.; Daugherty, James R.; Dupont, William D.; Stein, C. Michael

    2016-01-01

    Background & Aims Proton-pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective non-steroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. Methods This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow up. The study endpoints were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Results Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% CI, 0.63–0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94–1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84–1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39–0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. Conclusions In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper

  20. Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

    International Nuclear Information System (INIS)

    Alashkham, Abduelmenem; Paterson, Catherine; Rauchhaus, Petra; Nabi, Ghulam

    2016-01-01

    Purpose: To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. Methods and Materials: A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. χ"2 tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. Results: The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ"2 (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001). Conclusion: Patients who were taking ACEIs were

  1. Can Angiotensin-Converting Enzyme Inhibitors Reduce the Incidence, Severity, and Duration of Radiation Proctitis?

    Energy Technology Data Exchange (ETDEWEB)

    Alashkham, Abduelmenem, E-mail: alashkham@yahoo.com [Academic Section of Urology, Division of Cancer Research, School of Medicine, University of Dundee, Scotland (United Kingdom); Paterson, Catherine [Academic Section of Urology, Division of Cancer Research, School of Medicine, University of Dundee, Scotland (United Kingdom); Rauchhaus, Petra [Tayside Clinical Trials Unit, School of Medicine, University of Dundee, Scotland (United Kingdom); Nabi, Ghulam [Academic Section of Urology, Division of Cancer Research, School of Medicine, University of Dundee, Scotland (United Kingdom)

    2016-01-01

    Purpose: To determine whether participants taking angiotensin-converting enzyme inhibitors (ACEIs) and treated with radical radiation therapy with neoadjuvant/adjuvant hormone therapy have less incidence, severity, and duration of radiation proctitis. Methods and Materials: A propensity score analysis of 817 patients who underwent radical radiation therapy with neoadjuvant or adjuvant hormone therapy as primary line management in a cohort study during 2009 to 2013 was conducted. Patients were stratified as follows: group 1, hypertensive patients taking ACEIs (as a study group); group 2, nonhypertensive patients not taking ACEIs; and group 3, hypertensive patients not taking ACEIs (both as control groups). The incidence, severity, and duration of proctitis were the main outcome. χ{sup 2} tests, Mann-Whitney U tests, analysis of variance, risk ratio (RR), confidence interval (CI), Kaplan-Meier plots, and log-rank tests were used. Results: The mean age of the participants was 68.91 years, with a follow-up time of 3.38 years. Based on disease and age-matched comparison, there was a statistically significant difference of proctitis grading between the 3 groups: χ{sup 2} (8, n=308) = 72.52, P<.001. The Mann-Whitney U test indicated that grades of proctitis were significantly lower in hypertensive patients taking ACEIs than in nonhypertensive patients not taking ACEIs and hypertensive patients not taking ACEIs (P<.001). The risk ratio (RR) of proctitis in hypertensive patients taking ACEIs was significantly lower than in hypertensive patients not taking ACEIs (RR 0.40, 95% CI 0.30-0.53, P<.001) and in nonhypertensive patients not taking ACEIs (RR 0.58, 95% CI 0.44-0.77, P<.001). Time to event analysis revealed that hypertensive patients taking ACEIs were significantly different from the control groups (P<.0001). Furthermore, hypertensive patients taking ACEIs had significantly faster resolution of proctitis (P<.0001). Conclusion: Patients who were taking ACEIs were

  2. The oral histone deacetylase inhibitor ITF2357 reduces cytokines and protects islet ß cells in vivo and in vitro

    DEFF Research Database (Denmark)

    Lewis, Eli C; Blaabjerg, Lykke; Størling, Joachim

    2011-01-01

    of histone deacetylases (HDAC) are used commonly in humans but also possess antiinflammatory and cytokine-suppressing properties. Here we show that oral administration of the HDAC inhibitor ITF2357 to mice normalized streptozotocin (STZ)-induced hyperglycemia at the clinically relevant doses of 1.25-2.5 mg...... production and decreased apoptosis rates from 14.3% (vehicle) to 2.6% (ITF2357). Inducible nitric oxide synthase (iNOS) levels decreased in association with reduced islet-derived nitrite levels. In peritoneal macrophages and splenocytes, ITF2357 inhibited the production of nitrite, as well as that of TNFa...... and IFN¿ at an IC(50) of 25-50 nmol/L. In the insulin-producing INS cells challenged with the combination of IL-1ß plus IFN¿, apoptosis was reduced by 50% (P orally active HDAC inhibitor ITF2357 favors ß-cell survival during inflammatory conditions....

  3. Reducing environmental risk of excessively fertilized soils and improving cucumber growth by Caragana microphylla-straw compost application in long-term continuous cropping systems.

    Science.gov (United States)

    Tian, Yongqiang; Wang, Qing; Zhang, Weihua; Gao, Lihong

    2016-02-15

    Continuous cropping is a common agricultural practice in the word. In China, farmers often apply excessive fertilizers to fields in an attempt to maintain yields in continuous cropping systems. However, this practice often results in high nutrient concentrations in soils, nutrient pollution in leaching water and more crop disease. Here, we investigated 8 different soils from continuously cropped cucumbers in Northern China that grouped into those with extremely high nutrient levels (EHNL) and those with lower nutrient levels (LNL). All soils were treated with Caragana microphylla-straw (CMS) compost addition, and then were used to measure soil physiochemical and microbial properties, leaching water quality, plant root growth and cucumber fruit yield. In general, the EHNL-soil showed higher nitrate, phosphorus and potassium concentrations in the leaching water compared to the LNL-soil. However, the CMS compost application increased soil nutrient and water holding capacities, total microbial biomass (bacteria and fungi), root length, plant biomass and fruit yields, but decreased nutrient concentrations in the leaching water from the EHNL-soil. In addition, the CMS compost decreased the number of Fusarium oxysporum f. sp. cucumerinum in soils with very high concentration of mineral nitrogen. Our results infer that CMS compost application was an effective method for reducing environmental risk of excessively fertilized soils. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Topical application of a protein kinase C inhibitor reduces skin and hair pigmentation

    NARCIS (Netherlands)

    Park, Hee-Young; Lee, Jin; González, Salvador; Middelkamp-Hup, Maritza A.; Kapasi, Sameer; Peterson, Shaun; Gilchrest, Barbara A.

    2004-01-01

    To determine whether inhibition of PKC-beta activity decreases pigmentation, paired cultures of primary human melanocytes were first pretreated with bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30 min, and then treated with TPA for an additional 90 min to activate PKC

  5. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach

    NARCIS (Netherlands)

    Rohof, Wout O.; Bennink, Roelof J.; Boeckxstaens, Guy E.

    2014-01-01

    The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease

  6. Verapamil and angiotensin-converting enzyme inhibitors in patients with coronary artery disease and reduced left ventricular ejection fraction

    DEFF Research Database (Denmark)

    Hansen, J F; Tingsted, L; Rasmussen, Verner

    1996-01-01

    Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been.......4 to 2.5 +/- 0.6 (p attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function...

  7. Treatment with acarbose, an alpha-glucosidase inhibitor, reduces increased albumin excretion in streptozotocin-diabetic rats.

    Science.gov (United States)

    Cohen, M P; Vasselli, J R; Neuman, R G; Witt, J

    1995-10-01

    1. We examined the effect of the alpha-glucosidase inhibitor acarbose on urinary albumin excretion (UAE) in streptozotocin diabetic rats. 2. Treatment with acarbose for 8 weeks after induction of diabetes prevented the significant increase in UAE observed in untreated diabetic rats relative to nondiabetic controls. 3. Acarbose significantly reduced integrated glycemia, which correlated with albumin excretion rates, and exerts a salutary effect on diabetic renal dysfunction.

  8. Combining Urease and Nitrification Inhibitors with Incorporation Reduces Ammonia and Nitrous Oxide Emissions and Increases Corn Yields.

    Science.gov (United States)

    Drury, Craig F; Yang, Xueming; Reynolds, W Dan; Calder, Wayne; Oloya, Tom O; Woodley, Alex L

    2017-09-01

    Less than 50% of applied nitrogen (N) fertilizer is typically recovered by corn ( L.) due to climatic constraints, soil degradation, overapplication, and losses to air and water. Two application methods, two N sources, and two inhibitors were evaluated to reduce N losses and enhance crop uptake. The treatments included broadcast urea (BrUrea), BrUrea with a urease inhibitor (BrUrea+UI), BrUrea with a urease and a nitrification inhibitor (BrUrea+UI+NI), injection of urea ammonium nitrate (InjUAN), and injected with one or both inhibitors (InjUAN+UI, InjUAN+UI+NI), and a control. The BrUrea treatment lost 50% (64.4 kg N ha) of the applied N due to ammonia volatilization, but losses were reduced by 64% with BrUrea+UI+NI (23.0 kg N ha) and by 60% with InjUAN (26.1 kg N ha). Ammonia losses were lower and crop yields were greater in 2014 than 2013 as a result of the more favorable weather when N was applied in 2014. When ammonia volatilization was reduced by adding a urease inhibitor, NO emissions were increased by 30 to 31% with BrUrea+UI and InjUAN+UI compared with BrUrea and InjUAN, respectively. Pollution swapping was avoided when both inhibitors were used (BrUrea+UI+NI, InjUAN+UI+NI) as both ammonia volatilization and NO emissions were reduced, and corn grain yields increased by 5% with BrUrea+UI+NI and by 7% with InjUAN+UI+NI compared with BrUrea and InjUAN, respectively. The combination of two N management strategies (InjUAN+UI+NI) increased yields by 19% (12.9 t ha) compared with BrUrea (10.8 t ha). Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  9. Reducing excess sludge in a biological treatment system using chemical compounds; Reduccion de fangos en exceso de un sistema biologico de depuracion mediante el empleo de compuestos quimicos

    Energy Technology Data Exchange (ETDEWEB)

    Aragon Cruz, C.; Quiroga Alonso, J. M.; Coello Oviedo, M. D.

    2009-07-01

    In the active sludge treatment of waste water, the generation of residual sludge is a major proble due to the cost of dealing with it and the dwindling number of place for disposing of it. A proposal is made for minimising the amount of excess sludge generated using chemical compounds that uncouple its metabolism. An assessment is made of the effectiveness of four such chemical compounds, two organic (2,4-dinitrophenol DNP-and 3,3', 4',5-tetrachlorosalicylanilide- TCS) and two metals (copper and zinc) in order to obtain the optimum amount required. It was found that both TCS and zinc can reduce the bacteria growth rate (Yobs) by over 30% without hardly affecting the elimination organic matter. (Author) 22 refs.

  10. The cannabinoid transporter inhibitor OMDM-2 reduces social interaction: Further evidence for transporter-mediated endocannabinoid release.

    Science.gov (United States)

    Seillier, Alexandre; Giuffrida, Andrea

    2018-03-01

    Experimental evidence suggests that the transport of endocannabinoids might work bi-directionally. Accordingly, it is possible that pharmacological blockade of the latter affects not only the re-uptake, but also the release of endocannabinoids, thus preventing them from stimulating CB 1 receptors. We used biochemical, pharmacological, and behavioral approaches to investigate the effects of the transporter inhibitor OMDM-2 on social interaction, a behavioral assay that requires activation of CB 1 receptors. The underlying mechanisms of OMDM-2 were compared with those of the Fatty Acid Amide Hydrolase (FAAH) inhibitor URB597. Systemic administration of OMDM-2 reduced social interaction, but in contrast to URB597-induced social deficit, this effect was not reversed by the TRPV1 antagonist capsazepine. The CB 1 antagonist AM251, which did not affect URB597-induced social withdrawal, exacerbated OMDM-2 effect. In addition, the potent CB 1 agonist CP55,940 reversed OMDM-2-, but not URB597-, induced social withdrawal. Blockade of CB 1 receptor by AM251 reduced social interaction and the cholecystokinin CCK2 antagonist LY225910 reversed this effect. Similarly, OMDM-2-induced social withdrawal was reversed by LY225910, whereas URB597 effect was not. Elevation of endocannabinoid levels by URB597 or JZL184, an inhibitor of 2-AG degradation, failed to reverse OMDM-2-induced social withdrawal, and did not show additive effects on cannabinoid measurements when co-administered with OMDM-2. Taken together, these findings indicate that OMDM-2 impaired social interaction in a manner that is consistent with reduced activation of presynaptic CB 1 receptors. As cannabinoid reuptake inhibitors may impair endocannabinoid release, caution should be taken when using these drugs to enhance endocannabinoid tone in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Excessive growth.

    Science.gov (United States)

    Narayanaswamy, Vasudha; Rettig, Kenneth R; Bhowmick, Samar K

    2008-09-01

    Tall stature and excessive growth syndrome are a relatively rare concern in pediatric practice. Nevertheless, it is important to identify abnormal accelerated growth patterns in children, which may be the clue in the diagnosis of an underlying disorder. We present a case of pituitary gigantism in a 2 1/2-year-old child and discuss the signs, symptoms, laboratory findings, and the treatment. Brief discussions on the differential diagnosis of excessive growth/tall stature have been outlined. Pituitary gigantism is very rare in the pediatrics age group; however, it is extremely rare in a child that is less than 3 years of age. The nature of pituitary adenoma and treatment options in children with this condition have also been discussed.

  12. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    OpenAIRE

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-01-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlyso...

  13. Reduced Levels of Tissue Inhibitors of Metalloproteinases in UVB-Irradiated Corneal Epithelium

    Czech Academy of Sciences Publication Activity Database

    Ardan, Taras; Němcová, Lucie; Bohuslavová, Božena; Klezlová, A.; Popelka, Štěpán; Studenovská, Hana; Hrnčiarová, Eva; Čejková, Jitka; Motlík, Jan

    2016-01-01

    Roč. 92, č. 5 (2016), s. 720-727 ISSN 0031-8655 R&D Projects: GA ČR GPP302/10/P155; GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 ; RVO:61389013 ; RVO:68378041 Keywords : tissue inhibitors of metalloproteinases * matrix metalloproteinases Subject RIV: EB - Genetics ; Molecular Biology; CD - Macromolecular Chemistry (UMCH-V) Impact factor: 2.121, year: 2016

  14. Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

    Science.gov (United States)

    Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

    2006-03-01

    Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

  15. Reduced intensity conditioning is superior to nonmyeloablative conditioning for older chronic myelogenous leukemia patients undergoing hematopoietic cell transplant during the tyrosine kinase inhibitor era

    DEFF Research Database (Denmark)

    Warlick, Erica; Ahn, Kwang Woo; Pedersen, Tanya L

    2012-01-01

    Tyrosine kinase inhibitors (TKIs) and reduced intensity conditioning (RIC)/nonmyeloablative (NMA) conditioning hematopoietic cell transplants (HCTs) have changed the therapeutic strategy for chronic myelogenous leukemia (CML) patients. We analyzed post-HCT outcomes of 306 CML patients reported to...

  16. Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT).

    Science.gov (United States)

    Allmark, Peter; Tod, Angela M

    2014-03-01

    Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess winter deaths (EWDs) is a public health priority; however, EWD seems clearly to be socially determined such that nudges arguably have little role. This article defends two claims: (i) nudges could have a place in tackling even the heavily socially determined problem of EWD. We draw on evidence from an empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that in some cases the risk of cold is within the person's control to some extent such that environmental modifications to influence behaviour such as nudges are possible. (ii) Some uses of behavioural insights in the form of nudges are acceptable, including some in the area of EWD. We suggest a question-based framework by which to judge the ethical acceptability of nudges.

  17. Excess of methyl donor in the perinatal period reduces postnatal leptin secretion in rat and interacts with the effect of protein content in diet.

    Directory of Open Access Journals (Sweden)

    Fanny Giudicelli

    Full Text Available Methionine, folic acid, betaine and choline interact in the one-carbon metabolism which provides methyl groups for methylation reactions. An optimal intake of these nutrients during pregnancy is required for successful completion of fetal development and evidence is growing that they could be involved in metabolic long-term programming. However, the biological pathways involved in the action of these nutrients are still poorly known. This study investigated the interaction between methyl donors and protein content in maternal diet during the preconceptual, pregnancy and lactation periods and the consequences on the rat offspring in the short and long term. Methyl donor supplementation reduced leptin secretion in offspring, whereas insulin levels were mostly affected by protein restriction. The joint effect of protein restriction and methyl donor excess strongly impaired postnatal growth in both gender and long term weight gain in male offspring only, without affecting food intake. In addition, rats born from protein restricted and methyl donor supplemented dams gained less weight when fed a hypercaloric diet. Methylation of the leptin gene promoter in adipose tissue was increased in methyl donor supplemented groups but not affected by protein restriction only. These results suggest that maternal methyl donor supplementation may influence energy homeostasis in a gender-dependent manner, without affecting food intake. Moreover, we showed that macronutrients and micronutrients in maternal diet interact to influence the programming of the offspring.

  18. Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack

    Science.gov (United States)

    Brookes, Rebecca L.; Crichton, Siobhan; Wolfe, Charles D.A.; Yi, Qilong; Li, Linxin; Hankey, Graeme J.; Rothwell, Peter M.

    2018-01-01

    Background and Purpose— A variant in the histone deacetylase 9 (HDAC9) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. Methods— Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. Results— A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3–0.7; P=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29–0.77; P=0.003). Conclusions— These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke. PMID:29247141

  19. Hemophilia A Pseudoaneurysm in a Patient with High Responding Inhibitors Complicating Total Knee Arthroplasty: Embolization: A Cost-Reducing Alternative to Medical Therapy

    International Nuclear Information System (INIS)

    Kickuth, Ralph; Anderson, Suzanne; Peter-Salonen, Kristiina; Laemmle, Bernhard; Eggli, Stefan; Triller, Juergen

    2006-01-01

    Joint hemorrhages are very common in patients with severe hemophilia. Inhibitors in patients with hemophilia are allo-antibodies that neutralize the activity of the clotting factor. After total knee replacement, rare intra-articular bleeding complications might occur that do not respond to clotting factor replacement. We report a 40-year-old male with severe hemophilia A and high responding inhibitors presenting with recurrent knee joint hemorrhage after bilateral knee prosthetic surgery despite adequate clotting factor treatment. There were two episodes of marked postoperative hemarthrosis requiring extensive use of subsititution therapy. Eleven days postoperatively, there was further hemorrhage into the right knee. Digital subtraction angiography diagnosed a complicating pseudoaneurysm of the inferior lateral geniculate artery and embolization was successfully performed. Because clotting factor replacement therapy has proved to be excessively expensive and prolonged, especially in patients with inhibitors, we recommend the use of cost-effective early angiographic embolization

  20. The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in decerebrate rats.

    Science.gov (United States)

    Copp, Steven W; Kim, Joyce S; Ruiz-Velasco, Victor; Kaufman, Marc P

    2016-02-01

    Mechanical and metabolic stimuli from contracting muscles evoke reflex increases in blood pressure, heart rate and sympathetic nerve activity. Little is known, however, about the nature of the mechano-gated channels on the thin fibre muscle afferents that contribute to evoke this reflex, termed the exercise pressor reflex. We determined the effect of GsMTx4, an inhibitor of mechano-gated Piezo channels, on the exercise pressor reflex evoked by intermittent contraction of the triceps surae muscles in decerebrated, unanaesthetized rats. GsMTx4 reduced the pressor, cardioaccelerator and renal sympathetic nerve responses to intermittent contraction but did not reduce the pressor responses to femoral arterial injection of compounds that stimulate the metabolically-sensitive thin fibre muscle afferents. Expression levels of Piezo2 channels were greater than Piezo1 channels in rat dorsal root ganglia. Our findings suggest that mechanically-sensitive Piezo proteins contribute to the generation of the mechanical component of the exercise pressor reflex in rats. Mechanical and metabolic stimuli within contracting skeletal muscles evoke reflex autonomic and cardiovascular adjustments. In cats and rats, gadolinium has been used to investigate the role played by the mechanical component of this reflex, termed the exercise pressor reflex. Gadolinium, however, has poor selectivity for mechano-gated channels and exerts multiple off-target effects. We tested the hypothesis that GsMTX4, a more selective mechano-gated channel inhibitor than gadolinium and a particularly potent inhibitor of mechano-gated Piezo channels, reduced the exercise pressor reflex in decerebrate rats. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 5, GsMTx4: 12 ± 5 mmHg, P acid. Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the peak pressor (control: 24 ± 2, GsMTx4: 14 ± 3 mmHg, P reflex in

  1. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus.

    Science.gov (United States)

    Kalia, Nitin Pal; Mahajan, Priya; Mehra, Rukmankesh; Nargotra, Amit; Sharma, Jai Parkash; Koul, Surrinder; Khan, Inshad Ali

    2012-10-01

    To delineate the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide) as an inhibitor of the NorA efflux pump and its impact on invasion of macrophages by Staphylococcus aureus. Capsaicin in combination with ciprofloxacin was tested for activity against S. aureus SA-1199B (NorA overproducing), SA-1199 (wild-type) and SA-K1758 (norA knockout). The role of NorA in the intracellular invasion of S. aureus and the ability of capsaicin to inhibit this invasion was established in J774 macrophage cell lines. The three-dimensional structure of NorA was predicted using an in silico approach and docking studies of capsaicin were performed. Capsaicin significantly reduced the MIC of ciprofloxacin for S. aureus SA-1199 and SA-1199B. Furthermore, capsaicin also extended the post-antibiotic effect of ciprofloxacin by 1.1 h at MIC concentration. There was a decrease in mutation prevention concentration of ciprofloxacin when combined with capsaicin. Inhibition of ethidium bromide efflux by NorA-overproducing S. aureus SA-1199B confirmed the role of capsaicin as a NorA efflux pump inhibitor (EPI). The most significant finding of this study was the ability of capsaicin to reduce the intracellular invasion of S. aureus SA-1199B (NorA overproducing) in J774 macrophage cell lines by 2 log(10). This study, for the first time, has shown that capsaicin, a novel EPI, not only inhibits the NorA efflux pump of S. aureus but also reduces the invasiveness of S. aureus, thereby reducing its virulence.

  2. Nordic Walking as an Exercise Intervention to Reduce Pain in Women With Aromatase Inhibitor-Associated Arthralgia: A Feasibility Study.

    Science.gov (United States)

    Fields, Jo; Richardson, Alison; Hopkinson, Jane; Fenlon, Deborah

    2016-10-01

    Women taking aromatase inhibitors as treatment for breast cancer commonly experience joint pain and stiffness (aromatase inhibitor-associated arthralgia [AIAA]), which can cause problems with adherence. There is evidence that exercise might be helpful, and Nordic walking could reduce joint pain compared to normal walking. To determine the feasibility of a trial of Nordic walking as an exercise intervention for women with AIAA. A feasibility study was carried out in a sample of women with AIAA using a randomized control design. Women were randomized to exercise (six-week supervised group Nordic walking training once per week with an increasing independent element, followed by six weeks 4 × 30 minutes/week independent Nordic walking); or enhanced usual care. Data were collected on recruitment, retention, exercise adherence, safety, and acceptability. The Brief Pain Inventory, GP Physical Activity Questionnaire, and biopsychosocial measures were completed at baseline, six and 12 weeks. Forty of 159 eligible women were recruited and attrition was 10%. There was no increased lymphedema and no long-term or serious injury. Adherence was >90% for weekly supervised group Nordic walking, and during independent Nordic walking, >80% women managed one to two Nordic walking sessions per week. From baseline to study end point, overall activity levels increased and pain reduced in both the intervention and control groups. Our findings indicate that women with AIAA are prepared to take up Nordic walking, complete a six-week supervised course and maintain increased activity levels over a 12-week period with no adverse effects. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  3. The calcineurin inhibitor tacrolimus reduces proteinuria in membranous nephropathy accompanied by a decrease in angiopoietin-like-4.

    Directory of Open Access Journals (Sweden)

    Lei Peng

    Full Text Available Tacrolimus is an anticalcineurinic agent with potent immunosuppressive activity that has recently been shown to have the added benefit of reducing proteinuria in membranous nephropathy (MN patients. However, its potential mechanisms remain unknown. To reveal the mechanism, rat cohorts were administered tacrolimus or vehicle from days 7 to 28 after the induction of passive Heymann nephritis (PHN. PHN induction resulted in heavy proteinuria and increased expression of desmin, a marker of injured podocytes. We also showed that the glomerular expression of angiopoietin-like-4 (Angptl4 was markedly upregulated in PHN rats and human MN followed by an increase in urine Angptl4 excretion. In addition, increased Angptl4 expression may be related to podocyte injury and proteinuria. Furthermore, upregulated Angptl4 expression primarily colocalized with podocytes rather than endothelial or mesangial cells, indicating that podocytes may be the source of Angptl4, which then gradually migrated to the glomerular basement membrane over time. However, tacrolimus treatment markedly reduced glomerular and urinary Angptl4, accompanied by a reduction in the established proteinuria and the promotion of podocyte repair. Additionally, glomerular immune deposits and circulating IgG levels induced by PHN clearly decreased following tacrolimus treatment. In conclusion, this is the first demonstration that the calcineurin inhibitor tacrolimus can reduce Angptl4 in podocytes accompanied by a decrease in established proteinuria and promotion of podocyte repair in MN.

  4. A new mechanism for reduced sensitivity to demethylation-inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis.

    Science.gov (United States)

    Diaz-Trujillo, Caucasella; Chong, Pablo; Stergiopoulos, Ioannis; Cordovez, Viviane; Guzman, Mauricio; De Wit, Pierre J G M; Meijer, Harold J G; Scalliet, Gabriel; Sierotzki, Helge; Lilia Peralta, Esther; Arango Isaza, Rafael E; Kema, Gerrit H J

    2017-11-04

    The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications, with a major contribution from sterol demethylation-inhibitors (DMIs). The continued use of DMIs places considerable selection pressure on natural P. fijiensis populations, enabling the selection of novel genotypes with reduced sensitivity. The hitherto explanatory mechanism for this reduced sensitivity was the presence of non-synonymous point mutations in the target gene Pfcyp51, encoding the sterol 14α-demethylase enzyme. Here, we demonstrate a second mechanism involved in DMI sensitivity of P. fijiensis. We identified a 19-bp element in the wild-type (wt) Pfcyp51 promoter that concatenates in strains with reduced DMI sensitivity. A polymerase chain reaction (PCR) assay identified up to six Pfcyp51 promoter repeats in four field populations of P. fijiensis in Costa Rica. We used transformation experiments to swap the wt promoter of a sensitive field isolate with a promoter from a strain with reduced DMI sensitivity that comprised multiple insertions. Comparative in vivo phenotyping showed a functional and proportional up-regulation of Pfcyp51, which consequently decreased DMI sensitivity. Our data demonstrate that point mutations in the Pfcyp51 coding domain, as well as promoter inserts, contribute to the reduced DMI sensitivity of P. fijiensis. These results provide new insights into the importance of the appropriate use of DMIs and the need for the discovery of new molecules for black Sigatoka management. © 2017 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.

  5. Low-Dose Dextromethorphan, a NADPH Oxidase Inhibitor, Reduces Blood Pressure and Enhances Vascular Protection in Experimental Hypertension

    Science.gov (United States)

    Wu, Tao-Cheng; Chao, Chih-Yu; Lin, Shing-Jong; Chen, Jaw-Wen

    2012-01-01

    Background Vascular oxidative stress may be increased with age and aggravate endothelial dysfunction and vascular injury in hypertension. This study aimed to investigate the effects of dextromethorphan (DM), a NADPH oxidase inhibitor, either alone or in combination treatment, on blood pressure (BP) and vascular protection in aged spontaneous hypertensive rats (SHRs). Methodology/Principal Findings Eighteen-week-old WKY rats and SHRs were housed for 2 weeks. SHRs were randomly assigned to one of the 12 groups: untreated; DM monotherapy with 1, 5 or 25 mg/kg/day; amlodipine (AM, a calcium channel blocker) monotherapy with 1 or 5 mg/kg/day; and combination therapy of DM 1, 5 or 25 mg/kg/day with AM 1 or 5 mg/kg/day individually for 4 weeks. The in vitro effects of DM were also examined. In SHRs, AM monotherapy dose-dependently reduced arterial systolic BP. DM in various doses significantly and similarly reduced arterial systolic BP. Combination of DM with AM gave additive effects on BP reduction. DM, either alone or in combination with AM, improved aortic endothelial function indicated by ex vivo acetylcholine-induced relaxation. The combination of low-dose DM with AM gave most significant inhibition on aortic wall thickness in SHRs. Plasma total antioxidant status was significantly increased by all the therapies except for the combination of high-dose DM with high-dose AM. Serum nitrite and nitrate level was significantly reduced by AM but not by DM or the combination of DM with AM. Furthermore, in vitro treatment with DM reduced angiotensin II-induced reactive oxygen species and NADPH oxidase activation in human aortic endothelial cells. Conclusions/Significance Treatment of DM reduced BP and enhanced vascular protection probably by inhibiting vascular NADPH oxidase in aged hypertensive animals with or without AM treatment. It provides the potential rationale to a novel combination treatment with low-dose DM and AM in clinical hypertension. PMID:23049937

  6. Low-dose dextromethorphan, a NADPH oxidase inhibitor, reduces blood pressure and enhances vascular protection in experimental hypertension.

    Directory of Open Access Journals (Sweden)

    Tao-Cheng Wu

    Full Text Available BACKGROUND: Vascular oxidative stress may be increased with age and aggravate endothelial dysfunction and vascular injury in hypertension. This study aimed to investigate the effects of dextromethorphan (DM, a NADPH oxidase inhibitor, either alone or in combination treatment, on blood pressure (BP and vascular protection in aged spontaneous hypertensive rats (SHRs. METHODOLOGY/PRINCIPAL FINDINGS: Eighteen-week-old WKY rats and SHRs were housed for 2 weeks. SHRs were randomly assigned to one of the 12 groups: untreated; DM monotherapy with 1, 5 or 25 mg/kg/day; amlodipine (AM, a calcium channel blocker monotherapy with 1 or 5 mg/kg/day; and combination therapy of DM 1, 5 or 25 mg/kg/day with AM 1 or 5 mg/kg/day individually for 4 weeks. The in vitro effects of DM were also examined. In SHRs, AM monotherapy dose-dependently reduced arterial systolic BP. DM in various doses significantly and similarly reduced arterial systolic BP. Combination of DM with AM gave additive effects on BP reduction. DM, either alone or in combination with AM, improved aortic endothelial function indicated by ex vivo acetylcholine-induced relaxation. The combination of low-dose DM with AM gave most significant inhibition on aortic wall thickness in SHRs. Plasma total antioxidant status was significantly increased by all the therapies except for the combination of high-dose DM with high-dose AM. Serum nitrite and nitrate level was significantly reduced by AM but not by DM or the combination of DM with AM. Furthermore, in vitro treatment with DM reduced angiotensin II-induced reactive oxygen species and NADPH oxidase activation in human aortic endothelial cells. CONCLUSIONS/SIGNIFICANCE: Treatment of DM reduced BP and enhanced vascular protection probably by inhibiting vascular NADPH oxidase in aged hypertensive animals with or without AM treatment. It provides the potential rationale to a novel combination treatment with low-dose DM and AM in clinical hypertension.

  7. Dietary Selenium Deficiency or Excess Reduces Sperm Quality and Testicular mRNA Abundance of Nuclear Glutathione Peroxidase 4 in Rats.

    Science.gov (United States)

    Zhou, Ji-Chang; Zheng, Shijie; Mo, Junluan; Liang, Xiongshun; Xu, Yuanfei; Zhang, Huimin; Gong, Chunmei; Liu, Xiao-Li; Lei, Xin Gen

    2017-10-01

    Background: Glutathione peroxidase (GPX) 4 and selenoprotein P (SELENOP) are abundant, and several variants are expressed in the testis. Objective: We determined the effects of dietary selenium deficiency or excess on sperm quality and expressions of GPX4 and SELENOP variants in rat testis and liver. Methods: After weaning, male Sprague-Dawley rats were fed a Se-deficient basal diet (BD) for 5 wk until they were 9 wk old [mean ± SEM body weight (BW) = 256 ± 5 g]. They were then fed the BD diet alone (deficient) or with 0.25 (adequate), 3 (excess), or 5 (excess) mg Se/kg for 4 wk. Testis, liver, blood, and semen were collected to assay for selenoprotein mRNA and protein abundances, selenium concentration, GPX activity, 8-hydroxy-deoxyguanosine concentration, and sperm quality. Results: Dietary selenium supplementations elevated ( P selenium concentrations and GPX activities. Compared with those fed BD + 0.25 mg Se/kg, rats fed BD showed lower ( P selenium-adequate group. Compared with the selenium-adequate group, dietary selenium deficiency (BD) or excess (BD + 3 or 5 mg Se/kg) resulted in 45-77% lower ( P selenium concentrations in similar ways to sperm parameters and may be used as a sensitive marker to assess appropriate Se status for male function. © 2017 American Society for Nutrition.

  8. A Controlled Intervention to Promote a Healthy Body Image, Reduce Eating Disorder Risk and Prevent Excessive Exercise among Trainee Health Education and Physical Education Teachers

    Science.gov (United States)

    Yager, Zali; O'Dea, Jennifer

    2010-01-01

    This study examined the impact of two interventions on body image, eating disorder risk and excessive exercise among 170 (65% female) trainee health education and physical education (HE & PE) teachers of mean (standard deviation) age 21.6 (2.3) who were considered an "at-risk" population for poor body image and eating disorders. In the first year…

  9. Bauhinia bauhinioides cruzipain inhibitor reduces endothelial proliferation and induces an increase of the intracellular Ca2+ concentration.

    Science.gov (United States)

    Bilgin, Mehmet; Neuhof, Christiane; Doerr, Oliver; Benscheid, Utz; Andrade, Sheila S; Most, Astrid; Abdallah, Yaser; Parahuleva, Mariana; Guenduez, Dursun; Oliva, Maria L; Erdogan, Ali

    2010-12-01

    Proteinase inhibitors, isolated from different types of Bauhinia, have an effect on apoptosis, angiogenesis and inflammation. The Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a Kunitz-type inhibitor and inactivates the cysteine proteinases cruzipain and cruzain from Trypanosoma cruzi. Cruzipain and tissue kallikrein have similar biochemical properties, e.g. the proteolytic cleavage of the kininogen precursor of lys-bradykinin. Tissue kallikrein stimulation in endothelial cells causes migration and capillary tube formation. The aim of this study was to examine whether the antiproliferative effect of BbCI is dependent on changes of the intracellular calcium concentration and membrane hyperpolarization. Endothelial cells were isolated from human umbilical cord veins (HUVEC). For proliferation experiments, HUVEC were incubated with BbCI (10-100 μmol/L) for 48 h. The proliferation was detected by cell counting with a Neubauer chamber. The effect of BbCI (10-100 μM) on the membrane potential was measured with the fluorescence dye DiBAC4(3) and the effect on [Ca+2]i with the fluorescence probe Fluo-3 AM. The change of the fluorescence intensity was determined with a GENios plate reader (Tecan). The experiments showed that BbCI (10-100 μmol/L) reduces the endothelial cell proliferation significantly in a concentration-dependent manner with a maximum effect at 100 μmol/L (35.1±1.8% as compared to control (p≤0.05; n=45)). As compared to the control, the addition of BbCI (100 μmol/L) caused a significant increase of systolic Ca2+ of 28.4±5.0% after 30 min incubation. HUVEC treatment with BbCI (100 μmol/L) showed a weak but significant decrease of the membrane potential of 9.5±0.9% as compared to control (p≤0.05; n=80). BbCI influenced significantly the endothelial proliferation, the intracellular Ca2+ concentration and the membrane potential.

  10. Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells

    Directory of Open Access Journals (Sweden)

    Lev Shapira

    2016-12-01

    Full Text Available Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1 fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s. Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA, Suberohydroxamic Acid (SBX, Valporic Acid (VPA and Suberoylanilide Hydoxamic Acid (SAHA. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero and U2OS, which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX, which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in

  11. An investigation into the effects of maternal supplementation with excess iodine on the mechanisms and impacts of reduced IgG absorption in the lamb postpartum.

    Science.gov (United States)

    McGovern, F M; Sweeney, T; Ryan, M T; Lott, S; Campion, F P; Boland, T M

    2017-04-01

    An experiment was conducted to determine: (1) the effect of excess maternal I supplementation on the thyroid hormone status of the ewe and her progeny; (2) potential mechanisms underpinning the failure of passive transfer associated with excess I and (3) the growing lambs' response to natural gastrointestinal infection. Twin-bearing ewes received one of two treatments (n 32/treatment group): basal diet (C) or C plus 26·6 mg of iodine/ewe per d (I), supplied as calcium iodate. Ewes were individually fed from day 119 of gestation to parturition. Progeny of I ewes had lower (Plamb at 24 h postpartum; however, thyroid hormone receptor-β (THRB) and β-2-microglobulin (B2M) expression declined (Plamb postpartum. These effects were followed by an enhancement of average daily gain and lower N. battus FEC in the pre-weaning period of I-supplemented lambs.

  12. Reducing the concentration to 0.4% enantiomeric excess hyperbaric levobupivacaine (s75: r25) provides unilateral spinal anesthesia. Study with different volumes.

    Science.gov (United States)

    Imbelloni, Luiz Eduardo; Gouveia, Marildo A; Carneiro, Antonio Fernando; Grigorio, Renata

    2012-01-01

    Unilateral spinal anesthesia may be obtained with hypobaric or hyperbaric solution. The objective of this study was to compare different doses of enantiomeric excess hyperbaric levobupivacaine to achieve unilateral spinal anesthesia. One hundred and twenty patients were randomized to receive 4 mg, 6 mg or 8 mg of 0.4% enantiomeric excess levobupivacaine. The solutions were administered at the L3-L4, with the patient in a lateral position and kept at this position according to dose administration for 5, 10 or 15 minutes. Sensory block (pinprick) and motor block (scale 0-3) were compared between the operated and contralateral sides. The onset of analgesia was rapid and comparable between groups. Sensory block was significantly higher in the operated than in nonoperated limb at all times of evaluation. Increasing the dose by 1 mL (2mg) corresponded to an increase of two segments in the mode for the operated side. In the operated side, motor block (MB = 3) of patients occurred in 31 (77.5%) with 4 mg, 38 (95%) with 6 mg, and 40 (100%) with 8 mg. There was a positive correlation between increased dose, blockade duration, and hypotension. All patients were satisfied with the technique used. Spinal anesthesia with different volumes of enantiomeric excess hyperbaric bupivacaine (S75: R25) provided a 78% incidence of unilateral spinal block, with the smallest dose used (4 mg) the most efficient. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

  13. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Directory of Open Access Journals (Sweden)

    Toshifumi Tezuka

    Full Text Available Plasminogen activator inhibitor (PAI-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp. IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  14. IMD-4690, a novel specific inhibitor for plasminogen activator inhibitor-1, reduces allergic airway remodeling in a mouse model of chronic asthma via regulating angiogenesis and remodeling-related mediators.

    Science.gov (United States)

    Tezuka, Toshifumi; Ogawa, Hirohisa; Azuma, Masahiko; Goto, Hisatsugu; Uehara, Hisanori; Aono, Yoshinori; Hanibuchi, Masaki; Yamaguchi, Yoichi; Fujikawa, Tomoyuki; Itai, Akiko; Nishioka, Yasuhiko

    2015-01-01

    Plasminogen activator inhibitor (PAI)-1 is the principal inhibitor of plasminogen activators, and is responsible for the degradation of fibrin and extracellular matrix. IMD-4690 is a newly synthesized inhibitor for PAI-1, whereas the effect on allergic airway inflammation and remodeling is still unclear. We examined the in vivo effects by using a chronic allergen exposure model of bronchial asthma in mice. The model was generated by an immune challenge for 8 weeks with house dust mite antigen, Dermatophagoides pteronyssinus (Dp). IMD-4690 was intraperitoneally administered during the challenge. Lung histopathology, hyperresponsiveness and the concentrations of mediators in lung homogenates were analyzed. The amount of active PAI-1 in the lungs was increased in mice treated with Dp. Administration with IMD-4690 reduced an active/total PAI-1 ratio. IMD-4690 also reduced the number of bronchial eosinophils in accordance with the decreased expressions of Th2 cytokines in the lung homogenates. Airway remodeling was inhibited by reducing subepithelial collagen deposition, smooth muscle hypertrophy, and angiogenesis. The effects of IMD-4690 were partly mediated by the regulation of TGF-β, HGF and matrix metalloproteinase. These results suggest that PAI-1 plays crucial roles in airway inflammation and remodeling, and IMD-4690, a specific PAI-1 inhibitor, may have therapeutic potential for patients with refractory asthma due to airway remodeling.

  15. Glycation inhibitors extend yeast chronological lifespan by reducing advanced glycation end products and by back regulation of proteins involved in mitochondrial respiration.

    Science.gov (United States)

    Kazi, Rubina S; Banarjee, Reema M; Deshmukh, Arati B; Patil, Gouri V; Jagadeeshaprasad, Mashanipalya G; Kulkarni, Mahesh J

    2017-03-06

    Advanced Glycation End products (AGEs) are implicated in aging process. Thus, reducing AGEs by using glycation inhibitors may help in attenuating the aging process. In this study using Saccharomyces cerevisiae yeast system, we show that Aminoguanidine (AMG), a well-known glycation inhibitor, decreases the AGE modification of proteins in non-calorie restriction (NR) (2% glucose) and extends chronological lifespan (CLS) similar to that of calorie restriction (CR) condition (0.5% glucose). Proteomic analysis revealed that AMG back regulates the expression of differentially expressed proteins especially those involved in mitochondrial respiration in NR condition, suggesting that it switches metabolism from fermentation to respiration, mimicking CR. AMG induced back regulation of differentially expressed proteins could be possibly due to its chemical effect or indirectly by glycation inhibition. To delineate this, Metformin (MET), a structural analog of AMG and a mild glycation inhibitor and Hydralazine (HYD), another potent glycation inhibitor but not structural analog of AMG were used. HYD was more effective than MET in mimicking AMG suggesting that glycation inhibition was responsible for restoration of differentially expressed proteins. Thus glycation inhibitors particularly AMG, HYD and MET extend yeast CLS by reducing AGEs, modulating the expression of proteins involved in mitochondrial respiration and possibly by scavenging glucose. This study reports the role of glycation in aging process. In the non-caloric restriction condition, carbohydrates such as glucose promote protein glycation and reduce CLS. While, the inhibitors of glycation such as AMG, HYD, MET mimic the caloric restriction condition by back regulating deregulated proteins involved in mitochondrial respiration which could facilitate shift of metabolism from fermentation to respiration and extend yeast CLS. These findings suggest that glycation inhibitors can be potential molecules that can be used

  16. Replacement treatment during extinction training with the atypical dopamine uptake inhibitor, JHW-007, reduces relapse to methamphetamine seeking.

    Science.gov (United States)

    Dassanayake, Ashlea F; Canales, Juan J

    2018-04-03

    There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial. Here, we compared in rats the ability of the BZT analogue and high affinity dopamine (DA) reuptake inhibitor, JHW-007, and the antidepressant, trazodone, administered during extinction sessions after chronic METH self-administration, to alter METH-primed reinstatement of drug seeking. The data showed that trazodone produced paradoxical effects on lever pressing during extinction of METH self-administration, decreasing active, but increasing inactive, lever pressing. JHW-007 did not have any observable effects on extinction training. Importantly, JHW-007 significantly attenuated METH-primed reinstatement, whereas trazodone enhanced it. These findings lend support to the candidacy of selective DA uptake blockers, such as JHW-007, as potential treatments for METH addiction, but not to the use of antidepressant medication as a single therapeutic approach for relapse prevention. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

    Science.gov (United States)

    Ibáñez, Lourdes; López-Bermejo, Abel; Díaz, Marta; Marcos, Maria Victoria; de Zegher, Francis

    2011-08-01

    Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. This was a randomized, open-label study over 7 yr. The study was conducted at a university hospital. Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.

  18. Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial lv

    DEFF Research Database (Denmark)

    Gullestad, Lars; Eiskjaer, Hans; Gustafsson, Finn

    2016-01-01

    The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus...

  19. The costs of reducing the excess CO{sub 2} emissions. Reduction potential and costs in certain sector; Hvad koster det at reducere CO{sup 2}-mankoen? - Reduktionspotentiale og omkostninger i udvalgte sektorer

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-07-01

    The report presents the results from the project 'The costs of reducing the excess CO{sub 2} emissions - reduction potential and costs in certain sectors'. The aim of the project has been to elucidate the full extent of the reduction potentials and the costs for certain CO{sub 2} reducing initiatives, which are not included in the present projections of the excess CO{sub 2} emissions. The initiatives included in this report are: Accumulation of methane from Danish disposal facilities; Accumulation of methane from disposal facilities in Russia; Reduction in the use of industrial greenhouse gases; Aquifer disposal of CO{sub 2} in the underground; Offshore CO{sub 2} disposal in oil fields in the North Sea. Furthermore, the report presents a general evaluation of the potential of methane accumulation from wastewater treatment. (ba)

  20. Excess Entropy and Diffusivity

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Excess Entropy and Diffusivity. Excess entropy scaling of diffusivity (Rosenfeld,1977). Analogous relationships also exist for viscosity and thermal conductivity.

  1. Integrated economic and life cycle assessment of thermochemical production of bioethanol to reduce production cost by exploiting excess of greenhouse gas savings

    International Nuclear Information System (INIS)

    Reyes Valle, C.; Villanueva Perales, A.L.; Vidal-Barrero, F.; Ollero, P.

    2015-01-01

    Highlights: • Assessment of economics and sustainability of thermochemical ethanol production. • Exploitation of excess CO 2 saving by either importing fossil energy or CO 2 trading. • Significant increase in alcohol production by replacing biomass with natural gas. • CO 2 emission trading is not cost-competitive versus import of fossil energy. • Lowest ethanol production cost for partial oxidation as reforming technology. - Abstract: In this work, two options are investigated to enhance the economics of the catalytic production of bioethanol from biomass gasification by exploiting the excess of CO 2 emission saving: (i) to import fossil energy, in the form of natural gas and electricity or (ii) to trade CO 2 emissions. To this end, an integrated life cycle and economic assessment is carried out for four process configurations, each using a different light hydrocarbon reforming technology: partial oxidation, steam methane reforming, tar reforming and autothermal reforming. The results show that for all process configurations the production of bioethanol and other alcohols significantly increases when natural gas displaces biomass, maintaining the total energy content of the feedstock. The economic advantage of the partial substitution of biomass by natural gas depends on their prices and this is explored by carrying out a sensitivity analysis, taking historical prices into account. It is also concluded that the trade of CO 2 emissions is not cost-competitive compared to the import of natural gas if the CO 2 emission price remains within historical European prices. The CO 2 emission price would have to double or even quadruple the highest CO 2 historical price for CO 2 emission trading to be a cost-competitive option

  2. A new mechanism for reduced sensitivity to demethylation-inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis

    NARCIS (Netherlands)

    Díaz-Trujillo, C.; Chong, P.; Stergiopoulos, I.; Meijer, H.J.G.; Wit, de P.J.G.M.; Kema, G.H.J.

    2018-01-01

    The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications with a major share for sterol demethylation-inhibitors

  3. A new mechanism for reduced sensitivity to demethylation-inhibitor fungicides in the fungal banana black Sigatoka pathogen Pseudocercospora fijiensis

    NARCIS (Netherlands)

    Díaz-Trujillo, C.; Chong, P.; Stergiopoulos, I.; Meijer, H.J.G.; Wit, de P.J.G.M.; Kema, G.H.J.

    2017-01-01

    The Dothideomycete Pseudocercospora fijiensis, previously Mycosphaerella fijiensis, is the causal agent of black Sigatoka, one of the most destructive diseases of bananas and plantains. Disease management depends on fungicide applications with a major share for sterol demethylation-inhibitors

  4. The MAO-A inhibitor clorgyline reduces ethanol-induced locomotion and its volitional intake in mice.

    Science.gov (United States)

    Ledesma, Juan Carlos; Escrig, Miguel Angel; Pastor, Raúl; Aragon, Carlos M G

    2014-01-01

    Hydrogen peroxide is the co-substrate used by the enzyme catalase to form Compound I (the catalase-H2O2 system), which is the major pathway for the conversion of ethanol (EtOH) into acetaldehyde in the brain. This acetaldehyde has been involved in many of the effects of EtOH. Previous research demonstrated that treatments that change the levels of cerebral H2O2 available to catalase modulate the locomotor-stimulating effects of EtOH and its volitional intake in rodents. However, the source of H2O2 which is used by catalase to form Compound I and mediates the psychoactive actions of EtOH is unknown. One cause of the generation of H2O2 in the brain comes from the deamination of biogenic amines by the activity of MAO-A. Here we explore the consequences of the administration of the MAO-A inhibitor clorgyline on EtOH-induced locomotion and voluntary EtOH drinking. For the locomotor activity tests, we injected Swiss (RjOrl) mice intraperitoneally (IP) with clorgyline (0-10mg/kg) and later (0.5-8h) with EtOH (0-3.75 g/kg; IP). Following these treatments, mice were placed in locomotor activity chambers to measure their locomotion. For the drinking experiments, mice of the C57BL/6J strain were injected IP with clorgyline prior to offering them an EtOH (20%) solution following a drinking-in-the-dark procedure. Additional experiments were performed to assess the selectivity of this compound in altering EtOH-stimulated locomotion and EtOH intake. Moreover, we indirectly tested the ability of clorgyline to reduce brain H2O2 levels. We showed that this treatment selectively reduced EtOH-induced locomotion and its self-administration. Moreover, this compound decreased central H2O2 levels available to catalase. We suggest that H2O2 derived from the deamination of biogenic amines by the activity of MAO-A could determine the formation of brain EtOH-derived acetaldehyde. This centrally-formed acetaldehyde within the neurons of the aminergic system could play a role in the

  5. Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.

