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  1. Intrathecal NGF administration reduces reactive astrocytosis and changes neurotrophin receptors expression pattern in a rat model of neuropathic pain.

    PubMed

    Cirillo, Giovanni; Cavaliere, Carlo; Bianco, Maria Rosaria; De Simone, Antonietta; Colangelo, Anna Maria; Sellitti, Stefania; Alberghina, Lilia; Papa, Michele

    2010-01-01

    Nerve growth factor (NGF), an essential peptide for sensory neurons, seems to have opposite effects when administered peripherally or directly to the central nervous system. We investigated the effects of 7-days intrathecal (i.t.) infusion of NGF on neuronal and glial spinal markers relevant to neuropathic behavior induced by chronic constriction injury (CCI) of the sciatic nerve. Allodynic and hyperalgesic behaviors were investigated by Von Frey and thermal Plantar tests, respectively. NGF-treated animals showed reduced allodynia and thermal hyperalgesia, compared to control animals. We evaluated on lumbar spinal cord the expression of microglial (ED-1), astrocytic (GFAP and S-100beta), and C- and Adelta-fibers (SubP, IB-4 and Cb) markers. I.t. NGF treatment reduced reactive astrocytosis and the density of SubP, IB4 and Cb positive fibers in the dorsal horn of injured animals. Morphometric parameters of proximal sciatic nerve stump fibers and cells in DRG were also analyzed in CCI rats: myelin thickness was reduced and DRG neurons and satellite cells appeared hypertrophic. I.t. NGF treatment showed a beneficial effect in reversing these molecular and morphological alterations. Finally, we analyzed by immunohistochemistry the expression pattern of neurotrophin receptors TrkA, pTrkA, TrkB and p75(NTR). Substantial alterations in neurotrophin receptors expression were observed in the spinal cord of CCI and NGF-treated animals. Our results indicate that i.t. NGF administration reverses the neuro-glial morphomolecular changes occurring in neuropathic animals paralleled by alterations in neurotrophin receptors ratio, and suggest that NGF is effective in restoring homeostatic conditions in the spinal cord and maintaining analgesia in neuropathic pain.

  2. Acute Morphine Administration Reduces Cell-Mediated Immunity and Induces Reactivation of Latent Herpes Simplex Virus Type 1 in BALB/c Mice

    PubMed Central

    Mojadadi, Shafi; Jamali, Abbas; Khansarinejad, Behzad; Soleimanjahi, Hoorieh; Bamdad, Taravat

    2009-01-01

    Acute morphine administration is known to alter the course of herpes simplex virus infection. In this study, the effect of acute morphine administration on the reactivation of latent herpes was investigated in a mouse model. Because of the important role of cytolytic T lymphocyte (CTL) activity in the inhibition of herpes simplex virus type 1 (HSV-1) reactivation, the effect of acute morphine administration on CTL responses was also evaluated. Furthermore, lymphocyte proliferation and IFN-γ production were evaluated for their roles in the induction of the CTL response. The findings showed that acute morphine administration significantly reduced CTL responses, lymphocyte proliferation, and IFN-γ production. Furthermore, acute morphine administration has been shown to reactivate latent HSV-1. Previous studies have shown that cellular immune responses have important roles in the inhibition of HSV reactivation. These findings suggest that suppression of a portion of the cellular immune response after acute morphine administration may constitute one part of the mechanism that induces HSV reactivation. PMID:19403060

  3. Intrathecal Administration of Mesenchymal Stem Cells Reduces the Reactive Oxygen Species and Pain Behavior in Neuropathic Rats

    PubMed Central

    Zhang, En Ji; Ko, Young Kwon

    2014-01-01

    Background Neuropathic pain induced by spinal or peripheral nerve injury is very resistant to common pain killers, nerve block, and other pain management approaches. Recently, several studies using stem cells suggested a new way to control the neuropatic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate whether intrathecal rat mesenchymal stem cells (rMSCs) were able to decrease pain behavior, as well as the relationship between rMSCs and reactive oxygen species (ROS). Methods Neuropathic pain of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats (n = 10 in each group). Mechanical sensitivity was assessed using Von Frey filaments at 3, 7, 10, 12, 14, 17, and 24 days post-ligation. rMSCs (10 µl, 1 × 105) or phosphate buffer saline (PBS, 10 µl) was injected intrathecally at 7 days post-ligation. Dihydroethidium (DHE), an oxidative fluorescent dye, was used to detect ROS at 24 days post-ligation. Results Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw after 3 days post-ligation. ROS expression was increased significantly (P < 0.05) in spinal dorsal horn of L5. Intrathecal rMSCs significantly (P < 0.01) alleviated the allodynia at 10 days after intrathecal injection (17 days post-ligation). Intrathecal rMSCs administration significantly (P < 0.05) reduced ROS expression in the spinal dorsal horn. Conclusions These results suggest that rMSCs may modulate neuropathic pain generation through ROS expression after spinal nerve ligation. PMID:25031809

  4. Reducing nurse medicine administration errors.

    PubMed

    Ofosu, Rose; Jarrett, Patricia

    Errors in administering medicines are common and can compromise the safety of patients. This review discusses the causes of drug administration error in hospitals by student and registered nurses, and the practical measures educators and hospitals can take to improve nurses' knowledge and skills in medicines management, and reduce drug errors.

  5. Reducing the cost of administrative justice

    SciTech Connect

    Tourtellotte, J.R.

    1982-11-01

    In virtually every sector of government regulation, the complaint has been lodged that the costs of administrative justice are too high. These costs in time, money, resources, and productivity can have a profound effect on the individual consumer. When applied to an energy technology such as nuclear power, costs of administrative justice can transcent time and money to have even more profound and pervasive soeietal effects. Societal costs can be expressed in terms of their impact on important national concerns, that is, the standard of living, technological superiority, and the national energy equation. Some views are presented on the interests involved in the regulation of nuclear power and what can be done to bring those interests into better balance so as to reduce the cost of administrative justice.

  6. Increasing Class C fly ash reduces alkali silica reactivity

    SciTech Connect

    Hicks, J.K.

    2007-07-01

    Contrary to earlier studies, it has been found that incremental additions of Class C fly ash do reduce alkali silica reactivity (ASR), in highly reactive, high alkali concrete mixes. AST can be further reduced by substituting 5% metakaolin or silica fume for the aggregate in concrete mixes with high (more than 30%) Class C fly ash substitution. The paper reports results of studies using Class C fly ash from the Labadie Station plant in Missouri which typically has between 1.3 and 1.45% available alkalis by ASTM C311. 7 figs.

  7. A test of reactive scope: Reducing reactive scope causes delayed wound healing.

    PubMed

    DuRant, S E; Arciniega, M L; Bauer, C M; Romero, L M

    2016-09-15

    Reactive scope predicts that all animals have an adaptive ability to respond to stressors in their environment, termed reactive homeostasis, and that only when an animal's response to stressful stimuli exceeds a certain threshold (homeostatic overload) will stress have pathological effects. While this framework has successfully helped interpret effects of stressors on wildlife, no study has designed an experiment to directly test this framework. This study was designed to expose house sparrows (Passer domesticus) to treatments that would result in varying ranges of reactive homeostasis during chronic stress, which based on the reactive scope model should cause birds with the lowest reactive homeostasis range to exhibit signs of pathology during a subsequent challenge. To modulate the reactive homeostasis range, we altered allostatic load of birds by exposing them to chronic stress while either elevating, blocking, or not manipulating corticosterone. After concluding chronic stress treatments, birds were exposed to the subsequent challenge of a superficial wound. Individuals treated with corticosterone during chronic stress (high allostatic load) experienced the most pathology, including both weight loss and slower wound healing. Unmanipulated birds (medium allostatic load) also experienced weight loss but had normal healing rates, while birds with blocked corticosterone (low allostatic load) had minimal weight loss and normal healing rates. Our results indicate that increased allostatic load reduces the reactive homeostasis range, thereby causing individuals to cross the homeostatic overload threshold sooner, and thus support the reactive scope framework.

  8. Pupillometry reveals reduced unconscious emotional reactivity in autism.

    PubMed

    Nuske, Heather J; Vivanti, Giacomo; Hudry, Kristelle; Dissanayake, Cheryl

    2014-09-01

    Recent theoretical conceptualisations have suggested that emotion processing impairments in autism stem from disruption to the sub-cortical, rapid emotion-processing system. We argue that a clear way to ascertain whether this system is affected in autism is by measuring unconscious emotional reactivity. Using backwards masking, we presented fearful expressions non-consciously (subliminally) as well as consciously (supraliminally), and measured pupillary responses as an index of emotional reactivity in 19 children with autism and 19 typically developing children, aged 2-5 years. The pupillary responses of the children with autism revealed reduced unconscious emotional reactivity, with no group differences on consciously presented emotion. Together, these results indicate a hyporesponsiveness to non-consciously presented emotion suggesting a fundamental difference in emotion processing in autism, which requires consciousness and more time. PMID:25017502

  9. Tamoxifen reduces fat mass by boosting reactive oxygen species.

    PubMed

    Liu, L; Zou, P; Zheng, L; Linarelli, L E; Amarell, S; Passaro, A; Liu, D; Cheng, Z

    2015-01-01

    As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4-5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study. PMID:25569103

  10. DRESS Syndrome Caused by Cross-reactivity Between Vancomycin and Subsequent Teicoplanin Administration: A Case Report.

    PubMed

    Miyazu, Daisuke; Kodama, Nobuhiro; Yamashita, Daiki; Tanaka, Hirokazu; Inoue, Sachiko; Imakyure, Osamu; Hirakawa, Masaaki; Shuto, Hideki; Kataoka, Yasufumi

    2016-01-01

    BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening syndrome comprising severe skin eruption, fever, eosinophilia, lymphadenopathy, and involvement of internal organs. Here, we describe a case of DRESS syndrome caused by cross-reactivity between vancomycin and subsequent teicoplanin administration. CASE REPORT A 79-year-old male was admitted to our hospital for the treatment of injuries incurred in a traffic accident. Eosinophilia and lung dysfunction appeared after vancomycin administration. These symptoms were improved temporarily by withdrawal of vancomycin and administration of corticosteroid, but exacerbated by subsequent teicoplanin administration. These symptoms disappeared after discontinuation of teicoplanin. Based on comprehensive assessment of the overall clinical course, we judged that DRESS syndrome was induced by cross-reactivity between vancomycin and subsequent teicoplanin administration. Using the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system, we categorized DRESS syndrome related to vancomycin and teicoplanin as "probable." We describe, for the first time, DRESS syndrome (defined using the RegiSCAR scoring system) caused by cross-reactivity between vancomycin and subsequent teicoplanin administration. CONCLUSIONS Clinicians should be aware that DRESS syndrome can be induced by cross-reactivity between vancomycin and teicoplanin. PMID:27572807

  11. DRESS Syndrome Caused by Cross-reactivity Between Vancomycin and Subsequent Teicoplanin Administration: A Case Report

    PubMed Central

    Miyazu, Daisuke; Kodama, Nobuhiro; Yamashita, Daiki; Tanaka, Hirokazu; Inoue, Sachiko; Imakyure, Osamu; Hirakawa, Masaaki; Shuto, Hideki; Kataoka, Yasufumi

    2016-01-01

    Patient: Male, 79 Final Diagnosis: DRESS Symptoms: Eosinophilia • fever • interstitial pneumonitis • skin rash Medication: Teicoplanin • vancomycin Clinical Procedure: — Specialty: Infectious Diseases Objective: Adverse events of drug therapy Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening syndrome comprising severe skin eruption, fever, eosinophilia, lymphadenopathy, and involvement of internal organs. Here, we describe a case of DRESS syndrome caused by cross-reactivity between vancomycin and subsequent teicoplanin administration. Case Report: A 79-year-old male was admitted to our hospital for the treatment of injuries incurred in a traffic accident. Eosinophilia and lung dysfunction appeared after vancomycin administration. These symptoms were improved temporarily by withdrawal of vancomycin and administration of corticosteroid, but exacerbated by subsequent teicoplanin administration. These symptoms disappeared after discontinuation of teicoplanin. Based on comprehensive assessment of the overall clinical course, we judged that DRESS syndrome was induced by cross-reactivity between vancomycin and subsequent teicoplanin administration. Using the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system, we categorized DRESS syndrome related to vancomycin and teicoplanin as “probable.” We describe, for the first time, DRESS syndrome (defined using the RegiSCAR scoring system) caused by cross-reactivity between vancomycin and subsequent teicoplanin administration. Conclusions: Clinicians should be aware that DRESS syndrome can be induced by cross-reactivity between vancomycin and teicoplanin. PMID:27572807

  12. Stress granules inhibit apoptosis by reducing reactive oxygen species production.

    PubMed

    Takahashi, Masahiko; Higuchi, Masaya; Matsuki, Hideaki; Yoshita, Manami; Ohsawa, Toshiaki; Oie, Masayasu; Fujii, Masahiro

    2013-02-01

    Cells can undergo two alternative fates following exposure to environmental stress: they either induce apoptosis or inhibit apoptosis and then repair the stress-induced alterations. These processes minimize cell loss and prevent the survival of cells with aberrant DNA and protein alterations. These two alternative fates are partly controlled by stress granules (SGs). While arsenite, hypoxia, and heat shock induce the formation of SGs that inhibit apoptosis, X-ray irradiation and genotoxic drugs do not induce SGs, and they are more prone to trigger apoptosis. However, it is unclear precisely how SGs control apoptosis. This study found that SGs suppress the elevation of reactive oxygen species (ROS), and this suppression is essential for inhibiting ROS-dependent apoptosis. This antioxidant activity of SGs is controlled by two SG components, GTPase-activating protein SH3 domain binding protein 1 (G3BP1) and ubiquitin-specific protease 10 (USP10). G3BP1 elevates the steady-state ROS level by inhibiting the antioxidant activity of USP10. However, following exposure to arsenite, G3BP1 and USP10 induce the formation of SGs, which uncovers the antioxidant activity of USP10. We also found that the antioxidant activity of USP10 requires the protein kinase activity of ataxia telangiectasia mutated (ATM). This work reveals that SGs are critical redox regulators that control cell fate under stress conditions.

  13. Effects of combined administration of vitamins C and E on reactive hyperemia and inflammatory process in chronic smokers.

    PubMed

    Tousoulis, Dimitris; Antoniades, Charalambos; Tentolouris, Costas; Tsioufis, Costas; Toutouza, Marina; Toutouzas, Pavlos; Stefanadis, Christodoulos

    2003-10-01

    Purpose of this study was to investigate the effect of combined administration of antioxidant vitamins C and E on endothelial function and serum levels of inflammatory markers such as tumor necrosis factor alpha (TNF-alpha), interleukines 1b (IL-1b) and 6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin in chronic smokers. Forty-three smokers were randomly divided into four groups receiving vitamin C 2 g/day (group A), vitamin C 2 g/day plus vitamin E 400 IU/day (group B), vitamin C 2 g/day plus vitamin E 800 IU/day (group C) or no antioxidant treatment (group D), for 4 weeks. Forearm blood flow (FBF) was measured using venous occlusion strain gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) was expressed as the percentage change from baseline to post reactive hyperemia blood flow. RH% was significantly increased in groups B (P<0.05) and C (P<0.01), but remained unaffected in groups A and D. Serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1 were significantly reduced in group C (P<0.05, respectively), but remained unaffected in groups A, B and D. Thus, short term administration of vitamins C (2 g/day) and E (800 IU/day) reduces serum levels of IL-1b, IL-6, sVCAM-1 and sICAM-1, and improves forearm vasodilatory response to reactive hyperemia in healthy young smokers, while monotherapy with vitamin C alone is ineffective.

  14. Early life adversity reduces stress reactivity and enhances impulsive behavior: Implications for health behaviors

    PubMed Central

    Lovallo, William R.

    2012-01-01

    Altered reactivity to stress, either in the direction of exaggerated reactivity or diminished reactivity, may signal a dysregulation of systems intended to maintain homeostasis and a state of good health. Evidence has accumulated that diminished reactivity to psychosocial stress may signal poor health outcomes. One source of diminished cortisol and autonomic reactivity is the experience of adverse rearing during childhood and adolescence. The Oklahoma Family Health Patterns Project has examined a cohort of 426 healthy young adults with and without a family history of alcoholism. Regardless of family history, persons who had experienced high degrees of adversity prior to age 16 had a constellation of changes including reduced cortisol and heart rate reactivity, diminished cognitive capacity, and unstable regulation of affect, leading to behavioral impulsivity and antisocial tendencies. We present a model whereby this constellation of physiological, cognitive, and affective tendencies is consistent with altered central dopaminergic activity leading to changes in brain function that may foster impulsive and risky behaviors. These in turn may promote greater use of alcohol other drugs along with adopting poor health behaviors. This model provides a pathway from early life adversity to low stress reactivity that forms a basis for risky behaviors and poor health outcomes. PMID:23085387

  15. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy

    PubMed Central

    Ni, Rui; Cao, Ting; Xiong, Sidong; Ma, Jian; Fan, Guo-Chang; Lacefield, James C.; Lu, Yanrong; Le Tissier, Sydney; Peng, Tianqing

    2016-01-01

    Aims The mitochondria are important sources of reactive oxygen species (ROS) in the heart. Mitochondrial ROS production has been implicated in the pathogenesis of diabetic cardiomyopathy, suggesting that therapeutic strategies specifically targeting mitochondrial ROS may have benefit in this disease. We investigated the therapeutic effects of mitochondria-targeted antioxidant mito-TEMPO on diabetic cardiomyopathy. Methods The mitochondria-targeted antioxidant mito-TEMPO was administrated after diabetes onset in a mouse model of streptozotocin-induced type-1 diabetes and type-2 diabetic db/db mice. Cardiac adverse changes were analyzed and myocardial function assessed. Cultured adult cardiomyocytes were stimulated with high glucose, and mitochondrial superoxide generation and cell death were measured. Results Incubation with high glucose increased mitochondria superoxide generation in cultured cardiomyocytes, which was prevented by mito-TEMPO. Co-incubation with mito-TEMPO abrogated high glucose-induced cell death. Mitochondrial ROS generation, and intracellular oxidative stress levels were induced in both type-1 and type-2 diabetic mouse hearts. Daily injection of mito-TEMPO for 30 days inhibited mitochondrial ROS generation, prevented intracellular oxidative stress levels, decreased apoptosis and reduced myocardial hypertrophy in diabetic hearts, leading to improvement of myocardial function in both type-1 and type-2 diabetic mice. Incubation with mito-TEMPO or inhibition of Nox2-containing NADPH oxidase prevented oxidative stress levels and cell death in high glucose-stimulated cardiomyocytes. Mechanistic study revealed that the protective effects of mito-TEMPO were associated with down-regulation of ERK1/2 phosphorylation. Conclusions Therapeutic inhibition of mitochondrial ROS by mito-TEMPO reduced adverse cardiac changes and mitigated myocardial dysfunction in diabetic mice. Thus, mitochondria-targeted antioxidants may be an effective therapy for diabetic

  16. Leptin levels are reduced by intravenous ghrelin administration and correlated with cue-induced alcohol craving.

    PubMed

    Haass-Koffler, C L; Aoun, E G; Swift, R M; de la Monte, S M; Kenna, G A; Leggio, L

    2015-01-01

    Increasing evidence supports the role of appetite-regulating pathways, including ghrelin and leptin, in alcoholism. This study tested the hypothesis that intravenous exogenous ghrelin administration acutely decreases endogenous serum leptin levels, and that changes in leptin levels negatively correlate with alcohol craving. This was a double-blind, placebo-controlled human laboratory study. Non-treatment-seeking, alcohol-dependent, heavy drinkers (n=45) were randomized to receive intravenous ghrelin or placebo, followed by a cue-reactivity procedure, during which participants were exposed to neutral (juice) and alcohol trial cues. There was a main effect for intravenous ghrelin administration, compared with placebo, in reducing serum leptin levels (P<0.01). Post hoc analysis showed significant differences in serum leptin levels at the alcohol trial (P<0.05) that persisted at the end of the experiment (P<0.05). By contrast, there were no significant differences in serum leptin levels at the juice trial (P=not significant (NS)). The change of serum leptin level at the alcohol trial correlated with the increase in alcohol urge (P<0.05), whereas urge to drink juice was not correlated with the leptin change at the juice trial (P=NS). These findings provide preliminary evidence of ghrelin-leptin cross-talk in alcoholic individuals and suggest that their relationship may have a role in alcohol craving.

  17. Ethanol self-administration in Maudsley reactive and Maudsley nonreactive inbred rats.

    PubMed

    Adams, Nelson; Mitchell, Pamela S; Campbell, Santiba D; Samson, Herman H

    2002-04-01

    This study was performed to investigate ethanol self-administration in inbred Maudsley rats, which were selected for differences in stress susceptibility and which often differ in their home cage ethanol consumption. Adult, male, Maudsley reactive (MR/Har) and Maudsley nonreactive (MNRA/Har) rats were tested in a standard protocol for the sucrose-substitution procedure for the initiation of self-administration of ethanol in an operant setting. Before and after initiation for self-administration in the operant setting, rats were tested for home cage consumption of 10% (vol./vol.) ethanol in a two-bottle test for 14 consecutive days. During the sucrose-substitution procedure, MNRA/Har rats consumed more sucrose and ethanol than did MR/Har rats. In addition, MNRA/Har rats self-administered a greater amount of ethanol during a concentration manipulation with the use of a fixed ratio (FR) 4 response requirement. However, both strains self-administered low amounts of 10% ethanol (MNRA/Har, 0.15 g/kg/day; MR/Har, 0.08 g/kg/day) after concentration manipulation compared with those observed in outbred rats and alcohol-preferring rats tested under identical conditions in other studies. Both MR/Har and MNRA/Har rats markedly increased their ethanol intake in the home cage after the initiation protocol, but there was no difference between MR/Har and MNRA/Har on that measure. The failure of MR/Har rats to self-administer ethanol was inconsistent with their home cage drinking in other studies, and this is distinctly different from the self-administration pattern of high-alcohol-drinking rat lines tested in this paradigm.

  18. Single dose testosterone administration reduces loss chasing in healthy females.

    PubMed

    Wu, Yin; Liu, Jinting; Qu, Lujing; Eisenegger, Christoph; Clark, Luke; Zhou, Xiaolin

    2016-09-01

    Testosterone has been linked to modulation of impulsivity and risky choice, potentially mediated by changes in reward or punishment sensitivity. This study investigated the effect of testosterone on risk-taking and the adjustment of risk-taking on trials following a gain or a loss. Loss chasing is operationalized herein as the propensity to recover losses by increasing risky choice. Healthy female participants (n=26) received a single-dose of 0.5mg sublingual testosterone in a double-blind, placebo-controlled crossover design. At 240min post-administration, participants performed a gambling task with a high and a low risk option. In the placebo condition, participants were more likely to choose the high risk option following losses compared to wins. This effect was abolished on the testosterone session. Ignoring prior outcomes, no overall changes in risk-taking were observed. Our data indicate that testosterone affects human decision-making via diminishing sensitivity to punishment. PMID:27236486

  19. Peripheral oxytocin administration reduces ethanol consumption in rats.

    PubMed

    MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon; Wardley, Krystal; Deogan, Sumeet; Thomas, Cameron; Peris, Joanna

    2016-01-01

    The neuropeptide oxytocin interacts with mesolimbic dopamine neurons to mediate reward associated with filial behaviors, but also other rewarding behaviors such as eating or taking drugs of abuse. Based on its efficacy to decrease intake of other abused substances, oxytocin administration is implicated as a possible treatment for excessive alcohol consumption. We tested this hypothesis by measuring ethanol intake in male Sprague-Dawley rats injected with oxytocin or saline using two different ethanol self-administration paradigms. First, a dose-response curve was constructed for oxytocin inhibition of fluid intake using a modified drinking-in-the-dark model with three bottles containing .05% saccharine, 10% ethanol in saccharine, and 15% ethanol in saccharine. Doses of oxytocin tested were 0.05, 0.1, 0.3, and 0.5mg/kg (I.P.). Next, rats received 0.3mg/kg oxytocin preceding operant sessions in which they were trained to lever-press for either plain gelatin or ethanol gelatin in order to compare oxytocin inhibition of ethanol intake versus caloric intake. For the three-bottle choice study, rats consumed significantly less ethanol when treated with the three higher doses of oxytocin on the injection day. In the operant study, 0.3mg/kg oxytocin significantly decreased ethanol gel consumption to a greater extent than plain gel consumption, both in terms of the amount of gel eaten and calories consumed. These data affirm oxytocin's efficacy for decreasing ethanol intake in rats, and confirm clinical studies suggesting oxytocin as a potential treatment for alcoholism.

  20. Peripheral oxytocin administration reduces ethanol consumption in rats

    PubMed Central

    MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon; Wardley, Krystal; Deogan, Sumeet; Thomas, Cameron; Peris, Joanna

    2016-01-01

    The neuropeptide oxytocin interacts with mesolimbic dopamine neurons to mediate reward associated with filial behaviors, but also other rewarding behaviors such as eating or taking drugs of abuse. Based on its efficacy to decrease intake of other abused substances, oxytocin administration is implicated as a possible treatment for excessive alcohol consumption. We tested this hypothesis by measuring ethanol intake in male Sprague–Dawley rats injected with oxytocin or saline using two different ethanol self-administration paradigms. First, a dose–response curve was constructed for oxytocin inhibition of fluid intake using a modified drinking-in-the-dark model with three bottles containing .05% saccharine, 10% ethanol in saccharine, and 15% ethanol in saccharine. Doses of oxytocin tested were 0.05, 0.1, 0.3, and 0.5 mg/kg (I.P.). Next, rats received 0.3 mg/kg oxytocin preceding operant sessions in which they were trained to lever-press for either plain gelatin or ethanol gelatin in order to compare oxytocin inhibition of ethanol intake versus caloric intake. For the three-bottle choice study, rats consumed significantly less ethanol when treated with the three higher doses of oxytocin on the injection day. In the operant study, 0.3 mg/kg oxytocin significantly decreased ethanol gel consumption to a greater extent than plain gel consumption, both in terms of the amount of gel eaten and calories consumed. These data affirm oxytocin's efficacy for decreasing ethanol intake in rats, and confirm clinical studies suggesting oxytocin as a potential treatment for alcoholism. PMID:26519603

  1. Reactivity of retinal blood flow to 100% oxygen breathing after lipopolysaccharide administration in healthy subjects.

    PubMed

    Kolodjaschna, Julia; Berisha, Fatmire; Lasta, Michael; Polska, Elzbieta; Fuchsjäger-Mayrl, Gabriele; Schmetterer, Leopold

    2008-08-01

    Administration of low doses of Escherichia coli endotoxin (LPS) to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate the retinal vascular reactivity after LPS infusion. In a randomized placebo-controlled cross-over study, 18 healthy male volunteers received 20 IU/kg LPS or placebo as an intravenous bolus infusion. Outcome parameters were measured at baseline and 4h after LPS/placebo administration. At baseline and at 4h after administration a short period of 100% oxygen inhalation was used to assess retinal vasoreactivity to this stimulus. Perimacular white blood cell velocity, density and flux were assessed with the blue-field entoptic technique, retinal branch arterial and venous diameters were measured with a retinal vessel analyzer and red blood cell velocity in retinal branch veins was measured with laser Doppler velocimetry. LPS is associated with peripheral blood leukocytosis and increased white blood cell density in ocular microvessels (p<0.001). In addition, retinal arterial (p=0.02) and venous (p<0.01) diameters were increased. All retinal hemodynamic parameters showed a decrease during 100% oxygen breathing. This decrease was significantly blunted by LPS for all retinal outcome parameters except venous diameter (p=0.04 for white blood cell velocity, p=0.0002 for white blood cell density, p<0.0001 for white blood cell flux, p=0.01 for arterial diameter, p=0.02 for red blood cell velocity and p=0.006 for red blood cell flux). These data indicate that LPS-induced inflammation induces vascular dysregulation in the retina. This may provide a link between inflammation and vascular dysregulation. Further studies are warranted to investigate whether this model may be suitable to study inflammation induced vascular dysregulation in the eye.

  2. Prophylactic Bacteriophage Administration More Effective than Post-infection Administration in Reducing Salmonella enterica serovar Enteritidis Shedding in Quail.

    PubMed

    Ahmadi, Mosab; Karimi Torshizi, M Amir; Rahimi, Shaban; Dennehy, John J

    2016-01-01

    Infections caused by Salmonella bacteria, often through poultry products, are a serious public health issue. Because of drawbacks associated with antibiotic prophylaxis, alternative treatments are sought. Bacterial viruses (bacteriophages) may provide an effective alternative, but concerns remain with respect to bacteriophage stability and effectiveness. To this end, we assessed the stability of a novel bacteriophage isolated from poultry excreta, siphovirus PSE, and its effectiveness in reducing Salmonella enterica serovar Enteritidis colonization in vitro and in vivo. Moreover, we sought to determine how the timing (prophylactic or therapeutic) and route (oral gavage or vent lip) of PSE administration impacted its effectiveness. Here we report that significant quantities of viable PSE bacteriophages were recovered following exposure to high and low pH, high temperatures, and bile salts, testifying to its ability to survive extreme conditions. In addition, we found that ileal lactic acid bacteria and Streptococcus spp. counts increased, but colibacilli and total aerobe counts decreased, in quail receiving phage PSE through both oral gavage and vent lip routes. In other experiments, we assessed the efficiency of PSE administration, in both prophylactic and therapeutic contexts, via either oral gavage or vent lip administration, on S. Enteritidis colonization of quail cecal tonsils. Our results demonstrate that administration of PSE as a preventive agent could reduce the S. Enteritidis colonization more effectively than post-challenge administration. Furthermore, oral administration of PSE phage is a more effective prophylactic tool for reduction of S. Enteritidis shedding in poultry than is vent lip administration. PMID:27555842

  3. Prophylactic Bacteriophage Administration More Effective than Post-infection Administration in Reducing Salmonella enterica serovar Enteritidis Shedding in Quail

    PubMed Central

    Ahmadi, Mosab; Karimi Torshizi, M. Amir; Rahimi, Shaban; Dennehy, John J.

    2016-01-01

    Infections caused by Salmonella bacteria, often through poultry products, are a serious public health issue. Because of drawbacks associated with antibiotic prophylaxis, alternative treatments are sought. Bacterial viruses (bacteriophages) may provide an effective alternative, but concerns remain with respect to bacteriophage stability and effectiveness. To this end, we assessed the stability of a novel bacteriophage isolated from poultry excreta, siphovirus PSE, and its effectiveness in reducing Salmonella enterica serovar Enteritidis colonization in vitro and in vivo. Moreover, we sought to determine how the timing (prophylactic or therapeutic) and route (oral gavage or vent lip) of PSE administration impacted its effectiveness. Here we report that significant quantities of viable PSE bacteriophages were recovered following exposure to high and low pH, high temperatures, and bile salts, testifying to its ability to survive extreme conditions. In addition, we found that ileal lactic acid bacteria and Streptococcus spp. counts increased, but colibacilli and total aerobe counts decreased, in quail receiving phage PSE through both oral gavage and vent lip routes. In other experiments, we assessed the efficiency of PSE administration, in both prophylactic and therapeutic contexts, via either oral gavage or vent lip administration, on S. Enteritidis colonization of quail cecal tonsils. Our results demonstrate that administration of PSE as a preventive agent could reduce the S. Enteritidis colonization more effectively than post-challenge administration. Furthermore, oral administration of PSE phage is a more effective prophylactic tool for reduction of S. Enteritidis shedding in poultry than is vent lip administration. PMID:27555842

  4. Reactivity of cellulose reducing end in pyrolysis as studied by methyl glucoside-impregnation.

    PubMed

    Matsuoka, Seiji; Kawamoto, Haruo; Saka, Shiro

    2016-02-01

    For better understanding of the roles of cellulose reducing ends during thermal degradation of cellulose and wood, cellulose samples impregnated with methyl-β-D-glucopyranoside (GlcβOMe), a simple non-reducing sugar model, were pyrolyzed under N2 at relatively low temperatures of 200-280 °C. By the impregnation, cellulose was rather stabilized against discoloration and weight-loss through converting the reducing ends into the glycosides with GlcβOMe. Alternatively, polymerization and discoloration of GlcβOMe were accelerated in the presence of cellulose. A mechanism via reducing sugars as reactive intermediates formed through hydrolysis is proposed to explain these phenomena. These information would be useful to understand the interactions between cellulose and hemicellulose in wood cell wall as well as the role of the reducing ends in cellulose thermal degradation. PMID:26717548

  5. Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus.

    PubMed Central

    Devesa, M; Khudyakov, Y E; Capriles, F; Blitz, L; Fields, H A; Liprandi, F; Pujol, F H

    1997-01-01

    Antibody reactivities to hepatitis C virus (HCV) antigens and to synthetic peptides derived from different parts of the HCV genome (core, NS4, and NS5) were evaluated in HCV-infected hemodialysis patients. In the RIBA 3 assay, NS5 was significantly less recognizable by sera of hemodialysis patients compared to other HCV-infected subjects. Among hemodialysis patients, those coinfected with hepatitis B virus (HBV) (positive for hepatitis B surface antigen [HBsAg+]) showed a reduction in reactivity to C33 and C100. Sera of only 23% of the hemodialysis patients (37 of 161) reacted with more than three of eight peptides tested, significantly fewer than the 60% (12 of 20) of the sera of other HCV-infected patients tested (P = 0.001). This immunosuppression was also manifested by a reduced frequency of recognition of additional peptides on follow-up. An even more reduced reactivity was observed among the HBV-coinfected patients (HBsAg+). The low-responder hemodialysis patients were not infected with any particular genotype of HCV, and the same HCV genotypes observed in the whole group of hemodialysis patients (1a, 1b, 2a, and 3a) were found circulating in the low-responder group. Even in this low-responder population, the good performance of two peptides (peptide 716, corresponding to a portion of the core, and peptide 59, corresponding to a portion of NS4) corroborates the immunodominance of the conserved epitopes within these peptides. PMID:9384281

  6. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

    PubMed

    Caballero, A E; Arora, S; Saouaf, R; Lim, S C; Smakowski, P; Park, J Y; King, G L; LoGerfo, F W; Horton, E S; Veves, A

    1999-09-01

    Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT

  7. Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

    PubMed Central

    Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

    2012-01-01

    Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

  8. Simulated gastrointestinal digestion reduces the allergic reactivity of shrimp extract proteins and tropomyosin.

    PubMed

    Gámez, Cristina; Zafra, Ma Paz; Sanz, Verónica; Mazzeo, Carla; Ibáñez, Ma Dolores; Sastre, Joaquín; del Pozo, Victoria

    2015-04-15

    Shrimp are highly allergenic foods. Current management are limited to the avoidance of foods. Therefore, there is an unmet need for a safe and effective therapy using modified allergens. This study focuses on assessing the potential for modification of the allergenicity of shrimp proteins following heat treatment or simulated gastric digestion. Shrimp proteins do not reduce their IgE reactivity after heat treatment but it is reduced by simulated gastric digestion in a time- and dose-dependent manner. Tropomyosin in shrimp extract is worse digested than purified tropomyosin. After 60 min of 10 U/μg pepsin digestion, a strong inhibition was produced in the in vivo skin reactivity of shrimp extracts and in activation of basophils from allergic patients. Immunisation experiments performed in rabbits demonstrated that digested boiled shrimp extract is able to induce IgG antibodies that block the IgE binding to the untreated boiled shrimp extract in shrimp-allergic patients. Building on our observations, digestion treatment could be an effective method for reducing shrimp allergenicity while maintaining the immunogenicity.

  9. Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals

    PubMed Central

    Moran-Santa Maria, Megan M.; Baker, Nathaniel L.; Ramakrishnan, Viswanathan; Brady, Kathleen T.; McRae-Clark, Aimee

    2014-01-01

    Background Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals, thus medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. Objectives To examine the impact of acute administration of the α-2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. Methods In a double-blind, placebo-controlled study, cocaine-dependent individuals (N=84), were randomized to receive either 2 mg guanfacine (n=50) or placebo (n=34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n=26; placebo n=15) or a no-stress (guanfacine n=24; placebo n=19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. Results The no-stress guanfacine group reported greater craving in response to cocaine-cues as compared to the neutral cue (p<0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline (p=0.032). The cocaine-cue increased subjective stress in the guanfacine (p<0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all p>0.70). Conclusion This study found no effects of a single 2 mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic treatment strategy. PMID:25140866

  10. Reduced reactivity to air on HF-treated YBa2Cu3O7 - x surfaces

    NASA Astrophysics Data System (ADS)

    Vasquez, R. P.; Hunt, B. D.; Foote, M. C.

    1989-06-01

    Treatment of YBa2Cu3O7-x films with a nonaqueous solution of HF in absolute ethanol results in the formation of an oxyfluoride with relative Y:Ba:Cu concentrations of 1:4:3 on the surface, as determined by x-ray photoelectron spectroscopy. The passivation properties of chemically treated films were tested by monitoring the growth of the high binding energy O 1s peak, associated with nonsuperconducting surface species, as a function of air exposure time, for both HF-treated and untreated films. The native oxyfluoride is shown to reduce the reactivity of the superconductor to air.

  11. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    SciTech Connect

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian

    2014-11-01

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.

  12. Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring.

    PubMed

    Sanders, Marijke W; Fazzi, Gregorio E; Janssen, Ger M J; de Leeuw, Peter W; Blanco, Carlos E; De Mey, Jo G R

    2004-06-01

    Fetal malnutrition and hypoxia may modify organ system maturation and result in cardiovascular diseases in the adult. We tested whether intrauterine stress (IUS) leads to persistent alterations of renal biology. In rats, intrauterine stress was induced by ligation of the uterine arteries at day 17 of pregnancy. Renal arteries of the 21-day-old male offspring were isolated to study pharmacological reactivity. Kidneys were dissected to analyze renal structure and beta-adrenoceptor expression. At 21 days of age, half of the animals underwent unilateral left nephrectomy. At the age of 12 weeks, rats were instrumented for blood pressure monitoring, blood sampling, and renal function measurements. After IUS, litter size and birth weight were reduced, whereas the hematocrit was increased. Renal arterial responses to beta-adrenergic stimulation and sensitivity to adenylyl cyclase activation were increased, along with the renal expression of beta2-adrenoceptors. At 21 days and at 6 months of age, the number and density of the glomeruli were reduced, whereas their size was increased. The filtration fraction and urinary albumin concentration were increased 12 weeks after intrauterine stress. In control rats, removal of the left kidney at 21 days of age did not affect kidney function and blood pressure. However, after IUS, the remaining right kidney failed to compensate for the loss of the left kidney, and blood pressure was increased. In conclusion, prenatal stress transiently modifies renal arterial reactivity and results in long-lasting adverse effects on renal structure and function and on renal compensatory mechanisms. PMID:15117909

  13. Evidence for reactive reduced phosphorus species in the early Archean ocean

    PubMed Central

    Pasek, Matthew A.; Harnmeijer, Jelte P.; Buick, Roger; Gull, Maheen; Atlas, Zachary

    2013-01-01

    It has been hypothesized that before the emergence of modern DNA–RNA–protein life, biology evolved from an “RNA world.” However, synthesizing RNA and other organophosphates under plausible early Earth conditions has proved difficult, with the incorporation of phosphorus (P) causing a particular problem because phosphate, where most environmental P resides, is relatively insoluble and unreactive. Recently, it has been proposed that during the Hadean–Archean heavy bombardment by extraterrestrial impactors, meteorites would have provided reactive P in the form of the iron–nickel phosphide mineral schreibersite. This reacts in water, releasing soluble and reactive reduced P species, such as phosphite, that could then be readily incorporated into prebiotic molecules. Here, we report the occurrence of phosphite in early Archean marine carbonates at levels indicating that this was an abundant dissolved species in the ocean before 3.5 Ga. Additionally, we show that schreibersite readily reacts with an aqueous solution of glycerol to generate phosphite and the membrane biomolecule glycerol–phosphate under mild thermal conditions, with this synthesis using a mineral source of P. Phosphite derived from schreibersite was, hence, a plausible reagent in the prebiotic synthesis of phosphorylated biomolecules and was also present on the early Earth in quantities large enough to have affected the redox state of P in the ocean. Phosphorylated biomolecules like RNA may, thus, have first formed from the reaction of reduced P species with the prebiotic organic milieu on the early Earth. PMID:23733935

  14. Evidence for reactive reduced phosphorus species in the early Archean ocean.

    PubMed

    Pasek, Matthew A; Harnmeijer, Jelte P; Buick, Roger; Gull, Maheen; Atlas, Zachary

    2013-06-18

    It has been hypothesized that before the emergence of modern DNA-RNA-protein life, biology evolved from an "RNA world." However, synthesizing RNA and other organophosphates under plausible early Earth conditions has proved difficult, with the incorporation of phosphorus (P) causing a particular problem because phosphate, where most environmental P resides, is relatively insoluble and unreactive. Recently, it has been proposed that during the Hadean-Archean heavy bombardment by extraterrestrial impactors, meteorites would have provided reactive P in the form of the iron-nickel phosphide mineral schreibersite. This reacts in water, releasing soluble and reactive reduced P species, such as phosphite, that could then be readily incorporated into prebiotic molecules. Here, we report the occurrence of phosphite in early Archean marine carbonates at levels indicating that this was an abundant dissolved species in the ocean before 3.5 Ga. Additionally, we show that schreibersite readily reacts with an aqueous solution of glycerol to generate phosphite and the membrane biomolecule glycerol-phosphate under mild thermal conditions, with this synthesis using a mineral source of P. Phosphite derived from schreibersite was, hence, a plausible reagent in the prebiotic synthesis of phosphorylated biomolecules and was also present on the early Earth in quantities large enough to have affected the redox state of P in the ocean. Phosphorylated biomolecules like RNA may, thus, have first formed from the reaction of reduced P species with the prebiotic organic milieu on the early Earth. PMID:23733935

  15. Evidence for reactive reduced phosphorus species in the early Archean ocean.

    PubMed

    Pasek, Matthew A; Harnmeijer, Jelte P; Buick, Roger; Gull, Maheen; Atlas, Zachary

    2013-06-18

    It has been hypothesized that before the emergence of modern DNA-RNA-protein life, biology evolved from an "RNA world." However, synthesizing RNA and other organophosphates under plausible early Earth conditions has proved difficult, with the incorporation of phosphorus (P) causing a particular problem because phosphate, where most environmental P resides, is relatively insoluble and unreactive. Recently, it has been proposed that during the Hadean-Archean heavy bombardment by extraterrestrial impactors, meteorites would have provided reactive P in the form of the iron-nickel phosphide mineral schreibersite. This reacts in water, releasing soluble and reactive reduced P species, such as phosphite, that could then be readily incorporated into prebiotic molecules. Here, we report the occurrence of phosphite in early Archean marine carbonates at levels indicating that this was an abundant dissolved species in the ocean before 3.5 Ga. Additionally, we show that schreibersite readily reacts with an aqueous solution of glycerol to generate phosphite and the membrane biomolecule glycerol-phosphate under mild thermal conditions, with this synthesis using a mineral source of P. Phosphite derived from schreibersite was, hence, a plausible reagent in the prebiotic synthesis of phosphorylated biomolecules and was also present on the early Earth in quantities large enough to have affected the redox state of P in the ocean. Phosphorylated biomolecules like RNA may, thus, have first formed from the reaction of reduced P species with the prebiotic organic milieu on the early Earth.

  16. Evidence for reactive reduced phosphorus species in the early Archean ocean

    NASA Astrophysics Data System (ADS)

    Pasek, Matthew A.; Harnmeijer, Jelte P.; Buick, Roger; Gull, Maheen; Atlas, Zachary

    2013-06-01

    It has been hypothesized that before the emergence of modern DNA-RNA-protein life, biology evolved from an "RNA world." However, synthesizing RNA and other organophosphates under plausible early Earth conditions has proved difficult, with the incorporation of phosphorus (P) causing a particular problem because phosphate, where most environmental P resides, is relatively insoluble and unreactive. Recently, it has been proposed that during the Hadean-Archean heavy bombardment by extraterrestrial impactors, meteorites would have provided reactive P in the form of the iron-nickel phosphide mineral schreibersite. This reacts in water, releasing soluble and reactive reduced P species, such as phosphite, that could then be readily incorporated into prebiotic molecules. Here, we report the occurrence of phosphite in early Archean marine carbonates at levels indicating that this was an abundant dissolved species in the ocean before 3.5 Ga. Additionally, we show that schreibersite readily reacts with an aqueous solution of glycerol to generate phosphite and the membrane biomolecule glycerol-phosphate under mild thermal conditions, with this synthesis using a mineral source of P. Phosphite derived from schreibersite was, hence, a plausible reagent in the prebiotic synthesis of phosphorylated biomolecules and was also present on the early Earth in quantities large enough to have affected the redox state of P in the ocean. Phosphorylated biomolecules like RNA may, thus, have first formed from the reaction of reduced P species with the prebiotic organic milieu on the early Earth.

  17. Mothers' depressive symptoms predict both increased and reduced negative reactivity: aversion sensitivity and the regulation of emotion.

    PubMed

    Dix, Theodore; Moed, Anat; Anderson, Edward R

    2014-07-01

    This study examined whether, as mothers' depressive symptoms increase, their expressions of negative emotion to children increasingly reflect aversion sensitivity and motivation to minimize ongoing stress or discomfort. In multiple interactions over 2 years, negative affect expressed by 319 mothers and their children was observed across variations in mothers' depressive symptoms, the aversiveness of children's immediate behavior, and observed differences in children's general negative reactivity. As expected, depressive symptoms predicted reduced maternal negative reactivity when child behavior was low in aversiveness, particularly with children who were high in negative reactivity. Depressive symptoms predicted high negative reactivity and steep increases in negative reactivity as the aversiveness of child behavior increased, particularly when high and continued aversiveness from the child was expected (i.e., children were high in negative reactivity). The findings are consistent with the proposal that deficits in parenting competence as depressive symptoms increase reflect aversion sensitivity and motivation to avoid conflict and suppress children's aversive behavior.

  18. Reduced emotional and cardiovascular reactivity to emotionally evocative stimuli in major depressive disorder.

    PubMed

    Jin, Alvin B; Steding, Lindsey H; Webb, Andrea K

    2015-07-01

    Major Depressive Disorder (MDD) is a highly debilitating mental health concern that affects a large number of adults in the United States. The emotional context insensitivity (ECI) hypothesis argues that individuals with MDD disengage from the environment to defend themselves from futile activity. In the current study, electrocardiogram and pupillometry were recorded from 50 participants (MDD n=25, never depressed control n=25) during the display of emotionally evocative images, sounds, and movie clips. Individuals with MDD reported reduced change in happiness to positively- and negatively-valenced images and sounds. Heart rate reactivity also was reduced in individuals with MDD when viewing images and watching movie clips. These results suggest that individuals with MDD may have some difficulty engaging with certain environmental stimuli. PMID:25931112

  19. Application of aziridine reactive rinses in a post-development process to reduce photoresist pattern collapse

    NASA Astrophysics Data System (ADS)

    Yeh, Wei-Ming; Lawson, Richard A.; Tolbert, Laren M.; Henderson, Clifford L.

    2012-03-01

    One of the problems for lithographic processes at very small feature scales is pattern collapse caused by unbalanced capillary forces experienced by the photoresist patterns during the final deionized water rinse and drying process. The use of surfactants or super critical fluids to reduce collapse problems has been proposed and studied by many research groups. However, the patterns rinsed with low surface tension fluids appear in many cases to shrink or such treatments cause other feature deformations. Super critical fluid processing requires major changes to the ways in which current track systems operate and can result in swelling and deformation of the resist features as well. Instead of utilizing super critical fluids or adding surfactants to the rinse liquid, one general methodology we have pursued for alleviating such pattern collapse problems involves the actual strengthening of the resist feature itself during wet processing in the development and rinse cycle. One method we have investigated extensively is the use of post-development resist surface crosslinking reactions while the resist structures are still in their wet state, a process we term "reactive rinsing". Such reactive rinse processes have shown significant impact on improving resist pattern collapse. However, previous chemistries used for such reactive rinse processes have either: (1) been complex mixtures that potentially have long term stability problems (i.e. thus making their application in a fab environment more difficult) or (2) been specific to a certain resist types in that the chemistries react with only certain resist functional groups that may not be present in all resists of interest (e.g. some chemistries only work with phenolic resins such as those found in DUV or EUV resists). Therefore, the goal of this work has been to investigate other novel reactive rinse chemistries that are both more robust and which can function with different families of resist materials. Poly

  20. Application Of Immobilized Sulfate Reducing Bacteria For Permeable Reactive Barriers In Abandoned Coal Mines

    NASA Astrophysics Data System (ADS)

    Kim, K.; Hur, W.; Choi, S.; Min, K.; Baek, H.

    2006-05-01

    The decline of the Korean coal industry has been drastic in production and consumption. This has been resulted mainly from the environmental concern and the collapse of commercial viability, which has eventually necessitated the government to implement the coal industry rationalization policies to reduce coal production and close down uneconomical mines. The overall drainage rates from abandoned coal mines reaches up to 80,000 ton/day. As a measure of controlling the acid mine drainage from abandoned coal mines, reactive materials in the pathways of drainage, designed to intercept and to transform the contaminants into environmentally acceptable forms can be applied at mines with small drainage rates. The main objective of this study is to design a permeable reactive barrier(PRB) to treat low flow and/or low contaminant loads of acid mine drainage. The PRB is comprised of immobilized sulfate reducing bacteria in hard beads and limestone to remove heavy metals and to raise the pH of AMD. A laboratory reactor was used to prepare a mixed culture of sulfate reducing bacteria. The microbes were separated and mixed with biodegradable matrix to form spherical beads. In order to maintain the viability of micro-organisms for a prolonged period, substrates such as saw dust, polysaccharide or glycerol was supplemented for the beads preparation. The strength of beads fortified by powered limestone to control the permeability of PRB. Different mixtures of limestone and the immobilized beads were tested to determine hydraulic conductivity and AMD treatment capacities. The characteristics of the spherical beads at various pH of AMD was investigated.