    Science.gov (United States)

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Smalley, Walter E; Daugherty, James R; Dupont, William D; Stein, C Michael

    2016-12-01

    Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the

  6. EPA and California Air Resources Board Approve Remedy to Reduce Excess NOx Emissions from Automatic Transmission “Generation 2” 2.0-Liter Diesel Vehicles

    Science.gov (United States)

    On May 17, 2017, EPA and the California Air Resources Board (CARB) approved an emissions modification proposed by Volkswagen that will reduce NOx emissions from automatic transmission diesel Passats for model years 2012-2014.

  7. TNF-α inhibitors reduce the pathological Th1 -Th17 /Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients.

    Science.gov (United States)

    Campanati, Anna; Orciani, Monia; Lazzarini, Raffaella; Ganzetti, Giulia; Consales, Veronica; Sorgentoni, Giulia; Di Primio, Roberto; Offidani, Annamaria

    2017-04-01

    Psoriasis is a disease characterized by an imbalance between Th 1 and Th 17 and Th 2 inflammatory axes, in which cutaneous mesenchymal stem cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th 1 and Th 17 cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis; however, their effects on MSCs derived from patients with psoriasis have been only partially described. The aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of patients with psoriasis. Resident MSCs from skin of patients with psoriasis and healthy subjects have been isolated, characterized and profiled by PCR and ELISA for the expression of 22 cytokines involved in Th 1 , Th 2 and Th 17 pathways, both before and after 12 weeks therapy with TNF-α inhibitors. The administration of TNF-α inhibitors for 12-weeks acts on MSCs as follows: it reduces the expression of several Th 1 -Th 17 cytokines whose levels are elevated at baseline (IL-6, IL-8, IL-12, IL-23A, IFN-γ, TNF-α, CCL2, CCL20, CXCL2, CXCL5, IL-17A, IL-17C, IL-17F, IL-21, G-CSF). Similarly, it enhances the expression of several Th 2 cytokines which are underexpressed at baseline (IL-2, IL-4, IL-5), reducing the expression of those overexpressed at baseline (TGF-β and IL-13). TNF-α inhibitors could contribute to reduce the pathological imbalance between the Th 1 -Th 17 vs Th 2 axis in MSCs of patients with psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. A COX-2 inhibitor reduces muscle soreness, but does not influence recovery and adaptation after eccentric exercise

    DEFF Research Database (Denmark)

    Paulsen, G; Egner, I M; Drange, M

    2010-01-01

    The aim of this study was to investigate the effect of a cyclooxygenase (COX)-2 inhibitor on the recovery of muscle function, inflammation, regeneration after, and adaptation to, unaccustomed eccentric exercise. Thirty-three young males and females participated in a double-blind, placebo-controll......The aim of this study was to investigate the effect of a cyclooxygenase (COX)-2 inhibitor on the recovery of muscle function, inflammation, regeneration after, and adaptation to, unaccustomed eccentric exercise. Thirty-three young males and females participated in a double-blind, placebo...

  9. Metastasis is strongly reduced by the matrix metalloproteinase inhibitor Galardin in the MMTV-PymT transgenic breast cancer model

    DEFF Research Database (Denmark)

    Almholt, Kasper; Juncker-Jensen, Anna; Lærum, Ole Didrik

    2008-01-01

    Matrix metalloproteinases (MMP) have several roles that influence cancer progression and dissemination. However, low molecular weight metalloproteinase inhibitors (MPI) have not yet been tested in transgenic/spontaneous metastasis models. We have tested Galardin/GM6001, a potent MPI that reacts w...

  10. Tranexamic acid, an inhibitor of plasminogen activation, reduces urinary collagen cross-link excretion in both experimental and rheumatoid arthritis

    NARCIS (Netherlands)

    Ronday, H.K.; TeKoppele, J.M.; Greenwald, R.A.; Moak, S.A.; Roos, J.A.D.M. de; Dijkmans, B.A.C.; Breedveld, F.C.; Verheijen, J.H.

    1998-01-01

    The plasminogen activation system is one of the enzyme systems held responsible for bone and cartilage degradation in rheumatoid arthritis (RA). In this study, we evaluated the effect of tranexamic acid (TEA), an inhibitor of plasminogen activation, on urinary collagen cross-link excretion and

  11. Restoring conjunctival tolerance by topical nuclear factor-κB inhibitors reduces preservative-facilitated allergic conjunctivitis in mice.

    Science.gov (United States)

    Guzmán, Mauricio; Sabbione, Florencia; Gabelloni, María Laura; Vanzulli, Silvia; Trevani, Analía Silvina; Giordano, Mirta Nilda; Galletti, Jeremías Gastón

    2014-09-04

    To evaluate the role of nuclear factor-κB (NF-κB) activation in eye drop preservative toxicity and the effect of topical NF-κB inhibitors on preservative-facilitated allergic conjunctivitis. Balb/c mice were instilled ovalbumin (OVA) combined with benzalkonium chloride (BAK) and/or NF-κB inhibitors in both eyes. After immunization, T-cell responses and antigen-induced ocular inflammation were evaluated. Nuclear factor-κB activation and associated inflammatory changes also were assessed in murine eyes and in an epithelial cell line after BAK exposure. Benzalkonium chloride promoted allergic inflammation and leukocyte infiltration of the conjunctiva. Topical NF-κB inhibitors blocked the disruptive effect of BAK on conjunctival immunological tolerance and ameliorated subsequent ocular allergic reactions. In line with these findings, BAK induced NF-κB activation and the secretion of IL-6 and granulocyte-monocyte colony-stimulating factor in an epithelial cell line and in the conjunctiva of instilled mice. In addition, BAK favored major histocompatibility complex (MHC) II expression in cultured epithelial cells in an NF-κB-dependent fashion after interaction with T cells. Benzalkonium chloride triggers conjunctival epithelial NF-κB activation, which seems to mediate some of its immune side effects, such as proinflammatory cytokine release and increased MHC II expression. Breakdown of conjunctival tolerance by BAK favors allergic inflammation, and this effect can be prevented in mice by topical NF-κB inhibitors. These results suggest a new pharmacological target for preservative toxicity and highlight the importance of conjunctival tolerance in ocular surface homeostasis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  12. Supplementation with a new trypsin inhibitor from peanut is associated with reduced fasting glucose, weight control, and increased plasma CCK secretion in an animal model.

    Science.gov (United States)

    Serquiz, Alexandre C; Machado, Richele J A; Serquiz, Raphael P; Lima, Vanessa C O; de Carvalho, Fabiana Maria C; Carneiro, Marcella A A; Maciel, Bruna L L; Uchôa, Adriana F; Santos, Elizeu A; Morais, Ana H A

    2016-12-01

    Ingestion of peanuts may have a beneficial effect on weight control, possibly due to the satietogenic action of trypsin inhibitors. The aim of this study was to isolate a new trypsin inhibitor in a typical Brazilian peanut sweet (paçoca) and evaluate its effect in biochemical parameters, weight gain and food intake in male Wistar rats. The trypsin inhibitor in peanut paçoca (AHTI) was isolated. Experimental diets were prepared with AIN-93G supplemented with AHTI. Animals had their weight and food intake monitored. Animals were anesthetized, euthanized, and their bloods collected by cardiac puncture for dosage of cholecystokinin (CCK) and other biochemical parameters. Supplementation with AHTI significantly decreased fasting glucose, body weight gain, and food intake. These effects may be attributed to increased satiety, once supplemented animals showed no evidence of impaired nutritional status and also because AHTI increased CCK production. Thus, our results indicate that AHTI, besides reducing fasting glucose, can reduce weight gain via food intake reduction.

  13. Contemporary protease inhibitors and cardiovascular risk

    DEFF Research Database (Denmark)

    Lundgren, Jens; Mocroft, Amanda; Ryom, Lene

    2018-01-01

    PURPOSE OF REVIEW: To review the evidence linking use of HIV protease inhibitors with excess risk of cardiovascular disease (CVD) in HIV+ populations. RECENT FINDINGS: For the two contemporary most frequently used protease inhibitors, darunavir and atazanavir [both pharmacologically boosted...

  14. PE859, a novel tau aggregation inhibitor, reduces aggregated tau and prevents onset and progression of neural dysfunction in vivo.

    Directory of Open Access Journals (Sweden)

    Michiaki Okuda

    Full Text Available In tauopathies, a neural microtubule-associated protein tau (MAPT is abnormally aggregated and forms neurofibrillary tangle. Therefore, inhibition of the tau aggregation is one of the key approaches for the treatment of these diseases. Here, we have identified a novel tau aggregation inhibitor, PE859. An oral administration of PE859 resulted in the significant reduction of sarkosyl-insoluble aggregated tau along with the prevention of onset and progression of the motor dysfunction in JNPL3 P301L-mutated human tau transgenic mice. These results suggest that PE859 is useful for the treatment of tauopathies.

  15. Plasma NGAL and glomerular filtration rate in cardiac transplant recipients treated with standard or reduced calcineurin inhibitor levels

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Gude, Einar; Sigurdardottir, Vilborg

    2014-01-01

    GFR) at baseline (R(2) = 0.21; p year (median [25-75 % percentiles]: ΔmGFR 5.5 [-0.5-11.5] vs -1 [-7-4] ml/min/1.73 m(2); p = 0.006). Baseline P-NGAL predicted mGFR after 1 year (R(2) = 0.18; p ...: P-NGAL was measured in 88 cardiac transplantation patients (median 5 years post-transplant) with renal dysfunction randomized to continuation of conventional calcineurin inhibitor-based immunosuppression or switching to an everolimus-based regimen. RESULTS: P-NGAL correlated with measured GFR (m...

  16. Excessive Daytime Sleepiness

    Directory of Open Access Journals (Sweden)

    Yavuz Selvi

    2016-06-01

    Full Text Available Excessive daytime sleepiness is one of the most common sleep-related patient symptoms, with preva-lence in the community estimated to be as high as 18%. Patients with excessive daytime sleepiness may exhibit life threatening road and work accidents, social maladjustment, decreased academic and occupational performance and have poorer health than comparable adults. Thus, excessive daytime sleepiness is a serious condition that requires investigation, diagnosis and treatment primarily. As with most medical condition, evaluation of excessive daytime sleepiness begins a precise history and various objective and subjective tools have been also developed to assess excessive daytime sleepiness. The most common causes of excessive daytime sleepiness are insufficient sleep hygiene, chronic sleep deprivation, medical and psychiatric conditions and sleep disorders, such as obstructive sleep apnea, medications, and narcolepsy. Treatment option should address underlying contributors and promote sleep quantity by ensuring good sleep hygiene. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 114-132

  17. A Trypsin Inhibitor from Tamarind Reduces Food Intake and Improves Inflammatory Status in Rats with Metabolic Syndrome Regardless of Weight Loss

    Directory of Open Access Journals (Sweden)

    Fabiana M. C. Carvalho

    2016-09-01

    Full Text Available Trypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS. Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1 Cafeteria diet; (2 Cafeteria diet + TTI (25 mg/kg; and (3 Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL and triglycerides (TG (Kruskal–Wallis, p < 0.05. Interleukin-6 (IL-6 production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatment.

  18. Lignin Sulfonation and SO2 Addition Enhance the Hydrolyzability of Deacetylated and Then Steam-Pretreated Poplar with Reduced Inhibitor Formation.

    Science.gov (United States)

    Tang, Yong; Dou, Xiaoli; Hu, Jinguang; Jiang, Jianxin; Saddler, Jack N

    2018-01-01

    The merit of deacetylation of corn stover prior to pretreatment is decreasing the formation of inhibitors and improving enzyme hydrolysis, proved in dilute acid pretreatment. However, few studies are done on how deacetylation would affect bioconversion process containing steam explosion. In this study, the effect of deacetylation on steam explosion was conducted using poplar as substrate. About 57 to 90% of acetyl group in poplar, depending on alkaline types and concentration, was removed by dilute alkaline deacetylation in 6 h. Deacetylation eliminated over 85% of inhibitor formation during downstream steam explosion. However, deacetylation prior to steam explosion decreased the dissolution of hemicellulose, thus reducing the cellulose accessibility of pretreated poplar, finally resulting in 5-20% decrease in glucose yield and 20-35% decrease in xylose yield. The addition of 5% SO 2 during steam explosion significantly improved the hydrolysis of deacetylated and pretreated poplar without significantly increasing the concentration of inhibitors. Incorporating 45 mmol/kg sulfoacid group in lignin fraction of deacetylated and then pretreated poplar dramatically improved the xylose yield to about 100% and increased the glucose yield by 30%.

  19. The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in rats with ligated femoral arteries.

    Science.gov (United States)

    Copp, Steven W; Kim, Joyce S; Ruiz-Velasco, Victor; Kaufman, Marc P

    2016-05-01

    Mechanical and metabolic stimuli arising from contracting muscles evoke the exercise pressor reflex. This reflex is greater in a rat model of simulated peripheral arterial disease in which a femoral artery is chronically ligated than it is in rats with freely perfused femoral arteries. The role played by the mechanically sensitive component of the exaggerated exercise pressor reflex in ligated rats is unknown. We tested the hypothesis that the mechano-gated channel inhibitor GsMTx4, a relatively selective inhibitor of mechano-gated Piezo channels, reduces the exercise pressor reflex in decerebrate rats with ligated femoral arteries. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the pressor response to Achilles tendon stretch (a purely mechanical stimulus) but had no effect on the pressor responses to intra-arterial injection of α,β-methylene ATP or lactic acid (purely metabolic stimuli). Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced both the integrated pressor area (control 535 ± 21, GsMTx4 218 ± 24 mmHg·s; P reflex contributes to the exaggerated exercise pressor reflex during intermittent hindlimb muscle contractions in rats with ligated femoral arteries. Copyright © 2016 the American Physiological Society.

  20. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    International Nuclear Information System (INIS)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn; Tajima, Shigeru; Hikono, Hirokazu; Saito, Takehiko; Aida, Yoko

    2014-01-01

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC 50 values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets

  1. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Tajima, Shigeru [Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640 (Japan); Hikono, Hirokazu; Saito, Takehiko [Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2014-07-18

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

  2. Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple myeloma cell proliferation and adhesion and suppresses osteoclast formation

    International Nuclear Information System (INIS)

    Nguyen, Aaron N.; Stebbins, Elizabeth G.; Henson, Margaret; O'Young, Gilbert; Choi, Sun J.; Quon, Diana; Damm, Debby; Reddy, Mamatha; Ma, Jing Y.; Haghnazari, Edwin; Kapoun, Ann M.; Medicherla, Satyanarayana; Protter, Andy; Schreiner, George F.; Kurihara, Noriyoshi; Anderson, Judy; Roodman, G. David; Navas, Tony A.; Higgins, Linda S.

    2006-01-01

    The multiple myeloma (MM) bone marrow (BM) microenvironment plays a critical role in supporting tumor growth and survival as well as in promoting formation of osteolytic lesions. Recent results suggest that the p38 mitogen-activated protein kinase (MAPK) is an important factor in maintaining this activated environment. In this report, we demonstrate that the p38α MAPK inhibitor, SCIO-469, suppresses secretion of the tumor-supportive factors IL-6 and VEGF from BM stromal cells (BMSCs) as well as cocultures of BMSCs with MM cells, resulting in reduction in MM cell proliferation. Additionally, we show that SCIO-469 prevents TNFα-induced adhesion of MM cells to BMSCs through an ICAM-1- and VCAM-1-independent mechanism. Microarray analysis revealed a novel set of TNFα-induced chemokines in BMSCs that is strongly inhibited by SCIO-469. Furthermore, reintroduction of chemokines CXCL10 and CCL8 to BMSCs overcomes the inhibitory effect of SCIO-469 on TNFα-induced MM adhesion. Lastly, we show that SCIO-469 inhibits secretion and expression of the osteoclast-activating factors IL-11, RANKL, and MIP-1α as well as prevents human osteoclast formation in vitro. Collectively, these results suggest that SCIO-469 treatment can suppress factors in the bone marrow microenvironment to inhibit MM cell proliferation and adhesion and also to alleviate osteolytic activation in MM

  3. Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.

    Science.gov (United States)

    List, James F; Whaley, Jean M

    2011-03-01

    Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.

  4. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  5. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  6. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer

  7. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension.

    Science.gov (United States)

    Kuan, Yi-Chun; Huang, Kuang-Wei; Yen, Der-Jen; Hu, Chaur-Jong; Lin, Cheng-Li; Kao, Chia-Hung

    2016-10-01

    The effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) on dementia risk in patients with type 2 diabetes mellitus (DM) and hypertension remain unknown. We investigated the effects of ACEIs and ARBs on dementia risk in patients with type 2 DM and hypertension. We conducted a cohort study by using the Taiwan National Health Insurance Research Database. We included 2377 patients receiving ACEIs and 1780 patients receiving ARBs in the ACEI and ARB cohorts, respectively. We included a comparable number of patients not receiving ACEIs and ARBs as controls in the non-ACEI and non-ARB cohorts through propensity score matching. The effect of ACEIs and ARBs on dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. During the 12-year follow-up period, compared with the non-ACEI cohort, all-cause dementia risk decreased by 26% in the ACEI cohort [hazard ratio (HR)=0.74, 95% confidence interval (CI)=0.56-0.96]. The all-cause dementia risk was nearly 40% lower in the ARB cohort than in the non-ARB cohort (HR=0.60, 95% CI=0.37-0.97). These drugs prevented the occurrence of vascular dementia (VD), however, this effect was nonsignificant for Alzheimer's dementia (AD). Treatment duration- and dosage-related protection effects on dementia occurrence were observed. ACEIs and ARBs may effectively prevent all-cause dementia, particularly VD, in patients with type 2 DM and hypertension. Moreover, compared with ACEIs, ARBs appear to be more advantageous in dementia prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Systemic delivery of a glucosylceramide synthase inhibitor reduces CNS substrates and increases lifespan in a mouse model of type 2 Gaucher disease.

    Directory of Open Access Journals (Sweden)

    Mario A Cabrera-Salazar

    Full Text Available Neuropathic Gaucher disease (nGD, also known as type 2 or type 3 Gaucher disease, is caused by a deficiency of the enzyme glucocerebrosidase (GC. This deficiency impairs the degradation of glucosylceramide (GluCer and glucosylsphingosine (GluSph, leading to their accumulation in the brains of patients and mouse models of the disease. These accumulated substrates have been thought to cause the severe neuropathology and early death observed in patients with nGD and mouse models. Substrate accumulation is evident at birth in both nGD mouse models and humans affected with the most severe type of the disease. Current treatment of non-nGD relies on the intravenous delivery of recombinant human glucocerebrosidase to replace the missing enzyme or the administration of glucosylceramide synthase inhibitors to attenuate GluCer production. However, the currently approved drugs that use these mechanisms do not cross the blood brain barrier, and thus are not expected to provide a benefit for the neurological complications in nGD patients. Here we report the successful reduction of substrate accumulation and CNS pathology together with a significant increase in lifespan after systemic administration of a novel glucosylceramide synthase inhibitor to a mouse model of nGD. To our knowledge this is the first compound shown to cross the blood brain barrier and reduce substrates in this animal model while significantly enhancing its lifespan. These results reinforce the concept that systemically administered glucosylceramide synthase inhibitors could hold enhanced therapeutic promise for patients afflicted with neuropathic lysosomal storage diseases.

  9. Systemic delivery of a glucosylceramide synthase inhibitor reduces CNS substrates and increases lifespan in a mouse model of type 2 Gaucher disease.

    Science.gov (United States)

    Cabrera-Salazar, Mario A; Deriso, Matthew; Bercury, Scott D; Li, Lingyun; Lydon, John T; Weber, William; Pande, Nilesh; Cromwell, Mandy A; Copeland, Diane; Leonard, John; Cheng, Seng H; Scheule, Ronald K

    2012-01-01

    Neuropathic Gaucher disease (nGD), also known as type 2 or type 3 Gaucher disease, is caused by a deficiency of the enzyme glucocerebrosidase (GC). This deficiency impairs the degradation of glucosylceramide (GluCer) and glucosylsphingosine (GluSph), leading to their accumulation in the brains of patients and mouse models of the disease. These accumulated substrates have been thought to cause the severe neuropathology and early death observed in patients with nGD and mouse models. Substrate accumulation is evident at birth in both nGD mouse models and humans affected with the most severe type of the disease. Current treatment of non-nGD relies on the intravenous delivery of recombinant human glucocerebrosidase to replace the missing enzyme or the administration of glucosylceramide synthase inhibitors to attenuate GluCer production. However, the currently approved drugs that use these mechanisms do not cross the blood brain barrier, and thus are not expected to provide a benefit for the neurological complications in nGD patients. Here we report the successful reduction of substrate accumulation and CNS pathology together with a significant increase in lifespan after systemic administration of a novel glucosylceramide synthase inhibitor to a mouse model of nGD. To our knowledge this is the first compound shown to cross the blood brain barrier and reduce substrates in this animal model while significantly enhancing its lifespan. These results reinforce the concept that systemically administered glucosylceramide synthase inhibitors could hold enhanced therapeutic promise for patients afflicted with neuropathic lysosomal storage diseases.

  10. Reduced systemic toxicity and preserved vestibular toxicity following co-treatment with nitriles and CYP2E1 inhibitors: a mouse model for hair cell loss.

    Science.gov (United States)

    Saldaña-Ruíz, Sandra; Boadas-Vaello, Pere; Sedó-Cabezón, Lara; Llorens, Jordi

    2013-10-01

    Several nitriles, including allylnitrile and cis-crotononitrile, have been shown to be ototoxic and cause hair cell degeneration in the auditory and vestibular sensory epithelia of mice. However, these nitriles can also be lethal due in large part to the microsomal metabolic release of cyanide, which is mostly dependent on the activity of the 2E1 isoform of the cytochrome P450 (CYP2E1). In this study, we co-administered mice with a nitrile and, to reduce their lethal effects, a selective CYP2E1 inhibitor: diallylsulfide (DAS) or trans-1,2-dichloroethylene (TDCE). Both in female 129S1/SvImJ (129S1) mice co-treated with DAS and cis-crotononitrile and in male RjOrl:Swiss/CD-1 (Swiss) mice co-treated with TDCE and allylnitrile, the nitrile caused a dose-dependent loss of vestibular function, as assessed by a specific behavioral test battery, and of hair cells, as assessed by hair bundle counts using scanning electron microscopy. In the experiments, the CYP2E1 inhibitors provided significant protection against the lethal effects of the nitriles and did not diminish the vestibular toxicity as assessed by behavioral effects in comparison to animals receiving no inhibitor. Additional experiments using a single dose of allylnitrile demonstrated that TDCE does not cause hair cell loss on its own and does not modify the vestibular toxicity of the nitrile in either male or female 129S1 mice. In all the experiments, high vestibular dysfunction scores in the behavioral test battery predicted extensive to complete loss of hair cells in the utricles. This provides a means of selecting animals for subsequent studies of vestibular hair cell regeneration or replacement.

  11. Hyperhidrosis (Excessive Sweating)

    Science.gov (United States)

    ... who have this type are otherwise healthy. In medical terminology, the word “primary” means that the cause is not another medical condition. Secondary hyperhidrosis In medical terminology, “secondary” means that the excessive sweating (hyperhidrosis) has ...

  12. Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial

    DEFF Research Database (Denmark)

    Gullestad, Lars; Mortensen, Svend-Aage; Eiskjær, Hans

    2010-01-01

    Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required....

  13. Brown Recluse spider bite mediated hemolysis: clinical features, a possible role for complement inhibitor therapy, and reduced RBC surface glycophorin A as a potential biomarker of venom exposure.

    Directory of Open Access Journals (Sweden)

    Eric A Gehrie

    Full Text Available The venom of Loxosceles reclusa (Brown Recluse spider can cause a severe, life-threatening hemolysis in humans for which no therapy is currently available in the USA beyond supportive measures. Because this hemolysis is uncommon, relatively little is known about its clinical manifestation, diagnosis, or management. Here, we aimed to clarify the clinical details of envenomation, to determine the efficacy of the complement inhibitor eculizumab to prevent the hemolysis in vitro, and to investigate markers of exposure to Brown Recluse venom.We performed a 10-year chart review of cases of Brown Recluse spider bite-mediated hemolysis at our institution. We also designed an in vitro assay to test the efficacy of eculizumab to inhibit hemolysis of venom exposed red blood cells. Finally, we compared levels of CD55, CD59 and glycophorin A on venom exposed versus venom-naïve cells.Most victims of severe Brown Recluse spider mediated hemolysis at our institution are children and follow an unpredictable clinical course. Brown Recluse spider bite mediated hemolysis is reduced by 79.2% (SD=18.8% by eculizumab in vitro. Erythrocyte glycophorin A, but not CD55 or CD59, is reduced after red blood cells are incubated with venom in vitro.Taken together, our laboratory data and clinical observations indicate that L. reclusa venom exposure results in non-specific antibody and complement fixation on red blood cells, resulting in complement mediated hemolysis that is curtailed by the complement inhibitor eculizumab in vitro. Glycophorin A measurement by flow cytometry may help to identify victims of L. reclusa envenomation.

  14. Excess Early Mortality in Schizophrenia

    DEFF Research Database (Denmark)

    Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo

    2014-01-01

    Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality...... as well as possible ways to reduce it. Persons with schizophrenia have an exceptionally short life expectancy. High mortality is found in all age groups, resulting in a life expectancy of approximately 20 years below that of the general population. Evidence suggests that persons with schizophrenia may...... not have seen the same improvement in life expectancy as the general population during the past decades. Thus, the mortality gap not only persists but may actually have increased. The most urgent research agenda concerns primary candidates for modifiable risk factors contributing to this excess mortality...

  15. Quorum sensing signals are produced by Aeromonas salmonicida and quorum sensing inhibitors can reduce production of a potential virulence factor

    DEFF Research Database (Denmark)

    Rasch, Maria; Kastbjerg, Vicky Gaedt; Bruhn, Jesper Bartholin

    2007-01-01

    Many pathogens control production of virulence factors by self-produced signals in a process called quorum sensing (QS). We demonstrate that acyl homoserine lactone (AHL) signals, which enable bacteria to express certain phenotypes in relation to cell density, are produced by a wide spectrum...... of Aeromonas salmonicida strains. All 31 typical strains were AHL producers as were 21 of 26 atypical strains, but on a strain population basis, production of virulence factors such as protease, lipase, A-layer or pigment did not correlate with the production and accumulation of AHLs in the growth medium...... of Aeromonas salmonicida. The most efficient compound N-(heptylsulfanylacetyl)-L-homoserine lactone (HepS-AHL), reduced protease production by a factor of 10. Five extracellular proteases were detected on gelatin-containing sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels and 3...

  16. Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines

    International Nuclear Information System (INIS)

    Mokhtari, Reza Bayat; Kumar, Sushil; Islam, Syed S; Yazdanpanah, Mehrdad; Adeli, Khosrow; Cutz, Ernest; Yeger, Herman

    2013-01-01

    Bronchial carcinoids are pulmonary neuroendocrine cell-derived tumors comprising typical (TC) and atypical (AC) malignant phenotypes. The 5-year survival rate in metastatic carcinoid, despite multiple current therapies, is 14-25%. Hence, we are testing novel therapies that can affect the proliferation and survival of bronchial carcinoids. In vitro studies were used for the dose–response (AlamarBlue) effects of acetazolamide (AZ) and sulforaphane (SFN) on clonogenicity, serotonin-induced growth effect and serotonin content (LC-MS) on H-727 (TC) and H-720 (AC) bronchial carcinoid cell lines and their derived NOD/SCID mice subcutaneous xenografts. Tumor ultra structure was studied by electron microscopy. Invasive fraction of the tumors was determined by matrigel invasion assay. Immunohistochemistry was conducted to study the effect of treatment(s) on proliferation (Ki67, phospho histone-H3) and neuroendocrine phenotype (chromogranin-A, tryptophan hydroxylase). Both compounds significantly reduced cell viability and colony formation in a dose-dependent manner (0–80 μM, 48 hours and 7 days) in H-727 and H-720 cell lines. Treatment of H-727 and H-720 subcutaneous xenografts in NOD/SCID mice with the combination of AZ + SFN for two weeks demonstrated highly significant growth inhibition and reduction of 5-HT content and reduced the invasive capacity of H-727 tumor cells. In terms of the tumor ultra structure, a marked reduction in secretory vesicles correlated with the decrease in 5-HT content. The combination of AZ and SFN was more effective than either single agent. Since the effective doses are well within clinical range and bioavailability, our results suggest a potential new therapeutic strategy for the treatment of bronchial carcinoids

  17. Chickens treated with a nitric oxide inhibitor became more resistant to Plasmodium gallinaceum infection due to reduced anemia, thrombocytopenia and inflammation

    Science.gov (United States)

    2013-01-01

    Malaria is a serious infectious disease caused by parasites of the Plasmodium genus that affect different vertebrate hosts. Severe malaria leads to host death and involves different pathophysiological phenomena such as anemia, thrombocytopenia and inflammation. Nitric oxide (NO) is an important effector molecule in this disease, but little is known about its role in avian malaria models. Plasmodium gallinaceum- infected chickens were treated with aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase, to observe the role of NO in the pathogenesis of this avian model. AG increased the survival of chickens, but also induced higher parasitemia. Treated chickens demonstrated reduced anemia and thrombocytopenia. Moreover, erythrocytes at different stages of maturation, heterophils, monocytes and thrombocytes were infected by Plasmodium gallinaceum and animals presented a generalized leucopenia. Activated leukocytes and thrombocytes with elongated double nuclei were observed in chickens with higher parasitemia; however, eosinophils were not involved in the infection. AG reduced levels of hemozoin in the spleen and liver, indicating lower inflammation. Taken together, the results suggest that AG reduced anemia, thrombocytopenia and inflammation, explaining the greater survival rate of the treated chickens. PMID:23398940

  18. Glad you brought it up: a patient-centred programme to reduce proton-pump inhibitor prescribing in general medical practice.

    Science.gov (United States)

    Murie, Jill; Allen, Jane; Simmonds, Ray; de Wet, Carl

    2012-01-01

    Many patients unnecessarily receive proton-pump inhibitor (PPI) drugs long term with significant financial and safety implications. Educating, empowering and supporting patients to self-manage their symptoms can lead to significant and sustained reductions in PPI prescribing. We aimed to implement a programme to reduce inappropriate PPI prescribing. Eligible patients in one general medical practice in rural Scotland were invited for participation between November 2008 and February 2010. Patients attended special nurse advisor clinics, completed dyspepsia questionnaires, received information, formulated self-management plans and were offered flexible support. Of the study population, 437/2883 (15%) were prescribed PPIs. Of these, 166 (38%) were judged eligible for participation. After 12 months, 138/157 (83%) had reduced or stopped their PPIs, while 19/157 (11%) had reverted. The estimated annual net saving in the prescribing budget was ?3180.67. Self-reported understanding of symptom self-management increased from 6/20 (30%) to 18/20 (90%) patients after participation in the programme. A patient-centred programme delivered by a specialist nurse significantly reduced PPI prescribing with financial and potential therapeutic benefits. The vast majority of eligible patients were able to 'step down and off' or 'step off' PPI use after 12 months without any complications or deteriorating symptom control. Further research with larger cohorts of practices and patients is needed to develop a feasible, acceptable and effective programme if similar benefits are to be achieved for primary care in general.

  19. Superconductors with excess quasiparticles

    International Nuclear Information System (INIS)

    Elesin, V.F.; Kopaev, Y.V.

    1981-01-01

    This review presents a systematic kinetic theory of nonequilibrium phenomena in superconductors with excess quasiparticles created by electromagnetic or tunnel injection. The energy distributions of excess quasiparticles and of nonequilibrium phonons, dependence of the order parameter on the power and frequency (or intensity) of the electromagnetic field, magnetic properties of nonequilibrium superconductors, I-V curves of superconductor-insulator-superconductor junctions, and other properties are described in detail. The stability of superconducting states far from thermodynamic equilibrium is investigated and it is shown that characteristic instabilities leading to the formation of nonuniform states of a new type or phase transitions of the first kind are inherent to superconductors with excess quasiparticles. The results are compared with experimental data

  20. Excess wind power

    DEFF Research Database (Denmark)

    Østergaard, Poul Alberg

    2005-01-01

    Expansion of wind power is an important element in Danish climate change abatement policy. Starting from a high penetration of approx 20% however, momentary excess production will become an important issue in the future. Through energy systems analyses using the EnergyPLAN model and economic...... analyses it is analysed how excess productions are better utilised; through conversion into hydrogen of through expansion of export connections thereby enabling sales. The results demonstrate that particularly hydrogen production is unviable under current costs but transmission expansion could...

  1. A randomized, comparative pilot trial of family-based interpersonal psychotherapy for reducing psychosocial symptoms, disordered-eating, and excess weight gain in at-risk preadolescents with loss-of-control-eating.

    Science.gov (United States)

    Shomaker, Lauren B; Tanofsky-Kraff, Marian; Matherne, Camden E; Mehari, Rim D; Olsen, Cara H; Marwitz, Shannon E; Bakalar, Jennifer L; Ranzenhofer, Lisa M; Kelly, Nichole R; Schvey, Natasha A; Burke, Natasha L; Cassidy, Omni; Brady, Sheila M; Dietz, Laura J; Wilfley, Denise E; Yanovski, Susan Z; Yanovski, Jack A

    2017-09-01

    Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children's psychosocial functioning, LOC-eating, and body mass. A randomized, controlled pilot trial was conducted with 29 children, 8 to 13 years who had overweight/obesity and LOC-eating. Youth-parent dyads were randomized to 12-week FB-IPT (n = 15) or FB-HE (n = 14) and evaluated at post-treatment, six-months, and one-year. Changes in child psychosocial functioning, LOC-eating, BMI, and adiposity by dual-energy-X-ray-absorptiometry were assessed. Missing follow-up data were multiply imputed. FB-IPT feasibility and acceptability were indicated by good attendance (83%) and perceived benefits to social interactions and eating. Follow-up assessments were completed by 73% FB-IPT and 86% FB-HE at post-treatment, 60% and 64% at six-months, and 47% and 57% at one-year. At post-treatment, children in FB-IPT reported greater decreases in depression (95% CI -7.23, -2.01, Cohen's d = 1.23) and anxiety (95% CI -6.08, -0.70, Cohen's d = .79) and less odds of LOC-eating (95% CI -3.93, -0.03, Cohen's d = .38) than FB-HE. At six-months, children in FB-IPT had greater reductions in disordered-eating attitudes (95% CI -0.72, -0.05, Cohen's d = .66) and at one-year, tended to have greater decreases in depressive symptoms (95% CI -8.82, 0.44, Cohen's d = .69) than FB-HE. There was no difference in BMI gain between the groups. Family-based approaches that address interpersonal and emotional underpinnings of LOC-eating in preadolescents with overweight/obesity show preliminary promise, particularly for reducing internalizing symptoms. Whether observed psychological benefits translate into sustained prevention of disordered-eating or excess

  2. A Randomized, Comparative Pilot Trial of Family-Based Interpersonal Psychotherapy for Reducing Psychosocial Symptoms, Disordered-eating, and Excess Weight Gain in At-Risk Preadolescents with Loss-of-control-eating

    Science.gov (United States)

    Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Matherne, Camden E.; Mehari, Rim D.; Olsen, Cara H.; Marwitz, Shannon E.; Bakalar, Jennifer L.; Ranzenhofer, Lisa M.; Kelly, Nichole R.; Schvey, Natasha A.; Burke, Natasha L.; Cassidy, Omni; Brady, Sheila M.; Dietz, Laura J.; Wilfley, Denise E.; Yanovski, Susan Z.; Yanovski, Jack A.

    2018-01-01

    Objective Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children’s psychosocial functioning, LOC-eating, and body mass. Method A randomized, controlled pilot trial was conducted with 29 children, 8 to 13 years who had overweight/obesity and LOC-eating. Youth-parent dyads were randomized to 12-week FB-IPT (n=15) or FB-HE (n=14) and evaluated at post-treatment, six-months, and one-year. Changes in child psychosocial functioning, LOC-eating, BMI, and adiposity by dual-energy-X-ray-absorptiometry were assessed. Missing follow-up data were multiply imputed. Results FB-IPT feasibility and acceptability were indicated by good attendance (83%) and perceived benefits to social interactions and eating. Follow-up assessments were completed by 73% FB-IPT and 86% FB-HE at post-treatment, 60% and 64% at six-months, and 47% and 57% at one-year. At post-treatment, children in FB-IPT reported greater decreases in depression (95% CI −7.23, −2.01, Cohen’s d=1.23) and anxiety (95% CI −6.08, −0.70, Cohen’s d=.79) and less odds of LOC-eating (95% CI −3.93, −0.03, Cohen’s d=.38) than FB-HE. At six-months, children in FB-IPT had greater reductions in disordered-eating attitudes (95% CI −0.72, −0.05, Cohen’s d=.66) and at one-year, tended to have greater decreases in depressive symptoms (95% CI −8.82, 0.44, Cohen’s d=.69) than FB-HE. There was no difference in BMI gain between the groups. Discussion Family-based approaches that address interpersonal and emotional underpinnings of LOC-eating in preadolescents with overweight/obesity show preliminary promise, particularly for reducing internalizing symptoms. Whether observed psychological benefits translate into sustained prevention of

  3. Reduced susceptibility of Enterococcus spp. isolates from Cairo University Hospital to tigecycline: Highlight on the influence of proton pump inhibitors.

    Science.gov (United States)

    Hassan, Reem Mostafa; Ghaith, Doaa Mohammad; Ismail, Dalia Kadry; Zafer, Mai Mahmoud

    2018-03-01

    The incidence of reduced susceptibility to tigecycline (TIG) is increasing. This study aimed to analyse the in vitro activity of TIG against Enterococcus spp. isolates recovered from hospitalised patients and to evaluate the effect of omeprazole on the in vitro antimicrobial activity of TIG against several enterococcal species. A total of 67 Enterococcus clinical isolates were identified by MALDI-TOF/MS and multiplex PCR. Minimum inhibitory concentrations (MICs) of TIG alone and in combination with omeprazole (10, 30 and 60mg/L) were determined by broth microdilution. Antibiotic susceptibility to other antibiotics was determined by disk diffusion. The presence of van, tet(X) and tet(X1) genes was tested by multiplex PCR. Of the 67 Enterococcus isolates, 2 (3.0%) were resistant to TIG and 13 (19.4%) were intermediate-resistant according to EUCAST. The frequencies of resistance to norfloxacin (80.6%), doxycycline (80.6%), levofloxacin (74.6%) and ciprofloxacin (71.6%) were highest, whilst that of vancomycin (25.4%) was lowest. The vanA gene was detected in 11 Enterococcus isolates (8 Enterococcus faecalis, 3 Enterococcus faecium), vanB in 3 Enterococcus isolates (2 E. faecium, 1 E. faecalis) and vanC-2/3 in 3 Enterococcus casseliflavus. Nine isolates (13.4%) were positive for tet(X1). TIG resistance occurred both in patients receiving or not TIG and/or omeprazole. Omeprazole increased TIG MICs by 4-128-fold. The possibility of selection of TIG-non-susceptible Enterococcus in the gut may occur with long-term use of omeprazole. Omeprazole influenced TIG activity in a concentration-dependent manner. To our knowledge; this is the first report of TIG-non-susceptible Enterococcus spp. in Egypt. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  4. Disposition of excess material

    International Nuclear Information System (INIS)

    Hall, J.C.

    1978-01-01

    This paper reviews briefly the means available to an enrichment customer to dispose of excess material scheduled for delivery under a fixed-commitment contract, other than through termination of the related separative work. The methods are as follows: (1) sales; (2) use in facilities covered by other DOE contracts; and (3) assignment

  5. HIV Excess Cancers JNCI

    Science.gov (United States)

    In 2010, an estimated 7,760 new cancers were diagnosed among the nearly 900,000 Americans known to be living with HIV infection. According to the first comprehensive study in the United States, approximately half of these cancers were in excess of what wo

  6. The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib

    OpenAIRE

    Booth, Laurence; Roberts, Jane L.; Poklepovic, Andrew; Kirkwood, John; Sander, Cindy; Avogadri-Connors, Francesca; Cutler Jr, Richard E.; Lalani, Alshad S.; Dent, Paul

    2017-01-01

    ABSTRACT The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFR...

  7. Aromatase inhibitors in pediatrics.

    Science.gov (United States)

    Wit, Jan M; Hero, Matti; Nunez, Susan B

    2011-10-25

    Aromatase, an enzyme located in the endoplasmic reticulum of estrogen-producing cells, catalyzes the rate-limiting step in the conversion of androgens to estrogens in many tissues. The clinical features of patients with defects in CYP19A1, the gene encoding aromatase, have revealed a major role for this enzyme in epiphyseal plate closure, which has promoted interest in the use of inhibitors of aromatase to improve adult height. The availability of the selective aromatase inhibitors letrozole and anastrozole--currently approved as adjuvant therapy for breast cancer--have stimulated off-label use of aromatase inhibitors in pediatrics for the following conditions: hyperestrogenism, such as aromatase excess syndrome, Peutz-Jeghers syndrome, McCune-Albright syndrome and functional follicular ovarian cysts; hyperandrogenism, for example, testotoxicosis (also known as familial male-limited precocious puberty) and congenital adrenal hyperplasia; pubertal gynecomastia; and short stature and/or pubertal delay in boys. Current data suggest that aromatase inhibitors are probably effective in the treatment of patients with aromatase excess syndrome or testotoxicosis, partially effective in Peutz-Jeghers and McCune-Albright syndrome, but probably ineffective in gynecomastia. Insufficient data are available in patients with congenital adrenal hyperplasia or functional ovarian cysts. Although aromatase inhibitors appear effective in increasing adult height of boys with short stature and/or pubertal delay, safety concerns, including vertebral deformities, a decrease in serum HDL cholesterol levels and increase of erythrocytosis, are reasons for caution.

  8. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: an ecological study.

    Science.gov (United States)

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2012-01-01

    The influenza A (H1N1) pandemic swept across the globe from April 2009 to August 2010 affecting millions. Many WHO Member States relied on antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Such drugs have been found to be effective in reducing severity and duration of influenza illness, and likely reduced morbidity during the pandemic. However, it is less clear whether NAIs used during the pandemic reduced H1N1 mortality. Country-level data on supply of oseltamivir and zanamivir were used to predict H1N1 mortality (per 100,000 people) from July 2009 to August 2010 in forty-two WHO Member States. Poisson regression was used to model the association between NAI supply and H1N1 mortality, with adjustment for economic, demographic, and health-related confounders. After adjustment for potential confounders, each 10% increase in kilograms of oseltamivir, per 100,000 people, was associated with a 1.6% reduction in H1N1 mortality over the pandemic period (relative rate (RR) = 0.84 per log increase in oseltamivir supply). While the supply of zanamivir was considerably less than that of oseltamivir in each Member State, each 10% increase in kilogram of active zanamivir, per 100,000, was associated with a 0.3% reduction in H1N1 mortality (RR = 0.97 per log increase). While there are limitations to the ecologic nature of these data, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics.

  9. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice

    Science.gov (United States)

    Gerasimova, Maria; Rose, Michael A.; Masuda, Takahiro; Satriano, Joseph; Mayoux, Eric; Koepsell, Hermann; Thomson, Scott C.; Rieg, Timo

    2013-01-01

    Our previous work has shown that gene knockout of the sodium-glucose cotransporter SGLT2 modestly lowered blood glucose in streptozotocin-diabetic mice (BG; from 470 to 300 mg/dl) and prevented glomerular hyperfiltration but did not attenuate albuminuria or renal growth and inflammation. Here we determined effects of the SGLT2 inhibitor empagliflozin (300 mg/kg of diet for 15 wk; corresponding to 60–80 mg·kg−1·day−1) in type 1 diabetic Akita mice that, opposite to streptozotocin-diabetes, upregulate renal SGLT2 expression. Akita diabetes, empagliflozin, and Akita + empagliflozin similarly increased renal membrane SGLT2 expression (by 38–56%) and reduced the expression of SGLT1 (by 33–37%) vs. vehicle-treated wild-type controls (WT). The diabetes-induced changes in SGLT2/SGLT1 protein expression are expected to enhance the BG-lowering potential of SGLT2 inhibition, and empagliflozin strongly lowered BG in Akita (means of 187–237 vs. 517–535 mg/dl in vehicle group; 100–140 mg/dl in WT). Empagliflozin modestly reduced GFR in WT (250 vs. 306 μl/min) and completely prevented the diabetes-induced increase in glomerular filtration rate (GFR) (255 vs. 397 μl/min). Empagliflozin attenuated increases in kidney weight and urinary albumin/creatinine ratio in Akita in proportion to hyperglycemia. Empagliflozin did not increase urinary glucose/creatinine ratios in Akita, indicating the reduction in filtered glucose balanced the inhibition of glucose reabsorption. Empagliflozin attenuated/prevented the increase in systolic blood pressure, glomerular size, and molecular markers of kidney growth, inflammation, and gluconeogenesis in Akita. We propose that SGLT2 inhibition can lower GFR independent of reducing BG (consistent with the tubular hypothesis of diabetic glomerular hyperfiltration), while attenuation of albuminuria, kidney growth, and inflammation in the early diabetic kidney may mostly be secondary to lower BG. PMID:24226524

  10. Excessive crying in infants

    Directory of Open Access Journals (Sweden)

    Ricardo Halpern

    2016-05-01

    Conclusion: Excessive crying in the early months is a prevalent symptom; the pediatrician's attention is necessary to understand and adequately manage the problem and offer support to exhausted parents. The prescription of drugs of questionable action and with potential side effects is not a recommended treatment, except in extreme situations. The effectiveness of dietary treatments and use of probiotics still require confirmation. There is incomplete evidence regarding alternative treatments such as manipulation techniques, acupuncture, and use of the herbal supplements and behavioral interventions.

  11. Three-year follow-up of a randomised controlled trial to reduce excessive weight gain in the first two years of life: protocol for the POI follow-up study

    Directory of Open Access Journals (Sweden)

    Rachael W. Taylor

    2016-08-01

    Full Text Available Abstract Background The Prevention of Overweight in Infancy (POI study was a four-arm randomised controlled trial (RCT in 802 families which assessed whether additional education and support on sleep (Sleep group; food, physical activity and breastfeeding (FAB group; or both (Combination group, reduced excessive weight gain from birth to 2 years of age, compared to usual care (Control group. The study had high uptake at recruitment (58 % and retention at 2 years (86 %. Although the FAB intervention produced no significant effect on BMI or weight status at 2 years, the odds of obesity were halved in those who received the sleep intervention, despite no apparent effect on sleep duration. We speculate that enhanced self-regulatory behaviours may exist in the Sleep group. Self-regulation was not measured in our initial intervention, but extensive measures have been included in this follow-up study. Thus, the overall aim of the POI follow-up is to determine the extent to which augmented parental support and education on infant sleep, feeding, diet, and physical activity in the first 2 years of life reduces BMI at 3.5 and 5 years of age, and to determine the role of self-regulation in any such relationship. Methods/design We will contact all 802 families and seek renewed consent to participate in the follow-up study. The families have received no POI intervention since the RCT finished at 2 years of age. Follow-up data collection will occur when the children are aged 3.5 and 5 years (i.e. up to 3 years post-intervention. Outcomes of interest include child anthropometry, body composition (DXA scan, diet (validated food frequency questionnaire, physical activity (accelerometry, sleep (questionnaire and accelerometry, and self-regulation (questionnaires and neuropsychological assessment. Discussion Our follow-up study has been designed primarily to enable us to determine whether the intriguing benefit of the sleep intervention suggested at 2

  12. ACTIVATION PARAMETERS AND EXCESS THERMODYANAMIC ...

    African Journals Online (AJOL)

    Applying these data, viscosity-B-coefficients, activation parameters (Δμ10≠) and (Δμ20≠) and excess thermodynamic functions, viz., excess molar volume (VE), excess viscosity, ηE and excess molar free energy of activation of flow, (GE) were calculated. The value of interaction parameter, d, of Grunberg and Nissan ...