  1. Ultra-fast self-assembly and stabilization of reactive nanoparticles in reduced graphene oxide films

    NASA Astrophysics Data System (ADS)

    Chen, Yanan; Egan, Garth C.; Wan, Jiayu; Zhu, Shuze; Jacob, Rohit Jiji; Zhou, Wenbo; Dai, Jiaqi; Wang, Yanbin; Danner, Valencia A.; Yao, Yonggang; Fu, Kun; Wang, Yibo; Bao, Wenzhong; Li, Teng; Zachariah, Michael R.; Hu, Liangbing

    2016-08-01

    Nanoparticles hosted in conductive matrices are ubiquitous in electrochemical energy storage, catalysis and energetic devices. However, agglomeration and surface oxidation remain as two major challenges towards their ultimate utility, especially for highly reactive materials. Here we report uniformly distributed nanoparticles with diameters around 10 nm can be self-assembled within a reduced graphene oxide matrix in 10 ms. Microsized particles in reduced graphene oxide are Joule heated to high temperature (~1,700 K) and rapidly quenched to preserve the resultant nano-architecture. A possible formation mechanism is that microsized particles melt under high temperature, are separated by defects in reduced graphene oxide and self-assemble into nanoparticles on cooling. The ultra-fast manufacturing approach can be applied to a wide range of materials, including aluminium, silicon, tin and so on. One unique application of this technique is the stabilization of aluminium nanoparticles in reduced graphene oxide film, which we demonstrate to have excellent performance as a switchable energetic material.

  2. Ultra-fast self-assembly and stabilization of reactive nanoparticles in reduced graphene oxide films.

    PubMed

    Chen, Yanan; Egan, Garth C; Wan, Jiayu; Zhu, Shuze; Jacob, Rohit Jiji; Zhou, Wenbo; Dai, Jiaqi; Wang, Yanbin; Danner, Valencia A; Yao, Yonggang; Fu, Kun; Wang, Yibo; Bao, Wenzhong; Li, Teng; Zachariah, Michael R; Hu, Liangbing

    2016-01-01

    Nanoparticles hosted in conductive matrices are ubiquitous in electrochemical energy storage, catalysis and energetic devices. However, agglomeration and surface oxidation remain as two major challenges towards their ultimate utility, especially for highly reactive materials. Here we report uniformly distributed nanoparticles with diameters around 10 nm can be self-assembled within a reduced graphene oxide matrix in 10 ms. Microsized particles in reduced graphene oxide are Joule heated to high temperature (∼1,700 K) and rapidly quenched to preserve the resultant nano-architecture. A possible formation mechanism is that microsized particles melt under high temperature, are separated by defects in reduced graphene oxide and self-assemble into nanoparticles on cooling. The ultra-fast manufacturing approach can be applied to a wide range of materials, including aluminium, silicon, tin and so on. One unique application of this technique is the stabilization of aluminium nanoparticles in reduced graphene oxide film, which we demonstrate to have excellent performance as a switchable energetic material. PMID:27515900

  3. Ultra-fast self-assembly and stabilization of reactive nanoparticles in reduced graphene oxide films

    PubMed Central

    Chen, Yanan; Egan, Garth C.; Wan, Jiayu; Zhu, Shuze; Jacob, Rohit Jiji; Zhou, Wenbo; Dai, Jiaqi; Wang, Yanbin; Danner, Valencia A.; Yao, Yonggang; Fu, Kun; Wang, Yibo; Bao, Wenzhong; Li, Teng; Zachariah, Michael R.; Hu, Liangbing

    2016-01-01

    Nanoparticles hosted in conductive matrices are ubiquitous in electrochemical energy storage, catalysis and energetic devices. However, agglomeration and surface oxidation remain as two major challenges towards their ultimate utility, especially for highly reactive materials. Here we report uniformly distributed nanoparticles with diameters around 10 nm can be self-assembled within a reduced graphene oxide matrix in 10 ms. Microsized particles in reduced graphene oxide are Joule heated to high temperature (∼1,700 K) and rapidly quenched to preserve the resultant nano-architecture. A possible formation mechanism is that microsized particles melt under high temperature, are separated by defects in reduced graphene oxide and self-assemble into nanoparticles on cooling. The ultra-fast manufacturing approach can be applied to a wide range of materials, including aluminium, silicon, tin and so on. One unique application of this technique is the stabilization of aluminium nanoparticles in reduced graphene oxide film, which we demonstrate to have excellent performance as a switchable energetic material. PMID:27515900

  4. Reducing the Matrix Effect in Organic Cluster SIMS Using Dynamic Reactive Ionization

    NASA Astrophysics Data System (ADS)

    Tian, Hua; Wucher, Andreas; Winograd, Nicholas

    2016-09-01

    Dynamic reactive ionization (DRI) utilizes a reactive molecule, HCl, which is doped into an Ar cluster projectile and activated to produce protons at the bombardment site on the cold sample surface with the presence of water. The methodology has been shown to enhance the ionization of protonated molecular ions and to reduce salt suppression in complex biomatrices. In this study, we further examine the possibility of obtaining improved quantitation with DRI during depth profiling of thin films. Using a trehalose film as a model system, we are able to define optimal DRI conditions for depth profiling. Next, the strategy is applied to a multilayer system consisting of the polymer antioxidants Irganox 1098 and 1010. These binary mixtures have demonstrated large matrix effects, making quantitative SIMS measurement not feasible. Systematic comparisons of depth profiling of this multilayer film between directly using GCIB, and under DRI conditions, show that the latter enhances protonated ions for both components by 4- to ~15-fold, resulting in uniform depth profiling in positive ion mode and almost no matrix effect in negative ion mode. The methodology offers a new strategy to tackle the matrix effect and should lead to improved quantitative measurement using SIMS.

  5. Reduced Myelination and Increased Glia Reactivity Resulting from Severe Neonatal Hyperbilirubinemia.

    PubMed

    Barateiro, Andreia; Chen, Shujuan; Yueh, Mei-Fei; Fernandes, Adelaide; Domingues, Helena Sofia; Relvas, João; Barbier, Olivier; Nguyen, Nghia; Tukey, Robert H; Brites, Dora

    2016-01-01

    Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to describe moderate to severe neurologic dysfunction observed in children exposed to excessive levels of total serum bilirubin (TSB) during the neonatal period. Here we use a new mouse model that targets deletion of the Ugt1 locus and the Ugt1a1 gene in liver to promote hyperbilirubinemia-induced seizures and central nervous system toxicity. The accumulation of TSB in these mice leads to diffuse yellow coloration of brain tissue and a marked cerebellar hypoplasia that we characterize as kernicterus. Histologic studies of brain tissue demonstrate that the onset of severe neonatal hyperbilirubinemia, characterized by seizures, leads to alterations in myelination and glia reactivity. Kernicterus presents as axonopathy with myelination deficits at different brain regions, including pons, medulla oblongata, and cerebellum. The excessive accumulation of TSB in the early neonatal period (5 days after birth) promotes activation of the myelin basic protein (Mbp) gene with an accelerated loss of MBP that correlates with a lack of myelin sheath formation. These changes were accompanied by increased astroglial and microglial reactivity, possibly as a response to myelination injury. Interestingly, cerebellum was the area most affected, with greater myelination impairment and glia burden, and showing a marked loss of Purkinje cells and reduced arborization of the remaining ones. Thus, kernicterus in this model displays not only axonal damage but also myelination deficits and glial activation in different brain regions that are usually related to the neurologic sequelae observed after severe hyperbilirubinemia.

  6. Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach.

    PubMed

    Blaiss, Cory A; Janak, Patricia H

    2007-05-01

    The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.

  7. Post-training, but not Post-reactivation, Administration of Amphetamine and Anisomycin Modulates Pavlovian Conditioned Approach

    PubMed Central

    Blaiss, Cory A.; Janak, Patricia H.

    2007-01-01

    The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6 hrs after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3 hrs after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e. amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable. PMID:17258476

  8. Curcumin Reduces Amyloid Fibrillation of Prion Protein and Decreases Reactive Oxidative Stress

    PubMed Central

    Lin, Chi-Fen; Yu, Kun-Hua; Jheng, Cheng-Ping; Chung, Raymond; Lee, Cheng-I

    2013-01-01

    Misfolding and aggregation into amyloids of the prion protein (PrP) is responsible for the development of fatal transmissible neurodegenerative diseases. Various studies on curcumin demonstrate promise for the prevention of Alzheimer’s disease and inhibition of PrPres accumulation. To evaluate the effect of curcumin on amyloid fibrillation of prion protein, we first investigated the effect of curcumin on mouse prion protein (mPrP) in a cell-free system. Curcumin reduced the prion fibril formation significantly. Furthermore, we monitored the change in apoptosis and reactive oxygen species (ROS) level upon curcumin treatment in mouse neuroblastoma cells (N2a). Curcumin effectively rescues the cells from apoptosis and decreases the ROS level caused by subsequent co-incubation with prion amyloid fibrils. The assays in cell-free mPrP and in N2a cells of this work verified the promising effect of curcumin on the prevention of transmissible neurodegenerative diseases. PMID:25437204

  9. REDUCTIVE DEHALOGENATION OF HALOMETHANES IN IRON- AND SULFATE-REDUCING SEDIMENTS. 1. REACTIVITY PATTERN ANALYSIS

    EPA Science Inventory

    The incorporation of reductive transformations into environmental fate models requires the characterization of natural reductants in well-characterized sediments and aquifer materials. For this purpose, reactivity patterns (i.e., the range and relative order of reactivity) for a...

  10. Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice.

    PubMed

    Ibarra, Alvin; Feuillere, Nicolas; Roller, Marc; Lesburgere, Edith; Beracochea, Daniel

    2010-05-01

    This study aimed to determine the effects of chronic (15 consecutive days of treatment) per os administration of Melissa officinalis L. extract (Cyracos, Naturex) on anxiety-like reactivity in mice. As measured by HPLC, Cyracos contains significant amounts of rosmarinic acid and the triterpenoids oleanolic acid and ursolic acid, which inhibit gamma-aminobutyric acid transaminase (GABA-T) activity and increase GABA levels in the brain (Awad et al., 2007; Awad et al., 2009). Thus, we evaluated Cyracos use in independent groups of C57BL/6 mice with regard to anxiety-like reactivity in an elevated plus maze and an open field task. We found that Cyracos significantly reduced anxiety-like reactivity in the elevated plus maze dose-dependently, but no significant effect was observed in the open field task. Parallel experiments in independent groups of mice showed that the Cyracosdose at which it exerted anxiolytic-like effects in the elevated plus maze did not alter exploratory or circadian activities. Therefore, our results demonstrate that Cyracos has anxiolytic-like effects under moderate stress conditions and does not alter activity levels.

  11. Apolipoprotein A-I expression suppresses COX-2 expression by reducing reactive oxygen species in hepatocytes.

    PubMed

    Mao, Jing; Liu, Wei; Wang, Yutong

    2014-11-21

    Abnormal lipid metabolism may contribute to the increase of reactive oxygen species (ROS) and inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH). Apolipoprotein A-I (apoA-I) accepts cellular cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies revealed that the overexpression of ABCA1 or apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of apoA-I overexpression on ROS and genes involved in inflammation in both BEL-7402 hepatocytes and mice. Human apoA-I was overexpressed by transfection in BEL-7402 hepatocytes and by an adenoviral vector in C57BL/6J mice fed a methionine choline-deficient diet. The overexpression of apoA-I in both models resulted in decreased ROS and lipid peroxidation levels, as well as a reduced MAPK phosphorylation and decreased expression levels of c-Fos and COX-2. These results suggest that apoA-I overexpression can reduce steatosis by decreasing ROS levels and suppressing COX-2-induced inflammation in hepatocytes. MAPK and c-Fos are involved in this regulatory process.

  12. Shock Reactivity Study on Standard and Reduced Sensitivity RDX of Different Particle Size Distributions

    NASA Astrophysics Data System (ADS)

    McGregor, Nicholas; Lindfors, Allen

    2007-06-01

    Embedded gauge experiments have been performed using a three inch high velocity powder gun to assess the effects of RDX particle size and crystal quality on shock induced reactivity in support of the Combat Safe Insensitive Munitions (CSIM) program. Four monomodal experimental compositions containing 73% solids loading by weight and 27% HTPB binder were tested. The compositions were made using either standard or reduced sensitivity grades of RDX in Class 5 or Class 1 150-300 micron sieve cut particle size classes. Results have shown marked changes in the mode of reaction between the two particle size classes. Both RDX grades at the Class 1 sieve cut particle size distribution showed significant reaction at the shock front as well as behind the front. The Class 5 RDX compositions however showed little reaction at the shock front with rapid growth behind the front. Similar input pressures resulted in a full detonation in a similar distance for like RDX grades. Reaction modes were similar but occurring at greater input pressures for the reduced sensitivity grade of RDX compared to the corresponding particle size distribution standard grade RDX counterpart.

  13. Shock Reactivity Study on Standard and Reduced Sensitivity Rdx of Different Particle Size Distributions

    NASA Astrophysics Data System (ADS)

    McGregor, N. M.; Lindfors, A. J.

    2007-12-01

    Embedded gauge experiments have been performed using a three inch high velocity powder gun to assess the effects of RDX particle size and crystal quality on shock induced reactivity in support of the Combat Safe Insensitive Munitions (CSIM) program. Four monomodal experimental compositions containing 73% solids loading by weight and 27% HTPB binder were tested. The compositions were made using either standard or reduced sensitivity grades of RDX in Class 5 or Class 1 150-300 micron sieve cut particle size classes. Results have shown marked changes in the mode of reaction between the two particle size classes. Both RDX grades at the Class 1 sieve cut particle size distribution showed significant reaction at the shock front as well as behind the front. The Class 5 RDX compositions however showed little reaction at the shock front with rapid growth behind the front. Reaction modes were similar but occurring at greater input pressures for the reduced sensitivity grade of RDX compared to the corresponding particle size distribution standard grade RDX counterpart.

  14. Reducing School Administration to a Technicality? Philosophical Reflections of Senior German School Administrators in the Context of New Public Management-Based Vocational School Reform

    ERIC Educational Resources Information Center

    Wittmann, Eveline

    2006-01-01

    Vocational schools in Germany are currently undergoing administrative reform. The main idea behind this reform, taken from the administrative paradigm of New Public Management, has been to grant schools extended autonomy but to make them more accountable for their results. Critics emphasize that such reform tends to reduce school administration to…

  15. ACUPUNCTURE INHIBITS GABA NEURON ACTIVITY IN THE VENTRAL TEGMENTAL AREA AND REDUCES ETHANOL SELF-ADMINISTRATION

    PubMed Central

    Yang, Chae Ha; Yoon, Seong Shoon; Hansen, David M.; Wilcox, Jeffrey D.; Blumell, Bryan R; Park, Jung Jae; Steffensen, Scott C.

    2010-01-01

    Background Withdrawal from chronic ethanol enhances ventral tegmental area (VTA) GABA neuron excitability and reduces mesolimbic dopamine (DA) neurotransmission, which is suppressed by acupuncture at Shenmen (HT7) points (Zhao et al., 2006). The aim of this study was to evaluate the effects of HT7 acupuncture on VTA GABA neuron excitability, ethanol inhibition of VTA GABA neuron firing rate, and ethanol self-administration. A role for opioid receptors (ORs) in ethanol and acupuncture effects is also explored. Methods Using electrophysiological methods in mature rats, we evaluated the effects of HT7 stimulation and opioid antagonists on VTA GABA neuron firing rate. Using behavioral paradigms in rats, we evaluated the effects of HT7 stimulation and opioid antagonists on ethanol self-administration using a modification of the sucrose fading procedure. Results HT7 stimulation produced a biphasic modulation of VTA GABA neuron firing rate characterized by transient enhancement followed by inhibition and subsequent recovery in 5 min. HT7 inhibition of VTA GABA neuron firing rate was blocked by systemic administration of the non-selective μ-opioid receptor (MOR) antagonist naloxone. HT7 stimulation significantly reduced ethanol suppression of VTA GABA neuron firing rate, which was also blocked by naloxone. HT7 acupuncture reduced ethanol self-administration without affecting sucrose consumption. Systemic administration of the δ-opioid receptor (DOR) antagonist naltrindole blocked ethanol suppression of VTA GABA neuron firing rate and significantly reduced ethanol self-administration without affecting sucrose consumption. Conclusions These findings suggest that DOR-mediated opioid modulation of VTA GABA neurons may mediate acupuncture’s role in modulating mesolimbic DA release and suppressing the reinforcing effects of ethanol. PMID:20860620

  16. Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats.

    PubMed

    Redondo-Castro, Elena; Navarro, Xavier

    2014-02-01

    Ibuprofen is commonly used as an anti-inflammatory analgesic drug, although it is not amongst the first-line treatments for neuropathic pain. Its main effects are mediated by non-specific inhibition of COX enzymes, but it also exerts some COX-independent effects, such as the inhibition of RhoA signaling and the modulation of glial activity. These effects have boosted the use of ibuprofen as a tool to promote axonal regeneration and to increase functional recovery after neural injuries, although with controversial results showing positive and negative outcomes of ibuprofen treatment in several experimental models. We have evaluated the effects of ibuprofen administered at 60 mg/kg twice a day to rats subjected to a mild spinal cord contusion. Our results indicate that ibuprofen ameliorates mechanical hyperalgesia in rats by reducing central hyperexcitability, but failed to produce improvements in the recovery of locomotion. Despite an early effect on reducing microglial reactivity, the ibuprofen treatment did not provide histological evidence of neuroprotection; indeed the volume of cord tissue spared rostral to the lesion was decreased in ibuprofen treated rats. In summary, the early modulation of neuroinflammation produced by the administration of ibuprofen seems to eventually lead to a worse resolution of detrimental events occurring in the secondary injury phase, but also to reduce the development of neuropathic pain.

  17. Insulin counter-regulatory factors, fibrinogen and C-reactive protein during olanzapine administration: effects of the antidiabetic metformin.

    PubMed

    Baptista, Trino; Sandia, Ignacio; Lacruz, Anny; Rangel, Nairy; de Mendoza, Soaira; Beaulieu, Serge; Contreras, Quilianio; Galeazzi, Tatiana; Vargas, Doritza

    2007-03-01

    In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent. PMID:17293706

  18. Selenium-Containing Amphiphiles Reduced and Stabilized Gold Nanoparticles: Kill Cancer Cells via Reactive Oxygen Species.

    PubMed

    Li, Tianyu; Li, Feng; Xiang, Wentian; Yi, Yu; Chen, Yuyan; Cheng, Liang; Liu, Zhuang; Xu, Huaping

    2016-08-31

    Selenium has attracted increasing interest in recent decades because of the function of regulating the redox balance in the human body. However, biomedical studies of selenium are still limited. Gold nanoparticles (AuNPs), typically prepared by a first reduction step followed by a second stabilization step, are widely applied in biomedical studies. However, their own anticancer activity is less studied. Here, we report 2 nm AuNPs with significant anticancer activity (IC50 = 20 μM) that is stabilized by a selenium-containing amphiphile EGSe-tMe. The AuNPs are prepared by simply mixing chloroauric acid (HAuCl4) with EGSe-tMe, which acts as both a reducing agent and a stabilizer. In contrast to AuNPs prepared by EGSe-tMe, EGSe-tMe alone and typically prepared AuNPs show little anticancer activity even at concentrations up to 250 μM. Mechanistic studies suggest that selenium in cooperation with AuNPs can induce high concentrations of reactive oxygen species (ROS) in cancer cells, leading to cellular apoptosis. PMID:27517121

  19. Chemical Reactivity Probes for Assessing Abiotic Natural Attenuation by Reducing Iron Minerals.

    PubMed

    Fan, Dimin; Bradley, Miranda J; Hinkle, Adrian W; Johnson, Richard L; Tratnyek, Paul G

    2016-02-16

    Increasing recognition that abiotic natural attenuation (NA) of chlorinated solvents can be important has created demand for improved methods to characterize the redox properties of the aquifer materials that are responsible for abiotic NA. This study explores one promising approach: using chemical reactivity probes (CRPs) to characterize the thermodynamic and kinetic aspects of contaminant reduction by reducing iron minerals. Assays of thermodynamic CRPs were developed to determine the reduction potentials (ECRP) of suspended minerals by spectrophotometric determination of equilibrium CRP speciation and calculations using the Nernst equation. ECRP varied as expected with mineral type, mineral loading, and Fe(II) concentration. Comparison of ECRP with reduction potentials measured potentiometrically using a Pt electrode (EPt) showed that ECRP was 100-150 mV more negative than EPt. When EPt was measured with small additions of CRPs, the systematic difference between EPt and ECRP was eliminated, suggesting that these CRPs are effective mediators of electron transfer between mineral and electrode surfaces. Model contaminants (4-chloronitrobenzene, 2-chloroacetophenone, and carbon tetrachloride) were used as kinetic CRPs. The reduction rate constants of kinetic CRPs correlated well with the ECRP for mineral suspensions. Using the rate constants compiled from literature for contaminants and relative mineral reduction potentials based on ECRP measurements, qualitatively consistent trends were obtained, suggesting that CRP-based assays may be useful for estimating abiotic NA rates of contaminants in groundwater.

  20. Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats.

    PubMed

    Levin, Edward D; Wells, Corinne; Johnson, Joshua E; Rezvani, Amir H; Bymaster, Frank P; Rose, Jed E

    2015-10-01

    A wider diversity of drug treatments to aid smoking cessation is needed to help tailor the most efficacious treatment for different types of smokers. This study was conducted to determine whether amitifadine, which inhibits re-uptake of dopamine, norepinephrine and serotonin, would decrease nicotine self-administration at doses that do not cause adverse side effects. Adult female Sprague-Dawley rats were trained to self-administer nicotine intravenous (IV) and were given acute doses of amitifadine in a repeated measures counterbalanced design. Effects of amitifadine on locomotor activity and food motivated responding were also evaluated. Chronic amitifadine effects were also examined. The 30 mg/kg amitifadine dose significantly reduced nicotine self-administration. The 5 and 10 mg/kg doses reduced nicotine self-administration during the first 15 min of the session when the greatest amount of nicotine was self-administered. The 30 mg/kg amitifadine dose, but not the lower doses caused a significant reduction in locomotor activity averaged over the one-hour session and reduced food motivated responding. The 10 mg/kg dose caused hypoactivity at the beginning of the session, but 5 mg/kg did not cause any hypoactivity. The effects of chronic amitifadine treatment (10 mg/kg) over the course of 15 sessions was also determined. Amitifadine caused a significant reduction in nicotine self-administration, which was not seen to diminish over two consecutive weeks of treatment and a week after enforced abstinence. Amitifadine significantly reduced nicotine self-administration. This prompts further research to determine if amitifadine might be an effective treatment for smoking cessation.

  1. Oral Administration of Surfactant Protein-A Reduces Pathology in an Experimental Model of Necrotizing Enterocolitis

    PubMed Central

    Quintanilla, Hector D.; Liu, Yuying; Fatheree, Nicole Y.; Atkins, Constance L.; Hashmi, Syed S.; Floros, Joanna; McCormack, Francis X.; Rhoads, Jon Marc; Alcorn, Joseph L.

    2016-01-01

    OBJECTIVES Necrotizing enterocolitis (NEC) frequently results in significant morbidity and mortality in premature infants. Others reported that mice deficient in pulmonary surfactant protein-A (SP-A) born and raised in a nonhygienic environment succumb to significant gastrointestinal tract pathology, and enteral administration of purified SP-A significantly reduced mortality. We hypothesized that oral administration of purified SP-A can ameliorate pathology in an experimental model of neonatal NEC. METHODS Experimental NEC was induced in newborn Sprague-Dawley rat pups by daily formula gavage and intermittent exposure to hypoxia. Purified human SP-A (5 μg/day) was administered by oral gavage. After 4 days, surviving pups were sacrificed, and intestinal pathology was assessed by histological examination of distal terminal ileal sections. Intestinal levels of inflammatory cytokines (IL-1β, IFN-γ and TNF-α) were assessed by ELISA and levels of toll-like receptor 4 (TLR4) by western analysis. RESULTS 61% of the gavaged rat pups that survived to day 4 met the criteria for experimental NEC after hypoxia while treatment with SP-A significantly reduced mortality and assessment of NEC. Intestinal levels of pro-inflammatory cytokines were significantly increased in pups exposed to hypoxia. Administration of SP-A to pups exposed to hypoxia significantly reduced IL-1β and TNF-α levels, but had little effect on elevated levels of IFN-γ. SP-A treatment of hypoxia-exposed pups significantly reduced expression of intestinal TLR4, key in NEC pathogenesis. CONCLUSIONS In a rat model of experimental neonatal NEC, oral administration of SP-A reduces intestinal levels of pro-inflammatory cytokines and TLR4 protein, and ameliorates adverse outcomes associated with gastrointestinal pathologies. PMID:25539191

  2. Live Video Classroom Observation: An Effective Approach to Reducing Reactivity in Collecting Observational Information for Teacher Professional Development

    ERIC Educational Resources Information Center

    Liang, Jiwen

    2015-01-01

    This paper examines the significance of live video classroom observations of teaching practice to reduce reactivity (the observer effect) so as to obtain more credible observational information for teacher professional development in a secondary school in the largest city in southern China. Although much has been discussed regarding the use of…

  3. Reduced visual cortex grey matter volume in children and adolescents with reactive attachment disorder

    PubMed Central

    Shimada, Koji; Takiguchi, Shinichiro; Mizushima, Sakae; Fujisawa, Takashi X.; Saito, Daisuke N.; Kosaka, Hirotaka; Okazawa, Hidehiko; Tomoda, Akemi

    2015-01-01

    Child maltreatment increases the risk for psychiatric disorders throughout childhood and into adulthood. One negative outcome of child maltreatment can be a disorder of emotional functioning, reactive attachment disorder (RAD), where the child displays wary, watchful, and emotionally withdrawn behaviours. Despite its clinical importance, little is known about the potential neurobiological consequences of RAD. The aim of this study was to elucidate whether RAD was associated with alterations in grey matter volume (GMV). High-resolution magnetic resonance imaging datasets were obtained for children and adolescents with RAD (n = 21; mean age = 12.76 years) and typically developing (TD) control subjects (n = 22; mean age = 12.95 years). Using a whole-brain voxel-based morphometry approach, structural images were analysed controlling for age, gender, full scale intelligence quotient, and total brain volume. The GMV was significantly reduced by 20.6% in the left primary visual cortex (Brodmann area 17) of the RAD group compared to the TD group (p = .038, family-wise error-corrected cluster level). This GMV reduction was related to an internalising problem measure of the Strength and Difficulties Questionnaire. The visual cortex has been viewed as part of the neurocircuit regulating the stress response to emotional visual images. Combined with previous studies of adults with childhood maltreatment, early adverse experience (e.g. sensory deprivation) may affect the development of the primary visual system, reflecting in the size of the visual cortex in children and adolescents with RAD. These visual cortex GMV abnormalities may also be associated with the visual emotion regulation impairments of RAD, leading to an increased risk for later psychopathology. PMID:26288752

  4. Reduced visual cortex grey matter volume in children and adolescents with reactive attachment disorder.

    PubMed

    Shimada, Koji; Takiguchi, Shinichiro; Mizushima, Sakae; Fujisawa, Takashi X; Saito, Daisuke N; Kosaka, Hirotaka; Okazawa, Hidehiko; Tomoda, Akemi

    2015-01-01

    Child maltreatment increases the risk for psychiatric disorders throughout childhood and into adulthood. One negative outcome of child maltreatment can be a disorder of emotional functioning, reactive attachment disorder (RAD), where the child displays wary, watchful, and emotionally withdrawn behaviours. Despite its clinical importance, little is known about the potential neurobiological consequences of RAD. The aim of this study was to elucidate whether RAD was associated with alterations in grey matter volume (GMV). High-resolution magnetic resonance imaging datasets were obtained for children and adolescents with RAD (n = 21; mean age = 12.76 years) and typically developing (TD) control subjects (n = 22; mean age = 12.95 years). Using a whole-brain voxel-based morphometry approach, structural images were analysed controlling for age, gender, full scale intelligence quotient, and total brain volume. The GMV was significantly reduced by 20.6% in the left primary visual cortex (Brodmann area 17) of the RAD group compared to the TD group (p = .038, family-wise error-corrected cluster level). This GMV reduction was related to an internalising problem measure of the Strength and Difficulties Questionnaire. The visual cortex has been viewed as part of the neurocircuit regulating the stress response to emotional visual images. Combined with previous studies of adults with childhood maltreatment, early adverse experience (e.g. sensory deprivation) may affect the development of the primary visual system, reflecting in the size of the visual cortex in children and adolescents with RAD. These visual cortex GMV abnormalities may also be associated with the visual emotion regulation impairments of RAD, leading to an increased risk for later psychopathology. PMID:26288752

  5. Aluminum water treatment residuals as permeable reactive barrier sorbents to reduce phosphorus losses.

    PubMed

    Miller, Matthew L; Bhadha, Jehangir H; O'Connor, George A; Jawitz, James W; Mitchell, Jennifer

    2011-05-01

    Two aluminum water treatment residuals (Al-WTRs) from water treatment plants in Manatee County, FL and Punta Gorda, FL were evaluated as potential permeable reactive barrier (PRB) media to reduce groundwater phosphorus (P) losses. Short-term (<24h) P sorption kinetics and long-term P sorption capacity were determined using batch equilibration studies. Phosphorus desorption was characterized following P loadings of 10, 20, 30, 40 and >70 g kg(-1). Sorption and desorption studies were conducted on the <2.0mm material and three size fractions within the <2.0mm material. The effect of dissolved organic carbon (DOC) on P retention was determined by reacting Al-WTRs with P-spiked groundwater samples of varying initial DOC concentrations. Phosphorus sorption kinetics were rapid for all size fractions of both Al-WTRs (>98% P sorption effectiveness at shaking times ≥2 h). The effect of DOC was minimal at <150 mg DOCL(-1), but modest reductions (<22%) in P sorption effectiveness occurred at 587 mg DOC L(-1). The P sorption capacities of the Manatee and Punta Gorda Al-WTRs (<2.0mm) are ∼44 g kg(-1) and >75 g kg(-1), respectively, and the lifespan of an Al-WTR PRB is likely many decades. Desorption was minimal (<2% of the P sorbed) for cumulative P loadings <40 g kg(-l), but increased (<9% of the P sorbed) at cumulative P loads >70 g kg(-1). The <2.0mm Manatee and Punta Gorda Al-WTRs are regarded as ideal PRB media for P remediation.

  6. Distribution and reactivity of O2-reducing components in sediments from a layered aquifer.

    PubMed

    Hartog, Niels; Griffioen, Jasper; van der Weijden, Cornelis H

    2002-06-01

    The redox status of subsurface aqueous systems is controlled by the reactivity of solid redox-sensitive species and by the inflow of such species dissolved in groundwater. The reactivity toward molecular oxygen (O2) of solid reductants present in three particle size fractions of sediments from a pristine aquifer was characterized during 54 days. The stoichiometric relationships between carbon dioxide (CO2) production and O2 consumption was used in combination with sulfate production to discriminate between the contributions of sedimentary organic matter (0-87%), pyrite (6-100%), and siderite (0-43%) as the dominant reductants. The observed simultaneous oxidation of these reductants indicates that they are reactive on the same time scales. The measured reduction capacity 18-84 micromol O2/g) ranged from 8 to 42% of the total reduction capacity present as pyrite and organic carbon in the total sediment fraction (<2 mm). Fine fractions (<63 microm) were 10-250 times more reactive than their corresponding total fractions. Oxygen consumption rates decreased continuously during carbonate buffered conditions, due to a decreasing reactivity of reductants. Acidification accelerated pyrite oxidation but impeded SOM respiration. Our findings indicate that the geological history of aquifer sediments affects the amounts of organic matter, pyrite and siderite present, while environmental conditions, such as pH and microbial activity, are important in controlling the reactivity of these reductants. These controls should be considered when assessing the natural reduction activity of aquifer sediments in either natural or polluted systems.

  7. Water-Gas Shift and Methane Reactivity on Reducible Perovskite-Type Oxides

    PubMed Central

    2015-01-01

    Comparative (electro)catalytic, structural, and spectroscopic studies in hydrogen electro-oxidation, the (inverse) water-gas shift reaction, and methane conversion on two representative mixed ionic–electronic conducting perovskite-type materials La0.6Sr0.4FeO3−δ (LSF) and SrTi0.7Fe0.3O3−δ (STF) were performed with the aim of eventually correlating (electro)catalytic activity and associated structural changes and to highlight intrinsic reactivity characteristics as a function of the reduction state. Starting from a strongly prereduced (vacancy-rich) initial state, only (inverse) water-gas shift activity has been observed on both materials beyond ca. 450 °C but no catalytic methane reforming or methane decomposition reactivity up to 600 °C. In contrast, when starting from the fully oxidized state, total methane oxidation to CO2 was observed on both materials. The catalytic performance of both perovskite-type oxides is thus strongly dependent on the degree/depth of reduction, on the associated reactivity of the remaining lattice oxygen, and on the reduction-induced oxygen vacancies. The latter are clearly more reactive toward water on LSF, and this higher reactivity is linked to the superior electrocatalytic performance of LSF in hydrogen oxidation. Combined electron microscopy, X-ray diffraction, and Raman measurements in turn also revealed altered surface and bulk structures and reactivities. PMID:26045733

  8. The effects of smoking deprivation and nicotine administration on emotional reactivity.

    PubMed

    Cinciripini, Paul M; Robinson, Jason D; Carter, Brian L; Lam, Cho; Wu, XiFeng; de Moor, Carl A; Baile, Walter F; Wetter, David W

    2006-06-01

    Although converging lines of evidence suggest that nicotine and mood are related at a fundamental biological level, this link has not been reliably demonstrated in laboratory studies. In this study, startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes associated with motivation. Smokers (N = 115) completed four laboratory sessions crossing deprivation (12-hr deprived vs. nondeprived) with nicotine spray (active vs. placebo). Participants viewed affective pictures (positive, negative, neutral) and pictures involving cigarette cues, while startle probes were administered. Deprivation decreased startle responding to cigarette cues, suggesting an activation of appetitive processes. Nicotine administration suppressed overall startle responding during deprivation. In addition, during deprivation, random exposure to negative stimuli over two blocks of trials resulted in decreased adaptation of the startle response, suggesting that some sensitization to negative emotional cues may take place during nicotine withdrawal. These effects are consistent with formulations of addiction, stressing that withdrawal may both increase the reinforcement salience of smoking stimuli and decrease habituation to negative emotional stimuli.

  9. The effects of smoking deprivation and nicotine administration on emotional reactivity.

    PubMed

    Cinciripini, Paul M; Robinson, Jason D; Carter, Brian L; Lam, Cho; Wu, XiFeng; de Moor, Carl A; Baile, Walter F; Wetter, David W

    2006-06-01

    Although converging lines of evidence suggest that nicotine and mood are related at a fundamental biological level, this link has not been reliably demonstrated in laboratory studies. In this study, startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes associated with motivation. Smokers (N = 115) completed four laboratory sessions crossing deprivation (12-hr deprived vs. nondeprived) with nicotine spray (active vs. placebo). Participants viewed affective pictures (positive, negative, neutral) and pictures involving cigarette cues, while startle probes were administered. Deprivation decreased startle responding to cigarette cues, suggesting an activation of appetitive processes. Nicotine administration suppressed overall startle responding during deprivation. In addition, during deprivation, random exposure to negative stimuli over two blocks of trials resulted in decreased adaptation of the startle response, suggesting that some sensitization to negative emotional cues may take place during nicotine withdrawal. These effects are consistent with formulations of addiction, stressing that withdrawal may both increase the reinforcement salience of smoking stimuli and decrease habituation to negative emotional stimuli. PMID:16801296

  10. Combined local and systemic bleomycin administration in electrochemotherapy to reduce the number of treatment sessions

    PubMed Central

    Tellado, Matias; Olaiz, Nahuel; Michinski, Sebastian; Marshall, Guillermo

    2016-01-01

    Background Electrochemotherapy (ECT), a medical treatment widely used in human patients for tumor treatment, increases bleomycin toxicity by 1000 fold in the treated area with an objective response rate of around 80%. Despite its high response rate, there are still 20% of cases in which the patients are not responding. This could be ascribed to the fact that bleomycin, when administered systemically, is not reaching the whole tumor mass properly because of the characteristics of tumor vascularization, in which case local administration could cover areas that are unreachable by systemic administration. Patients and methods We propose combined bleomycin administration, both systemic and local, using companion animals as models. We selected 22 canine patients which failed to achieve a complete response after an ECT treatment session. Eleven underwent another standard ECT session (control group), while 11 received a combined local and systemic administration of bleomycin in the second treatment session. Results According to the WHO criteria, the response rates in the combined administration group were: complete response (CR) 54% (6), partial response (PR) 36% (4), stable disease (SD) 10% (1). In the control group, these were: CR 0% (0), PR 19% (2), SD 63% (7), progressive disease (PD) 18% (2). In the combined group 91% objective responses (CR+PR) were obtained. In the control group 19% objective responses were obtained. The difference in the response rate between the treatment groups was significant (p < 0.01). Conclusions Combined local and systemic bleomycin administration was effective in previously to ECT non responding canine patients. The results indicate that this approach could be useful and effective in specific population of patients and reduce the number of treatment sessions needed to obtain an objective response. PMID:27069450

  11. Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine.

    PubMed

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott; Fujii, Mei; Goto, Akiko; Kanda, Yusuke; Koizumi, Akira; Kuroiwa, Hirotoshi; Mibayashi, Satoko; Muranishi, Yumi; Otaki, Soichiro; Sumikawa, Minako; Tanaka, Koh-Ichi; Nishiyama, Nobuyoshi; Uhl, George R; Takemura, Motohiko

    2015-01-01

    In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or β-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by μ-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety.

  12. Memory Impairment and Reduced Exploratory Behavior in Mice after Administration of Systemic Morphine

    PubMed Central

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott; Fujii, Mei; Goto, Akiko; Kanda, Yusuke; Koizumi, Akira; Kuroiwa, Hirotoshi; Mibayashi, Satoko; Muranishi, Yumi; Otaki, Soichiro; Sumikawa, Minako; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Uhl, George R; Takemura, Motohiko

    2015-01-01

    In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or β-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by μ-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety. PMID:25987850

  13. Losartan administration reduces fibrosis but hinders functional recovery after volumetric muscle loss injury.

    PubMed

    Garg, Koyal; Corona, Benjamin T; Walters, Thomas J

    2014-11-15

    Losartan is a Food and Drug Administration approved antihypertensive medication that is recently emerging as an antifibrotic therapy. Previously, losartan has been successfully used to reduce fibrosis and improve both muscle regeneration and function in several models of recoverable skeletal muscle injuries, such as contusion and laceration. In this study, the efficacy of losartan treatment in reducing fibrosis and improving regeneration was determined in a Lewis rat model of volumetric muscle loss (VML) injury. VML has been defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment. It is among the top 10 causes for wounded service members to be medically retired from the military. This study shows that, after several weeks of recovery, VML injury results in little to no muscle regeneration, but is marked by persistent inflammation, chronic upregulation of profibrotic markers and extracellular matrix (i.e., collagen type I), and fat deposition at the defect site, which manifest irrecoverable deficits in force production. Losartan administration at 10 mg·kg(-1)·day(-1) was able to modulate the gene expression of fibrotic markers and was also effective at reducing fibrosis (i.e., the deposition of collagen type I) in the injured muscle. However, there were no improvements in muscle regeneration, and deleterious effects on muscle function were observed instead. We propose that, in the absence of regeneration, reduction in fibrosis worsens the ability of the VML injured muscle to transmit forces, which ultimately results in decreased muscle function.

  14. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

    PubMed

    Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

    2016-03-01

    Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration

  15. Evaluation of chronic alcohol self-administration by a 3-bottle choice paradigm in adult male rats. Effects on behavioural reactivity, spatial learning and reference memory.

    PubMed

    Cacace, Silvana; Plescia, Fulvio; La Barbera, Marco; Cannizzaro, Carla

    2011-06-01

    Chronic ethanol consumption is able to modify emotional behaviour and cognition in humans. In particular, the effects exerted by alcohol may depend on doses, time and modalities of administration. In this study we investigated, in adult male rats, ethanol self-administration and preference patterns using a 3-bottle choice paradigm with water, 10% ethanol solution, and white wine (10%, v/v), along a four-week period. The influence of alcohol free-access on novelty-induced explorative behaviour in the open field, and on spatial learning and reference memory in the Morris water maze was also evaluated. Our results indicate that: (i) rats show a higher preference for alcohol, in the first two weeks of the paradigm, displaying a higher consumption of 10% ethanol solution than white wine; in the last two weeks, they reduce their alcoholic preference, drinking the same moderate amounts of the two alcoholic beverages; (ii) at the fourth week of the free-access paradigm rats show a high explorative behaviour in the central squares of the open field and an improvement in spatial information processing in the new-place learning task of the Morris water maze. In conclusion our data suggest that, interestingly, rats exposed to the free-access paradigm were able to self-regulate their alcoholic intake, and indicated that a moderate alcohol consumption was able to induce an increase in behavioural reactivity and an enhancement in spatial learning flexibility.

  16. Postprandial Administration of Intranasal Insulin Intensifies Satiety and Reduces Intake of Palatable Snacks in Women

    PubMed Central

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-01-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value. PMID:22344561

  17. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women.

    PubMed

    Hallschmid, Manfred; Higgs, Suzanne; Thienel, Matthias; Ott, Volker; Lehnert, Hendrik

    2012-04-01

    The role of brain insulin signaling in the control of food intake in humans has not been thoroughly defined. We hypothesized that the hormone contributes to the postprandial regulation of appetite for palatable food, and assessed the effects on appetite and snack intake of postprandial versus fasted intranasal insulin administration to the brain in healthy women. Two groups of subjects were intranasally administered 160 IU insulin or vehicle after lunch. Two hours later, consumption of cookies of varying palatability was measured under the pretext of a taste test. In a control study, the effects of intranasal insulin administered to fasted female subjects were assessed. Compared with placebo, insulin administration in the postprandial but not in the fasted state decreased appetite as well as intake and rated palatability of chocolate chip cookies (the most palatable snack offered). In both experiments, intranasal insulin induced a slight decrease in plasma glucose but did not affect serum insulin concentrations. Data indicate that brain insulin acts as a relevant satiety signal during the postprandial period, in particular reducing the intake of highly palatable food, and impacts peripheral glucose homeostasis. Postprandial intranasal insulin administration might be useful in curtailing overconsumption of snacks with accentuated rewarding value.

  18. Reducing avoidable time delays in immediate medication administration - learning from a failed intervention

    PubMed Central

    Nagar, Sachin; davey, nicola

    2015-01-01

    Stat medications are regularly prescribed on hospital wards as part of the ongoing care for patients. Because they are prescribed at variable times that do not coincide with regular nursing drug administration times, they rely on good communication and vigilance on staff to ensure they are administered in a timely manner. Delays in drug administration can lengthen patient recovery times, prolong admission, and can lead to avoidable patient harm and suffering. While working on a geriatrics ward I noticed that there were often significant delays in administration of stat medications which occurred on a regular basis. I therefore investigated this by collecting data over a two week period to assess the situation based on our current practice. After root cause analysis (figure 1), it became clear that communication between staff was a significant factor in delayed administration. A solution was implemented in the form of “ward bay wall charts” to aid documentation and communication of stat medication requirements between nursing and medical staff with the intention to reduce delays by improving communication. After gaining support of medical and nursing staff, a trial was undertaken and a further two weeks of data collected to see the effect of the intervention. The results showed that there was an increase in the median time delay (1 hour 34 minutes to 2 hours 26 minutes, a 55% increase in median time delay) after the implementation of the my intervention, suggesting that it actually made communication worse, creating more delays. Subsequent feedback and analysis showed that this was due to a number of factors that led to worsened communication between staff and therefore an increase in medication delays. Early recognition allowed the intervention to be promptly withdrawn and a re-assessment of the nature of the initial problem. This project highlights the importance of measurement in determining if an intervention actually works and is an improvement on current

  19. Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

    PubMed Central

    Ayers, Luke W; Missig, Galen; Schulkin, Jay; Rosen, Jeffrey B

    2011-01-01

    Oxytocin is known to have anti-anxiety and anti-stress effects. Using a fear-potentiated startle paradigm in rats, we previously demonstrated that subcutaneously administered oxytocin suppressed acoustic startle following fear conditioning compared with startle before fear conditioning (termed background anxiety), but did not have an effect on cue-specific fear-potentiated startle. The findings suggest oxytocin reduces background anxiety, an anxious state not directly related to cue-specific fear, but sustained beyond the immediate threat. The goal of the present study was to compare the effects of centrally and peripherally administered oxytocin on background anxiety and cue-specific fear. Male rats were given oxytocin either subcutaneously (SC) or intracerebroventricularly (ICV) into the lateral ventricles before fear-potentiated startle testing. Oxytocin doses of 0.01 and 0.1 μg/kg SC reduced background anxiety. ICV administration of oxytocin at doses from 0.002 to 20 μg oxytocin had no effect on background anxiety or cue-specific fear-potentiated startle. The 20 μg ICV dose of oxytocin did reduce acoustic startle in non-fear conditioned rats. These studies indicate that oxytocin is potent and effective in reducing background anxiety when delivered peripherally, but not when delivered into the cerebroventricular system. Oxytocin given systemically may have anti-anxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in many anxiety and mental health disorder patients. PMID:21796104

  20. Composition, Reactivity, and Regulations of Extracellular Metal-Reducing Structures (Bacterial Nanowires) Produced by Dissimilatory Metal Reducing Bacteria

    SciTech Connect

    Scholten, Johannes

    2006-06-01

    This research proposal seeks to describe the composition and function of electrically conductive appendages known as bacterial nanowires. This project targets bacterial nanowires produced by dissimilatory metal reducing bacteria Shewanella and Geobacter. Specifically, this project will investigate the role of these structures in the reductive transformation of iron oxides as solid phase electron acceptors, as well as uranium as a dissolved electron acceptor that forms nanocrystalline particles of uraninite upon reduction.

  1. Anisomycin in the Medial Prefrontal Cortex Reduces Reconsolidation of Cocaine-associated Memories in the Rat Self-administration Model

    PubMed Central

    Sorg, Barbara A.; Todd, Ryan P.; Slaker, Megan; Churchill, Lynn

    2015-01-01

    We tested the hypothesis that infusion of anisomycin into the medial prefrontal cortex (mPFC) disrupts the reconsolidation of a cocaine-associated memory in the rat cocaine self-administration model. Male Sprague-Dawley rats were trained to lever press for cocaine self-administration (0.5 mg/kg/infusion) along with a cue light presentation on an FR1 followed by an FR3 schedule of reinforcement for 2 hr/day. Rats were then given extinction sessions or an equivalent forced abstinence period followed by a 5 min memory reactivation session during which time they received an ip cocaine injection (10 mg/kg, ip) and were allowed to press for contingent cue light presentation. Immediately after reactivation, they were administered an intra-mPFC infusion of vehicle or anisomycin. Two additional control groups received extinction and either no memory reactivation and intra-mPFC infusions as above or intra-mPFC infusions 6 hr after memory reactivation. A fourth group received forced abstinence and intra-mPFC infusions immediately after memory reactivation. Combined cocaine + cue-induced reinstatement was given 2–3 days (early) and 8–12 days (late) later. Rats given anisomycin in the Extinction + Reactivation demonstrated decreased reinstatement, while anisomycin treatment did not alter behavior in any of the other three groups. These results suggest that extinction training may recruit the mPFC such that it renders the memory susceptible to disruption by anisomycin. These findings have implications for using extinction training prior to or in conjunction with other therapies, including reconsolidation disruption, to enhance prefrontal control over drug-seeking behavior. PMID:25576371

  2. Tritium excretion after intravenous administration of tritium labelled adrenaline and noradrenaline and digital vascular reactivity to adrenaline and noradrenaline in normotensive and labile hypertensive subjects.

    PubMed

    De Guia, D; Mendlowitz, M; Vlachakis, N D; Gitlow, S E; Nissenbaum, M

    1980-01-01

    1. The 24-h urinary excretion of tritium after tritiated adrenaline administration and digital vascular reactivity to exogenously administered adrenaline and noradrenaline were measured in ten normotensive and in twenty-eight labile essential hypertensive subjects. Tritiated noradrenaline excretion and apparent noradrenaline secretion rate were also measured in ten and eleven of these subjects, respectively. 2. Despite overlapping, the mean 24-h tritium excretion after 3H-adrenaline administration as well as reactivity to adrenaline were significantly greater in the hypertensive than in the normotensive subjects, whether or not they had increased responsiveness to noradrenaline. Significant correlation, however, was observed between tritium excretion of adrenaline and reactivity to adrenaline in both labile hypertensive and normotensive subjects. These measurements were also both significantly correlated with percentage variability in systolic and diastolic blood pressure in the labile hypertensive subjects. 3. No significant correlation was observed between adrenaline as against noradrenaline measurements, whether physiological or biochemical, in either hypertensive or normotensive subjects.

  3. Oral supplementation of butyrate reduces mucositis and intestinal permeability associated with 5-Fluorouracil administration.

    PubMed

    Ferreira, Talita Mayra; Leonel, Alda Jusceline; Melo, Marco Antônio; Santos, Rosana R G; Cara, Denise Carmona; Cardoso, Valbert N; Correia, Maria I T D; Alvarez-Leite, Jacqueline I

    2012-07-01

    Mucositis affects about 40 % of patients undergoing chemotherapy. Short chain fatty acids (SCFA), mainly butyrate, are claimed to improve mucosal integrity, reduce intestinal permeability and act as anti-inflammatory agents for the colon mucosa. We evaluated the effects of oral administration of SCFA or butyrate in the 5FU-induced mucositis. Mice received water, SCFA or butyrate during all experiment (10 days) and a single dose of 5FU (200 mg/kg) 3 days before euthanasia. We evaluated inflammatory and histological score by morphometry, and by activity of enzymes specific to neutrophil, eosinophil and macrophage and TLR-4, TNF-alpha and IL6 expressions. Intestinal permeability and tight junction protein ZO-1 expression were evaluated. Mice from the 5FU (5-Fluorouracil) group presented weight loss, ulcerations and inflammatory infiltration of neutrophils and eosinophils, increased expression of IL6 and TNF-alpha and increased intestinal permeability. SCFA minimized intestinal damage, reduced ulcerations without affecting intestinal permeability. Butyrate alone was more efficient at improving those parameters than in SCFA solution and also reduced intestinal permeability. The expression of pro-inflammatory cytokines and ZO-1 tended to be higher in the SCFA supplemented but not in the butyrate supplemented group. We showed the beneficial effects of butyrate on intestinal mucositis and its promising function as an adjuvant in the treatment of diseases not only of the colon, but also of the small intestine.