  13. Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress.

    Science.gov (United States)

    Ollier, S; Beaudoin, F; Vanacker, N; Lacasse, P

    2016-12-01

    When cows are unable to consume enough feed to support milk production, they often fall into severe negative energy balance. This leads to a weakened immune system and increases their susceptibility to infectious diseases. Reducing the milk production of cows subjected to acute nutritional stress decreases their energy deficit. The aim of this study was to compare the effects on metabolism and immune function of reducing milk production using quinagolide (a prolactin-release inhibitor) or dexamethasone in feed-restricted cows. A total of 23 cows in early/mid-lactation were fed for 5 d at 55.9% of their previous dry matter intake to subject them to acute nutritional stress. After 1 d of feed restriction and for 4 d afterward (d 2 to 5), cows received twice-daily i.m. injections of water (control group; n=8), 2mg of quinagolide (QN group; n=7), or water after a first injection of 20mg of dexamethasone (DEX group; n=8). Feed restriction decreased milk production, but the decrease was greater in the QN and DEX cows than in the control cows on d 2 and 3. As expected, feed restriction reduced the energy balance, but the reduction was lower in the QN cows than in the control cows. Feed restriction decreased plasma glucose concentration and increased plasma nonesterified fatty acid (NEFA) and β-hydroxybutyrate (BHB) concentrations. The QN cows had higher glucose concentration and lower BHB concentration than the control cows. The NEFA concentration was also lower in the QN cows than in the control cows on d 2. Dexamethasone injection induced transient hyperglycemia concomitant with a reduction in milk lactose concentration; it also decreased BHB concentration and decreased NEFA initially but increased it later. Feed restriction and quinagolide injections did not affect the blood concentration or activity of polymorphonuclear leukocytes (PMN), whereas dexamethasone injection increased PMN blood concentration but decreased the proportion of PMN capable of inducing oxidative

  14. T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice.

    Directory of Open Access Journals (Sweden)

    Vince N Montes

    Full Text Available Adipose tissue inflammation and specifically, pro-inflammatory macrophages are believed to contribute to insulin resistance (IR in obesity in humans and animal models. Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role of the T cell response in adipose tissue of mice fed an obesogenic diet, we used two agents (CTLA-4 Ig and anti-CD40L antibody that block co-stimulation, which is essential for full T cell activation. C57BL/6 mice were fed an obesogenic diet for 16 weeks, and concomitantly either treated with CTLA-4 Ig, anti-CD40L antibody or an IgG control (300 µg/week. The treatments altered the immune cell composition of adipose tissue in obese mice. Treated mice demonstrated a marked reduction in pro-inflammatory adipose tissue macrophages and activated CD8+ T cells. Mice treated with anti-CD40L exhibited reduced weight gain, which was accompanied by a trend toward improved IR. CTLA-4 Ig treatment, however, was not associated with improved IR. These data suggest that the presence of pro-inflammatory T cells and macrophages can be altered with co-stimulatory inhibitors, but may not be a significant contributor to the whole body IR phenotype.

  15. A multimodal RAGE-specific inhibitor reduces amyloid β–mediated brain disorder in a mouse model of Alzheimer disease

    Science.gov (United States)

    Deane, Rashid; Singh, Itender; Sagare, Abhay P.; Bell, Robert D.; Ross, Nathan T.; LaRue, Barbra; Love, Rachal; Perry, Sheldon; Paquette, Nicole; Deane, Richard J.; Thiyagarajan, Meenakshisundaram; Zarcone, Troy; Fritz, Gunter; Friedman, Alan E.; Miller, Benjamin L.; Zlokovic, Berislav V.

    2012-01-01

    In Alzheimer disease (AD), amyloid β peptide (Aβ) accumulates in plaques in the brain. Receptor for advanced glycation end products (RAGE) mediates Aβ-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a high-affinity RAGE-specific inhibitor (FPS-ZM1) that blocked Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro and in the mouse brain in vivo. FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibited RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 bound exclusively to RAGE, which inhibited β-secretase activity and Aβ production and suppressed microglia activation and the neuroinflammatory response. Blockade of RAGE actions at the BBB and in the brain reduced Aβ40 and Aβ42 levels in brain markedly and normalized cognitive performance and cerebral blood flow responses in aged APPsw/0 mice. Our data suggest that FPS-ZM1 is a potent multimodal RAGE blocker that effectively controls progression of Aβ-mediated brain disorder and that it may have the potential to be a disease-modifying agent for AD. PMID:22406537

  16. TGF-β Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis.

    Directory of Open Access Journals (Sweden)

    Michael R Davies

    Full Text Available Rotator cuff tears represent a large burden of muscle-tendon injuries in our aging population. While small tears can be repaired surgically with good outcomes, critical size tears are marked by muscle atrophy, fibrosis, and fatty infiltration, which can lead to failed repair, frequent re-injury, and chronic disability. Previous animal studies have indicated that Transforming Growth Factor-β (TGF-β signaling may play an important role in the development of these muscle pathologies after injury. Here, we demonstrated that inhibition of TGF-β1 signaling with the small molecule inhibitor SB431542 in a mouse model of massive rotator cuff tear results in decreased fibrosis, fatty infiltration, and muscle weight loss. These observed phenotypic changes were accompanied by decreased fibrotic, adipogenic, and atrophy-related gene expression in the injured muscle of mice treated with SB431542. We further demonstrated that treatment with SB431542 reduces the number of fibro/adipogenic progenitor (FAP cells-an important cellular origin of rotator cuff muscle fibrosis and fatty infiltration, in injured muscle by promoting apoptosis of FAPs. Together, these data indicate that the TGF-β pathway is a critical regulator of the degenerative muscle changes seen after massive rotator cuff tears. TGF-β promotes rotator cuff muscle fibrosis and fatty infiltration by preventing FAP apoptosis. TGF-β regulated FAP apoptosis may serve as an important target pathway in the future development of novel therapeutics to improve muscle outcomes following rotator cuff tear.

  17. AI-2 quorum-sensing inhibitors affect the starvation response and reduce virulence in several Vibrio species, most likely by interfering with LuxPQ.

    Science.gov (United States)

    Brackman, Gilles; Celen, Shari; Baruah, Kartik; Bossier, Peter; Van Calenbergh, Serge; Nelis, Hans J; Coenye, Tom

    2009-12-01

    The increase of disease outbreaks caused by Vibrio species in aquatic organisms as well as in humans, together with the emergence of antibiotic resistance in Vibrio species, has led to a growing interest in alternative disease control measures. Quorum sensing (QS) is a mechanism for regulating microbial gene expression in a cell density-dependent way. While there is good evidence for the involvement of auto-inducer 2 (AI-2)-based interspecies QS in the control of virulence in multiple Vibrio species, only few inhibitors of this system are known. From the screening of a small panel of nucleoside analogues for their ability to disturb AI-2-based QS, an adenosine derivative with a p-methoxyphenylpropionamide moiety at C-3' emerged as a promising hit. Its mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of Vibrio harveyi AI-2 QS mutants. Our results indicate that this compound, as well as a truncated analogue lacking the adenine base, block AI-2-based QS without interfering with bacterial growth. The active compounds affected neither the bioluminescence system as such nor the production of AI-2, but most likely interfered with the signal transduction pathway at the level of LuxPQ in V. harveyi. The most active nucleoside analogue (designated LMC-21) was found to reduce the Vibrio species starvation response, to affect biofilm formation in Vibrio anguillarum, Vibrio vulnificus and Vibrio cholerae, to reduce pigment and protease production in V. anguillarum, and to protect gnotobiotic Artemia from V. harveyi-induced mortality.

  18. Heat Shock Cognate 70 Inhibitor, VER-155008, Reduces Memory Deficits and Axonal Degeneration in a Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Ximeng Yang

    2018-01-01

    Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disorder resulting in structural brain changes and memory impairment. We hypothesized that reconstructing neural networks is essential for memory recovery in AD. Heat shock cognate 70 (HSC70, a member of the heat shock protein family of molecular chaperones, is upregulated in AD patient brains, and recent studies have demonstrated that HSC70 facilitates axonal degeneration and pathological progression in AD. However, the direct effects of HSC70 inhibition on axonal development and memory function have never been investigated. In this study, we examined the effects of a small-molecule HSC70 inhibitor, VER-155008, on axonal morphology and memory function in a mouse model of AD (5XFAD mice. We found that VER-155008 significantly promoted axonal regrowth in amyloid β-treated neurons in vitro and improved object recognition, location, and episodic-like memory in 5XFAD mice. Furthermore, VER-155008 penetrated into the brain after intraperitoneal administration, suggesting that VER-155008 acts in the brain in situ. Immunohistochemistry revealed that VER-155008 reduced bulb-like axonal swelling in the amyloid plaques in the perirhinal cortex and CA1 in 5XFAD mice, indicating that VER-155008 also reverses axonal degeneration in vivo. Moreover, the two main pathological features of AD, amyloid plaques and paired helical filament tau accumulation, were reduced by VER-155008 administration in 5XFAD mice. This is the first report to show that the inhibition of HSC70 function may be critical for axonal regeneration and AD-like symptom reversal. Our study provides evidence that HSC70 can be used as a new therapeutic target for AD treatment.

  19. Identification and Functional Characterization of Sugarcane Invertase Inhibitor (ShINH1: A Potential Candidate for Reducing Pre- and Post-harvest Loss of Sucrose in Sugarcane

    Directory of Open Access Journals (Sweden)

    Suresha G. Shivalingamurthy

    2018-05-01

    Full Text Available In sugarcane, invertase enzymes play a key role in sucrose accumulation and are also involved in futile reactions where sucrose is continuously degraded during the pre- and post-harvest period, thereby reducing sugar yield and recovery. Invertase inhibitor (INVINH proteins play a key role in post-translation regulation of plant invertases through which sucrose hydrolysis is controlled. INVINH proteins are small (18 kDa members of the pectin methylesterase inhibitor superfamily and they are moderately conserved across plants. In the present study, we identified two INVINH genes from sugarcane, ShINH1 and ShINH2. In silico characterization of the encoded proteins revealed 43% sequence identity at the amino acid level, confirming the non-allelic nature of the proteins. The presence of putative signal peptide and subcellular targeting sequences revealed that ShINH1 and ShINH2 likely have apoplasmic and vacuolar localization, respectively. Experimental visualization of ShINH1–GFP revealed that ShINHI is indeed exported to the apoplast. Differential tissue-specific and developmental expression of ShINH1 between leaf, stalk, flower and root suggest that it plays a role in controlling source-sink metabolic regulation during sucrose accumulation in sugarcane. ShINH1 is expressed at relatively high levels in leaves and stalk compared to flowers and roots, and expression decreases significantly toward internodal maturity during stalk development. ShINH1 is expressed at variable levels in flowers with no specific association to floral maturity. Production of recombinant ShINH1 enabled experimental validation of protein function under in vitro conditions. Recombinant ShINH1 potently inhibited acid invertase (IC50 22.5 nM, making it a candidate for controlling pre- and post-harvest deterioration of sucrose in sugarcane. Our results indicate that ShINH1 and ShINH2 are likely to play a regulatory role in sucrose accumulation and contribute to the improvement

  20. Excessive crying in infants

    Directory of Open Access Journals (Sweden)

    Ricardo Halpern

    2016-05-01

    Full Text Available Objective: Review the literature on excessive crying in young infants, also known as infantile colic, and its effects on family dynamics, its pathophysiology, and new treatment interventions. Data source: The literature review was carried out in the Medline, PsycINFO, LILACS, SciELO, and Cochrane Library databases, using the terms “excessive crying,” and “infantile colic,” as well technical books and technical reports on child development, selecting the most relevant articles on the subject, with emphasis on recent literature published in the last five years. Summary of the findings: Excessive crying is a common symptom in the first 3 months of life and leads to approximately 20% of pediatric consultations. Different prevalence rates of excessive crying have been reported, ranging from 14% to approximately 30% in infants up to 3 months of age. There is evidence linking excessive crying early in life with adaptive problems in the preschool period, as well as with early weaning, maternal anxiety and depression, attention deficit hyperactivity disorder, and other behavioral problems. Several pathophysiological mechanisms can explain these symptoms, such as circadian rhythm alterations, central nervous system immaturity, and alterations in the intestinal microbiota. Several treatment alternatives have been described, including behavioral measures, manipulation techniques, use of medication, and acupuncture, with controversial results and effectiveness. Conclusion: Excessive crying in the early months is a prevalent symptom; the pediatrician's attention is necessary to understand and adequately manage the problem and offer support to exhausted parents. The prescription of drugs of questionable action and with potential side effects is not a recommended treatment, except in extreme situations. The effectiveness of dietary treatments and use of probiotics still require confirmation. There is incomplete evidence regarding alternative treatments

  1. A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation.

    Science.gov (United States)

    Mori, Tadashi; Hidaka, Masafumi; Ikuji, Hiroko; Yoshizawa, Ibuki; Toyohara, Haruhiko; Okuda, Toru; Uchida, Chiyoko; Asano, Tomoichiro; Yotsu-Yamashita, Mari; Uchida, Takafumi

    2014-01-01

    The peptidyl prolyl cis/trans isomerase Pin1 enhances the uptake of triglycerides and the differentiation of fibroblasts into adipose cells in response to insulin stimulation. Pin1 downregulation could be a potential approach to prevent and treat obesity-related disorders. In order to identify an inhibitor of Pin1 that exhibited minimal cytotoxicity, we established a high-throughput screen for Pin1 inhibitors and used this method to identify an inhibitor from 1,056 crude fractions of two natural product libraries. The candidate, a phlorotannin called 974-B, was isolated from the seaweed, Ecklonia kurome. 974-B inhibited the differentiation of mouse embryonic fibroblasts and 3T3-L1 cells into adipose cells without inducing cytotoxicity. We discovered the Pin1 inhibitor, 974-B, from the seaweed, E. kurome, and showed that it blocks the differentiation of fibroblasts into adipose cells, suggesting that 974-B could be a lead drug candidate for obesity-related disorders.

  2. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

    Directory of Open Access Journals (Sweden)

    María Miana

    2015-06-01

    Full Text Available Extracellular matrix (ECM remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX family of amine oxidases, including LOX and LOX-like (LOXL isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD. Interestingly, treatment with β-aminopropionitrile (BAPN, a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters – it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4, as well as the increase in suppressor of cytokine signaling 3 (SOCS3 and dipeptidyl peptidase 4 (DPP4 levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX

  3. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats.

    Science.gov (United States)

    Miana, María; Galán, María; Martínez-Martínez, Ernesto; Varona, Saray; Jurado-López, Raquel; Bausa-Miranda, Belén; Antequera, Alfonso; Luaces, María; Martínez-González, José; Rodríguez, Cristina; Cachofeiro, Victoria

    2015-06-01

    Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD). Interestingly, treatment with β-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters - it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA) index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4), as well as the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX activity for

  4. Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins).

    Science.gov (United States)

    Prasad, G V Ramesh; Kim, S Joseph; Huang, Michael; Nash, Michelle M; Zaltzman, Jeffrey S; Fenton, Stanley S A; Cattran, Daniel C; Cole, Edward H; Cardella, Carl J

    2004-11-01

    Statins have anti-inflammatory effects, modify endothelial function and improve peripheral insulin resistance. We hypothesized that statins influence the development of new-onset diabetes mellitus in renal transplant recipients. The records of all previously non-diabetic adults who received an allograft in Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow-up through December 31, 2002. All patients receiving cyclosporine or tacrolimus, mycophenolate mofetil and prednisone were included. New-onset diabetes was diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose > or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two occasions. Statin use prior to diabetes development was recorded along with other variables. Cox proportional hazards models analyzing statin use as a time-dependent covariate were performed. Three hundred fourteen recipients met study criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n = 49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p = 0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation.

  5. The Virtual Diphoton Excess

    CERN Document Server

    Stolarski, Daniel

    2016-01-01

    Interpreting the excesses around 750 GeV in the diphoton spectra to be the signal of a new heavy scalar decaying to photons, we point out the possibility of looking for correlated signals with virtual photons. In particular, we emphasize that the effective operator that generates the diphoton decay will also generate decays to two leptons and a photon, as well as to four leptons, independently of the new resonance couplings to $Z\\gamma$ and $ZZ$. Depending on the relative sizes of these effective couplings, we show that the virtual diphoton component can make up a sizable, and sometimes dominant, contribution to the total $2\\ell \\gamma$ and $4\\ell$ partial widths. We also discuss modifications to current experimental cuts in order to maximize the sensitivity to these virtual photon effects. Finally, we briefly comment on prospects for channels involving other Standard Model fermions as well as more exotic decay possibilities of the putative resonance.

  6. Abundance, Excess, Waste

    Directory of Open Access Journals (Sweden)

    Rox De Luca

    2016-02-01

    Her recent work focuses on the concepts of abundance, excess and waste. These concerns translate directly into vibrant and colourful garlands that she constructs from discarded plastics collected on Bondi Beach where she lives. The process of collecting is fastidious, as is the process of sorting and grading the plastics by colour and size. This initial gathering and sorting process is followed by threading the components onto strings of wire. When completed, these assemblages stand in stark contrast to the ease of disposability associated with the materials that arrive on the shoreline as evidence of our collective human neglect and destruction of the environment around us. The contrast is heightened by the fact that the constructed garlands embody the paradoxical beauty of our plastic waste byproducts, while also evoking the ways by which those byproducts similarly accumulate in randomly assorted patterns across the oceans and beaches of the planet.

  7. Topiramate Induced Excessive Sialorrhea

    Directory of Open Access Journals (Sweden)

    Ersel Dag

    2015-11-01

    Full Text Available It is well-known that drugs such as clozapine and lithium can cause sialorrhea. On the other hand, topiramate has not been reported to induce sialorrhea. We report a case of a patient aged 26 who was given antiepileptic and antipsychotic drugs due to severe mental retardation and intractable epilepsy and developed excessive sialorrhea complaint after the addition of topiramate for the control of seizures. His complaints continued for 1,5 years and ended after giving up topiramate. We presented this case since it was a rare sialorrhea case induced by topiramate. Clinicians should be aware of the possibility of sialorrhea development which causes serious hygiene and social problems when they want to give topiramate to the patients using multiple drugs.

  8. Androgen excess: Investigations and management.

    Science.gov (United States)

    Lizneva, Daria; Gavrilova-Jordan, Larisa; Walker, Walidah; Azziz, Ricardo

    2016-11-01

    Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response. Copyright © 2016. Published by Elsevier Ltd.

  9. Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Santos Cavaiola T

    2018-04-01

    Full Text Available Tricia Santos Cavaiola, Jeremy Pettus Division of Endocrinology and Metabolism, University of California San Diego, San Diego, CA, USA Abstract: As the first cardiovascular (CV outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM, the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME® trial, which investigated the sodium glucose cotransporter 2 (SGLT2 inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL, which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. Keywords: canagliflozin, cardiovascular outcomes, dapagliflozin, empagliflozin, mechanisms, sodium glucose cotransporter 2 inhibitors

  10. Histone deacetylase inhibitors restore IL-10 expression in lipopolysaccharide-induced cell inflammation and reduce IL-1β and IL-6 production in breast silicone implant in C57BL/6J wild-type murine model.

    Science.gov (United States)

    Di Liddo, Rosa; Valente, Sergio; Taurone, Samanta; Zwergel, Clemens; Marrocco, Biagina; Turchetta, Rosaria; Conconi, Maria Teresa; Scarpa, Carlotta; Bertalot, Thomas; Schrenk, Sandra; Mai, Antonello; Artico, Marco

    2016-01-20

    Among epigenetic enzymes, histone deacetylases (HDACs) are responsible for regulating the expression of an extensive array of genes by reversible deacetylation of nuclear histones as well as a large number of non-histone proteins. Initially proposed for cancer therapy, recently the interest for HDAC inhibitors (HDACi) as orally active, safe, and anti-inflammatory agents is rising due to their ability in reducing the severity of inflammatory and autoimmune diseases. In particular, selective HDAC3, HDAC6, and HDAC8 inhibitors have been described to downregulate the expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-1β, and IL-6). Herein, using KB31, C2C12, and 3T3-J2 cell lines, we demonstrated that, under lipopolysaccharide-induced in vitro inflammation, HDAC3/6/8 inhibitor MC2625 and HDAC6-selective inhibitor MC2780 were effective at a concentration of 30 ng/mL to downregulate mRNA expression of pro-inflammatory cytokines (IL-1β and IL-6) and to promote the transcription of IL-10 gene, without affecting the cell viability. Afterwards, we investigated by immunohistochemistry the activity of MC2625 and MC2780 at a concentration of 60 ng/kg animal weight to regulate silicone-triggered immune response in C57BL/6J female mice. Our findings evidenced the ability of such inhibitors to reduce host inflammation in silicone implants promoting a thickness reduction of peri-implant fibrous capsule, upregulating IL-10 expression, and reducing the production of both IL-1β and IL-6. These results underline the potential application of MC2625 and MC2780 in inflammation-related diseases.

  11. Ganetespib, an HSP90 inhibitor, kills Epstein-Barr virus (EBV)-infected B and T cells and reduces the percentage of EBV-infected cells in the blood.

    Science.gov (United States)

    Shatzer, Amber; Ali, Mir A; Chavez, Mayra; Dowdell, Kennichi; Lee, Min-Jung; Tomita, Yusuke; El-Hariry, Iman; Trepel, Jane B; Proia, David A; Cohen, Jeffrey I

    2017-04-01

    HSP90 inhibitors have been shown to kill Epstein-Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells with ganetespib, an HSP90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed EBV-positive B and T cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV-positive lymphomas and prolonged survival in SCID mice inoculated with one EBV-transformed B-cell line, but not another B-cell line. The former cell line showed lower levels of EBNA-1 after treatment with ganetespib in vitro. Treatment of a patient with T-cell chronic active EBV with ganetespib reduced the percentage of EBV-positive cells in the peripheral blood. These data indicate that HSP90 inhibitors may have a role in the therapy of certain EBV-associated diseases.

  12. SGLT2 inhibitors.

    Science.gov (United States)

    Dardi, I; Kouvatsos, T; Jabbour, S A

    2016-02-01

    Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. APC/C Dysfunction Limits Excessive Cancer Chromosomal Instability.

    Science.gov (United States)

    Sansregret, Laurent; Patterson, James O; Dewhurst, Sally; López-García, Carlos; Koch, André; McGranahan, Nicholas; Chao, William Chong Hang; Barry, David J; Rowan, Andrew; Instrell, Rachael; Horswell, Stuart; Way, Michael; Howell, Michael; Singleton, Martin R; Medema, René H; Nurse, Paul; Petronczki, Mark; Swanton, Charles

    2017-02-01

    Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization. APC/C impairment caused adaptation to MPS1 inhibitors, revealing a likely resistance mechanism to therapies targeting the spindle assembly checkpoint. Finally, CRISPR-mediated introduction of cancer somatic mutations in the APC/C subunit cancer driver gene CDC27 reduces chromosome segregation errors, whereas reversal of an APC/C subunit nonsense mutation increases CIN. Subtle variations in mitotic duration, determined by APC/C activity, influence the extent of CIN, allowing cancer cells to dynamically optimize fitness during tumor evolution. We report a mechanism whereby cancers balance the evolutionary advantages associated with CIN against the fitness costs caused by excessive genome instability, providing insight into the consequence of CDC27 APC/C subunit driver mutations in cancer. Lengthening of mitosis through APC/C modulation may be a common mechanism of resistance to cancer therapeutics that increase chromosome segregation errors. Cancer Discov; 7(2); 218-33. ©2017 AACR.See related commentary by Burkard and Weaver, p. 134This article is highlighted in the In This Issue feature, p. 115. ©2017 American Association for Cancer Research.

  14. The angiotensin converting enzyme inhibitor trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function

    DEFF Research Database (Denmark)

    Abdulla, Jawdat; Burchardt, Hans; Z Abildstrøm, Steen

    2003-01-01

    /day of furosemide was spared in trandolapril arm (P=0.001). CONCLUSIONS: Trandolapril had a mild diuretic-sparing effect. These results emphasis the importance of explaining to patients that ACE inhibitors provide protection against death and hospitalisation for heart failure but do not have any significant effect...

  15. Hunger, escaping excess.

    Science.gov (United States)

    Gardner, G; Halweil, B

    2000-01-01

    According to the WHO, in spite of decades of global food surpluses, half of humanity, in both rich and poor nations, is still malnourished. Malnutrition has become a significant impediment to development in rich and poor countries, alike. At the individual level, both hunger and poor eating habits reduce a person's physical fitness, increase susceptibility to illness, and shorten lifespan. In addition, children deprived of adequate nutrients during development can suffer from permanently reduced mental capacity. At the national level, poor eating hampers educational performance, curtails economic productivity, increases the burden on health care, and reduces well-being. Confronting this epidemic of poor eating will have widespread benefits, but the myths and misconceptions permeating humanity¿s understanding of malnutrition should be addressed first. It is noted that the major cause of hunger is poverty, not scarcity of food; it is the lack of access to the goods and services essential for a healthy life. On the other hand, for those who have access to plenty of food, dietary intake includes meat, dairy products, and highly processed items loaded with fat and sugar. This leads to the problem of obesity, a condition that increases susceptibility to disease and disability, reduces worker productivity, and shortens lifespan. In view of this, efforts to improve nutrition should focus on poverty eradication, health education, agricultural change, and policy change towards promotion of good nutrition.

  16. The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.

    Science.gov (United States)

    Booth, Laurence; Roberts, Jane L; Poklepovic, Andrew; Kirkwood, John; Sander, Cindy; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dent, Paul

    2018-02-01

    The FDA approved irreversible inhibitor of ERBB1/2/4, neratinib, was recently shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET and mutant K-RAS via autophagic degradation. In the present studies, in a dose-dependent fashion, neratinib reduced the expression levels of mutant K-RAS or of mutant N-RAS, which was augmented in an additive to greater than additive fashion by the HDAC inhibitors sodium valproate and AR42. Neratinib could reduce PDGFRα levels in GBM cells, that was enhanced by sodium valproate. Knock down of Beclin1 or of ATG5 prevented neratinib and neratinib combined with sodium valproate / AR42 from reducing the expression of mutant N-RAS in established PDX and fresh PDX models of ovarian cancer and melanoma, respectively. Neratinib and the drug combinations caused the co-localization of mutant RAS proteins and ERBB2 with Beclin1 and cathepsin B. The drug combination activated the AMP-dependent protein kinase that was causal in enhancing HMG Co A reductase phosphorylation. Collectively, our data reinforce the concept that the irreversible ERBB1/2/4 inhibitor neratinib has the potential for use in the treatment of tumors expressing mutant RAS proteins.

  17. New Estimation of the Dosage of Scale Inhibitor in the Cooling Water System

    Directory of Open Access Journals (Sweden)

    Jiang Jiaomei

    2011-01-01

    Full Text Available In the cooling water system, excessive use of organic phosphate scale inhibitors is harmful to environment. Reducing the dosage of the organic phosphate scale inhibitor is important. A self-made jacketed crystallizer was used in this experiment. The critical pH values have been determined in cooling water systems with series of Ca2+ concentrations by adding different concentration of the scale inhibitor ATMP (Amino Trimethylene Phosphonic Acid according to the calcium carbonate Metastable zone theory. A model equation at 45 °C and pH=9 was proposed to estimate the lowest dose of the scale inhibitor ATMP. The measured pH value was approximate to the expected pH value in two cooling water systems through verification test.

  18. Antidepressant induced excessive yawning and indifference

    Directory of Open Access Journals (Sweden)

    Bruno Palazzo Nazar

    2015-03-01

    Full Text Available Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

  19. Evaluation of novel arginine based inhibitors of DDAH and investigations into radical hydroacylation of vinyl sulfonates

    OpenAIRE

    Khanom, N.

    2010-01-01

    The thesis is in two main sections. In the first section, studies on methylarginine processing enzymes are presented. Dimethyalrginine dimethylaminohydrolase (DDAH) is a class of enzymes involved in the metabolism of methylarginines ADMA and L-NMMA, which indirectly regulate physiological nitric oxide levels. It is desirable to inhibit excess NO in pathological situations, and the arginine mimetic L-257 is a DDAH inhibitor which reduces levels of NO. Synthesis of ester analo...

  20. The Histone Deacetylase Inhibitor, Vorinostat, Reduces Tumor Growth at the Metastatic Bone Site and Associated Osteolysis, but Promotes Normal Bone Loss

    OpenAIRE

    Pratap, Jitesh; Akech, Jacqueline; Wixted, John J.; Szabo, Gabriela; Hussain, Sadiq; McGee-Lawrence, Meghan E.; Li, Xiaodong; Bedard, Krystin; Dhillon, Robinder J.; van Wijnen, Andre J.; Stein, Janet L.; Stein, Gary S.; Westendorf, Jennifer J.; Lian, Jane B.

    2010-01-01

    Vorinostat, an oral histone deacetylase inhibitor with anti-tumor activity, is in clinical trials for hematological and solid tumors that metastasize and compromise bone structure. Consequently, there is a requirement to establish the effects of vorinostat on tumor growth within bone. Breast (MDA-231) and prostate (PC3) cancer cells were injected into tibias of SCID/NCr mice and the effects of vorinostat on tumor growth and osteolytic disease were assessed by radiography, μCT, histological an...

  1. Effects of reducing blood pressure on renal outcomes in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

    Science.gov (United States)

    Scheen, A J; Delanaye, P

    2017-04-01

    Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function. While systemic BP reduction associated to empagliflozin therapy may have contributed to the renal benefits reported in EMPA-REG OUTCOME, other local mechanisms related to kidney homoeostasis most probably also played a role in the overall protection observed in the trial. Copyright © 2017. Published by Elsevier Masson SAS.

  2. A miR-21 inhibitor enhances apoptosis and reduces G2-M accumulation induced by ionizing radiation in human glioblastoma U251 cells

    International Nuclear Information System (INIS)

    Li, Yi; Li, Qiang; Asai, Akio; Kawamoto, Keiji; Zhao Shiguang; Zhen Yunbo; Teng Lei

    2011-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs that take part in diverse biological processes by suppressing target gene expression. Elevated expression of miR-21 has been reported in many types of human cancers. Radiotherapy is a standard adjuvant treatment for patients with glioblastoma. However, the resistance of glioblastoma cells to radiation limits the success of this treatment. In this study, we found that miR-21 expression was upregulated in response to ionizing radiation (IR) in U251 cells, which suggested that miR-21 could be involved in the response of U251 cells to radiation. We showed that a miR-21 inhibitor enhanced IR-induced glioblastoma cell growth arrest and increased the level of apoptosis, which was probably caused by abrogation of the G 2 -M arrest induced by IR. Further research demonstrated that the miR-21 inhibitor induced the upregulation of Cdc25A. Taken together, these findings suggest that miR-21 inhibitor can increase IR-induced growth arrest and apoptosis in U251 glioblastoma cells, at least in part by abrogating G 2 -M arrest, and that Cdc25A is a potential target of miR-21. (author)

  3. Does excessive pronation cause pain?

    DEFF Research Database (Denmark)

    Olesen, C G; Nielsen, Rasmus Gottschalk N; Rathleff, Michael Skovdal

    2008-01-01

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist of ...

  4. Health economics of treating haemophilia A with inhibitors.

    Science.gov (United States)

    Knight, C

    2005-11-01

    Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement.

  5. Cardiovascular effects of sodium glucose cotransporter 2 inhibitors

    Science.gov (United States)

    Cavaiola, Tricia Santos; Pettus, Jeremy

    2018-01-01

    As the first cardiovascular (CV) outcome trial of a glucose-lowering agent to demonstrate a reduction in the risk of CV events in patients with type 2 diabetes mellitus (T2DM), the EMPAgliflozin Removal of Excess Glucose: Cardiovascular OUTCOME Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME®) trial, which investigated the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, has generated great interest among health care professionals. CV outcomes data for another SGLT2 inhibitor, canagliflozin, have been published recently in the CANagliflozin CardioVascular Assessment Study (CANVAS) Program, as have CV data from the retrospective real-world study Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors (CVD-REAL), which compared SGLT2 inhibitors with other classes of glucose-lowering drugs. This review discusses the results of these three studies and, with a focus on EMPA-REG OUTCOME, examines the possible mechanisms by which SGLT2 inhibitors may reduce CV risk in patients with T2DM. PMID:29695924

  6. Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and Intracellular Invasion of Bacteria.

    Science.gov (United States)

    Singh, Samsher; Kalia, Nitin P; Joshi, Prashant; Kumar, Ajay; Sharma, Parduman R; Kumar, Ashok; Bharate, Sandip B; Khan, Inshad A

    2017-01-01

    This study elucidated the role of boeravinone B, a NorA multidrug efflux pump inhibitor, in biofilm inhibition. The effects of boeravinone B plus ciprofloxacin, a NorA substrate, were evaluated in NorA-overexpressing, wild-type, and knocked-out Staphylococcus aureus (SA-1199B, SA-1199, and SA-K1758, respectively). The mechanism of action was confirmed using the ethidium bromide accumulation and efflux assay. The role of boeravinone B as a human P -glycoprotein ( P -gp) inhibitor was examined in the LS-180 (colon cancer) cell line. Moreover, its role in the inhibition of biofilm formation and intracellular invasion of S. aureus in macrophages was studied. Boeravinone B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin against S. aureus and its methicillin-resistant strains; the effect was stronger in SA-1199B. Furthermore, time-kill kinetics revealed that boeravinone B plus ciprofloxacin, at subinhibitory concentration (0.25 × MIC), is as equipotent as that at the MIC level. This combination also had a reduced mutation prevention concentration. Boeravinone B reduced the efflux of ethidium bromide and increased the accumulation, thus strengthening the role as a NorA inhibitor. Biofilm formation was reduced by four-eightfold of the minimal biofilm inhibitory concentration of ciprofloxacin, effectively preventing bacterial entry into macrophages. Boeravinone B effectively inhibited P -gp with half maximal inhibitory concentration (IC 50 ) of 64.85 μM. The study concluded that boeravinone B not only inhibits the NorA-mediated efflux of fluoroquinolones but also considerably inhibits the biofilm formation of S. aureus. Its P -gp inhibition activity demonstrates its potential as a bioavailability and bioefficacy enhancer.

  7. HIV-1 tropism for the central nervous system: Brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor

    International Nuclear Information System (INIS)

    Martin-Garcia, Julio; Cao, Wei; Varela-Rohena, Angel; Plassmeyer, Matthew L.; Gonzalez-Scarano, Francisco

    2006-01-01

    We previously described envelope glycoproteins of an HIV-1 isolate adapted in vitro for growth in microglia that acquired a highly fusogenic phenotype and lower CD4 dependence, as well as resistance to inhibition by anti-CD4 antibodies. Here, we investigated whether similar phenotypic changes are present in vivo. Envelope clones from the brain and spleen of an HIV-1-infected individual with neurological disease were amplified, cloned, and sequenced. Phylogenetic analysis demonstrated clustering of sequences according to the tissue of origin, as expected. Functional clones were then used in cell-to-cell fusion assays to test for CD4 and co-receptor utilization and for sensitivity to various antibodies and inhibitors. Both brain- and spleen-derived envelope clones mediated fusion in cells expressing both CD4 and CCR5 and brain envelopes also used CCR3 as co-receptor. We found that the brain envelopes had a lower CD4 dependence, since they efficiently mediated fusion in the presence of low levels of CD4 on the target cell membrane, and they were significantly more resistant to blocking by anti-CD4 antibodies than the spleen-derived envelopes. In contrast, we observed no difference in sensitivity to the CCR5 antagonist TAK-779. However, brain-derived envelopes were significantly more resistant than those from spleen to the fusion inhibitor T-1249 and concurrently showed slightly greater fusogenicity. Our results suggest an increased affinity for CD4 of brain-derived envelopes that may have originated from in vivo adaptation to replication in microglial cells. Interestingly, we note the presence of envelopes more resistant to a fusion inhibitor in the brain of an untreated, HIV-1-infected individual

  8. Does Excessive Pronation Cause Pain?

    DEFF Research Database (Denmark)

    Mølgaard, Carsten Møller; Olesen Gammelgaard, Christian; Nielsen, R. G.

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist...... of antipronation shoes or insoles, which latest was studied by Kulce DG., et al (2007). So far there have been no randomized controlled studies showing methods that the effect of this treatment has not been documented. Therefore the authors can measure the effect of treatments with insoles. Some of the excessive...

  9. Ablation of TRPM5 in Mice Results in Reduced Body Weight Gain and Improved Glucose Tolerance and Protects from Excessive Consumption of Sweet Palatable Food when Fed High Caloric Diets.

    Directory of Open Access Journals (Sweden)

    Marie H Larsson

    Full Text Available The calcium activated cation channel transient receptor potential channel type M5 (TRPM5 is part of the downstream machinery of the taste receptors and have been shown to play a central role in taste signalling. In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells. The aim of this study was to investigate the effects of TRPM5 gene ablation on body weight, insulin sensitivity and other metabolic parameters in long-term high caloric diet induced obesity. Trpm5-/- mice gained significantly less body weight and fat mass on both palatable carbohydrate and fat rich cafeteria diet and 60% high fat diet (HFD and developed less insulin resistance compared to wild type mice. A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight. In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball. Thus the palatable sugar containing diet induced overeating was prevented in Trpm5-/- mice. This indicates that sweet taste induced overeating may be a cause for the increased energy intake and glucose intolerance development seen for wild type mice on a sugar and high fat rich cafeteria diet compared to when on a high fat diet. This study point to an important role for the taste signalling system and TRPM5 in diet induced glucose intolerance.

  10. Developing BACE-1 inhibitors for FXS

    Directory of Open Access Journals (Sweden)

    Cara J Westmark

    2013-05-01

    Full Text Available Fragile X syndrome (FXS is a debilitating genetic disorder with no cure and few therapeutic options. Excessive signaling through metabotropic glutamate receptor 5 (mGluR5 in FXS leads to increased translation of numerous synaptic proteins and exaggerated long-term depression (LTD. Two of the overexpressed proteins are amyloid-beta protein precursor (APP and its metabolite amyloid-beta (Aβ, which have been well-studied in Alzheimer’s disease (AD. Here we discus the possibility that pharmaceuticals under study for the modulation of these proteins in AD might be viable therapeutic strategies for FXS. Specifically, a recently identified acetyltransferase (ATase inhibitor that reduces the levels and activity of β-site APP cleaving enzyme (BACE-1 has strong potential to attenuate BACE-1 activity and maintain homeostatic levels APP catabolites in FXS.

  11. Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.

    Science.gov (United States)

    Scheen, André J

    2016-11-01

    Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. UCCB01-125, a dimeric inhibitor of PSD-95, reduces inflammatory pain without disrupting cognitive or motor performance: Comparison with the NMDA receptor antagonist MK-801

    DEFF Research Database (Denmark)

    Andreasen, Jesper T.; Bach, Anders; Gynther, Mikko

    2013-01-01

    Excessive N-Methyl-d-aspartate receptor (NMDAR)-dependent production of nitric oxide (NO) is involved in the development and maintenance of chronic pain states, and is mediated by postsynaptic density protein-95 (PSD-95). By binding to both the NMDAR and neuronal NO synthase (nNOS), PSD-95 mediates...... a specific coupling between NMDAR activation and NO production. NMDAR antagonism shows anti-nociceptive action in humans and animal models of chronic pain but is associated with severe disturbances of cognitive and motor functions. An alternative approach to modulate the NMDAR-related activity is to perturb......'s adjuvant (CFA) model of inflammatory pain. To examine side-effect profiles we also compared the effects of UCCB01-125 and MK-801 in tests of attention, long-term memory, and motor performance. When administered concurrently with CFA, both MK-801 and UCCB01-125 prevented the development of CFA...

  13. Escitalopram is a weak inhibitor of the CYP2D6 catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain

    DEFF Research Database (Denmark)

    Noehr-Jensen, L; Zwisler, S T; Larsen, F

    2009-01-01

    Tramadol is O–demethylated to the active metabolite (+)–O–desmethyltramadol ((+)–M1) via CYP2D6, an enzyme that is weakly inhibited by escitalopram. We investigated the possibility of a pharmacokinetic (PK) and pharmacodynamic (PD) effect of escitalopram on tramadol metabolism. Fifteen healthy...... subjects completed this randomized, double–blind, three–phase, crossover trial. Combinations of escitalopram 20 mg/day or placebo together with tramadol 150 mg or placebo were used. Blood samples for pharmacokinetics were drawn at 0–24 h after medication. The analgesic effect of (+)–M was assessed...... AUEC1–12 of CPT were 4,140 and 4,388 cm·s after placebo and escitalopram, respectively (P = 0.71). Although escitalopram is a weak inhibitor of CYP2D6, it does not impair the analgesic effect of tramadol....

  14. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Directory of Open Access Journals (Sweden)

    Reed JW

    2016-10-01

    Full Text Available James W Reed Morehouse School of Medicine, Atlanta, GA, USA Abstract: SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM. These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose

  15. 24 CFR 236.60 - Excess Income.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Excess Income. 236.60 Section 236... § 236.60 Excess Income. (a) Definition. Excess Income consists of cash collected as rent from the... Rent. The unit-by-unit requirement necessitates that, if a unit has Excess Income, the Excess Income...

  16. Risk of hormone escape in a human prostate cancer model depends on therapy modalities and can be reduced by tyrosine kinase inhibitors.

    Directory of Open Access Journals (Sweden)

    Charlotte Guyader

    Full Text Available Almost all prostate cancers respond to androgen deprivation treatment but many recur. We postulated that risk of hormone escape--frequency and delay--are influenced by hormone therapy modalities. More, hormone therapies induce crucial biological changes involving androgen receptors; some might be targets for escape prevention. We investigated the relationship between the androgen deprivation treatment and the risk of recurrence using nude mice bearing the high grade, hormone-dependent human prostate cancer xenograft PAC120. Tumor-bearing mice were treated by Luteinizing-Hormone Releasing Hormone (LHRH antagonist alone, continuous or intermittent regimen, or combined with androgen receptor (AR antagonists (bicalutamide or flutamide. Tumor growth was monitored. Biological changes were studied as for genomic alterations, AR mutations and protein expression in a large series of recurrent tumors according to hormone therapy modalities. Therapies targeting Her-2 or AKT were tested in combination with castration. All statistical tests were two-sided. Tumor growth was inhibited by continuous administration of the LH-RH antagonist degarelix (castration, but 40% of tumors recurred. Intermittent castration or complete blockade induced by degarelix and antiandrogens combination, inhibited tumor growth but increased the risk of recurrence (RR as compared to continuous castration (RR(intermittent: 14.5, RR(complete blockade: 6.5 and 1.35. All recurrent tumors displayed new quantitative genetic alterations and AR mutations, whatever the treatment modalities. AR amplification was found after complete blockade. Increased expression of Her-2/neu with frequent ERK/AKT activation was detected in all variants. Combination of castration with a Her-2/neu inhibitor decreased recurrence risk (0.17 and combination with an mTOR inhibitor prevented it. Anti-hormone treatments influence risk of recurrence although tumor growth inhibition was initially similar. Recurrent

  17. Alpha-glucosidase inhibitor, acarbose, improves glycamic control and reduces body weight in type 2 diabetes: Findings on indian patients from the pooled data analysis

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2013-01-01

    Full Text Available Alpha-glucosidase inhibitors are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycemia (PPG. The higher carbohydrate in the Indian diets lead to greater prandial glycemic excursion, increased glucosidase, and incretin activity in the gut and may need special therapeutic strategies to tackle these glucose peaks. This is the subgroup analysis of Indian subjects who participated in the GlucoVIP study that investigated the effectiveness and tolerability of acarbose as add-on or monotherapy in a range of patients with type 2 diabetes mellitus. A total of 1996 Indian patients were included in the effectiveness analysis. After 12.5 weeks (mean, the mean change in 2-hour PPG from baseline was −74.4 mg/dl, mean HbA1c decreased by -1.0%, and mean fasting blood glucose decreased by -37.9 mg/dl. The efficacy of acarbose was rated "very good" or "good" in 91.1% of patients, and tolerability as "very good" or "good" in 88.0% of patients. The results of this observational study suggest that acarbose was effective and well tolerated in the Indian patients with T2DM.

  18. Supply of neuraminidase inhibitors related to reduced influenza A (H1N1) mortality during the 2009-2010 H1N1 pandemic: summary of an ecological study.

    Science.gov (United States)

    Miller, Paula E; Rambachan, Aksharananda; Hubbard, Roderick J; Li, Jiabai; Meyer, Alison E; Stephens, Peter; Mounts, Anthony W; Rolfes, Melissa A; Penn, Charles R

    2013-09-01

    When the influenza A (H1N1) pandemic spread across the globe from April 2009 to August 2010, many WHO Member States used antiviral drugs, specifically neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza patients in critical condition. Antivirals have been found to be effective in reducing severity and duration of influenza illness, and likely reduce morbidity; however, it is unclear whether NAIs used during the pandemic reduced H1N1 mortality. To assess the association between antivirals and influenza mortality, at an ecologic level, country-level data on supply of oseltamivir and zanamivir were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July 2009 to August 2010 in 42 WHO Member States. From this analysis, it was found that each 10% increase in kilograms of oseltamivir, per 100 000 people, was associated with a 1·6% reduction in H1N1 mortality over the pandemic period [relative rate (RR) = 0·84 per log increase in oseltamivir supply]. Each 10% increase in kilogram of active zanamivir, per 100 000, was associated with a 0·3% reduction in H1N1 mortality (RR = 0·97 per log increase). While limitations exist in the inference that can be drawn from an ecologic evaluation, this analysis offers evidence of a protective relationship between antiviral drug supply and influenza mortality and supports a role for influenza antiviral use in future pandemics. This article summarises the original study described previously, which can be accessed through the following citation: Miller PE, Rambachan A, Hubbard RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An Ecological Study. PLoS ONE 7(9): e43491. © 2013 Blackwell Publishing Ltd.

  19. Excessive or unwanted hair in women

    Science.gov (United States)

    Hypertrichosis; Hirsutism; Hair - excessive (women); Excessive hair in women; Hair - women - excessive or unwanted ... Women normally produce low levels of male hormones (androgens). If your body makes too much of this ...

  20. Excessive masturbation after epilepsy surgery.

    Science.gov (United States)

    Ozmen, Mine; Erdogan, Ayten; Duvenci, Sirin; Ozyurt, Emin; Ozkara, Cigdem

    2004-02-01

    Sexual behavior changes as well as depression, anxiety, and organic mood/personality disorders have been reported in temporal lobe epilepsy (TLE) patients before and after epilepsy surgery. The authors describe a 14-year-old girl with symptoms of excessive masturbation in inappropriate places, social withdrawal, irritability, aggressive behavior, and crying spells after selective amygdalohippocampectomy for medically intractable TLE with hippocampal sclerosis. Since the family members felt extremely embarrassed, they were upset and angry with the patient which, in turn, increased her depressive symptoms. Both her excessive masturbation behavior and depressive symptoms remitted within 2 months of psychoeducative intervention and treatment with citalopram 20mg/day. Excessive masturbation is proposed to be related to the psychosocial changes due to seizure-free status after surgery as well as other possible mechanisms such as Kluver-Bucy syndrome features and neurophysiologic changes associated with the cessation of epileptic discharges. This case demonstrates that psychiatric problems and sexual changes encountered after epilepsy surgery are possibly multifactorial and in adolescence hypersexuality may be manifested as excessive masturbation behavior.

  1. Reducing TNF receptor 2+ regulatory T cells via the combined action of azacitidine and the HDAC inhibitor, panobinostat for clinical benefit in acute myeloid leukemia patients.

    Science.gov (United States)

    Govindaraj, Chindu; Tan, Peter; Walker, Patricia; Wei, Andrew; Spencer, Andrew; Plebanski, Magdalena

    2014-02-01

    Acute myeloid leukemia (AML) provides an environment that enables immune suppression, resulting in functionally defective effector T cells; regulatory T cells (Treg) are significant contributors to the impaired antitumor immune response. As TNF is present at high levels in AML and TNF receptor-2 (TNFR2)-expressing Tregs identify highly functional Tregs, we examine the hypothesis that TNFR2(+) Tregs are a relevant Treg subset in this cancer. We also determine the effect of the novel combinatorial therapy of the demethylating agent, azacitidine with the histone deacetylase inhibitor, panobinostat on Tregs, particularly TNFR2(+) Tregs. Thirty healthy donors and 14 patients with AML were enrolled in this study. Patients were treated with azacitidine and panobinostat for 28-day cycles. The frequency and functional relevance of TNFR2(+) Tregs were analyzed subsequently. We report that TNFR2(+) Tregs are increased in AML and have a high migration potential toward the bone marrow. Furthermore, we demonstrate that the level of TNFR2(+) Tregs in the peripheral blood and the bone marrow of patients are decreased in vivo after exposure to panobinostat and azacitidine. Reductions in TNFR2(+) Tregs were associated with increases in Interferon (IFN)-γ and interleukin (IL)-2 production by effector T cells within the bone marrow and beneficial clinical responses. In vitro mechanistic studies indicated panobinostat as the primary driver for the reduction of Tregs. Our study provides for the first time, in vivo validation of the ability of panobinostat in combination with azacitidine to suppress prevalent TNFR2(+) Tregs, resulting in clinical benefits within patients with AML. ©2013 AACR.

  2. Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+,K+-ATPase

    Directory of Open Access Journals (Sweden)

    D. M. Djuric

    1996-01-01

    Full Text Available The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, β-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase was evaluated in a histamine H3 receptor agonist-induced ((Rα-methylhistamine, (Rα-MeHA endothelium-dependent rat aorta relaxation assay. (Rα-MeHA (0.1 nM – 0.01 mM relaxed endothelium-dependent rat aorta, with a pD2 value of 8.22 ± 0.06, compared with a pD2 value of 7.98 ± 0.02 caused by histamine (50% and 70% relaxation, respectively. The effect of (Rα-MeHA (0.1 nM – 0.01 mM was competitively antagonized by thioperamide (1, 10 and 30 nM (pA2 = 9.21 ± 0.40; slope = 1.03 ± 0.35 but it was unaffected by pyrilamine (100 nM, cimetidine (1 μM, atropine (10 μM, propranolol (1 μM, indomethacin (10 μM or nordthydroguaiaretic acid (0.1 mM. Inhibitors of nitric oxide synthase, L-NG-monomethylarginine (L-NMMA, 10 μM and NG-nitro-L-arginine methylester (L-NOARG, 10 μM inhibited the relaxation effect of (Rα-MeHA, by approximately 52% and 70%, respectively. This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 μM. Methylene blue (10 μM and ouabain (10 μM inhibited relaxation (Rα-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (Rα-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and β-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na+,K+-ATPase in (Rα-MeHA-induced endothelium-dependent rat aorta relaxation.

  3. Impact of sodium–glucose cotransporter 2 inhibitors on blood pressure

    Science.gov (United States)

    Reed, James W

    2016-01-01

    SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM. Boolean searches were conducted that included terms related to BP or hypertension with terms for SGLT2 inhibitors, canagliflozin, dapagliflozin, or empagliflozin using PubMed, Google, and Google Scholar. Data from numerous randomized controlled trials of SGLT2 inhibitors in patients with T2DM demonstrated clinically relevant reductions in both systolic and diastolic BP, assessed via seated office measurements and 24-hour ambulatory BP monitoring. Observed BP lowering was not associated with compensatory increases in heart rate. Circadian BP rhythm was also maintained. The mechanism of SGLT2 inhibitor-associated BP reduction is not fully understood, but is assumed to be related to osmotic diuresis and natriuresis. Other factors that may also contribute to BP reduction include SGLT2 inhibitor-associated decreases in body weight and reduced arterial stiffness. Local inhibition of the renin–angiotensin–aldosterone system secondary to increased delivery of sodium to the juxtaglomerular apparatus during SGLT2 inhibition has also been postulated. Although SGLT2 inhibitors are not indicated as BP-lowering agents, the modest decreases in systolic and diastolic BP observed with SGLT2 inhibitors may provide an extra clinical advantage for the majority of patients with T2DM, in addition to improving blood glucose control. PMID:27822054

  4. [Syk inhibitors].

    Science.gov (United States)

    Kimura, Yukihiro; Chihara, Kazuyasu; Takeuchi, Kenji; Sada, Kiyonao

    2013-07-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in the University of Fukui in 1991. Syk is known to be essential for the various physiological functions, especially in hematopoietic lineage cells. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis, and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure, and function of Syk, and then describe the novel Syk inhibitors and their current status. Furthermore, we will introduce our findings of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel target of Syk.

  5. Severe rhabdomyolysis after excessive bodybuilding.

    Science.gov (United States)

    Finsterer, J; Zuntner, G; Fuchs, M; Weinberger, A

    2007-12-01

    A 46-year-old male subject performed excessive physical exertion during 4-6 h in a studio for body builders during 5 days. He was not practicing sport prior to this training and denied the use of any aiding substances. Despite muscle aching already after 1 day, he continued the exercises. After the last day, he recognized tiredness and cessation of urine production. Two days after discontinuation of the training, a Herpes simplex infection occurred. Because of acute renal failure, he required hemodialysis. There were absent tendon reflexes and creatine kinase (CK) values up to 208 274 U/L (normal: <170 U/L). After 2 weeks, CK had almost normalized and, after 4 weeks, hemodialysis was discontinued. Excessive muscle training may result in severe, hemodialysis-dependent rhabdomyolysis. Triggering factors may be prior low fitness level, viral infection, or subclinical metabolic myopathy.

  6. Syk inhibitors.

    Science.gov (United States)

    Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

    2013-01-01

    Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

  7. Verification of excess defense material

    International Nuclear Information System (INIS)

    Fearey, B.L.; Pilat, J.F.; Eccleston, G.W.; Nicholas, N.J.; Tape, J.W.

    1997-01-01

    The international community in the post-Cold War period has expressed an interest in the International Atomic Energy Agency (IAEA) using its expertise in support of the arms control and disarmament process in unprecedented ways. The pledges of the US and Russian presidents to place excess defense materials under some type of international inspections raises the prospect of using IAEA safeguards approaches for monitoring excess materials, which include both classified and unclassified materials. Although the IAEA has suggested the need to address inspections of both types of materials, the most troublesome and potentially difficult problems involve approaches to the inspection of classified materials. The key issue for placing classified nuclear components and materials under IAEA safeguards is the conflict between these traditional IAEA materials accounting procedures and the US classification laws and nonproliferation policy designed to prevent the disclosure of critical weapon-design information. Possible verification approaches to classified excess defense materials could be based on item accountancy, attributes measurements, and containment and surveillance. Such approaches are not wholly new; in fact, they are quite well established for certain unclassified materials. Such concepts may be applicable to classified items, but the precise approaches have yet to be identified, fully tested, or evaluated for technical and political feasibility, or for their possible acceptability in an international inspection regime. Substantial work remains in these areas. This paper examines many of the challenges presented by international inspections of classified materials

  8. The GABA uptake inhibitor beta-alanine reduces pilocarpine-induced tremor and increases extracellular GABA in substantia nigra pars reticulata as measured by microdialysis.

    Science.gov (United States)

    Ishiwari, Keita; Mingote, Susana; Correa, Merce; Trevitt, Jennifer T; Carlson, Brian B; Salamone, John D

    2004-12-30

    Substantia nigra pars reticulata (SNr) is a major output nucleus of the basal ganglia that receives GABAergic projections from neostriatum and globus pallidus. Previous research has shown that local pharmacological manipulations of GABA in SNr can influence tremulous jaw movements in rats. Tremulous jaw movements are defined as rapid vertical deflections of the lower jaw that resemble chewing but are not directed at a particular stimulus, and evidence indicates that these movements share many characteristics with parkinsonian tremor in humans. In order to investigate the role of GABA in motor functions related to tremor, the present study tested the GABA uptake blocker beta-alanine for its ability to reduce pilocarpine-induced tremulous jaw movements. In a parallel experiment, the effect of an active dose of beta-alanine on dialysate levels of GABA in SNr was assessed using microdialysis methods. GABA levels in dialysis samples were measured using high performance liquid chromatography with electrochemical detection. beta-Alanine (250-500 mg/kg) significantly reduced tremulous jaw movements induced by pilocarpine (4.0 mg/kg). Moreover, systemic administration of beta-alanine at a dose that reduced tremulous jaw movements (500 mg/kg) resulted in a substantial increase in extracellular levels of GABA in SNr compared to the pre-injection baseline. Thus, the present results are consistent with the hypothesis that GABAergic tone in SNr plays a role in the regulation of tremulous jaw movements. This research may lead to a better understanding of how parkinsonian symptoms are modulated by SNr GABA mechanisms.

  9. Excess water dynamics in hydrotalcite: QENS study

    Indian Academy of Sciences (India)

    dynamics of excess water in hydrotalcite sample with varied content of excess water are reported. Translational motion of excess water can be best described by random transla- tional jump diffusion model. The observed increase in translational diffusivity with increase in the amount of excess water is attributed to the ...

  10. 34 CFR 300.16 - Excess costs.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Excess costs. 300.16 Section 300.16 Education... DISABILITIES General Definitions Used in This Part § 300.16 Excess costs. Excess costs means those costs that... for an example of how excess costs must be calculated.) (Authority: 20 U.S.C. 1401(8)) ...

  11. Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

    Directory of Open Access Journals (Sweden)

    S.R. Martins

    2006-02-01

    Full Text Available Cholecystokinin (CCK influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM and cerulein (EC50: 58; 95% CI: 18-281 nM induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 µM in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 µM L-NOARG from 73 ± 5.1 to 19 ± 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

  12. Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

    Science.gov (United States)

    Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

    2018-03-05

    Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

  13. Industrial excess heat for district heating in Denmark

    International Nuclear Information System (INIS)

    Bühler, Fabian; Petrović, Stefan; Karlsson, Kenneth; Elmegaard, Brian

    2017-01-01

    Highlights: •Method for utilisation potential of industrial excess heat for district heating. •Industrial excess heat from thermal processes is quantified at single production units. •Linking of industrial excess heat sources and district heating demands done in GIS. •Excess heat recovery using direct heat transfer and heat pumps. •5.1% of the Danish district heating demand could be supplied by industrial excess heat. -- Abstract: Excess heat is available from various sources and its utilisation could reduce the primary energy use. The accessibility of this heat is however dependent amongst others on the source and sink temperature, amount and potential users in its vicinity. In this work a new method is developed which analyses excess heat sources from the industrial sector and how they could be used for district heating. This method first allocates excess heat to single production units by introducing and validating a new approach. Spatial analysis of the heat sources and consumers are then performed to evaluate the potential for using them for district heating. In this way the theoretical potential of using the excess heat for covering the heating demand of buildings is determined. Through the use of industry specific temperature profiles the heat usable directly or via heat pumps is further found. A sensitivity analysis investigates the impact of future energy efficiency measures in the industry, buildings and the district heating grid on the national potential. The results show that for the case study of Denmark, 1.36 TWh of district heat could be provided annually with industrial excess heat from thermal processes which equals 5.1% of the current demand. More than half of this heat was found to be usable directly, without the need for a heat pump.

  14. Identification and Evaluation of Cases for Excess Heat Utilisation Using GIS

    DEFF Research Database (Denmark)

    Bühler, Fabian; Petrovic, Stefan; Ommen, Torben Schmidt

    2018-01-01

    Excess heat is present in many sectors, and its utilization could reduce the primary energy use and emission of greenhouse gases. This work presents a geographical mapping of excess heat, in which excess heat from the industry and utility sector was distributed to specific geographical locations...

  15. Excess electron transport in cryoobjects

    International Nuclear Information System (INIS)

    Eshchenko, D.G.; Storchak, V.G.; Brewer, J.H.; Cottrell, S.P.; Cox, S.F.J.

    2003-01-01

    Experimental results on excess electron transport in solid and liquid phases of Ne, Ar, and solid N 2 -Ar mixture are presented and compared with those for He. Muon spin relaxation technique in frequently switching electric fields was used to study the phenomenon of delayed muonium formation: excess electrons liberated in the μ + ionization track converge upon the positive muons and form Mu (μ + e - ) atoms. This process is shown to be crucially dependent upon the electron's interaction with its environment (i.e., whether it occupies the conduction band or becomes localized in a bubble of tens of angstroms in radius) and upon its mobility in these states. The characteristic lengths involved are 10 -6 -10 -4 cm, the characteristic times range from nanoseconds to tens microseconds. Such a microscopic length scale sometimes enables the electron spend its entire free lifetime in a state which may not be detected by conventional macroscopic techniques. The electron transport processes are compared in: liquid and solid helium (where electron is localized in buble); liquid and solid neon (where electrons are delocalized in solid and the coexistence of localized and delocalized electrons states was found in liquid recently); liquid and solid argon (where electrons are delocalized in both phases); orientational glass systems (solid N 2 -Ar mixtures), where our results suggest that electrons are localized in orientational glass. This scaling from light to heavy rare gases enables us to reveal new features of excess electron localization on microscopic scale. Analysis of the experimental data makes it possible to formulate the following tendency of the muon end-of-track structure in condensed rare gases. The muon-self track interaction changes from the isolated pair (muon plus the nearest track electron) in helium to multi-pair (muon in the vicinity of tens track electrons and positive ions) in argon

  16. Prevalence of excessive screen time and associated factors in adolescents

    Directory of Open Access Journals (Sweden)

    Joana Marcela Sales de Lucena

    2015-12-01

    Full Text Available Objective: To determine the prevalence of excessive screen time and to analyze associated factors among adolescents. Methods: This was a cross-sectional school-based epidemiological study with 2874 high school adolescents with age 14-19 years (57.8% female from public and private schools in the city of João Pessoa, PB, Northeast Brazil. Excessive screen time was defined as watching television and playing video games or using the computer for more than 2 h/day. The associated factors analyzed were: sociodemographic (gender, age, economic class, and skin color, physical activity and nutritional status of adolescents. Results: The prevalence of excessive screen time was 79.5% (95%CI 78.1-81.1 and it was higher in males (84.3% compared to females (76.1%; p<0.001. In multivariate analysis, adolescent males, those aged 14-15 year old and the highest economic class had higher chances of exposure to excessive screen time. The level of physical activity and nutritional status of adolescents were not associated with excessive screen time. Conclusions: The prevalence of excessive screen time was high and varied according to sociodemographic characteristics of adolescents. It is necessary to develop interventions to reduce the excessive screen time among adolescents, particularly in subgroups with higher exposure.

  17. The rate of aucubin, a secondary metabolite in Plantago lanceolata and potential nitrification inhibitor, needed to reduce ruminant urine patch nitrous oxide emissions

    Science.gov (United States)

    Gardiner, C. A.; Clough, T.; Cameron, K.; Di, H.; Edwards, G. R.

    2017-12-01

    Nitrous oxide (N2O) losses derived from grazing ruminant livestock urine patches account for 40% of global N2O emissions. It has been shown that Plantago lanceolata, an herb species used in grazed pastures, contains an active secondary metabolite (aucubin) that has the potential to be excreted by grazing ruminants and inhibit nitrification in the urine patch, a key step in soil N2O production. However, the urinary excretion rate of aucubin needed to significantly reduce urine patch N2O emissions remains unknown. Aucubin was dissolved in bovine urine at three rates (47, 243, and 486 kg ha-1), based on rates used in Dietz et al. (2013) and the calculated highest potential aucubin application rate, from Gardiner et al. (2017). A control, along with a urine treatment and the three aucubin treatments (all urine applied at 700 kg N ha-1), was applied to 20 g soil and incubated in the laboratory for 35 d. Soils were monitored for surface pH, inorganic N concentration (NH4+/NO3-), and gas (N2O and CO2) fluxes. This experiment is currently underway and the results will be presented at the conference. Dietz M, Machill S, Hoffmann H, Schmidtke K 2013. Inhibitory effects of Plantago lanceolata L. on soil N mineralization. Plant and Soil 368: 445-458. Gardiner CA, Clough TJ, Cameron KC, Di HJ, Edwards GR, de Klein CAM 2017. The potential inhibitory effects of Plantago lanceolata and its active secondary metabolite aucubin on soil nitrification and nitrous oxide emissions under ruminant urine patch conditions. Manuscript submitted for publication.

  18. Inactivation of proteinaceous protease inhibitors of soybeans by isolated fungi

    NARCIS (Netherlands)

    Meijer, M.M.T.; Spekking, W.T.J.; Sijtsma, L.; Bont, de J.A.M.

    1995-01-01

    Proteinaceous protease inhibitors, Kunitz Soybean Trypsin Inhibitor (KSTI) and Bowman Birk Inhibitor (BBI), in legume seeds reduce the digestibility of proteins in feed of monogastric animals. Enzymatic inactivation of these inhibitors will increase the nutritional value of the feed. The aim of this

  19. Excess electron transport in cryoobjects

    CERN Document Server

    Eshchenko, D G; Brewer, J H; Cottrell, S P; Cox, S F J

    2003-01-01

    Experimental results on excess electron transport in solid and liquid phases of Ne, Ar, and solid N sub 2 -Ar mixture are presented and compared with those for He. Muon spin relaxation technique in frequently switching electric fields was used to study the phenomenon of delayed muonium formation: excess electrons liberated in the mu sup + ionization track converge upon the positive muons and form Mu (mu sup + e sup -) atoms. This process is shown to be crucially dependent upon the electron's interaction with its environment (i.e., whether it occupies the conduction band or becomes localized in a bubble of tens of angstroms in radius) and upon its mobility in these states. The characteristic lengths involved are 10 sup - sup 6 -10 sup - sup 4 cm, the characteristic times range from nanoseconds to tens microseconds. Such a microscopic length scale sometimes enables the electron spend its entire free lifetime in a state which may not be detected by conventional macroscopic techniques. The electron transport proc...

  20. Initial clinical experience with the first drug (sacubitril/valsartan) in a new class - angiotensin receptor neprilysin inhibitors in patients with heart failure with reduced left ventricular ejection fraction in Poland.

    Science.gov (United States)

    Kałużna-Oleksy, Marta; Kolasa, Jolanta; Migaj, Jacek; Pawlak, Agnieszka; Lelonek, Małgorzata; Nessler, Jadwiga; Straburzyńska-Migaj, Ewa

    2018-01-01

    Sacubitril/valsartan is the first drug from a new class of angiotensin receptor neprilysin inhibitors (ARNIs) recommended in the new European Society of Cardiology guidelines instead of angiotensin converting enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB) that are used if ACEI are not tolerated. Sacubitril/valsartan is recommended for further reduction in the risk of hospitalisation or death in outpatients with heart failure with reduced ejection fraction (HFrEF) if symptoms continue despite optimal treatment with ACEI/ARB, beta-blockers, and mineralocorticoid antagonists. The aim of this study is to present the initial experience with regard to the effectiveness, tolerance, and safety of sacubitril/valsartan in the outpatient cardiology practice in Poland. The study is a retrospective analysis of data obtained through a questionnaire filled in by the physicians who initiated the sacubitril/valsartan treatment in patients with HFrEF between 1 June 2016 and 30 September 2016. Patients were followed-up for three months. The analysis included data on 28 patients aged 61 ± 16 years, of whom 85.7% were males. The drug was used in patients in New York Heart Association (NYHA) class I-III. In 25 (89.2%) patients sacubitril/valsartan was started at the lowest dose (24/26 mg BID). During follow-up the sacubitril/valsartan-treated patients had a reduction in HF symptoms assessed using the NYHA functional class (p = 0.001), a significant drop in N-terminal-pro B-type natriuretic peptide levels (mean, from 2900 to 2270 pg/mL; p = 0.008), and improved exercise tolerance, which occurred shortly after treatment initiation - after a mean of 28 days. It was demonstrated that the use of sacubitril/valsartan in outpatients with HFrEF is safe and is associated with a significant clinical improvement.

  1. Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

    Science.gov (United States)

    Ramos, Isaac Corro; Versteegh, Matthijs M; de Boer, Rudolf A; Koenders, Jolanda M A; Linssen, Gerard C M; Meeder, Joan G; Rutten-van Mölken, Maureen P M H

    2017-12-01

    To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647. LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  2. 34 CFR 668.166 - Excess cash.

    Science.gov (United States)

    2010-07-01

    ... the Secretary for the costs the Secretary incurred in providing that excess cash to the institution... 34 Education 3 2010-07-01 2010-07-01 false Excess cash. 668.166 Section 668.166 Education..., DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS Cash Management § 668.166 Excess cash. (a...

  3. 10 CFR 904.10 - Excess energy.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Excess energy. 904.10 Section 904.10 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.10 Excess energy. (a) If excess Energy is determined by the United States to be available...

  4. 7 CFR 985.56 - Excess oil.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Excess oil. 985.56 Section 985.56 Agriculture... HANDLING OF SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Volume Limitations § 985.56 Excess oil. Oil of any class in excess of a producer's applicable annual allotment shall be identified as...

  5. Excess costs of social anxiety disorder in Germany.

    Science.gov (United States)

    Dams, Judith; König, Hans-Helmut; Bleibler, Florian; Hoyer, Jürgen; Wiltink, Jörg; Beutel, Manfred E; Salzer, Simone; Herpertz, Stephan; Willutzki, Ulrike; Strauß, Bernhard; Leibing, Eric; Leichsenring, Falk; Konnopka, Alexander

    2017-04-15

    Social anxiety disorder is one of the most frequent mental disorders. It is often associated with mental comorbidities and causes a high economic burden. The aim of our analysis was to estimate the excess costs of patients with social anxiety disorder compared to persons without anxiety disorder in Germany. Excess costs of social anxiety disorder were determined by comparing two data sets. Patient data came from the SOPHO-NET study A1 (n=495), whereas data of persons without anxiety disorder originated from a representative phone survey (n=3213) of the general German population. Missing data were handled by "Multiple Imputation by Chained Equations". Both data sets were matched using "Entropy Balancing". Excess costs were calculated from a societal perspective for the year 2014 using general linear regression with a gamma distribution and log-link function. Analyses considered direct costs (in- and outpatient treatment, rehabilitation, and professional and informal care) and indirect costs due to absenteeism from work. Total six-month excess costs amounted to 451€ (95% CI: 199€-703€). Excess costs were mainly caused by indirect excess costs due to absenteeism from work of 317€ (95% CI: 172€-461€), whereas direct excess costs amounted to 134€ (95% CI: 110€-159€). Costs for medication, unemployment and disability pension was not evaluated. Social anxiety disorder was associated with statistically significant excess costs, in particular due to indirect costs. As patients in general are often unaware of their disorder or its severity, awareness should be strengthened. Prevention and early treatment might reduce long-term indirect costs. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Medical Ethics and Protection from Excessive Radiation

    International Nuclear Information System (INIS)

    Ruzicka, I.

    1998-01-01

    Among artificial sources of ionic radiation people are most often exposed to those emanating from X-ray diagnostic equipment. However, responsible usage of X-ray diagnostic methods may considerably reduce the general exposure to radiation. A research on rational access to X-ray diagnostic methods conducted at the X-ray Cabinet of the Tresnjevka Health Center was followed by a control survey eight years later of the rational methods applied, which showed that the number of unnecessary diagnostic examining was reduced for 34 % and the diagnostic indications were 10-40 $ more precise. The results therefore proved that radiation problems were reduced accordingly. The measures applied consisted of additional training organized for health care workers and a better education of the population. The basic element was then the awareness of both health care workers and the patients that excessive radiation should be avoided. The condition for achieving this lies in the moral responsibility of protecting the patients' health. A radiologist, being the person that promotes and carries out this moral responsibility, should organize and hold continual additional training of medical doctors, as well as education for the patients, and apply modern equipment. The basis of such an approach should be established by implementing medical ethics at all medical schools and faculties, together with the promotion of a wider intellectual and moral integrity of each medical doctor. (author)

  7. Phytoextraction of excess soil phosphorus

    International Nuclear Information System (INIS)

    Sharma, Nilesh C.; Starnes, Daniel L.; Sahi, Shivendra V.

    2007-01-01

    In the search for a suitable plant to be used in P phytoremediation, several species belonging to legume, vegetable and herb crops were grown in P-enriched soils, and screened for P accumulation potentials. A large variation in P concentrations of different plant species was observed. Some vegetable species such as cucumber (Cucumis sativus) and yellow squash (Cucurbita pepo var. melopepo) were identified as potential P accumulators with >1% (dry weight) P in their shoots. These plants also displayed a satisfactory biomass accumulation while growing on a high concentration of soil P. The elevated activities of phosphomonoesterase and phytase were observed when plants were grown in P-enriched soils, this possibly contributing to high P acquisition in these species. Sunflower plants also demonstrated an increased shoot P accumulation. This study shows that the phytoextraction of phosphorus can be effective using appropriate plant species. - Crop plants such as cucumber, squash and sunflower accumulate phosphorus and thus can be used in the phytoextraction of excess phosphorus from soils

  8. Phytoextraction of excess soil phosphorus

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Nilesh C. [Department of Biology, Western Kentucky University, 1906 College Heights Boulevard 11080, Bowling Green, KY 42101-1080 (United States); Starnes, Daniel L. [Department of Biology, Western Kentucky University, 1906 College Heights Boulevard 11080, Bowling Green, KY 42101-1080 (United States); Sahi, Shivendra V. [Department of Biology, Western Kentucky University, 1906 College Heights Boulevard 11080, Bowling Green, KY 42101-1080 (United States)]. E-mail: shiv.sahi@wku.edu

    2007-03-15

    In the search for a suitable plant to be used in P phytoremediation, several species belonging to legume, vegetable and herb crops were grown in P-enriched soils, and screened for P accumulation potentials. A large variation in P concentrations of different plant species was observed. Some vegetable species such as cucumber (Cucumis sativus) and yellow squash (Cucurbita pepo var. melopepo) were identified as potential P accumulators with >1% (dry weight) P in their shoots. These plants also displayed a satisfactory biomass accumulation while growing on a high concentration of soil P. The elevated activities of phosphomonoesterase and phytase were observed when plants were grown in P-enriched soils, this possibly contributing to high P acquisition in these species. Sunflower plants also demonstrated an increased shoot P accumulation. This study shows that the phytoextraction of phosphorus can be effective using appropriate plant species. - Crop plants such as cucumber, squash and sunflower accumulate phosphorus and thus can be used in the phytoextraction of excess phosphorus from soils.

  9. International Climate Migration: Evidence for the Climate Inhibitor Mechanism and the Agricultural Pathway.

    Science.gov (United States)

    Nawrotzki, Raphael J; Bakhtsiyarava, Maryia

    2017-05-01

    Research often assumes that, in rural areas of developing countries, adverse climatic conditions increase (climate driver mechanism) rather than reduce (climate inhibitor mechanism) migration, and that the impact of climate on migration is moderated by changes in agricultural productivity (agricultural pathway). Using representative census data in combination with high-resolution climate data derived from the novel Terra Populus system, we explore the climate-migration relationship in rural Burkina Faso and Senegal. We construct four threshold-based climate measures to investigate the effect of heat waves, cold snaps, droughts and excessive precipitation on the likelihood of household-level international outmigration. Results from multi-level logit models show that excessive precipitation increases international migration from Senegal while heat waves decrease international mobility in Burkina Faso, providing evidence for the climate inhibitor mechanism. Consistent with the agricultural pathway, interaction models and results from a geographically weighted regression (GWR) reveal a conditional effect of droughts on international outmigration from Senegal, which becomes stronger in areas with high levels of groundnut production. Moreover, climate change effects show a clear seasonal pattern, with the strongest effects appearing when heat waves overlap with the growing season and when excessive precipitation occurs prior to the growing season.

  10. International Climate Migration: Evidence for the Climate Inhibitor Mechanism and the Agricultural Pathway

    Science.gov (United States)

    Nawrotzki, Raphael J.; Bakhtsiyarava, Maryia

    2016-01-01

    Research often assumes that, in rural areas of developing countries, adverse climatic conditions increase (climate driver mechanism) rather than reduce (climate inhibitor mechanism) migration, and that the impact of climate on migration is moderated by changes in agricultural productivity (agricultural pathway). Using representative census data in combination with high-resolution climate data derived from the novel Terra Populus system, we explore the climate-migration relationship in rural Burkina Faso and Senegal. We construct four threshold-based climate measures to investigate the effect of heat waves, cold snaps, droughts and excessive precipitation on the likelihood of household-level international outmigration. Results from multi-level logit models show that excessive precipitation increases international migration from Senegal while heat waves decrease international mobility in Burkina Faso, providing evidence for the climate inhibitor mechanism. Consistent with the agricultural pathway, interaction models and results from a geographically weighted regression (GWR) reveal a conditional effect of droughts on international outmigration from Senegal, which becomes stronger in areas with high levels of groundnut production. Moreover, climate change effects show a clear seasonal pattern, with the strongest effects appearing when heat waves overlap with the growing season and when excessive precipitation occurs prior to the growing season. PMID:28943813

  11. Management of excessive gingival display: Lip repositioning technique

    Directory of Open Access Journals (Sweden)

    Upasana Sthapak

    2015-01-01

    Full Text Available The lips form the frame of a smile and define the esthetic zone. Excessive gingival display during smile is often referred to as "gummy smile". A successful management of excessive gingival display with lip repositioning procedure has shown excellent results. The procedure involves removing a strip of partial thickness mucosa from maxillary vestibule, then suturing it back to the lip mucosa at the level of mucogingival junction. This technique results in restricted muscle pull and a narrow vestibule, thereby reducing the gingival display. In this case gummy smile was treated by modification of Rubinstein and Kostianovsky′s surgical lip repositioning technique which resulted in a harmonious smile.

  12. Excess-pressure suppression device in a reactor container

    International Nuclear Information System (INIS)

    Nishio, Masahide

    1985-01-01

    Purpose: To reliably decrease the radioactivity of radioactive gases when they are released externally. Constitution: The exit of a gas exhaust pipe for discharging gases in a reactor container, on generation of an excess pressure in the reactor container upon loss of coolant accident, is adapted to be always fluided in the cooling tank. Then, the exhaust gases discharged in the cooling tank is realeased to the atmosphere. In this way, the excess pressure in the reactor container can be prevented previously and the radioactivity of the gases released externally is significantly reduced by the scrubbing effect. (Kamimura, M.)

  13. Recommended treatment strategies for patients with excessive daytime sleepiness.

    Science.gov (United States)

    Rosenberg, Russell P

    2015-10-01

    Excessive daytime sleepiness (EDS) is a common and bothersome phenomenon. It can be associated with insufficient sleep syndrome, narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, shift work disorder, Kleine-Levin syndrome, or Parkinson's disease. Once the underlying cause of the excessive sleepiness is determined, clinicians must select the most appropriate behavioral and pharmacologic interventions to reduce daytime sleepiness, alleviate other symptoms, improve functioning, and ensure the safety of patients and those around them. Patient history, adverse effects, and efficacy in specific conditions should be considered in pharmacologic treatment options for patients with EDS. © Copyright 2015 Physicians Postgraduate Press, Inc.

  14. Excess cash holdings and shareholder value

    OpenAIRE

    Lee, Edward; Powell, Ronan

    2011-01-01

    We examine the determinants of corporate cash holdings in Australia and the impact on shareholder wealth of holding excess cash. Our results show that a trade-off model best explains the level of a firm’s cash holdings in Australia. We find that 'transitory' excess cash firms earn significantly higher risk-adjusted returns compared to 'persistent' excess cash firms, suggesting that the market penalises firms that hoard cash. The marginal value of cash also declines with larger cash balances, ...

  15. Physical activity and exercise dependence during inpatient treatment of longstanding eating disorders: an exploratory study of excessive and non-excessive exercisers.

    Science.gov (United States)

    Bratland-Sanda, Solfrid; Sundgot-Borgen, Jorunn; Rø, Øyvind; Rosenvinge, Jan H; Hoffart, Asle; Martinsen, Egil W

    2010-04-01

    To describe changes in physical activity (PA) and exercise dependence score during treatment of eating disorders (ED), and to explore correlations among changes in PA, exercise motivation, exercise dependence score and ED psychopathology in excessive and non-excessive exercisers. Thirty-eight adult females receiving inpatient treatment for anorexia nervosa, bulimia nervosa or ED not otherwise specified participated in this prospective study. Assessments included accelerometer assessed PA, Exercise Dependence Scale, Reasons for Exercise Inventory, ED Examination, and ED Inventory. Amount of PA was significantly reduced in non-excessive exercisers during treatment, in excessive exercisers there was a trend towards reduced amount of PA from admission to discharge. In excessive exercisers, reduced ED psychopathology was correlated with reduction in exercise dependence score and perceived importance of exercise to regulate negative affects, but not with importance of exercise for weight/appearance. These associations were not found in non-excessive exercisers. Excessive exercise is an important issue in longstanding ED, and the excessive exercising patients need help to develop alternative strategies to regulate negative affects.

  16. Syndromes associated with nutritional deficiency and excess.

    Science.gov (United States)

    Jen, Melinda; Yan, Albert C

    2010-01-01

    Normal functioning of the human body requires a balance between nutritional intake and metabolism, and imbalances manifest as nutritional deficiencies or excess. Nutritional deficiency states are associated with social factors (war, poverty, famine, and food fads), medical illnesses with malabsorption (such as Crohn disease, cystic fibrosis, and after bariatric surgery), psychiatric illnesses (eating disorders, autism, alcoholism), and medications. Nutritional excess states result from inadvertent or intentional excessive intake. Cutaneous manifestations of nutritional imbalance can herald other systemic manifestations. This contribution discusses nutritional deficiency and excess syndromes with cutaneous manifestations of particular interest to clinical dermatologists. Copyright © 2010. Published by Elsevier Inc.

  17. Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients?

    Directory of Open Access Journals (Sweden)

    Foley JE

    2016-01-01

    Full Text Available James E Foley,1 Vaishali Bhosekar,2 Ryuzo Kawamori3 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Healthcare Pvt Ltd, Hyderabad, Telangana, India; 3Sportology Center, Juntendo University Graduate School of Medicine, Juntendo University, Tokyo, Japan Background: Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM may respond more favorably to a DPP-4 (dipeptidyl peptidase-4 inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid] between Japanese and Caucasian populations. Methods: This analysis pooled data from 19 studies of drug-naïve patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338 who had been treated in Japan and Caucasian patients (n=1,275 who were treated elsewhere. Change from baseline (Δ in glycated hemoglobin (HbA1c at 12 weeks (in millimoles per mole versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. Results: At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program, while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. ΔHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r2=0.36; and 0.41, r2=0.15, and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean ΔHbA1c was greater by 1.7 mmol

  18. Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice.

    Science.gov (United States)

    Kangawa, Yumi; Yoshida, Toshinori; Abe, Hajime; Seto, Yoshiki; Miyashita, Taishi; Nakamura, Michi; Kihara, Tohru; Hayashi, Shim-Mo; Shibutani, Makoto

    2017-04-04

    Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongmei [Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P.R. of China (China); Liao, Zhongxing, E-mail: zliao@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhuang, Yan; Xu, Ting; Nguyen, Quynh-Nhu; Levy, Lawrence B.; O' Reilly, Michael [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gold, Kathryn A. [Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-12-01

    Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available for analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.

  20. Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing.

    Science.gov (United States)

    Schott, Gisela; Martinez, Yolanda V; Ediriweera de Silva, R Erandie; Renom-Guiteras, Anna; Vögele, Anna; Reeves, David; Kunnamo, Ilkka; Marttila-Vaara, Minna; Sönnichsen, Andreas

    2017-10-16

    Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project. Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention. Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c companies and authored or

  1. Sodium-glucose co-transporter 2 (SGLT2 inhibitors: a growing class of anti-diabetic agents

    Directory of Open Access Journals (Sweden)

    Eva M Vivian

    2014-12-01

    Full Text Available Although several treatment options are available to reduce hyperglycemia, only about half of individuals with diagnosed diabetes mellitus (DM achieve recommended glycemic targets. New agents that reduce blood glucose concentrations by novel mechanisms and have acceptable safety profiles are needed to improve glycemic control and reduce the complications associated with type 2 diabetes mellitus (T2DM. The renal sodium-glucose co-transporter 2 (SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors of SGLT2 lower blood glucose independent of the secretion and action of insulin by inhibiting renal reabsorption of glucose, thereby promoting the increased urinary excretion of excess glucose. Canagliflozin, dapagliflozin, and empagliflozin are SGLT2 inhibitors approved as treatments for T2DM in the United States, Europe, and other countries. Canagliflozin, dapagliflozin, and empagliflozin increase renal excretion of glucose and improve glycemic parameters in patients with T2DM when used as monotherapy or in combination with other antihyperglycemic agents. Treatment with SGLT2 inhibitors is associated with weight reduction, lowered blood pressure, and a low intrinsic propensity to cause hypoglycemia. Overall, canagliflozin, dapagliflozin, and empagliflozin are well tolerated. Cases of genital infections and, in some studies, urinary tract infections have been more frequent in canagliflozin-, dapagliflozin-, and empagliflozin-treated patients compared with those receiving placebo. Evidence from clinical trials suggests that SGLT2 inhibitors are a promising new treatment option for T2DM.

  2. Bladder calculus presenting as excessive masturbation.

    Science.gov (United States)

    De Alwis, A C D; Senaratne, A M R D; De Silva, S M P D; Rodrigo, V S D

    2006-09-01

    Masturbation in childhood is a normal behaviour which most commonly begins at 2 months of age, and peaks at 4 years and in adolescence. However excessive masturbation causes anxiety in parents. We describe a boy with a bladder calculus presenting as excessive masturbation.

  3. Measuring excess capital capacity in agricultural production

    NARCIS (Netherlands)

    Zhengfei, G.; Kumbhakar, S.C.; Myers, R.J.; Oude Lansink, A.G.J.M.

    2009-01-01

    We introduce the concept "excess capital capacity" and employ a stochastic input requirement frontier to measure excess capital capacity in agricultural production. We also propose a two-step estimation method that allows endogenous regressors in stochastic frontier models. The first step uses

  4. The excessively crying infant : etiology and treatment

    NARCIS (Netherlands)

    Akhnikh, S.; Engelberts, A.C.; Sleuwen, B.E. van; Hoir, M.P. L’; Benninga, M.A.

    2014-01-01

    Excessive crying, often described as infantile colic, is the cause of 10% to 20% of all early pediatrician visits of infants aged 2 weeks to 3 months. Although usually benign and selflimiting, excessive crying is associated with parental exhaustion and stress. However, and underlying organic cause

  5. Part B Excess Cost Quick Reference Document

    Science.gov (United States)

    Ball, Wayne; Beridon, Virginia; Hamre, Kent; Morse, Amanda

    2011-01-01

    This Quick Reference Document has been prepared by the Regional Resource Center Program ARRA/Fiscal Priority Team to aid RRCP State Liaisons and other (Technical Assistance) TA providers in understanding the general context of state questions surrounding excess cost. As a "first-stop" for TA providers in investigating excess cost…

  6. Excessive Internet gaming and decision making: do excessive World of Warcraft players have problems in decision making under risky conditions?

    Science.gov (United States)

    Pawlikowski, Mirko; Brand, Matthias

    2011-08-15

    The dysfunctional behavior of excessive Internet gamers, such as preferring the immediate reward (to play World of Warcraft) despite the negative long-term consequences may be comparable with the dysfunctional behavior in substance abusers or individuals with behavioral addictions, e.g. pathological gambling. In these disorders, general decision-making deficits have been demonstrated. Hence, the aim of the present work was to examine decision-making competences of excessive World of Warcraft players. Nineteen excessive Internet gamers (EIG) and a control group (CG) consisting of 19 non-gamers were compared with respect to decision-making abilities. The Game of Dice Task (GDT) was applied to measure decision-making under risky conditions. Furthermore psychological-psychiatric symptoms were assessed in both groups. The EIG showed a reduced decision-making ability in the GDT. Furthermore the EIG group showed a higher psychological-psychiatric symptomatology in contrast to the CG. The results indicate that the reduced decision-making ability of EIG is comparable with patients with other forms of behavioral addiction (e.g. pathological gambling), impulse control disorders or substance abusers. Thus, these results suggest that excessive Internet gaming may be based on a myopia for the future, meaning that EIG prefer to play World of Warcraft despite the negative long-term consequences in social or work domains of life. 2011 Elsevier Ltd. All rights reserved.

  7. 75 FR 27572 - Monthly Report of Excess Income and Annual Report of Uses of Excess Income

    Science.gov (United States)

    2010-05-17

    ... Income and Annual Report of Uses of Excess Income AGENCY: Office of the Chief Information Officer, HUD... permitted to retain Excess Income for projects under terms and conditions established by HUD. Owners must request to retain some or all of their Excess Income. The request must be submitted through http://www.pay...

  8. SGLT2 inhibitors: molecular design and potential differences in effect.

    Science.gov (United States)

    Isaji, Masayuki

    2011-03-01

    The physiological and pathological handling of glucose via sodium-glucose cotransporter-2 (SGLT2) in the kidneys has been evolving, and SGLT2 inhibitors have been focused upon as a novel drug for treating diabetes. SGLT2 inhibitors enhance renal glucose excretion by inhibiting renal glucose reabsorption. Consequently, SGLT2 inhibitors reduce plasma glucose insulin independently and improve insulin resistance in diabetes. To date, various SGLT2 inhibitors have been developed and evaluated in clinical studies. The potency and positioning of SGLT2 inhibitors as an antidiabetic drug are dependent on their characteristic profile, which induces selectivity, efficacy, pharmacokinetics, and safety. This profile decides which SGLT2 inhibitors can be expected for application of the theoretical concept of reducing renal glucose reabsorption for the treatment of diabetes. I review the structure and advancing profile of various SGLT2 inhibitors, comparing their similarities and differences, and discuss the expected SGLT2 inhibitors for an emerging category of antidiabetic drugs.

  9. An excess noise measurement system for weak responsivity avalanche photodiodes

    Science.gov (United States)

    Qiao, Liang; Dimler, Simon J.; Baharuddin, Aina N. A. P.; Green, James E.; David, John P. R.

    2018-06-01

    A system for measuring, with reduced photocurrent, the excess noise associated with the gain in avalanche photodiodes (APDs), using a transimpedance amplifier front-end and based on phase-sensitive detection is described. The system can reliably measure the excess noise power of devices, even when the un-multiplied photocurrent is low (~10 nA). This is more than one order of magnitude better than previously reported systems and represents a significantly better noise signal to noise ratio. This improvement in performance has been achieved by increasing the value of the feedback resistor and reducing the op-amp bandwidth. The ability to characterise APD performance with such low photocurrents enables the use of low power light sources such as light emitting diode rather than lasers to investigate the APD noise performance.

  10. Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

    Science.gov (United States)

    Chan, Francis K L; Kyaw, Moe; Tanigawa, Tetsuya; Higuchi, Kazuhide; Fujimoto, Kazuma; Cheong, Pui Kuan; Lee, Vivian; Kinoshita, Yoshikazu; Naito, Yuji; Watanabe, Toshio; Ching, Jessica Y L; Lam, Kelvin; Lo, Angeline; Chan, Heyson; Lui, Rashid; Tang, Raymond S Y; Sakata, Yasuhisa; Tse, Yee Kit; Takeuchi, Toshihisa; Handa, Osamu; Nebiki, Hiroko; Wu, Justin C Y; Abe, Takashi; Mishiro, Tsuyoshi; Ng, Siew C; Arakawa, Tetsuo

    2017-01-01

    It is not clear whether H 2 -receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186. Copyright © 2017 AGA

  11. Fiscal 1996 international research cooperation project. Feasibility study of finding out the seeds of international joint research (technology for effective use of saturated hydrocarbon, technology for reducing excess of aromatic hydrocarbon, high-grade treatment technology of petroleum coke); 1996 nendo kokusai kenkyu kyoryoku jigyo. Kokusai kyodo kenkyu seeds hakkutsu no tame no FS chosa (howa tanka suiso no yuko riyo gijutsu, hokozoku tanka suiso no yojo taisaku gijutsu, sekiyu cokes no kodo shori gijutsu)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    This project is aimed at internationally cooperating in the R and D of industrial technology and improving industrial technology of Japan. For it, the following three technologies were investigated: (1) technology for effective use of saturated hydrocarbon, (2) technology for reducing excess of aromatic hydrocarbon, (3) high-grade treatment technology of petroleum coke. In (1), surveys were conducted of technologies of effective use of natural gas and effective use of C4 saturated hydrocarbon. Surveyed were a method for producing synthesis gas from natural gas, a technology to liquefy natural gas into fuel following the synthesis gas production process, a technology to liquefy natural gas into fuel without the synthesis gas production process, and the trend of effective use of C4 saturated hydrocarbon. In (2), surveys were made of process to reduce production of aromatic hydrocarbon as much as possible, process to effectively separate aromatic hydrocarbon, and process to convert excess aromatic hydrocarbon into polymer, etc. In (3), surveys were conducted on petroleum coke and pitch in terms of production methods, the supply/demand situation, property characteristics, usability to new fields, etc. 170 refs., 114 figs., 65 tabs.

  12. Excessive crying in infants with regulatory disorders.

    Science.gov (United States)

    Maldonado-Duran, M; Sauceda-Garcia, J M

    1996-01-01

    The authors point out a correlation between regulatory disorders in infants and the problem of excessive crying. The literature describes other behavioral problems involving excessive crying in very young children, but with little emphasis on this association. The recognition and diagnosis of regulatory disorders in infants who cry excessively can help practitioners design appropriate treatment interventions. Understanding these conditions can also help parents tailor their caretaking style, so that they provide appropriate soothing and stimulation to their child. In so doing, they will be better able to develop and preserve a satisfactory parent-child relationship, as well as to maintain their own sense of competence and self-esteem as parents.

  13. The control of neutrophil chemotaxis by inhibitors of cathepsin G and chymotrypsin.

    Science.gov (United States)

    Lomas, D A; Stone, S R; Llewellyn-Jones, C; Keogan, M T; Wang, Z M; Rubin, H; Carrell, R W; Stockley, R A

    1995-10-06

    Neutrophil chemotaxis plays an important role in the inflammatory response and when excessive or persistent may augment tissue damage. The effects of inhibitors indicated the involvement of one or more serine proteinases in human neutrophil migration and shape change in response to a chemoattractant. Monospecific antibodies, chloromethylketone inhibitors, and reactive-site mutants of alpha 1-antitrypsin and alpha 1-antichymotrypsin were used to probe the specificity of the proteinases involved in chemotaxis. Antibodies specific for cathepsin G inhibited chemotaxis. Moreover, rapid inhibitors of cathepsin G and alpha-chymotrypsin suppressed neutrophil chemotaxis to the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and zymosan-activated serum in multiple blind well assays and to fMLP in migration assays under agarose. The concentrations of antichymotrypsin mutants that reduced chemotaxis by 50% would inactivate free cathepsin G with a half-life of 1.5-3 s, whereas the concentrations of chloromethylketones required to produce a similar inhibition of chemotaxis would inactivate cathepsin G with a half-life of 345 s. These data suggest different modes of action for these two classes of inhibitors. Indeed the chloromethylketone inhibitors of cathepsin G (Z-Gly-Leu-Phe-CMK) and to a lesser extent of chymotrypsin (Cbz-Gly-Gly-Phe-CMK) mediated their effect by preventing a shape change in the purified neutrophils exposed to fMLP. Antichymotrypsin did not affect shape change in response to fMLP even at concentrations that were able to reduce neutrophil chemotaxis by 50%. These results support the involvement of cell surface proteinases in the control of cell migration and show that antichymotrypsin and chloromethylketones have differing modes of action. This opens the possibility for the rational design of anti-inflammatory agents targeted at neutrophil membrane enzymes.

  14. Ultrasonic reduction of excess sludge from the activated sludge system

    International Nuclear Information System (INIS)

    Zhang Guangming; Zhang Panyue; Yang Jinmei; Chen Yanming

    2007-01-01

    Sludge treatment has long become the most challenging problem in wastewater treatment plants. Previous studies showed that ozone or chlorine effectively liquefies sludge into substrates for bio-degradation in the aeration tank, and thus reduces the excess sludge. This paper employs ultrasound to reduce the excess sludge from the sequential batch reactor (SBR) system. Partial sludge was disintegrated into dissolved substrates by ultrasound in an external sono-tank and was then returned to the SBR for bio-degradation. The results showed that ultrasound (25 kHz) effectively liquefied the sludge. The most effective conditions for sludge reduction were as following: sludge sonication ratio of 3/14, ultrasound intensity of 120 kW/kgDS, and sonication duration of 15 min. The amount of excess sludge was reduced by 91.1% to 17.8 mg/(L d); the organic content and settleability of sludge in the SBR were not impacted. The chemical oxygen demand (COD) removal efficiency was 81.1%, the total nitrogen (TN) removal efficiency was 17-66%, and high phosphorus concentration in the effluent was observed

  15. Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steriodal anti-inflammatory drugs: a nested case-control study

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; Fernandes, Robert W.; van der Palen, Jacobus Adrianus Maria; van Roon, Eric N.; van de Laar, Mart A F J

    2007-01-01

    Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven.