  4. Cerebrolysin administration reduces oxidative stress-induced apoptosis in lymphocytes from healthy individuals.

    PubMed

    Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Muresanu, Dafin; Federico, Antonio

    2012-11-01

    Cerebrolysin is the only drug available for clinical use containing active fragments of some important neurotrophic factors obtained from purified porcine brain proteins, which has long been used for the treatment of dementia and stroke sequels. Cerebrolysin has growth factor-like activities and promotes neuronal survival and sprouting, however, its molecular mechanism still needs to be determined. It has been shown that Cerebrolysin may interact with proteolytic pathways linked to apoptosis. Administration of Cerebrolysin significantly reduces the number of apoptotic neurons after glutamate exposure. Furthermore, it has been reported that Cerebrolysin inhibits free radicals formation and lipid peroxidation. In vitro we evaluated the protective effects of Cerebrolysin towards spontaneous and induced apoptotic death in cells from healthy individuals. Peripheral blood lymphocytes (PBLs) from 10 individuals were used as cell model; 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analysed using flow cytometry and fluorescence microscopy. Our results showed that Cerebrolysin significantly reduced the number of apoptotic PBLs after dRib treatment, although it had no significative effects on cells cultured in standard conditions. Our work showed a protective effect of Cerebrolysin on oxidative stress-induced apoptosis and suggested that PBLs can be used as an easy obtainable and handy cell model to verify Cerebrolysin effects in neurodegenerative pathologies.

  5. Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers.

    PubMed

    Ipser, Jonathan C; Terburg, David; Syal, Supriya; Phillips, Nicole; Solms, Mark; Panksepp, Jaak; Malcolm-Smith, Susan; Thomas, Kevin; Stein, Dan J; van Honk, Jack

    2013-01-01

    In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain. PMID:22651957

  6. Reduced nucleus accumbens reactivity and adolescent depression following early-life stress.

    PubMed

    Goff, B; Gee, D G; Telzer, E H; Humphreys, K L; Gabard-Durnam, L; Flannery, J; Tottenham, N

    2013-09-26

    Depression is a common outcome for those having experienced early-life stress (ELS). For those individuals, depression typically increases during adolescence and appears to endure into adulthood, suggesting alterations in the development of brain systems involved in depression. Developmentally, the nucleus accumbens (NAcc), a limbic structure associated with reward learning and motivation, typically undergoes dramatic functional change during adolescence; therefore, age-related changes in NAcc function may underlie increases in depression in adolescence following ELS. The current study examined the effects of ELS in 38 previously institutionalized children and adolescents in comparison to a group of 31 youths without a history of ELS. Consistent with previous research, the findings showed that depression was higher in adolescents than children with a history of ELS. Additionally, functional magnetic resonance imaging results showed atypical NAcc development, where the ELS group did not show a typical increase in NAcc reactivity during adolescence. Consequently, the ELS group showed NAcc hypoactivation during adolescence, and lower NAcc reactivity was correlated with higher depression scores. The results have important implications for understanding how ELS may influence increases in depression via neural development during the transition to adolescence and highlight the importance of identifying at-risk individuals in childhood, a potential critical period for depression-targeted intervention. PMID:23262241

  7. Reduced Nucleus Accumbens Reactivity and Adolescent Depression following Early-life Stress

    PubMed Central

    Goff, Bonnie; Gee, Dylan G.; Telzer, Eva H.; Humphreys, Kathryn L.; Gabard-Durnam, Laurel; Flannery, Jessica; Tottenham, Nim

    2013-01-01

    Depression is a common outcome for those having experienced early life stress (ELS). For those individuals, depression typically increases during adolescence and appears to endure into adulthood, suggesting alterations in the development of brain systems involved in depression. Developmentally, the nucleus accumbens (NAcc), a limbic structure associated with reward learning and motivation, typically undergoes dramatic functional change during adolescence; therefore, age-related changes in NAcc function may underlie increases in depression in adolescence following ELS. The current study examined the effects of ELS in 38 previously institutionalized children and adolescents in comparison to a group of 31 youth without a history of ELS. Consistent with previous research, the findings showed that depression was higher in adolescents than children with a history of ELS. Additionally, fMRI results showed atypical NAcc development, where the ELS group did not show a typical increase in NAcc reactivity during adolescence. Consequently, the ELS group showed NAcc hypoactivation during adolescence, and lower NAcc reactivity was correlated with higher depression scores. The results have important implications for understanding how ELS may influence increases in depression via neural development during the transition to adolescence and highlight the importance of identifying at-risk individuals in childhood, a potential critical period for depression-targeted intervention. PMID:23262241

  8. Composition, Reactivity and Regulation of Extracellular Metal-Reducing Structures (Bacterial Nanowires) Produced by Dissimilatory Metal - Reducing Bacteria.

    SciTech Connect

    Beveridge, Terrance J; Whitfield, Christopher

    2013-03-06

    This is the final technical report for the project. There were two objectives in the proposal. The first was to describe the composition and function of electrically conductive appendages, known as bacterial nanowires, which resemble pili but are longer and are electrically conductive. They were first identified on the dissimilatory metal-reducing bacteria (DMRB), Shewanella and Geobacter. Specifically, this project investigated the role of these structures in: (i) the reductive transformation of iron oxides as solid phase electron acceptors; (ii) the use of as uranium as a dissolved electron acceptor to form nanocrystalline particles of uraninite upon reduction. The Beveridge group investigated these processes using advanced cryo-transmission electron microscopy (cryoTEM) to visualize the points of connection between the distal ends of nanowires and the effect they have on solid phase Fe minerals. At the same time, immuno-electron microscopy was applied in an attempt to identify where metal reductases and cytochromes are located on the cell surface, or in the nanowires. The second objective was to define the surface physicochemistry of Shewanella spp. in an attempt to decipher how weak bonding (electrostatics and hydrophobicity) affects the adherence of the bacteria to Fe oxides. This bonding could be dictated by the chemistry of lipopolysaccharide (LPS), or the presence/absence of capsular polysaccharide.

  9. Reduced activity of monoamine oxidase in the rat brain following repeated nandrolone decanoate administration.

    PubMed

    Birgner, Carolina; Kindlundh-Högberg, Anna M S; Oreland, Lars; Alsiö, Johan; Lindblom, Jonas; Schiöth, Helgi B; Bergström, Lena

    2008-07-11

    Anabolic androgenic steroids (AAS) are known as doping agents within sports and body-building, but are currently also abused by other groups in society in order to promote increased courage and aggression. We previously showed that 14 days of daily intramuscular injections of the AAS nandrolone decanoate (15 mg/kg) reduced the extracellular levels of the dopaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens shell using microdialysis. The aim of the present study was to investigate whether the same dose regimen of nandrolone decanoate may affect the activities of the dopamine-metabolizing enzymes monoamine oxidases A and B (MAO-A and MAO-B). A radiometric assay was used to determine the activities of MAO-A and MAO-B in rat brain tissues after 14 days of daily i.m. nandrolone decanoate injections at the doses 3 and 15 mg/kg. Gene transcript contents of MAO-A, MAO-B and cathecol-O-methyltransferase (COMT) were measured with quantitative real-time reverse transcription PCR. 3 mg/kg of nandrolone decanoate significantly reduced the activity of both MAO-A and -B in the caudate putamen. 15 mg/kg of nandrolone decanoate significantly reduced the activity of MAO-A in the amygdala and increased the gene transcript level of MAO-B in the substantia nigra. In conclusion, imbalanced MAO activities may contribute to explain the impulsive and aggressive behaviour often described in AAS abusers. The reduced MAO activities observed are in line with our previously presented findings of decreased extracellular levels of DOPAC and HVA in the rat brain, indicating decreased monoaminergic activity following repeated AAS administration. PMID:18539264

  10. Reduced yield stress for zirconium exposed to iodine: Reactive force field simulation

    SciTech Connect

    Rossi, Matthew L.; Taylor, Christopher D.; van Duin, Adri C. T.

    2014-11-04

    Iodine-induced stress-corrosion cracking (ISCC), a known failure mode for nuclear fuel cladding, occurs when iodine generated during the irradiation of a nuclear fuel pellet escapes the pellet through diffusion or thermal cracking and chemically interacts with the inner surface of the clad material, inducing a subsequent effect on the cladding’s resistance to mechanical stress. To complement experimental investigations of ISCC, a reactive force field (ReaxFF) compatible with the Zr-I chemical and materials systems has been developed and applied to simulate the impact of iodine exposure on the mechanical strength of the material. The study shows that the material’s resistance to stress (as captured by the yield stress of a high-energy grain boundary) is related to the surface coverage of iodine, with the implication that ISCC is the result of adsorption-enhanced decohesion.

  11. Reduced yield stress for zirconium exposed to iodine: Reactive force field simulation

    DOE PAGES

    Rossi, Matthew L.; Taylor, Christopher D.; van Duin, Adri C. T.

    2014-11-04

    Iodine-induced stress-corrosion cracking (ISCC), a known failure mode for nuclear fuel cladding, occurs when iodine generated during the irradiation of a nuclear fuel pellet escapes the pellet through diffusion or thermal cracking and chemically interacts with the inner surface of the clad material, inducing a subsequent effect on the cladding’s resistance to mechanical stress. To complement experimental investigations of ISCC, a reactive force field (ReaxFF) compatible with the Zr-I chemical and materials systems has been developed and applied to simulate the impact of iodine exposure on the mechanical strength of the material. The study shows that the material’s resistance tomore » stress (as captured by the yield stress of a high-energy grain boundary) is related to the surface coverage of iodine, with the implication that ISCC is the result of adsorption-enhanced decohesion.« less

  12. Local Structure, Electronic Behavior, and Electrocatalytic Reactivity of CO-Reduced Platinum-Iron Oxide Nanoparticles

    SciTech Connect

    Duchesne, Paul N.; Chen, Guangxu; Zheng, Nanfeng; Zhang, Peng

    2014-02-18

    A series of platinum–iron oxide nanoparticles was synthesized using a “clean” CO-reduction method that employed different ratios of Pt-Fe precursor salts in oleylamine at elevated temperatures. High-resolution transmission electron microscopy (HRTEM) and energy-dispersive X-ray spectroscopy (EDS) studies revealed that nearly monodisperse (i.e., with relative standard deviations of less than 15%) nanoparticles with mean diameters of 3.5–4.4 nm and varied elemental compositions (Pt54Fe46 Pt70Fe30, and Pt87Fe13) were obtained. X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) measurements at the Pt L3- and Fe K-edges revealed that these nanoparticles all consisted of a Pt core with amorphous iron oxide on the surface. Furthermore, it was observed that the local structure (e.g., Pt–Pt bond distance and coordination number) and electronic behavior of the Pt–FeO nanoparticles (e.g., Pt d electron density and Fe valence state) are dependent on the Pt-Fe precursor ratios used in their synthesis. Quantum mechanical ab initio calculations were employed to interpret the results from X-ray spectroscopy and help elucidate the relationships between local structure and electronic properties in the nanoparticle samples. Finally, the surface reactivity of these nanoparticles in the oxygen reduction reaction (ORR) was explored, demonstrating higher electrocatalytic activity for all three platinum–iron oxide samples in comparison with a commercial Pt catalyst. The surface reactivity was also found to be sensitive to the Pt-Fe ratios of the nanoparticles and could be correlated with their local structure and electronic behavior.

  13. Modifying Memory for a Museum Tour in Older Adults: Reactivation-Related Updating that Enhances and Distorts Memory is Reduced in Aging

    PubMed Central

    St Jacques, Peggy L.; Montgomery, Daniel; Schacter, Daniel L.

    2015-01-01

    Memory reactivation, the activation of a latent memory trace when we are reminded of a past experience, strengthens memory but can also contribute to distortions if new information present during reactivation is integrated with existing memory. In a previous study in young adults we found that the quality of memory reactivation, manipulated using the principle of encoding specificity and indexed by recollection ratings, modulated subsequent true and false memories for events experienced during a museum tour. Here, we examined age-related changes in the quality of memory reactivation on subsequent memory. Young and older adults reactivated memories for museum stops immediately followed by the presentation of a novel lure photo from an alternate tour version (i.e., reactivation plus new information). There was an increase in subsequent true memories for reactivated targets and for subsequent false memories for lures that followed reactivated targets, when compared to baseline target and lure photos. However, the influence of reactivation on subsequent memories was reduced in older adults. These data reveal that aging alters reactivation-related updating processes that allow memories to be strengthened and updated with new information-consequently reducing memory distortions in older compared to young adults. PMID:24993055

  14. Modifying memory for a museum tour in older adults: Reactivation-related updating that enhances and distorts memory is reduced in ageing.

    PubMed

    St Jacques, Peggy L; Montgomery, Daniel; Schacter, Daniel L

    2015-01-01

    Memory reactivation, the activation of a latent memory trace when we are reminded of a past experience, strengthens memory but can also contribute to distortions if new information present during reactivation is integrated with existing memory. In a previous study in young adults we found that the quality of memory reactivation, manipulated using the principle of encoding specificity and indexed by recollection ratings, modulated subsequent true and false memories for events experienced during a museum tour. Here in this study, we examined age-related changes in the quality of memory reactivation on subsequent memory. Memories of museum stops in young and older adults were reactivated and then immediately followed by the presentation of a novel lure photo from an alternate tour version (i.e., reactivation plus new information). There was an increase in subsequent true memories for reactivated targets and for subsequent false memories for lures that followed reactivated targets, when compared to baseline target and lure photos. However, the influence of reactivation on subsequent memories was reduced in older adults. These data reveal that ageing alters reactivation-related updating processes that allow memories to be strengthened and updated with new information, consequently reducing memory distortions in older adults compared to young adults.

  15. Reduced reactivity to air on HF-treated YBa2Cu3O(7-x)surfaces

    NASA Technical Reports Server (NTRS)

    Vasquez, R. P.; Hunt, B. D.; Foote, M. C.

    1989-01-01

    Treatment of YBa2Cu3O(7-x) films with a nonaqueous solution of HF in absolute ethanol results in the formation of an oxyfluoride with relative Y:Ba:Cu concentrations of 1:4:3 on the surface, as determined by X-ray photoelectron spectroscopy. The passivation properties of chemically treated films were tested by monitoring the growth of the high binding energy O 1s peak, associated with nonsuperconducting surface species, as a function of air exposure time, for both HF-treated and untreated films. The native oxyfluoride is shown to reduce the reactivity of the superconductor to air.

  16. Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats.

    PubMed

    Jia, Xiaoming; Chen, Yanfeng; Zidichouski, Jeffrey; Zhang, Junzeng; Sun, Changhao; Wang, Yanwen

    2008-11-01

    The objective of the present study was to determine the beneficial effects and the safety of oral administration of the combination of berberine (BBR) and plant stanols (PS) on plasma lipid profiles in male Sprague-Dawley rats. Four groups of animals were fed a cornstarch-casein-sucrose-based high-cholesterol (2%, w:w) and high-fat (27.5%) diet. Three treatment groups were supplemented with either BBR (100mgkg(-1)bodyweightd(-1)), PS (1% in diet, w:w), or the combination of both (BBRPS). After 6 wk, animals were sacrificed and followed immediately with the collection of blood and organ samples. Lipid analysis revealed that PS lowered plasma total cholesterol (T-C) by 18% (p=0.067) and non-HDL-cholesterol (non-HDL-C) by 29% (p=0.013) as compared with the control, while BBR had no effect on both T-C and non-HDL-C. The combination treatment of BBRPS reduced plasma T-C by 41% (p=0.0002) and non-HDL-C by 59% (p<0.0001) compared to the control group. BBR reduced plasma TG levels by 31% at a marginal significance relative to the control (p=0.054), whereas PS had no effect. BBRPS showed an additive effect of BBR and PS on plasma TAG. PS and BBRPS both decreased liver cholesterol (p=0.0027 and 0.0002, respectively). BBR and PS, either alone or in combination, did not show any toxic effects as assessed by plasma concentration of hepatic biochemical parameters. These results demonstrate that BBR and PS, when combined, synergistically lower plasma cholesterol levels and significantly reduce liver cholesterol, without the observation of any toxic effects.

  17. Effectiveness of Diesel Oxidation Catalyst in Reducing HC and CO Emissions from Reactivity Controlled Compression Ignition

    SciTech Connect

    Prikhodko, Vitaly Y; Curran, Scott; Parks, II, James E; Wagner, Robert M

    2013-01-01

    Reactivity Controlled Compression Ignition (RCCI) has been shown to allow for diesel-like or better brake thermal efficiency with significant reductions in nitrogen oxide (NOX) particulate matter (PM) emissions. Hydrocarbon (HC) and carbon monoxide (CO) emission levels, on the other hand, are similar to those of port fuel injected gasoline engines. The higher HC and CO emissions combined with the lower exhaust temperatures with RCCI operation present a challenge for current exhaust aftertreatments. The reduction of HC and CO emissions in a lean environment is typically achieved with an oxidation catalyst. In this work, several diesel oxidation catalysts (DOC) with different precious metal loadings were evaluated for effectiveness to control HC and CO emissions from RCCI combustion in a light-duty multi-cylinder engine operating on gasoline and diesel fuels. Each catalyst was evaluated in a steady-state engine operation with temperatures ranging from 160 to 260 C. A shift to a higher light-off temperature was observed during the RCCI operation. In addition to the steady-state experiments, the performances of the DOCs were evaluated during multi-mode engine operation by switching from diesel-like combustion at higher exhaust temperature and low HC/CO emissions to RCCI combustion at lower temperature and higher HC/CO emissions. High CO and HC emissions from RCCI generated an exotherm keeping the catalyst above the light-off temperature.

  18. Piperlongumine Suppresses Dendritic Cell Maturation by Reducing Production of Reactive Oxygen Species and Has Therapeutic Potential for Rheumatoid Arthritis.

    PubMed

    Xiao, Youjun; Shi, Maohua; Qiu, Qian; Huang, Mingcheng; Zeng, Shan; Zou, Yaoyao; Zhan, Zhongping; Liang, Liuqin; Yang, Xiuyan; Xu, Hanshi

    2016-06-15

    Piperlongumine (PLM) is a natural product from the plant Piper longum that inhibits platelet aggregation, atherosclerosis plaque formation, and tumor cell growth. It has potential value in immunomodulation and the management of autoimmune diseases. In this study, we investigated the role of PLM in regulating the differentiation and maturation of dendritic cells (DCs), a critical regulator of immune tolerance, and evaluated its clinical effects in a rheumatoid arthritis mouse model. We found that PLM treatment reduced LPS-induced murine bone marrow-derived DC maturation, characterized by reduced expression of CD80/86, secretion of MCP-1, IL-12p70, IL-6, TNFα, IFN-γ, and IL-23, and reduced alloproliferation of T cells; however, PLM does not affect cell differentiation. Furthermore, PLM reduced intracellular reactive oxygen species (ROS) production by DCs and inhibited the activation of p38, JNK, NF-κB, and PI3K/Akt signaling pathways. Conversely, PLM increased the expression of GSTP1 and carbonyl reductase 1, two enzymes that counteract ROS effects. ROS inhibition by exogenous N-acetyl-l-cysteine suppressed DC maturation. PLM treatment improved the severity of arthritis and reduced in vivo splenic DC maturation, collagen-specific CD4(+) T cell responses, and ROS production in mice with collagen-induced arthritis. Taken together, these results suggest that PLM inhibits DC maturation by reducing intracellular ROS production and has potential as a therapeutic agent for rheumatoid arthritis.

  19. Progesterone administration reduces the behavioural and physiological responses of ewes to abrupt weaning of lambs.

    PubMed

    Freitas-de-Melo, A; Banchero, G; Hötzel, M J; Damián, J P; Ungerfeld, R

    2013-08-01

    Abrupt weaning, a usual management in sheep productive systems, may provoke behavioural and physiological responses indicative of stress in ewes and lambs. Progesterone (P4) has anxiolytic and sedative effects through the union of its metabolites that contain 3α-hydroxyl group to the γ-aminobutyricacidA receptor. Our first aim was to determine whether P4 administration reduces the behavioural and physiological responses of ewes to abrupt weaning of lambs. A complementary aim was to determine whether P4 treatment affects the milk yield and composition of ewes, and the BW of their lambs. In experiment 1, seven ewes received P4 treatment for 32 days (group E1-P4), and eight ewes remained as an untreated control group (group E1-C). BW of the lambs was recorded during P4 treatment. Lambs were weaned at 59 days (Day 0 = weaning). The main behaviours of the ewes before and after weaning were recorded using 10 min scan sampling. The ewes' serum total protein, albumin and globulin concentrations were measured before and after weaning of the lambs. In experiment 2, milk yield and composition were determined in two different groups of six ewes treated with P4 (group E2-P4) for 16 days and in five untreated controls (group E2-C). The BW of lambs increased with time (P = 0.001) in both groups and did not differ. The percentage of observations in which the ewes were seen pacing on Day 0 was greater in the E1-C group than in the E1-P4 group (P = 0.0007). Similarly, the percentage of observations in which the ewes were recorded vocalizing on Day 0 was greater in the E1-C group than in the E1-P4 group (P = 0.04). The percentage of observations in which E1-C ewes were recorded lying did not change from Days 0 to 1; however, it increased in E1-P4 ewes. Total serum protein concentration did not change in E1-P4 ewes from Days 0 to 3, although a decrease was seen in E1-C ewes (P = 0.04). Serum globulin concentration was greater in E1-P4 ewes on Day 3 than in E1-C ewes (P = 0.0008). In

  20. Mission possible: creating a technology infrastructure to help reduce administrative costs.

    PubMed

    Alper, Michael

    2003-01-01

    Controlling administrative costs associated with managed care benefits has traditionally been considered a "mission impossible" in healthcare, with the unreasonably high cost of paperwork and administration pushing past the $420 billion mark. Why administrative costs remain a critical problem in healthcare while other industries have alleviated their administrative burdens must be carefully examined. This article looks at the key factors contributing to high administrative costs and how these costs can be controlled in the future with "mission possible" tools, including business process outsourcing, IT outsourcing, technology that helps to bring "consumerism" to managed care, and an IT infrastructure that improves quality and outcomes. PMID:14983647

  1. Norepinephrine Reduces Reactive Oxygen Species (ROS) and DNA Damage in Ovarian Surface Epithelial Cells

    PubMed Central

    Patel, Pooja R; Hegde, Muralidhar L; Theruvathu, Jacob; Mitra, Sankar A; Boldogh, Istvan; Sowers, Lawrence

    2015-01-01

    Objective To determine the role of norepinephrine (NE) on DNA damage and reactive oxygen species (ROS) generation in ovarian surface epithelial cells. Method Non-tumorigenic, immortalized ovarian surface epithelial cells were treated with NE, bleomycin, and bleomycin followed by NE. The comet assay was performed on each treatment group to determine the amount of single and double-strand breaks induced by treatments. ROS levels for each treatment group were measured using the H2DCF-DA fluorescence assay. Finally, RNA transcripts were measured for each treatment group with regards to the expression of DNA repair and oxidative stress genes. Results The mean tail moment of untreated cells was significantly greater than that of cells treated with NE (p=0.02). The mean tail moment of cells treated with bleomycin was significantly greater than that of cells treated with bleomycin followed by NE (p<0.01). Treatment with NE resulted in significantly less ROS generation than in untreated cells (p<0.01). NE treatment after hydrogen peroxide treatment resulted in a noticeable decrease in ROS generation. Genes associated with oxidative stress were upregulated in cells treated with bleomycin, however this upregulation was blunted when bleomycin-treated cells were treated subsequently with NE. Conclusion NE is associated with decreased DNA damage and ROS production in ovarian surface epithelial cells. This effect is protective in the presence of the oxidative-damaging agent bleomycin. These results suggest an additional physiologic role for the stress hormone NE, in protecting ovarian surface epithelial cells from oxidative stress. PMID:26167254

  2. Reactive Iron and Iron-Reducing Bacteria in Louisiana Continental Shelf Sediments

    EPA Science Inventory

    The Mississippi and Atchafalaya Rivers release sediments containing 15 x 106 t of iron onto the Louisiana continental shelf (LCS) each year. Iron oxides reaching the seafloor may be utilized as electron acceptors by iron-reducing bacteria for organic matter oxidation or become r...

  3. Blind sequential lineup administration reduces both false identifications and confidence in those false identifications.

    PubMed

    Charman, Steve D; Quiroz, Vanessa

    2016-10-01

    One of the most recommended procedures proposed by eyewitness experts is the use of double-blind lineups, in which the administrator does not know the identity of the suspect in the lineup. But despite the near universality of this recommendation, there is surprisingly little empirical research to support the claim that nonblind administration inflates false identifications. What little research has been conducted has shown conflicting findings with regard to the conditions under which nonblind administration affects false identifications, as well as its effects on witness confidence. The current study attempts to elucidate this effect. Student-participants (n = 312) were randomly assigned to play the role of either a lineup administrator (who were either told the identity of the suspect in the lineup or not) or a mock crime witness. Following unbiased instructions, administrators presented either a target-present or target-absent sequential lineup to the witness while being surreptitiously videorecorded. Nonblind administration significantly inflated false, but not correct, identifications, and significantly inflated witness confidence in those false identifications. Video recordings indicated that nonblind administrators were significantly more likely than blind administrators to smile (a) while the witness was viewing a photograph of the suspect, and (b) after a suspect identification. Results provide stronger support for the use of blind lineup administration by broadening the conditions under which nonblind administration is shown to inflate false identifications. Possible reconciliations for conflicting findings in the literature are discussed. (PsycINFO Database Record

  4. Nonevaluative social support reduces cardiovascular reactivity in young women during acutely stressful performance situations.

    PubMed

    Fontana, A M; Diegnan, T; Villeneuve, A; Lepore, S J

    1999-02-01

    We tested whether the presence of a stranger reduces cardiovascular responses during stressful tasks if the evaluation potential of the stranger is minimized and whether cardiovascular responses are affected by the quality of support in a friendship. Undergraduate women performed stressful tasks in one of three conditions: Alone, with a same-sex Stranger, or with a same-sex best Friend. The stranger and friend could not hear participants' responses. Alone women had the greatest increases in SBP and HR while women in the Stranger and Friend conditions did not differ in their responses. In the Friend condition, HR responses were smallest in women who were highly satisfied with the support that they generally received from their friend. We conclude that the presence of a nonevaluative friend or stranger can reduce cardiovascular responses and that the quality of supportive ties modulates the impact of those ties on responses to stress. PMID:10196730

  5. Controlling reactive oxygen species in skin at their source to reduce skin aging.

    PubMed

    Kern, Dale G; Draelos, Zoe D; Meadows, Christiaan; James Morré, D; Morré, Dorothy M

    2010-01-01

    Activity of an age-related, superoxide-forming, cell-surface oxidase (arNOX) comparing dermis, epidermis, serum, and saliva from female and male subjects ages 28-72 years measured spectrophotometrically using reduction of ferricytochrome c correlated with oxidative skin damage as estimated from autofluoresence of skin using an Advanced Glycation End products Reader (AGE-Reader; DiagnOptics B.V., Netherlands). By reducing arNOX activity in skin with arNOX-inhibitory ingredients (NuSkin's ageLOC technology), skin appearance was improved through decreased protein cross-linking and an accelerated increase in collagen.

  6. Controlling reactive oxygen species in skin at their source to reduce skin aging.

    PubMed

    Kern, Dale G; Draelos, Zoe D; Meadows, Christiaan; James Morré, D; Morré, Dorothy M

    2010-01-01

    Activity of an age-related, superoxide-forming, cell-surface oxidase (arNOX) comparing dermis, epidermis, serum, and saliva from female and male subjects ages 28-72 years measured spectrophotometrically using reduction of ferricytochrome c correlated with oxidative skin damage as estimated from autofluoresence of skin using an Advanced Glycation End products Reader (AGE-Reader; DiagnOptics B.V., Netherlands). By reducing arNOX activity in skin with arNOX-inhibitory ingredients (NuSkin's ageLOC technology), skin appearance was improved through decreased protein cross-linking and an accelerated increase in collagen. PMID:19954332

  7. Enzymatic Hydrolysis Does Not Reduce the Biological Reactivity of Soybean Proteins for All Allergic Subjects.

    PubMed

    Panda, Rakhi; Tetteh, Afua O; Pramod, Siddanakoppalu N; Goodman, Richard E

    2015-11-01

    Many soybean protein products are processed by enzymatic hydrolysis to attain desirable functional food properties or in some cases to reduce allergenicity. However, few studies have investigated the effects of enzymatic hydrolysis on the allergenicity of soybean products. In this study the allergenicity of soybean protein isolates (SPI) hydrolyzed by Alcalase, trypsin, chymotrypsin, bromelain, or papain was evaluated by IgE immunoblots using eight soybean-allergic patient sera. The biological relevance of IgE binding was evaluated by a functional assay using a humanized rat basophilic leukemia (hRBL) cell line and serum from one subject. Results indicated that hydrolysis of SPI by the enzymes did not reduce the allergenicity, and hydrolysis by chymotrypsin or bromelain has the potential to increase the allergenicity of SPI. Two-dimensional (2D) immunoblot and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the chymotrypsin-hydrolyzed samples indicated fragments of β-conglycinin protein are responsible for the apparent higher allergenic potential of digested SPI.

  8. Reduced Efficacy of Praziquantel Against Schistosoma mansoni Is Associated With Multiple Rounds of Mass Drug Administration

    PubMed Central

    Crellen, Thomas; Walker, Martin; Lamberton, Poppy H. L.; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Cotton, James A.; Webster, Joanne P.

    2016-01-01

    Background. Mass drug administration (MDA) with praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane. Methods. We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6–12 years before and 25–27 days after treatment with praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds. Results. The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%–93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%–99.08%) or 1 round (95% BCI, 95.51%–98.96%) of MDA. We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8–9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal praziquantel efficacy set by the World Health Organization. Conclusions. The reduced efficacy of praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored. PMID:27470241

  9. Mindfulness meditation associated with alterations in bottom-up processing: psychophysiological evidence for reduced reactivity.

    PubMed

    van den Hurk, Paul A M; Janssen, Barbara H; Giommi, Fabio; Barendregt, Henk P; Gielen, Stan C

    2010-11-01

    Mental training by meditation has been related to changes in high-level cognitive functions that involve top-down processing. The aim of this study was to investigate whether the practice of meditation is also related to alterations in low-level, bottom-up processing. Therefore, intersensory facilitation (IF) effects in a group of mindfulness meditators (MM) were compared to IF effects in an age- and gender-matched control group. Smaller and even absent IF effects were found in the MM group, which suggests that changes in bottom-up processing are associated with MM. Furthermore, reduced interference of a visual warning stimulus with the IF effects was found, which suggests an improved allocation of attentional resources in mindfulness meditators, even across modalities.

  10. Synthesis and Reactivity of Low-Coordinate Titanium Synthons Supported by a Reduced Redox-Active Ligand.

    PubMed

    Clark, Kensha Marie

    2016-07-01

    To further explore the reactivity and redox capability of the bis-arylimino acenaphthylene ligand (BIAN) in early transition metal complexes, the coordinatively unsaturated titanium synthons, [(dpp-BAAN)Ti(R)2] ([dpp-BAAN](2-) = N,N'-bis(2,6-diisopropylphenylamido)acenaphthylene and R = O(t)Bu (2) or CH2C(CH3)3 (3)), in which the BAAN ligand is reduced by two electrons, were isolated in good yields via sterically induced radical elimination reactions. Addition of p-tolyl azide to complex 3 initiated reductive elimination of the neopentyl ligands to generate a putative imido species. The imido species was trapped by a second oxidative addition of chloride ligands to yield the titanium imido complex, [(dpp-BIAN)Ti[═N(4-C6H4Me)]Cl2 (4). These reactions demonstrate that the BAAN ligand can provide redox equivalents for enhanced reactivity that includes oxidative addition and reductive elimination at d(0) metal centers. PMID:27304996

  11. Synthesis and Reactivity of Low-Coordinate Titanium Synthons Supported by a Reduced Redox-Active Ligand.

    PubMed

    Clark, Kensha Marie

    2016-07-01

    To further explore the reactivity and redox capability of the bis-arylimino acenaphthylene ligand (BIAN) in early transition metal complexes, the coordinatively unsaturated titanium synthons, [(dpp-BAAN)Ti(R)2] ([dpp-BAAN](2-) = N,N'-bis(2,6-diisopropylphenylamido)acenaphthylene and R = O(t)Bu (2) or CH2C(CH3)3 (3)), in which the BAAN ligand is reduced by two electrons, were isolated in good yields via sterically induced radical elimination reactions. Addition of p-tolyl azide to complex 3 initiated reductive elimination of the neopentyl ligands to generate a putative imido species. The imido species was trapped by a second oxidative addition of chloride ligands to yield the titanium imido complex, [(dpp-BIAN)Ti[═N(4-C6H4Me)]Cl2 (4). These reactions demonstrate that the BAAN ligand can provide redox equivalents for enhanced reactivity that includes oxidative addition and reductive elimination at d(0) metal centers.

  12. Integration of Genome-Scale Metabolic Nodels of Iron-Reducing Bacteria With Subsurface Flow and Geochemical Reactive Transport Models

    NASA Astrophysics Data System (ADS)

    Scheibe, T. D.; Mahadevan, R.; Fang, Y.; Garg, S.; Long, P. E.; Lovley, D. M.

    2008-12-01

    Several field and laboratory experiments have demonstrated that the growth and activity of iron-reducing bacteria can be stimulated in many subsurface environments by amendment of groundwater with a soluble electron donor. Under strong iron-reducing conditions, these organisms mediate reactions that can impact a wide range of subsurface contaminants including chlorinated hydrocarbons, metals, and radionuclides. Therefore there is strong interest in in-situ bioremediation as a potential technology for cleanup of contaminated aquifers. To evaluate and design bioremediation systems, as well as to evaluate the viability of monitored natural attenuation as an alternative, quantitative models of biogeochemically reactive transport are needed. To date, most such models represent microbial activity in terms of kinetic rate (e.g., Monod- type) formulations. Such models do not account for fundamental changes in microbial functionality (such as utilization of alternative respiratory pathways) that occur as the result of spatial and temporal variations in the geochemical environment experienced by microorganisms. Constraint-based genome-scale in silico models of microbial metabolism present an alternative to simplified rate formulations that provide flexibility to account for changes in microbial function in response to local geochemical conditions. We have developed and applied a methodology for coupling a constraint-based in silico model of Geobacter sulfurreducens with a conventional model of groundwater flow, transport, and geochemical reaction. Two uses of the in silico model are tested: 1) incorporation of modified microbial growth yield coefficients based on the in silico model, and 2) variation of reaction rates in a reactive transport model based on in silico modeling of a range of local geochemical conditions. Preliminary results from this integrated model will be presented.

  13. Reactivity of partially reduced arylhydroxylamine and nitrosoarene metabolites of 2,4,6-trinitrotoluene (TNT) toward biomass and humic acids.

    PubMed

    Ahmad, Farrukh; Hughes, Joseph B

    2002-10-15

    Sequential anaerobic/aerobic treatment of 2,4,6-trinitrotoluene (TNT) generally results in the incorporation of residues into biomass and natural organic matter fractions of a system. To better understand the potential contribution of hydroxylamine and nitroso moieties in these reactions, studies were conducted using model systems taking advantage of the biocatalytic-activity of Clostridium acetobutylicum that does not produce aminated TNT derivatives. To evaluate binding to biomass only, systems containing cell-free extracts of C. acetobutylicum and molecular hydrogen as a reductant were employed. At the end of treatment, mass balance studies showed that 10% of the total 14C was associated with an insoluble protein-containing precipitate that could not be extracted with organic solvents. Model reactions were conducted between a mixture of 2,4-dihydroxylamino-6-nitrotoluene (DHA6NT) and 4-hydroxylamino-2,6-dinitrotoluene (4HADNT) and 1-thioglycerol to test the involvement of the nitroso-thiol reaction in binding to biomass. It was demonstrated that DHA6NT formed a new and relatively polar product with 1-thioglycerol only in the presence of oxygen. The oxygen requirement confirmed that the nitroso functionality was responsible for the binding reaction. The reactivity of arylhydroxylamino and nitrosoarene functionalities toward International Humic Substance Society (IHSS) peat humic acid was evaluated under anaerobic and aerobic conditions, respectively. 4HADNT showed no appreciable reactivity toward peat humic acid. Conversely, the nitrosoarene compound, nitrosobenzene, showed rapid reactivity with peat humic acid (50% removal in 48 h). When tested with two other humic acids (selected on the basis of their protein content), it became apparent that the proteinaceous fraction was responsible at least in part for the nitrosoarene's removal from solution. Furthermore, the pretreatment of the humic acids with a selective thiol derivatizing agent had a considerable effect

  14. Administration of PPARβ/δ agonist reduces copper-induced liver damage in mice: possible implications in clinical practice.

    PubMed

    Sanchez-Siles, Alvaro A; Ishimura, Norihisa; Rumi, Mohammad A K; Tamagawa, Yuji; Ito, Satoko; Ishihara, Shunji; Nabika, Toru; Kinoshita, Yoshikazu

    2011-07-01

    In this study we investigated if peroxisome proliferator-activated receptor β/δ activation protects from copper-induced acute liver damage. Mice treated with copper had significant body weight loss, serum alanine aminotransferase increase, modest changes in liver histology, increase of tumor necrosis factor α and macrophage inflammatory protein 2 mRNA and 8-hydroxy-2'-deoxyguanosine. Mice treated with copper and peroxisome proliferator-activated receptor β/δ agonist GW0742 had significantly less body weight loss, less serum alanine aminotransferase increase, less tumor necrosis factor α, macrophage inflammatory protein-2 and 8-hydroxy-2'-deoxyguanosine upregulation than copper treated mice. The opposite effect was observed in mice treated with copper and peroxisome proliferator-activated receptor β/δ antagonist GSK0660. In vitro, copper induced reactive oxygen species, which was lower in cells treated with GW0742 or transfected with peroxisome proliferator-activated receptor β/δ expression vector; together, transfection and GW0742 had an additive reactive oxygen species-reducing effect. Copper also upregulated Fas ligand and Caspase 3/7 activity, effects that were significantly lower in cells also treated with GW0742. In conclusion, peroxisome proliferator-activated receptor β/δ activation reduced copper-induced reactive oxygen species, pro-inflammatory and acute phase reaction cytokines in mice liver. Peroxisome proliferator-activated receptor β/δ agonists could become useful in the management of copper-induced liver damage.

  15. Administration of haloperidol with biperiden reduces mRNAs related to the ubiquitin-proteasome system in mice.

    PubMed

    Iwata, Shin-Ichi; Morioka, Hirofumi; Iwabuchi, Mika; Shinohara, Kazuya; Maeda, Maki; Shimizu, Takao; Miyata, Atsuro

    2005-06-15

    In order to find molecules affected by administration of an antipsychotic drug with an antimuscarinic drug, which is a common prescription used to prevent extrapyramidal adverse effects caused by the antipsychotic drugs, gene expression profiling in the frontal cortex was studied in mice. After 14 days of administration with 2 mg/kg haloperidol, a typical antipsychotic drug, and 2 mg/kg biperiden, a high-affinity antagonist for muscarinic receptors in the brain, approximately 500 mRNAs related to synaptic function were investigated. The levels of the mRNAs related to the ubiquitin-related systems were significantly reduced after the combined administration. However, the separate administration of either haloperidol or biperiden had little effect on the levels of the mRNAs. This result suggests that coadministration of haloperidol and biperiden specifically affects the ubiquitin-related system.

  16. Treadmill exercise reduces self-administration of morphine in male rats.

    PubMed

    Hosseini, Mahmoud; Alaei, Hojjat Allah; Naderi, Asieh; Sharifi, Mohammad Reza; Zahed, Reza

    2009-06-01

    Exercise can activate the same pathways as morphine. The aim of the present study was to clarify the effect of short-term and mid-term exercises on the self-administration of morphine in rats. Male Wistar rats were initially trained to receive small pellets of food by pressing the active lever in self-administration apparatus. Rats were divided into 4 groups: Saline, Morphine, Exercise 1 (11 days) and Exercise 2 (30 days). Their jugular vein was cannulated. The animals were placed in self-administration apparatus and allowed to self-administer morphine (0.5mg per infusion all test groups) or saline (Saline group) during consecutive days, for 2h/sessions. In the group 1 the rats were running before each session of self-administration and of group Exercise 2, 30 days before surgery as well as before each session. The pressing numbers of active and passive levers in each group and among different groups were compared. The number of active lever pressing of Morphine group was significantly higher than Saline group (p<0.001). In Exercise 1 and Exercise 2 groups, the number of active lever pressing was significantly lower than Morphine group (p<0.001). As exercise can activate many neurotransmitter systems involved in the addiction process and increase the release of endorphins, it is likely that could decrease the morphine self-administration in this experimental setup. PMID:19131225

  17. Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.

    PubMed

    Yardley, Megan M; Neely, Michael; Huynh, Nhat; Asatryan, Liana; Louie, Stan G; Alkana, Ronald L; Davies, Daryl L

    2014-09-10

    Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans.

  18. Multiday administration of ivermectin is effective in reducing alcohol intake in mice at doses shown to be safe in humans.

    PubMed

    Yardley, Megan M; Neely, Michael; Huynh, Nhat; Asatryan, Liana; Louie, Stan G; Alkana, Ronald L; Davies, Daryl L

    2014-09-10

    Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans. PMID:25004078

  19. Better cognitive control of emotional information is associated with reduced pro-inflammatory cytokine reactivity to emotional stress.

    PubMed

    Shields, Grant S; Kuchenbecker, Shari Young; Pressman, Sarah D; Sumida, Ken D; Slavich, George M

    2016-01-01

    Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants' cognitive control of emotional information using an emotional Stroop task. We also assessed participants' cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

  20. Reducing Cytoplasmic Polyamine Oxidase Activity in Arabidopsis Increases Salt and Drought Tolerance by Reducing Reactive Oxygen Species Production and Increasing Defense Gene Expression

    PubMed Central

    Sagor, G. H. M.; Zhang, Siyuan; Kojima, Seiji; Simm, Stefan; Berberich, Thomas; Kusano, Tomonobu

    2016-01-01

    The link between polyamine oxidases (PAOs), which function in polyamine catabolism, and stress responses remains elusive. Here, we address this issue using Arabidopsis pao mutants in which the expression of the five PAO genes is knocked-out or knocked-down. As the five single pao mutants and wild type (WT) showed similar response to salt stress, we tried to generate the mutants that have either the cytoplasmic PAO pathway (pao1 pao5) or the peroxisomal PAO pathway (pao2 pao3 pao4) silenced. However, the latter triple mutant was not obtained. Thus, in this study, we used two double mutants, pao1 pao5 and pao2 pao4. Of interest, pao1 pao5 mutant was NaCl- and drought-tolerant, whereas pao2 pao4 showed similar sensitivity to those stresses as WT. To reveal the underlying mechanism of salt tolerance, further analyses were performed. Na uptake of the mutant (pao1 pao5) decreased to 75% of WT. PAO activity of the mutant was reduced to 62% of WT. The content of reactive oxygen species (ROS) such as hydrogen peroxide, a reaction product of PAO action, and superoxide anion in the mutant became 81 and 72% of the levels in WT upon salt treatment. The mutant contained 2.8-fold higher thermospermine compared to WT. Moreover, the mutant induced the genes of salt overly sensitive-, abscisic acid (ABA)-dependent- and ABA-independent- pathways more strongly than WT upon salt treatment. The results suggest that the Arabidopsis plant silencing cytoplasmic PAOs shows salinity tolerance by reducing ROS production and strongly inducing subsets of stress-responsive genes under stress conditions. PMID:26973665

  1. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats.

    PubMed

    Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F

    2015-03-13

    The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence.

  2. Serum Insulin Levels Are Reduced by Intravenous Ghrelin Administration but Do Not Correlate with Alcohol Craving in Alcohol-Dependent Individuals

    PubMed Central

    Giovenco, Danielle E.; Lee, Mary R.; Zywiak, William H.; de la Monte, Suzanne M.; Kenna, George A.; Swift, Robert M.

    2016-01-01

    Background: Increasing evidence supports a role for appetite-regulating pathways like ghrelin, insulin, and leptin in alcoholism. We previously reported that intravenous (i.v.) exogenous ghrelin increases alcohol craving. We also reported i.v. ghrelin reduces endogenous serum leptin, whose levels, in turn, negatively correlated with alcohol craving. Exogenous ghrelin administration decreases insulin secretion both in vitro and in vivo experiments. This study tested the hypothesis that i.v. ghrelin may also decrease endogenous serum insulin levels in alcoholic individuals. Additionally, we explored possible correlations between serum insulin and alcohol craving, since a correlation between insulin and alcohol craving was previously reported. Methods: This was a double-blind, placebo-controlled human laboratory study (n=43). Non-treatment-seeking, alcohol-dependent, heavy drinkers were randomized to receive i.v. ghrelin or placebo, followed by an alcohol cue-reactivity procedure. Results: There was a main effect for i.v. ghrelin, compared to placebo in reducing serum insulin (P<.05). There was also a time effect (P<.001) but not ghrelin x time interaction (P>.05). We did not find a correlation between the reduction of serum insulin and alcohol craving (P>.05). The change in serum insulin was consistent with a parallel reduction in serum connective-peptide in the ghrelin group compared with placebo, although this difference did not reach statistical significance (P=.076). No similar effects were found for other glucose-regulating hormones analyzed i.e. glucagon, glucagon-like peptide-1, and gastric inhibitory peptide (Ps>.05). Conclusions: These findings indicate i.v. ghrelin administration has an effect on reducing serum insulin in alcohol-dependent individuals; however, the reduction of insulin did not correlate with changes in alcohol cue-elicited craving. We speculate that, unlike for leptin, the interactions between ghrelin and insulin relationship are limited at

  3. Kefir administration reduced progression of renal injury in STZ-diabetic rats by lowering oxidative stress.

    PubMed

    Punaro, Giovana R; Maciel, Fabiane R; Rodrigues, Adelson M; Rogero, Marcelo M; Bogsan, Cristina S B; Oliveira, Marice N; Ihara, Silvia S M; Araujo, Sergio R R; Sanches, Talita R C; Andrade, Lucia C; Higa, Elisa M S

    2014-02-15

    This study aimed at assessing the effects of Kefir, a probiotic fermented milk, on oxidative stress in diabetic animals. The induction of diabetes was achieved in adult male Wistar rats using streptozotocin (STZ). The animals were distributed into four groups as follows: control (CTL); control Kefir (CTLK); diabetic (DM) and diabetic Kefir (DMK). Starting on the 5th day of diabetes, Kefir was administered by daily gavage at a dose of 1.8 mL/day for 8 weeks. Before and after Kefir treatment, the rats were placed in individual metabolic cages to obtain blood and urine samples to evaluate urea, creatinine, proteinuria, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and C-reactive protein (CRP). After sacrificing the animals, the renal cortex was removed for histology, oxidative stress and NOS evaluation. When compared to CTL rats, DM rats showed increased levels of glycemia, plasmatic urea, proteinuria, renal NO, superoxide anion, TBARS, and plasmatic CRP; also demonstrated a reduction in urinary urea, creatinine, and NO. However, DMK rats showed a significant improvement in most of these parameters. Despite the lack of differences observed in the expression of endothelial NO synthase (eNOS), the expression of inducible NO synthase (iNOS) was significantly lower in the DMK group when compared to DM rats, as assessed by Western blot analysis. Moreover, the DMK group presented a significant reduction of glycogen accumulation within the renal tubules when compared to the DM group. These results indicate that Kefir treatment may contribute to better control of glycemia and oxidative stress, which is associated with the amelioration of renal function, suggesting its use as a non-pharmacological adjuvant to delay the progression of diabetic complications.

  4. Supplemental Intravenous Crystalloid Administration Does Not Reduce the Risk of Surgical Wound Infection

    PubMed Central

    Kabon, Barbara; Akça, Ozan; Taguchi, Akiko; Nagele, Angelika; Jebadurai, Ratnaraj; Arkilic, Cem F.; Sharma, Neeru; Ahluwalia, Arundhathi; Galandiuk, Susan; Fleshman, James; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Wound perfusion and oxygenation are important determinants of the development of postoperative wound infections. Supplemental fluid administration significantly increases tissue oxygenation in surrogate wounds in the subcutaneous tissue of the upper arm in perioperative surgical patients. We tested the hypothesis that supplemental fluid administration during and after elective colon resections decreases the incidence of postoperative wound infections. Patients undergoing open colon resection were randomly assigned to small (n=124, 8 mL·kg-1·h-1) or large volume (n=129, 16-18 mL·kg-1·h-1) fluid management. Our major outcomes were two distinct criteria for diagnosis of surgical wound infections: 1) purulent exudate combined with a culture positive for pathogenic bacteria and 2) Center for Disease Control criteria for diagnosis of surgical wound infections. All wound infections diagnosed using either criterion by a blinded observer in the 15 days following surgery were considered in the analysis. Wound healing was evaluated with the ASEPSIS scoring system. Of the patients given small fluid administration, 14 had surgical wound infections; 11 given large fluid therapy had infections, P=0.46. ASEPSIS wound healing scores were similar in both groups: 7±16 (small volume) vs. 8±14 (large volume), P=0.70. Our results suggest that supplemental hydration in the range tested does not impact wound infection rate. PMID:16244030

  5. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models.

    PubMed

    Anderson, Rachel I; Becker, Howard C; Adams, Benjamin L; Jesudason, Cynthia D; Rorick-Kehn, Linda M

    2014-01-01

    To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX) receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573) on home cage ethanol consumption were tested in ethanol-preferring (P) rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark) model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting non-specific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting non-specific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol consumption

  6. Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species.