  16. Predictors of excessive use of social media and excessive online gaming in Czech teenagers.

    Science.gov (United States)

    Spilková, Jana; Chomynová, Pavla; Csémy, Ladislav

    2017-12-01

    Background and aims Young people's involvement in online gaming and the use of social media are increasing rapidly, resulting in a high number of excessive Internet users in recent years. The objective of this paper is to analyze the situation of excessive Internet use among adolescents in the Czech Republic and to reveal determinants of excessive use of social media and excessive online gaming. Methods Data from secondary school students (N = 4,887) were collected within the 2015 European School Survey Project on Alcohol and Other Drugs. Logistic regression models were constructed to describe the individual and familial discriminative factors and the impact of the health risk behavior of (a) excessive users of social media and (b) excessive players of online games. Results The models confirmed important gender-specific distinctions - while girls are more prone to online communication and social media use, online gaming is far more prevalent among boys. The analysis did not indicate an influence of family composition on both the excessive use of social media and on excessive online gaming, and only marginal effects for the type of school attended. We found a connection between the excessive use of social media and binge drinking and an inverse relation between excessive online gaming and daily smoking. Discussion and conclusion The non-existence of significant associations between family environment and excessive Internet use confirmed the general, widespread of this phenomenon across the social and economic strata of the teenage population, indicating a need for further studies on the topic.

  17. Relative contributions of norepinephrine and serotonin transporters to antinociceptive synergy between monoamine reuptake inhibitors and morphine in the rat formalin model.

    Directory of Open Access Journals (Sweden)

    Fei Shen

    -mediated antinociceptive synergy; yet, excess serotonin, acting via 5-HT3 receptors, may reduce the potential for synergistic interactions. Thus, in the rat formalin model, the balance between norepinephrine and serotonin transporter inhibition influences the degree of antinociceptive synergy observed between monoamine reuptake inhibitors and morphine.

  18. Excess Entropy Production in Quantum System: Quantum Master Equation Approach

    Science.gov (United States)

    Nakajima, Satoshi; Tokura, Yasuhiro

    2017-12-01

    For open systems described by the quantum master equation (QME), we investigate the excess entropy production under quasistatic operations between nonequilibrium steady states. The average entropy production is composed of the time integral of the instantaneous steady entropy production rate and the excess entropy production. We propose to define average entropy production rate using the average energy and particle currents, which are calculated by using the full counting statistics with QME. The excess entropy production is given by a line integral in the control parameter space and its integrand is called the Berry-Sinitsyn-Nemenman (BSN) vector. In the weakly nonequilibrium regime, we show that BSN vector is described by ln \\breve{ρ }_0 and ρ _0 where ρ _0 is the instantaneous steady state of the QME and \\breve{ρ }_0 is that of the QME which is given by reversing the sign of the Lamb shift term. If the system Hamiltonian is non-degenerate or the Lamb shift term is negligible, the excess entropy production approximately reduces to the difference between the von Neumann entropies of the system. Additionally, we point out that the expression of the entropy production obtained in the classical Markov jump process is different from our result and show that these are approximately equivalent only in the weakly nonequilibrium regime.

  19. Atomic absorption photometry of excess Zn in ZnO

    Energy Technology Data Exchange (ETDEWEB)

    Lott, K.; Shinkarenko, S.; Tuern, L. [Department of Materials Science, Tallinn University of Technology, Ehitajate tee 5, 19086 Tallinn (Estonia); Kirsanova, T.; Grebennik, A.; Vishnjakov, A. [Department of Physical Chemistry, D. Mendelejev University of Chemical Technology of Russia, Miusskaya Sq. 9, 125047 Moscow (Russian Federation)

    2005-02-01

    Zn excess in ZnO is built up automatically at high temperatures. Excess Zn in hydrothermally grown ZnO single crystals were investigated by the atomic absorption photometry (AAP) method. To determine the excess zinc in ZnO samples, the AAP of zinc vapour was used in the conditions of solid-vapour equilibrium. Zn AAP allowed to eliminate excess Zn connected differentially in ZnO samples. To fix Zn non-stoichiometry, all the ZnO samples tested were previously heat treated at temperature interval from 850 to 900 C and at fixed Zn vapour pressures from 0.1 to 0.9 of saturated zinc vapour pressure at given treatment temperature. The analysis of temperature dependence of zinc vapour pressure indicated that the impurity metals take active role in the determination of non-stoichiometric zinc. The impurities Mn, Fe, Co, Ni and Cu form oxides which will reduce during annealing in Zn vapor up to metals form. During AAP measurement in optical cuvette, these metals react with ZnO and give additional Zn vapor pressure. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  20. Explaining CMS lepton excesses with supersymmetry

    CERN Multimedia

    CERN. Geneva; Prof. Allanach, Benjamin

    2014-01-01

    1) Kostas Theofilatos will give an introduction to CMS result 2) Ben Allanach: Several CMS analyses involving di-leptons have recently reported small 2.4-2.8 sigma local excesses: nothing to get too excited about, but worth keeping an eye on nonetheless. In particular, a search in the $lljj p_T$(miss) channel, a search for $W_R$ in the $lljj$ channel and a di-leptoquark search in the $lljj$ channel and $ljj p_T$(miss) channel have all yielded small excesses. We interpret the first excess in the MSSM, showing that the interpretation is viable in terms of other constraints, despite only having squark masses of around 1 TeV. We can explain the last three excesses with a single R-parity violating coupling that predicts a non-zero contribution to the neutrinoless double beta decay rate.

  1. The High Price of Excessive Alcohol Consumption

    Centers for Disease Control (CDC) Podcasts

    This podcast is based on the October 2011 release of a report estimating the economic cost of excessive drinking. Excessive alcohol consumption cost the U. S. $223.5 billion in 2006, or about $1.90 per drink. Over three-quarters (76%) of these costs were due to binge drinking, defined as consuming 4 or more alcoholic beverages per occasion for women or 5 or more drinks per occasion for men.

  2. Romanian welfare state between excess and failure

    Directory of Open Access Journals (Sweden)

    Cristina Ciuraru-Andrica

    2012-12-01

    Full Text Available Timely or not, our issue can bring back to life some prolific discussions, sometimes diametrical. We strike the social assistance, where, at this moment, is still uncertain if, once unleashed the excess, the failure will come inevitably or there is a “Salvation Ark”. However, the difference between the excess and the failure of the welfare state is almost intangible, the reason of his potential failure being actually the abuses made until the start of depression.

  3. Brazilian air traffic controllers exhibit excessive sleepiness.

    Science.gov (United States)

    Ribas, Valdenilson Ribeiro; de Almeida, Cláudia Ângela Vilela; Martins, Hugo André de Lima; Alves, Carlos Frederico de Oliveira; Alves, Marcos José Pinheiro Cândido; Carneiro, Severino Marcos de Oliveira; Ribas, Valéria Ribeiro; de Vasconcelos, Carlos Augusto Carvalho; Sougey, Everton Botelho; de Castro, Raul Manhães

    2011-01-01

    Excessive sleepiness (ES) is an increased tendency to initiate involuntary sleep for naps at inappropriate times. The objective of this study was to assess ES in air traffic controllers (ATCo). 45 flight protection professionals were evaluated, comprising 30 ATCo, subdivided into ATCo with ten or more years in the profession (ATCo≥10, n=15) and ATCo with less than ten years in the profession (ATCoair traffic controllers exhibit excessive sleepiness.

  4. Discovery of natural mouse serum derived HIV-1 entry inhibitor(s).

    Science.gov (United States)

    Wei, M; Chen, Y; Xi, J; Ru, S; Ji, M; Zhang, D; Fang, Q; Tang, B

    Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s). Our findings provide important information about novel natural HIV entry inhibitors in mouse serum.

  5. Tissue factor pathway inhibitor in paediatric patients with nephrotic ...

    African Journals Online (AJOL)

    elevated TFPI blood levels could therefore be accounted for by excessive endothelial release of this inhibitor .... that diastolic blood pressure was higher in the proteinuria group than in either the remission or the control .... dilated veins around the umbilicus, renal biopsy findings of fibrin deposition inside the glomeruli and in ...

  6. New vector bosons and the diphoton excess

    Directory of Open Access Journals (Sweden)

    Jorge de Blas

    2016-08-01

    Full Text Available We consider the possibility that the recently observed diphoton excess at ∼750 GeV can be explained by the decay of a scalar particle (φ to photons. If the scalar is the remnant of a symmetry-breaking sector of some new gauge symmetry, its coupling to photons can be generated by loops of the charged massive vectors of the broken symmetry. If these new W′ vector bosons carry color, they can also generate an effective coupling to gluons. In this case the diphoton excess could be entirely explained in a simplified model containing just φ and W′. On the other hand, if W′ does not carry color, we show that, provided additional colored particles exist to generate the required φ to gluon coupling, the diphoton excess could be explained by the same W′ commonly invoked to explain the diboson excess at ∼2 TeV. We also explore possible connections between the diphoton and diboson excesses with the anomalous tt¯ forward–backward asymmetry.

  7. The US program for disposition of excess weapons plutonium

    International Nuclear Information System (INIS)

    Bunn, M.

    1997-01-01

    After an exhaustive interagency study, the United States has declared that 52.7 tons of plutonium, over half of its stockpile, is excess to its military needs, and has decided to pursue a dual-track approach to eliminating this excess stockpile, burning some of it once-through as power-reactor fuel, and immobilizing the remainder with intensely radioactive fission products. This effort represents a significant step toward increasing the irreversibility of nuclear arms reductions and reducing the risk of nuclear proliferation. The United States expects to complete disposition of this material over the next 2-3 decades, at a net discounted present cost of approximately $1.5 billion. Intemational verification and stringent security and accounting for the material are planned for the entire program

  8. Operation of transition-edge sensors with excess thermal noise

    International Nuclear Information System (INIS)

    Maasilta, I J; Kinnunen, K M; Nuottajaervi, A K; Leppaeniemi, J; Luukanen, A

    2006-01-01

    The superconducting transition-edge sensor (TES) is currently one of the most attractive choices for ultra-high resolution calorimetry in the keV x-ray band, and is being considered for future ESA and NASA missions. We have performed a study on the noise characteristics of Au/Ti bilayer TESs, at operating temperatures around ∼100 mK, with the SQUID readout at 1.5 K. Experimental results indicate that without modifications the back-action noise from the SQUID chip degrades the noise characteristics significantly. We present a simple and effective solution to the problem: by installing an extra shunt resistor which absorbs the excess radiation from the SQUID input, we have reduced the excess thermal (photon) noise power down by approximately a factor of five, allowing high resolution operation of the sensors

  9. Limiting law excess sum rule for polyelectrolytes.

    Science.gov (United States)

    Landy, Jonathan; Lee, YongJin; Jho, YongSeok

    2013-11-01

    We revisit the mean-field limiting law screening excess sum rule that holds for rodlike polyelectrolytes. We present an efficient derivation of this law that clarifies its region of applicability: The law holds in the limit of small polymer radius, measured relative to the Debye screening length. From the limiting law, we determine the individual ion excess values for single-salt electrolytes. We also consider the mean-field excess sum away from the limiting region, and we relate this quantity to the osmotic pressure of a dilute polyelectrolyte solution. Finally, we consider numerical simulations of many-body polymer-electrolyte solutions. We conclude that the limiting law often accurately describes the screening of physical charged polymers of interest, such as extended DNA.

  10. Explaining excess morbidity amongst homeless shelter users

    DEFF Research Database (Denmark)

    Benjaminsen, Lars; Birkelund, Jesper Fels

    2018-01-01

    AIMS: This article analyses excess morbidity amongst homeless shelter users compared to the general Danish population. The study provides an extensive control for confounding and investigates to what extent excess morbidity is explained by homelessness or other risk factors. METHODS: Data set...... includes administrative micro-data for 4,068,926 Danes who were 23 years or older on 1 January 2007. Nationwide data on shelter use identified 14,730 individuals as shelter users from 2002 to 2006. Somatic diseases were measured from 2007 to 2011 through diagnosis data from hospital discharges. The risk...... of somatic diseases amongst shelter users was analysed through a multivariate model that decomposed the total effect into a direct effect and indirect effects mediated by other risk factors. RESULTS: The excess morbidity associated with shelter use is substantially lower than in studies that did not include...

  11. The High Price of Excessive Alcohol Consumption

    Centers for Disease Control (CDC) Podcasts

    2011-10-17

    This podcast is based on the October 2011 release of a report estimating the economic cost of excessive drinking. Excessive alcohol consumption cost the U. S. $223.5 billion in 2006, or about $1.90 per drink. Over three-quarters (76%) of these costs were due to binge drinking, defined as consuming 4 or more alcoholic beverages per occasion for women or 5 or more drinks per occasion for men.  Created: 10/17/2011 by National Center for Chronic Disease Prevention and Health Promotion.   Date Released: 10/17/2011.

  12. Excess Sodium Tetraphenylborate and Intermediates Decomposition Studies

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, M.J.

    1998-12-07

    The stability of excess amounts of sodium tetraphenylborate (NaTPB) in the In-Tank Precipitation (ITP) facility depends on a number of variables. Concentration of palladium, initial benzene, and sodium ion as well as temperature provide the best opportunities for controlling the decomposition rate. This study examined the influence of these four variable on the reactivity of palladium-catalyzed sodium tetraphenylborate decomposition. Also, single effects tests investigated the reactivity of simulants with continuous stirring and nitrogen ventilation, with very high benzene concentrations, under washed sodium concentrations, with very high palladium concentrations, and with minimal quantities of excess NaTPB.

  13. On the excess energy of nonequilibrium plasma

    International Nuclear Information System (INIS)

    Timofeev, A. V.

    2012-01-01

    The energy that can be released in plasma due to the onset of instability (the excess plasma energy) is estimated. Three potentially unstable plasma states are considered, namely, plasma with an anisotropic Maxwellian velocity distribution of plasma particles, plasma with a two-beam velocity distribution, and an inhomogeneous plasma in a magnetic field with a local Maxwellian velocity distribution. The excess energy can serve as a measure of the degree to which plasma is nonequilibrium. In particular, this quantity can be used to compare plasmas in different nonequilibrium states.

  14. 26 CFR 54.4981A-1T - Tax on excess distributions and excess accumulations (temporary).

    Science.gov (United States)

    2010-04-01

    ... Revenue Code of 1986, as added by section 1133 of the Tax Reform Act of 1986 (Pub. L. 99-514) (TRA '86...) Determine the value of the individual's adjusted account balance on the next valuation date by adding (or... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Tax on excess distributions and excess...

  15. Analytical estimation of control rod shadowing effect for excess reactivity measurement of HTTR

    International Nuclear Information System (INIS)

    Nakano, Masaaki; Fujimoto, Nozomu; Yamashita, Kiyonobu

    1999-01-01

    The fuel addition method is generally used for the excess reactivity measurement of the initial core. The control rod shadowing effect for the excess reactivity measurement has been estimated analytically for High Temperature Engineering Test Reactor (HTTR). 3-dimensional whole core analyses were carried out. The movements of control rods in measurements were simulated in the calculation. It was made clear that the value of excess reactivity strongly depend on combinations of measuring control rods and compensating control rods. The differences in excess reactivity between combinations come from the control rod shadowing effect. The shadowing effect is reduced by the use of plural number of measuring and compensating control rods to prevent deep insertion of them into the core. The measured excess reactivity in the experiments is, however, smaller than the estimated value with shadowing effect. (author)

  16. Excessive daytime sleepiness among depressed patients | Mume ...

    African Journals Online (AJOL)

    Background: Excessive daytime sleepiness (EDS) has been reported among depressed patients in many populations. Many depressed patients seek medical attention partly to deal with EDS, but this sleep disorder is often overlooked in clinical practice. Objectives: The objectives of this study were to determine the ...

  17. Excessive daytime sleepiness, nocturnal sleep duration and ...

    African Journals Online (AJOL)

    Background and objectives. Short nocturnal sleep duration resulting in sleep debt may be a cause of excessive daytime sleepiness (EDS). Severity of depression (psychopathology) has been found to be directly related to EDS. There is an association between sleep duration and mental health, so there may therefore be an ...

  18. Excess Sodium Tetraphenylborate and Intermediates Decomposition Studies

    International Nuclear Information System (INIS)

    Barnes, M.J.; Peterson, R.A.

    1998-04-01

    The stability of excess amounts of sodium tetraphenylborate (NaTPB) in the In-Tank Precipitation (ITP) facility depends on a number of variables. Concentration of palladium, initial benzene, and sodium ion as well as temperature provide the best opportunities for controlling the decomposition rate. This study examined the influence of these four variables on the reactivity of palladium-catalyzed sodium tetraphenylborate decomposition. Also, single effects tests investigated the reactivity of simulants with continuous stirring and nitrogen ventilation, with very high benzene concentrations, under washed sodium concentrations, with very high palladium concentrations, and with minimal quantities of excess NaTPB. These tests showed the following.The testing demonstrates that current facility configuration does not provide assured safety of operations relative to the hazards of benzene (in particular to maintain the tank headspace below 60 percent of the lower flammability limit (lfl) for benzene generation rates of greater than 7 mg/(L.h)) from possible accelerated reaction of excess NaTPB. Current maximal operating temperatures of 40 degrees C and the lack of protection against palladium entering Tank 48H provide insufficient protection against the onset of the reaction. Similarly, control of the amount of excess NaTPB, purification of the organic, or limiting the benzene content of the slurry (via stirring) and ionic strength of the waste mixture prove inadequate to assure safe operation

  19. Excess Sodium Tetraphenylborate and Intermediates Decomposition Studies

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, M.J. [Westinghouse Savannah River Company, AIKEN, SC (United States); Peterson , R.A.

    1998-04-01

    The stability of excess amounts of sodium tetraphenylborate (NaTPB) in the In-Tank Precipitation (ITP) facility depends on a number of variables. Concentration of palladium, initial benzene, and sodium ion as well as temperature provide the best opportunities for controlling the decomposition rate. This study examined the influence of these four variables on the reactivity of palladium-catalyzed sodium tetraphenylborate decomposition. Also, single effects tests investigated the reactivity of simulants with continuous stirring and nitrogen ventilation, with very high benzene concentrations, under washed sodium concentrations, with very high palladium concentrations, and with minimal quantities of excess NaTPB. These tests showed the following.The testing demonstrates that current facility configuration does not provide assured safety of operations relative to the hazards of benzene (in particular to maintain the tank headspace below 60 percent of the lower flammability limit (lfl) for benzene generation rates of greater than 7 mg/(L.h)) from possible accelerated reaction of excess NaTPB. Current maximal operating temperatures of 40 degrees C and the lack of protection against palladium entering Tank 48H provide insufficient protection against the onset of the reaction. Similarly, control of the amount of excess NaTPB, purification of the organic, or limiting the benzene content of the slurry (via stirring) and ionic strength of the waste mixture prove inadequate to assure safe operation.

  20. Can Excess Bilirubin Levels Cause Learning Difficulties?

    Science.gov (United States)

    Pretorius, E.; Naude, H.; Becker, P. J.

    2002-01-01

    Examined learning problems in South African sample of 7- to 14-year-olds whose mothers reported excessively high infant bilirubin shortly after the child's birth. Found that this sample had lowered verbal ability with the majority also showing impaired short-term and long-term memory. Findings suggested that impaired formation of astrocytes…

  1. Excessive daytime sleepiness among depressed patients | Mume ...

    African Journals Online (AJOL)

    Abstract. Background: Excessive daytime sleepiness (EDS) has been reported among depressed patients in many populations. Many depressed patients seek medical attention partly to deal with EDS, but this sleep disorder is often overlooked in clinical practice. Objectives: The objectives of this study were to determine the ...

  2. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2013-10-01

    NUMBER Phospholipids as Biomarkers for Excessive Alcohol Use 5b. GRANT NUMBER W81XWH-12-1-0497 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...suspected of alcohol abuse. Toxicol Lett, 151(1), 235-241. Graham, D. P., Cardon , A. L., & Uhl, G. R. (2008). An update on substance use and treatment

  3. Excessive infant crying: Definitions determine risk groups

    NARCIS (Netherlands)

    Reijneveld, S.A.; Brugman, E.; Hirasing, R.A.

    2002-01-01

    We assessed risk groups for excessive infant crying using 10 published definitions, in 3179 children aged 1-6 months (response: 96.5%). Risk groups regarding parental employment, living area, lifestyle, and obstetric history varied by definition. This may explain the existence of conflicting

  4. Excessive prices as abuse of dominance?

    DEFF Research Database (Denmark)

    la Cour, Lisbeth; Møllgaard, Peter

    2007-01-01

    firm abused its position by charging excessive prices. We also test whether tightening of the Danish competition act has altered the pricing behaviour on the market. We discuss our results in the light of a Danish competition case against the dominant cement producer that was abandoned by the authority...

  5. Excessive oral intake caffeine altered cerebral cortex ...

    African Journals Online (AJOL)

    Caffeine is commonly consumed in an effort to enhance speed in performance and wakefulness. However, little is known about the deleterious effects it can produce on the brain, this study aimed at determining the extents of effects and damage that can be caused by excessive consumption of caffeine on the cerebral cortex ...

  6. 43 CFR 426.12 - Excess land.

    Science.gov (United States)

    2010-10-01

    ... advertise the sale of the property in farm journals and in newspapers within the county in which the land...; (ii) A recordable contract is amended to remove excess land when the landowner's entitlement increases... eligible buyer at a price and on terms approved by Reclamation; (C) The sale from the previous landowner is...

  7. SGLT2 Inhibitors and the Diabetic Kidney.

    Science.gov (United States)

    Fioretto, Paola; Zambon, Alberto; Rossato, Marco; Busetto, Luca; Vettor, Roberto

    2016-08-01

    Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether

  8. Conventional physics can explain cold fusion excess heat

    Science.gov (United States)

    Chubb, S. R.

    In 1989, when Fleischmann, Pons and Hawkins (FP), claimed they had created room temperature, nuclear fusion in a solid, a firestorm of controversy erupted. Beginning in 1991, the Office of Naval Research began a decade-long study of the FP excess heat effect. This effort documented the fact that the excess heat that FP observed is the result of a form of nuclear fusion that can occur in solids at reduced temperature, dynamically, through a deuteron (d)+d□4He reaction, without high-energy particles or □ rays. A key reason this fact has not been accepted is the lack of a cogent argument, based on fundamental physical ideas, justifying it. In the paper, this question is re-examined, based on a generalization of conventional energy band theory that applies to finite, periodic solids, in which d's are allowed to occupy wave-like, ion band states, similar to the kinds of states that electrons occupy in ordinary metals. Prior to being experimentally observed, the Ion Band State Theory (IBST) of cold fusion predicted a potential d+d□4He reaction, without high energy particles, would explain the excess heat, the 4He would be found in an unexpected place (outside heat-producing electrodes), and high-loading, x□1, in PdDx, would be required.

  9. Novel 11β-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV.

    Directory of Open Access Journals (Sweden)

    Stéphanie M Boudon

    Full Text Available Activity and selectivity assessment of new bi-aryl amide 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1 inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11β-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11β-HSD1 over 11β-HSD2, 17β-HSD1 and 17β-HSD2. These inhibitors also potently inhibited 11β-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme and in intact primary human keratinocytes expressing endogenous 11β-HSD1. Moreover, compounds 2b, 3e and 12e were tested for their activity in human skin biopsies. They were able to prevent, at least in part, both the cortisone- and the UV-mediated decreases in collagen content. Thus, inhibition of 11β-HSD1 by these compounds can be further investigated to delay or prevent UV-mediated skin damage and skin aging.

  10. Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4-phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety.

    Science.gov (United States)

    Ogino, Masaki; Nakada, Yoshihisa; Negoro, Nobuyuki; Itokawa, Shigekazu; Nishimura, Satoshi; Sanada, Tsukasa; Satomi, Tomoko; Kita, Shunbun; Kubo, Kazuki; Marui, Shogo

    2011-01-01

    As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti-atherosclerotic agents, we recently reported the discovery of the (4-phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl]-6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs.

  11. Excessive Gambling and Online Gambling Communities.

    Science.gov (United States)

    Sirola, Anu; Kaakinen, Markus; Oksanen, Atte

    2018-04-05

    The Internet provides an accessible context for online gambling and gambling-related online communities, such as discussion forums for gamblers. These communities may be particularly attractive to young gamblers who are active Internet users. The aim of this study was to examine the use of gambling-related online communities and their relevance to excessive gambling among 15-25-year-old Finnish Internet users (N = 1200). Excessive gambling was assessed by using the South Oaks Gambling Screen. Respondents were asked in a survey about their use of various kinds of gambling-related online communities, and sociodemographic and behavioral factors were adjusted. The results of the study revealed that over half (54.33%) of respondents who had visited gambling-related online communities were either at-risk gamblers or probable pathological gamblers. Discussion in these communities was mainly based on sharing gambling tips and experiences, and very few respondents said that they related to gambling problems and recovery. In three different regression models, visiting gambling-related online communities was a significant predictor for excessive gambling (with 95% confidence level) even after adjusting confounding factors. The association of visiting such sites was even stronger among probable pathological gamblers than among at-risk gamblers. Health professionals working with young people should be aware of the role of online communities in terms of development and persistence of excessive gambling. Monitoring the use of online gambling communities as well as utilizing recovery-oriented support both offline and online would be important in preventing further problems. Gambling platforms should also include warnings about excessive gambling and provide links to helpful sources.

  12. Technologies for utilization of industrial excess heat: Potentials for energy recovery and CO2 emission reduction

    International Nuclear Information System (INIS)

    Broberg Viklund, Sarah; Johansson, Maria T.

    2014-01-01

    Highlights: • Technologies for recovery and use of industrial excess heat were investigated. • Heat harvesting, heat storage, heat utilization, and heat conversion technologies. • Heat recovery potential for Gävleborg County in Sweden was calculated. • Effects on global CO 2 emissions were calculated for future energy market scenarios. - Abstract: Industrial excess heat is a large untapped resource, for which there is potential for external use, which would create benefits for industry and society. Use of excess heat can provide a way to reduce the use of primary energy and to contribute to global CO 2 mitigation. The aim of this paper is to present different measures for the recovery and utilization of industrial excess heat and to investigate how the development of the future energy market can affect which heat utilization measure would contribute the most to global CO 2 emissions mitigation. Excess heat recovery is put into a context by applying some of the excess heat recovery measures to the untapped excess heat potential in Gävleborg County in Sweden. Two different cases for excess heat recovery are studied: heat delivery to a district heating system and heat-driven electricity generation. To investigate the impact of excess heat recovery on global CO 2 emissions, six consistent future energy market scenarios were used. Approximately 0.8 TWh/year of industrial excess heat in Gävleborg County is not used today. The results show that with the proposed recovery measures approximately 91 GWh/year of district heating, or 25 GWh/year of electricity, could be supplied from this heat. Electricity generation would result in reduced global CO 2 emissions in all of the analyzed scenarios, while heat delivery to a DH system based on combined heat and power production from biomass would result in increased global CO 2 emissions when the CO 2 emission charge is low

  13. Histone Deacetylase Inhibitors as Anticancer Drugs.

    Science.gov (United States)

    Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

    2017-07-01

    Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  14. Histone Deacetylase Inhibitors as Anticancer Drugs

    Directory of Open Access Journals (Sweden)

    Tomas Eckschlager

    2017-07-01

    Full Text Available Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC and histone acetyltransferases (HAT. HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

  15. SEARCH OF NEW SYNTHETIC INHIBITORS OF TYROSINASE

    Directory of Open Access Journals (Sweden)

    Yu. Shesterenko

    2017-11-01

    Full Text Available Melanin pigmentation of skin plays the most important role in the protection of organism against UV-irradiation, but the excessive accumulation of melanin brings to toxic melanodermia, melasma, lentigo and other skin lesions. Tyrosinase is the key enzyme of skin melanin pigment biosynthesis. In spite of certain progress in investigation of natural and synthetic tyrosinase inhibitors, actuality of such studies is of a high level, because the existing inhibitors are in some cases unstable, expensive, toxic, requires complex methods of synthesis or isolation from natural sources. The aim of the work is screening of new tyrosinase inhibitors, using the enzyme, isolated from Agaricus bisporus. Tyrosinase was isolated from Agaricus bisporus mushrooms by a modified method. It was found, that the introduction of polyethylene glycol 4000 in the extraction process promotes 3-fold reduction of polyphenol content, which leads to increase purity of enzyme with an increase in its activity by 25%. A search for new tyrosinase inhibitors among a wide range of compounds, including derivatives of 3-chloro-1,4-naphthoquinone, isatin, 3-hydroxy-2-naphthoic acid, etc was conducted. The studied substances did not displayed inhibitory effect at concentration of 0,1-0,5 mmol/dm3.

  16. Excessive users of violent video games do not show emotional desensitization: an fMRI study.

    Science.gov (United States)

    Szycik, Gregor R; Mohammadi, Bahram; Hake, Maria; Kneer, Jonas; Samii, Amir; Münte, Thomas F; Te Wildt, Bert T

    2017-06-01

    Playing violent video games have been linked to long-term emotional desensitization. We hypothesized that desensitization effects in excessive users of violent video games should lead to decreased brain activations to highly salient emotional pictures in emotional sensitivity brain regions. Twenty-eight male adult subjects showing excessive long-term use of violent video games and age and education matched control participants were examined in two experiments using standardized emotional pictures of positive, negative and neutral valence. No group differences were revealed even at reduced statistical thresholds which speaks against desensitization of emotion sensitive brain regions as a result of excessive use of violent video games.

  17. ILLUSION OF EXCESSIVE CONSUMPTION AND ITS EFFECTS

    Directory of Open Access Journals (Sweden)

    MUNGIU-PUPĂZAN MARIANA CLAUDIA

    2015-12-01

    Full Text Available The aim is to explore, explain and describe this phenomenon to a better understanding of it and also the relationship between advertising and the consumer society members. This paper aims to present an analysis of excessive and unsustainable consumption, the evolution of a phenomenon, and the ability to find a way to combat. Unfortunately, studies show that this tendency to accumulate more than we need to consume excess means that almost all civilizations fined and placed dogmatic among the values that children learn early in life. This has been perpetuated since the time when the goods or products does not get so easy as today. Anti-consumerism has emerged in response to this economic system, not on the long term. We are witnessing the last two decades to establish a new phase of consumer capitalism: society hiperconsumtion.

  18. Country Fundamentals and Currency Excess Returns

    Directory of Open Access Journals (Sweden)

    Daehwan Kim

    2014-06-01

    Full Text Available We examine whether country fundamentals help explain the cross-section of currency excess returns. For this purpose, we consider fundamental variables such as default risk, foreign exchange rate regime, capital control as well as interest rate in the multi-factor model framework. Our empirical results show that fundamental factors explain a large part of the cross-section of currency excess returns. The zero-intercept restriction of the factor model is not rejected for most currencies. They also reveal that our factor model with country fundamentals performs better than a factor model with usual investment-style factors. Our main empirical results are based on 2001-2010 balanced panel data of 19 major currencies. This paper may fill the gap between country fundamentals and practitioners' strategies on currency investment.

  19. Excess plutonium disposition: The deep borehole option

    International Nuclear Information System (INIS)

    Ferguson, K.L.

    1994-01-01

    This report reviews the current status of technologies required for the disposition of plutonium in Very Deep Holes (VDH). It is in response to a recent National Academy of Sciences (NAS) report which addressed the management of excess weapons plutonium and recommended three approaches to the ultimate disposition of excess plutonium: (1) fabrication and use as a fuel in existing or modified reactors in a once-through cycle, (2) vitrification with high-level radioactive waste for repository disposition, (3) burial in deep boreholes. As indicated in the NAS report, substantial effort would be required to address the broad range of issues related to deep bore-hole emplacement. Subjects reviewed in this report include geology and hydrology, design and engineering, safety and licensing, policy decisions that can impact the viability of the concept, and applicable international programs. Key technical areas that would require attention should decisions be made to further develop the borehole emplacement option are identified

  20. Subdwarf ultraviolet excesses and metal abundances

    International Nuclear Information System (INIS)

    Carney, B.W.

    1979-01-01

    The relation between stellar ultraviolet excesses and abundances is reexamined with the aid of new data, and an investigation is made of the accuracy of previous abundance analyses. A high-resolution echellogram of the subdwarf HD 201891 is analyzed to illustrate some of the problems. Generally, the earliest and latest analytical techniques yield consistent results for dwarfs. New UBV data yield normalized ultraviolet excesses, delta (U-B)/sub 0.6/, which are compared to abundances to produce a graphical relation that may be used to estimate [Fe/H] to +- 0.2 dex, given UBV colors accurate to +- 0.01 mag. The relation suggests a possible discontinuity between the halo and old-disk stars

  1. Neurological manifestations of excessive alcohol consumption.

    Science.gov (United States)

    Planas-Ballvé, Anna; Grau-López, Laia; Morillas, Rosa María; Planas, Ramón

    2017-12-01

    This article reviews the different acute and chronic neurological manifestations of excessive alcohol consumption that affect the central or peripheral nervous system. Several mechanisms can be implicated depending on the disorder, ranging from nutritional factors, alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition and early treatment of these manifestations is essential given their association with high morbidity and significantly increased mortality. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  2. Equine goiter associated with excess dietary iodine.

    Science.gov (United States)

    Eroksuz, H; Eroksuz, Y; Ozer, H; Ceribasi, A O; Yaman, I; Ilhan, N

    2004-06-01

    Naturally occurring goiter cases are described in 2 newborn Arabian foals whose mares were supplemented with excess iodine during the final 24 w of the pregnancy. Six nursing foals and 2 mares were also affected clinically with thyroid hypertrophy. At least 12 times the maximum tolerable level of iodine supplementation was given, as the daily iodine intake for each mare was 299 mg. The prevalence of goiter cases was 2 and 9% in the mares and foals, respectively.

  3. Contrast induced hyperthyroidism due to iodine excess

    OpenAIRE

    Mushtaq, Usman; Price, Timothy; Laddipeerla, Narsing; Townsend, Amanda; Broadbridge, Vy

    2009-01-01

    Iodine induced hyperthyroidism is a thyrotoxic condition caused by exposure to excessive iodine. Historically this type of hyperthyroidism has been described in areas of iodine deficiency. With advances in medicine, iodine induced hyperthyroidism has been observed following the use of drugs containing iodine—for example, amiodarone, and contrast agents used in radiological imaging. In elderly patients it is frequently difficult to diagnose and control contrast related hyperthyroidism, as most...

  4. Excessive current in wide superconducting films

    International Nuclear Information System (INIS)

    Volotskaya, V.G.; Sivakov, A.G.; Turutanov, O.G.

    1986-01-01

    The resistive state of a wide long film due to superconductivity destruction by current is studied. The voltage-independent excess current I 0 is observed on I-V curves at high transport currents. The two-dimensional image of the current-carrying sample obtained by laser scanning technique in this current range indicates that the whole film is in the resistive state. The current I 0 is measured as a function of magnetic field and SHF power

  5. Search for bright stars with infrared excess

    Energy Technology Data Exchange (ETDEWEB)

    Raharto, Moedji, E-mail: moedji@as.itb.ac.id [Astronomy Research Division, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132 (Indonesia)

    2014-03-24

    Bright stars, stars with visual magnitude smaller than 6.5, can be studied using small telescope. In general, if stars are assumed as black body radiator, then the color in infrared (IR) region is usually equal to zero. Infrared data from IRAS observations at 12 and 25μm (micron) with good flux quality are used to search for bright stars (from Bright Stars Catalogues) with infrared excess. In magnitude scale, stars with IR excess is defined as stars with IR color m{sub 12}−m{sub 25}>0; where m{sub 12}−m{sub 25} = −2.5log(F{sub 12}/F{sub 25})+1.56, where F{sub 12} and F{sub 25} are flux density in Jansky at 12 and 25μm, respectively. Stars with similar spectral type are expected to have similar color. The existence of infrared excess in the same spectral type indicates the existence of circum-stellar dust, the origin of which is probably due to the remnant of pre main-sequence evolution during star formation or post AGB evolution or due to physical process such as the rotation of those stars.

  6. Earnings Quality Measures and Excess Returns.

    Science.gov (United States)

    Perotti, Pietro; Wagenhofer, Alfred

    2014-06-01

    This paper examines how commonly used earnings quality measures fulfill a key objective of financial reporting, i.e., improving decision usefulness for investors. We propose a stock-price-based measure for assessing the quality of earnings quality measures. We predict that firms with higher earnings quality will be less mispriced than other firms. Mispricing is measured by the difference of the mean absolute excess returns of portfolios formed on high and low values of a measure. We examine persistence, predictability, two measures of smoothness, abnormal accruals, accruals quality, earnings response coefficient and value relevance. For a large sample of US non-financial firms over the period 1988-2007, we show that all measures except for smoothness are negatively associated with absolute excess returns, suggesting that smoothness is generally a favorable attribute of earnings. Accruals measures generate the largest spread in absolute excess returns, followed by smoothness and market-based measures. These results lend support to the widespread use of accruals measures as overall measures of earnings quality in the literature.

  7. An update on the LHC monojet excess

    Science.gov (United States)

    Asadi, Pouya; Buckley, Matthew R.; DiFranzo, Anthony; Monteux, Angelo; Shih, David

    2018-03-01

    In previous work, we identified an anomalous number of events in the LHC jets+MET searches characterized by low jet multiplicity and low-to-moderate transverse energy variables. Here, we update this analysis with results from a new ATLAS search in the monojet channel which also shows a consistent excess. As before, we find that this "monojet excess" is well-described by the resonant production of a heavy colored state decaying to a quark and a massive invisible particle. In the combined ATLAS and CMS data, we now find a local (global) preference of 3.3 σ (2.5 σ) for the new physics model over the Standard Model-only hypothesis. As the signal regions containing the excess are systematics-limited, we consider additional cuts to enhance the signal-to-background ratio. We show that binning finer in H T and requiring the jets to be more central can increase S/B by a factor of ˜1 .5.

  8. Internet addiction or excessive internet use.

    Science.gov (United States)

    Weinstein, Aviv; Lejoyeux, Michel

    2010-09-01

    Problematic Internet addiction or excessive Internet use is characterized by excessive or poorly controlled preoccupations, urges, or behaviors regarding computer use and Internet access that lead to impairment or distress. Currently, there is no recognition of internet addiction within the spectrum of addictive disorders and, therefore, no corresponding diagnosis. It has, however, been proposed for inclusion in the next version of the Diagnostic and Statistical Manual of Mental Disorder (DSM). To review the literature on Internet addiction over the topics of diagnosis, phenomenology, epidemiology, and treatment. Review of published literature between 2000-2009 in Medline and PubMed using the term "internet addiction. Surveys in the United States and Europe have indicated prevalence rate between 1.5% and 8.2%, although the diagnostic criteria and assessment questionnaires used for diagnosis vary between countries. Cross-sectional studies on samples of patients report high comorbidity of Internet addiction with psychiatric disorders, especially affective disorders (including depression), anxiety disorders (generalized anxiety disorder, social anxiety disorder), and attention deficit hyperactivity disorder (ADHD). Several factors are predictive of problematic Internet use, including personality traits, parenting and familial factors, alcohol use, and social anxiety. Although Internet-addicted individuals have difficulty suppressing their excessive online behaviors in real life, little is known about the patho-physiological and cognitive mechanisms responsible for Internet addiction. Due to the lack of methodologically adequate research, it is currently impossible to recommend any evidence-based treatment of Internet addiction.

  9. The Role of Androgen Excess in Metabolic Dysfunction in Women : Androgen Excess and Female Metabolic Dysfunction.

    Science.gov (United States)

    Escobar-Morreale, Héctor F

    2017-01-01

    Polycystic ovary syndrome (PCOS) is characterized by the association of androgen excess with chronic oligoovulation and/or polycystic ovarian morphology, yet metabolic disorders and classic and nonclassic cardiovascular risk factors cluster in these women from very early in life. This chapter focuses on the mechanisms underlying the association of PCOS with metabolic dysfunction, focusing on the role of androgen excess on the development of visceral adiposity and adipose tissue dysfunction.

  10. Eficacia del consejo médico para la reducción del consumo excesivo de alcohol: Metaanálisis de estudios españoles en atención primaria Effectiveness of medical advice for reducing excessive alcohol conssumption: Meta-analysis of Spanish studies in primary care

    Directory of Open Access Journals (Sweden)

    J. Ballesteros

    2003-04-01

    Full Text Available Introducción: Revisiones sistemáticas previas han apoyado la eficacia del consejo médico, como intervención breve, en el abordaje de bebedores excesivos detectados en la asistencia primaria. Sin embargo, estos resultados no pueden extrapolarse directamente a poblaciones que, como las mediterráneas, no están representadas en dichas revisiones. El objetivo de este estudio fue actualizar la evidencia sobre la eficacia de la intervención breve en consumidores excesivos de alcohol según estudios españoles. Métodos: Búsqueda de estudios en bases bibliográficas y consultas a expertos para localizar estudios no publicados. Se calcularon las estimaciones combinadas para dos variables de resultado, la reducción del consumo de alcohol y la disminución de la frecuencia de bebedores excesivos. Resultados: Dos de los 5 estudios localizados no estaban incluidos en una revisión previa. La eficacia de la intervención breve fue moderada para la disminución del consumo de alcohol (d = - 0,46; intervalo de confianza (IC del 95%, - 0,29 a - 0,63; p Introduction: Former systematic reviews have backed the efficacy of medical counselling, a form of brief intervention, on the treatment of excessive drinkers detected in primary care settings. Nevertheless, these results cannot be applied without criticism to Mediterranean populations which, so far, have not been represented in the aforementioned studies. The aim of the present study was to update the results on the efficacy of brief interventions in primary care by pooling Spanish studies. Methods: Studies were searched for by using appropriate databases and also by consulting to experts in the field to retrieve grey literature. Pooled estimations of effect sizes were calculated for two outcomes, the reduction in the amount of alcohol consumption and the decrease in the number of excessive drinkers. Results: Two over the 5 retrieved studies were not included in a former review. The effect size regarding

  11. Monoamine Oxidase Inhibitors (MAOIs)

    Science.gov (United States)

    ... health-medications/index.shtml. Accessed May 16, 2016. Hirsch M, et al. Monoamine oxidase inhibitors (MAOIs) for ... www.uptodate.com/home. Accessed May 16, 2016. Hirsch M, et al. Discontinuing antidepressant medications in adults. ...

  12. Swift recovery of Sphagnum nutrient concentrations after excess supply.

    Science.gov (United States)

    Limpens, Juul; Heijmans, Monique M P D

    2008-08-01

    Although numerous studies have addressed the effects of increased N deposition on nutrient-poor environments such as raised bogs, few studies have dealt with to what extent, and on what time-scale, reductions in atmospheric N supply would lead to recovery of the ecosystems in question. Since a considerable part of the negative effects of elevated N deposition on raised bogs can be related to an imbalance in tissue nutrient concentrations of the dominant peat-former Sphagnum, changes in Sphagnum nutrient concentration after excess N supply may be used as an early indicator of ecosystem response. This study focuses on the N and P concentrations of Sphagnum magellanicum and Sphagnum fallax before, during and after a factorial fertilization experiment with N and P in two small peatlands subject to a background bulk deposition of 2 g N m(-2) year(-1). Three years of adding N (4.0 g N m(-2) year(-1)) increased the N concentration, and adding P (0.3 g P m(-2) year(-1)) increased the P concentration in Sphagnum relative to the control treatment at both sites. Fifteen months after the nutrient additions had ceased, N concentrations were similar to the control whereas P concentrations, although strongly reduced, were still slightly elevated. The changes in the N and P concentrations were accompanied by changes in the distribution of nutrients over the capitulum and the stem and were congruent with changes in translocation. Adding N reduced the stem P concentration, whereas adding P reduced the stem N concentration in favor of the capitulum. Sphagnum nutrient concentrations quickly respond to reductions in excess nutrient supply, indicating that a management policy aimed at reducing atmospheric nutrient input to bogs can yield results within a few years.

  13. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  14. Does obfuscating excessive CEO pay work? The influence of remuneration report readability on say-on-pay votes

    NARCIS (Netherlands)

    Hooghiemstra, Reggy; Kuang, Yu Flora; Qin, Bo

    2017-01-01

    This paper assesses whether reducing ‘readability’ is an effective obfuscation strategy for influencing the level of shareholder say-on-pay voting dissent in firms with excessive CEO pay. Based on a sample of UK-listed firms, our results indicate that in cases of excessive CEO pay, a less readable

  15. Excessive sleep duration and quality of life.

    Science.gov (United States)

    Ohayon, Maurice M; Reynolds, Charles F; Dauvilliers, Yves

    2013-06-01

    Using population-based data, we document the comorbidities (medical, neurologic, and psychiatric) and consequences for daily functioning of excessive quantity of sleep (EQS), defined as a main sleep period or 24-hour sleep duration ≥ 9 hours accompanied by complaints of impaired functioning or distress due to excessive sleep, and its links to excessive sleepiness. A cross-sectional telephone study using a representative sample of 19,136 noninstitutionalized individuals living in the United States, aged ≥ 18 years (participation rate = 83.2%). The Sleep-EVAL expert system administered questions on life and sleeping habits; health; and sleep, mental, and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision; International Classification of Sleep Disorders: Diagnostic and Coding Manual II, International Classification of Diseases and Related Health Problems, 10th edition). Sleeping at least 9 hours per 24-hour period was reported by 8.4% (95% confidence interval = 8.0-8.8%) of participants; EQS (prolonged sleep episode with distress/impairment) was observed in 1.6% (1.4-1.8%) of the sample. The likelihood of EQS was 3 to 12× higher among individuals with a mood disorder. EQS individuals were 2 to 4× more likely to report poor quality of life than non-EQS individuals as well as interference with socioprofessional activities and relationships. Although between 33 and 66% of individuals with prolonged sleep perceived it as a major problem, only 6.3 to 27.5% of them reported having sought medical attention. EQS is widespread in the general population, co-occurring with a broad spectrum of sleep, medical, neurologic, and psychiatric disorders. Therefore, physicians must recognize EQS as a mixed clinical entity indicating careful assessment and specific treatment planning. © 2013 American Neurological Association.

  16. Identification and Evaluation of Cases for Excess Heat Utilisation Using GIS

    Directory of Open Access Journals (Sweden)

    Fabian Bühler

    2018-03-01

    Full Text Available Excess heat is present in many sectors, and its utilization could reduce the primary energy use and emission of greenhouse gases. This work presents a geographical mapping of excess heat, in which excess heat from the industry and utility sector was distributed to specific geographical locations in Denmark. Based on this mapping, a systematic approach for identifying cases for the utilization of excess heat is proposed, considering the production of district heat and process heat, as well as power generation. The technical and economic feasibility of this approach was evaluated for six cases. Special focus was placed on the challenges for the connection of excess heat sources to heat users. To account for uncertainties in the model input, different methods were applied to determine the uncertainty of the results and the most important model parameters. The results show how the spatial mapping of excess heat sources can be used to identify their utilization potentials. The identified case studies show that it can be economically feasible to connect the heat sources to the public energy network or to use the heat to generate electricity. The uncertainty analysis suggests that the results are indicative and are particularly useful for a fast evaluation, comparison and prioritization of possible matches. The excess heat temperature and obtainable energy price were identified as the most important input parameters.

  17. Severe excessive daytime sleepiness induced by hydroxyurea.

    Science.gov (United States)

    Revol, Bruno; Joyeux-Faure, Marie; Albahary, Marie-Victoire; Gressin, Remy; Mallaret, Michel; Pepin, Jean-Louis; Launois, Sandrine H

    2017-06-01

    Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  18. psi and excess leptons in photoproduction

    International Nuclear Information System (INIS)

    Ritson, D.M.

    1976-03-01

    The A-dependence of psi photoproduction was measured on beryllium and tantalum. From this it is found sigma/sub psi N/ = 2.75 +- 0.90 mb. A study was made of excess leptons relative to pion production in photoproduction. A μ/π ratio of 1.40 +- 0.25 x 10 -4 was found at 20 GeV incident photon energy. The energy dependence of psi photoproduction was determined and appeared to have a ''pseudo-threshold'' at 12 GeV

  19. Desaturation of excess intramyocellular triacylglycerol in obesity

    DEFF Research Database (Denmark)

    Haugaard, S B; Madsbad, S; Mu, Huiling

    2010-01-01

    , however, was increased twofold in obese women compared to obese men (Pfasting glucose (P...OBJECTIVE: Excess intramyocellular triacylglycerol (IMTG), found especially in obese women, is slowly metabolized and, therefore, prone to longer exposure to intracellular desaturases. Accordingly, it was hypothesized that IMTG content correlates inversely with IMTG fatty acid (FA) saturation...... in sedentary subjects. In addition, it was validated if IMTG palmitic acid is associated with insulin resistance as suggested earlier. DESIGN: Cross-sectional human study. SUBJECTS: In skeletal muscle biopsies, which were obtained from sedentary subjects (34 women, age 48+/-2 years (27 obese including 7 type 2...

  20. Conservative treatment of excessive anterior pelvic tilt

    DEFF Research Database (Denmark)

    Brekke, Anders Falk

    of Clinical Research, University of Southern Denmark, Denmark 3Department of Physiotherapy, University College Zealand, Denmark 4Center for Evidence-Based Medicine, Odense University Hospital, Denmark Correspondence Anders Falk Brekke E-mail: afbrekke@health.sdu.dk Mob: +45 7248 2626 Add: Sdr. Boulevard 29......Conservative treatment of excessive anterior pelvic tilt: A systematic review Anders Falk Brekke1,2,3, Søren Overgaard1,2, Asbjørn Hróbjartsson4, Anders Holsgaard-Larsen1,2 1Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital 2Department...

  1. Inland excess water mapping using hyperspectral imagery

    Directory of Open Access Journals (Sweden)

    Csendes Bálint

    2016-01-01

    Full Text Available Hyperspectral imaging combined with the potentials of airborne scanning is a powerful tool to monitor environmental processes. The aim of this research was to use high resolution remotely sensed data to map the spatial extent of inland excess water patches in a Hungarian study area that is known for its oil and gas production facilities. Periodic floodings show high spatial and temporal variability, nevertheless, former studies have proven that the affected soil surfaces can be accurately identified. Besides separability measurements, we performed spectral angle classification, which gave a result of 85% overall accuracy and we also compared the generated land cover map with LIDAR elevation data.

  2. Monoamine Oxidase B Inhibitors in Parkinson's Disease.

    Science.gov (United States)

    Dezsi, Livia; Vecsei, Laszlo

    2017-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder with a prevalence increasing with age. Oxidative stress and glutamate toxicity are involved in its pathomechanism. There are still many unmet needs of PD patients, including the alleviation of motor fluctuations and dyskinesias, and the development of therapies with neuroprotective potential. To give an overview of the pharmacological properties, the efficacy and safety of the monoamine oxidase B (MAO-B) inhibitors in the treatment of PD, with special focus on the results of randomized clinical trials. A literature search was conducted in PubMed for 'PD treatment', 'MAO-B inhibitors', 'selegiline', 'rasagiline', 'safinamide' and 'clinical trials' with 'MAO-B inhibitors' in 'Parkinson' disease'. MAO-B inhibitors have a favorable pharmacokinetic profile, improve the dopamine deficient state and may have neuroprotective properties. Safinamide exhibits an anti-glutamatergic effect as well. When applied as monotherapy, MAO-B inhibitors provide a modest, but significant improvement of motor function and delay the need for levodopa. Rasagiline and safinamide were proven safe and effective when added to a dopamine agonist in early PD. As add-on to levodopa, MAO-B inhibitors significantly reduced off-time and were comparable in efficacy to COMT inhibitors. Improvements were achieved as regards certain non-motor symptoms as well. Due to the efficacy shown in clinical trials and their favorable side-effect profile, MAO-B inhibitors are valuable drugs in the treatment of PD. They are recommended as monotherapy in the early stages of the disease and as add-on therapy to levodopa in advanced PD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Use of anaerobic hydrolysis pretreatment to enhance ultrasonic disintegration of excess sludge.

    Science.gov (United States)

    Li, Xianjin; Zhu, Tong; Shen, Yang; Chai, Tianyu; Xie, Yuanhua; You, Meiyan; Wang, Youzhao

    2016-01-01

    To improve the excess sludge disintegration efficiency, reduce the sludge disintegration cost, and increase sludge biodegradability, a combined pretreatment of anaerobic hydrolysis (AH) and ultrasonic treatment (UT) was proposed for excess sludge. Results showed that AH had an advantage in dissolving flocs, modifying sludge characteristics, and reducing the difficulty of sludge disintegration, whereas UT was advantageous in damaging cell walls, releasing intracellular substances, and decomposing macromolecular material. The combined AH-UT process was an efficient method for excess sludge pretreatment. The optimized solution involved AH for 3 days, followed by UT for 10 min. After treatment, chemical oxygen demand, protein, and peptidoglycan concentrations reached 3,949.5 mg O2/L, 752.5 mg/L and 619.1 mg/L, respectively. This work has great significance for further engineering applications, namely, reducing energy consumption, increasing the sludge disintegration rate, and improving the biochemical properties of sludge.

  4. Evaluation of Excess Heat Utilization in District Heating Systems by Implementing Levelized Cost of Excess Heat

    Directory of Open Access Journals (Sweden)

    Borna Doračić

    2018-03-01

    Full Text Available District heating plays a key role in achieving high primary energy savings and the reduction of the overall environmental impact of the energy sector. This was recently recognized by the European Commission, which emphasizes the importance of these systems, especially when integrated with renewable energy sources, like solar, biomass, geothermal, etc. On the other hand, high amounts of heat are currently being wasted in the industry sector, which causes low energy efficiency of these processes. This excess heat can be utilized and transported to the final customer by a distribution network. The main goal of this research was to calculate the potential for excess heat utilization in district heating systems by implementing the levelized cost of excess heat method. Additionally, this paper proves the economic and environmental benefits of switching from individual heating solutions to a district heating system. This was done by using the QGIS software. The variation of different relevant parameters was taken into account in the sensitivity analysis. Therefore, the final result was the determination of the maximum potential distance of the excess heat source from the demand, for different available heat supplies, costs of pipes, and excess heat prices.

  5. The effect of histone deacetylase inhibitors on AHSP expression

    Science.gov (United States)

    Ziari, Katayoun; Ranjbaran, Reza; Nikouyan, Negin

    2018-01-01

    Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p sodium valproate had a more considerable effect than sodium phenylbutyrate (p sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S) and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with β-hemoglobinopathies. PMID:29389946

  6. Multiscale estimation of excess mass from gravity data

    Science.gov (United States)

    Castaldo, Raffaele; Fedi, Maurizio; Florio, Giovanni

    2014-06-01

    We describe a multiscale method to estimate the excess mass of gravity anomaly sources, based on the theory of source moments. Using a multipole expansion of the potential field and considering only the data along the vertical direction, a system of linear equations is obtained. The choice of inverting data along a vertical profile can help us to reduce the interference effects due to nearby anomalies and will allow a local estimate of the source parameters. A criterion is established allowing the selection of the optimal highest altitude of the vertical profile data and truncation order of the series expansion. The inversion provides an estimate of the total anomalous mass and of the depth to the centre of mass. The method has several advantages with respect to classical methods, such as the Gauss' method: (i) we need just a 1-D inversion to obtain our estimates, being the inverted data sampled along a single vertical profile; (ii) the resolution may be straightforward enhanced by using vertical derivatives; (iii) the centre of mass is also estimated, besides the excess mass; (iv) the method is very robust versus noise; (v) the profile may be chosen in such a way to minimize the effects from interfering anomalies or from side effects due to the a limited area extension. The multiscale estimation of excess mass method can be successfully used in various fields of application. Here, we analyse the gravity anomaly generated by a sulphide body in the Skelleftea ore district, North Sweden, obtaining source mass and volume estimates in agreement with the known information. We show also that these estimates are substantially improved with respect to those obtained with the classical approach.

  7. Some considerations for excess zeroes in substance abuse research.

    Science.gov (United States)

    Bandyopadhyay, Dipankar; DeSantis, Stacia M; Korte, Jeffrey E; Brady, Kathleen T

    2011-09-01

    Count data collected in substance abuse research often come with an excess of "zeroes," which are typically handled using zero-inflated regression models. However, there is a need to consider the design aspects of those studies before using such a statistical model to ascertain the sources of zeroes. We sought to illustrate hurdle models as alternatives to zero-inflated models to validate a two-stage decision-making process in situations of "excess zeroes." We use data from a study of 45 cocaine-dependent subjects where the primary scientific question was to evaluate whether study participation influences drug-seeking behavior. The outcome, "the frequency (count) of cocaine use days per week," is bounded (ranging from 0 to 7). We fit and compare binomial, Poisson, negative binomial, and the hurdle version of these models to study the effect of gender, age, time, and study participation on cocaine use. The hurdle binomial model provides the best fit. Gender and time are not predictive of use. Higher odds of use versus no use are associated with age; however once use is experienced, odds of further use decrease with increase in age. Participation was associated with higher odds of no-cocaine use; once there is use, participation reduced the odds of further use. Age and study participation are significantly predictive of cocaine-use behavior. The two-stage decision process as modeled by a hurdle binomial model (appropriate for bounded count data with excess zeroes) provides interesting insights into the study of covariate effects on count responses of substance use, when all enrolled subjects are believed to be "at-risk" of use.

  8. Biological sludge solubilisation for reduction of excess sludge production in wastewater treatment process.

    Science.gov (United States)

    Yamaguchi, T; Yao, Y; Kihara, Y

    2006-01-01

    A novel sludge disintegration system (JFE-SD system) was developed for the reduction of excess sludge production in wastewater treatment plants. Chemical and biological treatments were applied to disintegrate excess sludge. At the first step, to enhance biological disintegration, the sludge was pretreated with alkali. At the second step, the sludge was disintegrated by biological treatment. Many kinds of sludge degrading microorganisms integrated the sludge. The efficiency of the new sludge disintegration system was confirmed in a full-scale experiment. The JFE-SD system reduced excess sludge production by approximately 50% during the experimental period. The quality of effluent was kept at quite a good level. Economic analysis revealed that this system could significantly decrease the excess sludge treatment cost.

  9. Altered cardiorespiratory coupling in young male adults with excessive online gaming.

    Science.gov (United States)

    Chang, Jae Seung; Kim, Eun Young; Jung, Dooyoung; Jeong, Seong Hoon; Kim, Yeni; Roh, Myoung-Sun; Ahn, Yong Min; Hahm, Bong-Jin

    2015-09-01

    This study aimed to investigate changes in heart rate variability and cardiorespiratory coupling in male college students with problematic Internet use (PIU) excessive gaming type during action video game play to assess the relationship between PIU tendency and central autonomic regulation. Electrocardiograms and respiration were simultaneously recorded from 22 male participants with excessive online gaming and 22 controls during action video game play. Sample entropy (SampEn) was computed to assess autonomic regularity, and cross-SampEn was calculated to quantify autonomic coordination. During video game play, reduced cardiorespiratory coupling (CRC) was observed in individuals with PIU excessive gaming type compared with controls, implicating central autonomic dysregulation. The PIU tendency was associated with the severity of autonomic dysregulation. These findings indicate impaired CRC in PIU excessive gaming type, which may reflect alterations of central inhibitory control over autonomic responses to pleasurable online stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Nonintrusive verification attributes for excess fissile materials

    International Nuclear Information System (INIS)

    Nicholas, N.J.; Eccleston, G.W.; Fearey, B.L.

    1997-10-01

    Under US initiatives, over two hundred metric tons of fissile materials have been declared to be excess to national defense needs. These excess materials are in both classified and unclassified forms. The US has expressed the intent to place these materials under international inspections as soon as practicable. To support these commitments, members of the US technical community are examining a variety of nonintrusive approaches (i.e., those that would not reveal classified or sensitive information) for verification of a range of potential declarations for these classified and unclassified materials. The most troublesome and potentially difficult issues involve approaches for international inspection of classified materials. The primary focus of the work to date has been on the measurement of signatures of relevant materials attributes (e.g., element, identification number, isotopic ratios, etc.), especially those related to classified materials and items. The authors are examining potential attributes and related measurement technologies in the context of possible verification approaches. The paper will discuss the current status of these activities, including their development, assessment, and benchmarking status

  11. Preferential solvation: dividing surface vs excess numbers.

    Science.gov (United States)

    Shimizu, Seishi; Matubayasi, Nobuyuki

    2014-04-10

    How do osmolytes affect the conformation and configuration of supramolecular assembly, such as ion channel opening and actin polymerization? The key to the answer lies in the excess solvation numbers of water and osmolyte molecules; these numbers are determinable solely from experimental data, as guaranteed by the phase rule, as we show through the exact solution theory of Kirkwood and Buff (KB). The osmotic stress technique (OST), in contrast, purposes to yield alternative hydration numbers through the use of the dividing surface borrowed from the adsorption theory. However, we show (i) OST is equivalent, when it becomes exact, to the crowding effect in which the osmolyte exclusion dominates over hydration; (ii) crowding is not the universal driving force of the osmolyte effect (e.g., actin polymerization); (iii) the dividing surface for solvation is useful only for crowding, unlike in the adsorption theory which necessitates its use due to the phase rule. KB thus clarifies the true meaning and limitations of the older perspectives on preferential solvation (such as solvent binding models, crowding, and OST), and enables excess number determination without any further assumptions.

  12. [Disability attributable to excess weight in Spain].

    Science.gov (United States)

    Martín-Ramiro, José Javier; Alvarez-Martín, Elena; Gil-Prieto, Ruth

    2014-08-19

    To estimate the disability attributable to higher than optimal body mass index in the Spanish population in 2006. Excess body weight prevalence data were obtained from the 2006 National Health Survey (NHS), while the prevalence of associated morbidities was extracted from the 2006 NHS and from a national hospital data base. Population attributable fractions were applied and disability attributable was expressed as years life with disability (YLD). In 2006, in the Spanish population aged 35-79 years, 791.650 YLD were lost due to higher than optimal body mass index (46.7% in males and 53.3% in females). Overweight (body mass index 25-29.9) accounted for 45.7% of total YLD. Males YLD were higher than females under 60. The 35-39 quinquennial group showed a difference for males of 16.6% while in the 74-79 group the difference was 23.8% for women. Osteoarthritis and chronic back pain accounted for 60% of YLD while hypertensive disease and type 2 diabetes mellitus were responsible of 37%. Excess body weight is a health risk related to the development of various diseases with an important associated disability burden and social and economical cost. YLD analysis is a useful monitor tool for disease control interventions. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Control rod excess withdrawal prevention device

    International Nuclear Information System (INIS)

    Takayama, Yoshihito.

    1992-01-01

    Excess withdrawal of a control rod of a BWR type reactor is prevented. That is, the device comprises (1) a speed detector for detecting the driving speed of a control rod, (2) a judging circuit for outputting an abnormal signal if the driving speed is greater than a predetermined level and (3) a direction control valve compulsory closing circuit for controlling the driving direction of inserting and withdrawing a control rod based on an abnormal signal. With such a constitution, when the with drawing speed of a control rod is greater than a predetermined level, it is detected by the speed detector and the judging circuit. Then, all of the direction control valve are closed by way of the direction control valve compulsory closing circuit. As a result, the operation of the control rod is stopped compulsorily and the withdrawing speed of the control rod can be lowered to a speed corresponding to that upon gravitational withdrawal. Accordingly, excess withdrawal can be prevented. (I.S)

  14. Total-body sodium and sodium excess

    International Nuclear Information System (INIS)

    Aloia, J.F.; Cohn, S.H.; Abesamis, C.; Babu, T.; Zanzi, I.; Ellis, K.

    1980-01-01

    Total-body levels of sodium (TBNa), chlorine (TBCI), calcium (TBCa), and potassium (TBK) were measured by neutron activation and analysis of results by whole body counting in 66 postmenopausal women. The relationship between TBNa, and TBCl, TBK, and TBCa on the one hand, and height and weight on the other, were found to compare with those previously reported. The hypothesis that TBNa and TBCl are distributed normally could not be rejected. The sodium excess (Na/sub es/) is defined as the sodium that is present in excess of that associated with the extracellular fluid (chlorine) space; the Na/sub es/ approximates nonexchangeable bone sodium. In these 66 postmenopausal women, and in patients with different endocrinopathies previously described, the values on Na/sub es/ did not differ from the normal values except in the thyrotoxicosis patients, where they were decreased. A close relationship between Na/sub es/ and TBCa was maintained in the endocrinopathies studied. This relationship was found in conditions accompanied by either an increment or a loss of skeletal mass. It appears that the NA/sub es/ value is primarily dependent upon the calcium content of bone

  15. Molecular simulation of excess isotherm and excess enthalpy change in gas-phase adsorption.

    Science.gov (United States)

    Do, D D; Do, H D; Nicholson, D

    2009-01-29

    We present a new approach to calculating excess isotherm and differential enthalpy of adsorption on surfaces or in confined spaces by the Monte Carlo molecular simulation method. The approach is very general and, most importantly, is unambiguous in its application to any configuration of solid structure (crystalline, graphite layer or disordered porous glass), to any type of fluid (simple or complex molecule), and to any operating conditions (subcritical or supercritical). The behavior of the adsorbed phase is studied using the partial molar energy of the simulation box. However, to characterize adsorption for comparison with experimental data, the isotherm is best described by the excess amount, and the enthalpy of adsorption is defined as the change in the total enthalpy of the simulation box with the change in the excess amount, keeping the total number (gas + adsorbed phases) constant. The excess quantities (capacity and energy) require a choice of a reference gaseous phase, which is defined as the adsorptive gas phase occupying the accessible volume and having a density equal to the bulk gas density. The accessible volume is defined as the mean volume space accessible to the center of mass of the adsorbate under consideration. With this choice, the excess isotherm passes through a maximum but always remains positive. This is in stark contrast to the literature where helium void volume is used (which is always greater than the accessible volume) and the resulting excess can be negative. Our definition of enthalpy change is equivalent to the difference between the partial molar enthalpy of the gas phase and the partial molar enthalpy of the adsorbed phase. There is no need to assume ideal gas or negligible molar volume of the adsorbed phase as is traditionally done in the literature. We illustrate this new approach with adsorption of argon, nitrogen, and carbon dioxide under subcritical and supercritical conditions.

  16. Percolation model of excess electrical noise in transition-edge sensors

    International Nuclear Information System (INIS)

    Lindeman, M.A.; Anderson, M.B.; Bandler, S.R.; Bilgri, N.; Chervenak, J.; Gwynne Crowder, S.; Fallows, S.; Figueroa-Feliciano, E.; Finkbeiner, F.; Iyomoto, N.; Kelley, R.; Kilbourne, C.A.; Lai, T.; Man, J.; McCammon, D.; Nelms, K.L.; Porter, F.S.; Rocks, L.E.; Saab, T.; Sadleir, J.; Vidugiris, G.

    2006-01-01

    We present a geometrical model to describe excess electrical noise in transition-edge sensors (TESs). In this model, a network of fluctuating resistors represents the complex dynamics inside a TES. The fluctuations can cause several resistors in series to become superconducting. Such events short out part of the TES and generate noise because much of the current percolates through low resistance paths. The model predicts that excess white noise increases with decreasing TES bias resistance (R/R N ) and that perpendicular zebra stripes reduce noise and alpha of the TES by reducing percolation

  17. Member for conducting excess heat away from heat sources

    International Nuclear Information System (INIS)

    Cooke-Yarborough, E.H.

    1975-01-01

    Should a radioisotope-powered engine (e.g., a Stirling cycle engine for generating electricity) stop working for any reason, the radioisotope heat source will continue to generate heat. This will result in a rise in temperature which may cause overheating of and possible damage to the engine as well as to the heat source itself. The invention provides a support/location member for conducting excess heat from the heat source and which, in normal operation of the engine, will impede the conduction of heat away from the heat source and so reduce thermal losses. The member is of elongated form and comprises a stack of heat-conductive slugs disposed in a tube and in interspaced relationship along the axis of the tube. The tube supports the slugs in axial alignment. Means are provided for attaching an end one of the slugs to the heat source and means operable on overheating of said end one of the slugs are also provided whereby the slugs are able to move into heat-conducting contact with each other so as to conduct the excess heat away from said heat source. The slugs may be brazed to the tube whereby progressive overheating of the slugs along the stack results in an overheated slug being freed from attachment to the tube so as to allow the overheated slug to move along the stack and engage the next slug in line in heat-conducting contact. (U.S.)

  18. Tryptophan levels, excessive exercise, and nutritional status in anorexia nervosa.

    Science.gov (United States)

    Favaro, A; Caregaro, L; Burlina, A B; Santonastaso, P

    2000-01-01

    It has been hypothesized that reduced dietary availability of tryptophan may be the cause of impaired serotonin activity in underweight anorexics. The study reported here evaluated the relationship between tryptophan availability in the blood and nutritional status in anorexia nervosa. The total amount of tryptophan and the ratio between tryptophan and other large neutral amino acids (TRP/LNAA) were assessed in a sample of 16 starving anorexic patients. Body weight and composition and energy intake were evaluated in all patients. All subjects also completed self-reported questionnaires such as the Hopkins Symptom Checklist and Eating Disorders Inventory (EDI). The TRP/LNAA ratio seems to be higher in patients with a more severe catabolic status. It is, in fact, significantly inversely correlated with body mass index, body fat, muscle mass, daily energy intake, and daily tryptophan intake. The TRP/LNAA ratio also correlates with growth hormone and the EDI drive for thinness. Patients who exercise excessively had significantly higher TRP/LNAA ratios. In starving anorexic patients, the TRP/LNAA ratio does not seem to be determined by the content of tryptophan in the diet, but it correlates with measures of catabolism. The relationship of the TRP/LNAA ratio to excessive exercise and starvation indicates the importance of further investigations exploring the role of tryptophan availability in maintaining anorexia nervosa.

  19. Metabolic acclimation to excess light intensity in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Davis, Maria C; Fiehn, Oliver; Durnford, Dion G

    2013-07-01

    There are several well-described acclimation responses to excess light in green algae but the effect on metabolism has not been thoroughly investigated. This study examines the metabolic changes during photoacclimation to high-light (HL) stress in Chlamydomonas reinhardtii using nuclear magnetic resonance and mass spectrometry. Using principal component analysis, a clear metabolic response to HL intensity was observed on global metabolite pools, with major changes in the levels of amino acids and related nitrogen metabolites. Amino acid pools increased during short-term photoacclimation, but were especially prominent in HL-acclimated cultures. Unexpectedly, we observed an increase in mitochondrial metabolism through downstream photorespiratory pathways. The expression of two genes encoding key enzymes in the photorespiratory pathway, glycolate dehydrogenase and malate synthase, were highly responsive to the HL stress. We propose that this pathway contributes to metabolite pools involved in nitrogen assimilation and may play a direct role in photoacclimation. Our results suggest that primary and secondary metabolism is highly pliable and plays a critical role in coping with the energetic imbalance during HL exposure and a necessary adjustment to support an increased growth rate that is an effective energy sink for the excess reducing power generated during HL stress. © 2013 John Wiley & Sons Ltd.

  20. Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Yuri A. Blednov

    2014-05-01

    Full Text Available Some anti-inflammatory medications reduce alcohol consumption in rodent models. Inhibition of phosphodiesterases (PDE increases cAMP and reduces inflammatory signaling. Rolipram, an inhibitor of PDE4, markedly reduced ethanol intake and preference in mice and reduced ethanol seeking and consumption in alcohol-preferring fawn-hooded rats (Hu et al., 2011;Wen et al., 2012. To determine if these effects were specific for PDE4, we compared nine PDE inhibitors with different subtype selectivity: propentofylline (nonspecific, vinpocetine (PDE1, olprinone, milrinone (PDE3, zaprinast (PDE5, rolipram, mesopram, piclamilast, and CDP840 (PDE4. Alcohol intake was measured in C57BL/6J male mice using 24-hour two-bottle choice and two-bottle choice with limited (three-hour access to alcohol. Only the selective PDE4 inhibitors reduced ethanol intake and preference in the 24-hour two-bottle choice test. For rolipram, piclamilast, and CDP840, this effect was observed after the first 6 hours but not after the next 18 hours. Mesopram, however, produced a long-lasting reduction of ethanol intake and preference. In the limited access test, rolipram, piclamilast, and mesopram reduced ethanol consumption and total fluid intake and did not change preference for ethanol, whereas CDP840 reduced both consumption and preference without altering total fluid intake. Our results provide novel evidence for a selective role of PDE4 in regulating ethanol drinking in mice. We suggest that inhibition of PDE4 may be an unexplored target for medication development to reduce excessive alcohol consumption.

  1. Management of Excess Reactive Nitrogen in the Environment

    Science.gov (United States)

    Galloway, J. N.; Theis, T.; Doering, O.

    2011-12-01

    Managing the impacts of excessive reactive nitrogen (Nr) in the environment is a complex problem that begins with the recognition of the obligate dietary need for Nr by all living populations. The human solution to this need has been to devise ways to bring Nr into the biosphere (via the Haber-Bosch process) to grow food. Other Nr is created as a by-product of fossil-fuel combustion. The net result is the introduction of more than five times the Nr created by natural processes in the U.S., only a fraction of which is converted back to diatomic nitrogen through denitrification. This presentation summarizes findings and recommendations of the newly-released US EPA Science Advisory Board's Integrated Nitrogen Committee report, "Reactive Nitrogen in the United States: An Analysis of Flows, Consequences, and Management Options", that deal specifically with approaches for solving the excess Nr problem. These can be grouped into four general areas: (1) Recognition of the Problem. Until there is recognition that excess Nr is a serious problem with economic, health, and societal consequences, there will be little willingness to expend resources on this issue. Education, communication and outreach are critically important to engender in regulators, and the public at large, sufficient will to undertake the large scale effort needed to reduce Nr in the environment. (2) Development of Integrated Regulatory Approaches. Given what is known about the way Nr behaves, efforts to deal with excess Nr must be organized in a way that reflects the nature of the problem. Unfortunately, most approaches tend to conceive of Nr issues within a narrowly focused disciplinary model, and our policy and regulatory institutions are often bound by enabling legislation that stresses source-by-source, chemical-by-chemical, and media-by-media. The resulting regulatory structure that has evolved for problems such as Nr that affect human health and the environment is apt to miss the complex nature of the

  2. Rasagiline (TVP-1012): a new selective monoamine oxidase inhibitor for Parkinson's disease.

    Science.gov (United States)

    Guay, David R P

    2006-12-01

    This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug-interaction potential, indications, dosing, and potential role of rasagiline mesylate, a new selective monoamine oxidase (MAO) type B (MAO-B) inhibitor, in the treatment of Parkinson's disease. A MEDLINE/PUBMED search (1986 through September 2006) was conducted to identify studies involving rasagiline written in English. Additional references were obtained from the bibliographies of these studies. All studies evaluating any aspect of rasagiline, including in vitro, in vivo (animal), and human studies, were reviewed. Rasagiline mesylate was developed with the goal of producing a selective MAO-B inhibitor that is not metabolized to (presumed) toxic metabolites (eg, amphetamine and methamphetamine, which are byproducts of the metabolism of selegiline, another selective MAO-B inhibitor). In vitro and in vivo data have confirmed the drug's selectivity for MAO-B. Rasagiline is almost completely eliminated by oxidative metabolism (catalyzed by cytochrome P-450 [CYP] isozyme 1A2) followed by renal excretion of conjugated parent compound and metabolites. Drug clearance is sufficiently slow to allow once-daily dosing. Several studies have documented its efficacy as monotherapy for early-stage disease and as adjunctive therapy in L-dopa recipients with motor fluctuations. As monotherapy, rasagiline is well tolerated with an adverse-effect profile similar to that of placebo. As adjunctive therapy, it exhibits the expected adverse effects of dopamine excess, which can be ameliorated by reducing the L-dopa dosage. CYP1A2 inhibitors slow the elimination of rasagiline and mandate dosage reduction. Hepatic impairment has an analogous effect. The recommended dosage regimens for monotherapy and adjunctive therapy are 1 and 0.5 mg PO QD, respectively. Despite the well-documented selectivity of rasagiline, the manufacturer recommends virtually all of the dietary (vis

  3. 31 CFR 353.12 - Disposition of excess.

    Science.gov (United States)

    2010-07-01

    ... necessary to adjust the excess. Instructions for adjustment of the excess can be obtained by email at [email protected] or by writing to Bureau of the Public Debt, Parkersburg, WV 26106-1328. [68 FR 24805...

  4. Iodine Excess is a Risk Factor for Goiter Formation

    African Journals Online (AJOL)

    Key Words: Iodine excess, Goiter, Sub Saharan Africa. Iodine Excess is a ... synthesis leading to increased thyroid stimulating hormone ..... study done in Uganda revealed a similar picture ... significant association, probably due to recall bias.

  5. Production of ethanol from excess ethylene

    DEFF Research Database (Denmark)

    Kadhim, Adam S.; Carlsen, Kim B.; Bisgaard, Thomas

    2012-01-01

    will focus on the synthetic method, which employs direct hydration of ethylene. A conceptual process design of an ethyl alcohol producing plant is performed in a MSc-level course on Process Design at the Department of Chemical and Biochemical Engineering at DTU. In the designed process, 190 proof ethyl...... alcohol (azeotropic mixture) is produced from excess ethylene containing propylene and methane as impurities. The design work is based on a systematic approach consisting of 12 tasks performed in a specified hierarchy. According to this 12-tasks design procedure, information about the product and process...... of the designed process. The resulting design utilizes 75 million kg/year ethylene feed in order to obtain an ethyl alcohol production of 90.5 million kg/year. The total capital investment has been estimated to 43 million USD and the total product cost without depreciation estimated to 58.5 million USD...

  6. Excessive Fragmentary Myoclonus: What Do We Know?

    Directory of Open Access Journals (Sweden)

    Jiří Nepožitek

    2017-03-01

    Full Text Available Excessive fragmentary myoclonus (EFM is a polysomnographic finding registered by the surface electromyography (EMG and characterized as a result of the muscle activity consisting of sudden, isolated, arrhythmic, asynchronous and asymmetric brief twitches. The EMG potentials are defined by the exact criteria in The International Classification of the Sleep Disorders, 3rd edition and they appear with high intensity in all sleep stages. Clinical significance of EFM is unclear. It was observed in combination with other diseases and features such as obstructive and central sleep apnea, narcolepsy, periodic limb movements, insomnia, neurodegenerative disorders and peripheral nerve dysfunction. Relation to such wide range of diseases supports the opinion that EFM is nor a specific sleep disorder nor a specific polysomnographic sign. The option that EFM is a normal variant has also not been ruled out so far.

  7. Di-photon excess illuminates dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Backović, Mihailo [Center for Cosmology, Particle Physics and Phenomenology - CP3,Universite Catholique de Louvain, Louvain-la-neuve (Belgium); Mariotti, Alberto [Theoretische Natuurkunde and IIHE/ELEM, Vrije Universiteit Brussel,Pleinlaan 2, B-1050 Brussels (Belgium); International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium); Redigolo, Diego [Laboratoire de Physique Théorique et Hautes Energies, CNRS UMR 7589,Universiteé Pierre et Marie Curie, 4 place Jussieu, F-75005, Paris (France)

    2016-03-22

    We propose a simplified model of dark matter with a scalar mediator to accommodate the di-photon excess recently observed by the ATLAS and CMS collaborations. Decays of the resonance into dark matter can easily account for a relatively large width of the scalar resonance, while the magnitude of the total width combined with the constraint on dark matter relic density leads to sharp predictions on the parameters of the Dark Sector. Under the assumption of a rather large width, the model predicts a signal consistent with ∼300 GeV dark matter particle and ∼750 GeV scalar mediator in channels with large missing energy. This prediction is not yet severely bounded by LHC Run I searches and will be accessible at the LHC Run II in the jet plus missing energy channel with more luminosity. Our analysis also considers astro-physical constraints, pointing out that future direct detection experiments will be sensitive to this scenario.

  8. Di-photon excess illuminates dark matter

    International Nuclear Information System (INIS)

    Backović, Mihailo; Mariotti, Alberto; Redigolo, Diego

    2016-01-01

    We propose a simplified model of dark matter with a scalar mediator to accommodate the di-photon excess recently observed by the ATLAS and CMS collaborations. Decays of the resonance into dark matter can easily account for a relatively large width of the scalar resonance, while the magnitude of the total width combined with the constraint on dark matter relic density leads to sharp predictions on the parameters of the Dark Sector. Under the assumption of a rather large width, the model predicts a signal consistent with ∼300 GeV dark matter particle and ∼750 GeV scalar mediator in channels with large missing energy. This prediction is not yet severely bounded by LHC Run I searches and will be accessible at the LHC Run II in the jet plus missing energy channel with more luminosity. Our analysis also considers astro-physical constraints, pointing out that future direct detection experiments will be sensitive to this scenario.

  9. Research of Precataclysmic Variables with Radius Excesses

    Science.gov (United States)

    Deminova, N. R.; Shimansky, V. V.; Borisov, N. V.; Gabdeev, M. M.; Shimanskaya, N. N.

    2017-06-01

    The results of spectroscopic observations of the pre-cataclysmic variable NSVS 14256825, which is a HW Vir binary system, were analyzed. The chemical composition is determined, the radial velocities and equivalent widths of a given star are measured. The fundamental parameters of the components were determined (R1 = 0.166 R⊙ , M2 = 0.100 M⊙ , R2 = 0.122 R⊙). It is shown that the secondary component has a mass close to the mass of brown dwarfs. A comparison of two close binary systems is made: HS 2333 + 3927 and NSVS 14256825. A radius-to-mass relationship for the secondary components of the studied pre-cataclysmic variables is constructed. It is concluded that an excess of radii relative to model predictions for MS stars is observed in virtually all systems.

  10. Excess plutonium disposition using ALWR technology

    International Nuclear Information System (INIS)

    Phillips, A.; Buckner, M.R.; Radder, J.A.; Angelos, J.G.; Inhaber, H.

    1993-02-01

    The Office of Nuclear Energy of the Department of Energy chartered the Plutonium Disposition Task Force in August 1992. The Task Force was created to assess the range of practicable means of disposition of excess weapons-grade plutonium. Within the Task Force, working groups were formed to consider: (1) storage, (2) disposal,and(3) fission options for this disposition,and a separate group to evaluate nonproliferation concerns of each of the alternatives. As a member of the Fission Working Group, the Savannah River Technology Center acted as a sponsor for light water reactor (LWR) technology. The information contained in this report details the submittal that was made to the Fission Working Group of the technical assessment of LWR technology for plutonium disposition. The following aspects were considered: (1) proliferation issues, (2) technical feasibility, (3) technical availability, (4) economics, (5) regulatory issues, and (6) political acceptance

  11. Propylene Glycol Poisoning From Excess Whiskey Ingestion

    Directory of Open Access Journals (Sweden)

    Courtney A. Cunningham MD

    2015-09-01

    Full Text Available In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.

  12. Origin of Tungsten Excess in Komatiites

    Science.gov (United States)

    Becker, H.; Brandon, A. D.; Walker, R. J.

    2004-12-01

    The limited database available for W abundances in komatiites (n=7, Newsom et al., 1996) suggests that when melting and fractional crystallization effects are filtered out, these komatiites have about 10 times higher W, compared to other mantle-derived mafic-ultramafic magmas (MORB, OIB). The excess of W in the komatiites relative to lithophile highly incompatible elements becomes obvious when compared with the low concentrations of the light REE Ce and Nd (about 1-2 ug/g in many komatiites, compared to > 10 ug/g in most MORB and OIB). In order to increase the komatiite W database, komatiite samples from Phanerozoic (Gorgona Island) and Archean terraines (Boston Creek/Canada, Belingwe/South Africa, 2.7 Ga) were dissolved and W was separated in order to obtain W concentrations by isotope dilution. Except for one sample from Gorgona Island with low W (23 ng/g), samples from all three locales show high W (516 to 2643 ng/g), with most samples containing near 700 ng/g W. Three Hawaiian picrites (H23, LO-02-04, MK-1-6) were also analyzed for comparative purposes and contain 75, 163 and 418 ng/g W, respectively. The W concentrations in the Hawaiian picrites are comparable or lower than W concentrations in Hawaiian tholeiites (Newsom et al., 1996). Mass balance considerations suggest that it is unlikely that the W excess in komatiites reflects W contributions to the mantle sources of komatiites from the outer core. The W enrichment could result from shallow-level alteration processes if primary W abundances of komatiites were low and W was added via fluids, containing W and other fluid-mobile elements derived from crustal rocks. Because most W in such samples would be of crustal origin, small contributions from the outer core may be difficult to detect using 182W systematics (Schersten et al., 2003).

  13. Vitamin paradox in obesity: Deficiency or excess?

    Science.gov (United States)

    Zhou, Shi-Sheng; Li, Da; Chen, Na-Na; Zhou, Yiming

    2015-08-25

    Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.

  14. Excessive anticoagulation with warfarin or phenprocoumon may have multiple causes

    DEFF Research Database (Denmark)

    Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton

    2012-01-01

    Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation.......Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation....

  15. JAK inhibitors in autoinflammation.

    Science.gov (United States)

    Hoffman, Hal M; Broderick, Lori

    2018-06-11

    Interferonopathies are a subset of autoinflammatory disorders with a prominent type I IFN gene signature. Treatment of these patients has been challenging, given the lack of response to common autoinflammatory therapeutics including IL-1 and TNF blockade. JAK inhibitors (Jakinibs) are a family of small-molecule inhibitors that target the JAK/STAT signaling pathway and have shown clinical efficacy, with FDA and European Medicines Agency (EMA) approval for arthritic and myeloproliferative syndromes. Sanchez and colleagues repurposed baricitinib to establish a significant role for JAK inhibition as a novel therapy for patients with interferonopathies, demonstrating the power of translational rare disease research with lifesaving effects.

  16. Cathepsin D inhibitors

    Directory of Open Access Journals (Sweden)

    M. Gacko

    2007-11-01

    Full Text Available Inhibitors of cathepsin D belong to chemical compounds that estrify carboxyl groups of the Asp33 and Asp231residues of its catalytic site, penta-peptides containing statin, i.e. the amino acid similar in structure to the tetraedric indirectproduct, and polypeptides found in the spare organs of many plants and forming permanent noncovalent complexes withcathepsin. Cathepsin D activity is also inhibited by alpha2-macroglobulin and antibodies directed against this enzyme.Methods used to determine the activity and concentration of these inhibitors and their analytical, preparative and therapeuticapplications are discussed.

  17. Fertilizing nature: a tragedy of excess in the commons.

    Directory of Open Access Journals (Sweden)

    Allen G Good

    2011-08-01

    Full Text Available Globally, we are applying excessive nitrogen (N fertilizers to our agricultural crops, which ultimately causes nitrogen pollution to our ecosphere. The atmosphere is polluted by N₂O and NO(x gases that directly and indirectly increase atmospheric warming and climate change. Nitrogen is also leached from agricultural lands as the water-soluble form NO₃⁻, which increases nutrient overload in rivers, lakes, and oceans, causing "dead zones", reducing property values and the diversity of aquatic life, and damaging our drinking water and aquatic-associated industries such as fishing and tourism. Why do some countries show reductions in fertilizer use while others show increasing use? What N fertilizer application reductions could occur, without compromising crop yields? And what are the economic and environmental benefits of using directed nutrient management strategies?

  18. Development of ARDS after Excessive Kath Consumption: A Case Report

    Directory of Open Access Journals (Sweden)

    Marlene Wewalka

    2011-01-01

    Full Text Available Khat is a drug widely used in the Horn of Africa and the Arabian Peninsula. Khat leaves contain, among other substances, the psychoactive alkaloid cathinone, which induce central nervous system stimulation leading to euphoria, hyperactivity, restlessness, and insomnia. However, it also could cause psychological adverse effects such as lethargy, sleepiness, psychoses, and depression necessitating pharmacologic treatment. Here we report the case of a 35-year-old man from Somalia who became unconscious and developed aspiration pneumonia and subsequent ARDS after excessive consumption of khat leaves. His unconsciousness was possibly caused by the sleepiness developed after khat consumption and a benzodiazepine intake by the patient himself. Thus, khat-induced adverse effects should not primarily be treated pharmacologically, but patients should be urged to quit khat consumption in order to eliminate or, at least, reduce the severity of present psychological adverse effects.

  19. Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption

    Directory of Open Access Journals (Sweden)

    Boutin Jean A

    2010-10-01

    Full Text Available Abstract Background Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts. Methods Human osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours. The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue. Results Of the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently. Conclusions In conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.

  20. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  1. Excessive Testing and Pupils in the Public Schools

    Science.gov (United States)

    Ediger, Marlow

    2017-01-01

    This article explores the question of excessive testing in public schools, its value in the educational process, and the impact that excessive testing may have on the student and the family unit. While assessments are valuable when used properly, excessive testing may lead to problems with unforeseen consequences.

  2. Identification of fermentation inhibitors in wood hydrolyzates and removal of inhibitors by ion exchange and liquid-liquid extraction

    Science.gov (United States)

    Luo, Caidian

    1998-12-01

    Common methods employed in the ethanol production from biomass consist of chemical or enzymatic degradation of biomass into sugars and then fermentation of sugars into ethanol or other chemicals. However, some degradation products severely inhibit the fermentation processes and substantially reduce the efficiency of ethanol production. How to remove inhibitors from the reaction product mixture and increase the production efficiency are critical in the commercialization of any processes of energy from biomass. The present study has investigated anion exchange and liquid-liquid extraction as potential methods for inhibitor removal. An analytical method has been developed to identify the fermentation inhibitors in a hydrolyzate. The majority of inhibitors present in hybrid poplar hydrolyzate have positively been identified. Ion exchange with weak basic Dowex-MWA-1 resin has been proved to be an effective mean to remove fermentation inhibitors from hybrid poplar hydrolyzate and significantly increase the fermentation productivity. Extraction with n-butanol might be a preferred way to remove inhibitors from wood hydrolyzates and improve the fermentability of sugars in the hydrolyzates. n-Butanol also removes some glucose, mannose and xylose from the hydrolyzate. Inhibitor identification reveals that lignin and sugar degradation compounds including both aromatic and aliphatic aldehydes and carboxylic acids formed in hydrolysis, plus fatty acids and other components from wood extractives are major fermentation inhibitors in Sacchromyces cerevisiae fermentation. There are 35 components identified as fermentation inhibitors. Among them, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid, syringic acid, syringaldehyde, and ferulic acid are among the most abundant aromatic inhibitors in hybrid poplar hydrolyzate. The conversion of aldehyde groups into carboxylic acid groups in the nitric acid catalyzed hydrolysis reduces the toxicity of the hydrolyzate. A wide spectrum of

  3. Spatiotemporal and economic analysis of industrial excess heat as a resource for district heating

    DEFF Research Database (Denmark)

    Bühler, Fabian; Petrović, Stefan; Holm, Fridolin Müller

    2018-01-01

    detailed analysis of the most suitable types of industries and the costs is required, allowing a targeted exploitation of this resource. This work extends the spatial and thermodynamic analysis, to account for the temporal match between industrial excess heat and district heating demands, as well...... as the costs for implementation and operation of the systems. This allows the determination of cost-effective district heating potentials, as well as the analysis of different industries and technological requirements. The results show that the temporal mismatch between excess heat and district heating demand...... and lack of demand, reduces the theoretical substitution potential by almost 30%. If heat storages are introduced, the total potential is reduced by only 10%. A majority of the excess heat can be utilised at socio-economic heating costs lower than the average Danish district heating price and the cost...

  4. Excess mortality and guideline-indicated care following non-ST-elevation myocardial infarction.

    Science.gov (United States)

    Dondo, Tatendashe B; Hall, Marlous; Timmis, Adam D; Gilthorpe, Mark S; Alabas, Oras A; Batin, Phillip D; Deanfield, John E; Hemingway, Harry; Gale, Chris P

    2017-08-01

    Adherence to guideline-indicated care for the treatment of non-ST-elevation myocardial infarction (NSTEMI) is associated with improved outcomes. We investigated the extent and consequences of non-adherence to guideline-indicated care across a national health system. A cohort study ( ClinicalTrials.gov identifier: NCT02436187) was conducted using data from the Myocardial Ischaemia National Audit Project ( n = 389,057 NSTEMI, n = 247 hospitals, England and Wales, 2003-2013). Accelerated failure time models were used to quantify the impact of non-adherence on survival according to dates of guideline publication. Over a period of 1,079,044 person-years (median 2.2 years of follow-up), 113,586 (29.2%) NSTEMI patients died. Of those eligible to receive care, 337,881 (86.9%) did not receive one or more guideline-indicated intervention; the most frequently missed were dietary advice ( n = 254,869, 68.1%), smoking cessation advice ( n = 245,357, 87.9%), P2Y12 inhibitors ( n = 192,906, 66.3%) and coronary angiography ( n = 161,853, 43.4%). Missed interventions with the strongest impact on reduced survival were coronary angiography (time ratio: 0.18, 95% confidence interval (CI): 0.17-0.18), cardiac rehabilitation (time ratio: 0.49, 95% CI: 0.48-0.50), smoking cessation advice (time ratio: 0.53, 95% CI: 0.51-0.57) and statins (time ratio: 0.56, 95% CI: 0.55-0.58). If all eligible patients in the study had received optimal care at the time of guideline publication, then 32,765 (28.9%) deaths (95% CI: 30,531-33,509) may have been prevented. The majority of patients hospitalised with NSTEMI missed at least one guideline-indicated intervention for which they were eligible. This was significantly associated with excess mortality. Greater attention to the provision of guideline-indicated care for the management of NSTEMI will reduce premature cardiovascular deaths.

  5. Influence of dietary protein and excess methionine on choline needs for young bobwhite quail

    Science.gov (United States)

    Serafin, J.A.

    1982-01-01

    Experiments were conducted with young Bobwhite quail (Colinus virginianus) to investigate the effect of differing dietary protein levels and nondetrimental amounts of excess methionine on choline needs. Growth and feed consumption of quail fed an adequate (27.3%) protein purified diet supplemented with 2000 mg/kg of choline were unaffected by increasing the level of excess methionine to 1.75%; however, greater amounts (2.0%, 2.25%) of excess methionine depressed growth (P less than .01), reduced feed consumption (P less than .01), and decreased feed utilization (P less than .05). Quail fed a purified diet containing 13.85% protein and 515 mg/kg of choline grew poorly. Growth was unaffected by additional choline in this diet. Growth was suboptimal among quail fed purified diets containing adequate or high (41.55%) levels of protein in which choline was limiting; however, a high level of protein did not in itself affect performance. Growth was improved by supplemental choline in these diets. Growth of quail fed purified diets with up to 1.35% excess methionine which were limiting (531 mg/kg) in choline was less than that of groups fed 2000 mg/kg of added dietary choline (P less than .01); however, excess methionine did not significantly influence growth of quail fed choline-deficient diets. These experiments indicate that neither high dietary protein nor excess methionine, fed at non-growth-depressing levels, increases dietary choline needs for young Bobwhite quail.

  6. A COMPREHENSIVE CENSUS OF NEARBY INFRARED EXCESS STARS

    Energy Technology Data Exchange (ETDEWEB)

    Cotten, Tara H.; Song, Inseok, E-mail: tara@physast.uga.edu, E-mail: song@physast.uga.edu [Department of Physics and Astronomy, University of Georgia, Athens, GA 30602 (United States)

    2016-07-01

    The conclusion of the Wide-Field Infrared Survey Explorer ( WISE ) mission presents an opportune time to summarize the history of using excess emission in the infrared as a tracer of circumstellar material and exploit all available data for future missions such as the James Webb Space Telescope . We have compiled a catalog of infrared excess stars from peer-reviewed articles and perform an extensive search for new infrared excess stars by cross-correlating the Tycho-2 and all-sky WISE (AllWISE) catalogs. We define a significance of excess in four spectral type divisions and select stars showing greater than either 3 σ or 5 σ significance of excess in the mid- and far-infrared. Through procedures including spectral energy distribution fitting and various image analyses, each potential excess source was rigorously vetted to eliminate false positives. The infrared excess stars from the literature and the new stars found through the Tycho-2 and AllWISE cross-correlation produced nearly 500 “Prime” infrared excess stars, of which 74 are new sources of excess, and >1200 are “Reserved” stars, of which 950 are new sources of excess. The main catalog of infrared excess stars are nearby, bright, and either demonstrate excess in more than one passband or have infrared spectroscopy confirming the infrared excess. This study identifies stars that display a spectral energy distribution suggestive of a secondary or post-protoplanetary generation of dust, and they are ideal targets for future optical and infrared imaging observations. The final catalogs of stars summarize the past work using infrared excess to detect dust disks, and with the most extensive compilation of infrared excess stars (∼1750) to date, we investigate various relationships among stellar and disk parameters.