    PubMed

    Kurioka, Takaomi; Matsunobu, Takeshi; Satoh, Yasushi; Niwa, Katsuki; Shiotani, Akihiro

    2014-12-01

    Reactive oxygen species (ROS) that form in the inner ear play an important role in noise-induced hearing loss (NIHL). Recent studies have revealed that molecular hydrogen (H2) has great potential for reducing ROS. In this study, we examined the potential of hydrogen gas to protect against NIHL. We tested this hypothesis in guinea pigs with 0.5%, 1.0% and 1.5% H2 inhalation in air for 5h a day after noise exposure, for five consecutive days. All animals underwent measurements for auditory brainstem response after the noise exposure; the results revealed that there was a better improvement in the threshold shift for the 1.0% and 1.5% H2-treated groups than the non-treated group. Furthermore, outer hair cell (OHC) loss was examined 7 days after noise exposure. A significantly higher survival rate of OHCs was observed in the 1.0% and 1.5% H2-treated group as compared to that of the non-treated group in the basal turn. Immunohistochemical analyses for 8-hydroxy-2'-deoxyguanosine (8-OHdG) were performed to examine the amount of oxidative DNA damage. While strong immunoreactivities against 8-OHdG were observed of the non-treated group, the H2-treated group showed decreased immunoreactivity for 8-OHdG. These findings strongly suggest that inhaled hydrogen gas protects against NIHL.

  7. Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of Reactive Oxygen Species for Neural Interfacing Applications

    PubMed Central

    Potter-Baker, Kelsey A.; Nguyen, Jessica K.; Kovach, Kyle M.; Gitomer, Martin M.; Srail, Tyler W.; Stewart, Wade G.; Skousen, John L.; Capadona, Jeffrey R.

    2014-01-01

    Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio-availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces. PMID:25132966

  8. Low gravity rotational culture and the integration of immunomodulatory stem cells reduce human islet allo-reactivity.

    PubMed

    Qureshi, Khalid M; Lee, Jou; Paget, Michelle B; Bailey, Clifford J; Curnow, S John; Murray, Hilary E; Downing, Richard

    2015-01-01

    Modification of human islets prior to transplantation may improve long-term clinical outcome in terms of diabetes management, by supporting graft function and reducing the potential for allo-rejection. Intragraft incorporation of stem cells secreting beta (β)-cell trophic and immunomodulatory factors represents a credible approach, but requires suitable culture methods to facilitate islet alteration without compromising integrity. This study employed a three-dimensional rotational cell culture system (RCCS) to achieve modification, preserve function, and ultimately influence immune cell responsiveness to human islets. Islets underwent intentional dispersal and rotational culture-assisted aggregation with amniotic epithelial cells (AEC) exhibiting intrinsic immunomodulatory potential. Reassembled islet constructs were assessed for functional integrity, and their ability to induce an allo-response in discrete T-cell subsets determined using mixed islet:lymphocyte reaction assays. RCCS supported the formation of islet:AEC aggregates with improved insulin secretory capacity compared to unmodified islets. Further, the allo-response of peripheral blood mononuclear cell (PBMC) and purified CD4+ and CD8+ T-cell subsets to AEC-bearing grafts was significantly (p < 0.05) attenuated. Rotational culture enables pre-transplant islet modification involving their integration with immunomodulatory stem cells capable of subduing the allo-reactivity of T cells relevant to islet rejection. The approach may play a role in achieving acute and long-term graft survival in islet transplantation.

  9. Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of Reactive Oxygen Species for Neural Interfacing Applications.

    PubMed

    Potter-Baker, Kelsey A; Nguyen, Jessica K; Kovach, Kyle M; Gitomer, Martin M; Srail, Tyler W; Stewart, Wade G; Skousen, John L; Capadona, Jeffrey R

    2014-04-28

    Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio-availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces. PMID:25132966

  10. Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of Reactive Oxygen Species for Neural Interfacing Applications.

    PubMed

    Potter-Baker, Kelsey A; Nguyen, Jessica K; Kovach, Kyle M; Gitomer, Martin M; Srail, Tyler W; Stewart, Wade G; Skousen, John L; Capadona, Jeffrey R

    2014-04-28

    Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio-availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces.

  11. Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats

    PubMed Central

    O'Brien, Emmanuelle Simon; Legastelois, Rémi; Houchi, Hakim; Vilpoux, Catherine; Alaux-Cantin, Stéphanie; Pierrefiche, Olivier; André, Etienne; Naassila, Mickaël

    2011-01-01

    A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5–40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment. PMID:21430652

  12. Reducing the stress of drug administration: implications for the 3Rs

    PubMed Central

    Stuart, Sarah A.; Robinson, Emma S.J.

    2015-01-01

    Restraint in animals is known to cause stress but is used during almost all scientific procedures in rodents, representing a major welfare and scientific issue. Administration of substances, a key part of most scientific procedures, almost always involves physical restraint of the animal. In this study, we developed a method to inject substances to rats using a non-restrained technique. We then compared the physiological, behavioral and emotional impacts of restrained versus non-restrained injection procedures. Our results highlight the negative welfare implications associated with physical restraint and demonstrate a method which can be used to avoid this. Our work shows how adopting strategies that avoid restraint can minimize a widespread source of stress in laboratory animals and improve welfare through refinement. PMID:26395864

  13. A 1-year lifestyle intervention for weight loss in individuals with type 2 diabetes reduces high C-reactive protein levels and identifies metabolic predictors of change

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: We examined whether a 1-year intensive lifestyle intervention (ILI) for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP) levels in obese individuals with diabetes and identified metabolic and fitness predictors of hs-CRP change. RESEARCH DESIGN AND METHODS: Look A...

  14. Multimodal system designed to reduce errors in recording and administration of drugs in anaesthesia: prospective randomised clinical evaluation

    PubMed Central

    Webster, Craig S; Hannam, Jacqueline; Mitchell, Simon J; Henderson, Robert; Reid, Papaarangi; Edwards, Kylie-Ellen; Jardim, Anisoara; Pak, Nick; Cooper, Jeremy; Hopley, Lara; Frampton, Chris; Short, Timothy G

    2011-01-01

    Objective To clinically evaluate a new patented multimodal system (SAFERSleep) designed to reduce errors in the recording and administration of drugs in anaesthesia. Design Prospective randomised open label clinical trial. Setting Five designated operating theatres in a major tertiary referral hospital. Participants Eighty nine consenting anaesthetists managing 1075 cases in which there were 10 764 drug administrations. Intervention Use of the new system (which includes customised drug trays and purpose designed drug trolley drawers to promote a well organised anaesthetic workspace and aseptic technique; pre-filled syringes for commonly used anaesthetic drugs; large legible colour coded drug labels; a barcode reader linked to a computer, speakers, and touch screen to provide automatic auditory and visual verification of selected drugs immediately before each administration; automatic compilation of an anaesthetic record; an on-screen and audible warning if an antibiotic has not been administered within 15 minutes of the start of anaesthesia; and certain procedural rules—notably, scanning the label before each drug administration) versus conventional practice in drug administration with a manually compiled anaesthetic record. Main outcome measures Primary: composite of errors in the recording and administration of intravenous drugs detected by direct observation and by detailed reconciliation of the contents of used drug vials against recorded administrations; and lapses in responding to an intermittent visual stimulus (vigilance latency task). Secondary: outcomes in patients; analyses of anaesthetists’ tasks and assessments of workload; evaluation of the legibility of anaesthetic records; evaluation of compliance with the procedural rules of the new system; and questionnaire based ratings of the respective systems by participants. Results The overall mean rate of drug errors per 100 administrations was 9.1 (95% confidence interval 6.9 to 11.4) with the new

  15. Proline accumulation protects Saccharomyces cerevisiae cells in stationary phase from ethanol stress by reducing reactive oxygen species levels.

    PubMed

    Takagi, Hiroshi; Taguchi, Junpei; Kaino, Tomohiro

    2016-08-01

    During fermentation processes, Saccharomyces cerevisiae cells are exposed to multiple stresses, including a high concentration of ethanol that represents toxicity through intracellular reactive oxygen species (ROS) generation. We previously reported that proline protected yeast cells from damage caused by various stresses, such as freezing and ethanol. As an anti-oxidant, proline is suggested to scavenge intracellular ROS. In this study, we examined the role of intracellular proline during ethanol treatment in S. cerevisiae strains that accumulate different concentrations of proline. When cultured in YPD medium, there was a significant accumulation of proline in the put1 mutant strain, which is deficient in proline oxidase, in the stationary phase. Expression of the mutant PRO1 gene, which encodes the γ-glutamyl kinase variant (Asp154Asn or Ile150Thr) with desensitization to feedback inhibition by proline in the put1 mutant strain, showed a prominent increase in proline content as compared with that of the wild-type strain. The oxidation level was clearly increased in wild-type cells after exposure to ethanol, indicating that the generation of ROS occurred. Interestingly, proline accumulation significantly reduces the ROS level and increases the survival rate of yeast cells in the stationary phase under ethanol stress conditions. However, there was not a clear correlation between proline content and survival rate in yeast cells. An appropriate level of intracellular proline in yeast might be important for its stress-protective effect. Hence, the engineering of proline metabolism could be promising for breeding stress-tolerant industrial yeast strains. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26833688

  16. Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein

    PubMed Central

    Ardoin, Stacy P; Schanberg, Laura Eve; Sandborg, Christy I; Barnhart, Huiman X; Evans, Greg W; Yow, Eric; Mieszkalski, Kelly L; Ilowite, Norman T; Eberhard, Anne; Imundo, Lisa F; Kimura, Yuki; Levy, Deborah; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L; Punaro, L; Singer, Nora G; Sherry, David D; McCurdy, Deborah K; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard M; Wagner-Weiner, Linda; Higgins, Gloria C; Brunner, Hermine I; Jung, Lawrence; Soep, Jennifer B; Reed, Ann M; Thompson, Susan D

    2014-01-01

    Objective Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. Methods Subgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or <4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or <110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or <1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. Results Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. Conclusions Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. ClinicalTrials.gov identifier NCT00065806. PMID:23436914

  17. PIM Kinase Inhibitors Kill Hypoxic Tumor Cells by Reducing Nrf2 Signaling and Increasing Reactive Oxygen Species.

    PubMed

    Warfel, Noel A; Sainz, Alva G; Song, Jin H; Kraft, Andrew S

    2016-07-01

    Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases represent a prosurvival pathway that is upregulated in response to hypoxia, in a HIF-1-independent manner. We demonstrate that pharmacologic or genetic inhibition of PIM kinases is significantly more toxic toward cancer cells in hypoxia as compared with normoxia. Xenograft studies confirm that PIM kinase inhibitors impede tumor growth and selectively kill hypoxic tumor cells in vivo Experiments show that PIM kinases enhance the ability of tumor cells to adapt to hypoxia-induced oxidative stress by increasing the nuclear localization and activity of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which functions to increase the expression of antioxidant genes. Small molecule PIM kinase inhibitors prevent Nrf2 from accumulating in the nucleus, reducing the transcription of cytoprotective genes and leading to the build-up of intracellular reactive oxygen species (ROS) to toxic levels in hypoxic tumor cells. This toxic effect of PIM inhibitors can be successfully blocked by ROS scavengers, including N-acetyl cystine and superoxide dismutase. Thus, inhibition of PIM kinases has the potential to oppose hypoxia-mediated therapeutic resistance and induce cell death in the hypoxic tumor microenvironment. Mol Cancer Ther; 15(7); 1637-47. ©2016 AACR. PMID:27196781

  18. Intravenous administration of tetramethylpyrazine reduces intestinal ischemia-reperfusion injury in rats.

    PubMed

    Tóth, Štefan; Pekárová, Tímea; Varga, Ján; Tóth, Štefan; Tomečková, Vladimíra; Gál, Peter; Veselá, Jarmila; Guzy, Juraj

    2013-01-01

    Intestinal ischemia-reperfusion injury (IIRI) is a life-threatening condition requiring prompt medical intervention. Tetramethylpyrazine (TMP) is a biologically active alkaloid isolated from Ligusticum wallichii. Previously, it was shown that TMP causes vasodilatation and inhibition of platelet aggregation as well as exhibits significant antioxidant effects. Therefore, the aim of the present study was to evaluate possible therapeutic effects of TMP in the prevention of IIRI. Wistar rats (n = 80) were randomly divided into eight experimental groups and subjected to a 1 h occlusion of cranial mesenteric artery followed by 0, 1, 12, and 24 h period of reperfusion. Thirty minutes before the IIRI animals received either TMP (30 mg/kg, i.v.) or identical volume of saline. In addition, a control group of 10 animals was not exposed to IIRI. Intestine morphology was evaluated by using histopathological injury index examination (HII), goblet and Paneth cells quantification as well as by applying immunofluorescent methods such as InSitu TUNEL and caspase-3 positivity assessment. Here we showed that preconditioning with TMP prior IIRI decreases the grade of injury. Significant reduction of HII was detected in TMP pretreated groups after 0, 1, and 12 h of reperfusion where injury reduction up to 75% was found. Lower histopathological damage in preconditioned groups was accompanied with increased number of secretory epithelial cells and decreased number of apoptotic cells. These results demonstrate the protective effect of TMP on the small intestine mucosa, suggesting administration of TMP as a molecule for pharmacological intervention against IIRI. PMID:23895154

  19. Chronic food administration of Salvia sclarea oil reduces animals' anxious and dominant behavior.

    PubMed

    Gross, Moshe; Nesher, Elimelech; Tikhonov, Tatiana; Raz, Olga; Pinhasov, Albert

    2013-03-01

    Recent studies indicate that an oil extract from Salvia sclarea may provide clinical benefits in various pathological conditions. In comparison to extracts from other Salvia species, S. sclarea oil contains twice as much omega-3 fatty acids, which are involved in eicosanoid synthesis pathways, and has been found to contain significant levels of the psychoactive monoterpane linalool. In the present study, we examined the mood stabilizing and anxiolytic-like effects of chronic food administration of S. sclarea oil extract on behavioral and physiological parameters of mice with prominent dominant and submissive features in behavioral assays used to test mood stabilizing and antidepressant drugs. Experimental animals received oil supplemented food from the age of 4 weeks or from conception via their pregnant dams. Each age group received either S. sclarea oil- or sunflower oil-enriched feed. Dominant animals, whose pregnant mothers received S. sclarea oil-enriched feed from the date of conception, showed a significant reduction of dominant and anxiety-like behavior, in comparison to their sunflower oil-treated counterparts. S. sclarea oil-treated submissive animals exhibited a similar tendency, and showed a significant reduction in blood corticosterone levels. These findings enforce the hypothesis that S. sclarea oil possesses anxiolytic properties.

  20. The glucagon-like peptide 1 (GLP-1) receptor agonist exendin-4 reduces cocaine self-administration in mice.

    PubMed

    Sørensen, Gunnar; Reddy, India A; Weikop, Pia; Graham, Devon L; Stanwood, Gregg D; Wortwein, Gitta; Galli, Aurelio; Fink-Jensen, Anders

    2015-10-01

    Glucagon-like peptide 1 (GLP-1) analogues are used for the treatment of type 2 diabetes. The ability of the GLP-1 system to decrease food intake in rodents has been well described and parallels results from clinical trials. GLP-1 receptors are expressed in the brain, including within the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Dopaminergic neurons in the VTA project to the NAc, and these neurons play a pivotal role in the rewarding effects of drugs of abuse. Based on the anatomical distribution of GLP-1 receptors in the brain and the well-established effects of GLP-1 on food reward, we decided to investigate the effect of the GLP-1 analogue exendin-4 on cocaine- and dopamine D1-receptor agonist-induced hyperlocomotion, on acute and chronic cocaine self-administration, on cocaine-induced striatal dopamine release in mice and on cocaine-induced c-fos activation. Here, we report that GLP-1 receptor stimulation reduces acute and chronic cocaine self-administration and attenuates cocaine-induced hyperlocomotion. In addition, we show that peripheral administration of exendin-4 reduces cocaine-induced elevation of striatal dopamine levels and striatal c-fos expression implicating central GLP-1 receptors in these responses. The present results demonstrate that the GLP-1 system modulates cocaine's effects on behavior and dopamine homeostasis, indicating that the GLP-1 receptor may be a novel target for the pharmacological treatment of drug addiction.

  1. Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

    PubMed

    Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

    2012-01-01

    The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

  2. Local inhibition of elastase reduces EMILIN1 cleavage reactivating lymphatic vessel function in a mouse lymphoedema model

    PubMed Central

    Pivetta, Eliana; Wassermann, Bruna; Belluz, Lisa Del Bel; Danussi, Carla; Modica, Teresa Maria Elisa; Maiorani, Orlando; Bosisio, Giulia; Boccardo, Francesco; Canzonieri, Vincenzo; Colombatti, Alfonso

    2016-01-01

    Lymphatic vasculature critically depends on the connections of lymphatic endothelial cells with the extracellular matrix (ECM), which are mediated by anchoring filaments (AFs). The ECM protein EMILIN1 is a component of AFs and is involved in the regulation of lymphatic vessel functions: accordingly, Emilin1−/− mice display lymphatic vascular morphological alterations, leading to functional defects such as mild lymphoedema, lymph leakage and compromised lymph drainage. In the present study, using a mouse post-surgical tail lymphoedema model, we show that the acute phase of acquired lymphoedema correlates with EMILIN1 degradation due to neutrophil elastase (NE) released by infiltrating neutrophils. As a consequence, the intercellular junctions of lymphatic endothelial cells are weakened and drainage to regional lymph nodes is severely affected. The local administration of sivelestat, a specific NE inhibitor, prevents EMILIN1 degradation and reduces lymphoedema, restoring a normal lymphatic functionality. The finding that, in human secondary lymphoedema samples, we also detected cleaved EMILIN1 with the typical bands of an NE-dependent pattern of fragmentation establishes a rationale for a powerful strategy that targets NE inhibition. In conclusion, the attempts to block EMILIN1 degradation locally represent the basis for a novel ‘ECM’ pharmacological approach to assessing new lymphoedema treatments. PMID:26920215

  3. [Reducing work stress in geriatric care: a training program for nursing team and administrators].

    PubMed

    Zimber, A; Rudolf, A; Teufel, S

    2001-10-01

    Caregivers of the residents in nursing homes are exposed to a high degree of physical and mental stress. The purpose of this study was to develop and to test the effects of skill training aimed at reducing occupational stress. The training consisting of 12 sessions of 90 minutes each was designed for nursing assistants and for care supervisors, respectively. Contents of the program are communicating with the demented, coping with job stress and cooperating with colleagues and subordinates, respectively. Eleven homes for the elderly and nursing homes were involved in the pilot study; 88 caregivers participated in the training, 34 of them were supervisors and 54 nursing assistants. The participants mainly appreciated the contents of the training. A controlled study design was applied to evaluate the training effects. 56 participants assessed their competencies, their job conditions and their health status at the beginning, at the end of the training as well as 12 weeks after the intervention had been finished. 56 persons completed the questionnaire receiving no training. Among the training participants, particularly the self-care skills improved. In addition, occupational stress could be reduced and the climate with the residents improved significantly, whereas the frequency of health problems did not change. Compared to the changes also observed in the control group, statistically significant effects were confined to the improvement of the climate with the residents. Care supervisors in general reported a higher benefit from the training than did nursing assistants. The results of the pilot study were used to adapt the training to the caregivers' needs.

  4. Co-administration of meso 2,3-dimercaptosuccinic acid monoesters reduces arsenic concentration and oxidative stress in gallium arsenide exposed rats.

    PubMed

    Flora, Swaran J S; Bhatt, Kapil; Dwivedi, Nidhi; Pachauri, Vidhu; Kushwah, Pramod K

    2011-07-01

    1. Gallium arsenide (GaAs), a semiconductor, exerts toxicity as a result of its constitutive moieties; that is, gallium and arsenic that becomes dissociated after exposure. The present study focuses on reducing arsenic concentration from the target organs using monoesters of meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination. 2. Animals were exposed to GaAs (0.0014 mol/kg, orally for 8 weeks) and then treated with monoisoamyl DMSA (MiADMSA), monocyclohexyl DMSA (MchDMSA) or monomethyl DMSA (MmDMSA) either individually (0.3 mmol/kg, orally) or in combination (0.15 mmol/kg each, orally) for five consecutive days. 3. GaAs exposure significantly inhibited blood δ-aminolevulinic acid dehydrogenase (ALAD), suggesting alterations in the heme synthesis pathway. Whereas a significant increase in blood, liver and kidney reactive oxygen species accompanied by an increase in lipid peroxidation points to the involvement of oxidative stress in GaAs toxicity. 4. GaAs also significantly disturbed glutathione metabolism. Hepatic and renal catalase activity decreased significantly, whereas hepatic and renal superoxide dismutase activity, as well as serum transaminases activity, showed marginal increase. Treatment with MiADMSA in combination with MchDMSA showed better therapeutic efficacy compared with other treatments in the aforementioned variables. 5. Co-administration of MiADMSA with MchDMSA provided better therapeutic effects, including reduction of arsenic burden, compared with all other treatments.

  5. Administration of C1 inhibitor reduces neutrophil activation in patients with sepsis.

    PubMed

    Zeerleder, Sacha; Caliezi, Christoph; van Mierlo, Gerard; Eerenberg-Belmer, Anke; Sulzer, Irmela; Hack, C Erik; Wuillemin, Walter A

    2003-07-01

    Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-alpha(1)-antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.

  6. Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats.

    PubMed

    Ramos, Denise Barbosa; Muller, Gabriel Cardozo; Rocha, Guilherme Botter Maio; Dellavia, Gustavo Hirata; Almeida, Roberto Farina; Pettenuzzo, Leticia Ferreira; Loureiro, Samanta Oliveira; Hansel, Gisele; Horn, Ângelo Cássio Magalhães; Souza, Diogo Onofre; Ganzella, Marcelo

    2016-03-01

    In addition to its intracellular roles, the nucleoside guanosine (GUO) also has extracellular effects that identify it as a putative neuromodulator signaling molecule in the central nervous system. Indeed, GUO can modulate glutamatergic neurotransmission, and it can promote neuroprotective effects in animal models involving glutamate neurotoxicity, which is the case in brain ischemia. In the present study, we aimed to investigate a new in vivo GUO administration route (intranasal, IN) to determine putative improvement of GUO neuroprotective effects against an experimental model of permanent focal cerebral ischemia. Initially, we demonstrated that IN [(3)H] GUO administration reached the brain in a dose-dependent and saturable pattern in as few as 5 min, presenting a higher cerebrospinal GUO level compared with systemic administration. IN GUO treatment started immediately or even 3 h after ischemia onset prevented behavior impairment. The behavior recovery was not correlated to decreased brain infarct volume, but it was correlated to reduced mitochondrial dysfunction in the penumbra area. Therefore, we showed that the IN route is an efficient way to promptly deliver GUO to the CNS and that IN GUO treatment prevented behavioral and brain impairment caused by ischemia in a therapeutically wide time window.

  7. TREATMENT OF METALS IN GROUND WATER USING AN ORGANIC-BASED SULFATE-REDUCING PERMEABLE REACTIVE BARRIER

    EPA Science Inventory

    A pilot permeable reactive barrier (PRB) consisting of a mixture of leaf compost, zero-valent iron (ZVI) filings, limestone and pea gravel was evaluated at a former phosphate fertilizer manufacturing facility in Charleston, S.C. The PRB is designed to treat arsenic and heavy met...

  8. Diazepam administration after prolonged status epilepticus reduces neurodegeneration in the amygdala but not in the hippocampus during epileptogenesis

    PubMed Central

    Qashu, Felicia; Figueiredo, Taiza H.; Aroniadou-Anderjaska, Vassiliki; Apland, James P.; Braga, Maria F. M.

    2009-01-01

    An episode of status epilepticus (SE), if left untreated, can lead to death, or brain damage with long-term neurological consequences, including the development of epilepsy. The most common first-line treatment of SE is administration of benzodiazepines (BZs). However, the efficacy of BZs in terminating seizures is reduced with time after the onset of SE; this is accompanied by a reduced efficacy in protecting the hippocampus against neuronal damage, and is associated with impaired function and internalization of hippocampal GABAA receptors. In the present study, using Fluoro-Jade C staining, we found that administration of diazepam to rats at 3 h after the onset of kainic acid-induced SE, at a dose sufficient to terminate SE, had no protective effect on the hippocampus, but produced a significant reduction in neuronal degeneration in the amygdala, piriform cortex, and endopiriform nucleus, examined on days 7−9 after SE. Thus, in contrast to the hippocampus, the amygdala and other limbic structures are responsive to neuroprotection by BZs after prolonged SE, suggesting that GABAA receptors are not significantly altered in these structures during SE. PMID:19127342

  9. Prophylactic administration of a combined prebiotic and probiotic, or therapeutic administration of enrofloxacin, to reduce the incidence of bacterial chondronecrosis with osteomyelitis in broilers.

    PubMed

    Wideman, R F; Al-Rubaye, A; Kwon, Y M; Blankenship, J; Lester, H; Mitchell, K N; Pevzner, I Y; Lohrmann, T; Schleifer, J

    2015-01-01

    Bacteria entering the bloodstream via translocation from the gastrointestinal tract spread hematogenously and can trigger bacterial chondronecrosis with osteomyelitis (BCO) by infecting osteochondrotic microfractures in the epiphyseal-physeal cartilage of the proximal femora and tibiae. In experiment 1, broilers were fed control feed or the same feed containing BacPack 2X, which includes the prebiotic IMW50 (a mannan oligosaccharide beta-glucan yeast cell wall product) plus the probiotic Calsporin (Bacillus subtilis C-3102). Broilers reared on wire flooring consistently developed higher incidences of BCO than hatchmates reared on wood shavings litter (≥24 vs. ≤4%, respectively; P=0.001). Adding BacPack 2X to the feed on d 1 through 56 delayed the age of onset and reduced the cumulative incidence of BCO on wire flooring when compared with broilers fed the control feed (24.0 vs. 40.7%, respectively; P=0.003). In experiment 2, broilers reared on wire flooring received tap water on d 1 through 62 (control group) or therapeutic levels of the potent fluoroquinolone antimicrobial enrofloxacin in the water on d 35 through 54 (enrofloxacin group). During enrofloxacin administration, half as many birds developed BCO in the enrofloxacin group when compared with the control group (8.1 vs. 19.5%, respectively, on d 35 through 54; P=0.001), whereas both groups had similar BCO incidences subsequent to withdrawing enrofloxacin on d 55 through 62 (14.8 vs. 18.2% for the enrofloxacin vs. control groups; P=0.386). Cumulative lameness incidences for d 1 through 62 were higher for the control group than for the enrofloxacin group (39.0 vs. 25.8%, respectively; P=0.003). These results demonstrate that wire flooring imposes a rigorous challenge that leads to high incidences of BCO that can be difficult to suppress, even with therapeutic doses of enrofloxacin. Prophylactically adding BacPack 2X to the feed reduced the incidence of BCO lameness by a proportion similar to that achieved

  10. Acetaldehyde self-administration by a two-bottle choice paradigm: consequences on emotional reactivity, spatial learning, and memory.

    PubMed

    Plescia, Fulvio; Brancato, Anna; Venniro, Marco; Maniaci, Giuseppe; Cannizzaro, Emanuele; Sutera, Flavia Maria; De Caro, Viviana; Giannola, Libero Italo; Cannizzaro, Carla

    2015-03-01

    Acetaldehyde, the first alcohol metabolite, is responsible for many pharmacological effects that are not clearly distinguishable from those exerted by its parent compound. It alters motor performance, induces reinforced learning and motivated behavior, and produces different reactions according to the route of administration and the relative accumulation in the brain or in the periphery. The effective activity of oral acetaldehyde represents an unresolved field of inquiry that deserves further investigation. Thus, this study explores the acquisition and maintenance of acetaldehyde drinking behavior in adult male rats, employing a two-bottle choice paradigm for water and acetaldehyde solution (from 0.9% to 3.2% v/v), over 8 weeks. The behavioral consequences exerted by chronic acetaldehyde intake are assessed by a set of different tests: trials in an open-field arena and elevated-plus maze provided information on both general motor and explorative activity, and anxiety-driven behavioral responses. The Morris water maze allowed the exploration of cognitive processes such as spatial learning and memory. Determination of acetaldehyde levels in the brain was carried out at the end of the drinking paradigm. Our results indicate that rats exposed for the first time to acetaldehyde at 0.9% displayed a regular and stable daily drinking pattern that reached higher values and a "peaks and drops" shaped-trend when acetaldehyde concentration was increased to 3.2%. Accordingly, an increase in acetaldehyde levels in the brain was determined compared to non-acetaldehyde drinking rats. Acetaldehyde intake during the free-choice paradigm exerted an anxiogenic response in the open-field arena and elevated-plus maze, which in turn correlates with an enhancement in cognitive flexibility and spatial orientation skills, when an adaptive response to a stressful environmental challenge was required. These findings further support the idea that acetaldehyde is indeed a centrally active and

  11. Reduced expression of NO-sensitive guanylyl cyclase in reactive astrocytes of Alzheimer disease, Creutzfeldt-Jakob disease, and multiple sclerosis brains.

    PubMed

    Baltrons, María Antonia; Pifarré, Paula; Ferrer, Isidre; Carot, José Miguel; García, Agustina

    2004-12-01

    In Alzheimer's disease (AD) brains increased NO synthase (NOS) expression is found in reactive astrocytes surrounding amyloid plaques. We have recently shown that treatment with beta-amyloid peptides or IL-1beta down-regulates NO-sensitive soluble guanylyl cyclase (sGC) in cultured astrocytes and in adult rat brain. In this work, we have examined sGC activity and expression in postmortem brain tissue of AD patients and matched controls. No significant alteration was observed in basal or NO-stimulated sGC activity, nor in sGC beta1 and alpha1 subunit levels in cortical extracts of AD brains. Immunohistochemistry showed intense and widespread labeling of sGC beta1 in cortical and hippocampal neurons and white matter fibrillar astrocytes, while grey matter astrocytes were faintly stained. In AD, expression of sGC in neurons and fibrillar astrocytes is not altered but is markedly reduced in reactive astrocytes surrounding amyloid plaques. Immunostaining for sGC beta1 was also lacking in reactive astrocytes in cortex and subcortical white matter in Creutzfeldt-Jakob disease brains and in subacute and chronic plaques in multiple sclerosis (MS) brains. Thus, induction of astrocyte reactivity is associated with decreased capacity to generate cGMP in response to NO both in vitro and in vivo. This effect may be related to the development of the astroglial inflammatory response. PMID:15571982

  12. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

    PubMed Central

    Spaziano, Giuseppe; Piegari, Elena; Matteis, Maria; Cappetta, Donato; Esposito, Grazia; Russo, Rosa; Tartaglione, Gioia; De Palma, Raffaele; Rossi, Francesco; D’Agostino, Bruno

    2016-01-01

    Background The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce. Objectives To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model. Methods GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro. Results Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties. Conclusion Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide

  13. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  14. Administrative Methods for Reducing Crime in Primary and Secondary Schools: A Regression Analysis of the U.S. Department of Education School Survey of Crime and Safety

    ERIC Educational Resources Information Center

    Noonan, James H.

    2011-01-01

    Since the 1999 Columbine High School shooting school administrators have been tasked with creating positive education environments while also maximizing the safety of the students and staff. However, limited resources require school administrators to only employ safety policies which are actually effective in reducing crime. In order to help…

  15. Clinical and Administrative Approaches to Improving the Efficiency of Joint Arthroplasty and Reducing Hospital Length of Stay.

    PubMed

    Booth, Robert E

    2015-10-01

    In the current health care environment, it is more important than ever for orthopedic surgeons to strive for optimal efficiency and effectiveness. For maximum efficiency, patients can be preselected to limit patient types that commonly require a greater investment of the practice's time and resources. Structuring surgical practices for efficiency may involve rethinking the staffing model, anticipating problems that may occur with individual patients, and enhancing internal and external communications. Turnover time between patients must be measured and minimized, and activity in the operating room--including the surgeon's own technique--must be evaluated and refined where necessary. Clinical advances that can enhance efficiency should be considered. Among such advances are tranexamic acid, intravenous acetaminophen, and bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc). Intravenous acetaminophen and liposomal bupivacaine, in particular, can significantly improve efficiency by reducing the administration of opioid medication during the postoperative period, and thereby reducing opioid-related side effects. Liposomal bupivacaine has also been shown to shorten the hospital length of stay and, in many cases, eliminate the need for costly and inefficient nerve blocks. PMID:26447430

  16. Postischemic, systemic administration of polyamine-modified superoxide dismutase reduces hippocampal CA1 neurodegeneration in rat global cerebral ischemia.

    PubMed

    Wengenack, T M; Curran, G L; Poduslo, J F

    1997-04-18

    Antioxidant enzymes such as superoxide dismutase (SOD) have shown neuroprotective effects in animal models of cerebral ischemia, but only at very high doses. Modifications to increase the plasma half-life or blood-brain barrier (BBB) permeability of SOD have resulted in limited neuroprotective effects. No one has demonstrated neuroprotection with postischemic administration. The specific aim of the present study was to administer systemically a polyamine-modified SOD, having increased BBB permeability and preserved enzymatic activity, following global cerebral ischemia in rats and analyze the effects on the selective vulnerability of CA1 hippocampal neurons. Following 12 min of four-vessel occlusion, global cerebral ischemia, male Wistar rats were dosed (i.v.) with either saline, native SOD (5000 U/kg), polyamine-modified SOD (5000 U/kg), or enzymatically inactive, polyamine-modified SOD (2.1 mg/kg) twice daily for 3 days. Neuroprotective effects on hippocampal CA1 neurons were assessed using standard histological methods. Saline-treated animals had very few remaining CA1 neurons (1.44 +/- 0.60 neurons/reticle; x +/- S.E.M.) compared to sham rats (58.57 +/- 0.69). Native (10.38 +/- 2.96) or inactive, polyamine-modified SOD (7.32 +/- 2.68) did not show significant neuroprotective effects. Polyamine-modified SOD, however, resulted in the survival of significantly more CA1 neurons (24.61 +/- 5.90; P < 0.01). Postischemic, systemic administration of polyamine-modified SOD, having increased BBB permeability and preserved enzymatic activity, significantly reduced hippocampal CA1 neuron loss following global cerebral ischemia. Similar modification of other antioxidant enzymes and neurotrophic factors with polyamines may provide a useful technique for the systemic delivery of therapeutic proteins across the BBB for the treatment of stroke and other neurodegenerative disorders. PMID:9134958

  17. Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis

    PubMed Central

    Chen, Lufang; Xu, Keying; Gui, Qifeng; Chen, Yue; Chen, Deying; Yang, Yunmei

    2016-01-01

    A number of clinical trials have demonstrated that the use of probiotics has the potential to prevent nosocomial infections. However, the mechanism underlying probiotic-induced anti-infection and sepsis remains to be investigated. In the present study, 200 µl/day of Lactobacillus rhamnosus GG (LGG) or normal saline (control) was orally administrated to 4-week-old C57BL6 mice 4 weeks prior to cecal ligation and puncture (CLP). A number of mice were sacrificed 24 h after CLP, and the remaining mice were used for survival studies. Ileum tissues were collected to evaluate the injury on the intestine. Blood samples were also obtained to investigate the changed metabolic pattern in mice that underwent different treatments using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). In the survival studies, the mortality of CLP-induced septic mice pretreated with LGG was significantly lower compared with untreated mice (P=0.029). Ileum mucosal damage was evident in the control septic mice. Based on the data of UPLC-QTOF-MS, phosphatidylcholines were increased and lysophosphatidylcholines (LPCs) that contained polyunsaturated fatty acids were decreased in septic mice, whereas saturated fatty acid LPCs reveal no significant difference between septic and sham mice. In addition, the metabolic profile in the septic mice pretreated with LGG was much closer to that of sham mice compared with control septic mice. The results of the present study suggest that probiotic pre-administration reduces the mortality in septic mice by decreasing ileum mucosal damage, increasing the gut barrier integrity and altering global serum metabolic profiles. PMID:27588102

  18. Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead-induced hypertension.

    PubMed

    Bravo, Yanauri; Quiroz, Yasmir; Ferrebuz, Atilio; Vaziri, Nosratola D; Rodríguez-Iturbe, Bernardo

    2007-08-01

    Hypertension is a likely consequence of chronic lead exposure in humans, especially in association with reduced renal function and in high risk populations. Numerous studies have demonstrated that oxidative stress plays an important role in the pathogenesis of experimental lead-induced hypertension and we have shown recently that tubulointerstitial immune cell infiltration is a feature of chronic low-dose lead exposure. Since oxidative stress, renal inflammation, and angiotensin activity are closely linked characteristics in experimental models of hypertension, we decided to investigate whether lead-induced hypertension would be ameliorated by suppressing renal inflammation with the immunosuppressive drug mycophenolate mofetil (MMF). We studied rats exposed for 14 wk to lead acetate (100 ppm in the drinking water) that, in addition, received either MMF, 20 mg.kg(-1).day(-1) by gastric gavage (Pb.MMF group, n = 12) or vehicle (Pb group, n = 12). Control rats received MMF alone (n = 5) or neither lead nor MMF (n = 6). All rats were killed at the end of the experiment. Low-dose lead exposure resulted in mild to moderate tubular cell damage and a progressive increment in blood pressure, oxidative stress, interstitial accumulation of lymphocytes and macrophages, NF-kappaB activation, and increased renal angiotensin II level. The administration of MMF suppressed the tubulointerstitial accumulation of lymphocytes and macrophages and prevented the hypertension, oxidative stress, and NF-kappaB activation and reduced the heightened renal angiotensin content associated with chronic lead exposure. We conclude that interstitial inflammation plays an important role in lead-induced hypertension.

  19. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    PubMed

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P < 0.001), but was unchanged in BAL (P = 0.061). Exercise time was shorter in TYR-free (59.8 ± 19.0 min vs. 66.2 ± 16.9 min in TYR-free and BAL respectively; P = 0.036). Heart rate (P = 0.298), core (P = 0.134) and skin (P = 0.384) temperature, RPE (P > 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  20. Development of PEGylated serum albumin with multiple reduced thiols as a long-circulating scavenger of reactive oxygen species for the treatment of fulminant hepatic failure in mice.

    PubMed

    Katsumi, Hidemasa; Nishikawa, Makiya; Nishiyama, Kazushi; Hirosaki, Rikiya; Nagamine, Narumi; Okamoto, Haruka; Mizuguchi, Hironori; Kusamori, Kosuke; Yasui, Hiroyuki; Yamashita, Fumiyoshi; Hashida, Mitsuru; Sakane, Toshiyasu; Yamamoto, Akira

    2014-04-01

    Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and D-galactosamine (LPS/D-GalN) into mice. The LPS/D-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, L-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.

  1. Experimental and Theoretical Assessment of the Lifetime of a Gaseous-Reduced Vadose Zone Permeable Reactive Barrier

    SciTech Connect

    Thornton, Edward C.; Zhong, Lirong; Oostrom, Mart; Deng, Baolin

    2007-11-20

    The feasibility of using gaseous reduction to establish a vadose zone permeable reactive barrier was evaluated through a combination of laboratory testing activities and consideration of fundamental vadose zone transport concepts. For the experimental evaluation, a series of laboratory column tests were conducted in which sediment was first treated with diluted hydrogen sulfide. Water containing dissolved oxygen was then pumped through the columns at different flow rates to determine the reoxidation rate and the reductive capacity of the treated sediment. The results indicated that the treated sediment has a significant reductive capacity consistent with the basic reactions associated with the treatment and reoxidation processes. The observed reductive capacity was found to be dependent on the flow rate of water during the reoxidation phase of the tests. At lower flow rates, the reductive capacity approached the maximum value predicted on the basis of the treatment reaction. Thus, laboratory treatment tests should reliably predict the reductive capacity of the barrier under field conditions. A theoretical approach was undertaken to estimate the lifetime of the vadose zone barrier. An initial model assumed that the barrier lifetime is determined by the reoxidation of the barrier owing to the transport of oxygen through a vadose zone interval in which all sediment is unsaturated. The results of this evaluation suggest that barrier reoxidation is primarily related to diffusion of oxygen through the gas-filled portion of the sediment pore space. If so, the barrier lifetime could be fairly short (several years). However, the presence of finer grained strata with higher moisture content could potentially increase the barrier lifetime to 100 years or more owing to a decrease in the effective diffusion coefficient for oxygen. Thus, detailed stratagraphic characterization and modeling is needed to provide an accurate assessment of barrier lifetime at specific sites.

  2. Use of Less Reactive Materials and More Stable Gases to Reduce Corrosive Wear When Lubricating with Halogenated Gases

    NASA Technical Reports Server (NTRS)

    Buckley, Donald H.; Johnson, Robert L.

    1960-01-01

    The gases CF2Cl-CF2Cl, CF2Cl2, and CF2Br-CF2Br were used to lubricate metals, cermets, and ceramics in this study. One of the criteria for determining the effectiveness of a reactive-gas-lubricated systems is the stability of the halogen-containing gas molecule. The carbon-to-halogen bond in the ethane molecule has extremely good thermal stability superior to the methane analogs (CF2Cl2 and CF2Br2) used in earlier research. For this reason, the ethane compounds CF2Cl-CF2Cl and CF2Br-CF2Br were considered as high-temperature lubricants. Friction and wear studies were made with a hemisphere (3/16-in. rad.) rider sliding in a circumferential path on the flat surface of a rotating disk (21/2-in. diam. ). The specimens of metal alloys, cermets, and ceramics were run In an atmosphere of the various gases with a load of 1200 grams, sliding velocities from 75 to 8000 feet per minute, and temperatures from 75 to 1400 F. The gas CF2Cl-CF2Cl was found to be an effective lubricant for the cermet LT-LB (59.0 Cr, 19.0 Al2O3, 20.0 Mo, 2.0 Ti) and the ceramic Al2O3 sliding on Stellite Star J (cobalt-base alloy) at temperatures to 1400 F. The bromine-containing gas CF2Br-CF2Br was found to give friction and wear values that can be considered to be in a region of effective boundary lubrication for the cermet K175D (nickel-bonded metal carbide) sliding on the metal Hastelloy R-235 (nickel-base alloy) at temperatures to 1200 F.

  3. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    SciTech Connect

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-05-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease.

  4. Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces Inflammation and Prevents Lethal Sepsis.

    PubMed

    Heinbockel, Lena; Marwitz, Sebastian; Barcena Varela, Sergio; Ferrer-Espada, Raquel; Reiling, Norbert; Goldmann, Torsten; Gutsmann, Thomas; Mier, Walter; Schürholz, Tobias; Drömann, Daniel; Brandenburg, Klaus; Martinez de Tejada, Guillermo

    2015-01-01

    Sepsis is still a major cause of death and many efforts have been made to improve the physical condition of sepsis patients and to reduce the high mortality rate associated with this disease. While achievements were implemented in the intensive care treatment, all attempts within the field of novel therapeutics have failed. As a consequence new medications and improved patient stratification as well as a thoughtful management of the support therapies are urgently needed. In this study, we investigated the simultaneous administration of ibuprofen as a commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5 (Aspidasept), a newly developed antimicrobial peptide. Here, we show a synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction in plasma levels of both tumor necrosis factor α and prostaglandin E, as a likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX pro-inflammatory cascades, respectively. This finding is further characterised and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic global effect both on the number of regulated genes as well as on associated gene ontology and pathway expression. Overall, ibuprofen potentiated the anti-inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that NSAIDs could be useful to supplement future anti-sepsis therapies. PMID:26197109

  5. Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands

    PubMed Central

    Bottomley, C; Tome, H; Pitakaka, R; Butcher, R; Sokana, O; Kako, H; Solomon, A W; Mabey, D C

    2016-01-01

    Objectives Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. Methods Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. Results 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). Conclusions This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination. PMID:26888658

  6. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    SciTech Connect

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-05-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls. All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p < 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p < 0.05) and pericardial effusion (p < 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p < 0.05) or IB (p < 0.01) and in the untreated, unirradiated rabbits (p < 0.01). Early administrative of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusin, and improved survival in this experimental model of radiation-induced heart disease.

  7. Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces Inflammation and Prevents Lethal Sepsis.

    PubMed

    Heinbockel, Lena; Marwitz, Sebastian; Barcena Varela, Sergio; Ferrer-Espada, Raquel; Reiling, Norbert; Goldmann, Torsten; Gutsmann, Thomas; Mier, Walter; Schürholz, Tobias; Drömann, Daniel; Brandenburg, Klaus; Martinez de Tejada, Guillermo

    2015-01-01

    Sepsis is still a major cause of death and many efforts have been made to improve the physical condition of sepsis patients and to reduce the high mortality rate associated with this disease. While achievements were implemented in the intensive care treatment, all attempts within the field of novel therapeutics have failed. As a consequence new medications and improved patient stratification as well as a thoughtful management of the support therapies are urgently needed. In this study, we investigated the simultaneous administration of ibuprofen as a commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5 (Aspidasept), a newly developed antimicrobial peptide. Here, we show a synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction in plasma levels of both tumor necrosis factor α and prostaglandin E, as a likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX pro-inflammatory cascades, respectively. This finding is further characterised and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic global effect both on the number of regulated genes as well as on associated gene ontology and pathway expression. Overall, ibuprofen potentiated the anti-inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that NSAIDs could be useful to supplement future anti-sepsis therapies.

  8. Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces Inflammation and Prevents Lethal Sepsis

    PubMed Central

    Barcena Varela, Sergio; Ferrer-Espada, Raquel; Reiling, Norbert; Goldmann, Torsten; Gutsmann, Thomas; Mier, Walter; Schürholz, Tobias; Drömann, Daniel; Brandenburg, Klaus; Martinez de Tejada, Guillermo

    2015-01-01

    Sepsis is still a major cause of death and many efforts have been made to improve the physical condition of sepsis patients and to reduce the high mortality rate associated with this disease. While achievements were implemented in the intensive care treatment, all attempts within the field of novel therapeutics have failed. As a consequence new medications and improved patient stratification as well as a thoughtful management of the support therapies are urgently needed. In this study, we investigated the simultaneous administration of ibuprofen as a commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5 (Aspidasept), a newly developed antimicrobial peptide. Here, we show a synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction in plasma levels of both tumor necrosis factor α and prostaglandin E, as a likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX pro-inflammatory cascades, respectively. This finding is further characterised and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic global effect both on the number of regulated genes as well as on associated gene ontology and pathway expression. Overall, ibuprofen potentiated the anti-inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that NSAIDs could be useful to supplement future anti-sepsis therapies. PMID:26197109

  9. Melatonin administration induced reactivation in the seminal gland of the soay rams during non-breeding season: An ultrastructural and morphometrical study.

    PubMed

    Mokhtar, Doaa M; Abd-Elhafeez, Hanan H; Abou-Elmagd, Ahmed; Hassan, Ahmed H S

    2016-02-01

    Fifteen adult Soay rams were used in this experiment. Eight animals were given subcutaneous implants containing melatonin, while the other seven animals were used as control. After 11 weeks, the rams were killed and the seminal vesicles were examined by light and electron microscope. In contrast to the control grouped animals, the melatonin treated rams showed morphological, morphometrical, and ultrastructural changes as a result of reactivation of the glandular tissues of the seminal glands. The ratio of interstitial connective tissues to glandular tissues was reduced in the treated group. Melatonin induced an evident significant increase in number and height of principal cells that showed signs of increased secretory activity; apical cytoplasmic protrusions became well developed and covering the inner surface of the glandular end-pieces, also, the basal cells were significantly increased in number. The main cytological alteration in the principal cells of the seminal vesicles in treated animals was prominent increase in the concentrically arranged membranes of sER, secretory vacuoles and glycogen granules and appearance of numerous lysosomes and multivesicular bodies. Interstitial Cajal- like cells were significantly increased in number and formed a network around the epithelium and between smooth muscle cells in the treated group. The main components of these cells were mitochondria, rER, sER, and many caveolae. The cytological alterations were accompanied by subepithelial and intraepithelial nonmyelinated nerve terminals in the treated animals. The results support the view that melatonin activates and increases the secretory activity of seminal gland in sheep.

  10. Melatonin administration induced reactivation in the seminal gland of the soay rams during non-breeding season: An ultrastructural and morphometrical study.

    PubMed

    Mokhtar, Doaa M; Abd-Elhafeez, Hanan H; Abou-Elmagd, Ahmed; Hassan, Ahmed H S

    2016-02-01

    Fifteen adult Soay rams were used in this experiment. Eight animals were given subcutaneous implants containing melatonin, while the other seven animals were used as control. After 11 weeks, the rams were killed and the seminal vesicles were examined by light and electron microscope. In contrast to the control grouped animals, the melatonin treated rams showed morphological, morphometrical, and ultrastructural changes as a result of reactivation of the glandular tissues of the seminal glands. The ratio of interstitial connective tissues to glandular tissues was reduced in the treated group. Melatonin induced an evident significant increase in number and height of principal cells that showed signs of increased secretory activity; apical cytoplasmic protrusions became well developed and covering the inner surface of the glandular end-pieces, also, the basal cells were significantly increased in number. The main cytological alteration in the principal cells of the seminal vesicles in treated animals was prominent increase in the concentrically arranged membranes of sER, secretory vacuoles and glycogen granules and appearance of numerous lysosomes and multivesicular bodies. Interstitial Cajal- like cells were significantly increased in number and formed a network around the epithelium and between smooth muscle cells in the treated group. The main components of these cells were mitochondria, rER, sER, and many caveolae. The cytological alterations were accompanied by subepithelial and intraepithelial nonmyelinated nerve terminals in the treated animals. The results support the view that melatonin activates and increases the secretory activity of seminal gland in sheep. PMID:26611365

  11. The administration of Sheng Hua Tang immediately after delivery to reduce the incidence of retained placenta in Holstein dairy cows.

    PubMed

    Cui, Dongan; Wang, Xuezhi; Wang, Lei; Wang, Xurong; Zhang, Jingyan; Qin, Zhe; Li, Jianxi; Yang, Zhiqiang

    2014-03-15

    Sheng Hua Tang, a classical herbal formula consisting of Radix Angelicae sinensis, Ligustici rhizoma, Semen persicae, Zingiberis rhizoma, and Radix glycyrrhizae, is known to be beneficial in alleviating postpartum diseases and facilitating a return to normal reproductive function. This study investigated whether the administration of Sheng Hua Tang within 2 to 4 hours after delivery was effective as a preventive treatment for reducing the risk of retained placenta in Holstein dairy cows. A total of 357 cows, each of which had delivered its calf spontaneously, were randomly allocated to one of two groups. In the treatment group, the cows (n = 175) received Sheng Hua Tang with an oral dose of 0.36 g crude herb per kg·body weight once daily for three consecutive days. The controls (n = 182) received no treatment. The placental retention proportion was 4.0% and 17.0% within 12 hours after delivery in the treated and control animals, respectively (P < 0.01). We found decreases in the calving-to-first-service interval (73.2 ± 25.1 vs. 81.9 ± 32.8 days; P < 0.01), calving-to-conception interval (93.4 ± 38.8 vs. 114.6 ± 42.9 days; P < 0.01), and service per conception (1.5 ± 0.8 vs. 1.9 ± 1.0 days; P < 0.01) in the treatment group compared with the control group. The first artificial insemination conception proportion was higher in the treatment group than in the control group (60.4% vs. 41.1%; P = 0.01). Moreover, the between-group difference in the proportion of cows that were pregnant within 180 days postpartum approached statistical significance (88.2% vs. 80.6%; P = 0.07). Sheng Hua Tang showed beneficial effects in reducing the incidence of retained placenta and improving subsequent reproductive performance in cows. This preventive treatment strategy would be effective in improving the management of puerperal health. The potential benefits of Sheng Hua Tang warrant further investigation to determine whether this preventive treatment strategy can be endorsed as

  12. The structure of reduced tryparedoxin peroxidase reveals a decamer and insight into reactivity of 2Cys-peroxiredoxins.