  7. Insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder in nurses having less than 11 hours in-between shifts.

    Directory of Open Access Journals (Sweden)

    Maria Fagerbakke Eldevik

    Full Text Available STUDY OBJECTIVE: To assess if less than 11 hours off work between work shifts (quick returns was related to insomnia, sleepiness, fatigue, anxiety, depression and shift work disorder among nurses. METHODS: A questionnaire including established instruments measuring insomnia (Bergen Insomnia Scale, sleepiness (Epworth Sleepiness Scale, fatigue (Fatigue Questionnaire, anxiety/depression (Hospital Anxiety and Depression Scale and shift work disorder was administered. Among the 1990 Norwegian nurses who participated in the study; 264 nurses had no quick returns, 724 had 1-30 quick returns and 892 had more than 30 quick returns during the past year. 110 nurses did not report the number of quick returns during the past year. The prevalence of insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder was calculated within the three groups of nurses. Crude and adjusted logistic regression analyses were performed to assess the relation between quick returns and such complaints. RESULTS: We found a significant positive association between quick returns and insomnia, excessive sleepiness, excessive fatigue and shift work disorder. Anxiety and depression were not related to working quick returns. CONCLUSIONS: There is a health hazard associated with quick returns. Further research should aim to investigate if workplace strategies aimed at reducing the number of quick returns may reduce complaints among workers.

  8. Insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder in nurses having less than 11 hours in-between shifts.

    Science.gov (United States)

    Eldevik, Maria Fagerbakke; Flo, Elisabeth; Moen, Bente Elisabeth; Pallesen, Ståle; Bjorvatn, Bjørn

    2013-01-01

    To assess if less than 11 hours off work between work shifts (quick returns) was related to insomnia, sleepiness, fatigue, anxiety, depression and shift work disorder among nurses. A questionnaire including established instruments measuring insomnia (Bergen Insomnia Scale), sleepiness (Epworth Sleepiness Scale), fatigue (Fatigue Questionnaire), anxiety/depression (Hospital Anxiety and Depression Scale) and shift work disorder was administered. Among the 1990 Norwegian nurses who participated in the study; 264 nurses had no quick returns, 724 had 1-30 quick returns and 892 had more than 30 quick returns during the past year. 110 nurses did not report the number of quick returns during the past year. The prevalence of insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift work disorder was calculated within the three groups of nurses. Crude and adjusted logistic regression analyses were performed to assess the relation between quick returns and such complaints. We found a significant positive association between quick returns and insomnia, excessive sleepiness, excessive fatigue and shift work disorder. Anxiety and depression were not related to working quick returns. There is a health hazard associated with quick returns. Further research should aim to investigate if workplace strategies aimed at reducing the number of quick returns may reduce complaints among workers.

  9. Aromatase inhibitors and breast cancer prevention.

    Science.gov (United States)

    Litton, Jennifer Keating; Arun, Banu K; Brown, Powel H; Hortobagyi, Gabriel N

    2012-02-01

    Endocrine therapy with selective estrogen receptor modulators (SERMs) has been the mainstay of breast cancer prevention trials to date. The aromatase inhibitors, which inhibit the final chemical conversion of androgens to estrogens, have shown increased disease-free survival benefit over tamoxifen in patients with primary hormone receptor-positive breast cancer, as well as reducing the risk of developing contralateral breast cancers. The aromatase inhibitors are being actively evaluated as prevention agents for women with a history of ductal carcinoma in situ as well as for women who are considered to be at high risk for developing primary invasive breast cancer. This review evaluates the available prevention data, as evidenced by the decrease in contralateral breast cancers, when aromatase inhibitors are used in the adjuvant setting, as well as the emerging data of the aromatase inhibitors specifically tested in the prevention setting for women at high risk. Exemestane is a viable option for breast cancer prevention. We continue to await further follow-up on exemestane as well as other aromatase inhibitors in the prevention setting for women at high risk of developing breast cancer or with a history of ductal carcinoma in situ.

  10. Transglutaminase inhibitor from milk

    NARCIS (Netherlands)

    Jong, G.A.H. de; Wijngaards, G.; Koppelman, S.J.

    2003-01-01

    Cross-linking experiments of skimmed bovine milk with bacterial transglutaminase isolated from Streptoverticillium mobaraense showed only some degree of formation of high-molecular-weight casein polymers. Studies on the nature of this phenomenon revealed that bovine milk contains an inhibitor of

  11. Inhibitors of histone demethylases

    DEFF Research Database (Denmark)

    Lohse, Brian; Kristensen, Jesper L; Kristensen, Line H

    2011-01-01

    Methylated lysines are important epigenetic marks. The enzymes involved in demethylation have recently been discovered and found to be involved in cancer development and progression. Despite the relative recent discovery of these enzymes a number of inhibitors have already appeared. Most of the i...

  12. ATLAS Z Excess in Minimal Supersymmetric Standard Model

    International Nuclear Information System (INIS)

    Lu, Xiaochuan; Terada, Takahiro

    2015-06-01

    Recently the ATLAS collaboration reported a 3 sigma excess in the search for the events containing a dilepton pair from a Z boson and large missing transverse energy. Although the excess is not sufficiently significant yet, it is quite tempting to explain this excess by a well-motivated model beyond the standard model. In this paper we study a possibility of the minimal supersymmetric standard model (MSSM) for this excess. Especially, we focus on the MSSM spectrum where the sfermions are heavier than the gauginos and Higgsinos. We show that the excess can be explained by the reasonable MSSM mass spectrum.

  13. Excessive nitrite affects zebrafish valvulogenesis through yielding too much NO signaling.

    Directory of Open Access Journals (Sweden)

    Junbo Li

    Full Text Available Sodium nitrite, a common food additive, exists widely not only in the environment but also in our body. Excessive nitrite causes toxicological effects on human health; however, whether it affects vertebrate heart valve development remains unknown. In vertebrates, developmental defects of cardiac valves usually lead to congenital heart disease. To understand the toxic effects of nitrite on valvulogenesis, we exposed zebrafish embryos with different concentrations of sodium nitrite. Our results showed that sodium nitrite caused developmental defects of zebrafish heart dose dependently. It affected zebrafish heart development starting from 36 hpf (hour post fertilization when heart initiates looping process. Comprehensive analysis on the embryos at 24 hpf and 48 hpf showed that excessive nitrite did not affect blood circulation, vascular network, myocardium and endocardium development. But development of endocardial cells in atrioventricular canal (AVC of the embryos at 48 hpf was disrupted by too much nitrite, leading to defective formation of primitive valve leaflets at 76 hpf. Consistently, excessive nitrite diminished expressions of valve progenitor markers including bmp4, has2, vcana and notch1b at 48 hpf. Furthermore, 3', 5'-cyclic guanosine monophosphate (cGMP, downstream of nitric oxide (NO signaling, was increased its level significantly in the embryos exposed with excessive nitrite and microinjection of soluble guanylate cyclase inhibitor ODQ (1H-[1], [2], [4]Oxadiazolo[4,3-a] quinoxalin-1-one, an antagonist of NO signaling, into nitrite-exposed embryos could partly rescue the cardiac valve malformation. Taken together, our results show that excessive nitrite affects early valve leaflet formation by producing too much NO signaling.

  14. 75 FR 30846 - Monthly Report of Excess Income and Annual Report of Uses of Excess Income (Correction)

    Science.gov (United States)

    2010-06-02

    ... Income and Annual Report of Uses of Excess Income (Correction) AGENCY: Office of the Chief Information.... Project owners are permitted to retain Excess Income for projects under terms and conditions established by HUD. Owners must request to retain some or all of their Excess Income. The request must be...

  15. Isolation and identification of java race amniotic membrane secretory leukocyte protease inhibitor gene

    Directory of Open Access Journals (Sweden)

    Elly Munadziroh

    2008-09-01

    Full Text Available Background: Secretory leukocyte protease inhibitor (SLPI has been found to facilitate epithelialization, maintain a normal epithelial phenotype, reduce inflammation, secrete growth factors such as IL-4, IL-6, IL-10, EGF, FGF, TGF, HGFand 2-microbulin. SLPI is serine protease inhibitor, which found in secretions such as whole saliva, seminal fluid, cervical mucus, synovial fluid, breast milk, tears, amniotic fluid and amniotic membrane. Impaired healing states are characterized by excessive proteolysis and oftenbacterial infection, leading to the hypothesis that SLPI may have a role in the healing process in oral inflammation and contributes to tissue repair in oral mucosa. The oral wound healing response is impaired in the SLPI sufficient mice since matrix synthesis and collagen deposition delayed. The objective of this research is to isolate and identify the amniotic membrane of Java Race SLPI Gene. Methods: SLPI RNA was isolated from Java Race amniotic membrane and the cDNA was amplified by polymerase chain reaction (PCR. Result: Through sequence analyses, SLPI cDNA was 530 nucleotide in length with a predicted molecular mass about 12 kDa. The nucleotide sequence showed that human SLPI from sample was 98% identical with human SLPI from gene bank. PCR analysis revealed that the mRNA of SLPI was highly expressed in the amniotic membrane from Java Race sample. Conclusion: it is demonstrated that human SLPI are highly conserved in sequence content as compared to the human SLPI from gene.

  16. Discovery of Fungal Denitrification Inhibitors by Targeting Copper Nitrite Reductase from Fusarium oxysporum.

    Science.gov (United States)

    Matsuoka, Masaki; Kumar, Ashutosh; Muddassar, Muhammad; Matsuyama, Akihisa; Yoshida, Minoru; Zhang, Kam Y J

    2017-02-27

    The efficient application of nitrogenous fertilizers is urgently required, as their excessive and inefficient use is causing substantial economic loss and environmental pollution. A significant amount of applied nitrogen in agricultural soils is lost as nitrous oxide (N 2 O) in the environment due to the microbial denitrification process. The widely distributed fungus Fusarium oxysporum is a major denitrifier in agricultural soils and its denitrification activity could be targeted to reduce nitrogen loss in the form of N 2 O from agricultural soils. Here, we report the discovery of first small molecule inhibitors of copper nitrite reductase (NirK) from F. oxysporum, which is a key enzyme in the fungal denitrification process. The inhibitors were discovered by a hierarchical in silico screening approach consisting of pharmacophore modeling and molecular docking. In vitro evaluation of F. oxysporum NirK activity revealed several pyrimidone and triazinone based compounds with potency in the low micromolar range. Some of these compounds suppressed the fungal denitrification in vivo as well. The compounds reported here could be used as starting points for the development of nitrogenous fertilizer supplements and coatings as a means to prevent nitrogen loss by targeting fungal denitrification.

  17. Energy potential of the modified excess sludge

    Directory of Open Access Journals (Sweden)

    Zawieja Iwona

    2017-01-01

    Full Text Available On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4, it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

  18. Energy potential of the modified excess sludge

    Science.gov (United States)

    Zawieja, Iwona

    2017-11-01

    On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4), it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

  19. Evaluation of a workplace brief intervention for excessive alcohol consumption: the workscreen project.

    Science.gov (United States)

    Richmond, R; Kehoe, L; Heather, N; Wodak, A

    2000-01-01

    The workplace provides a useful setting for early identification and intervention with individuals who have unhealthy lifestyles. The objective was to evaluate the effects of a workplace-based lifestyle intervention (Workscreen) to reduce excessive drinking. There were eight Australia Post networks randomly allocated to experimental and control conditions, comprising 67 worksites and 1206 employees. The experimental condition involved a broad spectrum lifestyle campaign, incorporating support from management, employee awareness of health, and brief interventions for high-risk behaviors, including excessive alcohol use. Focus groups identified relevant cultural factors. Changes in workplace culture and employee behavior were assessed 10 months after baseline. Males and females were analyzed separately. Over half of APOST employees participated at each screening point. In the experimental condition 61% of employees overall and 58% of those identified as excessive drinkers in Phase 1 responded to the lifestyle campaign by attending health assessments. Analyses focusing on the organization as a whole did not reveal significant reductions in excessive alcohol consumption among men or women. However, a significant reduction in number of drinks was observed in the experimental condition among women for whom completion of baseline and follow-up could be confirmed (P workplace-based lifestyle campaign can assist self-selected employees in reducing their alcohol consumption. There was a moderately high level of participation among those identified as drinking excessively, which supports our approach of embedding a low-intensity alcohol program within the context of a broader health promotion campaign. Copyright 2000 American Health Foundation and Academic Press.

  20. Dark matter "transporting" mechanism explaining positron excesses

    Science.gov (United States)

    Kim, Doojin; Park, Jong-Chul; Shin, Seodong

    2018-04-01

    We propose a novel mechanism to explain the positron excesses, which are observed by satellite-based telescopes including PAMELA and AMS-02, in dark matter (DM) scenarios. The novelty behind the proposal is that it makes direct use of DM around the Galactic Center where DM populates most densely, allowing us to avoid tensions from cosmological and astrophysical measurements. The key ingredients of this mechanism include DM annihilation into unstable states with a very long laboratory-frame life time and their "retarded" decay near the Earth to electron-positron pair(s) possibly with other (in)visible particles. We argue that this sort of explanation is not in conflict with relevant constraints from big bang nucleosynthesis and cosmic microwave background. Regarding the resultant positron spectrum, we provide a generalized source term in the associated diffusion equation, which can be readily applicable to any type of two-"stage" DM scenarios wherein production of Standard Model particles occurs at completely different places from those of DM annihilation. We then conduct a data analysis with the recent AMS-02 data to validate our proposal.

  1. Iron excess in recreational marathon runners.

    Science.gov (United States)

    Mettler, S; Zimmermann, M B

    2010-05-01

    Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. We investigated the iron status of 170 male and female recreational runners participating in the Zürich marathon. Iron deficiency was defined either as a plasma ferritin (PF) concentration or =4.5 (functional iron deficiency). After excluding subjects with elevated C-reactive protein concentrations, iron overload was defined as PF >200 microg/l. Iron depletion was found in only 2 out of 127 men (1.6% of the male study population) and in 12 out of 43 (28.0%) women. Functional iron deficiency was found in 5 (3.9%) and 11 (25.5%) male and female athletes, respectively. Body iron stores, calculated from the sTfR/PF ratio, were significantly higher (Pmarathon runners. Median PF among males was 104 microg/l, and the upper limit of the PF distribution in males was 628 microg/l. Iron overload was found in 19 out of 127 (15.0%) men but only 2 out of 43 in women (4.7%). Gender (male sex), but not age, was a predictor of higher PF (Pperformance, our findings indicate excess body iron may be common in male recreational runners and suggest supplements should only be used if tests of iron status indicate deficiency.

  2. Excessive Neural Responses and Visual Discomfort

    Directory of Open Access Journals (Sweden)

    L O'Hare

    2014-08-01

    Full Text Available Spatially and temporally periodic patterns can look aversive to some individuals (Wilkins et al, 1984, Brain, 107, 989-1017, especially clinical populations such as migraine (Marcus and Soso, 1989, Arch Neurol., 46(10, 1129-32 epilepsy (Wilkins, Darby and Binnie, 1979, Brain, 102, 1-25. It has been suggested that this might be due to excessive neural responses (Juricevic, Land, Wilkins and Webster, 2010, Perception, 39(7, 884-899. Spatial frequency content has been shown to affect both relative and absolute discomfort judgements for spatially periodic riloid stimuli (Clark, O'Hare and Hibbard, 2013, Perception, ECVP Supp.; O'Hare, Clark and Hibbard, 2013, Perception ECVP Supplement. The current study investigated the possibility of whether neural correlates of visual discomfort from periodic stimuli could be measured using EEG. Stimuli were first matched for perceived contrast using a self adjustment task. EEG measurements were then obtained, alongside subjective discomfort judgements. Subjective discomfort judgements support those found previously, under various circumstances, indicating that spatial frequency plays a role in the perceived discomfort of periodic images. However, trends in EEG responses do not appear to have a straightforward relationship to subjective discomfort judgements.

  3. What controls deuterium excess in global precipitation?

    Directory of Open Access Journals (Sweden)

    S. Pfahl

    2014-04-01

    Full Text Available The deuterium excess (d of precipitation is widely used in the reconstruction of past climatic changes from ice cores. However, its most common interpretation as moisture source temperature cannot directly be inferred from present-day water isotope observations. Here, we use a new empirical relation between d and near-surface relative humidity (RH together with reanalysis data to globally predict d of surface evaporation from the ocean. The very good quantitative agreement of the predicted hemispherically averaged seasonal cycle with observed d in precipitation indicates that moisture source relative humidity, and not sea surface temperature, is the main driver of d variability on seasonal timescales. Furthermore, we review arguments for an interpretation of long-term palaeoclimatic d changes in terms of moisture source temperature, and we conclude that there remains no sufficient evidence that would justify to neglect the influence of RH on such palaeoclimatic d variations. Hence, we suggest that either the interpretation of d variations in palaeorecords should be adapted to reflect climatic influences on RH during evaporation, in particular atmospheric circulation changes, or new arguments for an interpretation in terms of moisture source temperature will have to be provided based on future research.

  4. Complementary technologies for verification of excess plutonium

    International Nuclear Information System (INIS)

    Langner, D.G.; Nicholas, N.J.; Ensslin, N.; Fearey, B.L.; Mitchell, D.J.; Marlow, K.W.; Luke, S.J.; Gosnell, T.B.

    1998-01-01

    Three complementary measurement technologies have been identified as candidates for use in the verification of excess plutonium of weapons origin. These technologies: high-resolution gamma-ray spectroscopy, neutron multiplicity counting, and low-resolution gamma-ray spectroscopy, are mature, robust technologies. The high-resolution gamma-ray system, Pu-600, uses the 630--670 keV region of the emitted gamma-ray spectrum to determine the ratio of 240 Pu to 239 Pu. It is useful in verifying the presence of plutonium and the presence of weapons-grade plutonium. Neutron multiplicity counting is well suited for verifying that the plutonium is of a safeguardable quantity and is weapons-quality material, as opposed to residue or waste. In addition, multiplicity counting can independently verify the presence of plutonium by virtue of a measured neutron self-multiplication and can detect the presence of non-plutonium neutron sources. The low-resolution gamma-ray spectroscopic technique is a template method that can provide continuity of knowledge that an item that enters the a verification regime remains under the regime. In the initial verification of an item, multiple regions of the measured low-resolution spectrum form a unique, gamma-radiation-based template for the item that can be used for comparison in subsequent verifications. In this paper the authors discuss these technologies as they relate to the different attributes that could be used in a verification regime

  5. Cool WISPs for stellar cooling excesses

    Energy Technology Data Exchange (ETDEWEB)

    Giannotti, Maurizio [Physical Sciences, Barry University, 11300 NE 2nd Avenue, Miami Shores, FL 33161 (United States); Irastorza, Igor; Redondo, Javier [Departamento de Física Teórica, Universidad de Zaragoza, Pedro Cerbuna 12, E-50009, Zaragoza, España (Spain); Ringwald, Andreas, E-mail: mgiannotti@barry.edu, E-mail: igor.irastorza@cern.ch, E-mail: jredondo@unizar.es, E-mail: andreas.ringwald@desy.de [Theory group, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, D-22607 Hamburg (Germany)

    2016-05-01

    Several stellar systems (white dwarfs, red giants, horizontal branch stars and possibly the neutron star in the supernova remnant Cassiopeia A) show a mild preference for a non-standard cooling mechanism when compared with theoretical models. This exotic cooling could be provided by Weakly Interacting Slim Particles (WISPs), produced in the hot cores and abandoning the star unimpeded, contributing directly to the energy loss. Taken individually, these excesses do not show a strong statistical weight. However, if one mechanism could consistently explain several of them, the hint could be significant. We analyze the hints in terms of neutrino anomalous magnetic moments, minicharged particles, hidden photons and axion-like particles (ALPs). Among them, the ALP or a massless HP represent the best solution. Interestingly, the hinted ALP parameter space is accessible to the next generation proposed ALP searches, such as ALPS II and IAXO and the massless HP requires a multi TeV energy scale of new physics that might be accessible at the LHC.

  6. Cool WISPs for stellar cooling excesses

    International Nuclear Information System (INIS)

    Giannotti, Maurizio; Irastorza, Igor; Redondo, Javier; Ringwald, Andreas

    2016-01-01

    Several stellar systems (white dwarfs, red giants, horizontal branch stars and possibly the neutron star in the supernova remnant Cassiopeia A) show a mild preference for a non-standard cooling mechanism when compared with theoretical models. This exotic cooling could be provided by Weakly Interacting Slim Particles (WISPs), produced in the hot cores and abandoning the star unimpeded, contributing directly to the energy loss. Taken individually, these excesses do not show a strong statistical weight. However, if one mechanism could consistently explain several of them, the hint could be significant. We analyze the hints in terms of neutrino anomalous magnetic moments, minicharged particles, hidden photons and axion-like particles (ALPs). Among them, the ALP or a massless HP represent the best solution. Interestingly, the hinted ALP parameter space is accessible to the next generation proposed ALP searches, such as ALPS II and IAXO and the massless HP requires a multi TeV energy scale of new physics that might be accessible at the LHC.

  7. Excessive Additive Effect On Engine Oil Viscosity

    Directory of Open Access Journals (Sweden)

    Vojtěch Kumbár

    2014-01-01

    Full Text Available The main goal of this paper is excessive additive (for oil filling effect on engine oil dynamic viscosity. Research is focused to commercially distribute automotive engine oil with viscosity class 15W–40 designed for vans. There were prepared blends of new and used engine oil without and with oil additive in specific ratio according manufacturer’s recommendations. Dynamic viscosity of blends with additive was compared with pure new and pure used engine oil. The temperature dependence dynamic viscosity of samples was evaluated by using rotary viscometer with standard spindle. Concern was that the oil additive can moves engine oil of several viscosity grades up. It is able to lead to failure in the engine. Mathematical models were used for fitting experimental values of dynamic viscosity. Exponential fit function was selected, which was very accurate because the coefficient of determination R2 achieved high values (0.98–0.99. These models are able to predict viscosity behaviour blends of engine oil and additive.

  8. Cryolipolysis for reduction of excess adipose tissue.

    Science.gov (United States)

    Nelson, Andrew A; Wasserman, Daniel; Avram, Mathew M

    2009-12-01

    Controlled cold exposure has long been reported to be a cause of panniculitis in cases such as popsicle panniculitis. Cryolipolysis is a new technology that uses cold exposure, or energy extraction, to result in localized panniculitis and modulation of fat. Presently, the Zeltiq cryolipolysis device is FDA cleared for skin cooling, as well as various other indications, but not for lipolysis. There is, however, a pending premarket notification for noninvasive fat layer reduction. Initial animal and human studies have demonstrated significant reductions in the superficial fat layer thickness, ranging from 20% to 80%, following a single cryolipolysis treatment. The decrease in fat thickness occurs gradually over the first 3 months following treatment, and is most pronounced in patients with limited, discrete fat bulges. Erythema of the skin, bruising, and temporary numbness at the treatment site are commonly observed following treatment with the device, though these effects largely resolve in approximately 1 week. To date, there have been no reports of scarring, ulceration, or alterations in blood lipid or liver function profiles. Cryolipolysis is a new, noninvasive treatment option that may be of benefit in the treatment of excess adipose tissue.

  9. Di-photon excess at LHC and the gamma ray excess at the Galactic Centre

    Energy Technology Data Exchange (ETDEWEB)

    Hektor, Andi [National Institute of Chemical Physics and Biophysics,Rävala pst. 10, 10143 Tallinn (Estonia); Marzola, Luca [National Institute of Chemical Physics and Biophysics,Rävala pst. 10, 10143 Tallinn (Estonia); Institute of Physics, University of Tartu,Ravila 14c, 50411 Tartu (Estonia)

    2016-07-25

    Motivated by the recent indications for a 750 GeV resonance in the di-photon final state at the LHC, in this work we analyse the compatibility of the excess with the broad photon excess detected at the Galactic Centre. Intriguingly, by analysing the parameter space of an effective models where a 750 GeV pseudoscalar particles mediates the interaction between the Standard Model and a scalar dark sector, we prove the compatibility of the two signals. We show, however, that the LHC mono-jet searches and the Fermi LAT measurements strongly limit the viable parameter space. We comment on the possible impact of cosmic antiproton flux measurement by the AMS-02 experiment.

  10. Dynamics of the G-excess illusion

    Science.gov (United States)

    Baylor, K. A.; Reschke, M.; Guedry, F. E.; Mcgrath, B. J.; Rupert, A. H.

    1992-01-01

    The G-excess illusion is increasingly recognized as a cause of aviation mishaps especially when pilots perform high-speed, steeply banked turns at low altitudes. Centrifuge studies of this illusion have examined the perception of subject orientation and/or target displacement during maintained hypergravity with the subject's head held stationary. The transient illusory perceptions produced by moving the head in hypergravity are difficult to study onboard centrifuges because the high angular velocity ensures the presence of strong Coriolis cross-coupled semicircular canal effects that mask immediate transient otolith-organ effects. The present study reports perceptions following head movements in hypergravity produced by high-speed aircraft maintaining a banked attitude with low angular velocity to minimize cross-coupled effects. Methods: Fourteen subjects flew on the NASA KC-135 and were exposed to resultant gravity forces of 1.3, 1.5, and 1.8 G for 3 minute periods. On command, seated subjects made controlled head movements in roll, pitch, and yaw at 30 second intervals both in the dark and with faint targets at a distance of 5 feet. Results: head movement produced transient perception of target displacement and velocity at levels as low as 1.3 G. Reports of target velocity without appropriate corresponding displacement were common. At 1.8 G when yaw head movements were made from a face down position, 4 subjects reported oscillatory rotational target displacement with fast and slow alternating components suggestive of torsional nystagmus. Head movements evoked symptoms of nausea in most subjects, with 2 subjects and 1 observer vomiting. Conclusions: The transient percepts present conflicting signals, which introduced confusion in target and subject orientation. Repeated head movements in hypergravity generate nausea by mechanisms distinct from cross-coupled Coriolis effects.

  11. Implication of zinc excess on soil health.

    Science.gov (United States)

    Wyszkowska, Jadwiga; Boros-Lajszner, Edyta; Borowik, Agata; Baćmaga, Małgorzata; Kucharski, Jan; Tomkiel, Monika

    2016-01-01

    This study was undertaken to evaluate zinc's influence on the resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease. The experiment was conducted in a greenhouse of the University of Warmia and Mazury (UWM) in Olsztyn, Poland. Plastic pots were filled with 3 kg of sandy loam with pHKCl - 7.0 each. The experimental variables were: zinc applied to soil at six doses: 100, 300, 600, 1,200, 2,400 and 4,800 mg of Zn(2+) kg(-1) in the form of ZnCl2 (zinc chloride), and species of plant: oat (Avena sativa L.) cv. Chwat and white mustard (Sinapis alba) cv. Rota. Soil without the addition of zinc served as the control. During the growing season, soil samples were subjected to microbiological analyses on experimental days 25 and 50 to determine the abundance of organotrophic bacteria, actinomyces and fungi, and the activity of dehydrogenases, catalase and urease, which provided a basis for determining the soil resistance index (RS). The physicochemical properties of soil were determined after harvest. The results of this study indicate that excessive concentrations of zinc have an adverse impact on microbial growth and the activity of soil enzymes. The resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease decreased with an increase in the degree of soil contamination with zinc. Dehydrogenases were most sensitive and urease was least sensitive to soil contamination with zinc. Zinc also exerted an adverse influence on the physicochemical properties of soil and plant development. The growth of oat and white mustard plants was almost completely inhibited in response to the highest zinc doses of 2,400 and 4,800 mg Zn(2+) kg(-1).

  12. Millisecond Pulsars and the Galactic Center Excess

    Science.gov (United States)

    Gonthier, Peter L.; Koh, Yew-Meng; Kust Harding, Alice; Ferrara, Elizabeth C.

    2017-08-01

    Various groups including the Fermi team have confirmed the spectrum of the gamma- ray excess in the Galactic Center (GCE). While some authors interpret the GCE as evidence for the annihilation of dark matter (DM), others have pointed out that the GCE spectrum is nearly identical to the average spectrum of Fermi millisecond pul- sars (MSP). Assuming the Galactic Center (GC) is populated by a yet unobserved source of MSPs that has similar properties to that of MSPs in the Galactic Disk (GD), we present results of a population synthesis of MSPs from the GC. We establish parameters of various models implemented in the simulation code by matching characteristics of 54 detected Fermi MSPs in the first point source catalog and 92 detected radio MSPs in a select group of thirteen radio surveys and targeting a birth rate of 45 MSPs per mega-year. As a check of our simulation, we find excellent agreement with the estimated numbers of MSPs in eight globular clusters. In order to reproduce the gamma-ray spectrum of the GCE, we need to populate the GC with 10,000 MSPs having a Navarro-Frenk-White distribution suggested by the halo density of DM. It may be possible for Fermi to detect some of these MSPs in the near future; the simulation also predicts that many GC MSPs have radio fluxes S1400above 10 �μJy observable by future pointed radio observations. We express our gratitude for the generous support of the National Science Foundation (RUI: AST-1009731), Fermi Guest Investigator Program and the NASA Astrophysics Theory and Fundamental Program (NNX09AQ71G).

  13. Kinetic model of excess activated sludge thermohydrolysis.

    Science.gov (United States)

    Imbierowicz, Mirosław; Chacuk, Andrzej

    2012-11-01

    Thermal hydrolysis of excess activated sludge suspensions was carried at temperatures ranging from 423 K to 523 K and under pressure 0.2-4.0 MPa. Changes of total organic carbon (TOC) concentration in a solid and liquid phase were measured during these studies. At the temperature 423 K, after 2 h of the process, TOC concentration in the reaction mixture decreased by 15-18% of the initial value. At 473 K total organic carbon removal from activated sludge suspension increased to 30%. It was also found that the solubilisation of particulate organic matter strongly depended on the process temperature. At 423 K the transfer of TOC from solid particles into liquid phase after 1 h of the process reached 25% of the initial value, however, at the temperature of 523 K the conversion degree of 'solid' TOC attained 50% just after 15 min of the process. In the article a lumped kinetic model of the process of activated sludge thermohydrolysis has been proposed. It was assumed that during heating of the activated sludge suspension to a temperature in the range of 423-523 K two parallel reactions occurred. One, connected with thermal destruction of activated sludge particles, caused solubilisation of organic carbon and an increase of dissolved organic carbon concentration in the liquid phase (hydrolysate). The parallel reaction led to a new kind of unsolvable solid phase, which was further decomposed into gaseous products (CO(2)). The collected experimental data were used to identify unknown parameters of the model, i.e. activation energies and pre-exponential factors of elementary reactions. The mathematical model of activated sludge thermohydrolysis appropriately describes the kinetics of reactions occurring in the studied system. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Acid corrosion inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, N G

    1964-04-28

    An acid corrosion inhibitor is prepared by a 2-stage vacuum evaporation of effluents obtained from the ammonia columns of the coking oven plant. The effluent, leaving a scrubber in which the phenols are removed at a temperature of 98$C, passes through a quartz filter and flows into a heated chamber in which it is used for preheating a solution circulating through a vacuum unit, maintaining the temperature of the solution at 55$ to 60$C. The effluent enters a large tank in which it is boiled at 55$ to 60$C under 635 to 640 mm Hg pressure. Double evaporation of this solution yields a very effective acid corrosion inhibitor. Its corrosion-preventing effect is 97.9% compared with 90.1% for thiourea and 88.5% for urotropin under identical conditions.

  15. Benzoylurea Chitin Synthesis Inhibitors.

    Science.gov (United States)

    Sun, Ranfeng; Liu, Chunjuan; Zhang, Hao; Wang, Qingmin

    2015-08-12

    Benzoylurea chitin synthesis inhibitors are widely used in integrated pest management (IPM) and insecticide resistance management (IRM) programs due to their low toxicity to mammals and predatory insects. In the past decades, a large number of benzoylurea derivatives have been synthesized, and 15 benzoylurea chitin synthesis inhibitors have been commercialized. This review focuses on the history of commercial benzolyphenylureas (BPUs), synthetic methods, structure-activity relationships (SAR), action mechanism research, environmental behaviors, and ecotoxicology. Furthermore, their disadvantages of high risk to aquatic invertebrates and crustaceans are pointed out. Finally, we propose that the para-substituents at anilide of benzoylphenylureas should be the functional groups, and bipartite model BPU analogues are discussed in an attempt to provide new insight for future development of BPUs.

  16. Optimal Pile Arrangement for Minimizing Excess Pore Water Pressure Build-Up

    DEFF Research Database (Denmark)

    Barari, Amin; Saadati, Meysam; Ibsen, Lars Bo

    2013-01-01

    Numerical analysis of pile group in a liquefiable soil was considered to investigate the influence of pile spacing on excess pore pressure distribution and liquefaction potential. The analysis is conducted using a two-dimensional plain strain finite difference program considering a nonlinear...... constitutive model for sandy soil, strength and stiffness reduction, and pile-soil interaction. The Mohr-Coulomb constitutive model coupled with Byrne pore pressure build-up model have been employed in the analysis. Numerical analysis results show that pile groups have significant influence on the dynamic...... response of sandy soil as they reduce the amount of excess pore pressure development during seismic shaking and may even prevent liquefaction....

  17. Nonproliferation analysis of the reduction of excess separated plutonium and high-enriched uranium

    International Nuclear Information System (INIS)

    Persiani, P.J.

    1995-01-01

    The purpose of this preliminary investigation is to explore alternatives and strategies aimed at the gradual reduction of the excess inventories of separated plutonium and high-enriched uranium (HEU) in the civilian nuclear power industry. The study attempts to establish a technical and economic basis to assist in the formation of alternative approaches consistent with nonproliferation and safeguards concerns. The analysis addresses several options in reducing the excess separated plutonium and HEU, and the consequences on nonproliferation and safeguards policy assessments resulting from the interacting synergistic effects between fuel cycle processes and isotopic signatures of nuclear materials

  18. Analysis of civilian processing programs in reduction of excess separated plutonium and high-enriched uranium

    International Nuclear Information System (INIS)

    Persiani, P.J.

    1995-01-01

    The purpose of this preliminary investigation is to explore alternatives and strategies aimed at the gradual reduction of the excess inventories of separated plutonium and high-enriched uranium (HEU) in the civilian nuclear power industry. The study attempts to establish a technical and economic basis to assist in the formation of alternative approaches consistent with nonproliferation and safeguards concerns. The analysis addresses several options in reducing the excess separated plutonium and HEU, and the consequences on nonproliferation and safeguards policy assessments resulting from the interacting synergistic effects between fuel cycle processes and isotopic signatures of nuclear materials

  19. Optimization of polyhydroxylalkanoates production from excess activated sludge

    International Nuclear Information System (INIS)

    Chua, H.; Yu, P.H.F.; Ma, C.K.

    2000-01-01

    Polyhydroxy alkanoates (PHAS) produced by microbial fermentation are biodegradable and can be used as environmentally-friendly substitutes for conventional plastics to resolve the environmental problems associated with plastics wastes. However, widespread applications of PHA are hampered by high production cost. In this study, activated sludge bacteria from a conventional wastewater treatment process were induced, by controlling the carbon-nitrogen (C:N) ratio in the reactor liquor, to accumulate PHA as a low-cost source of biodegradable plastic. Specific polymer yield increased to a maximum of O.27 g polymer/g dry cell mass when the C:N ratio was increased from 24 to 144, whereas specific growth yield decreased with increasing C:N ratio. An optimum C:N ratio of 96 provided the highest overall polymer production yield of 0.09 g polymer/g carbonaceous substrate consumed. Moreover, an intermittent nitrogen feeding program was established to further optimize the polymer volumetric productivity. The overall polymer production yield of O.11 g polymer/g carbonaceous substrate consumed was achieved under C:N ratio of 96 by feeding nitrogen in the reactor liquor once every 4 cycles. While reducing the production costs of biodegradable plastics, this technique also reduced the amount of excess sludge generated from the wastewater treatment process as the polymer portion of biomass was extracted for use. (Author)

  20. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus : Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications

    NARCIS (Netherlands)

    Heerspink, Hiddo J. L.; Perkins, Bruce A.; Fitchett, David H.; Husain, Mansoor; Cherney, David Z. I.

    2016-01-01

    Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and

  1. Partitioning of excess mortality in population-based cancer patient survival studies using flexible parametric survival models

    Directory of Open Access Journals (Sweden)

    Eloranta Sandra

    2012-06-01

    through adapting treatment strategies and follow-up of patients towards reducing the excess mortality caused by side effects of the treatment.

  2. Cellular growth kinetics distinguish a cyclophilin inhibitor from an HSP90 inhibitor as a selective inhibitor of hepatitis C virus.

    Directory of Open Access Journals (Sweden)

    Rudolf K F Beran

    Full Text Available During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA and heat-shock protein 90 (HSP90 which have each been reported to inhibit replication of hepatitis C virus (HCV. By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino-17-demethoxygeldanamycin (17-AAG to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA, exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth.

  3. SGLT2 Inhibitors: Benefit/Risk Balance.

    Science.gov (United States)

    Scheen, André J

    2016-10-01

    Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions. Empagliflozin showed remarkable reductions in cardiovascular/all-cause mortality and in hospitalization for heart failure in patients with previous cardiovascular disease. Positive renal outcomes were also shown with empagliflozin. Mostly reported adverse events are genital mycotic infections, while urinary tract infections and events linked to volume depletion are rather rare. Concern about a risk of ketoacidosis and bone fractures has been recently raised, which deserves caution and further evaluation.

  4. Excess Weapons Plutonium Immobilization in Russia

    International Nuclear Information System (INIS)

    Jardine, L.; Borisov, G.B.

    2000-01-01

    The joint goal of the Russian work is to establish a full-scale plutonium immobilization facility at a Russian industrial site by 2005. To achieve this requires that the necessary engineering and technical basis be developed in these Russian projects and the needed Russian approvals be obtained to conduct industrial-scale immobilization of plutonium-containing materials at a Russian industrial site by the 2005 date. This meeting and future work will provide the basis for joint decisions. Supporting R and D projects are being carried out at Russian Institutes that directly support the technical needs of Russian industrial sites to immobilize plutonium-containing materials. Special R and D on plutonium materials is also being carried out to support excess weapons disposition in Russia and the US, including nonproliferation studies of plutonium recovery from immobilization forms and accelerated radiation damage studies of the US-specified plutonium ceramic for immobilizing plutonium. This intriguing and extraordinary cooperation on certain aspects of the weapons plutonium problem is now progressing well and much work with plutonium has been completed in the past two years. Because much excellent and unique scientific and engineering technical work has now been completed in Russia in many aspects of plutonium immobilization, this meeting in St. Petersburg was both timely and necessary to summarize, review, and discuss these efforts among those who performed the actual work. The results of this meeting will help the US and Russia jointly define the future direction of the Russian plutonium immobilization program, and make it an even stronger and more integrated Russian program. The two objectives for the meeting were to: (1) Bring together the Russian organizations, experts, and managers performing the work into one place for four days to review and discuss their work with each other; and (2) Publish a meeting summary and a proceedings to compile reports of all the

  5. Excessive exposures of diagnostic X-ray workers in India

    International Nuclear Information System (INIS)

    Ambiger, T.Y.; Shenoy, K.S.; Patel, P.H.

    1980-01-01

    The excessive exposures (i.e. exceeding 400 mrems per fortnight) of diagnostic X-ray workers revealed under the countrywide personnel monitoring programme in India have been analysed. The analysis covers the data collected over a period of ten years during 1965-1974. The radiation workers in medical X-ray diagnostic group receiving an excess dose are found to be less than 1%. Each case of the excess dose is throughly investigated and nongenuine cases are separated and causes for genuine excessive exposures are traced. The causes and the corrective measures are enumerated. (M.G.B.)

  6. Understanding Excess Emissions from Industrial Facilities: Evidence from Texas.

    Science.gov (United States)

    Zirogiannis, Nikolaos; Hollingsworth, Alex J; Konisky, David M

    2018-03-06

    We analyze excess emissions from industrial facilities in Texas using data from the Texas Commission on Environmental Quality. Emissions are characterized as excess if they are beyond a facility's permitted levels and if they occur during startups, shutdowns, or malfunctions. We provide summary data on both the pollutants most often emitted as excess emissions and the industrial sectors and facilities responsible for those emissions. Excess emissions often represent a substantial share of a facility's routine (or permitted) emissions. We find that while excess emissions events are frequent, the majority of excess emissions are emitted by the largest events. That is, the sum of emissions in the 96-100th percentile is often several orders of magnitude larger than the remaining excess emissions (i.e., the sum of emissions below the 95th percentile). Thus, the majority of events emit a small amount of pollution relative to the total amount emitted. In addition, a small group of high emitting facilities in the most polluting industrial sectors are responsible for the vast majority of excess emissions. Using an integrated assessment model, we estimate that the health damages in Texas from excess emissions are approximately $150 million annually.

  7. Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds.

    Science.gov (United States)

    Nakahata, Adriana Miti; Mayer, Barbara; Neth, Peter; Hansen, Daiane; Sampaio, Misako Uemura; Oliva, Maria Luiza Vilela

    2013-03-01

    In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix. Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor. While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin. The effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil. At 12.5 µM concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines. Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40 % of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration. Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs. Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies

  8. Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model.

    Science.gov (United States)

    Komla-Ebri, Davide; Dambroise, Emilie; Kramer, Ina; Benoist-Lasselin, Catherine; Kaci, Nabil; Le Gall, Cindy; Martin, Ludovic; Busca, Patricia; Barbault, Florent; Graus-Porta, Diana; Munnich, Arnold; Kneissel, Michaela; Di Rocco, Federico; Biosse-Duplan, Martin; Legeai-Mallet, Laurence

    2016-05-02

    Achondroplasia (ACH) is the most frequent form of dwarfism and is caused by gain-of-function mutations in the fibroblast growth factor receptor 3-encoding (FGFR3-encoding) gene. Although potential therapeutic strategies for ACH, which aim to reduce excessive FGFR3 activation, have emerged over many years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be evaluated. Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corrects the abnormal femoral growth plate and calvaria in organ cultures from embryos of the Fgfr3Y367C/+ mouse model of ACH. Moreover, we demonstrated that a low dose of NVP-BGJ398, injected subcutaneously, was able to penetrate into the growth plate of Fgfr3Y367C/+ mice and modify its organization. Improvements to the axial and appendicular skeletons were noticeable after 10 days of treatment and were more extensive after 15 days of treatment that started from postnatal day 1. Low-dose NVP-BGJ398 treatment reduced intervertebral disc defects of lumbar vertebrae, loss of synchondroses, and foramen-magnum shape anomalies. NVP-BGJ398 inhibited FGFR3 downstream signaling pathways, including MAPK, SOX9, STAT1, and PLCγ, in the growth plates of Fgfr3Y367C/+ mice and in cultured chondrocyte models of ACH. Together, our data demonstrate that NVP-BGJ398 corrects pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH.

  9. The effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate bone cement

    Science.gov (United States)

    Razali, N. N.; Sukardi, M. A.; Sopyan, I.; Mel, M.; Salleh, H. M.; Rahman, M. M.

    2018-01-01

    The objective of this study is to determine the effects of excess calcium on the handling and mechanical properties of hydrothermal derived calcium phosphate cement (CPC) for bone filling applications. Hydroxyapatite powder was synthesized via hydrothermal method using calcium oxide, CaO and ammonium dihydrogen phosphate, NH4H2PO4 as the calcium and phosphorus precursors respectively. The effects of calcium excess were evaluated by varying the CaO content at 0, 5 and 15 mole %. The precursors were then refluxed in distilled water at 90-100°C and dried overnight until the calcium phosphate powder was formed. CPC was then produced by mixing the synthesized powder with distilled water at the powder-to-liquid (P/L) ratio of 1.5. The result from the morphological properties of CPC shows the increase in agglomeration and particles size with 5 mole % of calcium excess but decreased with 15 mole % of calcium excess in CPC. This result was in agreement with the compressive strength result where the CPC increased its strength with 5 mole % of calcium excess but reduced with 15 mole % of calcium excess. The excess in calcium precursor also significantly improved the setting time but reduced the injectability of CPC.

  10. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    BACKGROUND: Two nucleos(t)ide reverse transcriptase inhibitors (NRTIs)--abacavir and didanosine--may each be associated with excess risk of myocardial infarction. The reproducibility of this finding in an independent dataset was explored and plausible biological mechanisms were sought. METHODS...

  11. Are SGLT2 inhibitors reasonable antihypertensive drugs and renoprotective?

    Science.gov (United States)

    Lovshin, J A; Gilbert, R E

    2015-06-01

    By eliminating glucose in the urine, the sodium-glucose-linked cotransporter-2 (SGLT2) inhibitors act as osmotic diuretics to lower blood pressure in addition to reducing plasma glucose and assisting with weight loss. While not approved as antihypertensive agents, the ability of this new class of antihyperglycemic agents to lower blood pressure is not insubstantial, and while not used primarily for this indication, they may assist diabetic individuals in attaining currently recommended blood pressure targets. In addition to lowering systemic pressure, preclinical and exploratory human studies suggest that SGLT2 inhibitors may also lower intraglomerular pressure, potentially reducing the rate of GFR decline in patients with diabetic nephropathy. However, given the lack of clinically meaningful endpoint data, the use of SGLT2 inhibitors, primarily, as either antihypertensive or renoprotective agents would, at present, be premature. Fortunately, further insight will be garnered from large, randomized controlled trials that will assess the effects of various SGLT2 inhibitors on cardiovascular and renal outcomes.

  12. HIV protease drug resistance and its impact on inhibitor design.

    Science.gov (United States)

    Ala, P J; Rodgers, J D; Chang, C H

    1999-07-01

    The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.

  13. DGAT inhibitors for obesity.

    Science.gov (United States)

    Matsuda, Daisuke; Tomoda, Hiroshi

    2007-10-01

    Obesity is characterized by the accumulation of triacylglycerol in adipocytes. Diacylglycerol acyltransferase (DGAT) catalyzes the final reaction of triacylgycerol synthesis. Two isozymes of DGAT, DGAT1 and DGAT2, have been reported. Increased DGAT2 activity has a role in steatosis, while DGAT1 plays a role in very (V)LDL synthesis; increased plasma VLDL concentrations may promote obesity and thus DGAT1 is considered a potential therapeutic target of inhibition for obesity control. Several DGAT inhibitors of natural and synthetic origin have been reported, and their future prospect as anti-obesity drugs is discussed in this review.

  14. The effect of histone deacetylase inhibitors on AHSP expression.

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Okhovat

    Full Text Available Alpha-hemoglobin stabilizing protein (AHSP is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired β-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms, γ-globin genes (HBG1/2, and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p < 0.05, except for the expression of BCL11A, which was down-regulated (p < 0.05 in the cells treated with both compounds relative to the levels measured for untreated cells. The findings indicated that sodium valproate had a more considerable effect than sodium phenylbutyrate (p < 0.0005 on BCL11A repression and the up-regulation of other studied genes. γ-Globin and AHSP gene expression continuously increased during the culture period in the treated cells, with the highest gene expression observed for 1 mM sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with β-hemoglobinopathies.

  15. Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

    OpenAIRE

    Zuo, Jun; Quinn, Kevin K.; Kye, Steve; Cooper, Paige; Damoiseaux, Robert; Krogstad, Paul

    2012-01-01

    No antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and prot...

  16. Non-genetic risk factors in haemophilia A inhibitor management

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren

    2016-01-01

    In haemophilia A (HA) management, antidrug antibodies, or inhibitors, are a serious complication that renders factor VIII (FVIII) replacement therapy ineffective, increases morbidity and reduces quality of life for affected patients. Inhibitor development aetiology is multifactorial and covers both...... stressed, injured or dying cells can activate an immune reaction, without the involvement of foreign antigens. Bleeds, trauma, surgery or concomitant infection could be events initiating danger signalling in HA patients, resulting in an immune reaction towards administered FVIII that otherwise would pass...

  17. The effect of excessive iodine diet on thyroid function

    International Nuclear Information System (INIS)

    Wang Yuhua; Li Yaming

    2009-01-01

    The modify of the thyroid cell structure can be induced by excessive iodine diet. Then the disordered thyroid function can result in a number of thyroid disease. The radionucline thyroid imaging play an important role in diagnoses of thyroid. Amplify on the effect of excessive diet on thyroid function will be worthy instructing what preparation should do before doing the thyroid nuclide imaging. (authors)

  18. Management of excessive movable tissue: a modified impression technique.

    Science.gov (United States)

    Shum, Michael H C; Pow, Edmond H N

    2014-08-01

    Excessive movable tissue is a challenge in complete denture prosthetics. A modified impression technique is presented with polyvinyl siloxane impression material and a custom tray with relief areas and perforations in the area of the excessive movable tissue. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  19. Excess isentropic compressibility and speed of sound of the ternary

    Indian Academy of Sciences (India)

    These excess properties of the binary mixtures were fitted to Redlich-Kister equation, while the Cibulka's equation was used to fit the values related to the values to the ternary system. These excess properties have been used to discuss the presence of significant interactions between the component molecules in the binary ...