    PubMed

    Alphey, M S; Bond, C S; Tetaud, E; Fairlamb, A H; Hunter, W N

    2000-07-21

    Tryparedoxin peroxidase (TryP) is a recently discovered 2Cys-peroxiredoxin involved in defence against oxidative stress in parasitic trypanosomatids. The crystal structure of recombinant Crithidia fasciculata TryP, in the reduced state, has been determined using multi-wavelength anomalous dispersion methods applied to a selenomethionyl derivative. The model comprises a decamer with 52 symmetry, ten chloride ions with 23 water molecules and has been refined, using data to 3.2 A resolution (1 A=0.1 nm), to an R-factor and R(free) of 27.3 and 28.6 %, respectively. Secondary structure topology places TryP along with tryparedoxin and glutathione peroxidase in a distinct subgroup of the thioredoxin super-family. The molecular details at the active site support ideas about the enzyme mechanism and comparisons with an oxidised 2Cys-peroxiredoxin reveal structural alterations induced by the change in oxidation state. These include a difference in quaternary structure from dimer (oxidised form) to decamer (reduced form). The 2Cys-peroxiredoxin assembly may prevent indiscriminate oligomerisation, localise ten peroxidase active sites and contribute to both the specificity of reduction by the redox partner tryparedoxin and attraction of peroxides into the active site.

  13. Reducing the Cost and Preserving the Reactivity in Noble-Metal-Based Catalysts: Oxidation of CO by Pt and Al-Pt Alloy Clusters Supported on Graphene.

    PubMed

    Koizumi, Kenichi; Nobusada, Katsuyuki; Boero, Mauro

    2016-04-01

    The oxidation mechanisms of CO to CO2 on graphene-supported Pt and Pt-Al alloy clusters are elucidated by reactive dynamical simulations. The general mechanism evidenced is a Langmuir-Hinshelwood (LH) pathway in which O2 is adsorbed on the cluster prior to the CO oxidation. The adsorbed O2 dissociates into two atomic oxygen atoms thus promoting the CO oxidation. Auxiliary simulations on alloy clusters in which other metals (Al, Co, Cr, Cu, Fe, Ni) replace a Pt atom have pointed to the aluminum doped cluster as a special case. In the nanoalloy, the reaction mechanism for CO oxidation is still a LH pathway with an activation barrier sufficiently low to be overcome at room temperature, thus preserving the catalyst efficiency. This provides a generalizable strategy for the design of efficient, yet sustainable, Pt-based catalysts at reduced cost. PMID:26878836

  14. Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size

    PubMed Central

    Cummins, Nathan W.; Sainski, Amy M.; Dai, Haiming; Natesampillai, Sekar; Pang, Yuan-Ping; Bren, Gary D.; de Araujo Correia, Maria Cristina Miranda; Sampath, Rahul; Rizza, Stacey A.; O'Brien, Daniel; Yao, Joseph D.

    2016-01-01

    ABSTRACT Understanding how some HIV-infected cells resist the cytotoxicity of HIV replication is crucial to enabling HIV cure efforts. HIV killing of CD4 T cells that replicate HIV can involve HIV protease-mediated cleavage of procaspase 8 to generate a fragment (Casp8p41) that directly binds and activates the mitochondrial proapoptotic protein BAK. Here, we demonstrate that Casp8p41 also binds with nanomolar affinity to the antiapoptotic protein Bcl-2, which sequesters Casp8p41 and prevents apoptosis. Further, we show that central memory CD4 T cells (TCM) from HIV-infected individuals have heightened expression of BCL-2 relative to procaspase 8, possibly explaining the persistence of HIV-infected TCM despite generation of Casp8p41. Consistent with this hypothesis, the selective BCL-2 antagonist venetoclax induced minimal killing of uninfected CD4 T cells but markedly increased the death of CD4 T cells and diminished cell-associated HIV DNA when CD4 T cells from antiretroviral therapy (ART)-suppressed HIV patients were induced with αCD3/αCD28 to reactivate HIV ex vivo. Thus, priming CD4 T cells from ART suppressed HIV patients with a BCL-2 antagonist, followed by HIV reactivation, achieves reductions in cell-associated HIV DNA, whereas HIV reactivation alone does not. IMPORTANCE HIV infection is incurable due to a long-lived reservoir of HIV+ memory CD4 T cells, and no clinically relevant interventions have been identified that reduce the number of these HIV DNA-containing cells. Since postintegration HIV replication can result in HIV protease generation of Casp8p41, which activates BAK, causing infected CD4 T cell death, we sought to determine whether this occurs in memory CD4 T cells. Here, we demonstrate that memory CD4 T cells can generate Casp8p41 and yet are intrinsically resistant to death induced by diverse stimuli, including Casp8p41. Furthermore, BCL-2 expression is relatively increased in these cells and directly binds and inhibits Casp8p41's

  15. Cadmium-Induced Hydrogen Sulfide Synthesis Is Involved in Cadmium Tolerance in Medicago sativa by Reestablishment of Reduced (Homo)glutathione and Reactive Oxygen Species Homeostases

    PubMed Central

    Cui, Weiti; Chen, Huiping; Zhu, Kaikai; Jin, Qijiang; Xie, Yanjie; Cui, Jin; Xia, Yan; Zhang, Jing; Shen, Wenbiao

    2014-01-01

    Until now, physiological mechanisms and downstream targets responsible for the cadmium (Cd) tolerance mediated by endogenous hydrogen sulfide (H2S) have been elusive. To address this gap, a combination of pharmacological, histochemical, biochemical and molecular approaches was applied. The perturbation of reduced (homo)glutathione homeostasis and increased H2S production as well as the activation of two H2S-synthetic enzymes activities, including L-cysteine desulfhydrase (LCD) and D-cysteine desulfhydrase (DCD), in alfalfa seedling roots were early responses to the exposure of Cd. The application of H2S donor sodium hydrosulfide (NaHS), not only mimicked intracellular H2S production triggered by Cd, but also alleviated Cd toxicity in a H2S-dependent fashion. By contrast, the inhibition of H2S production caused by the application of its synthetic inhibitor blocked NaHS-induced Cd tolerance, and destroyed reduced (homo)glutathione and reactive oxygen species (ROS) homeostases. Above mentioned inhibitory responses were further rescued by exogenously applied glutathione (GSH). Meanwhile, NaHS responses were sensitive to a (homo)glutathione synthetic inhibitor, but reversed by the cotreatment with GSH. The possible involvement of cyclic AMP (cAMP) signaling in NaHS responses was also suggested. In summary, LCD/DCD-mediated H2S might be an important signaling molecule in the enhancement of Cd toxicity in alfalfa seedlings mainly by governing reduced (homo)glutathione and ROS homeostases. PMID:25275379

  16. Small interfering-RNA to protein kinase C-delta reduces the proinflammatory effects of human C-reactive protein in biobreeding diabetic rats.

    PubMed

    Jialal, I; Machha, A; Devaraj, S

    2013-04-01

    Type 1 diabetes (T1DM) is a proinflammatory state characterized by increased C-reactive protein (CRP) levels. Previously we reported that human CRP accentuated macrophage activity in spontaneously diabetic biobreeding (BB) rats and also increased protein kinase C (PKC) delta. Hence we tested the effect of molecular inhibition of PKC delta on plasma and macrophage proinflammatory biomarkers using small interfering (si)RNA to PKC delta. Prior to administration of human CRP, daily for 3 days to diabetic rats, scrambled siRNA or siRNA to PKC delta was also delivered for the 3 days, and the animals were sacrificed on day 4. Peritoneal macrophages and plasma were obtained. Compared to scrambled siRNA, siRNA to PKC delta resulted in a significant decrease in biomediators of inflammation in plasma and from macrophages (IL-1, TNF-alpha, IL-6, MCP-1, KC/IL-8, and PAI -1). However, siRNA to PKC delta has no effect on superoxide release from macrophages. In conclusion, our novel data suggests that siRNA to PKC delta attenuates the proinflammatory effect of human CRP in spontaneously diabetic BB rats and could have implications with regard to attenuating inflammation and vascular complications in T1DM.

  17. Order of Administration of Math and Verbal Tests: An Ecological Intervention to Reduce Stereotype Threat on Girls' Math Performance

    ERIC Educational Resources Information Center

    Smeding, Annique; Dumas, Florence; Loose, Florence; Régner, Isabelle

    2013-01-01

    In 2 field experiments, we relied on the very features of real testing situations--where both math and verbal tests are administered--to examine whether order of test administration can, by itself, create vs. alleviate stereotype threat (ST) effects on girls' math performance. We predicted that taking the math test before the verbal test would be…

  18. A novel redox-active metalloporphyrin reduces reactive oxygen species and inflammatory markers but does not improve marginal mass engraftment in a murine donation after circulatory death islet transplantation model.

    PubMed

    Bruni, Antonio; Pepper, Andrew R; Gala-Lopez, Boris; Pawlick, Rena; Abualhassan, Nasser; Crapo, James D; Piganelli, Jon D; Shapiro, A M James

    2016-07-01

    Islet transplantation is a highly effective treatment for stabilizing glycemic control for select patients with type-1 diabetes. Despite improvements to clinical transplantation, single-donor transplant success has been hard to achieve routinely, necessitating increasing demands on viable organ availability. Donation after circulatory death (DCD) may be an alternative option to increase organ availability however, these organs tend to be more compromised. The use of metalloporphyrin anti-inflammatory and antioxidant (MnP) compounds previously demonstrated improved in vivo islet function in preclinical islet transplantation. However, the administration of MnP (BMX-001) in a DCD islet isolation and transplantation model has yet to be established. In this study, murine donors were subjected to a 15-min warm ischemic (WI) period prior to isolation and culture with or without MnP. Subsequent to one-hour culture, islets were assessed for in vitro viability and in vivo function. A 15-minute WI period significantly reduced islet yield, regardless of MnP-treatment relative to yields from standard isolation. MnP-treated islets did not improve islet viability compared to DCD islets alone. MnP-treatment did significantly reduce the presence of extracellular reactive oxygen species (ROS) (p < 0 .05). Marginal, syngeneic islets (200 islets) transplanted under the renal capsule exhibited similar in vivo outcomes regardless of WI or MnP-treatment. DCD islet grafts harvested 7 d post-transplant exhibited sustained TNF-α and IL-10, while MnP-treated islet-bearing grafts demonstrated reduced IL-10 levels. Taken together, 15-minute WI in murine islet isolation significantly impairs islet yield. DCD islets do indeed demonstrate in vivo function, though MnP therapy was unable to improve viability and engraftment outcomes. PMID:27220256

  19. Wheat Stripe Rust Resistance Protein WKS1 Reduces the Ability of the Thylakoid-Associated Ascorbate Peroxidase to Detoxify Reactive Oxygen Species.

    PubMed

    Gou, Jin-Ying; Li, Kun; Wu, Kati; Wang, Xiaodong; Lin, Huiqiong; Cantu, Dario; Uauy, Cristobal; Dobon-Alonso, Albor; Midorikawa, Takamufi; Inoue, Kentaro; Sánchez, Juan; Fu, Daolin; Blechl, Ann; Wallington, Emma; Fahima, Tzion; Meeta, Madhu; Epstein, Lynn; Dubcovsky, Jorge

    2015-06-01

    Stripe rust is a devastating fungal disease of wheat caused by Puccinia striiformis f. sp tritici (Pst). The WHEAT KINASE START1 (WKS1) resistance gene has an unusual combination of serine/threonine kinase and START lipid binding domains and confers partial resistance to Pst. Here, we show that wheat (Triticum aestivum) plants transformed with the complete WKS1 (variant WKS1.1) are resistant to Pst, whereas those transformed with an alternative splice variant with a truncated START domain (WKS1.2) are susceptible. WKS1.1 and WKS1.2 preferentially bind to the same lipids (phosphatidic acid and phosphatidylinositol phosphates) but differ in their protein-protein interactions. WKS1.1 is targeted to the chloroplast where it phosphorylates the thylakoid-associated ascorbate peroxidase (tAPX) and reduces its ability to detoxify peroxides. Increased expression of WKS1.1 in transgenic wheat accelerates leaf senescence in the absence of Pst. Based on these results, we propose that the phosphorylation of tAPX by WKS1.1 reduces the ability of the cells to detoxify reactive oxygen species and contributes to cell death. This response takes several days longer than typical hypersensitive cell death responses, thus allowing the limited pathogen growth and restricted sporulation that is characteristic of the WKS1 partial resistance response to Pst.

  20. Electrolysed reduced water decreases reactive oxygen species-induced oxidative damage to skeletal muscle and improves performance in broiler chickens exposed to medium-term chronic heat stress.

    PubMed

    Azad, M A K; Kikusato, M; Zulkifli, I; Toyomizu, M

    2013-01-01

    1. The present study was designed to achieve a reduction of reactive oxygen species (ROS)-induced oxidative damage to skeletal muscle and to improve the performance of broiler chickens exposed to chronic heat stress. 2. Chickens were given a control diet with normal drinking water, or diets supplemented with cashew nut shell liquid (CNSL) or grape seed extract (GSE), or a control diet with electrolysed reduced water (ERW) for 19 d after hatch. Thereafter, chickens were exposed to a temperature of either 34°C continuously for a period of 5 d, or maintained at 24°C, on the same diets. 3. The control broilers exposed to 34°C showed decreased weight gain and feed consumption and slightly increased ROS production and malondialdehyde (MDA) concentrations in skeletal muscle. The chickens exposed to 34°C and supplemented with ERW showed significantly improved growth performance and lower ROS production and MDA contents in tissues than control broilers exposed to 34°C. Following heat exposure, CNSL chickens performed better with respect to weight gain and feed consumption, but still showed elevated ROS production and skeletal muscle oxidative damage. GSE chickens did not exhibit improved performance or reduced skeletal muscle oxidative damage. 4. In conclusion, this study suggests that ERW could partially inhibit ROS-induced oxidative damage to skeletal muscle and improve growth performance in broiler chickens under medium-term chronic heat treatment.

  1. Electrolysed reduced water decreases reactive oxygen species-induced oxidative damage to skeletal muscle and improves performance in broiler chickens exposed to medium-term chronic heat stress.

    PubMed

    Azad, M A K; Kikusato, M; Zulkifli, I; Toyomizu, M

    2013-01-01

    1. The present study was designed to achieve a reduction of reactive oxygen species (ROS)-induced oxidative damage to skeletal muscle and to improve the performance of broiler chickens exposed to chronic heat stress. 2. Chickens were given a control diet with normal drinking water, or diets supplemented with cashew nut shell liquid (CNSL) or grape seed extract (GSE), or a control diet with electrolysed reduced water (ERW) for 19 d after hatch. Thereafter, chickens were exposed to a temperature of either 34°C continuously for a period of 5 d, or maintained at 24°C, on the same diets. 3. The control broilers exposed to 34°C showed decreased weight gain and feed consumption and slightly increased ROS production and malondialdehyde (MDA) concentrations in skeletal muscle. The chickens exposed to 34°C and supplemented with ERW showed significantly improved growth performance and lower ROS production and MDA contents in tissues than control broilers exposed to 34°C. Following heat exposure, CNSL chickens performed better with respect to weight gain and feed consumption, but still showed elevated ROS production and skeletal muscle oxidative damage. GSE chickens did not exhibit improved performance or reduced skeletal muscle oxidative damage. 4. In conclusion, this study suggests that ERW could partially inhibit ROS-induced oxidative damage to skeletal muscle and improve growth performance in broiler chickens under medium-term chronic heat treatment. PMID:23815735

  2. Wheat Stripe Rust Resistance Protein WKS1 Reduces the Ability of the Thylakoid-Associated Ascorbate Peroxidase to Detoxify Reactive Oxygen Species[OPEN

    PubMed Central

    Gou, Jin-Ying; Li, Kun; Wu, Kati; Wang, Xiaodong; Lin, Huiqiong; Cantu, Dario; Uauy, Cristobal; Dobon-Alonso, Albor; Midorikawa, Takamufi; Inoue, Kentaro; Sánchez, Juan; Fu, Daolin; Blechl, Ann; Wallington, Emma; Fahima, Tzion; Meeta, Madhu; Epstein, Lynn; Dubcovsky, Jorge

    2015-01-01

    Stripe rust is a devastating fungal disease of wheat caused by Puccinia striiformis f. sp tritici (Pst). The WHEAT KINASE START1 (WKS1) resistance gene has an unusual combination of serine/threonine kinase and START lipid binding domains and confers partial resistance to Pst. Here, we show that wheat (Triticum aestivum) plants transformed with the complete WKS1 (variant WKS1.1) are resistant to Pst, whereas those transformed with an alternative splice variant with a truncated START domain (WKS1.2) are susceptible. WKS1.1 and WKS1.2 preferentially bind to the same lipids (phosphatidic acid and phosphatidylinositol phosphates) but differ in their protein-protein interactions. WKS1.1 is targeted to the chloroplast where it phosphorylates the thylakoid-associated ascorbate peroxidase (tAPX) and reduces its ability to detoxify peroxides. Increased expression of WKS1.1 in transgenic wheat accelerates leaf senescence in the absence of Pst. Based on these results, we propose that the phosphorylation of tAPX by WKS1.1 reduces the ability of the cells to detoxify reactive oxygen species and contributes to cell death. This response takes several days longer than typical hypersensitive cell death responses, thus allowing the limited pathogen growth and restricted sporulation that is characteristic of the WKS1 partial resistance response to Pst. PMID:25991734

  3. Reactive Oxygen Species-Reducing Strategies Improve Pulmonary Arterial Responses to Nitric Oxide in Piglets with Chronic Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Dikalova, Anna; Slaughter, James C.; Kaplowitz, M.R.; Zhang, Y.; Aschner, Judy L.

    2013-01-01

    Abstract Aims: There are no effective treatments for chronic pulmonary hypertension in infants with cardiopulmonary disorders associated with hypoxia, such as those with chronic lung disease. These patients often have poor or inconsistent pulmonary dilator responses to inhaled nitric oxide (iNO) therapy for unknown reasons. One possible explanation for poor responsiveness to iNO is reduced NO bioavailability caused by interactions between reactive oxygen species (ROS) and NO. Our major aim was to determine if strategies to reduce ROS improve dilator responses to the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), in resistance pulmonary arteries (PRAs) from a newborn piglet model of chronic pulmonary hypertension. Results: The dilation to SNAP was significantly impaired in PRAs from piglets with chronic hypoxia-induced pulmonary hypertension. ROS scavengers, including cell-permeable and impermeable agents to degrade hydrogen peroxide (H2O2), improved dilation to SNAP in PRAs from chronically hypoxic piglets. Treatment with agents to inhibit nitric oxide synthase and NADPH oxidase, potential enzymatic sources of ROS, also improved dilation to SNAP in PRAs from hypoxic piglets. Innovation: Our studies are the first to utilize a newborn model of chronic pulmonary hypertension to evaluate the impact of a number of potential therapeutic strategies for ROS removal on responses to exogenous NO in the vessels most relevant to the regulation of pulmonary vascular resistance (PRA). Conclusions: Strategies aimed at reducing ROS merit further evaluation and consideration as therapeutic approaches to improve responses to iNO in infants with chronic pulmonary hypertension. Antioxid. Redox Signal. 18, 1727–1738. PMID:23244497

  4. Aerobic Exercise Training Prevents the Onset of Endothelial Dysfunction via Increased Nitric Oxide Bioavailability and Reduced Reactive Oxygen Species in an Experimental Model of Menopause

    PubMed Central

    Braga, Viviane A. V. N.; Couto, Gisele K.; Lazzarin, Mariana C.; Rossoni, Luciana V.; Medeiros, Alessandra

    2015-01-01

    Objective Previous studies have shown that estrogen deficiency, arising in postmenopause, promotes endothelial dysfunction. This study evaluated the effects of aerobic exercise training on endothelial dependent vasodilation of aorta in ovariectomized rats, specifically investigating the role of nitric oxide (NO) and reactive oxygen species (ROS). Methods Female Wistar rats ovariectomized (OVX – n=20) or with intact ovary (SHAM – n=20) remained sedentary (OVX and SHAM) or performed aerobic exercise training on a treadmill 5 times a week for a period of 8 weeks (OVX-TRA and SHAM-TRA). In the thoracic aorta the endothelium-dependent and –independent vasodilation was assessed by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Certain aortic rings were incubated with L-NAME to assess the NO modulation on the ACh-induced vasodilation. The fluorescence to dihydroethidium in aortic slices and plasma nitrite/nitrate concentrations were measured to evaluate ROS and NO bioavailability, respectively. Results ACh-induced vasodilation was reduced in OVX rats as compared SHAM (Rmax: SHAM: 86±3.3 vs. OVX: 57±3.0%, p<0.01). Training prevented this response in OVX-TRA (Rmax: OVX-TRA: 88±2.0%, p<0.01), while did not change it in SHAM-TRA (Rmax: SHAM-TRA: 80±2.2%, p<0.01). The L-NAME incubation abolished the differences in ACh-induced relaxation among groups. SNP-induced vasodilation was not different among groups. OVX reduced nitrite/nitrate plasma concentrations and increased ROS in aortic slices, training as effective to restore these parameters to the SHAM levels. Conclusions Exercise training, even in estrogen deficiency conditions, is able to improve endothelial dependent vasodilation in rat aorta via enhanced NO bioavailability and reduced ROS levels. PMID:25923465

  5. Comparison of effects of ezetimibe/simvastatin versus simvastatin versus atorvastatin in reducing C-reactive protein and low-density lipoprotein cholesterol levels.

    PubMed

    Pearson, Thomas; Ballantyne, Christie; Sisk, Christine; Shah, Arvind; Veltri, Enrico; Maccubbin, Darbie

    2007-06-15

    The lowering effects of ezetimibe/simvastatin combination therapy on low-density lipoprotein (LDL) cholesterol and high-sensitivity C-reactive protein (CRP) were compared with those of simvastatin or atorvastatin monotherapy in a large cohort of patients with primary hypercholesterolemia. To compare ezetimibe/simvastatin with simvastatin, data were combined from 3 identical, prospective 12-week trials in which patients were randomized to receive placebo; ezetimibe 10 mg; ezetimibe 10 mg added to simvastatin 10, 20, 40, or 80 mg; or simvastatin 10, 20, 40, or 80 mg. To compare ezetimibe/simvastatin with atorvastatin, data were analyzed from a phase III double-blind, active-controlled study in which patients were randomized equally to receive ezetimibe/simvastatin 10/10, 10/20, 10/40, or 10/80 mg or atorvastatin 10, 20, 40, or 80 mg for 6 weeks. When averaged across doses, ezetimibe/simvastatin produced significantly greater reductions compared with simvastatin alone in LDL cholesterol (52.5% vs 38.0%, respectively) and CRP levels (31.0% vs 14.3%, respectively). At each individual simvastatin dose, co-administration with ezetimibe produced significant further CRP reductions versus simvastatin alone. Ezetimibe/simvastatin was significantly more effective at lowering LDL cholesterol than atorvastatin when pooled across doses (53.4% vs 45.3%, respectively) and in each milligram-equivalent dose comparison. Reductions in CRP of similar magnitude were observed with ezetimibe/simvastatin and atorvastatin when averaged across doses and at each milligram-equivalent statin dose comparison. In conclusion, the lipid-modulating and anti-inflammatory effects of ezetimibe/simvastatin provide additional benefits not realized by statin monotherapy alone.

  6. Reducing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on alcohol self-administration in rats: Possible involvement of the GABAB receptor.

    PubMed

    Maccioni, Paola; Lorrai, Irene; Carai, Mauro A M; Riva, Antonella; Morazzoni, Paolo; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-05-16

    Recent studies demonstrated that treatment with saikosaponin A (SSA) - an active ingredient of the medicinal herb, Bupleurum falcatum L. - selectively suppressed, likely via a GABAB receptor-mediated mechanism, intravenous self-administration of morphine and cocaine in rats [Yoon et al., 2012; 2013]. The present study was designed to investigate whether the capacity of SSA to suppress morphine and cocaine self-administration extends to oral alcohol self-administration. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were trained to lever-respond on a Fixed Ratio (FR) 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested under the FR4 (measure of alcohol reinforcing properties) and Progressive Ratio (PR; measure of alcohol motivational properties) schedules of reinforcement. The possible involvement of the GABAB receptor system was investigated testing the effect of (a) pretreatment with the GABAB receptor antagonist, SCH50911, and (b) combined treatment with the positive allosteric modulator of the GABAB receptor, GS39783. Treatment with SSA (0, 0.25, 0.5, and 1mg/kg, i.p.) markedly reduced lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). Pretreatment with 2mg/kg SCH50911 (i.p.) resulted in a partial blockade of the reducing effect of 0.5mg/kg SSA on lever-responding for alcohol and amount of self-administered alcohol. Combination of per se ineffective doses of GS39783 (5mg/kg, i.g.) and SSA (0.1mg/kg, i.p.) reduced lever-responding for alcohol and amount of self-administered alcohol. These results (a) extend to alcohol self-administration the capacity of SSA to suppress morphine and cocaine self-administration in rats and (b) suggest that the GABAB receptor system is likely part of the neural substrate underlying the reducing effect of SSA on

  7. Association of postpartum maternal tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administration and timeliness of infant immunization.

    PubMed

    Kaur, Ishminder; George, Krissa J; Pena-Ricardo, Carolina; Kelly, Barbara A; Watson, Barbara

    2013-11-01

    A retrospective cohort study was conducted on infants of mothers delivering at an inner-city hospital in October 2009 where postpartum maternal tetanus toxoid, reduced diptheria toxoid and acellular pertussis (Tdap) vaccination had been initiated in May 2008. We compared mothers and infants in a Tdap intervention group discharged July 2008 (n=250) with a pre-Tdap control group discharged July 2007 (n=238). Postpartum maternal Tdap impacted positively timeliness of early infant immunization.

  8. Administration of Tranexamic Acid Reduces Postoperative Blood Loss in Calcaneal Fractures: A Randomized Controlled Trial.

    PubMed

    Xie, Bing; Tian, Jing; Zhou, Da-peng

    2015-01-01

    The present randomized controlled trial was undertaken to evaluate the effect of tranexamic acid (TXA) on reducing postoperative blood loss in calcaneal fractures. A total of 90 patients with a unilateral closed calcaneal fracture were randomized to the TXA (n = 45) and control (n = 45) groups. The corresponding groups received 15 mg/kg body weight of TXA or placebo (0.9% sodium chloride solution) intravenously before the skin incision was made. Open reduction and internal fixation was performed for all patients and selective bone grafting was performed. The patients were examined 3 months after surgery. The intraoperative and postoperative blood loss, blood test results, and wound complications were compared between the 2 groups. The complications of TXA were also investigated. No statistically significant differences were found in the baseline characteristics between the TXA and control groups. Also, no significant difference was noted in the intraoperative blood loss between the 2 groups. However, in the TXA group, the postoperative blood loss during the first 24 hours was significantly lower than that in the control group (110.0 ± 160.0 mL versus 320.0 ± 360.0 mL; p < .001). The incidence of wound complications was also reduced compared with that in the control group (7.3% versus 23.8%; p = .036). No significant difference was found in the incidence of thromboembolic events or adverse drug reactions between the 2 groups. We concluded that preoperative single-dose TXA can effectively reduce postoperative blood loss and wound complications in patients with calcaneal fractures and that no significant side effects developed compared with the control group.

  9. Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

    PubMed Central

    Coffey, M J; Phare, S M; George, S; Peters-Golden, M; Kazanjian, P H

    1998-01-01

    Neutrophil (PMN) dysfunction occurs in HIV infection. Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway that play a role in host defense and are synthesized by PMN. We investigated the synthesis of LT by PMN from HIV-infected subjects. There was a reduction (4.0+/-1.3% of control) in LT synthesis in PMN from HIV-infected compared with normal subjects. This was associated with reduced expression of 5-LO-activating protein (31.2+/-9.6% of normal), but not of 5-LO itself. Since HIV does not directly infect PMN, we considered that these effects were due to reduced release of cytokines, such as granulocyte colony-stimulating factor (G-CSF). We examined the effect of G-CSF treatment (300 microgram daily for 5 d) on eight HIV-infected subjects. PMN were studied in vitro before therapy (day 1) and on days 4 and 7. LTB4 synthesis was increased on day 4 of G-CSF treatment, and returned toward day 1 levels on day 7. 5-LO and 5-LO-activating protein expression were increased in parallel. As a functional correlate to this increase in PMN LT synthesis by G-CSF, we examined the effects on killing of Cryptococcus neoformans. Anticryptococcal activity of PMN from HIV-infected subjects was less than that of PMN from normal subjects. G-CSF treatment improved fungistatic activity of PMN. This increase in antifungal activity was attenuated by in vitro treatment with the LT synthesis inhibitor, MK-886. In conclusion, PMN from HIV-infected subjects demonstrate reduced 5-LO metabolism and antifungal activity in vitro, which was reversed by in vivo G-CSF therapy. PMID:9710433

  10. Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath test after co-administration of clopidogrel and proton pump inhibitors following percutaneous coronary intervention and correlation to platelet reactivity.

    PubMed

    Harvey, Adrien; Modak, Anil; Déry, Ugo; Roy, Mélanie; Rinfret, Stéphane; Bertrand, Olivier F; Larose, Éric; Rodés-Cabau, Josep; Barbeau, Gérald; Gleeton, Onil; Nguyen, Can Manh; Proulx, Guy; Noël, Bernard; Roy, Louis; Paradis, Jean-Michel; De Larochellière, Robert; Déry, Jean-Pierre

    2016-03-01

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the prevention of cardiovascular events following percutaneous coronary intervention (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent these events, proton pump inhibitors (PPI) are routinely prescribed. It has been reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 enzyme activity (phenotype) and its correlation with platelet reactivity following PPI therapy has not yet been fully described. In this study we attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the administration of PPI in coronary artery disease (CAD) patients treated with DAPT after PCI. Thirty (30) days after successful PCI with stent placement, 59 patients enrolled in the Evaluation of the Influence of Statins and Proton Pump Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov Identifier: NCT00930670) were recruited to participate in this sub study. Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet function was evaluated by vasodilator-stimulated phosphoprotein (VASP) phosphorylation and light transmittance aggregometry before and 30 d after treatment with antacid therapy. Patients randomized to esomeprazole and omeprazole had greater high on-treatment platelet reactivity and lowering of CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized to ranitidine and pantoprazole did not show any changes in platelet activity or CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, changes in CYP2C19 enzyme activity

  11. Difference in root K+ retention ability and reduced sensitivity of K+-permeable channels to reactive oxygen species confer differential salt tolerance in three Brassica species.

    PubMed

    Chakraborty, Koushik; Bose, Jayakumar; Shabala, Lana; Shabala, Sergey

    2016-08-01

    Brassica species are known to possess significant inter and intraspecies variability in salinity stress tolerance, but the cell-specific mechanisms conferring this difference remain elusive. In this work, the role and relative contribution of several key plasma membrane transporters to salinity stress tolerance were evaluated in three Brassica species (B. napus, B. juncea, and B. oleracea) using a range of electrophysiological assays. Initial root growth assay and viability staining revealed that B. napus was most tolerant amongst the three species, followed by B. juncea and B. oleracea At the mechanistic level, this difference was conferred by at least three complementary physiological mechanisms: (i) higher Na(+) extrusion ability from roots resulting from increased expression and activity of plasma membrane SOS1-like Na(+)/H(+) exchangers; (ii) better root K(+) retention ability resulting from stress-inducible activation of H(+)-ATPase and ability to maintain more negative membrane potential under saline conditions; and (iii) reduced sensitivity of B. napus root K(+)-permeable channels to reactive oxygen species (ROS). The last two mechanisms played the dominant role and conferred most of the differential salt sensitivity between species. Brassica napus plants were also more efficient in preventing the stress-induced increase in GORK transcript levels and up-regulation of expression of AKT1, HAK5, and HKT1 transporter genes. Taken together, our data provide the mechanistic explanation for differential salt stress sensitivity amongst these species and shed light on transcriptional and post-translational regulation of key ion transport systems involved in the maintenance of the root plasma membrane potential and cytosolic K/Na ratio as a key attribute for salt tolerance in Brassica species. PMID:27340231

  12. Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways

    PubMed Central

    2014-01-01

    Background Lysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes. Methods Cell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay. Results We found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein. Conclusions Baicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways. PMID:25012390

  13. Difference in root K+ retention ability and reduced sensitivity of K+-permeable channels to reactive oxygen species confer differential salt tolerance in three Brassica species

    PubMed Central

    Chakraborty, Koushik; Bose, Jayakumar; Shabala, Lana; Shabala, Sergey

    2016-01-01

    Brassica species are known to possess significant inter and intraspecies variability in salinity stress tolerance, but the cell-specific mechanisms conferring this difference remain elusive. In this work, the role and relative contribution of several key plasma membrane transporters to salinity stress tolerance were evaluated in three Brassica species (B. napus, B. juncea, and B. oleracea) using a range of electrophysiological assays. Initial root growth assay and viability staining revealed that B. napus was most tolerant amongst the three species, followed by B. juncea and B. oleracea. At the mechanistic level, this difference was conferred by at least three complementary physiological mechanisms: (i) higher Na+ extrusion ability from roots resulting from increased expression and activity of plasma membrane SOS1-like Na+/H+ exchangers; (ii) better root K+ retention ability resulting from stress-inducible activation of H+-ATPase and ability to maintain more negative membrane potential under saline conditions; and (iii) reduced sensitivity of B. napus root K+-permeable channels to reactive oxygen species (ROS). The last two mechanisms played the dominant role and conferred most of the differential salt sensitivity between species. Brassica napus plants were also more efficient in preventing the stress-induced increase in GORK transcript levels and up-regulation of expression of AKT1, HAK5, and HKT1 transporter genes. Taken together, our data provide the mechanistic explanation for differential salt stress sensitivity amongst these species and shed light on transcriptional and post-translational regulation of key ion transport systems involved in the maintenance of the root plasma membrane potential and cytosolic K/Na ratio as a key attribute for salt tolerance in Brassica species. PMID:27340231

  14. Continuous nicotine infusion reduces nicotine self-administration in rats with 23-h/day access to nicotine.

    PubMed

    LeSage, Mark G; Keyler, Dan E; Shoeman, Don; Raphael, Donna; Collins, Gregory; Pentel, Paul R

    2002-05-01

    The effects of continuous nicotine infusion on nicotine self-administration (NSA) were studied in rats as a model of nicotine replacement therapy (NRT) in humans. A NSA model in which rats had 23-h/day access to nicotine was used to approximate nicotine access conditions in cigarette smokers. In order to estimate serum nicotine concentrations associated with NSA, arterial and venous serum nicotine concentrations were measured during a simulation of NSA. Nicotine was noncontingently administered as 30 doses/12 h of 0.03 mg/kg/i.n.f. or 60 doses/12 h of 0.01 mg/kg/i.n.f. daily. Venous serum nicotine concentrations were measured after the first nicotine dose of the day, and arterial and venous concentrations were measured after doses in the middle of the day. The range of mean concentrations measured was similar to those reported in cigarette smokers (venous concentrations 6-59 ng/ml, arterial concentrations 42-96 ng/ml). The effects of continuous nicotine infusion on NSA were studied by noncontingently administering nicotine at various rates via osmotic pump to animals self-administering nicotine (0.01 or 0.03 mg/kg/i.n.f.) during 23-h/day sessions. Continuous nicotine infusion at all infusion rates substantially suppressed NSA, but suppression was rate-related only for the 0.01-mg/kg/inf NSA unit dose. Nicotine infusion rates producing venous serum nicotine concentrations equaling or exceeding the peak venous levels associated with simulated NSA were more effective than lower infusion rates only at the lower NSA unit dose. The highest nicotine infusion rate had no sustained effect on food-maintained responding, demonstrating its specificity for suppression of NSA. These data provide a model for studying NRT in the rat.

  15. Administrative initiatives for reducing inappropriate prescribing of psychotropic drugs in nursing homes: how successful have they been?

    PubMed

    Hughes, Carmel M; Lapane, Kate L

    2005-01-01

    The quality of nursing home care has been subject to intense investigation and scrutiny, particularly in the US. In particular, there has long been concern about the extensive use of psychotropic agents, notably antipsychotics, hypnotics and anxiolytics, in this setting. These drugs have been described as 'chemical restraints', in that they were used to sedate and subdue patients, partly to compensate for poor staffing levels and to minimise staff contact with patients. However, following a damning Institute of Medicine report to the US Congress, use of such drugs became regulated under a unique administrative initiative: the Nursing Home Reform Act, embedded within the Omnibus Budget Reconciliation Act 1987 (OBRA 87). Research has indicated that psychotropic drug use in nursing homes has declined markedly following the implementation of this regulation. In addition, explicit criteria for potentially inappropriate medication use were incorporated within the guidelines for nursing home inspectors from 1 July 1999. Because regulations have targeted poor prescribing, rather than promoting the use of effective drugs in older residents, it has been difficult to determine whether outcomes have improved for nursing home residents as a result. However, US government agencies have responded to continuing concerns about nursing home care through the implementation of quality indicators which are used to guide and plan inspections of such facilities and to compare nursing homes within the same state. Although there are a limited number of quality indicators relating to prescribing, this represents a move away from adversarial regulation, which focuses on poor practice, and attempts to improve quality of care. An important role for educational initiatives and interventions has been advocated by some commentators and these have proved to be successful in the nursing home environment. Other countries have not implemented such restrictive prescribing regulation in nursing homes

  16. Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats.

    PubMed

    Xue, YueQiang; Steketee, Jeffery D; Sun, WenLin

    2012-03-01

    Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment, which is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue to use cocaine despite potentially severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This study was aimed at testing the hypothesis that the central nucleus of the amygdala (CeN) plays a critical role in such regulation. To this end, rats were trained to press a lever to self-administer cocaine under a chained schedule: a response on one lever (cocaine-seeking lever) led to access to the other lever (cocaine-taking lever), on which a response was reinforced by cocaine and cues. Thereafter, responses on the seeking lever were punished by footshock with a probability of 0.5. Cocaine self-administration (SA) was significantly suppressed by punishment in an intensity-dependent manner. Interestingly, rats trained with daily 6-h (extended access) but not 2-h (limited access) sessions showed resistance to the lower intensity of punishment. Inactivation of the CeN induced a robust anti-punishment effect in both groups. These data provided evidence that the CeN is a critical neural substrate involved in regulation by punishment of cocaine SA. Rats with a history of extended cocaine SA appeared to be less sensitive to punishment. The decreased sensitivity could result from the neuroplastic changes induced by extended cocaine SA in the CeN.

  17. Administration of Saccharin to Neonatal Mice Influences Body Composition of Adult Males and Reduces Body Weight of Females

    PubMed Central

    Parlee, Sebastian D.; Simon, Becky R.; Scheller, Erica L.; Alejandro, Emilyn U.; Learman, Brian S.; Krishnan, Venkatesh; Bernal-Mizrachi, Ernesto

    2014-01-01

    Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice. PMID:24456165

  18. Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females.

    PubMed

    Parlee, Sebastian D; Simon, Becky R; Scheller, Erica L; Alejandro, Emilyn U; Learman, Brian S; Krishnan, Venkatesh; Bernal-Mizrachi, Ernesto; MacDougald, Ormond A

    2014-04-01

    Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice.

  19. Carnitine administration reduces cytokine levels, improves food intake, and ameliorates body composition in tumor-bearing rats.

    PubMed

    Laviano, Alessandro; Molfino, Alessio; Seelaender, Marilia; Frascaria, Teresa; Bertini, Giuseppe; Ramaccini, Cesarina; Bollea, Maria Rosa; Citro, Gennaro; Rossi Fanelli, Filippo

    2011-12-01

    Increased cytokine expression contributes to the pathogenesis of cancer anorexia?cachexia syndrome. Carnitine may reduce inflammation in chronic diseases. We tested the effects of L-propionylcarnitine (PC group) or saline (C group) on food intake (FI), body composition, and inflammatory status of MCA-sarcoma-bearing rats. On tumor appearance, rats were randomly assigned to daily i.p. injection of L-propionylcarnitine (250 mg/kgBW/d; n = 8) or saline (equal volume; n = 8). FI and fat-free mass wasting improved in PC rats only (p < .01 vs. controls). Cytokines? levels decreased in PC rats vs. controls (p < .02). Results suggest that carnitine may ameliorate cancer anorexia?cachexia, via reduction of the inflammatory status.

  20. Administration of prednisolone phosphate-liposomes reduces wound contraction in a rat partial-thickness wound model.

    PubMed

    Richters, Cornelia D; Paauw, Nanne J; Mayen, Ilvy; van Bloois, Louis; Metselaer, Josbert M; Storm, Gert; du Pont, John S; Hoekstra, Matthias J; Kreis, Robert W; Kamperdijk, Eduard W A

    2006-01-01

    Macrophages play an important role in the inflammatory phase of wound healing and their activity regulates fibroblasts and keratinocytes. Modulation of macrophage function may result in improvement of the wound healing process. Prednisolone phosphate (PLP) encapsulated into liposomes was administered to partial-thickness wounds in rats. A single dose of 75 microg/kg, applied directly after wounding, resulted in up to a 30% reduction of wound contraction at 28 days after wounding. This effect could not be achieved in the group that was administered free PLP or liposomes containing phosphate-buffered saline to the wound. The number of myofibroblasts was up to 50% lower in wounds treated with the liposomal PLP at 4 days after wounding. The number of macrophages present in the wounds was not statistically different between groups. Most probably, the production of cytokines and growth factors by macrophages is altered after phagocytosing the liposomes, resulting in reduced wound contraction. PMID:17014673

  1. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    PubMed

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  2. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    PubMed

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration. PMID:27305820

  3. Alpha Interferon Inhibits Human Herpesvirus 8 (HHV-8) Reactivation in Primary Effusion Lymphoma Cells and Reduces HHV-8 Load in Cultured Peripheral Blood Mononuclear Cells

    PubMed Central

    Monini, Paolo; Carlini, Francesca; Stürzl, Michael; Rimessi, Paola; Superti, Fabiana; Franco, Marina; Melucci-Vigo, Gianna; Cafaro, Aurelio; Goletti, Delia; Sgadari, Cecilia; Butto’, Stefano; Leone, Patrizia; Leone, Pasqualina; Chiozzini, Chiara; Barresi, Caterina; Tinari, Antonella; Bonaccorsi, Angela; Capobianchi, Maria R.; Giuliani, Massimo; di Carlo, Aldo; Andreoni, Massimo; Rezza, Giovanni; Ensoli, Barbara

    1999-01-01

    Infection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi’s sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-α), we analyzed the effects of IFN-α or anti-IFN-α antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-α inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-α inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-α was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-α Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-α Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-α reduced the HHV-8 load in PBMC. Thus, IFN-α appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-α may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation. PMID:10196299

  4. Oral Administration of Recombinant Lactococcus lactis Expressing HSP65 and Tandemly Repeated P277 Reduces the Incidence of Type I Diabetes in Non-Obese Diabetic Mice

    PubMed Central

    Ma, Yanjun; Liu, Jingjing; Hou, Jing; Dong, Yuankai; Lu, Yong; Jin, Liang; Cao, Rongyue; Li, Taiming; Wu, Jie

    2014-01-01

    Diabetes mellitus type 1 (DM1) is an autoimmune disease that gradually destroys insulin-producing beta-cells. We have previously reported that mucosal administration of fusion protein of HSP65 with tandem repeats of P277 (HSP65-6P277) can reduce the onset of DM1 in non-obese diabetic (NOD) mice. To deliver large amounts of the fusion protein and to enhance long-term immune tolerance effects, in the present study, we investigated the efficacy of using orally administrated L. lactis expressing HSP65-6P277 to reduce the incidence of DM1 in NOD mice. L. lactis strain NZ9000 was engineered to express HSP65-6P277 either constitutively or by nisin induction. After immunization via gavage with the recombinant L. lactis strains to groups of 4-week old female NOD mice for 36 weeks, we observed that oral administration of recombinant L. Lactis resulted in the prevention of hyperglycemia, improved glucose tolerance and reduced insulitis. Immunologic analysis showed that treatment with recombinant L. lactis induced HSP65- and P277- specific T cell immuno-tolerance, as well as antigen-specific proliferation of splenocytes. The results revealed that the DM1-preventing function was in part caused by a reduction in the pro-inflammatory cytokine IFN-γ and an increase in the anti-inflammatory cytokine IL-10. Orally administered recombinant L. lactis delivering HSP65-6P277 may be an effective therapeutic approach in preventing DM1. PMID:25157497

  5. Adolescent alcohol exposure reduces behavioral flexibility, promotes disinhibition, and increases resistance to extinction of ethanol self-administration in adulthood.

    PubMed

    Gass, Justin T; Glen, William Bailey; McGonigal, Justin T; Trantham-Davidson, Heather; Lopez, Marcelo F; Randall, Patrick K; Yaxley, Richard; Floresco, Stan B; Chandler, L Judson

    2014-10-01

    The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28-42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of

  6. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice.

    PubMed

    De Fazio, Luigia; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria C

    2016-01-01

    (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg((-1)) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg((-1)) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis.

  7. Preoperative administration of 0.2% chlorhexidine mouthrinse reduces the risk of bacteraemia associated with intra-alveolar tooth extraction.

    PubMed

    Ugwumba, Chinedu U; Adeyemo, Wasiu L; Odeniyi, Olalekan M; Arotiba, Godwin T; Ogunsola, Folasade T

    2014-12-01

    The aim of the study was to investigate the effect of preoperative 0.2% chlorhexidine mouthwash on the risk of bacteraemia following routine intra-alveolar tooth extraction. The study was a randomized controlled clinical study of 101 subjects who underwent intra-alveolar dental extractions under local anaesthesia. Subjects were randomly assigned to either chlorhexidine or a control group. The chlorhexidine group had 0.2% chlorhexidine mouthwash administered for 1 min before any dental manipulation, and the control group had a mouthrinse of sterile water. Blood samples were collected at baseline, 1 min and 15 min after the dental extractions. Subculture and further identification of the isolated bacteria were performed by conventional microbiological techniques. There was a statistically significant difference in the incidence of bacteraemia between the control group (52.4%) and chlorhexidine group (27.1%) (P = 0.012). Bacteraemia was most frequently detected at 1 min after extraction (33.3%). Of the 30 subjects who had positive blood culture at 1 min, bacteraemia persisted in 8 (26.7%) of the subjects after 15 min. Bacteria isolated included Staphylococcus aureus, Actinomycetes naesulendi, Prevotella species, Streptococcus spp., and Acinetobacter iwoffii. Routine use of 0.20% chlorhexidine mouthwash before dental extraction is recommended to reduce the risk of bacteraemia following tooth extraction. PMID:25028067

  8. E-government factors to reduce administrative and finance corruption in Arab countries: Case study Iraqi oil sector

    NASA Astrophysics Data System (ADS)

    Mohammed, M. A.; Eman, Y.; Hussein, A. H.; Hasson, A. R.

    2015-12-01

    Arab countries face the corruption issues in its several public organizations. The corruption in these countries is considered as the main challenge. The oil sector is one of the public sectors that have huge level of corruption. However, the Iraqi economy had become dependable on oil sector daring the last three decades, and on the contrary, of what other oil countries did. The capital is considered as one of the essential factor for economic development. The revenues of oil exports will stay the essential source for economic development in Iraq in the future in order to reduce being dependable on oil. Since the beginning of the 3rd thousands, the world witnessed great rise in the demand on oil, but the Iraqi exports of crude oil come to be less than its similarities in the seventeenths of last century. So our oil sector is still in need of deep study. This study focuses on technological technique that can make huge decrease for corruption in oil sector in Iraq. However, e-government is considered as the best techniques that can decrease the corruption. Thus, this study bases on challenges that effect on build successful e-government project in Iraqi oil industry.

  9. Dietary Geraniol by Oral or Enema Administration Strongly Reduces Dysbiosis and Systemic Inflammation in Dextran Sulfate Sodium-Treated Mice

    PubMed Central

    De Fazio, Luigia; Spisni, Enzo; Cavazza, Elena; Strillacci, Antonio; Candela, Marco; Centanni, Manuela; Ricci, Chiara; Rizzello, Fernando; Campieri, Massimo; Valerii, Maria C.

    2016-01-01

    (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory, antitumoral, and antimicrobial properties. It is widely used as a preservative in the food industry and as an antimicrobial agent in animal farming. The present study investigated the role of Ge-OH as an anti-inflammatory and anti-dysbiotic agent in the dextran sulfate sodium (DSS)-induced colitis mouse model. Ge-OH was orally administered to C57BL/6 mice at daily doses of 30 and 120 mg kg(−1) body weight, starting 6 days before DSS treatment and ending the day after DSS removal. Furthermore, Ge-OH 120 mg kg(−1) dose body weight was administered via enema during the acute phase of colitis to facilitate its on-site action. The results show that orally or enema-administered Ge-OH is a powerful antimicrobial agent able to prevent colitis-associated dysbiosis and decrease the inflammatory systemic profile of colitic mice. As a whole, Ge-OH strongly improved the clinical signs of colitis and significantly reduced cyclooxygenase-2 (COX-2) expression in colonocytes and in the gut wall. Ge-OH could be a powerful drug for the treatment of intestinal inflammation and dysbiosis. PMID:26973525

  10. Estradiol and Progesterone Administration After pMCAO Stimulates the Neurological Recovery and Reduces the Detrimental Effect of Ischemia Mainly in Hippocampus.

    PubMed

    Perez-Alvarez, Maria Jose; Mateos, Laura; Alonso, Alvaro; Wandosell, Francisco

    2015-12-01

    Epidemiological studies have suggested a differential response, males versus female, in stroke incidence and prognosis. These divergences in brain response after damage are based mostly on hormonal differences. To date, estradiol and progesterone administered independently have demonstrated neuroprotection after ischemia in animal models. Nonetheless, contradictory results were revealed using a combined administration. In order to evaluate the effects of combinatorial treatment administered after ischemia induction, we used two different approaches: in vivo and in vitro models. Male rats which underwent permanent middle cerebral artery occlusion were treated with a combination of estradiol/progesterone at 6, 24 and 48 h after injury and sacrificed at 54 h post-ischemia. The rat brains were evaluated for reactive gliosis, NeuN-positive neurons, levels of synapse-associated proteins and activity levels of PI3K/Akt/GSK3/β-catenin survival pathway. Also, primary cortical neurons were subjected to oxygen and glucose deprivation for 17 h and returned to a normal environment in the presence of estradiol or estradiol/progesterone. Cell viability was evaluated, and activity levels of the PI3K/Akt/GSK3/β-catenin pathway. Our results indicate that some beneficial effects of estradiol were abolished in the presence of progesterone, particularly in the cerebral cortex (core). However, the combinatorial treatment showed positive effects in the hippocampus.

  11. Dopaminergic activity is reduced in the prefrontal cortex and increased in the nucleus accumbens of rats predisposed to develop amphetamine self-administration.

    PubMed

    Piazza, P V; Rougé-Pont, F; Deminière, J M; Kharoubi, M; Le Moal, M; Simon, H

    1991-12-13

    Individual vulnerability to the reinforcing effects of drugs appear to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with higher locomotor responses to novelty (High Responders, HR) tend to acquire amphetamine SA, while animals with the lower responses (Low Responders, LR) do not. In this study, we examined whether activity of dopaminergic (DA) and serotoninergic (5-HT) systems differed between HR and LR animals. These transmitter systems are thought to be involved in the reinforcing effects of psychostimulants. Animals from both groups were sacrificed under basal conditions and after exposure for 30 or 120 min to a novel environment, and the DA, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-HT, and 5-hydroxyindolacetic acid (5-HIAA) contents were determined in the prefrontal cortex, nucleus accumbens and striatum. The HR rats displayed a specific neurochemical pattern: a higher DOPAC/DA ratio in the nucleus accumbens and striatum and a lower one in the prefrontal cortex. Furthermore, HR animals had lower overall 5-HT and 5-HIAA levels, corresponding to the mean of these compounds for the three structures studied over the three environmental conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1726140

  12. Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer.

    PubMed

    Kitamura, K; Takahashi, T; Kotani, T; Miyagaki, T; Yamaoka, N; Tsurumi, H; Noguchi, A; Yamaguchi, T

    1992-11-15

    This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft-bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer.

  13. Administration of human platelet-rich plasma reduces infarction volume and improves motor function in adult rats with focal ischemic stroke.

    PubMed

    Zhang, Ying; Ying, Guomin; Ren, Changhong; Jizhang, Yunneng; Brogan, David; Liu, Zongjian; Li, Sijie; Ding, Yuchuan; Borlongan, Cesar V; Zhang, Jian; Ji, Xunming

    2015-01-12

    Platelet-rich plasma (PRP) is a milieu of bioactive factors, including platelet derived growth factor, transforming growth factor beta, among many others. Despite accumulating evidence on PRP's safety and efficacy for treating musculoskeletal injuries, limited studies have been performed using PRP in brain disorders. This study aimed to explore the potential benefits of administration of human PRP lysate after ischemic stroke in rats. An ischemic stroke model was generated by occlusion of the right middle cerebral artery, then 90 min later, stroke rats were randomly assigned to receive local infusion to the ischemic area of human PRP lysate, human albumin solution (HSA), saline or no treatment at all. An additional group of stroke rats received systemic infusion of human PRP lysate to further assess the therapeutic effects of this treatment. Results showed that while local infusion of HSA or saline, and systemic administration of human PRP lysate, compared to no treatment significantly reduced infarct volume (37.4%, 40.1%, and 39.9% vs 49.7%) and neurological deficit score (2.2, 2.6, and 2.8 vs 3.7), the greatest neuroprotection (31.0% infarct volume and 1.6 neurological deficit score) was found in stroke animals that received local intra-arterial infusion of human PRP lysate (p's<0.05). In conclusion, administration of human PRP attenuates brain injury after focal ischemia. Our results suggest PRP should be investigated further as a potential point-of-care biomaterial following stroke. PMID:25452023

  14. Environmental enrichment, administered after establishment of cocaine self-administration, reduces lever pressing in extinction and during a cocaine context renewal test.

    PubMed

    Ranaldi, Robert; Kest, Karen; Zellner, Margaret; Hachimine-Semprebom, Priscila

    2011-08-01

    The objective of this study was to test the hypothesis that environmental enrichment (EE) administered to rats previously trained to self-administer cocaine would reduce responding in extinction and in a cocaine-context renewal test. Long-Evans male rats were trained to press an active lever reinforced by cocaine (1.0 mg/kg/injection) under a fixed-ratio 1 schedule of reinforcement (inactive lever presses produced no consequences). After stable responding was established, all rats were given a 10-day break from the operant chambers followed by random assignment to EE (larger cages equipped with visual and auditory stimuli) or control (standard housing) group conditions in which they lived for the remainder of the experiment. Ten days after this move, rats were exposed to 10 extinction-responding sessions in a context different from the one in which self-administration occurred, followed by a context-renewal session occurring in the original self-administration context. The EE group responded significantly less in both the extinction and context-renewal sessions compared with the control group. These results suggest that EE reduces the ability of cocaine-associated stimuli to control cocaine-related responding.

  15. Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

    NASA Technical Reports Server (NTRS)

    Cheung, E. V.; Tidball, J. G.

    2003-01-01

    OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

  16. Reactive arthritis

    PubMed Central

    Hind, C. R. K.

    1982-01-01

    Reactive arthritis is a rare complication of certain infections. The similar features and HLA associations with the seronegative arthropathies have raised the possibility that the latter may be forms of reactive arthritis. This review describes the clinical and epidemiological features, and the recent advances in our understanding of the underlying pathogenesis of reactive arthritis. PMID:7100033

  17. Bacteriophage administration significantly reduces Shigella colonization and shedding by Shigella-challenged mice without deleterious side effects and distortions in the gut microbiota

    PubMed Central

    Mai, Volker; Ukhanova, Maria; Reinhard, Mary K; Li, Manrong; Sulakvelidze, Alexander

    2015-01-01

    We used a mouse model to establish safety and efficacy of a bacteriophage cocktail, ShigActive™, in reducing fecal Shigella counts after oral challenge with a susceptible strain. Groups of inbred C57BL/6J mice challenged with Shigella sonnei strain S43-NalAcR were treated with a phage cocktail (ShigActive™) composed of 5 lytic Shigella bacteriophages and ampicillin. The treatments were administered (i) 1 h after, (ii) 3 h after, (iii) 1 h before and after, and (iv) 1 h before bacterial challenge. The treatment regimens elicited a 10- to 100-fold reduction in the CFU's of the challenge strain in fecal and cecum specimens compared to untreated control mice, (P < 0.05). ShigActiveTM treatment was at least as effective as treatment with ampicillin but had a significantly less impact on the gut microbiota. Long-term safety studies did not identify any side effects or distortions in overall gut microbiota associated with bacteriophage administration. Shigella phages may be therapeutically effective in a “classical phage therapy” approach, at least during the early stages after Shigella ingestion. Oral prophylactic “phagebiotic” administration of lytic bacteriophages may help to maintain a healthy gut microbiota by killing specifically targeted bacterial pathogens in the GI tract, without deleterious side effects and without altering the normal gut microbiota. PMID:26909243

  18. Endothelial Nitric Oxide Synthase Reduces Crescentic and Necrotic Glomerular Lesions, Reactive Oxygen Production, and MCP1 Production in Murine Lupus Nephritis

    PubMed Central

    Gilkeson, Gary S.; Mashmoushi, Ahmad K.; Ruiz, Phillip; Caza, Tiffany N.; Perl, Andras; Oates, Jim C.

    2013-01-01

    Systemic lupus erythematosus, in both animal models and in humans, is characterized by autoantibody production followed by immune complex deposition in target tissues. Ensuing target organ damage is modulated by reactive intermediates, including reactive nitrogen and oxygen species, through as of now incompletely understood mechanisms. Endothelial nitric oxide synthase is known to impact vascular reactivity; however its impact on reactive intermediate production and inflammatory renal disease is less well defined. In this study, we assessed the impact of endothelial nitric oxide synthase (eNOS) on disease in lupus prone MRL/lpr mice. Mice lacking eNOS developed earlier more severe disease with decreased survival. eNOS deficient mice died sooner and developed significantly more glomerular crescents, necrosis, inflammatory infiltrates and vasculitis, indicating a role for eNOS in modulating these renal lesions. Immune complex deposition was similar between groups, indicating the impact of eNOS is distal to antibody/complement glomerular deposition. Urinary nitric oxide production was decreased in the eNOS deficient mice, while proteinuria was increased. Urinary monocyte chemotactic protein-1 was also increased in the knockout mice. CD4+ T cells from MRL/lpr mice demonstrated mitochondrial hyperpolarization, increased nitric oxide and superoxide production and increased calcium flux compared to B6 control mice. Deficiency of eNOS resulted in decreased nitric oxide and mitochondrial calcium levels but had no effect on mitochondrial hyperpolarization. Renal cortices from MRL/lpr mice that are eNOS deficient demonstrated increased superoxide production, which was blocked by both nitric oxide synthase and NADPH oxidase inhibitors. These studies thus demonstrate a key role for eNOS in modulating renal disease in lupus prone MRL/lpr mice. The impact appears to be mediated by effects on superoxide production in the kidney, impacting downstream mediators such as monocyte

  19. Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

    PubMed Central

    YAMASHITA, KEISHI; SAKURAMOTO, SHINICHI; MIENO, HIROAKI; NEMOTO, MASAYUKI; SHIBATA, TOMOTAKA; KATADA, NATSUYA; OHTSUKI, SHIGEAKI; SAKAMOTO, YASUTOSHI; HOSHI, KEIKA; WANG, GUOQIN; HEMMI, OSAMU; SATOH, TOSHIHIKO; KIKUCHI, SHIRO; WATANABE, MASAHIKO

    2015-01-01

    Systemic abrogation of TGF-β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-β was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-β ranged from 1.85–43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-β between groups A and B (P=0.019). PSK reduced the plasma TGF-β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID:26137253

  20. Intrathecal Administration of Tempol Reduces Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Increasing SOD Activity and Inhibiting NGF Expression.

    PubMed

    Zhao, Baisong; Pan, Yongying; Wang, Zixin; Tan, Yonghong; Song, Xingrong

    2016-08-01

    We investigate the antinociceptive effect of intrathecal and intraperitoneal tempol administration in a rat model of chronic constriction injury (CCI)-induced neuropathic pain and explore the underlying antinociceptive mechanisms of tempol. Rats were randomly assigned to four groups (n = 8 per group): sham group, CCI group, Tem1 group (intrathecal injection of tempol), and Tem2 group (intraperitoneal injection of tempol). Neuropathic pain was induced by CCI of the sciatic nerve. Tempol was intrathecally or intraperitoneally administered daily for 7 days beginning on postoperative day one. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. Structural changes were examined by hematoxylin and eosin staining, toluidine blue staining, and electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using the thiobarbituric acid and nitroblue tetrazolium methods, respectively. Nerve growth factor (NGF) expression levels were determined by immunohistochemistry and Western blot. Intrathecal, but not intraperitoneal, injection of tempol produced a persistent antinociceptive effect. Intraperitoneal injection of tempol did not result in high enough concentration of tempol in the cerebrospinal fluid. Intrathecal, but not intraperitoneal, injection of tempol inhibited CCI-induced structural damage in the spinal cord reduced MDA levels, and increased SOD activities in the spinal cord. Furthermore, intrathecal, but not intraperitoneal, injection of tempol further downregulated the expression of NGF in the spinal cord following CCI, and this effect was blocked by p38MAPK inhibitor. Intrathecal injection of tempol produces antinociceptive effects and reduces CCI-induced structural damage in the spinal cord by increasing SOD activities and downregulating the expression of NGF via the p38MAPK pathway. Intraperitoneal administration of tempol does

  1. Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin.

    PubMed

    Wei, Qiang; Liu, Li; Cong, Zhe; Wu, Xiaoxian; Wang, Hui; Qin, Chuan; Molina, Patricia; Chen, Zhiwei

    2016-09-01

    Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ(9)-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ(9)-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ(9)-THC(+)SIV(+), Δ(9)-THC(+)SIV(-), PBO/SIV(+) and PBO/SIV(-) (n = 4/group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ(9)-THC(+)SIV(+) and PBO/SIV(+) macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4(+) T cells and higher persistent levels of Ki67(+)CD8(+) T cells compared with uninfected animals. Moreover, long-term Δ(9)-THC treatment reduced significantly the frequency of circulating IgE(+)B cells. Only one Δ(9)-THC(+)SIV(+) macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV(+) group during the study period. These findings indicate that chronic Δ(9)-THC administration resulted in reduction of IgE(+)B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin. PMID:27109234

  2. Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin.

    PubMed

    Wei, Qiang; Liu, Li; Cong, Zhe; Wu, Xiaoxian; Wang, Hui; Qin, Chuan; Molina, Patricia; Chen, Zhiwei

    2016-09-01

    Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ(9)-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ(9)-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ(9)-THC(+)SIV(+), Δ(9)-THC(+)SIV(-), PBO/SIV(+) and PBO/SIV(-) (n = 4/group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ(9)-THC(+)SIV(+) and PBO/SIV(+) macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4(+) T cells and higher persistent levels of Ki67(+)CD8(+) T cells compared with uninfected animals. Moreover, long-term Δ(9)-THC treatment reduced significantly the frequency of circulating IgE(+)B cells. Only one Δ(9)-THC(+)SIV(+) macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV(+) group during the study period. These findings indicate that chronic Δ(9)-THC administration resulted in reduction of IgE(+)B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin.

  3. Senior Administrators Should Have Administrative Contracts.

    ERIC Educational Resources Information Center

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  4. Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on operant self-administration of a chocolate-flavoured beverage in rats.

    PubMed

    Zaru, Alessandro; Maccioni, Paola; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo

    2013-06-01

    Treatment with a rational combination of standardized extracts of Phaseolus vulgaris and Cynara scolymus reduced food intake and glycemia in rats. The present study was designed to assess the effect of this extract combination and of each single extract in an experimental model of food craving, made up of rats displaying exaggerated seeking and taking behaviors for a chocolate-flavoured beverage. After training to lever-respond for the chocolate-flavoured beverage, rats were treated with vehicle, Phaseolus vulgaris extract alone (200 mg/kg), Cynara scolymus extract alone (400 mg/kg), or combination of Phaseolus vulgaris (200 mg/kg) and Cynara scolymus (400 mg/kg) extracts. The Phaseolus vulgaris extract and the extract combination exerted similar and substantial decrements in the number of lever-responses and amount of self-administered chocolate-flavoured beverage; conversely, the Cynara scolymus extract was totally ineffective. These results suggest that (i) the capacity of the extract combination to reduce the self-administration of the chocolate-flavoured beverage entirely relied on the Phaseolus vulgaris extract, (ii) Phaseolus vulgaris extract may interfere with the mechanisms regulating food-related addictive-like behaviors, and (iii) combinations of Phaseolus vulgaris and Cynara scolymus extracts may possess a broad spectrum of activities, from treatment of metabolic syndrome to overweight, obesity, and possibly food-related addictive disorders.

  5. Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect.

    PubMed

    Din, Fakhar Ud; Mustapha, Omer; Kim, Dong Wuk; Rashid, Rehmana; Park, Jong Hyuck; Choi, Ju Yeon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2015-08-01

    The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32°C. This SLN gave the mean particle size of about 190nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25°C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35°C existed as liquid at room temperature, but gelled at 30-36°C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and Cmax value compared to the hydrogel due to reduced initial burst effect. No

  6. Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect.

    PubMed

    Din, Fakhar Ud; Mustapha, Omer; Kim, Dong Wuk; Rashid, Rehmana; Park, Jong Hyuck; Choi, Ju Yeon; Ku, Sae Kwang; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2015-08-01

    The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32°C. This SLN gave the mean particle size of about 190nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25°C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35°C existed as liquid at room temperature, but gelled at 30-36°C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and Cmax value compared to the hydrogel due to reduced initial burst effect. No

  7. Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course antiretroviral treatment for prevention of maternal–infant transmission

    PubMed Central

    Kuhn, L; Meddows-Taylor, S; Gray, G; Trabattoni, D; Clerici, M; Shearer, G M; Tiemessen, C

    2001-01-01

    T-helper cell responses to HIV have been associated with protection against maternal-infant HIV transmission in the absence of antiretroviral treatment, but the effects of antiretroviral treatment, now widely used for prevention, on development of these cell-mediated responses is unknown. We tested whether development of T-helper cell responses to HIV and other antigens would be affected by exposure to short-course regimens of zidovudine-lamivudine (ZDV-3TC) given to prevent maternal-infant HIV transmission. Cord blood samples were collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in which they were treated with regimens of ZDV-3TC and from 29 infants whose HIV-infected mothers were not treated with any antiretroviral drugs. T-helper cell reactivity to HIV envelope peptides and other antigens was measured in vitro using a sensitive culture supernatant titration assay based on IL-2-dependent proliferation. Infants in the clinical trial were followed to 18 months to determine their HIV infection status, and venous blood samples were re-tested at 4·5 and 9 months for T-cell reactivity to HIV. HIV-stimulated T-helper cell reactivity in cord blood was detected 10-fold less frequently among those exposed to antiretroviral prophylaxis (2·4%) than among those unexposed (24·1%) (P = 0·007). Reductions in HIV-stimulated responses in cord blood occurred despite detectable HIV RNA (mean 3·38 standard deviation 0·76 log10 copies per ml) at delivery among treated women and occurred independent of treatment duration. Our results suggest that short-course antiretroviral treatment given to prevent maternal-infant HIV transmission may attenuate HIV-stimulated T-cell memory responses in the neonate. PMID:11298132

  8. Policy and health implications of using the U.S. Food and Drug Administration product design approach in reducing tobacco product risk.

    PubMed

    Givel, Michael

    2008-06-01

    Purported risk or harm reduction through product design change of cigarettes has occurred in three phases in the U.S. The first phase from the 1940s to the early 1960s included a gradual rise in filtered cigarettes. The second phase, which began in the early 1960s in response to the landmark 1964 U.S. Surgeon General's report that linked smoking with lung cancer and other diseases, included the introduction of purportedly low tar and nicotine cigarettes. Subsequent research found that both filters and low tar and nicotine cigarettes were ineffective approaches to reducing health risks associated with smoking. Despite this, these product design changes were used in tobacco industry marketing campaigns to allay consumer health concerns and stabilize tobacco markets and sales. Since 2004, a new risk or harm reduction phase has occurred with the backing by Philip Morris as well as major U.S. health groups of U.S. Food and Drug Administration legislation that would require disclosure of tobacco ingredients, ban misleading health claims, prohibit or reduce harmful ingredients, and require prior approval of tobacco design, performance changes, and modified risk tobacco products. However, current scientific literature indicates that there is no scientific consensus and little evidence on what tobacco ingredients are linked to particular morbidities and mortalities and at what levels. This will allow the tobacco industry to implicitly or explicitly claim their products are "safer." Instead, health advocates should advocate for scientifically proven policy measures such as smoke free public places or higher tobacco taxes that control and reduce tobacco markets and consumption.

  9. 17β-Estradiol (E-2) administration to male (NZB × SWR)F₁ mice results in increased Id(LN)F₁-reactive memory T-lymphocytes and accelerated glomerulonephritis.

    PubMed

    Feng, F; Silvin, C J; Fiore, N C; Stoll, M L; Price, K E; Shanley, P S; Silverstone, A E; Gavalchin, J

    2012-03-01

    While it has been shown that estradiol treatment accelerates the onset of lupus nephritis with autoantibody production and kidney damage in both male and female lupus-prone mice, the specific mechanism(s) involved are unknown. Our previous work has shown that alterations in Id(LN)F(1)-reactive T cells and Id(LN)F(1)+ antibodies correlated closely with the onset of autoimmune nephritis in female F(1) progeny of SWR and NZB (SNF(1)) mice, supporting a critical role for the Id(LN)F(1) idiotype in the development of disease. Since male SNF(1) mice normally do not develop nephritis, we tested whether administration of 17β-estradiol (E-2) to male SNF(1) mice would increase Id(LN)F(1) IgG levels and autoreactive T cells, and further, induce nephritis. We found that E-2-treated male SNF(1) mice developed nephritis with the same time course and mean survival as normal female SNF(1) mice. Moreover, it appeared that the mechanism involved increased serum Id(LN)F(1)(+)IgG and its deposition in kidney glomeruli, preceded by a striking twofold increase in T-lymphocytes expressing the memory phenotype (CD44(+)CD45RB(lo)) predominantly in the Id(LN)F(1)-reactive T-cell population. In addition, we noted that cells with this phenotype were increased in the nephritic kidneys of treated mice, suggesting a direct involvement of those cells in the renal pathology. E-2 treatment also induced increased numbers of pathogenic Id(LN)F(1)+ antibody-producing B cells and elevated presentation of pathogenic Id(LN)F(1)+ peptide. Taken together, these results suggest a mechanism of E-2-induced acceleration of autoimmune disease in lupus-prone mice may involve expansion of autoreactive idiotypic T and B-cell populations.

  10. REDUCING UNCERTAINTIES IN MODEL PREDICTIONS VIA HISTORY MATCHING OF CO2 MIGRATION AND REACTIVE TRANSPORT MODELING OF CO2 FATE AT THE SLEIPNER PROJECT

    SciTech Connect

    Zhu, Chen

    2015-03-31

    An important question for the Carbon Capture, Storage, and Utility program is “can we adequately predict the CO2 plume migration?” For tracking CO2 plume development, the Sleipner project in the Norwegian North Sea provides more time-lapse seismic monitoring data than any other sites, but significant uncertainties still exist for some of the reservoir parameters. In Part I, we assessed model uncertainties by applying two multi-phase compositional simulators to the Sleipner Benchmark model for the uppermost layer (Layer 9) of the Utsira Sand and calibrated our model against the time-lapsed seismic monitoring data for the site from 1999 to 2010. Approximate match with the observed plume was achieved by introducing lateral permeability anisotropy, adding CH4 into the CO2 stream, and adjusting the reservoir temperatures. Model-predicted gas saturation, CO2 accumulation thickness, and CO2 solubility in brine—none were used as calibration metrics—were all comparable with the interpretations of the seismic data in the literature. In Part II & III, we evaluated the uncertainties of predicted long-term CO2 fate up to 10,000 years, due to uncertain reaction kinetics. Under four scenarios of the kinetic rate laws, the temporal and spatial evolution of CO2 partitioning into the four trapping mechanisms (hydrodynamic/structural, solubility, residual/capillary, and mineral) was simulated with ToughReact, taking into account the CO2-brine-rock reactions and the multi-phase reactive flow and mass transport. Modeling results show that different rate laws for mineral dissolution and precipitation reactions resulted in different predicted amounts of trapped CO2 by carbonate minerals, with scenarios of the conventional linear rate law for feldspar dissolution having twice as much mineral trapping (21% of the injected CO2) as scenarios with a Burch-type or Alekseyev et al.–type rate law for feldspar dissolution (11%). So far, most reactive transport modeling (RTM) studies for

  11. Reduced dimensionality diatom--diatom reactive scattering: Application to a model H sub 2 +A sub 2 r arrow H+HA sub 2 reaction

    SciTech Connect

    Sun, Q.; Bowman, J.M. )

    1990-01-15

    We apply a recently formulated quantum theory of diatom--diatom reactions (Q. Sun and J. M. Bowman, Int. J. Quant. Chem., Quant. Chem. Symp. {bold 23}, 9 (1989)) to a model collinear H{sub 2}+A{sub 2}{r arrow}H+HA{sub 2} reaction, where A has the mass of a hydrogen atom. The theory assumes one diatom bond is nonreactive, and the reactive scattering Hamiltonian is written in terms of hyperspherical and cylindrical coordinates. The potential-energy surface used is the PK2 H+H{sub 2} surface augmented by a harmonic degree of freedom describing the nonreactive A{sub 2}. Details of the formulation and solution of the coupled-channel equations are given, along with convergence tests, and a discussion of the new state-to-state transition probabilities. In particular, the partial quenching of the well-known collinear H+H{sub 2} resonances is noted.

  12. The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.

    PubMed

    Harvey-Lewis, Colin; Li, Zhaoxia; Higgins, Guy A; Fletcher, Paul J

    2016-02-01

    Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction.

  13. Reduced Step Edges on Rutile TiO2(110) as Competing Defects to Oxygen Vacancies on the Terraces and Reactive Sites for Ethanol Dissociation

    NASA Astrophysics Data System (ADS)

    Martinez, U.; Hansen, J. Ø.; Lira, E.; Kristoffersen, H. H.; Huo, P.; Bechstein, R.; Lægsgaard, E.; Besenbacher, F.; Hammer, B.; Wendt, S.

    2012-10-01

    The rutile TiO2(110) surface is the most studied surface of titania and considered as a prototype of transition metal oxide surfaces. Reactions on flat TiO2(110)-(1×1) surfaces are well studied, but the processes occurring on the step edges have barely been considered. Based on scanning tunneling microscopy studies, we here present experimental evidence for the existence of O vacancies along the ⟨11¯1⟩R step edges (OS vac.’s) on rutile TiO2(110). Both the distribution of bridging O vacancies on the terraces and temperature-programed reaction experiments of ethanol-covered TiO2(110) point to the existence of the OS vac.’s. Based on experiments and density functional theory calculations, we show that OS vac.’s are reactive sites for ethanol dissociation via O-H bond scission. Implications of these findings are discussed.

  14. Mass Administration of Ivermectin for the Elimination of Onchocerciasis Significantly Reduced and Maintained Low the Prevalence of Strongyloides stercoralis in Esmeraldas, Ecuador

    PubMed Central

    Anselmi, Mariella; Buonfrate, Dora; Guevara Espinoza, Angel; Prandi, Rosanna; Marquez, Monica; Gobbo, Maria; Montresor, Antonio; Albonico, Marco; Racines Orbe, Marcia; Bisoffi, Zeno

    2015-01-01

    Objectives To evaluate the effect of ivermectin mass drug administration on strongyloidiasis and other soil transmitted helminthiases. Methods We conducted a retrospective analysis of data collected in Esmeraldas (Ecuador) during surveys conducted in areas where ivermectin was annually administered to the entire population for the control of onchocerciasis. Data from 5 surveys, conducted between 1990 (before the start of the distribution of ivermectin) and 2013 (six years after the interruption of the intervention) were analyzed. The surveys also comprised areas where ivermectin was not distributed because onchocerciasis was not endemic. Different laboratory techniques were used in the different surveys (direct fecal smear, formol-ether concentration, IFAT and IVD ELISA for Strongyloides stercoralis). Results In the areas where ivermectin was distributed the strongyloidiasis prevalence fell from 6.8% in 1990 to zero in 1996 and 1999. In 2013 prevalence in children was zero with stool examination and 1.3% with serology, in adult 0.7% and 2.7%. In areas not covered by ivermectin distribution the prevalence was 23.5% and 16.1% in 1996 and 1999, respectively. In 2013 the prevalence was 0.6% with fecal exam and 9.3% with serology in children and 2.3% and 17.9% in adults. Regarding other soil transmitted helminthiases: in areas where ivermectin was distributed the prevalence of T. trichiura was significantly reduced, while A. lumbricoides and hookworms were seemingly unaffected. Conclusions Periodic mass distribution of ivermectin had a significant impact on the prevalence of strongyloidiasis, less on trichuriasis and apparently no effect on ascariasis and hookworm infections. PMID:26540412

  15. Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.

    PubMed

    Rivera, Patricia; Pérez-Martín, Margarita; Pavón, Francisco J; Serrano, Antonia; Crespillo, Ana; Cifuentes, Manuel; López-Ávalos, María-Dolores; Grondona, Jesús M; Vida, Margarita; Fernández-Llebrez, Pedro; de Fonseca, Fernando Rodríguez; Suárez, Juan

    2013-01-01

    Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60%) diets were treated with daidzein (50 mg kg(-1)) for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ), and immunohistochemical markers of hippocampal cell apoptosis (caspase-3), gliosis (GFAP and Iba-1), food reward factor FosB and estrogen receptor alpha (ERα) were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU)-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet.

  16. Reactive Power from Distributed Energy

    SciTech Connect

    Kueck, John; Kirby, Brendan; Rizy, Tom; Li, Fangxing; Fall, Ndeye

    2006-12-15

    Distributed energy is an attractive option for solving reactive power and distribution system voltage problems because of its proximity to load. But the cost of retrofitting DE devices to absorb or produce reactive power needs to be reduced. There also needs to be a market mechanism in place for ISOs, RTOs, and transmission operators to procure reactive power from the customer side of the meter where DE usually resides. (author)

  17. Insulin improves in vitro survival of equine preantral follicles enclosed in ovarian tissue and reduces reactive oxygen species production after culture.

    PubMed

    Aguiar, F L N; Lunardi, F O; Lima, L F; Rocha, R M P; Bruno, J B; Magalhães-Padilha, D M; Cibin, F W S; Rodrigues, A P R; Gastal, M O; Gastal, E L; Figueiredo, J R

    2016-04-01

    This study investigated the effect of insulin concentration on the in vitro culture of equine preantral follicles enclosed in ovarian tissue. Ovarian tissue samples were immediately fixed (noncultured control) or cultured for 1 or 7 days in α-MEM(+) supplemented with 0 ng/mL, 10 ng/mL, or 10 μg/mL insulin. Ovarian tissues were processed and analyzed by classical histology. Culture medium samples were collected after 1 and 7 days of culture for steroid and reactive oxygen species (ROS) analyses. The percentage of morphologically normal follicles was greater (P < 0.001) in insulin-treated groups after 1 day of culture; likewise, more (P < 0.02) normal follicles were observed after 7 days of culture in medium supplemented with 10-ng/mL insulin. Furthermore, an increase (P < 0.01) in developing (transition, primary, and secondary) follicles between Days 1 and 7 of culture was observed only with the 10-ng/mL insulin treatment. ROS production after 1 or 7 days of culture was lower (P < 0.0001) in medium with 10-ng/mL insulin than the other treatments. Ovarian tissues containing preantral follicles were able to produce estradiol and progesterone after 1 and 7 days of culture; however, treatments did not differ in steroid production. In conclusion, the use of a physiological concentration (10 ng/mL) of insulin rather than the previously reported concentration (10 μg/mL) for in vitro culture of equine preantral follicles improved follicular survival and growth and lowered oxidative stress. Results from this study shed light on new perspectives for producing an appropriate medium to improve equine preantral follicle in vitro survival and growth.

  18. Hyperbaric Oxygen Reduces Production of Reactive Oxygen Species in Neutrophils from Polytraumatized Patients Yielding in the Inhibition of p38 MAP Kinase and Downstream Pathways.

    PubMed

    Grimberg-Peters, Deborah; Büren, Carina; Windolf, Joachim; Wahlers, Thorsten; Paunel-Görgülü, Adnana

    2016-01-01

    Trauma represents the leading cause of death among young people in western countries. Among the beneficial role of neutrophils in host defence, excessive priming and activation of neutrophils after major trauma lead to an overwhelming inflammatory response and secondary host tissue injury due to the release of toxic metabolites and enzymes. Hyperbaric oxygen (HBO) therapy has been proposed to possess antiinflammatory effects and might represent an appropriate therapeutic option to lower inflammation in a broad range of patients. Here, we studied the effects of HBO on the activity of neutrophils isolated from severely injured patients (days 1-2 after trauma), in fact on the production of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs). We found exposure to HBO therapy to significantly diminish phorbol-12-myristate-13-acetate (PMA)-induced ROS production in neutrophils isolated from patients and healthy volunteers. At the same time, marked decrease in NETs release was found in control cells and a less pronounced reduction in patient neutrophils. Impaired ability to produce ROS following exposure to HBO was demonstrated to be linked to a strong downregulation of the activity of p38 MAPK. Only slight suppression of ERK activity could be found. In addition, HBO did not influence neutrophil chemotaxis or apoptosis, respectively. Collectively, this study shows for the first time that HBO therapy suppresses ROS production in inflammatory human neutrophils, and thus might impair ROS-dependent pathways, e.g. kinases activation and NETs release. Thus, HBO might represent a feasible therapy for patients suffering from systemic inflammation, including those with multiple trauma. PMID:27529549

  19. Hyperbaric Oxygen Reduces Production of Reactive Oxygen Species in Neutrophils from Polytraumatized Patients Yielding in the Inhibition of p38 MAP Kinase and Downstream Pathways

    PubMed Central

    Windolf, Joachim; Wahlers, Thorsten

    2016-01-01

    Trauma represents the leading cause of death among young people in western countries. Among the beneficial role of neutrophils in host defence, excessive priming and activation of neutrophils after major trauma lead to an overwhelming inflammatory response and secondary host tissue injury due to the release of toxic metabolites and enzymes. Hyperbaric oxygen (HBO) therapy has been proposed to possess antiinflammatory effects and might represent an appropriate therapeutic option to lower inflammation in a broad range of patients. Here, we studied the effects of HBO on the activity of neutrophils isolated from severely injured patients (days 1–2 after trauma), in fact on the production of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs). We found exposure to HBO therapy to significantly diminish phorbol-12-myristate-13-acetate (PMA)-induced ROS production in neutrophils isolated from patients and healthy volunteers. At the same time, marked decrease in NETs release was found in control cells and a less pronounced reduction in patient neutrophils. Impaired ability to produce ROS following exposure to HBO was demonstrated to be linked to a strong downregulation of the activity of p38 MAPK. Only slight suppression of ERK activity could be found. In addition, HBO did not influence neutrophil chemotaxis or apoptosis, respectively. Collectively, this study shows for the first time that HBO therapy suppresses ROS production in inflammatory human neutrophils, and thus might impair ROS-dependent pathways, e.g. kinases activation and NETs release. Thus, HBO might represent a feasible therapy for patients suffering from systemic inflammation, including those with multiple trauma. PMID:27529549

  20. Cholesterol induces surface localization of polyphenols in model membranes thus enhancing vesicle stability against lysozyme, but reduces protection of distant double bonds from reactive-oxygen species.

    PubMed

    de Athayde Moncorvo Collado, Alejandro; Dupuy, Fernando G; Morero, Roberto D; Minahk, Carlos

    2016-07-01

    The main scope of the present study was to analyze the membrane interaction of members of different classes of polyphenols, i.e. resveratrol, naringenin, epigallocatechin gallate and enterodiol, in model systems of different compositions and phase states. In addition, the possible association between membrane affinity and membrane protection against both lipid oxidation and bilayer-disruptive compounds was studied. Gibbs monolayer experiments indicated that even though polyphenols showed poor surface activity, it readily interacted with lipid films. Actually, a preferential interaction with expanded monolayers was observed, while condensed and cholesterol-containing monolayers decreased the affinity of these phenolic compounds. On the other hand, fluorescence anisotropy studies showed that polyphenols were able to modulate membrane order degree, but again this effect was dependent on the cholesterol concentration and membrane phase state. In fact, cholesterol induced a surface rather than deep into the hydrophobic core localization of phenolic compounds in the membranes. In general, the polyphenolic molecules tested had a better antioxidant activity when they were allowed to get inserted into the bilayers, i.e. in cholesterol-free membranes. On the other hand, a membrane-protective effect against bilayer permeabilizing activity of lysozyme, particularly in the presence of cholesterol, could be assessed. It can be hypothesized that phenolic compounds may protect membrane integrity by loosely covering the surface of lipid vesicles, once cholesterol push them off from the membrane hydrophobic core. However, this cholesterol-driven distribution may lead to a reduced antioxidant activity of linoleic acid double bonds.

  1. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

    SciTech Connect

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-12-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 {mu}g/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 {mu}g/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration.

  2. Sulfur K-Edge X-Ray Absorption Spectroscopy And Density Functional Theory Calculations on Superoxide Reduc Tase: Role of the Axial Thiolate in Reactivity

    SciTech Connect

    Dey, A.; Jenney, F.E., Jr.; Adams, M.W.; Johnson, M.K.; Hodgson, K.O.; Hedman, B.; Solomon, E.I.; /Stanford U., Chem. Dept. /Athens U. /SLAC, SSRL

    2007-10-26

    Superoxide reductase (SOR) is a non-heme iron enzyme that reduces superoxide to peroxide at a diffusion-controlled rate. Sulfur K-edge X-ray absorption spectroscopy (XAS) is used to investigate the ground-state electronic structure of the resting high-spin and CN{sup -} bound low-spin Fe{sup III} forms of the 1Fe SOR from Pyrococcus furiosus. A computational model with constrained imidazole rings (necessary for reproducing spin states), H-bonding interaction to the thiolate (necessary for reproducing Fe-S bond covalency of the high-spin and low-spin forms), and H-bonding to the exchangeable axial ligand (necessary to reproduce the ground state of the low-spin form) was developed and then used to investigate the enzymatic reaction mechanism. Reaction of the resting ferrous site with superoxide and protonation leading to a high-spin Fe{sup III}-OOH species and its subsequent protonation resulting in H2O2 release is calculated to be the most energetically favorable reaction pathway. Our results suggest that the thiolate acts as a covalent anionic ligand. Replacing the thiolate with a neutral noncovalent ligand makes protonation very endothermic and greatly raises the reduction potential. The covalent nature of the thiolate weakens the Fe{sup III} bond to the proximal oxygen of this hydroperoxo species, which raises its pKa by an additional 5 log units relative to the pK{sub a} of a primarily anionic ligand, facilitating its protonation. A comparison with cytochrome P450 indicates that the stronger equatorial ligand field from the porphyrin results in a low-spin Fe{sup III}-OOH species that would not be capable of efficient H2O2 release due to a spin-crossing barrier associated with formation of a high-spin 5C Fe{sup III} product. Additionally, the presence of the dianionic porphyrin {pi} ring in cytochrome P450 allows O-O heterolysis, forming an Fe{sup IV}-oxo porphyrin radical species, which is calculated to be extremely unfavorable for the non-heme SOR ligand

  3. Repeated methylphenidate administration during lactation reduces maternal behavior, induces maternal tolerance, and increases anxiety-like behavior in pups in adulthood.

    PubMed

    Ponchio, R A; Teodorov, E; Kirsten, T B; Coelho, C P; Oshiro, A; Florio, J C; Bernardi, M M

    2015-01-01

    Methylphenidate (MPD) is a dopamine uptake inhibitor and the most commonly prescribed drug for the treatment of attention-deficit/hyperactivity disorder in children. Several studies have shown that such stimulants as cocaine and amphetamine that are administered during gestation and lactation may disrupt maternal behavior. Also, MPD is used in lactation. Repeated MPD administration can induce either sensitization or tolerance. The aim of the present study was to investigate whether repeated MPD administration alters maternal behavior and promotes tolerance or sensitization in these females. The effects in adult offspring were also examined in models of anxiety. Methylphenidate (5mg/kg) was administered from lactation day 2 to 4, and maternal pup retrieval behavior was assessed. This treatment was continued until lactation day 7. At weaning, the dams received a challenge dose of MPD, and general activity was evaluated in the open field. Striatal monoamine and metabolite levels were also measured to determine whether this treatment promotes behavioral or biochemical plasticity. The long-term behavioral effects of MPD exposure were evaluated in pups in adulthood. The results showed an increase in the latency to retrieve the first, second, and third pups and a decrease in the number of dams that retrieved all pups. After a challenge dose of MPD, the dams exhibited a decrease in locomotion frequency, an increase in immobility duration in the open field, and a decrease in striatal serotonin levels. In pups, anxiety-like behavior increased in the light/dark box test. These results indicate that repeated MPD administration during early lactation impairs maternal behavior, likely by decreasing maternal motivation. Repeated MPD administration induced maternal tolerance at weaning after a challenge dose of MPD, suggesting the development of central nervous system plasticity. In pups, maternal exposure to MPD during early lactation induced long-term effects and increased

  4. Repeated methylphenidate administration during lactation reduces maternal behavior, induces maternal tolerance, and increases anxiety-like behavior in pups in adulthood.

    PubMed

    Ponchio, R A; Teodorov, E; Kirsten, T B; Coelho, C P; Oshiro, A; Florio, J C; Bernardi, M M

    2015-01-01

    Methylphenidate (MPD) is a dopamine uptake inhibitor and the most commonly prescribed drug for the treatment of attention-deficit/hyperactivity disorder in children. Several studies have shown that such stimulants as cocaine and amphetamine that are administered during gestation and lactation may disrupt maternal behavior. Also, MPD is used in lactation. Repeated MPD administration can induce either sensitization or tolerance. The aim of the present study was to investigate whether repeated MPD administration alters maternal behavior and promotes tolerance or sensitization in these females. The effects in adult offspring were also examined in models of anxiety. Methylphenidate (5mg/kg) was administered from lactation day 2 to 4, and maternal pup retrieval behavior was assessed. This treatment was continued until lactation day 7. At weaning, the dams received a challenge dose of MPD, and general activity was evaluated in the open field. Striatal monoamine and metabolite levels were also measured to determine whether this treatment promotes behavioral or biochemical plasticity. The long-term behavioral effects of MPD exposure were evaluated in pups in adulthood. The results showed an increase in the latency to retrieve the first, second, and third pups and a decrease in the number of dams that retrieved all pups. After a challenge dose of MPD, the dams exhibited a decrease in locomotion frequency, an increase in immobility duration in the open field, and a decrease in striatal serotonin levels. In pups, anxiety-like behavior increased in the light/dark box test. These results indicate that repeated MPD administration during early lactation impairs maternal behavior, likely by decreasing maternal motivation. Repeated MPD administration induced maternal tolerance at weaning after a challenge dose of MPD, suggesting the development of central nervous system plasticity. In pups, maternal exposure to MPD during early lactation induced long-term effects and increased

  5. Ketoconazole ion-exchange fiber complex: a novel method to reduce the individual difference of bioavailability in oral administration caused by gastric anacidity.

    PubMed

    Xin, Che; Li-hong, Wang; Jing, Yuan; Yang, Yang; Yue, Yuan; Qi-fang, Wang; San-ming, Li

    2013-01-01

    Water insoluble faintly alkaline drugs often have potential absorption problem in gastrointestinal tract in oral administration for patients with gastric anacidity. The purpose of the present study is to develop a novel method to improve the absorption of the water insoluble faintly alkaline drug in peroral administration. This method is based on ion exchange of ion-exchange fibers. Water-insoluble faintly alkaline drug ketoconazole was used as a model drug. Ketoconazole and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction. This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange. Confirmed by the X-ray diffraction and the differential scanning calorimetry (DSC), the ketoconazole combined onto the ion-exchange fibers was in a highly molecular level dispersed state. The improved dissolution of ketoconazole ion-exchange fiber complexes is likely to originate from this ketoconazole's highly dispersed state. Furthermore, due to this ketoconazole's highly dispersed state, ketoconazole ion-exchange fiber complexes significantly decreased the individual difference of absorption in oral administration of ketoconazole caused by the fluctuation of the acid degree in the gastric fluid.

  6. What Is Reactive Arthritis?

    MedlinePlus

    ... Arthritis PDF Version Size: 69 KB November 2014 What is Reactive Arthritis? Fast Facts: An Easy-to- ... Information About Reactive Arthritis and Other Related Conditions What Causes Reactive Arthritis? Sometimes, reactive arthritis is set ...

  7. Skin Injuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons) Irradiation

    PubMed Central

    Kiang, Juliann G.; Ledney, G. David

    2013-01-01

    Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI)) increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6) concentrations in serum were amplified by skin wound trauma. Herein, the IL-6-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), immunoglobulin M (IgM), and prostaglandin E2 (PGE2) were evaluated after skin injuries given following a mixed radiation environment that might be found after a nuclear incident. In this report, mice received 3 Gy of reactor-produced mixed field (n + γ-photons) radiations at 0.38 Gy/min followed by nonlethal skin wounding or burning. Both wounds and burns reduced survival and increased CRP, C3, and PGE2 in serum after radiation. Decreased IgM production along with an early rise in corticosterone followed by a subsequent decrease was noted for each RCI situation. These results suggest that RCI-induced alterations of corticosterone, CRP, C3, IgM, and PGE2 cause homeostatic imbalance and may contribute to reduced survival. Agents inhibiting these responses may prove to be therapeutic for RCI and improve related survival. PMID:24175013

  8. Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

    PubMed

    Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

    2014-04-23

    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

  9. IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis

    PubMed Central

    Mittal, Rahul; Gonzalez-Gomez, Ignacio; Panigrahy, Ashok; Goth, Kerstin; Bonnet, Richard

    2010-01-01

    Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10−/− mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis. PMID:20498022

  10. IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis.

    PubMed

    Mittal, Rahul; Gonzalez-Gomez, Ignacio; Panigrahy, Ashok; Goth, Kerstin; Bonnet, Richard; Prasadarao, Nemani V

    2010-06-01

    Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcgammaRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10-/- mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10-mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis. PMID:20498022

  11. Life events-induced decrease of corticosteroid type I receptors is associated with reduced corticosterone feedback and enhanced vulnerability to amphetamine self-administration.

    PubMed

    Maccari, S; Piazza, P V; Deminière, J M; Lemaire, V; Mormède, P; Simon, H; Angelucci, L; Le Moal, M

    1991-04-26

    In this study, we attempted to find out whether a social stress-induced increase in the vulnerability to acquire amphetamine self-administration was associated with a change in number of hippocampal corticosteroid receptors. This was examined in two types of sex-mixed colonies of rats. Animals were maintained for 4 weeks in: (1) 'stable social condition', membership did not change after constitution of the colony; (2) 'unstable social condition', the males were changed daily in a random design. The animals living in the 'stable social' conditions had: (1) a lower number of hippocampal type I corticosteroid receptors; (2) a longer duration of the increase in plasma corticosterone after exposure to novelty; (3) a higher vulnerability to acquire amphetamine self-administration. These findings suggest that a decrease in hippocampal type I corticosteroid receptors may be one of the biological mechanisms responsible for the impaired corticosterone feedback control observed in vulnerable animals. These findings throw more light on the role of hypothalamo-pituitary-adrenal axis in the modulation of adaptive behavior. The availability of drugs which are specific for corticosteroid receptors could represent a new approach to the therapy of certain behavioral disturbances. PMID:1860073

  12. Structural characteristics and reactivity/reducibility properties of dispersed and bilayered V{sub 2}O{sub 5}/TiO{sub 2}/SiO{sub 2} catalysts

    SciTech Connect

    Gao, X.; Wachs, I.E.; Bare, S.R.; Fierro, J.L.G.

    1999-01-28

    Dispersed and bilayered V{sub 2}O{sub 5}/TiO{sub 2}/SiO{sub 2} catalysts were successfully synthesized by the incipient wetness impregnation method, and their surface structures under various conditions were extensively investigated by combined in situ Raman, UV-vis-NIR diffuse reflectance and X-ray absorption near-edge spectroscopies, as well as X-ray photoelectron spectroscopy. Temperature-programmed reduction and methanol oxidation were employed as chemical probe reactions to examine the reducibility and reactivity/selectivity of these catalysts. The spectroscopic results revealed that both vanadium oxide and titanium oxide on SiO{sub 2} are dispersed as two-dimensional metal oxide overlayers. The surface vanadium oxide species on the dispersed TiO{sub 2}/SiO{sub 2} are predominantly isolated VO{sub 4} units [O{double_bond}V(O-support){sub 3}] in the dehydrated state and become polymerized VO{sub 5}/VO{sub 6} units upon hydration. The surface vanadium oxide species preferentially interact with the surface titanium oxide species on silica, and the V(V) cations possess oxygenated ligands of Si(IV){single_bond}O{sup {minus}} and Ti(IV){single_bond}O{sup {minus}} in the O{double_bond}V(O-support){sub 3} unit with varying ratios from 3:0 to 0:3, which depends on the vanadia and titania loadings. The varying ratio of the Si(IV){single_bond}O{sup {minus}} and Ti(IV){single_bond}O{sup {minus}} oxygenated ligands significantly affects the chemical properties of the isolated VO{sub 4} units. Consequently, the reducibility of the surface vanadium oxide species is altered and the reduction occurs over a wider temperature range. In addition, the methanol oxidation turn-over frequency of the surface VO{sub 4} species on TiO{sub 2}/SiO{sub 2} increases an order of magnitude relative to V{sub 2}O{sub 5}/SiO{sub 2}. Thus, the oxygenated ligands around the V cations play a critical role in determining the reactivity of the surface vanadium oxide species on the oxide supports.

  13. The Added Value of Water, Sanitation, and Hygiene Interventions to Mass Drug Administration for Reducing the Prevalence of Trachoma: A Systematic Review Examining

    PubMed Central

    Palmer, Stephanie L.

    2013-01-01

    Trachoma is the leading cause of infectious blindness worldwide. The SAFE strategy, the World Health Organization-recommended method to eliminate blinding trachoma, combines developments in water, sanitation, surgery, and antibiotic treatment. Current literature does not focus on the comprehensive effect these components have on one another. The present systematic review analyzes the added benefit of water, sanitation, and hygiene education interventions to preventive mass drug administration of azithromycin for trachoma. Trials were identified from the PubMed database using a series of search terms. Three studies met the complete criteria for inclusion. Though all studies found a significant change in reduction of active trachoma prevalence, the research is still too limited to suggest the impact of the “F” and “E” components on trachoma prevalence and ultimately its effects on blindness. PMID:23990843

  14. Optogenetic stimulation of VTA dopamine neurons reveals that tonic but not phasic patterns of dopamine transmission reduce ethanol self-administration.

    PubMed

    Bass, Caroline E; Grinevich, Valentina P; Gioia, Dominic; Day-Brown, Jonathan D; Bonin, Keith D; Stuber, Garret D; Weiner, Jeff L; Budygin, Evgeny A

    2013-01-01

    There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.