  20. 30 CFR 75.323 - Actions for excessive methane.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions for excessive methane. 75.323 Section... excessive methane. (a) Location of tests. Tests for methane concentrations under this section shall be made.... (1) When 1.0 percent or more methane is present in a working place or an intake air course, including...

  1. Excess molar volumes and isentropic compressibilities of binary

    Indian Academy of Sciences (India)

    Excess molar volumes (E) and deviation in isentropic compressibilities (s) have been investigated from the density and speed of sound measurements of six binary liquid mixtures containing -alkanes over the entire range of composition at 298.15 K. Excess molar volume exhibits inversion in sign in one binary ...

  2. Goodwill, Excess Returns, and Determinants of Value Creation and Overpayment

    NARCIS (Netherlands)

    Lycklama a Nijeholt, M.; Grift, Y.K.|info:eu-repo/dai/nl/073586358

    2007-01-01

    In this article we have investigated whether the determinants of excess returns (especially of target excess returns) are valid for purchased goodwill as well. Among them are acquirer’s and target’s Tobin’s q, and debt assets ratio, that explain value creation of acquisitions, and relative size,

  3. Criminal Liability of Managers for Excessive Risk-Taking?

    NARCIS (Netherlands)

    Tosza, S.T.

    2016-01-01

    The aim of the thesis was to analyse and evaluate the criminalisation of excessively risky decisions taken by managers of limited liability companies. The potentially disastrous consequences of excessive risk-taking were powerfully highlighted by the most recent financial crunch, although its

  4. Sanitization and Disposal of Excess Information Technology Equipment

    Science.gov (United States)

    2009-09-21

    Report No. D-2009-104 September 21, 2009 Sanitization and Disposal of Excess Information Technology Equipment...2009 2. REPORT TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Sanitization and Disposal of Excess Information Technology ...Defense (Networks and Information Integration)/DOD Chief Information Officer DRMS Defense Reutilization and Marketing Service IT Information

  5. 12 CFR 740.3 - Advertising of excess insurance.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Advertising of excess insurance. 740.3 Section... ACCURACY OF ADVERTISING AND NOTICE OF INSURED STATUS § 740.3 Advertising of excess insurance. Any advertising that mentions share or savings account insurance provided by a party other than the NCUA must...

  6. 40 CFR 57.304 - Bypass, excess emissions and malfunctions.

    Science.gov (United States)

    2010-07-01

    ... (performance level of interim constant controls) or § 57.303 (plantwide emission limitation) of this subpart... limitation, as well as the operating data, documents, and calculations used in determining the magnitude of the excess emissions; (3) Time and duration of the excess emissions; (4) Identity of the equipment...

  7. 19 CFR 10.625 - Refunds of excess customs duties.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Refunds of excess customs duties. 10.625 Section 10.625 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... and Apparel Goods § 10.625 Refunds of excess customs duties. (a) Applicability. Section 205 of the...

  8. A Practical Approach For Excess Bandwidth Distribution for EPONs

    KAUST Repository

    Elrasad, Amr

    2014-03-09

    This paper introduces a novel approach called Delayed Excess Scheduling (DES), which practically reuse the excess bandwidth in EPONs system. DES is suitable for the industrial deployment as it requires no timing constraint and achieves better performance compared to the previously reported schemes.

  9. Excess mortality in mothers of patients with polycystic ovary syndrome

    NARCIS (Netherlands)

    Louwers, Y. V.; Roest-Schalken, M. E.; Kleefstra, N.; van Lennep, J. Roeters; van den Berg, M.; Fauser, B. C. J. M.; Bilo, H. J. G.; Sijbrands, E. J. G.; Laven, J. S. E.

    STUDY QUESTION: Do diabetic parents of patients with polycystic ovary syndrome (PCOS) encounter excess mortality compared with the mortality of men and women with type 2 diabetes, recruited without selection for PCOS? SUMMARY ANSWER: Type 2 diabetes among mothers of PCOS patients results in excess

  10. 40 CFR 76.13 - Compliance and excess emissions.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Compliance and excess emissions. 76.13 Section 76.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.13 Compliance and excess emissions...

  11. Teachers' Knowledge of Anxiety and Identification of Excessive Anxiety in

    Science.gov (United States)

    Headley, Clea; Campbell, Marilyn A.

    2013-01-01

    This study examined primary school teachers' knowledge of anxiety and excessive anxiety symptoms in children. Three hundred and fifteen primary school teachers completed a questionnaire exploring their definitions of anxiety and the indications they associated with excessive anxiety in primary school children. Results showed that teachers had an…

  12. ON INFRARED EXCESSES ASSOCIATED WITH Li-RICH K GIANTS

    Energy Technology Data Exchange (ETDEWEB)

    Rebull, Luisa M. [Spitzer Science Center (SSC) and Infrared Science Archive (IRSA), Infrared Processing and Analysis Center - IPAC, 1200 E. California Blvd., California Institute of Technology, Pasadena, CA 91125 (United States); Carlberg, Joleen K. [NASA Goddard Space Flight Center, Code 667, Greenbelt, MD 20771 (United States); Gibbs, John C.; Cashen, Sarah; Datta, Ashwin; Hodgson, Emily; Lince, Megan [Glencoe High School, 2700 NW Glencoe Rd., Hillsboro, OR 97124 (United States); Deeb, J. Elin [Bear Creek High School, 9800 W. Dartmouth Pl., Lakewood, CO 80227 (United States); Larsen, Estefania; Altepeter, Shailyn; Bucksbee, Ethan; Clarke, Matthew [Millard South High School, 14905 Q St., Omaha, NE 68137 (United States); Black, David V., E-mail: rebull@ipac.caltech.edu [Walden School of Liberal Arts, 4230 N. University Ave., Provo, UT 84604 (United States)

    2015-10-15

    Infrared (IR) excesses around K-type red giants (RGs) have previously been discovered using Infrared Astronomy Satellite (IRAS) data, and past studies have suggested a link between RGs with overabundant Li and IR excesses, implying the ejection of circumstellar shells or disks. We revisit the question of IR excesses around RGs using higher spatial resolution IR data, primarily from the Wide-field Infrared Survey Explorer. Our goal was to elucidate the link between three unusual RG properties: fast rotation, enriched Li, and IR excess. Our sample of RGs includes those with previous IR detections, a sample with well-defined rotation and Li abundance measurements with no previous IR measurements, and a large sample of RGs asserted to be Li-rich in the literature; we have 316 targets thought to be K giants, about 40% of which we take to be Li-rich. In 24 cases with previous detections of IR excess at low spatial resolution, we believe that source confusion is playing a role, in that either (a) the source that is bright in the optical is not responsible for the IR flux, or (b) there is more than one source responsible for the IR flux as measured in IRAS. We looked for IR excesses in the remaining sources, identifying 28 that have significant IR excesses by ∼20 μm (with possible excesses for 2 additional sources). There appears to be an intriguing correlation in that the largest IR excesses are all in Li-rich K giants, though very few Li-rich K giants have IR excesses (large or small). These largest IR excesses also tend to be found in the fastest rotators. There is no correlation of IR excess with the carbon isotopic ratio, {sup 12}C/{sup 13}C. IR excesses by 20 μm, though relatively rare, are at least twice as common among our sample of Li-rich K giants. If dust shell production is a common by-product of Li enrichment mechanisms, these observations suggest that the IR excess stage is very short-lived, which is supported by theoretical calculations. Conversely, the

  13. How parents can affect excessive spending of time on screen-based activities.

    Science.gov (United States)

    Brindova, Daniela; Pavelka, Jan; Ševčikova, Anna; Žežula, Ivan; van Dijk, Jitse P; Reijneveld, Sijmen A; Geckova, Andrea Madarasova

    2014-12-12

    The aim of this study is to explore the association between family-related factors and excessive time spent on screen-based activities among school-aged children. A cross-sectional survey using the methodology of the Health Behaviour in School-aged Children study was performed in 2013, with data collected from Slovak (n = 258) and Czech (n = 406) 11- and 15-year-old children. The effects of age, gender, availability of a TV or computer in the bedroom, parental rules on time spent watching TV or working on a computer, parental rules on the content of TV programmes and computer work and watching TV together with parents on excessive time spent with screen-based activities were explored using logistic regression models. Two-thirds of respondents watch TV or play computer games at least two hours a day. Older children have a 1.80-times higher chance of excessive TV watching (CI: 1.30-2.51) and a 3.91-times higher chance of excessive computer use (CI: 2.82-5.43) in comparison with younger children. More than half of children have a TV (53%) and a computer (73%) available in their bedroom, which increases the chance of excessive TV watching by 1.59 times (CI: 1.17-2.16) and of computer use by 2.25 times (CI: 1.59-3.20). More than half of parents rarely or never apply rules on the length of TV watching (64%) or time spent on computer work (56%), and their children have a 1.76-times higher chance of excessive TV watching (CI: 1.26-2.46) and a 1.50-times greater chance of excessive computer use (CI: 1.07-2.08). A quarter of children reported that they are used to watching TV together with their parents every day, and these have a 1.84-times higher chance of excessive TV watching (1.25-2.70). Reducing time spent watching TV by applying parental rules or a parental role model might help prevent excessive time spent on screen-based activities.

  14. Nitrogen-15 studies on identifying fertilizer excess in environmental systems

    International Nuclear Information System (INIS)

    Freyer, H.D.; Aly, A.I.M.

    1975-01-01

    The feasibility of identifying fertilizer excesses in surface and ground waters on the basis of variations in the isotope ratio of nitrogen has been studied. The isotope ratio of the commonly used ammonium and nitrate fertilizers is similar to that of atmospheric nitrogen. These ratios are shifted when fertilizers are added to the soil. In the soil, fertilizer ammonium is oxidized and the nitrate formed is reduced in the heavy isotope. The fractionation factors are calculated. This artificially added nitrate becomes mixed with natural nitrate which, in general, is enriched in the heavy isotope. Only 50% (or even less) of the nitrate formed may stem from the added fertilizer. The mixing ratios are time-dependent, and different for various types and conditions of soil. In spite of this complexity, information on this isotopic process should be obtainable, if the isotope ratios of artificial and natural nitrate, respectively, are substantially different. Surface waters, in general, show no significant correlation between nitrate content and isotope ratio due to additions of sewage waters. Some data on ground waters from agricultural areas, however, where the nitrate content apparently resulted from fertilizers, gave a negative correlation of lower isotope ratios with higher nitrate contents. An inverse correlation was found in the isotope ratios of nitrate in untouched surface waters, and they even reflect the composition of the total soil nitrogen. (author)

  15. Apparent mineralocorticoid excess: time of manifestation and complications despite treatment.

    Science.gov (United States)

    Knops, Noël B B; Monnens, Leo A; Lenders, Jacques W; Levtchenko, Elena N

    2011-06-01

    Here we describe the case of a patient followed from birth because of a positive family history for apparent mineralocorticoid excess (AME) in an older brother. The patient, a girl, had normal serum electrolyte and blood pressure measurements in the first months after birth. Not until the age of 11 months did she develop anorexia and failure to thrive in combination with hypertension, hypokalemia, and metabolic alkalosis, which are consistent with the diagnosis of AME. This diagnosis was confirmed by mutation analysis of the HSD11B2 gene (C1228T). Treatment with amiloride and furosemide electrolyte disturbances normalized her blood pressure. At the age of 19 years she unexpectedly suffered a stroke. Additional investigations revealed no accepted risk factor for stroke. We discuss the possible underlying mechanisms for the delayed manifestation of hypertension and electrolyte disturbances in AME, propose an additional explanation for the stroke in this patient, and advise treatment with a mineralocorticoid receptor antagonist to reduce stroke risk in patients with AME.

  16. Excessive heat-associated gingival necrosis: a case report.

    Science.gov (United States)

    Barnes, P L; Rossi-Fedele, G

    2017-09-01

    Heat-delivery devices have been associated with relatively high temperatures. Previous basic research studies suggest that the risk for periodontal tissues is negligible, as the presence of the root filling materials, amongst other factors, reduce the risk of overheating. This report describes the case of a 45 year old male, who was undergoing restorative treatment in a multi-specialty dental practice. As part of his overall treatment planning, orthograde root canal retreatment for his maxillary left incisor teeth was deemed necessary, due to chronic apical periodontitis. Following cold lateral compaction, the coronal portion of the core material was severed using a System B Heat Source (Kerr Dental, Orange, CA, USA), with the patient reporting pain as well as a burning sensation. The following day the patient was seen by a periodontist and gingival necrosis in relation to the central incisor was found. The most likely cause of the complication was considered to be excessive heat during the operative procedure. The patient was followed up for a 2-year period and the soft tissues returned to their original condition without the need for periodontal treatment. © 2017 Australian Dental Association.

  17. Energetics and dynamics of excess electrons in simple fluids

    International Nuclear Information System (INIS)

    Space, B.

    1992-01-01

    Excess electronic dynamical and equilibrium properties are modeled in both polarizable and nonpolarizable noble gas fluids. Explicit dynamical calculations are carried out for excess electrons in fluid helium, where excess electronic eigenstates are localized. Energetics and dynamics are considered for fluids which span the entire range of polarizability present in the rare gases. Excess electronic eigenstates and eigenvalues are calculated for fluids of helium, argon and xenon. Both equilibrium and dynamical information is obtained from the calculation of these wavefunctions. A surface hopping trajectory method for studying nonadiabatic excess electronic relaxation in condensed systems is used to explore the nonadiabatic relaxation after photoexciting an equilibrated excess electron in dense fluid helium. The different types on nonadiabatic phenomena which are important in excess electronic relaxation are surveyed. The same surface hopping trajectory method is also used to study the rapid nonadiabatic relaxation after an excess electron is injected into unperturbed fluid helium. Several distinctively different relaxation processes, characterized by their relative importance at different times during the relaxation to a localized equilibrium state, are detailed. Though the dynamical properties of excess electrons under the conditions considered here have never been studied before, the behavior is remarkably similar to that observed in both experimental and theoretical studies of electron hydration dynamics, indicating that the processes described may be very general relaxation mechanisms for localization and trapping in fluids. Additionally, ground state energies of an excess electron, e 0 , are computed as a function of solvent density using model electron-atom pseudopotentials in fluid helium, argon, and xenon. The nonuniqueness of the pseudopotential description of electron-molecule interactions is demonstrated

  18. Pulmonary Toxicity of Cholinesterase Inhibitors

    National Research Council Canada - National Science Library

    Hilmas, Corey; Adler, Michael; Baskin, Steven I; Gupta, Ramesh C

    2006-01-01

    .... Whereas nerve agents were produced primarily for military deployment, other cholinesterase inhibitors were used for treating conditions such as myasthenia gravis and as pretreaunents for nerve agent exposure...

  19. Defense Inventory: Services Generally Have Reduced Excess Inventory, but Additional Actions Are Needed

    Science.gov (United States)

    2015-04-01

    MICAP Mission Impaired Capability Awaiting Parts OSD Office of the Secretary of Defense S & OP Sales and Operations Planning This is a work of...January 2013, the Army began to implement a Sales and Operations Planning ( S & OP ) process to improve its supply chain and inventory management...According to the Army Materiel Command officials, the Army’s decision to implement S & OP was recommended by an Integrated Project Team that concluded the

  20. RADIOPROTECTION CAMPAIGN AND CARD: EDUCATIONAL STRATEGIES THAT REDUCE CHILDREN'S EXCESSIVE EXPOSURE TO RADIOLOGICAL EXAMS.

    Science.gov (United States)

    Bernardo, Mônica Oliveira; Almeida, Fernando Antonio de; Morgado, Flavio

    2017-01-01

    To analyze the results of an initiative aimed at improving the reasonable use of radiological examinations, ensuring their technical quality, implementing a radioprotection campaign that includes training of the professional team, and introducing the radioprotection card for children under 12 years old as a tool for parents and doctors to control children's exposure to radiation. The study was held in a health care insurance system covering 140,000 people. A radioprotection campaign was implemented according to Image Gently • protocols, ensuring the lowest dose of radiation and the quality of examinations, and the radioprotection card was implemented. To assess the effectiveness of these actions, the number of radiological examinations performed at the pediatric emergency room in a period of one year preceding the campaign was compared with the number of radiological examinations performed one year after the campaign. The campaign was well accepted by all professionals, families, and patients involved. In the year following the implementation of radioprotection strategies, there was a 22% reduction of radiological examinations performed at the pediatric emergency room. There was also a 29% reduction in the request of two or more radiological examinations for the same child or examinations with two or more incidences. The campaign and the radioprotection card for children under 12 years old proved to be feasible strategies and correlated with a reduction in radiological examinations requested and performed at the pediatric emergency room.

  1. Assessment of the Use of Portals to Reduce Excess Material in Afloat Logistics Systems

    Science.gov (United States)

    2011-03-01

    485, 2005, p. 2092). APLs are technical documents prepared for individual equipment/components that are on board (NAVSUP P-485, 2005, p. 2093...at each stage must achieve a balance between having too much and not enough to meet demand. Inventory in this situation can be raw materials, work...their adverts. Take the example of the Nintendo Wii during the 2006 Christmas season. Nintendo’s advertisements were extensive to the point the

  2. Gender differences in excessive daytime sleepiness among Japanese workers.

    Science.gov (United States)

    Doi, Yuriko; Minowa, Masumi

    2003-02-01

    Excessive daytime sleepiness (EDS) is serious concern in the workplace with respect to errors, accidents, absenteeism, reduced productivity and impaired personal or professional life. Previous community studies found a female preponderance of EDS, however, there is little research on EDS and gender in occupational settings. We examined the gender differences in prevalence and risk factors of EDS among employees working at a telecommunications company in the Tokyo metropolitan area. Our outcome measure of EDS was the Epworth Sleepiness Scale (ESS). A self-administered questionnaire on health and sleep including ESS was distributed to 5,571 workers between December 1999 and January 2000, and 5,072 responses were returned (91.0%). A total of 4,722 full-time, non-manual and non-shift employees aged 20-59 were used for analysis (3,909 men and 813 women). Chi-squared tests and multiple logistic regression analyses were applied for examining the gender differences in the prevalence and risk factors of EDS. The prevalence rates of EDS were 13.3% for women and 7.2% for men (Pgenders, and being married worked as a protective factor against EDS for men alone. It is obvious that a ban on overtime work and a provision of mental health hygiene are the general strategies for reducing EDS at worksites. In the case of women, we suggest the formation of effective strategies for improving women's status at home and in the workplace must also be a solution for the prevention of EDS (e.g. promoting gender equality in the division of labor at home and strengthening family care policies for working women).

  3. Excess entropy scaling for the segmental and global dynamics of polyethylene melts.

    Science.gov (United States)

    Voyiatzis, Evangelos; Müller-Plathe, Florian; Böhm, Michael C

    2014-11-28

    The range of validity of the Rosenfeld and Dzugutov excess entropy scaling laws is analyzed for unentangled linear polyethylene chains. We consider two segmental dynamical quantities, i.e. the bond and the torsional relaxation times, and two global ones, i.e. the chain diffusion coefficient and the viscosity. The excess entropy is approximated by either a series expansion of the entropy in terms of the pair correlation function or by an equation of state for polymers developed in the context of the self associating fluid theory. For the whole range of temperatures and chain lengths considered, the two estimates of the excess entropy are linearly correlated. The scaled bond and torsional relaxation times fall into a master curve irrespective of the chain length and the employed scaling scheme. Both quantities depend non-linearly on the excess entropy. For a fixed chain length, the reduced diffusion coefficient and viscosity scale linearly with the excess entropy. An empirical reduction to a chain length-independent master curve is accessible for both dynamic quantities. The Dzugutov scheme predicts an increased value of the scaled diffusion coefficient with increasing chain length which contrasts physical expectations. The origin of this trend can be traced back to the density dependence of the scaling factors. This finding has not been observed previously for Lennard-Jones chain systems (Macromolecules, 2013, 46, 8710-8723). Thus, it limits the applicability of the Dzugutov approach to polymers. In connection with diffusion coefficients and viscosities, the Rosenfeld scaling law appears to be of higher quality than the Dzugutov approach. An empirical excess entropy scaling is also proposed which leads to a chain length-independent correlation. It is expected to be valid for polymers in the Rouse regime.

  4. Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight.

    Directory of Open Access Journals (Sweden)

    Laura Moreno-López

    Full Text Available INTRODUCTION: Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. METHODS: Fifty-two adolescents (16 with normal weight and 36 with excess weight were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ, the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM was used to assess possible between-group differences in regional gray matter (GM and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices and motivation/impulse control (hippocampus, prefrontal cortex. RESULTS: Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. CONCLUSION: Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

  5. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms.

    Directory of Open Access Journals (Sweden)

    Costanza Bogani

    Full Text Available BACKGROUND: Dysregulated signaling of the JAK/STAT pathway is a common feature of chronic myeloproliferative neoplasms (MPN, usually associated with JAK2V617F mutation. Recent clinical trials with JAK2 inhibitors showed significant improvements in splenomegaly and constitutional symptoms in patients with myelofibrosis but meaningful molecular responses were not documented. Accordingly, there remains a need for exploring new treatment strategies of MPN. A potential additional target for treatment is represented by the PI3K/AKT/mammalian target of rapamycin (mTOR pathway that has been found constitutively activated in MPN cells; proof-of-evidence of efficacy of the mTOR inhibitor RAD001 has been obtained recently in a Phase I/II trial in patients with myelofibrosis. The aim of the study was to characterize the effects in vitro of mTOR inhibitors, used alone and in combination with JAK2 inhibitors, against MPN cells. FINDINGS: Mouse and human JAK2V617F mutated cell lines and primary hematopoietic progenitors from MPN patients were challenged with an allosteric (RAD001 and an ATP-competitive (PP242 mTOR inhibitor and two JAK2 inhibitors (AZD1480 and ruxolitinib. mTOR inhibitors effectively reduced proliferation and colony formation of cell lines through a slowed cell division mediated by changes in cell cycle transition to the S-phase. mTOR inhibitors also impaired the proliferation and prevented colony formation from MPN hematopoietic progenitors at doses significantly lower than healthy controls. JAK2 inhibitors produced similar antiproliferative effects in MPN cell lines and primary cells but were more potent inducers of apoptosis, as also supported by differential effects on cyclinD1, PIM1 and BcLxL expression levels. Co-treatment of mTOR inhibitor with JAK2 inhibitor resulted in synergistic activity against the proliferation of JAK2V617F mutated cell lines and significantly reduced erythropoietin-independent colony growth in patients with

  6. microRNA-7 down-regulation mediates excessive collagen expression in localized scleroderma.

    Science.gov (United States)

    Etoh, Mitsuhiko; Jinnin, Masatoshi; Makino, Katsunari; Yamane, Keitaro; Nakayama, Wakana; Aoi, Jun; Honda, Noritoshi; Kajihara, Ikko; Makino, Takamitsu; Fukushima, Satoshi; Ihn, Hironobu

    2013-01-01

    Localized scleroderma (LSc), a connective tissue disorder restricted to the skin and subcutaneous tissue, is characterized by skin fibrosis due to an excessive deposition of types I collagen. The mechanism of such fibrosis is still unknown, but epigenetics may play some roles in the excessive collagen expression. In the present study, we investigated the mechanism of fibrosis seen in LSc, focusing on microRNA (miRNA). miRNA expression was determined by PCR array, real-time PCR, and in situ hybridization. The function of miRNA was evaluated using specific inhibitor. Immunoblotting was performed to detect α2(I) collagen protein. PCR array analysis using tissue miRNA demonstrated miR-7 level was significantly decreased in LSc skin as well as keloid tissue compared to normal skin in vivo. In situ hybridization also showed miR-7 expression in dermal fibroblasts was decreased in LSc dermis. The transfection of specific inhibitor for miR-7 into cultured normal dermal fibroblasts resulted in the up-regulation of α2(I) collagen protein in vitro. Also, the serum levels of miR-7 were significantly decreased in LSc patients compared with healthy controls, but serum miR-29a levels not. Systemic or local down-regulation of miR-7 may contribute to the pathogenesis of LSc via the overexpression of α2(I) collagen, and serum miR-7 may be useful as a disease marker. Investigation of the regulatory mechanisms of LSc by miRNA may lead to new treatments by the transfection into the lesional skin of this disease.

  7. Targeting Fibroblast Growth Factor 23 Signaling with Antibodies and Inhibitors, Is There a Rationale?

    Directory of Open Access Journals (Sweden)

    Seiji Fukumoto

    2018-02-01

    Full Text Available Fibroblast growth factor 23 (FGF23 is a phosphotropic hormone mainly produced by bone. FGF23 reduces serum phosphate by suppressing intestinal phosphate absorption through reducing 1,25-dihydroxyvitamin D and proximal tubular phosphate reabsorption. Excessive actions of FG23 result in several kinds of hypophosphatemic rickets/osteomalacia including X-linked hypophosphatemic rickets (XLH and tumor-induced osteomalacia. While neutral phosphate and active vitamin D are standard therapies for child patients with XLH, these medications have several limitations both in their effects and adverse events. Several approaches that inhibit FGF23 actions including anti-FGF23 antibodies and inhibitors of FGF signaling have been shown to improve phenotypes of model mice for FG23-related hypophosphatemic diseases. In addition, clinical trials indicated that a humanized anti-FGF23 antibody increased serum phosphate and improved quality of life in patients with XLH. Furthermore, circulatory FGF23 is high in patients with chronic kidney disease (CKD. Many epidemiological studies indicated the association between high FGF23 levels and various adverse events especially in patients with CKD. However, it is not known whether the inhibition of FGF23 activities in patients with CKD is beneficial for these patients. In this review, recent findings concerning the modulation of FGF23 activities are discussed.

  8. Timing of Excessive Weight Gain During Pregnancy Modulates Newborn Anthropometry.

    Science.gov (United States)

    Ruchat, Stephanie-May; Allard, Catherine; Doyon, Myriam; Lacroix, Marilyn; Guillemette, Laetitia; Patenaude, Julie; Battista, Marie-Claude; Ardilouze, Jean-Luc; Perron, Patrice; Bouchard, Luigi; Hivert, Marie-France

    2016-02-01

    Excessive gestational weight gain (GWG) is associated with increased birth weight and neonatal adiposity. However, timing of excessive GWG may have a differential impact on birth outcomes. The objective of this study was to compare the effect of early and mid/late excessive GWG on newborn anthropometry in the context of the Canadian clinical recommendations that are specific for first trimester and for second/third trimesters based on maternal pre-pregnancy BMI. We included 607 glucose-tolerant women in our main analyses, after excluding women who had less than the recommended total GWG. Maternal body weight was measured in early pregnancy, mid-pregnancy, and late pregnancy. Maternal and fetal clinical outcomes were collected, including newborn anthropometry. Women were divided into four groups according to the Canadian guidelines for GWG in the first and in the second/third trimesters: (1) "overall non-excessive" (reference group); (2) "early excessive GWG"; (3) "mid/late excessive GWG"; and (4) "overall excessive GWG." Differences in newborn anthropometry were tested across GWG categories. Women had a mean (±SD) pre-pregnancy BMI of 24.7 ± 5.2 kg/m(2) and total GWG of 15.3 ± 4.4 kg. Women with mid/late excessive GWG gave birth to heavier babies (gestational age-adjusted birth weight z-score 0.33 ± 0.91) compared with women in the reference group (0.00 ± 0.77, P = 0.007), whereas women with early excessive GWG gave birth to babies of similar weight (gestational age-adjusted z-score 0.01 ± 0.86) to the reference group (0.00 ± 0.77, P = 0.84). When we stratified our analyses and investigated women who gained within the recommendations for total GWG, mid/late excessive GWG specifically was associated with greater newborn size, similar to our main analyses. Excessive GWG in mid/late pregnancy in women who did not gain weight excessively in early pregnancy is associated with increased birth size, even in those who gained within the Canadian recommendations

  9. Thermodynamic properties of binary mixtures of tetrahydropyran with pyridine and isomeric picolines: Excess molar volumes, excess molar enthalpies and excess isentropic compressibilities

    International Nuclear Information System (INIS)

    Saini, Neeti; Jangra, Sunil K.; Yadav, J.S.; Sharma, Dimple; Sharma, V.K.

    2011-01-01

    Research highlights: → Densities, ρ and speeds of sound, u of tetrahydropyran (i) + pyridine or α-, β- or γ-picoline (j) binary mixtures at 298.15, 303.15 and 308.15 K and excess molar enthalpies, H E of the same set of mixtures at 308.15 K have been measured as a function of composition. → The observed densities and speeds of sound values have been employed to determine excess molar volumes, V E and excess isentropic compressibilities, κ S E . → Topology of the constituents of mixtures has been utilized (Graph theory) successfully to predict V E , H E and κ S E data of the investigated mixtures. → Thermodynamic data of the various mixtures have also been analyzed in terms of Prigogine-Flory-Patterson (PFP) theory. - Abstract: Densities, ρ and speeds of sound, u of tetrahydropyran (i) + pyridine or α-, β- or γ- picoline (j) binary mixtures at 298.15, 303.15 and 308.15 K and excess molar enthalpies, H E of the same set of mixtures at 308.15 K have been measured as a function of composition using an anton Parr vibrating-tube digital density and sound analyzer (model DSA 5000) and 2-drop micro-calorimeter, respectively. The resulting density and speed of sound data of the investigated mixtures have been utilized to predict excess molar volumes, V E and excess isentropic compressibilities, κ S E . The observed data have been analyzed in terms of (i) Graph theory; (ii) Prigogine-Flory-Patterson theory. It has been observed that V E , H E and κ S E data predicted by Graph theory compare well with their experimental values.

  10. Excess sludge reduction in activated sludge processes by integrating ultrasound treatment

    International Nuclear Information System (INIS)

    Perez-Elvira, S.; Fdz-Polanco, M.; Plaza, F. I.; Garralon, G.; Fdz-Polanco, F.

    2009-01-01

    Biological sludge produced in the activated sludge process can be minimised modifying the water line, the sludge line or the final disposal strategy. Selecting the water line the general idea is to reduce the sludge producing the yield coefficient by means of the called lysis cryptic growth process. The main techniques referenced in literature are onization, chlorination and chemical and heat treatment. Ultrasounds are widely used to increase anaerobic biodegradability but are not reported as system to control excess sludge production. (Author)

  11. Biological abatement of cellulase inhibitors

    Science.gov (United States)

    Bio-abatement uses a fungus to metabolize and remove fermentation inhibitors. To determine whether bio-abatement could alleviate enzyme inhibitor effects observed in biomass liquors after pretreatment, corn stover at 10% (w/v) solids was pretreated with either dilute acid or liquid hot water. The ...

  12. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

    2004-01-01

    -amylase inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha...

  13. Corrosion inhibitors. Manufacture and technology

    International Nuclear Information System (INIS)

    Ranney, M.W.

    1976-01-01

    Detailed information is presented relating to corrosion inhibitors. Areas covered include: cooling water, boilers and water supply plants; oil well and refinery operations; fuel and lubricant additives for automotive use; hydraulic fluids and machine tool lubes; grease compositions; metal surface treatments and coatings; and general processes for corrosion inhibitors

  14. Inhibitors of Microglial Neurotoxicity: Focus on Natural Products

    Directory of Open Access Journals (Sweden)

    Kyoungho Suk

    2011-01-01

    Full Text Available Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.

  15. Excessive L-cysteine induces vacuole-like cell death by activating endoplasmic reticulum stress and mitogen-activated protein kinase signaling in intestinal porcine epithelial cells.

    Science.gov (United States)

    Ji, Yun; Wu, Zhenlong; Dai, Zhaolai; Sun, Kaiji; Zhang, Qing; Wu, Guoyao

    2016-01-01

    High intake of dietary cysteine is extremely toxic to animals and the underlying mechanism remains largely unknown. This study was conducted to test the hypothesis that excessive L-cysteine induces cell death by activating endoplasmic reticulum (ER) stress and mitogen-activated protein kinase (MAPK) signaling in intestinal porcine epithelial cells. Jejunal enterocytes were cultured in the presence of 0-10 mmol/L L-cysteine. Cell viability, morphologic alterations, mRNA levels for genes involved in ER stress, protein abundances for glucose-regulated protein 78, C/EBP homologous protein (CHOP), alpha subunit of eukaryotic initiation factor-2 (eIF2α), extracellular signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal protein kinase (JNK1/2) were determined. The results showed that L-cysteine (5-10 mmol/L) reduced cell viability (P L-cysteine were not affected by the autophagy inhibitor 3-methyladenine. The protein abundances for CHOP, phosphorylated (p)-eIF2α, p-JNK1/2, p-p38 MAPK, and the spliced form of XBP-1 mRNA were enhanced (P L-cysteine induces vacuole-like cell death via the activation of ER stress and MAPK signaling in small intestinal epithelial cells. These signaling pathways may be potential targets for developing effective strategies to prevent the toxicity of dietary cysteine.

  16. Residing in economically distressed rural Appalachia is independently associated with excess body weight in college students.

    Science.gov (United States)

    Abshire, Demetrius A; Lennie, Terry A; Mudd-Martin, Gia T; Moser, Debra K

    2017-01-01

    -fold increased risk of overweight or obesity, controlling for sociodemographics, depressive symptoms, and health behaviors (odds ratio=6.36, 95%CI=1.97-20.48, p=0.002). Living in economically distressed rural Appalachia was associated with excess body weight in college students independent of sociodemographic factors, depressive symptoms, and obesity-related behaviors. Further research is needed to determine other characteristics of this region that are associated with excess body weight so that effective programs to reduce obesity risk can be implemented.

  17. Proton pump inhibitors and gastroenteritis

    International Nuclear Information System (INIS)

    Hassing, Robert-Jan; Verbon, Annelies; Visser, Herman de; Hofman, Albert; Stricker, Bruno H.

    2016-01-01

    An association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. The aim of this study was to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis in the prospective Rotterdam Study. The Rotterdam Study is a population-based cohort study among 14,926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. Furthermore, a nested case–control analysis was performed using the total cohort as a reference group. A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR 1.94; 95 % CI 1.15–3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95 % CI 3.81–9.91), using the total cohort as a reference in a nested case–control analysis. Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.

  18. A bioavailable cathepsin S nitrile inhibitor abrogates tumor development.

    Science.gov (United States)

    Wilkinson, Richard D A; Young, Andrew; Burden, Roberta E; Williams, Rich; Scott, Christopher J

    2016-04-21

    Cathepsin S has been implicated in a variety of malignancies with genetic ablation studies demonstrating a key role in tumor invasion and neo-angiogenesis. Thus, the application of cathepsin S inhibitors may have clinical utility in the treatment of cancer. In this investigation, we applied a cell-permeable dipeptidyl nitrile inhibitor of cathepsin S, originally developed to target cathepsin S in inflammatory diseases, in both in vitro and in vivo tumor models. Validation of cathepsin S selectivity was carried out by assaying fluorogenic substrate turnover using recombinant cathepsin protease. Complete kinetic analysis was carried out and true K i values calculated. Abrogation of tumour invasion using murine MC38 and human MCF7 cell lines were carried out in vitro using a transwell migration assay. Effect on endothelial tube formation was evaluated using primary HUVEC cells. The effect of inhibitor in vivo on MC38 and MCF7 tumor progression was evaluated using cells propagated in C57BL/6 and BALB/c mice respectively. Subsequent immunohistochemical staining of proliferation (Ki67) and apoptosis (TUNEL) was carried out on MCF7 tumors. We confirmed that this inhibitor was able to selectively target cathepsin S over family members K, V, L and B. The inhibitor also significantly reduced MC38 and MCF7 cell invasion and furthermore, significantly reduced HUVEC endothelial tubule formation in vitro. In vivo analysis revealed that the compound could significantly reduce tumor volume in murine MC38 syngeneic and MCF7 xenograft models. Immunohistochemical analysis of MCF7 tumors revealed cathepsin S inhibitor treatment significantly reduced proliferation and increased apoptosis. In summary, these results highlight the characterisation of this nitrile cathepsin S inhibitor using in vitro and in vivo tumor models, presenting a compound which may be used to further dissect the role of cathepsin S in cancer progression and may hold therapeutic potential.

  19. Can We Reconcile the TA Excess and Hotspot with Auger Observations?

    Energy Technology Data Exchange (ETDEWEB)

    Globus, Noemie; Piran, Tsvi [Racah Institute of Physics, The Hebrew University of Jerusalem, 91904 Jerusalem (Israel); Allard, Denis; Parizot, Etienne; Lachaud, Cyril [Laboratoire Astroparticule et Cosmologie, Université Paris Diderot/CNRS, 10 rue A. Domon et L. Duquet, F-75205 Paris Cedex 13 (France)

    2017-02-20

    The Telescope Array (TA) shows a 20° hotspot as well as an excess of ultra-high-energy cosmic-rays (UHECRs) above 50 EeV when compared with the Auger spectrum. We consider the possibility that both the TA excess and hotspot are due to a dominant source in the northern sky. We carry out detailed simulations of UHECR propagation in both the intergalactic medium and the Galaxy, using different values for the intergalactic magnetic field. We consider two general classes of sources: transients and steady, adopting a mixed UHECR composition that is consistent with the one found by Auger. The spatial location of the sources is drawn randomly. We generate Auger-like and TA-like data sets from which we determine the spectrum, the sky maps, and the level of anisotropy. We find that, while steady sources are favored over transients, it is unlikely to account for all the currently available observational data. While we reproduce fairly well the Auger spectrum for the vast majority of the simulated data sets, most of the simulated data sets with a spectrum compatible with that of TA (at most a few percent depending on density model tested) show a much stronger anisotropy than the one observed. We find that the rare cases in which both the spectrum and the anisotropy are consistent require a steady source within ∼10 Mpc, to account for the flux excess, and a strong extragalactic magnetic field ∼10 nG, to reduce the excessive anisotropy.

  20. A Structural Equation Model on Korean Adolescents' Excessive Use of Smartphones.

    Science.gov (United States)

    Lee, Hana; Kim, JooHyun

    2018-03-31

    We develop a unified structural model that defines multi-relationships between systematic factors causing excessive use of smartphones and the corresponding results. We conducted a survey with adolescents who live in Seoul, Pusan, Gangneung, Donghae, and Samcheok from Feb. to Mar. 2016. We utilized SPSS Ver. 22 and Amos Ver. 22 to analyze the survey result at a 0.05 significance level. To investigate demographic characteristics of the participants and their variations, we employed descriptive analysis. We adopted the maximum likelihood estimate method to verify the fitness of the hypothetical model and the hypotheses therein. We used χ 2 statistics, GFI, AGFI, CFI, NFI, IFI, RMR, and RMSEA to verify the fitness of our structural model. (1) Our proposed structural model demonstrated a fine fitness level. (2) Our proposed structural model could describe the excessive use of a smartphone with 88.6% accuracy. (3) The absence of the family function and relationship between friends, impulsiveness, and low self-esteem were confirmed as key factors that cause excessive use of smartphones. (4) Further, impulsiveness and low self-esteem are closely related to the absence of family functions and relations between friends by 68.3% and 54.4%, respectively. We suggest that nursing intervention programs from various angles are required to reduce adolescents' excessive use of smartphones. For example, family communication programs would be helpful for both parents and children. Consultant programs about friend relationship also meaningful for the program. Copyright © 2018. Published by Elsevier B.V.

  1. Fetal programming of adrenal androgen excess: lessons from a nonhuman primate model of polycystic ovary syndrome.

    Science.gov (United States)

    Abbott, David H; Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Conley, Alan J

    2008-01-01

    Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome (PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.

  2. Evaluation of effective dose and excess lifetime cancer risk from ...

    African Journals Online (AJOL)

    Evaluation of effective dose and excess lifetime cancer risk from indoor and outdoor gamma dose rate of university of Port Harcourt Teaching Hospital, Rivers State. ... Therefore, the management of University of Port Harcourt teaching hospital ...

  3. Implications of /sup 36/A excess on Venus

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, M [Tokyo Univ. (Japan). Inst. of Space and Aeronautical Science

    1979-05-01

    The finding of /sup 36/A excess on Venus by the mass-spectroscopic measurement of the Venus Pioneer appears to endorse the more rapid accretion theory of Venus than the Earth and the secondary origin of the terrestrial atmosphere.

  4. Gene Linked to Excess Male Hormones in Female Infertility Disorder

    Science.gov (United States)

    ... April 15, 2014 Gene linked to excess male hormones in female infertility disorder Discovery by NIH-supported ... may lead to the overproduction of androgens — male hormones similar to testosterone — occurring in women with polycystic ...

  5. Excess molar volumes and isentropic compressibilities of binary ...

    Indian Academy of Sciences (India)

    Excess molar volume; binary liquid mixtures; isentropic compressibility; intermolecular interactions. ... mixtures are essential for fluid flow, mass flow and heat transfer processes in chemical ... Experimentally determined values of density(ρ).

  6. Characteristics of adolescent excessive drinkers compared with consumers and abstainers

    NARCIS (Netherlands)

    Tomcikova, Zuzana; Geckova, Andrea Madarasova; van Dijk, Jitse P.; Reijneveld, Sijmen A.

    Introduction and Aims. This study aimed at comparing adolescent abstainers, consumers and excessive drinkers in terms of family characteristics (structure of family, socioeconomic factors), perceived social support, personality characteristics (extraversion, self-esteem, aggression) and well-being.

  7. Estimating the burden of disease attributable to excess body weight ...

    African Journals Online (AJOL)

    Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. ... Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ... lasting change in the determinants and impact of excess body weight.

  8. Industrial excess heat for district heating in Denmark

    DEFF Research Database (Denmark)

    Bühler, Fabian; Petrovic, Stefan; Karlsson, Kenneth Bernard

    2017-01-01

    analyses excess heat sources from the industrial sector and how they could be used for district heating. This method first allocates excess heat to single production units by introducing and validating a new approach. Spatial analysis of the heat sources and consumers are then performed to evaluate...... the potential for using them for district heating. In this way the theoretical potential of using the excess heat for covering the heating demand of buildings is determined. Through the use of industry specific temperature profiles the heat usable directly or via heat pumps is further found. A sensitivity...... analysis investigates the impact of future energy efficiency measures in the industry, buildings and the district heating grid on the national potential. The results show that for the case study of Denmark, 1.36 TWh of district heat could be provided annually with industrial excess heat from thermal...

  9. Targets to treat androgen excess in polycystic ovary syndrome.

    Science.gov (United States)

    Luque-Ramírez, Manuel; Escobar-Morreale, Héctor Francisco

    2015-01-01

    The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects.

  10. Modelling of excess noise attnuation by grass and forest | Onuu ...

    African Journals Online (AJOL)

    , guinea grass (panicum maximum) and forest which comprises iroko (milicia ezcelea) and white afara (terminalia superba) trees in the ratio of 2:1 approximately. Excess noise attenuation spectra have been plotted for the grass and forest for ...

  11. Iodine deficiency and iodine excess in Jiangsu Province, China

    NARCIS (Netherlands)

    Zhao, J.

    2001-01-01

    Keywords:
    iodine deficiency, iodine excess, endemic goiter, drinking water, iodine intake, thyroid function, thyroid size, iodized salt, iodized oil, IQ, physical development, hearing capacity, epidemiology, meta-analysis, IDD, randomized trial, intervention, USA, Bangladesh,

  12. Excess Volumes and Excess Isentropic Compressibilities of Binary Liquid Mixtures of Trichloroethylene with Esters at 303.15 K

    Science.gov (United States)

    Ramanaiah, S.; Rao, C. Narasimha; Nagaraja, P.; Venkateswarlu, P.

    2015-11-01

    Exces volumes, VE, and excess isentropic compressibilities, κSE, have been reported as a function of composition for binary liquid mixtures of trichloroethylene with ethyl acetate, n-propyl acetate, and n-butyl acetate at 303.15 K. Isentropic compressibilities are calculated using measured sound speeds and density data for pure components and for binary mixtures. Excess volumes and excess isentropic compressibilities are found to be negative for the three systems studied over the entire composition range at 303.15 K, whereas these values become more negative with an increase of carbon chain length. The results are discussed in terms of intermolecular interactions between unlike molecules.

  13. State dependent pseudo-resonances and excess noise

    OpenAIRE

    Papoff, F.; D'Alessandro, G.; Oppo, G.Luca

    2008-01-01

    We show that strong response to nonresonant modulations and excess noise are state dependent in generic nonlinear systems; i.e., they affect some output states but are absent from others. This is demonstrated in complex Swift-Hohenberg models relevant to optics, where it is caused by the non-normality of the linearized stability operators around selected output states, even though the cavity modes are orthogonal. In particular, we find the effective parameters that control excess noise and th...

  14. Variables of excessive computer internet use in childhood and adolescence

    OpenAIRE

    Thalemann, Ralf

    2010-01-01

    The aim of this doctoral thesis is the characterization of excessive computer and video gaming in terms of a behavioral addiction. Therefore, the development of a diagnostic psychometric instrument was central to differentiate between normal and pathological computer gaming in adolescence. In study 1, 323 children were asked about their video game playing behavior to assess the prevalence of pathological computer gaming. Data suggest that excessive computer and video game players use thei...

  15. Excessive computer game playing : evidence for addiction and aggression?

    OpenAIRE

    Grüsser, SM; Thalemann, R; Griffiths, MD

    2007-01-01

    Computer games have become an ever-increasing part of many adolescents’ day-to-day lives. Coupled with this phenomenon, reports of excessive gaming (computer game playing) denominated as “computer/video game addiction” have been discussed in the popular press as well as in recent scientific research. The aim of the present study was the investigation of the addictive potential of gaming as well as the relationship between excessive gaming and aggressive attitudes and behavior. A sample compri...

  16. A Portable Burn Pan for the Disposal of Excess Propellants

    Science.gov (United States)

    2016-06-01

    2013 - 06/01/2016 A Portable Burn Pan for the Disposal of Excess Propellants Michael Walsh USA CRREL USA CRREL 72 Lyme Road Hanover, NH 03755...Army Alaska XRF X-Ray Florescence vii ACKNOWLEDGEMENTS Project ER-201323, A Portable Burn Pan for the Disposal of Gun Propellants, was a very...contamination problem while allowing troops to train as they fight, we have developed a portable training device for burning excess gun propellants. 1.1

  17. Asymmetric Dark Matter Models and the LHC Diphoton Excess

    DEFF Research Database (Denmark)

    Frandsen, Mads T.; Shoemaker, Ian M.

    2016-01-01

    The existence of dark matter (DM) and the origin of the baryon asymmetry are persistent indications that the SM is incomplete. More recently, the ATLAS and CMS experiments have observed an excess of diphoton events with invariant mass of about 750 GeV. One interpretation of this excess is decays...... have for models of asymmetric DM that attempt to account for the similarity of the dark and visible matter abundances....

  18. Limiting excessive postoperative blood transfusion after cardiac procedures. A review.

    OpenAIRE

    Ferraris, V A; Ferraris, S P

    1995-01-01

    Analysis of blood product use after cardiac operations reveals that a few patients ( 80%). The risk factors that predispose a minority of patients to excessive blood use include patient-related factors, transfusion practices, drug-related causes, and procedure-related factors. Multivariate studies suggest that patient age and red blood cell volume are independent patient-related variables that predict excessive blood product transfusion aft...

  19. Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

    Science.gov (United States)

    Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

    2016-01-01

    Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

  20. Preventing excessive radon exposure in U.K. housing

    International Nuclear Information System (INIS)

    Miles, J.C.H.; Cliff, K.D.; Green, B.M.R.; Dixon, D.W.

    1992-01-01

    In the United Kingdom (UK) it has been recognized for some years that some members of the population received excessive radiation exposure in their homes from radon and its decay products. To prevent such exposures, an Action Level of 400 Bq m -3 was adopted in 1987. In January, 1990, the National Radiological Protection Board (NRPB) advised that the Action Level should be reduced to 200 Bq m -3 , and this advice was accepted by the Government. It is estimated that exposures in up to 100,000 UK homes exceed this Action Level; this amounts to about 0.5% of the available housing. The UK authorities have developed a strategy for preventing such exposures: (1) Areas in which it is estimated that >1% of homes exceed the Action Level for radon are being designated as Affected Areas, and a program to map such areas is under way. Households in these areas are advised to have radon measurements made by NRPB under a open-quotes freeclose quotes (Government-funded) scheme. (2) Householders found to have whole-house, whole-year average radon concentrations >200 Bq m -3 are advised to take remedial action and are provided with information on how this can be done. Partial grants toward remedial work are available in cases of financial need. So far, around 3000 such households have been identified. (3) Within Affected Areas, localities are being defined where new homes must incorporate precautions against radon exposure. In addition to this strategy, a joint case-control study of the risks of radon in homes is being undertaken by the Imperial Cancer Research Fund and NRPB, supported by the UK Government and the Commission of the European Communities