  15. Becoming Reactive by Concretization

    NASA Technical Reports Server (NTRS)

    Prieditis, Armand; Janakiraman, Bhaskar

    1992-01-01

    One way to build a reactive system is to construct an action table indexed by the current situation or stimulus. The action table describes what course of action to pursue for each situation or stimulus. This paper describes an incremental approach to constructing the action table through achieving goals with a hierarchical search system. These hierarchies are generated with transformations called concretizations, which add constraints to a problem and which can reduce the search space. The basic idea is that an action for a state is looked up in the action table and executed whenever the action table has an entry for that state; otherwise, a path is found to the nearest (cost-wise in a graph with costweighted arcs) state that has a mappring from a state in the next highest hierarchy. For each state along the solution path, the successor state in the path is cached in the action table entry for that state. Without caching, the hierarchical search system can logarithmically reduce search. When the table is complete the system no longer searches: it simply reacts by proceeding to the state listed in the table for each state. Since the cached information is specific only to the nearest state in the next highest hierarchy and not the goal, inter-goal transfer of reactivity is possible. To illustrate our approach, we show how an implemented hierarchical search system can completely reactive.

  16. Combined Photothermal and Surface-Enhanced Raman Spectroscopy Effect from Spiky Noble Metal Nanoparticles Wrapped within Graphene-Polymer Layers: Using Layer-by-layer Modified Reduced Graphene Oxide as Reactive Precursors.

    PubMed

    Li, Xiangming; Zhang, Yihe; Wu, Yaling; Duan, Yang; Luan, Xinglong; Zhang, Qian; An, Qi

    2015-09-01

    To fabricate functionally integrated hybrid nanoparticles holds high importance in biomedical applications and is still a challenging task. In this study, we report the first reduced graphene oxide (rGO)-nobel metal hybrid particles that present simultaneously the photothermal and surface-enhanced Raman spectroscopy (SERS) effect from the inorganic part and drug loading, dispersibility, and controllability features from LbL polyelectrolyte multilayers. The hybrid particles where spiky noble metal particles were wrapped within rGO-polyelectrolyte layers were prepared by a facile and controllable method. rGO template modified using polyethylenimine (PEI) and poly(acrylic acid) (PAA) via layer-by-layer technology served as the reactive precursors, and the morphologies of the particles could be facilely controlled via controlling the number of bilayers around the rGO template. The hybrid particle presented low cytotoxicity. After loading doxorubicin hydrochloride, the particles effectively induced cell death, and photothermal treatment further decreased cell viability. rGO-Ag hybrid particles could be prepared similarly. We expect the reported method provides an effective strategy to prepare rGO-noble metal hybrid nanoparticles that find potential biomedical applications. PMID:26269466

  17. Combined Photothermal and Surface-Enhanced Raman Spectroscopy Effect from Spiky Noble Metal Nanoparticles Wrapped within Graphene-Polymer Layers: Using Layer-by-layer Modified Reduced Graphene Oxide as Reactive Precursors.

    PubMed

    Li, Xiangming; Zhang, Yihe; Wu, Yaling; Duan, Yang; Luan, Xinglong; Zhang, Qian; An, Qi

    2015-09-01

    To fabricate functionally integrated hybrid nanoparticles holds high importance in biomedical applications and is still a challenging task. In this study, we report the first reduced graphene oxide (rGO)-nobel metal hybrid particles that present simultaneously the photothermal and surface-enhanced Raman spectroscopy (SERS) effect from the inorganic part and drug loading, dispersibility, and controllability features from LbL polyelectrolyte multilayers. The hybrid particles where spiky noble metal particles were wrapped within rGO-polyelectrolyte layers were prepared by a facile and controllable method. rGO template modified using polyethylenimine (PEI) and poly(acrylic acid) (PAA) via layer-by-layer technology served as the reactive precursors, and the morphologies of the particles could be facilely controlled via controlling the number of bilayers around the rGO template. The hybrid particle presented low cytotoxicity. After loading doxorubicin hydrochloride, the particles effectively induced cell death, and photothermal treatment further decreased cell viability. rGO-Ag hybrid particles could be prepared similarly. We expect the reported method provides an effective strategy to prepare rGO-noble metal hybrid nanoparticles that find potential biomedical applications.

  18. Phenylethynyl Containing Reactive Additives

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Smith, Joseph G., Jr. (Inventor); Hergenrother, Paul M. (Inventor)

    2002-01-01

    Phenylethynyl containing reactive additives were prepared from aromatic diamine, containing phenylethvnvl groups and various ratios of phthalic anhydride and 4-phenylethynviphthalic anhydride in glacial acetic acid to form the imide in one step or in N-methyl-2-pvrrolidinone to form the amide acid intermediate. The reactive additives were mixed in various amounts (10% to 90%) with oligomers containing either terminal or pendent phenylethynyl groups (or both) to reduce the melt viscosity and thereby enhance processability. Upon thermal cure, the additives react and become chemically incorporated into the matrix and effect an increase in crosslink density relative to that of the host resin. This resultant increase in crosslink density has advantageous consequences on the cured resin properties such as higher glass transition temperature and higher modulus as compared to that of the host resin.

  19. A Tariff for Reactive Power

    SciTech Connect

    Kueck, John D; Kirby, Brendan J; Li, Fangxing; Tufon, Christopher; Isemonger, Alan

    2008-07-01

    Two kinds of power are required to operate an electric power system: real power, measured in watts, and reactive power, measured in volt-amperes reactive or VARs. Reactive power supply is one of a class of power system reliability services collectively known as ancillary services, and is essential for the reliable operation of the bulk power system. Reactive power flows when current leads or lags behind voltage. Typically, the current in a distribution system lags behind voltage because of inductive loads such as motors. Reactive power flow wastes energy and capacity and causes voltage droop. To correct lagging power flow, leading reactive power (current leading voltage) is supplied to bring the current into phase with voltage. When the current is in phase with voltage, there is a reduction in system losses, an increase in system capacity, and a rise in voltage. Reactive power can be supplied from either static or dynamic VAR sources. Static sources are typically transmission and distribution equipment, such as capacitors at substations, and their cost has historically been included in the revenue requirement of the transmission operator (TO), and recovered through cost-of-service rates. By contrast, dynamic sources are typically generators capable of producing variable levels of reactive power by automatically controlling the generator to regulate voltage. Transmission system devices such as synchronous condensers can also provide dynamic reactive power. A class of solid state devices (called flexible AC transmission system devices or FACTs) can provide dynamic reactive power. One specific device has the unfortunate name of static VAR compensator (SVC), where 'static' refers to the solid state nature of the device (it does not include rotating equipment) and not to the production of static reactive power. Dynamic sources at the distribution level, while more costly would be very useful in helping to regulate local voltage. Local voltage regulation would reduce

  20. Failed detection of Bovine viral diarrhea virus 2 subgenotype a (BVDV-2a) by direct fluorescent antibody test on tissue samples due to reduced reactivity of field isolates to raw anti-BVDV antibody.

    PubMed

    Yan, Lifang; Pace, Lanny W; Baughman, Brittany; Wilson, Floyd D; Zhang, Shuping; Zhang, Michael Z

    2016-03-01

    Bovine viral diarrhea virus 1 (BVDV-1) is associated with mild or subclinical infections, whereas BVDV-2 is frequently implicated in outbreaks of severe thrombocytopenia and acute fatal disease. In the present study, the carcass of a beef breed cow and tissue samples of a beef calf were received for laboratory diagnosis. Both animals exhibited severe clinical signs compatible with thrombocytopenia or hemorrhagic syndrome. Direct fluorescent antibody test (DFAT) failed to detect BVDV antigen in the tissue specimens of both cases. However, immunohistochemistry (IHC) revealed the presence of BVDV antigen in oral and esophageal mucosa and Peyer patches of the beef breed cow. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) detected BVDV-2 in selected tissues of both animals. Subsequently, BVDV was isolated from both cases and subjected to genetic and serologic characterizations. Mutations in the 5'-untranslated genomic region (5'-UTR) primer and probe binding sites and the E2 gene were associated with reduced efficiency of an established real-time RT-PCR assay and amino acid alterations in the E2 glycoprotein, respectively. Both viral isolates were classified by real-time RT-PCR and phylogenetic analysis as BVDV-2 subgenotype a. Unlike BVDV reference strains Singer and 125c, the isolates cross-reacted with anti-BVDV-1 and anti-BVDV-2 reference sera, indicating antigenic variations in field isolates. The isolates also showed reduced reactivity to porcine anti-BVDV antiserum (the raw serum used to produce BVDV DFA conjugate). In summary, data from the present investigation indicated that genetic and antigenic variations affected the performance of detection assays, especially DFAT, highlighting the need for regular evaluation and modification of BVDV tests.

  1. Medical emergency teams are associated with reduced mortality across a major metropolitan health network after two years service: a retrospective study using government administrative data

    PubMed Central

    2012-01-01

    Introduction Medical emergency teams (MET) are implemented to ensure prompt clinical review of patients with deteriorating physiology with the intention of averting further deterioration, cardiac arrest and death. We sought to determine if MET implementation has led to reductions in hospital mortality across a large metropolitan health network utilising routine administrative data submitted by hospitals to the Department of Health Victoria. Methods The Victorian admissions episodes data set (VAED) contains data on all individual hospital separations in the State of Victoria, Australia. After gaining institutional ethics approval, we extracted data on all acute admissions to metropolitan hospitals for which we had information on the presence and timing of a MET system. Using logistic regression we determined whether there was an effect of MET implementation on mortality controlling for age, gender, Charlson comorbidity diagnostic groupings, emergency admission, same day admission, ICU admission, mechanical ventilation, year, indigenous ethnicity, liaison nurse service and hospital designation. Results 5911533 individual admissions and 73,599 associated deaths from July 1999 to June 2010 were included in the analysis. 52.2% were male and median age was 57(42-72 IQR). Mortality rates for MET and non-MET periods were 3.92 (3.88-3.95 95%CI) and 4.56 (4.51-4.61 95%CI) deaths per 1000 patient days with a rate ratio after adjustment for year of 0.88 (0.86-0.89 95%CI) P < 0.001. In a multivariable logistic regression, mortality was associated with a MET team being active in the hospital for more than 2 years. The odds ratio for mortality in hospitals where a MET system had been in place for greater than 4 years duration was 0.90 (0.88-0.92). Mortality during the first 2 years of a MET system being in place was not statistically different from pre-MET periods. Conclusions Utilising routinely collected administrative data we demonstrated that the presence of a hospital MET

  2. The 'reactive

    NASA Astrophysics Data System (ADS)

    Battista Piccardo, Giovanni; Guarnieri, Luisa

    2010-05-01

    The Ligurian ophiolitic peridotites [South Lanzo, Erro-Tobbio, Internal Ligurides and Corsica] are characterized by the abundance of spinel(Sp) peridotites showing depleted compositions and ranging from Cpx-poor Sp lherzolites to Sp harzburgites. They were recognized in the last decades as refractory residua by MORB-forming partial melting of the asthenosphere, and were similar to abyssal peridotites. Recent structural and compositional studies promoted a better understanding of their structural and compositional features and their genetic processes. In the field these depleted peridotites replace with primary contacts pyroxenite-bearing fertile Sp lherzolites that have been recognized as sub-continental lithospheric mantle. Field relationships evidence that decametric-hectometric bodies of pristine pyroxenite-veined lithospheric Sp lherzolites are preserved as structural remnants within the km-scale masses of depleted peridotites. The depleted peridotites show coarse-grained recrystallized textures and reaction micro-structures indicating pyroxene dissolution and olivine precipitation that have been considered as records of melt/peridotite interaction during reactive diffuse porous flow of undersaturated melts. They show, moreover, contrasting bulk and mineral chemistries that cannot be produced by simple partial melting and melt extraction. In particular, their bulk compositions are depleted in SiO2 and enriched in FeO with respect to refractory residua after any kind of partial melting, as calculated by Niu (1997), indicating that they cannot be formed by simple partial melting and melt extraction processes. Moreover, TiO2 content in Sp is usually significantly higher (up to 0.8-1.0 wt%) than typical TiO2 contents of spinels (usually < 0.1-0.2 wt %) in fertile mantle peridotites and melting refractory residua, indicating that spinel attained element equilibration with a Ti-bearing basaltic melt. The depleted peridotites usually show strongly variable Cpx modal

  3. Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of Amyloid-β in Th1- and Th17-Versions of Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Grant, Jacqueline L.; Ghosn, Eliver Eid Bou; Axtell, Robert C.; Herges, Katja; Kuipers, Hedwich F.; Woodling, Nathan S.; Andreasson, Katrin; Herzenberg, Leonard A.; Herzenberg, Leonore A.; Steinman, Lawrence

    2013-01-01

    β-amyloid-42 (Aβ42) and β-amyloid-40 (Aβ40), major components of senile plaque deposits in Alzheimer’s disease (AD), are considered neurotoxic and pro-inflammatory. In multiple sclerosis (MS), Aβ42 is upregulated in brain lesions and damaged axons. Here we found, unexpectedly, that treatment with either Aβ42 or Aβ40 peptides reduced motor paralysis and brain inflammation in four different models of experimental autoimmune encephalomyelitis (EAE) with attenuation of motor paralysis, reduction of inflammatory lesions in the central nervous system (CNS), and suppression of lymphocyte activation. Aβ42 and Aβ40 treatments were effective in reducing ongoing paralysis induced with adoptive transfer of either autoreactive Th1 or Th17 cells. High-dimensional 14-parameter flow cytometry of peripheral immune cell populations after in vivo Aβ42 and Aβ40 treatment revealed substantial modulations in the percentage of lymphoid and myeloid subsets during EAE. Major pro-inflammatory cytokines and chemokines were reduced in the blood following Aβ peptide treatment. Protection conferred by Aβ treatment did not require its delivery to the brain: adoptive transfer with lymphocytes from donors treated with Aβ42 attenuated EAE in WT recipient mice and Aβ deposition in the brain was not detected in treated EAE mice by immunohistochemical analysis. In contrast to the improvement in EAE with Aβ-treatment, EAE was worse in mice with genetic deletion of the amyloid precursor protein. Therefore, in the absence of Aβ there is exacerbated clinical EAE disease progression. Since Aβ42 and Aβ40 ameliorate experimental autoimmune inflammation targeting the CNS, we might now consider its potential anti-inflammatory role in other neuropathological conditions. PMID:22855462

  4. Continuous administration of low dose rates of physostigmine and hyoscine to guinea-pigs prevents the toxicity and reduces the incapacitation produced by soman poisoning.

    PubMed

    Wetherell, J R

    1994-12-01

    A regime was developed, using mini-osmotic pumps, for the continuous subcutaneous administration of low doses of physostigmine (12.1, 9.7, 4.85 and 2.43 micrograms h-1), in combination with hyoscine (1.94 or 0.39 micrograms h-1), to guinea-pigs for up to 13 days. Physostigmine, in combination with hyoscine, inhibited plasma cholinesterase, and red blood cell and brain acetylcholinesterase, in a concentration-dependent manner, did not affect the normal growth rate of guinea-pigs, and produced no obvious signs of poisoning. A dose rate of 4.85 micrograms h-1 physostigmine and 1.94 micrograms h-1 hyoscine was required to inhibit red cell acetylcholinesterase by 30% and brain acetylcholinesterase by 5-15%, with an accompanying plasma hyoscine concentration of 700-850 pg mL-1. There was an apparent decline in red cell acetylcholinesterase activity during the 13 days. Hyoscine levels were higher in the cholinergic-rich areas of the brain than in the plasma. Continuous pretreatment (1 or 6 days) with physostigmine (4.84 micrograms h-1) and hyoscine (1.94 micrograms h-1) provided complete protection against the lethal effects, and minimized the incapacitation and weight loss produced by soman at a dose equivalent to the LD99 value. Following soman challenge, guinea-pigs exhibited early signs of soman poisoning, but generally these signs of poisoning were minimal by 1-2 h. Extending the pretreatment time to 13 days protected 75% of the guinea-pigs against the lethal effects of soman poisoning. Red cell acetylcholinesterase activity, 24 h after soman poisoning, was higher following continuous pretreatment with physostigmine and hyoscine than after acute treatment with atropine. PMID:7714714

  5. Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model.

    PubMed

    Parra, Edwin Roger; Alveno, Renata Antunes; Faustino, Carolina Brito; Corrêa, Paula Yume Sato Serzedello; Vargas, Camilla Mutai; de Morais, Jymenez; Rangel, Maristela Peres; Velosa, Ana Paula Pereira; Fabro, Alexandre Todorovic; Teodoro, Walcy Rosolia; Capelozzi, Vera Luiza

    2016-08-01

    Type V collagen (Col V) is a "minor" component of normal lung extracellular matrix, which is subjected to decreased and abnormal synthesis in human lung infiltrating adenocarcinoma. We previously reported that a direct link between low amounts of Col V and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis. Moreover, this collagen species was able to trigger DNA fragmentation and impair survival of neoplastic cells. In this study, we have extended our investigation with the aim to obtain further evidence that the death induced by Col V-treatment is of the caspase-9 apoptotic type. We used (1) optical and electron microscopy, (2) quantitation of TUNEL-labeled cells and (3) analysis of the expression levels of Col V and selected genes coding for apoptosis-linked factors, by conventional RT-PCR. BALB/c mice were injected intraperitoneally with 1.5 g/kg body weight of urethane. After urethane injection, the animals received intranasal administration of 20 µg/20 µl of Col V every day during 2 months. We report here that Col V treatment was able to determine significant increase in Col V protein and gene expression and in the percentage of TUNEL-positive cells, to up-regulate caspase-9, resulting in low growth of tumor cells. Our data validate chemical carcinogenesis as a suitable "in vivo" model for further and more detailed studies on the molecular mechanisms of the death response induced by Col V in lung infiltrating adenocarcinoma opening new strategies for treatment.

  6. The administration of a polyvalent mechanical bacterial lysate in elderly patients with COPD results in serological signs of an efficient immune response associated with a reduced number of acute episodes.

    PubMed

    Ricci, Rossella; Palmero, Candida; Bazurro, Gyada; Riccio, Anna Maria; Garelli, Valentina; Di Marco, Eddi; Cirillo, Carmelina; Braido, Fulvio; Canonica, Giorgio Walter; Melioli, Giovanni

    2014-02-01

    The administration of a polyvalent mechanical bacterial lysate (PMBL) in elderly patients with COPD has been shown to reduce the number of exacerbation. This is largely related to the involvement of cells belonging to the innate and the adaptive immune system (including dendritic cells, granulocytes, T and B lymphocytes and NK cells) that actively cooperate inducing the production of specific opsonizing antibodies directed to the antigens of PMBL. We have evaluated the production of antibodies directed to respiratory and systemic pathogens in a group of elderly COPD patients, recruited in a clinical trial, ancillary to a larger multicenter double blind, placebo-controlled, parallel-designed clinical trial in which patients were randomized to daily receive either PMBL or placebo. The treated group not only experienced a reduced number of seroconversion, but also, better controlled the number of infectious episodes and COPD exacerbations. It was thus evident that the administration of PMBL resulted not only effective in inducing the secretion of specific antibodies, but also effective in reducing the infectious episodes trough the potentiation of the antibody-mediated arm of the immune response. PMID:23792312

  7. EBV reactivation as a target of luteolin to repress NPC tumorigenesis

    PubMed Central

    Wu, Chung-Chun; Fang, Chih-Yeu; Hsu, Hui-Yu; Chuang, Hsin-Ying; Cheng, Yu-Jhen; Chen, Yen-Ju; Chou, Sheng-Ping; Huang, Sheng-Yen; Lin, Su-Fang; Chang, Yao; Tsai, Ching-Hwa; Chen, Jen-Yang

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx. Although a combination of radiotherapy with chemotherapy is effective for therapy, relapse and metastasis after remission remain major causes of mortality. Epstein-Barr virus (EBV) is believed to be one of causes of NPC development. We demonstrated previously that EBV reactivation is important for the carcinogenesis of NPC. We sought, therefore, to determine whether EBV reactivation can be a target for retardation of relapse of NPC. After screening, we found luteolin is able to inhibit EBV reactivation. It inhibited EBV lytic protein expression and repressed the promoter activities of two major immediate-early genes, Zta and Rta. Furthermore, luteolin was shown to reduce genomic instability induced by recurrent EBV reactivation in NPC cells. EBV reactivation-induced NPC cell proliferation and migration, as well as matrigel invasiveness, were also repressed by luteolin treatment. Tumorigenicity in mice, induced by EBV reactivation, was decreased profoundly following luteolin administration. Together, these results suggest that inhibition of EBV reactivation is a novel approach to prevent the relapse of NPC. PMID:26967558

  8. Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

    PubMed Central

    Fekete, Éva M; Inoue, Koki; Zhao, Yu; Rivier, Jean E; Vale, Wylie W; Szücs, Attila; Koob, George F; Zorrilla, Eric P

    2009-01-01

    Brain corticotropin-releasing factor/urocortin (CRF/Ucn) systems are hypothesized to control feeding, with central administration of ‘type 2’ urocortins producing delayed anorexia. The present study sought to identify the receptor subtype, brain site, and behavioral mode of action through which Ucn 3 reduces nocturnal food intake in rats. Non-food-deprived male Wistar rats (n = 176) were administered Ucn 3 into the lateral (LV) or fourth ventricle, or into the ventromedial or paraventricular nuclei of the hypothalamus (VMN, PVN) or the medial amygdala (MeA), regions in which Ucn 3 is expressed in proximity to CRF2 receptors. LV Ucn 3 suppressed ingestion during the third–fourth post-injection hours. LV Ucn 3 anorexia was reversed by cotreatment with astressin2-B, a selective CRF2 antagonist and not observed following equimole subcutaneous or fourth ventricle administration. Bilateral intra-VMN and intra-PVN infusion, more potently than LV infusion, reduced the quantity (57–73%) and duration of ingestion (32–68%) during the third–fourth post-infusion hours. LV, intra-PVN and intra-VMN infusion of Ucn 3 slowed the eating rate and reduced intake by prolonging the post-meal interval. Intra-VMN Ucn 3 reduced feeding bout size, and intra-PVN Ucn 3 reduced the regularity of eating from pellet to pellet. Ucn 3 effects were behaviorally specific, because minimal effective anorectic Ucn 3 doses did not alter drinking rate or promote a conditioned taste aversion, and site-specific, because intra-MeA Ucn 3 produced a nibbling pattern of more, but smaller meals without altering total intake. The results implicate the VMN and PVN of the hypothalamus as sites for Ucn 3-CRF2 control of food intake. PMID:17019404

  9. Does the preoperative administration of tranexamic acid reduce perioperative blood loss and transfusion requirements after head neck cancer surgery? A randomized, controlled trial

    PubMed Central

    Das, Anjan; Chattopadhyay, Surajit; Mandal, Debabrata; Chhaule, Subinay; Mitra, Tapobrata; Mukherjee, Anindya; Mandal, Subrata Kumar; Chattopadhyay, Sandip

    2015-01-01

    Background: Head and neck cancer (HNC) surgery is associated with high intraoperative blood loss which may require urgent blood transfusion. Many strategies have been recommended to decrease the need for allogenic transfusion. Use of perioperative tranexamic acid (TA) has a promising role. Aims: This study was to evaluate the effectiveness of single preoperative bolus dose of TA on blood loss prevention and red blood cell transfusion in patients undergoing HNC surgery. Study Design: A prospective, double-blind, and randomized controlled study. Materials and Methods: From 2007 July to 2010 January; 80 patients, aged (35–55), of American Society of Anesthesiologists II-III scheduled for unilateral HNC surgeries were randomly received either TA (Group T) in a dose of 20 mg/kg diluted to 25 cc with normal saline or an equivalent volume of normal saline (Group C) in a tertiary care hospital. Hemoglobin (Hb) concentration, platelet count, packed cell volume, fibrinogen level, D-dimer level were measured pre- and post-operatively. Results: Saline (C) Group required more blood, colloid, crystalloid for blood loss. In Group T, 32 patients did not require transfusion of any blood products compared to five patients in Group C (P < 0.0001) and only eight units of blood was transfused in Group T, whereas a total of 42 units of blood was transfused in Group C. Even after numerous transfusions, Hb% after 6 h and 24 h in Group C were significantly low in comparison with Group T (P < 0.05). Conclusion: Thus, TA significantly reduces blood loss and chances of colloid, blood, and crystalloid transfusion caused by HNC surgery. PMID:26712979

  10. Oral administration of Lactobacillus reuteri during the first year of life reduces caries prevalence in the primary dentition at 9 years of age.

    PubMed

    Stensson, M; Koch, G; Coric, S; Abrahamsson, T R; Jenmalm, M C; Birkhed, D; Wendt, L-K

    2014-01-01

    The aim of this study was to evaluate the effect on oral health, at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730, to mothers during the last month of gestation and to children through the first year of life. The study was a single-blind, placebo-controlled, multicenter trial involving 113 children: 60 in the probiotic and 53 in the placebo group. The subjects underwent clinical and radiographic examination of the primary dentition and carious lesions, plaque and gingivitis were recorded. Saliva and plaque were sampled for determination of mutans streptococci (MS) and lactobacilli (LB) in saliva and plaque as well as salivary secretory IgA (SIgA). Forty-nine (82%) children in the probiotic group and 31 (58%) in the placebo group were caries-free (p < 0.01). The prevalence of approximal caries lesions was lower in the probiotic group (0.67 ± 1.61 vs. 1.53 ± 2.64; p < 0.05) and there were fewer sites with gingivitis compared to the placebo group (p < 0.05). There were no significant differences between the groups with respect to frequency of toothbrushing, plaque and dietary habits, but to intake of fluoride supplements (p < 0.05). There were no intergroup differences with respect to L. reuteri, MS, LB or SIgA in saliva. Within the limitation of this study it seems that daily supplementation with L. reuteri from birth and during the first year of life is associated with reduced caries prevalence and gingivitis score in the primary dentition at 9 years of age. PMID:24296746

  11. Abiotic oxidation of Fe(II) by reactive nitrogen species in cultures of the nitrate-reducing Fe(II) oxidizer Acidovorax sp. BoFeN1 - questioning the existence of enzymatic Fe(II) oxidation.

    PubMed

    Klueglein, N; Kappler, A

    2013-03-01

    Nitrate-reducing, Fe(II)-oxidizing bacteria were suggested to couple with enzymatic Fe(II) oxidation to nitrate reduction. Denitrification proceeds via intermediates (NO2 -, NO) that can oxidize Fe(II) abiotically at neutral and particularly at acidic pH. Here, we present a revised Fe(II) quantification protocol preventing artifacts during acidic Fe extraction and evaluate the contribution of abiotic vs. enzymatic Fe(II) oxidation in cultures of the nitrate-reducing, Fe(II) oxidizer Acidovorax sp. BoFeN1. Sulfamic acid used instead of HCl reacts with nitrite and prevents abiotic Fe(II) oxidation during Fe extraction. Abiotic experiments without sulfamic acid showed that acidification of oxic Fe(II) nitrite samples leads to 5.6-fold more Fe(II) oxidation than in anoxic samples because the formed NO becomes rapidly reoxidized by O(2) , therefore leading to abiotic oxidation and underestimation of Fe(II). With our revised protocol using sulfamic acid, we quantified oxidation of approximately 7 mm of Fe(II) by BoFeN1 within 4 days. Without addition of sulfamic acid, the same oxidation was detected within only 2 days. Additionally, abiotic incubation of Fe(II) with nitrite in the presence of goethite as surface catalyst led to similar abiotic Fe(II) oxidation rates as observed in growing BoFeN1 cultures. BoFeN1 growth was observed on acetate with N(2) O as electron acceptor. When adding Fe(II), no Fe(II) oxidation was observed, suggesting that the absence of reactive N intermediates (NO2 -, NO) precludes Fe(II) oxidation. The addition of ferrihydrite [Fe(OH)(3) ] to acetate/nitrate BoFeN1 cultures led to growth stimulation equivalent to previously described effects on growth by adding Fe(II). This suggests that elevated iron concentrations might provide a nutritional effect rather than energy-yielding Fe(II) oxidation. Our findings therefore suggest that although enzymatic Fe(II) oxidation by denitrifiers cannot be fully ruled out, its contribution to the observed Fe

  12. Administrative Synergy

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  13. Mark 22 Reactivity

    SciTech Connect

    Buckner, M.R.

    2001-07-02

    Calculations for reactivity held in control rods have underpredicted the observed Mark 22 reactivity. Reactivity predictions by charge designers have accounted for this by including large biases which change with exposure and reactor region. The purpose of this study was to thoroughly investigate the methods and data used in the reactivity calculations. The goal was to identify errors and improvements and make necessary corrections.

  14. Evidence for an expanded time-window to mitigate a reactivated fear memory by tamoxifen.

    PubMed

    da Silva, Thiago R; Takahashi, Reinaldo N; Bertoglio, Leandro J; Andreatini, Roberto; Stern, Cristina A J

    2016-10-01

    The mechanisms underpinning the persistence of emotional memories are inaccurately understood. Advancing the current level of understanding with regards to this aspect is of potential translational value for the treatment of post-traumatic stress disorder (PTSD), which stems from an abnormal aversive memory formation. Tamoxifen (TMX) is a drug used in chemotherapy for breast cancer and associated with poor cognitive performances. The present study investigated whether the systemic administration of TMX (1.0-50mg/kg) during and/or beyond the reconsolidation time-window could attenuate a reactivated contextual fear memory in laboratory animals. When administered 0, 6 or 9h (but not 12h) post-memory retrieval and reactivation, TMX (50mg/kg) reduced the freezing behavior in male rats re-exposed to the paired context on day 7, but not on day 1, suggesting a specific impairing effect on memory persistence. Importantly, this effect lasts up to 21 days, but it is prevented by omitting the memory retrieval or memory reactivation. When female rats in the diestrous or proestrous phase were used, the administration of TMX 6h after retrieving and reactivating the fear memory also impaired its persistence. Altogether, regardless of the gender, the present results indicate that the TMX is able to disrupt the persistence of reactivated fear memories in an expanded time-window, which could shed light on a new promising therapeutic strategy for PTSD. PMID:27554635

  15. Luteolin inhibits Epstein-Barr virus lytic reactivation by repressing the promoter activities of immediate-early genes.

    PubMed

    Wu, Chung-Chun; Fang, Chih-Yeu; Hsu, Hui-Yu; Chen, Yen-Ju; Chou, Sheng-Ping; Huang, Sheng-Yen; Cheng, Yu-Jhen; Lin, Su-Fang; Chang, Yao; Tsai, Ching-Hwa; Chen, Jen-Yang

    2016-08-01

    The lytic reactivation of Epstein-Barr virus (EBV) has been reported to be strongly associated with several human diseases, including nasopharyngeal carcinoma (NPC). Inhibition of the EBV lytic cycle has been shown to be of great benefit in the treatment of EBV-associated diseases. The administration of dietary compounds is safer and more convenient than other approaches to preventing EBV reactivation. We screened several dietary compounds for their ability to inhibit EBV reactivation in NPC cells. Among them, the flavonoid luteolin showed significant inhibition of EBV reactivation. Luteolin inhibited protein expression from EBV lytic genes in EBV-positive epithelial and B cell lines. It also reduced the numbers of EBV-reactivating cells detected by immunofluorescence analysis and reduced the production of virion. Furthermore, luteolin reduced the activities of the promoters of the immediate-early genes Zta (Zp) and Rta (Rp) and also inhibited Sp1-luc activity, suggesting that disruption of Sp1 binding is involved in the inhibitory mechanism. CHIP analysis revealed that luteolin suppressed the activities of Zp and Rp by deregulating Sp1 binding. Taken together, luteolin inhibits EBV reactivation by repressing the promoter activities of Zp and Rp, suggesting luteolin is a potential dietary compound for prevention of virus infection.

  16. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

    PubMed

    Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

    2015-12-01

    These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs.

  17. Gender differences in reactive and proactive aggression.

    PubMed

    Connor, Daniel F; Steingard, Ronald J; Anderson, Jennifer J; Melloni, Richard H

    2003-01-01

    The purpose of our investigation was to study gender differences in proactive and reactive aggression in a sample of 323 clinically referred children and adolescents (68 females and 255 males). Proactive aggression and reactive aggression were assessed using the Proactive/Reactive Aggression Scale. Demographic, historical, family, diagnostic, and treatment variables were entered into stepwise regression analyses to determine correlates of proactive and reactive aggression in males and females. Results reveal high rates of aggression in both males and females in the sample. Self reported drug use, expressed hostility, and experiences of maladaptive parenting were correlated with proactive aggression for both genders. Hyperactive/impulsive behaviors were correlated with male reactive aggression. An early age of traumatic stress and a low verbal IQ were correlated with female proactive aggression. Gender differences in correlates of proactive and reactive aggression may provide possible targets for research, prevention, and treatment efforts focused on reducing maladaptive aggression in clinically referred youth. PMID:12723901

  18. Administrative Ecology

    ERIC Educational Resources Information Center

    McGarity, Augustus C., III; Maulding, Wanda

    2007-01-01

    This article discusses how all four facets of administrative ecology help dispel the claims about the "impossibility" of the superintendency. These are personal ecology, professional ecology, organizational ecology, and community ecology. Using today's superintendency as an administrative platform, current literature describes a preponderance of…

  19. Administrative Support.

    ERIC Educational Resources Information Center

    Doran, Dorothy; And Others

    This guide is intended to assist business education teachers in administrative support courses. The materials presented are based on the Arizona validated occupational competencies and tasks for the occupations of receptionist, secretary, and administrative assistant. Word processing skills have been infused into each of the three sections. The…

  20. System for reactivating catalysts

    DOEpatents

    Ginosar, Daniel M.; Thompson, David N.; Anderson, Raymond P.

    2010-03-02

    A method of reactivating a catalyst, such as a solid catalyst or a liquid catalyst is provided. The method comprises providing a catalyst that is at least partially deactivated by fouling agents. The catalyst is contacted with a fluid reactivating agent that is at or above a critical point of the fluid reactivating agent and is of sufficient density to dissolve impurities. The fluid reactivating agent reacts with at least one fouling agent, releasing the at least one fouling agent from the catalyst. The at least one fouling agent becomes dissolved in the fluid reactivating agent and is subsequently separated or removed from the fluid reactivating agent so that the fluid reactivating agent may be reused. A system for reactivating a catalyst is also disclosed.

  1. Interventions delivered in clinical settings are effective in reducing risk of HIV transmission among people living with HIV: results from the Health Resources and Services Administration (HRSA)'s Special Projects of National Significance initiative.

    PubMed

    Myers, Janet J; Shade, Starley B; Rose, Carol Dawson; Koester, Kimberly; Maiorana, Andre; Malitz, Faye E; Bie, Jennifer; Kang-Dufour, Mi-Suk; Morin, Stephen F

    2010-06-01

    To support expanded prevention services for people living with HIV, the US Health Resources and Services Administration (HRSA) sponsored a 5-year initiative to test whether interventions delivered in clinical settings were effective in reducing HIV transmission risk among HIV-infected patients. Across 13 demonstration sites, patients were randomized to one of four conditions. All interventions were associated with reduced unprotected vaginal and/or anal intercourse with persons of HIV-uninfected or unknown status among the 3,556 participating patients. Compared to the standard of care, patients assigned to receive interventions from medical care providers reported a significant decrease in risk after 12 months of participation. Patients receiving prevention services from health educators, social workers or paraprofessional HIV-infected peers reported significant reduction in risk at 6 months, but not at 12 months. While clinics have a choice of effective models for implementing prevention programs for their HIV-infected patients, medical provider-delivered methods are comparatively robust.

  2. Administration of a Salmonella Enteritidis ΔhilAssrAfliG strain by coarse spray to newly hatched broilers reduces colonization and shedding of a Salmonella Enteritidis challenge strain.

    PubMed

    De Cort, W; Haesebrouck, F; Ducatelle, R; van Immerseel, F

    2015-01-01

    Consumption of contaminated poultry meat is still an important cause of Salmonella infections in humans. Colonization inhibition (CI) occurs when a live Salmonella strain is administered to chickens and subsequently protects against challenge with another Salmonella strain belonging to the same serotype. A Salmonella Enteritidis hilAssrAfliG deletion mutant has previously been proven to reduce colonization and shedding of a wild-type Salmonella Enteritidis strain in newly hatched broilers after experimental infection. In this study, we compared two administration routes for this strain. Administering the Salmonella Enteritidis ΔhilAssrAfliG strain through drinking water on the first day of life resulted in decreased fecal shedding and cecal colonization of a wild-type Salmonella Enteritidis challenge strain administered 24 h later using a seeder-bird model. When administering the CI strain by coarse spray on newly hatched broiler chicks, an even more pronounced reduction of cecal colonization was observed, and fecal shedding of the Salmonella Enteritidis challenge strain ceased during the course of the experiment. These data suggest that administering a Salmonella Enteritidis ΔhilAssrAfliG strain to newly hatched chicks using a coarse spray is a useful and effective method that reduces colonization and shedding of a wild-type Salmonella Enteritidis strain after early challenge. PMID:25535402

  3. The acetylcholinesterase inhibitor rivastigmine does not alter total choices for methamphetamine, but may reduce positive subjective effects, in a laboratory model of intravenous self-administration in human volunteers.

    PubMed

    De La Garza, R; Mahoney, J J; Culbertson, C; Shoptaw, S; Newton, T F

    2008-04-01

    money was available in an ascending versus descending sequence (p=0.49). The participants' years of methamphetamine use, recent use of methamphetamine (in the past 30 days), or baseline craving (indexed here as "Desire") on the day of the self-administration task were not predictive of number of choices for methamphetamine. In a subset of participants (N=8) for which data was available, individual dose of methamphetamine (3 x 3 mg, i.v.) produced significant increases in positive subjective effects, and a preliminary analysis revealed that 3 mg rivastigmine was associated with reductions in these responses, as compared to placebo. In summary, the current report indicates that there were no effects of rivastigmine on total choices for methamphetamine, that there were low levels of methamphetamine self-administration but these were 8 times greater than saline, and that choice behavior was insensitive to alternative reinforcers. In addition, we showed that rivastigmine may reduce the positive subjective effects produced by methamphetamine during self-administration.

  4. Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes

    PubMed Central

    Kanat, Manuela; Heinrichs, Markus; Mader, Irina; van Elst, Ludger Tebartz; Domes, Gregor

    2015-01-01

    The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a double-blind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies. PMID:25881796

  5. Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes.

    PubMed

    Kanat, Manuela; Heinrichs, Markus; Mader, Irina; van Elst, Ludger Tebartz; Domes, Gregor

    2015-10-01

    The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a double-blind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies.

  6. Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes.

    PubMed

    Kanat, Manuela; Heinrichs, Markus; Mader, Irina; van Elst, Ludger Tebartz; Domes, Gregor

    2015-10-01

    The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a double-blind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies. PMID:25881796

  7. Reactive behavior, learning, and anticipation

    NASA Technical Reports Server (NTRS)

    Whitehead, Steven D.; Ballard, Dana H.

    1989-01-01

    Reactive systems always act, thinking only long enough to 'look up' the action to execute. Traditional planning systems think a lot, and act only after generating fairly precise plans. Each represents an endpoint on a spectrum. It is argued that primitive forms of reasoning, like anticipation, play an important role in reducing the cost of learning and that the decision to act or think should be based on the uncertainty associated with the utility of executing an action in a particular situation. An architecture for an adaptable reactive system is presented and it is shown how it can be augmented with a simple anticipation mechanism that can substantially reduce the cost and time of learning.

  8. Administrative IT

    ERIC Educational Resources Information Center

    Grayson, Katherine, Ed.

    2006-01-01

    When it comes to Administrative IT solutions and processes, best practices range across the spectrum. Enterprise resource planning (ERP), student information systems (SIS), and tech support are prominent and continuing areas of focus. But widespread change can also be accomplished via the implementation of campuswide document imaging and sharing,…

  9. Database Administrator

    ERIC Educational Resources Information Center

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  10. ADMINISTRATIVE CLIMATE.

    ERIC Educational Resources Information Center

    BRUCE, ROBERT L.; CARTER, G.L., JR.

    IN THE COOPERATIVE EXTENSION SERVICE, STYLES OF LEADERSHIP PROFOUNDLY AFFECT THE QUALITY OF THE SERVICE RENDERED. ACCORDINGLY, MAJOR INFLUENCES ON ADMINISTRATIVE CLIMATE AND EMPLOYEE PRODUCTIVITY ARE EXAMINED IN ESSAYS ON (1) SOURCES OF JOB SATISFACTION AND DISSATISFACTION, (2) MOTIVATIONAL THEORIES BASED ON JOB-RELATED SATISFACTIONS AND NEEDS,…

  11. Engineering Administration.

    ERIC Educational Resources Information Center

    Naval Personnel Program Support Activity, Washington, DC.

    This book is intended to acquaint naval engineering officers with their duties in the engineering department. Standard shipboard organizations are analyzed in connection with personnel assignments, division operations, and watch systems. Detailed descriptions are included for the administration of directives, ship's bills, damage control, training…

  12. d-Cycloserine Attenuates Reactivity to Smoking Cues in Nicotine Dependent Smokers: A Pilot Investigation

    PubMed Central

    Santa Ana, Elizabeth J.; Rounsaville, Bruce J.; Frankforter, Tami L.; Nich, Charla; Babuscio, Theresa; Poling, James; Gonsai, Kishorchandra; Hill, Kevin P.; Carroll, Kathleen M.

    2009-01-01

    Increasing evidence indicates that smoking cues contribute to nicotine self-administration and attenuating conditioned reactivity to smoking cues may aid abstinence of smoking and prevention of smoking relapse in individuals with nicotine dependence. Based on prior studies showing that the partial N-methyl-d-aspartate (NMDA) agonist d-cycloserine (DCS) facilitates extinction of learned fear during behavioral exposure therapy in humans and facilitates extinction of cocaine-induced conditioned place preference in animals, we evaluated whether DCS would have potential for reducing reactivity to smoking cues when combined with cue exposure treatment in humans with nicotine dependence. In this double-blind placebo controlled pilot laboratory study, twenty-five smokers were recruited from the general community and randomized to DCS or placebo, plus cue exposure therapy. DCS significantly attenuated smoking cue reactivity in response to in-vivo smoking cues based on physiological reactivity and subjective urge-to-smoke ratings and led to a significantly smaller expired carbon monoxide (CO) level at the 1-week follow-up compared to placebo, although exploratory analyses indicated no effect on smoking behavior overall. These findings provide promising support for DCS combined with cue exposure therapy in attenuating conditioned reactivity to smoking cues. PMID:19592176

  13. Induction of reactivation of herpes simplex virus in murine sensory ganglia in vivo by cadmium.

    PubMed Central

    Fawl, R L; Roizman, B

    1993-01-01

    Herpes simplex viruses maintained in a latent state in sensory neurons in mice do not reactivate spontaneously, and therefore the factors or procedures which cause the virus to reactivate serve as a clue to the mechanisms by which the virus is maintained in a latent state. We report that cadmium sulfate induces latent virus to reactivate in 75 to 100% of mice tested. The following specific findings are reported. (i) The highest frequency of induction was observed after two to four daily administrations of 100 micrograms of cadmium sulfate. (ii) Zinc, copper, manganese, or nickel sulfate administered in equimolar amounts under the same regimen did not induce viral reactivation; however, zinc sulfate in molar ratios 25-fold greater than those of cadmium induced viral replication in 2 of 16 ganglia tested. (iii) Administration of zinc, nickel, or manganese prior to the cadmium sulfate reduced the incidence of ganglia containing infectious virus. (iv) Administration of cadmium daily during the first week after infection and at 2-day intervals to 13 days after infection resulted in the recovery from ganglia of infectious virus in titers 10- to 100-fold higher than those obtained from animals given saline. Moreover, infectious virus was recovered as late as 11 days after infection compared with 6 days in mice administered saline. (v) Administration of cadmium immediately after infection or repeatedly after establishment of latency did not exhaust the latent virus harbored by sensory neurons, inasmuch as the fraction of ganglia of mice administered cadmium and yielding infectious virus was similar to that observed in mice treated with saline. We conclude that induction of cadmium tolerance precludes reactivation of latent virus. If the induction of metallothionein genes was the sole factor required to cause reactivation of latent virus, it would have been expected that all metals which induce metallothioneins would also induce reactivation, which was not observed. The

  14. Phenylethynyl reactive diluents

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor)

    1995-01-01

    A composition of matter having a specified general structure is employed to terminate a nucleophilic reagent, resulting in the exclusive production of phenylethynyl terminated reactive oligomers which display unique thermal characteristics. A reactive diluent having a specified general structure is employed to decrease the melt viscosity of a phenylethynyl terminated reactive oligomer and to subsequently react with to provide a thermosetting material of enhanced density. These materials have features which make them attractive candidates for use as composite matrices and adhesives.

  15. Estradiol decreases cortical reactive astrogliosis after brain injury by a mechanism involving cannabinoid receptors.

    PubMed

    López Rodríguez, Ana Belén; Mateos Vicente, Beatriz; Romero-Zerbo, Silvana Y; Rodriguez-Rodriguez, Noé; Bellini, María José; Rodriguez de Fonseca, Fernando; Bermudez-Silva, Francisco Javier; Azcoitia, Iñigo; Garcia-Segura, Luis M; Viveros, María-Paz

    2011-09-01

    The neuroactive steroid estradiol reduces reactive astroglia after brain injury by mechanisms similar to those involved in the regulation of reactive gliosis by endocannabinoids. In this study, we have explored whether cannabinoid receptors are involved in the effects of estradiol on reactive astroglia. To test this hypothesis, the effects of estradiol, the cannabinoid CB1 antagonist/inverse agonist AM251, and the cannabinoid CB2 antagonist/inverse agonist AM630 were assessed in the cerebral cortex of male rats after a stab wound brain injury. Estradiol reduced the number of vimentin immunoreactive astrocytes and the number of glial fibrillary acidic protein immunoreactive astrocytes in the proximity of the wound. The effect of estradiol was significantly inhibited by the administration of either CB1 or CB2 receptor antagonists. The effect of estradiol may be in part mediated by alterations in endocannabinoid signaling because the hormone increased in the injured cerebral cortex the messenger RNA levels of CB2 receptors and of some of the enzymes involved in the synthesis and metabolism of endocannabinoids. These findings suggest that estradiol may decrease reactive astroglia in the injured brain by regulating the activity of the endocannabinoid system.

  16. Loss of the trpc4 gene is associated with a reduction in cocaine self-administration and reduced spontaneous ventral tegmental area dopamine neuronal activity, without deficits in learning for natural rewards.

    PubMed

    Klipec, William D; Burrow, Kristin R; O'Neill, Casey; Cao, Jun-Li; Lawyer, Chloe R; Ostertag, Eric; Fowler, Melissa; Bachtell, Ryan K; Illig, Kurt R; Cooper, Donald C

    2016-06-01

    Among the canonical transient receptor potential (TRPC) channels, the TRPC4 non-selective cation channel is one of the most abundantly expressed subtypes within mammalian corticolimbic brain regions, but its functional and behavioral role is unknown. To identify a function for TRPC4 channels we compared the performance of rats with a genetic knockout of the trpc4 gene (trpc4 KO) to wild-type (WT) controls on the acquisition of simple and complex learning for natural rewards, and on cocaine self-administration (SA). Despite the abundant distribution of TRPC4 channels through the corticolimbic brain regions, we found trpc4 KO rats exhibited normal learning in Y-maze and complex reversal shift paradigms. However, a deficit was observed in cocaine SA in the trpc4 KO group, which infused significantly less cocaine than WT controls despite displaying normal sucrose SA. Given the important role of ventral tegmental area (VTA) dopamine neurons in cocaine SA, we hypothesized that TRPC4 channels may regulate basal dopamine neuron excitability. Double-immunolabeling showed a selective expression of TRPC4 channels in a subpopulation of putative dopamine neurons in the VTA. Ex vivo recordings of spontaneous VTA dopamine neuronal activity from acute brain slices revealed fewer cells with high-frequency firing rates in trpc4 KO rats compared to WT controls. Since deletion of the trpc4 gene does not impair learning involving natural rewards, but reduces cocaine SA, these data demonstrate a potentially novel role for TRPC4 channels in dopamine systems and may offer a new pharmacological target for more effective treatment of a variety of dopamine disorders. PMID:26988269

  17. Loss of the trpc4 gene is associated with a reduction in cocaine self-administration and reduced spontaneous ventral tegmental area dopamine neuronal activity, without deficits in learning for natural rewards.

    PubMed

    Klipec, William D; Burrow, Kristin R; O'Neill, Casey; Cao, Jun-Li; Lawyer, Chloe R; Ostertag, Eric; Fowler, Melissa; Bachtell, Ryan K; Illig, Kurt R; Cooper, Donald C

    2016-06-01

    Among the canonical transient receptor potential (TRPC) channels, the TRPC4 non-selective cation channel is one of the most abundantly expressed subtypes within mammalian corticolimbic brain regions, but its functional and behavioral role is unknown. To identify a function for TRPC4 channels we compared the performance of rats with a genetic knockout of the trpc4 gene (trpc4 KO) to wild-type (WT) controls on the acquisition of simple and complex learning for natural rewards, and on cocaine self-administration (SA). Despite the abundant distribution of TRPC4 channels through the corticolimbic brain regions, we found trpc4 KO rats exhibited normal learning in Y-maze and complex reversal shift paradigms. However, a deficit was observed in cocaine SA in the trpc4 KO group, which infused significantly less cocaine than WT controls despite displaying normal sucrose SA. Given the important role of ventral tegmental area (VTA) dopamine neurons in cocaine SA, we hypothesized that TRPC4 channels may regulate basal dopamine neuron excitability. Double-immunolabeling showed a selective expression of TRPC4 channels in a subpopulation of putative dopamine neurons in the VTA. Ex vivo recordings of spontaneous VTA dopamine neuronal activity from acute brain slices revealed fewer cells with high-frequency firing rates in trpc4 KO rats compared to WT controls. Since deletion of the trpc4 gene does not impair learning involving natural rewards, but reduces cocaine SA, these data demonstrate a potentially novel role for TRPC4 channels in dopamine systems and may offer a new pharmacological target for more effective treatment of a variety of dopamine disorders.

  18. Oral administration of the Salmonella Typhimurium vaccine strain Nal2/Rif9/Rtt to laying hens at day of hatch reduces shedding and caecal colonization of Salmonella 4,12:i:-, the monophasic variant of Salmonella Typhimurium.

    PubMed

    Kilroy, Sofie; Raspoet, Ruth; Devloo, Rosalie; Haesebrouck, Freddy; Ducatelle, Richard; Van Immerseel, Filip

    2015-06-01

    A new monophasic variant of Salmonella Typhimurium, Salmonella enterica serotype 4,12:i:-, is rapidly emerging. This serotype is now considered to be among the 10 most common serovars isolated from humans in many countries in Europe and in the United States. The public health risk posed by these emerging monophasic Salmonella Typhimurium strains is considered comparable to that of classical Salmonella Typhimurium strains. The serotype 4,12:i:- is frequently isolated from pigs but also poultry are carrying strains from this serotype. In the current study, we evaluated the efficacy of the Salmonella Typhimurium strain Nal2/Rif9/Rtt, a strain contained in the commercially available live vaccines AviPro Salmonella Duo and AviPro Salmonella VacT, against infection with the emerging monophasic variant in poultry. Three independent trials were conducted. In all trials, laying type chicks were orally vaccinated with the Salmonella Typhimurium strain Nal2/Rif9/Rtt at d hatch, while the birds were challenged the next d with a different infection dose in each trial (low, high, and intermediate). For the intermediate-dose study, a seeder bird model was used in which one out of 3 animals were infected while all individual birds were infected in the other trials. Data obtained from each independent trial show that oral administration of the Salmonella Typhimurium strain Nal2/Rif9/Rtt at d hatch reduced shedding, caecal, and internal organ colonization of Salmonella Typhimurium 4,12:i:-, administered at d 2 life. This indicates that Salmonella Typhimurium strain Nal2/Rif9/Rtt can help to control Salmonella 4,12:i:- infections in poultry. PMID:25825785

  19. In Praise of Fewer Administrators.

    ERIC Educational Resources Information Center

    Nichols, Donald D.; Stuart, William H.

    In response to increasing financial pressures, Oakland Community College instituted a policy in the 1970s to reduce the number of college administrators as a means of saving staff costs. While student enrollments increased from 11,700 in 1970 to 24,000 in 1980, the number of administrators fell from 84 to 32. This reduction was realized through…

  20. Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine

    PubMed Central

    Bearson, Shawn M. D.; Bearson, Bradley L.; Loving, Crystal L.; Allen, Heather K.; Lee, InSoo; Madson, Darin; Kehrli, Marcus E.

    2016-01-01

    Salmonella-challenged pigs was less disturbed post-challenge in the Ad5-G-CSF-treated pigs than the Ad5-empty-treated pigs. This suggests that Ad5-G-CSF administration mitigated changes in the microbial community structure caused by Salmonella challenge. Collectively, these data suggest that delivery of a targeted immunostimulant to enhance neutropoiesis may be a strategy to reduce Salmonella colonization, potentially during periods of immunological stress. PMID:27610361

  1. Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine

    PubMed Central

    Bearson, Shawn M. D.; Bearson, Bradley L.; Loving, Crystal L.; Allen, Heather K.; Lee, InSoo; Madson, Darin; Kehrli, Marcus E.

    2016-01-01

    Salmonella-challenged pigs was less disturbed post-challenge in the Ad5-G-CSF-treated pigs than the Ad5-empty-treated pigs. This suggests that Ad5-G-CSF administration mitigated changes in the microbial community structure caused by Salmonella challenge. Collectively, these data suggest that delivery of a targeted immunostimulant to enhance neutropoiesis may be a strategy to reduce Salmonella colonization, potentially during periods of immunological stress.

  2. Prophylactic Administration of Vector-Encoded Porcine Granulocyte-Colony Stimulating Factor Reduces Salmonella Shedding, Tonsil Colonization, and Microbiota Alterations of the Gastrointestinal Tract in Salmonella-Challenged Swine.

    PubMed

    Bearson, Shawn M D; Bearson, Bradley L; Loving, Crystal L; Allen, Heather K; Lee, InSoo; Madson, Darin; Kehrli, Marcus E

    2016-01-01

    Salmonella-challenged pigs was less disturbed post-challenge in the Ad5-G-CSF-treated pigs than the Ad5-empty-treated pigs. This suggests that Ad5-G-CSF administration mitigated changes in the microbial community structure caused by Salmonella challenge. Collectively, these data suggest that delivery of a targeted immunostimulant to enhance neutropoiesis may be a strategy to reduce Salmonella colonization, potentially during periods of immunological stress. PMID:27610361

  3. Normalizing renal reducing ability prevents adriamycin-induced proteinuria

    SciTech Connect

    Oteki, Takaaki; Nagase, Sohji . E-mail: sohji-n@md.tsukuba.ac.jp; Yokoyama, Hidekatsu; Ohya, Hiroaki; Akatsuka, Takao; Tada, Mika; Ueda, Atsushi; Hirayama, Aki; Koyama, Akio

    2005-11-11

    Reactive oxygen species play an important role in adriamycin (ADR) nephropathy. We showed by in vivo electron paramagnetic resonance (EPR) that renal reducing ability (RRA) declined on the 7th day after ADR administration. Proteinuria appeared after the decline in RRA. The aim of this study was to prove by in vivo EPR whether the decline in RRA is altered by scavengers such as dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU) and that it is this change which is responsible for the proteinuria in ADR nephropathy. By showing that DMSO and DMTU ameliorate the RRA, we demonstrate that the decline in RRA is related to ADR-induced proteinuria.

  4. Reactive Leidenfrost droplets

    NASA Astrophysics Data System (ADS)

    Raufaste, C.; Bouret, Y.; Celestini, F.

    2016-05-01

    We experimentally investigate the reactivity of Leidenfrost droplets with their supporting substrates. Several organic liquids are put into contact with a copper substrate heated above their Leidenfrost temperature. As the liquid evaporates, the gaseous flow cleans the superficial copper oxide formed at the substrate surface and the reaction maintains a native copper spot below the evaporating droplet. The copper spot can reach several times the droplet size for the most reactive organic compounds. This study shows an interesting coupling between the physics of the Leidenfrost effect and the mechanics of reactive flows. Different applications are proposed such as drop motion tracking and vapor flow monitoring.

  5. METHOD OF ALLOYING REACTIVE METALS WITH ALUMINUM OR BERYLLIUM

    DOEpatents

    Runnalls, O.J.C.

    1957-10-15

    A halide of one or more of the reactive metals, neptunium, cerium and americium, is mixed with aluminum or beryllium. The mass is heated at 700 to 1200 deg C, while maintaining a substantial vacuum of above 10/sup -3/ mm of mercury or better, until the halide of the reactive metal is reduced and the metal itself alloys with the reducing metal. The reaction proceeds efficiently due to the volatilization of the halides of the reducing metal, aluminum or beryllium.

  6. Anticipation of Smoking Sufficiently Dampens Stress Reactivity in Nicotine Deprived Smokers

    PubMed Central

    Bradford, Daniel E.; Curtin, John J.; Piper, Megan E.

    2014-01-01

    Most smokers attempting to quit will relapse, even when using evidence-based cessation treatment. This illustrates the need for better understanding of the relapse process to thereby improve cessation treatments. While the impact of stress sensitivity on relapse is clear, little research has precisely examined stress reactivity in addicted individuals. Further, most research on relapse focuses on affect surrounding self-administration, and doesn't address potentially important pre-consumption processes such as anticipation of use. We examined the effects of anticipation and actual smoking on stress reactivity in 34 deprived smokers withdrawn for 24 hours and 37 non-deprived smokers, with 37 non-smoker controls. Using a cued shock stressor task, we measured stress reactivity via startle potentiation and self-reported anxiety. After completing the task once, smokers anticipated smoking a cigarette resting in front of them while they completed the task a second time. Smokers then smoked before completing the task a third and final time. Non-smokers anticipated and drank water as a control. Anticipation of smoking significantly attenuated both startle potentiation and self-reported anxiety to shock cues for deprived smokers relative to non-deprived smokers. Smokers' stress reactivity was not reduced by smoking beyond the prior effect of anticipation. These results suggest that anticipation, rather than actual drug consumption, may drive the primary reinforcing effect of reduced stress reactivity in smoking. Future research is needed to understand this effect of anticipation on drug use and determine whether anticipation would make an effective intervention target for addiction and other psychopathology which exhibits increased stress sensitivity. PMID:25688439

  7. Reactive power compensator

    DOEpatents

    El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.; Chen, Mingliang; Andexler, George; Huang, Tony

    1992-01-01

    A system and method for determining and providing reactive power compensation for an inductive load. A reactive power compensator (50,50') monitors the voltage and current flowing through each of three distribution lines (52a, 52b, 52c), which are supplying three-phase power to one or more inductive loads. Using signals indicative of the current on each of these lines when the voltage waveform on the line crosses zero, the reactive power compensator determines a reactive power compensator capacitance that must be connected to the lines to maintain a desired VAR level, power factor, or line voltage. Alternatively, an operator can manually select a specific capacitance for connection to each line, or the capacitance can be selected based on a time schedule. The reactive power compensator produces control signals, which are coupled through optical fibers (102/106) to a switch driver (110, 110') to select specific compensation capacitors (112) for connections to each line. The switch driver develops triggering signals that are supplied to a plurality of series-connected solid state switches (350), which control charge current in one direction in respect to ground for each compensation capacitor. During each cycle, current flows from ground to charge the capacitors as the voltage on the line begins to go negative from its positive peak value. The triggering signals are applied to gate the solid state switches into a conducting state when the potential on the lines and on the capacitors reaches a negative peak value, thereby minimizing both the potential difference and across the charge current through the switches when they begin to conduct. Any harmonic distortion on the potential and current carried by the lines is filtered out from the current and potential signals used by the reactive power compensator so that it does not affect the determination of the required reactive compensation.

  8. Reactive Power Compensator.

    DOEpatents

    El-Sharkawi, M.A.; Venkata, S.S.; Chen, M.; Andexler, G.; Huang, T.

    1992-07-28

    A system and method for determining and providing reactive power compensation for an inductive load. A reactive power compensator (50,50') monitors the voltage and current flowing through each of three distribution lines (52a, 52b, 52c), which are supplying three-phase power to one or more inductive loads. Using signals indicative of the current on each of these lines when the voltage waveform on the line crosses zero, the reactive power compensator determines a reactive power compensator capacitance that must be connected to the lines to maintain a desired VAR level, power factor, or line voltage. Alternatively, an operator can manually select a specific capacitance for connection to each line, or the capacitance can be selected based on a time schedule. The reactive power compensator produces control signals, which are coupled through optical fibers (102/106) to a switch driver (110, 110') to select specific compensation capacitors (112) for connections to each line. The switch driver develops triggering signals that are supplied to a plurality of series-connected solid state switches (350), which control charge current in one direction in respect to ground for each compensation capacitor. During each cycle, current flows from ground to charge the capacitors as the voltage on the line begins to go negative from its positive peak value. The triggering signals are applied to gate the solid state switches into a conducting state when the potential on the lines and on the capacitors reaches a negative peak value, thereby minimizing both the potential difference and across the charge current through the switches when they begin to conduct. Any harmonic distortion on the potential and current carried by the lines is filtered out from the current and potential signals used by the reactive power compensator so that it does not affect the determination of the required reactive compensation. 26 figs.

  9. Formation and Reactivity of Biogenic Iron Microminerals

    SciTech Connect

    Beveridge, Terrance J.; Ferris, F. Grant

    2001-08-15

    The overall purpose of the project was to explore and quantify the processes that control the formation and reactivity of biogenic iron microminerals and their impact on the solubility of metal contaminants. The research addressed how surface components of bacterial cells, extracellular organic material, and the aqueous geochemistry of the DIRB microenvironment impacts the mineralogy, chemical state and micromorphology of reduced iron phases.

  10. Formation and Reactivity of Biogenic Iron Microminerals

    SciTech Connect

    Beveridge, Terrance J.; Glasauer, Susan; Korenevsky, Anton; Ferris, F. Grant

    2000-08-08

    The overall purpose of the project is to explore and quantify the processes that control the formation and reactivity of biogenic iron microminerals and their impact on the solubility of metal contaminants. The research addresses how surface components of bacterial cells, extracellular organic material, and the aqueous geochemistry of the DIRB microenvironment impacts the mineralogy, chemical state and micromorphology of reduced iron phases.

  11. Influence of glucocorticoids on a time-of-day-dependent variation in intradermal reactivity to histamine in dogs.

    PubMed

    Goto, Shun; Shimizu, Sunao; Watanabe, Miwa; Osada, Hironari; Sasaki, Kazuaki; Shimoda, Minoru; Nagai, Makoto; Shirai, Junsuke; Itoh, Hiroshi; Ohmori, Keitaro

    2016-08-01

    The objectives of this study were to determine daily variation in intradermal reactivity to histamine in dogs and to evaluate a potential influence of glucocorticoids on reactivity. Wheal sizes formed after intradermal injections of histamine were measured every 6 h during a single 24 h period in six healthy dogs. To determine whether glucocorticoids were implicated in daily variation, intradermal reactivity to histamine was evaluated at 9:00 h and at 21:00 h during a single day in dogs that received oral prednisolone (a synthetic glucocorticoid) or oral trilostane (an inhibitor of endogenous glucocorticoid synthesis). Finally, the time required for the histamine reaction to diminish after an intravenous injection of hydrocortisone was also assessed. A significant time-of-day-dependent variation in intradermal reactivity to histamine was detected in dogs, with a larger wheal size observed at 9:00 h than at 21:00 h. Administration of prednisolone or trilostane disrupted this variation. Intradermal reactivity to histamine was significantly reduced 6 h after an intravenous injection of hydrocortisone. These results suggest that glucocorticoid secretion from the adrenal glands could be involved in the regulation of daily variation in histamine-mediated reactions in dogs. PMID:27387732

  12. Phenylethynyl terminated reactive oligomer

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G. (Inventor); Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor)

    1995-01-01

    A composition of matter having the general structure: ##STR1## (wherein X is F, Cl, or NO.sub.2, and Y is CO, SO.sub.2 or C(CF.sub.3).sub.2) is employed to terminate a nucleophilic reagent, resulting in the exclusive production of phenylethynyl terminated reactive oligomers which display unique thermal characteristics. A reactive diluent having the general structure: ##STR2## (wherein R is any aliphatic or aromatic moiety) is employed to decrease the melt viscosity of a phenylethynyl terminated reactive oligomer and to subsequently react therewith to provide a thermosetting material of enhanced density. These materials have features which make them attractive candidates for use as composite matrices and adhesives.

  13. Reactivation of Chagas Disease: Implications for Global Health.

    PubMed

    Perez, Catherine J; Lymbery, Alan J; Thompson, R C Andrew

    2015-11-01

    Reactivation of Chagas Disease (CD) is a global public health issue. Reactivation of disease can affect the management of CD and its clinical outcome, adding pressure to global health systems because it exacerbates symptoms, leading to misdiagnosis and delays in the administration of correct treatments. Concurrent infections complicate the issue of reactivation, because there are various parasites and disease treatment regimens that are able to influence or suppress the immune system of the host, reactivating disease within infected individuals. The effect of delayed symptoms of chronic CD and the potential for disease reactivation are of great importance to nonendemic regions of the world, where knowledge about CD is lacking and the potential for vectorial transmission is not known.

  14. Differential effects of rumination and distraction on ketamine induced modulation of resting state functional connectivity and reactivity of regions within the default-mode network.

    PubMed

    Lehmann, Mick; Seifritz, Erich; Henning, Anke; Walter, Martin; Böker, Heinz; Scheidegger, Milan; Grimm, Simone

    2016-08-01

    Distraction and rumination are distinct response styles that determine how an individual deals with negative thoughts and feelings. Rumination is accompanied by an elevated self-focus, which is associated with increased resting state functional connectivity and decreased reactivity within the default mode network. Interestingly, the NMDA receptor antagonist ketamine reduces functional connectivity in this network, while its effects on blood oxygenation level-dependent (BOLD) responses during stimulus perception are not known. Ketamine might lead to a more variable processing of the external world with an attenuated self-focus by reducing the resting state connectivity. Here, we used an emotional picture-viewing task in combination with functional magnetic resonance imaging to test the hypothesis that a single ketamine administration to healthy subjects increases BOLD reactivity to negative stimuli. We found a region specific increase in BOLD reactivity in the pregenual anterior cingulate cortex and not in a posterior control region after ketamine compared with placebo administration. Moreover, a linear regression revealed that the increase in BOLD reactivity was more pronounced for subjects with a low ability to apply distraction during negative experiences. Our results implicate that ketamine attenuates a potentially pathological increased self-focus during negative experiences. PMID:27075438

  15. Astragalosides reduce cisplatin ototoxicity in guinea pigs.

    PubMed

    Xiong, Min; He, Qinglian; Wang, Jian; Lai, Huangwen

    2011-01-01

    Cisplatin is known to cause high-frequency neurosensory hearing loss. While reactive oxygen species have been shown to play a role, reactive nitrogen species have been implicated, but not proven to be involved, in cisplatin ototoxicity. The purpose of the present study was to investigate the role of nitric oxide (NO) in cisplatin ototoxicity by administering astragalosides, a natural antioxidant, in conjunction with cisplatin. Guinea pigs were injected with cisplatin, astragalosides or both. Auditory brainstem-evoked responses (ABRs) were measured before and 3 days after cisplatin administration. The cochlear tissue was then assayed for NO and malondialdehyde (MDA), and cochleae were also examined by scanning electron microscopy. Cisplatin alone caused significant ABR threshold shifts at all stimuli tested, whereas astragalosides alone caused no shifts. There was a significant reduction in threshold shift for clicks, 8-kHz and 16-kHz tone bursts (but not 32 kHz) when astragalosides was given with cisplatin. Both the MDA concentration and the NO concentration in the astragalosides/cisplatin group were significantly lower than those of the cisplatin group. Correspondingly, the loss of outer hair cells in the astragalosides/cisplatin group was much less than that in the cisplatin group. This suggests that astragalosides reduces cisplatin ototoxicity by its antioxidant property. PMID:21494054

  16. Waking up the sleepers: HIV latency and reactivation.

    PubMed

    Mok, Hoi Ping; Lever, Andrew

    2008-12-01

    In a patient infected with HIV-1, the presence of latently infected cells from which the virus can be reactivated and rekindle HIV infection in the patient necessitates lifelong administration of antiretroviral treatment. The biology of HIV latency and viral silencing is now becoming clearer at a molecular and cellular level. However, our understanding of HIV-1 latency in vivo is still inadequate. Attempts to therapeutically reactivate the virus in infected patients have yielded disappointing results. This article reviews the research and clinical findings and discusses current thinking on the subject of HIV latency and reactivation.

  17. Modeling Atmospheric Reactive Nitrogen

    EPA Science Inventory

    Nitrogen is an essential building block of all proteins and thus an essential nutrient for all life. Reactive nitrogen, which is naturally produced via enzymatic reactions, forest fires and lightning, is continually recycled and cascades through air, water, and soil media. Human ...

  18. Reactive power compensating system

    DOEpatents

    Williams, Timothy J.; El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.

    1987-01-01

    The reactive power of an induction machine is compensated by providing fixed capacitors on each phase line for the minimum compensation required, sensing the current on one line at the time its voltage crosses zero to determine the actual compensation required for each phase, and selecting switched capacitors on each line to provide the balance of the compensation required.

  19. Reactive Power Compensating System.

    DOEpatents

    Williams, Timothy J.; El-Sharkawi, Mohamed A.; Venkata, Subrahmanyam S.

    1985-01-04

    The circuit was designed for the specific application of wind-driven induction generators. It has great potential for application in any situation where a varying reactive power load is present, such as with induction motors or generators, or for transmission network compensation.

  20. Reactive Oxygen Species Mediate Epstein-Barr Virus Reactivation by N-Methyl-N’-Nitro-N-Nitrosoguanidine

    PubMed Central

    Huang, Sheng-Yen; Fang, Chih-Yeu; Wu, Chung-Chun; Tsai, Ching-Hwa; Lin, Su-Fang; Chen, Jen-Yang

    2013-01-01

    N-nitroso compounds (NOCs) and Epstein-Barr virus (EBV) reactivation have been suggested to play a role in the development of nasopharyngeal carcinoma (NPC). Although chemicals have been shown to be a risk factor contributing to the carcinogenesis of NPC, the underlying mechanism is not fully understood. We demonstrated recently that N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) enhances the genomic instability and tumorigenicity of NPC cells via induction of EBV reactivation. However, the mechanisms that trigger EBV reactivation from latency remain unclear. Here, we address the role of ROS in induction of EBV reactivation under MNNG treatment. EBV reactivation was induced in over 70% of EBV-positive NA cells and the promoter of Rta (Rp) was activated after MNNG treatment. Inhibitor experiments revealed ATM, p38 MAPK and JNK were activated by ROS and involved in MNNG-induced EBV reactivation. Significantly, ROS scavengers N-acetyl-L-cysteine (NAC), catalase and reduced glutathione inhibited EBV reactivation under MNNG and H2O2 treatment, suggesting ROS mediate EBV reactivation. The p53 was essential for EBV reactivation and the Rp activation by MNNG. Moreover, the p53 was phosphorylated, translocated into nucleus, and bound to Rp following ROS stimulation. The results suggest ROS play an important role in initiation of EBV reactivation by MNNG through a p53-dependent mechanism. Our findings demonstrate novel signaling mechanisms used by NOCs to induce EBV reactivation and provide a novel insight into NOCs link the EBV reactivation in the contribution to the development of NPC. Notably, this study indicates that antioxidants might be effective for inhibiting N-nitroso compound-induced EBV reactivation and therefore could be promising preventive and therapeutic agents for EBV reactivation-associated malignancies. PMID:24376853

  1. Immune reactivity to food coloring.

    PubMed

    Vojdani, Aristo; Vojdani, Charlene

    2015-01-01

    Artificial food dyes are made from petroleum and have been approved by the US Food and Drug Administration (FDA) for the enhancement of the color of processed foods. They are widely used in the food and pharmaceutical industries to increase the appeal and acceptability of their products. Synthetic food colorants can achieve hues not possible for natural colorants and are cheaper, more easily available, and last longer. However, since the use of artificial food coloring has become widespread, many allergic and other immune reactive disorders have increasingly been reported. During the past 50 y, the amount of synthetic dye used in foods has increased by 500%. Simultaneously, an alarming rise has occurred in behavioral problems in children, such as aggression, attention deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The ingestion of food delivers the greatest foreign antigenic load that challenges the immune system. Artificial colors can also be absorbed via the skin through cosmetic and pharmaceutical products. The molecules of synthetic colorants are small, and the immune system finds it difficult to defend the body against them. They can also bond to food or body proteins and, thus, are able to act in stealth mode to circumvent and disrupt the immune system. The consumption of synthetic food colors, and their ability to bind with body proteins, can have significant immunological consequences. This consumption can activate the inflammatory cascade, can result in the induction of intestinal permeability to large antigenic molecules, and could lead to cross-reactivities, autoimmunities, and even neurobehavioral disorders. The Centers for Disease Control (CDC) recently found a 41% increase in diagnoses of ADHD in boys of high-school age during the past decade. More shocking is the legal amount of artificial colorants allowed by the FDA in the foods, drugs, and cosmetics that we consume and use every day. The consuming public is largely

  2. Immune reactivity to food coloring.

    PubMed

    Vojdani, Aristo; Vojdani, Charlene

    2015-01-01

    Artificial food dyes are made from petroleum and have been approved by the US Food and Drug Administration (FDA) for the enhancement of the color of processed foods. They are widely used in the food and pharmaceutical industries to increase the appeal and acceptability of their products. Synthetic food colorants can achieve hues not possible for natural colorants and are cheaper, more easily available, and last longer. However, since the use of artificial food coloring has become widespread, many allergic and other immune reactive disorders have increasingly been reported. During the past 50 y, the amount of synthetic dye used in foods has increased by 500%. Simultaneously, an alarming rise has occurred in behavioral problems in children, such as aggression, attention deficit disorder (ADD), and attention-deficit/hyperactivity disorder (ADHD). The ingestion of food delivers the greatest foreign antigenic load that challenges the immune system. Artificial colors can also be absorbed via the skin through cosmetic and pharmaceutical products. The molecules of synthetic colorants are small, and the immune system finds it difficult to defend the body against them. They can also bond to food or body proteins and, thus, are able to act in stealth mode to circumvent and disrupt the immune system. The consumption of synthetic food colors, and their ability to bind with body proteins, can have significant immunological consequences. This consumption can activate the inflammatory cascade, can result in the induction of intestinal permeability to large antigenic molecules, and could lead to cross-reactivities, autoimmunities, and even neurobehavioral disorders. The Centers for Disease Control (CDC) recently found a 41% increase in diagnoses of ADHD in boys of high-school age during the past decade. More shocking is the legal amount of artificial colorants allowed by the FDA in the foods, drugs, and cosmetics that we consume and use every day. The consuming public is largely

  3. Anti-cancer activity of bromelain nanoparticles by oral administration.

    PubMed

    Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

    2014-12-01

    Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy.

  4. [Biodegradation of reactive turquoise blue].

    PubMed

    Fu, L; Wen, X; Xu, L; Qian, Y

    2001-07-01

    In this study, the anaerobic degradation and the aerobic degradation of a kind of reactive dye--Reactive Turquoise Blue(RTB) were compared. The results proved that anaerobic sludge could only decompose RTB in the presence of glucose while aerobic sludge decomposed RTB with or without the presence of glucose (RTB of 20 mg/L was reduced by 37.4% through 24 hours' aerobic treatment with RTB as sole carbon source). The enhancement of glucose concentration was beneficial for both anaerobic and aerobic degradation of RTB: the anaerobic and the aerobic removal efficiencies were respectively 81.5% and 73.6% with RTB of 20 mg/L and glucose of 1200 mg/L. In the influent RTB concentration also had influence on the activity of anaerobic and aerobic microorganisms. When glucose concentration was 800 mg/L or 1200 mg/L and RTB concentration was 20 mg/L to 100 mg/L, anaerobic removal efficiency of RTB was higher than aerobic removal efficiency by 4.9%-27.2%, which meant that anaerobic bacteria is more powerful than aerobic bacteria in terms of RTB removal.

  5. Reactive Functionalized Membranes for Polychlorinated Biphenyl Degradation.

    PubMed

    Gui, Minghui; Ormsbee, Lindell E; Bhattacharyya, Dibakar

    2013-08-01

    Membranes have been widely used in water remediation (e.g. desalination and heavy metal removal) because of the ability to control membrane pore size and surface charge. The incorporation of nanomaterials into the membranes provides added benefits through increased reactivity with different functionality. In this study, we report the dechlorination of 2-chlorobiphenyl in the aqueous phase by a reactive membrane system. Fe/Pd bimetallic nanoparticles (NPs) were synthesized (in-situ) within polyacrylic acid (PAA) functionalized polyvinylidene fluoride (PVDF) membranes for degradation of polychlorinated biphenyls (PCBs). Biphenyl formed in the reduction was further oxidized into hydroxylated biphenyls and benzoic acid by an iron-catalyzed hydroxyl radical (OH•) reaction. The formation of magnetite on Fe surface was observed. This combined pathway (reductive/oxidative) could reduce the toxicity of PCBs effectively while eliminating the formation of chlorinated degradation byproducts. The successful manufacturing of full-scale functionalized membranes demonstrates the possibility of applying reactive membranes in practical water treatment.

  6. Reactive Air Aluminization

    SciTech Connect

    Choi, Jung-Pyung; Chou, Y. S.; Stevenson, Jeffry W.

    2011-10-28

    Ferritic stainless steels and other alloys are of great interest to SOFC developers for applications such as interconnects, cell frames, and balance of plant components. While these alloys offer significant advantages (e.g., low material and manufacturing cost, high thermal conductivity, and high temperature oxidation resistance), there are challenges which can hinder their utilization in SOFC systems; these challenges include Cr volatility and reactivity with glass seals. To overcome these challenges, protective coatings and surface treatments for the alloys are under development. In particular, aluminization of alloy surfaces offers the potential for mitigating both evaporation of Cr from the alloy surface and reaction of alloy constituents with glass seals. Commercial aluminization processes are available to SOFC developers, but they tend to be costly due to their use of exotic raw materials and/or processing conditions. As an alternative, PNNL has developed Reactive Air Aluminization (RAA), which offers a low-cost, simpler alternative to conventional aluminization methods.

  7. [Reactive arthritis. A review].

    PubMed

    Gutiérrez, F; Espinoza, L R

    1990-07-01

    The arthritides that meet the definition or reactive arthritis include the so-called seronegative spondyloarthropathies. Patients are usually aged less than thirty-two. Preceding infection is generally intestinal or venereal, although the involved agent may remain unknown. Enteric forms occur in small epidemics, whereas venereal forms correlate with a recent new sexual partner. The clinical picture varies in severity, with manifestations overlapping between disorders, and often the first complaint is extra-articular. Highly suggestive of reactive arthritis is "sausage" deformity of fingers and toes, pain and stiffness about multiple joints accompanied by radiating lower back discomfort, and enthesitis, particularly at the Achilles tendon. One out of six or seven patients becomes disabled; therapy aimed at preventing disability is vital since medication has little effect on spinal involvement. Antibiotic therapy may be effective in cases in which specific etiologic agents are well defined.

  8. Multifunctional reactive nanocomposite materials

    NASA Astrophysics Data System (ADS)

    Stamatis, Demitrios

    Many multifunctional nanocomposite materials have been developed for use in propellants, explosives, pyrotechnics, and reactive structures. These materials exhibit high reaction rates due to their developed reaction interfacial area. Two applications addressed in this work include nanocomposite powders prepared by arrested reactive milling (ARM) for burn rate modifiers and reactive structures. In burn rate modifiers, addition of reactive nanocomposite powders to aluminized propellants increases the burn rate of aluminum and thus the overall reaction rate of an energetic formulation. Replacing only a small fraction of aluminum by 8Al·MoO3 and 2B·Ti nanocomposite powders enhances the reaction rate with little change to the thermodynamic performance of the formulation; both the rate of pressure rise and maximum pressure measured in the constant volume explosion test increase. For reactive structures, nanocomposite powders with bulk compositions of 8Al·MoO3, 12Al·MoO3, and 8Al·3CuO were prepared by ARM and consolidated using a uniaxial die. Consolidated samples had densities greater than 90% of theoretical maximum density while maintaining their high reactivity. Pellets prepared using 8Al·MoO3 powders were ignited by a CO2 laser. Ignition delays increased at lower laser powers and greater pellet densities. A simplified numerical model describing heating and thermal initiation of the reactive pellets predicted adequately the observed effects of both laser power and pellet density on the measured ignition delays. To investigate the reaction mechanisms in nanocomposite thermites, two types of nanocomposite reactive materials with the same bulk compositions 8Al·MoO3 were prepared by different methods. One of the materials was manufactured by ARM and the other, so called metastable interstitial composite (MIC), by mixing of nano-scaled individual powders. Clear differences in the low-temperature redox reactions, welldetectable by differential scanning calorimetry

  9. MINE WASTE TECHNOLOGY PROGRAM - SULFATE REDUCING BACTERIA REACTIVE WALL DEMO

    EPA Science Inventory


    Efforts reported in this document focused on the demonstration of a passive technology that could be used for remediation of
    thousands of abandoned mines existing in the Western United States that emanate acid mine drainage (AMD). This passive remedial technology takes ad...

  10. Skylab reactivation mission report

    NASA Technical Reports Server (NTRS)

    Chubb, W. B.

    1980-01-01

    On July 11, 1979, Skylab impacted the Earth's surface. The debris dispersion area stretched from the South Eastern Indian Ocean across a sparsely populated section of Western Australia. The events leading to the reentry of Skylab are discussed and a final assessment of the Skylab debris impact footprint is presented. Also included are detailed evaluations of the various Skylab systems that were reactivated when control of Skylab was regained in mid-1978 after having been powered down since February 4, 1974.

  11. Reactivation of latent melioidosis.

    PubMed

    Johnson, A B; Ali, N

    1990-09-01

    Reports of melioidosis in residents of European countries are rare. We describe a case of reactivation of latent melioidosis in a United Kingdom resident. The case demonstrates the lack of clinical response to chemotherapy despite proven in vitro sensitivity of the organism to the drugs used. It is important to consider melioidosis as a cause of septicaemic illness in patients who have travelled to, or been resident in South-East Asia.

  12. Reactivation of latent melioidosis.

    PubMed Central

    Johnson, A. B.; Ali, N.

    1990-01-01

    Reports of melioidosis in residents of European countries are rare. We describe a case of reactivation of latent melioidosis in a United Kingdom resident. The case demonstrates the lack of clinical response to chemotherapy despite proven in vitro sensitivity of the organism to the drugs used. It is important to consider melioidosis as a cause of septicaemic illness in patients who have travelled to, or been resident in South-East Asia. PMID:2235805

  13. Multiscale reactive molecular dynamics

    PubMed Central

    Knight, Chris; Lindberg, Gerrick E.; Voth, Gregory A.

    2012-01-01

    Many processes important to chemistry, materials science, and biology cannot be described without considering electronic and nuclear-level dynamics and their coupling to slower, cooperative motions of the system. These inherently multiscale problems require computationally efficient and accurate methods to converge statistical properties. In this paper, a method is presented that uses data directly from condensed phase ab initio simulations to develop reactive molecular dynamics models that do not require predefined empirical functions. Instead, the interactions used in the reactive model are expressed as linear combinations of interpolating functions that are optimized by using a linear least-squares algorithm. One notable benefit of the procedure outlined here is the capability to minimize the number of parameters requiring nonlinear optimization. The method presented can be generally applied to multiscale problems and is demonstrated by generating reactive models for the hydrated excess proton and hydroxide ion based directly on condensed phase ab initio molecular dynamics simulations. The resulting models faithfully reproduce the water-ion structural properties and diffusion constants from the ab initio simulations. Additionally, the free energy profiles for proton transfer, which is sensitive to the structural diffusion of both ions in water, are reproduced. The high fidelity of these models to ab initio simulations will permit accurate modeling of general chemical reactions in condensed phase systems with computational efficiency orders of magnitudes greater than currently possible with ab initio simulation methods, thus facilitating a proper statistical sampling of the coupling to slow, large-scale motions of the system. PMID:23249062

  14. Prophylactic administration of vector-encoded porcine granulocyte-colony stimulating factor reduces Salmonella shedding,tonsil colonization,& microbiota alterations of the gastrointestinal tract in Salmonella-challenged swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella colonization of food animals is a concern for animal health and public health as a food safety risk. Various obstacles impede the effort to reduce asymptomatic Salmonella carriage in food animals, including the existence of numerous serovars and the ubiquitous nature of Salmonella. To d...

  15. Tuning effect of silyl protecting groups on the glycosylation reactivity of arabinofuranosyl thioglycosides.

    PubMed

    Liang, Xing-Yong; Bin, Hua-Chao; Yang, Jin-Song

    2013-06-01

    The tuning effect of silyl protecting groups on the glycosylation reactivity of arabinofuranosyl phenyl thioglycoside donors is presented. Silyl ethers on the 3-, 5-, and 3,5-positions of the arabinofuranose ring are found to have an arming effect on the donor reactivity, whereas the cyclic 3,5-acetal type protecting groups reduce the reactivity.

  16. Latent Herpes Viral Reactivation in Astronauts

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.; Mehta, S. K.; Stowe, R.

    2008-01-01

    Latent viruses are ubiquitous and reactivate during stressful periods with and without symptoms. Latent herpes virus reactivation is used as a tool to predict changes in the immune status in astronauts and to evaluate associated health risks. Methods: Viral DNA was detected by real time polymerase chain reaction in saliva and urine from astronauts before, during and after short and long-duration space flights. Results and Discussion: EpsteinBarr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivated, and viral DNA was shed in saliva (EBV and VZV) or urine (CMV). EBV levels in saliva during flight were 10fold higher than baseline levels. Elevations in EBV specific CD8+ T-cells, viral antibody titers, and specific cytokines were consistent with viral reactivation. Intracellular levels of cytokines were reduced in EBVspecific Tcells. CMV, rarely present in urine of healthy individuals, was shed in urine of 27% of astronauts during all phases of spaceflight. VZV, not found in saliva of asymptomatic individuals, was found in saliva of 50% of astronauts during spaceflight and 35 days after flight. VZV recovered from astronaut saliva was found to be live, infectious virus. DNA sequencing demonstrated that the VZV recovered from astronauts was from the common European strain of VZV. Elevation of stress hormones accompanied viral reactivation indicating involvement of the hypothalmic-pituitary-adrenal and sympathetic adrenal-medullary axes in the mechanism of viral reactivation in astronauts. A study of 53 shingles patients found that all shingles patients shed VZV DNA in their saliva and the VZV levels correlated with the severity of the disease. Lower VZV levels in shingles patients were similar to those observed in astronauts. We proposed a rapid, simple, and cost-effective assay to detect VZV in saliva of patients with suspected shingles. Early detection of VZV infection allows early medical intervention.

  17. A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice.

    PubMed

    Kassa, Jiri; Sepsova, Vendula; Matouskova, Lenka; Horova, Anna; Musilek, Kamil

    2015-03-01

    The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel oximes K727 and K733 is significantly lower compared to the oxime HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.

  18. Deferasirox Reduces Oxidative Stress in Patients With Transfusion Dependency

    PubMed Central

    Saigo, Katsuyasu; Kono, Mari; Takagi, Yuri; Takenokuchi, Mariko; Hiramatsu, Yasushi; Tada, Hiroshi; Hishita, Terutoshi; Misawa, Masahito; Imoto, Shion; Imashuku, Shinsaku

    2013-01-01

    Background Iron chelation therapy is useful against the over-accumulation of iron and is expected to reduce oxidative stress resulting from the Fenton reaction and Haber-Weiss reaction. We monitored oxidative status and serum ferritin levels after in vivo administration of deferasirox (DFS) and studied the in vitro effects of iron chelators on neutrophil function. Methods Nine patients suffering from transfusion dependency were recruited for this study, and derivatives of reactive oxygen metabolite (dROM) tests to detect serum hydroperoxide levels were evaluated in addition to serum ferritin levels. Human neutrophil reactive oxygen species (ROS) production was determined with flow cytometry. Results Ferritin levels decreased after DFS treatment (P = 0.068), and a significant reduction in dROM levels was measured (P = 0.031). Fifty microM DFS significantly inhibited ROS production induced by fMLP in vitro (P < 0.0001), and tended to inhibit that induced by PMA. On the other hand, deferioxamine failed to inhibit ROS production even at high concentrations. Conclusions In vivo administration of DFS resulted in the reduction of oxidative stress, and this effect was considered to depend not only on a reduction in iron storage but also on the ability of DFS to inhibit neutrophil ROS production in vitro at clinically relevant plasma levels. Further studies are needed to examine the effects of iron chelators. PMID:23390477

  19. Reactivity of organism in prolonged space flights

    NASA Technical Reports Server (NTRS)

    Vasilyev, P. V.

    1980-01-01

    An analysis of published data are presented as well as the results of experiments which show that the state of weightlessness and hypodynamia result in a reduced orthostatic and vestibular resistance, increased sensitivity to infections, decreased endurance of accelerations and physical exercises, and altered reactivity of the organism to drugs. Various consequences of weightlessness on the human body, especially weightlessness combined with other factors linked to long space flights are also considered.

  20. Formation and Reactivity of Biogenic Iron Microminerals

    SciTech Connect

    Beveridge, Terrance J.; Ferris, F. Grant

    1999-06-01

    The overall purpose of the project is to explore and quantify the processes that control the formation and reactivity of biogenic iron microminerals, and the impact of these processes on the solubility of metal contaminants, e.g., uranium, chromium and nickel. The research addresses how surface components of bacterial cells, extracellular organic material, and the aqueous geochemistry of the DIRB microenvironment impacts the mineralogy, chemical state and micromorphology of reduced iron phases.

  1. Interpersonal reactivity differences in Tourette syndrome.

    PubMed

    Eddy, Clare M; Macerollo, Antonella; Martino, Davide; Cavanna, Andrea E

    2015-08-30

    Tourette syndrome (TS) frequently involves complex tics with social significance, including imitation or socially inappropriate behaviour. This study explored every-day perspective taking and empathic tendencies in 95 patients with TS and 60 healthy controls. Analyses indicated that both males and females with TS exhibited a different interpersonal reactivity profile to controls, characterised by a reduced tendency to take other people's perspectives, and elevated personal distress in response to intense emotional situations (e.g. people experiencing crises). PMID:26144583

  2. 78 FR 42451 - Listing of Color Additives Exempt From Certification; Reactive Blue 246 and Reactive Blue 247...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-16

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 73 Listing of Color Additives Exempt From... color additive regulations in Sec. Sec. 73.3100 and 73.3106 (21 CFR 73.3100 and 73.3106), respectively... Blue 246), as color additives in contact lenses. We also corrected the nomenclature for Reactive...

  3. Reactive strategies for containing developing outbreaks of pandemic influenza

    PubMed Central

    2011-01-01

    Background In 2009 and the early part of 2010, the northern hemisphere had to cope with the first waves of the new influenza A (H1N1) pandemic. Despite high-profile vaccination campaigns in many countries, delays in administration of vaccination programs were common, and high vaccination coverage levels were not achieved. This experience suggests the need to explore the epidemiological and economic effectiveness of additional, reactive strategies for combating pandemic influenza. Methods We use a stochastic model of pandemic influenza to investigate realistic strategies that can be used in reaction to developing outbreaks. The model is calibrated to documented illness attack rates and basic reproductive number (R0) estimates, and constructed to represent a typical mid-sized North American city. Results Our model predicts an average illness attack rate of 34.1% in the absence of intervention, with total costs associated with morbidity and mortality of US$81 million for such a city. Attack rates and economic costs can be reduced to 5.4% and US$37 million, respectively, when low-coverage reactive vaccination and limited antiviral use are combined with practical, minimally disruptive social distancing strategies, including short-term, as-needed closure of individual schools, even when vaccine supply-chain-related delays occur. Results improve with increasing vaccination coverage and higher vaccine efficacy. Conclusions Such combination strategies can be substantially more effective than vaccination alone from epidemiological and economic standpoints, and warrant strong consideration by public health authorities when reacting to future outbreaks of pandemic influenza. PMID:21356128

  4. Behavioral responses to acute and sub-chronic administration of the synthetic cannabinoid JWH-018 in adult mice prenatally exposed to corticosterone.

    PubMed

    Macrì, Simone; Lanuzza, Lara; Merola, Gustavo; Ceci, Chiara; Gentili, Stefano; Valli, Antonella; Macchia, Teodora; Laviola, Giovanni

    2013-07-01

    Recent data indicate that both availability and consumption of synthetic and natural psychoactive substances, marketed under the name of "legal highs", has increased. Among them, the aminoalkylindole-derivative JWH-018 is widely distributed due to its capability of binding the cannabinoid receptors CB1 and CB2 thereby mimicking the effects of classical drug agonists. To address whether the behavioral effects of the synthetic compound JWH-018 are similar to those induced by classical cannabinoid agonists, we investigated, in outbred CD1 mice, the consequences of its acute and sub-chronic administration (0, 0.03, 0.1, or 0.3 mg/kg, IP) at the level of body temperature, pain perception, general locomotion, and anxiety. In order to address whether the exposure to precocious stressors-modified individual reactivity to this psychoactive substance, we also investigated its effects in adult mice previously exposed to prenatal stress in the form of corticosterone supplementation in the maternal drinking water (33 or 100 mg/L). In the absence of major effects on motor coordination, JWH-018-reduced body temperature, locomotion and pain reactivity, and increased indices of anxiety. Prenatal corticosterone administration-reduced individual sensitivity to the effects of JWH-018 administration in all the aforementioned parameters. This altered response is not due to variations in JWH-018 metabolism. Present data support the hypothesis that precocious stress may affect, in the long-term, the functional status, and reactivity of the endocannabinoid system.

  5. Oral co-administration of α-lipoic acid, quercetin and captopril prevents gallium arsenide toxicity in rats.

    PubMed

    Bhatt, Kapil; Flora, S J S

    2009-07-01

    Gallium arsenide (GaAs), an inter-metallic semiconductor, known to exhibit superior optical and electronic properties compared to silicon, promotes its use in semiconductor industries. Extensive use of GaAs will inevitably lead to an increase in the exposure of workers manufacturing these products. Antioxidants are exogenous or endogenous compounds acting in several ways, including scavenging reactive oxygen species (ROS) or their precursors, inhibiting ROS formation, and binding metal ions needed for the catalysis of ROS generation. In the present study we investigated the protective efficacy of α-lipoic acid, quercetin and captopril individually against gallium arsenide exposure. Co-administration of α-lipoic acid with GaAs was most effective in reducing GaAs induced inhibition of blood δ-aminolevulinic acid dehydratase (ALAD) activity, liver, kidney and brain reduced glutathione (GSH) level and elevation of oxidized glutathione (GSSG). Captopril, on the other hand was effective in reducing thiobarbituric acid reactive substance (TBARS) levels, while quercetin reduced ROS in liver and kidney. The results suggest comparatively better preventive efficacy of concomitant α-lipoic acid administration during Gallium arsenide exposure compared to quercetin and captopril in preventing GaAs induced oxidative stress.

  6. Reactivation of fear memory renders consolidated amygdala synapses labile.

    PubMed

    Kim, Jeongyeon; Song, Beomjong; Hong, Ingie; Kim, Jihye; Lee, Junuk; Park, Sungmo; Eom, Jae Yong; Lee, C Justin; Lee, Sukwon; Choi, Sukwoo

    2010-07-14

    It is believed that memory reactivation transiently renders consolidated memory labile and that this labile or deconsolidated memory is reconsolidated in a protein synthesis-dependent manner. The synaptic correlate of memory deconsolidation upon reactivation, however, has not been fully characterized. Here, we show that 3,5-dihydroxyphenylglycine (DHPG), an agonist for group I metabotropic glutamate receptors (mGluRI), induces synaptic depotentiation only at thalamic input synapses onto the lateral amygdala (T-LA synapses) where synaptic potentiation is consolidated, but not at synapses where synaptic potentiation is not consolidated. Using this mGluRI-induced synaptic depotentiation (mGluRI-depotentiation) as a marker of consolidated synapses, we found that mGluRI-depotentiation correlated well with the state of memory deconsolidation and reconsolidation in a predictable manner. DHPG failed to induce mGluRI-depotentiation in slices prepared immediately after reactivation when the reactivated memory was deconsolidated. DHPG induced mGluRI-depotentiation 1 h after reactivation when the reactivated memory was reconsolidated, but it failed to do so when reconsolidation was blocked by a protein synthesis inhibitor. To test the memory-specificity of mGluRI-depotentiation, conditioned fear was acquired twice using two discriminative tones (2.8 and 20 kHz). Under this condition, mGluRI-depotentiation was fully impaired in slices prepared immediately after reactivation with both tones, whereas mGluRI-depotentiation was partially impaired immediately after reactivation with the 20 kHz tone. Consistently, microinjection of DHPG into the LA 1 h after reactivation reduced fear memory retention, whereas DHPG injection immediately after reactivation failed to do so. Our findings suggest that, upon memory reactivation, consolidated T-LA synapses enter a temporary labile state, displaying insensitivity to mGluRI-depotentiation.

  7. Controlling Material Reactivity Using Architecture.

    PubMed

    Sullivan, Kyle T; Zhu, Cheng; Duoss, Eric B; Gash, Alexander E; Kolesky, David B; Kuntz, Joshua D; Lewis, Jennifer A; Spadaccini, Christopher M

    2016-03-01

    3D-printing methods are used to generate reactive material architectures. Several geometric parameters are observed to influence the resultant flame propagation velocity, indicating that the architecture can be utilized to control reactivity. Two different architectures, channels and hurdles, are generated, and thin films of thermite are deposited onto the surface. The architecture offers an additional route to control, at will, the energy release rate in reactive composite materials. PMID:26669517

  8. Processing of emotional reactivity and emotional memory over sleep

    PubMed Central

    Baran, Bengi; Pace-Schott, Edward F.; Ericson, Callie; Spencer, Rebecca M. C.

    2012-01-01

    Sleep enhances memories, particularly emotional memories. As such, it has been suggested that sleep deprivation may reduce post-traumatic stress disorder. This presumes that emotional memory consolidation is paralleled by a reduction in emotional reactivity, an association that has not yet been examined. In the present experiment, we utilized an incidental memory task in humans and obtained valence and arousal ratings during two sessions separated either by 12 hours of daytime wake or 12 hours including overnight sleep. Recognition accuracy was greater following sleep relative to wake for both negative and neutral pictures. While emotional reactivity to negative pictures was greatly reduced over wake, the negative emotional response was relatively preserved over sleep. Moreover, protection of emotional reactivity was associated with greater time in REM sleep. Recognition accuracy, however, was not associated with REM. Thus, we provide the first evidence that sleep enhances emotional memory while preserving emotional reactivity. PMID:22262901

  9. Optimized Reactive Power Compensation Using Fuzzy Logic Controller

    NASA Astrophysics Data System (ADS)

    George, S.; Mini, K. N.; Supriya, K.

    2015-03-01

    Reactive power flow in a long transmission line plays a vital role in power transfer capability and voltage stability in power system. Traditionally, shunt connected compensators are used to control reactive power in long transmission line. Thyristor controlled reactor is used to control reactive power under lightly loaded condition. By controlling firing angle of thyristor, it is possible to control reactive power in the transmission lines. However, thyristor controlled reactor will inject harmonic current into the system. An attempt to reduce reactive power injection will increase harmonic distortion in the line current and vice versa. Thus, there is a trade-off between reactive power injection and harmonics in current. By optimally controlling the reactive power injection, harmonics in current can be brought within the specified limit. In this paper, a Fuzzy Logic Controller is implemented to obtain optimal control of reactive power of the compensator to maintain voltage and harmonic in current within the limits. An algorithm which optimizes the firing angle in each fuzzy subset by calculating the rank of feasible firing angles is proposed for the construction of rules in Fuzzy Logic Controller. The novelty of the algorithm is that it uses a simple error formula for the calculation of the rank of the feasible firing angles in each fuzzy subset.

  10. Efect of periodontal disease and non surgical periodontal treatment on C-reactive protein. Evaluation of type 1 diabetic patients

    PubMed Central

    Llambés, Fernando; Hernández-Mijares, Antonio; Guiha, Rami; Bautista, Daniel; Caffesse, Raúl

    2012-01-01

    Objectives: The purpose of this study was to analyze how anti-infectious periodontal treatment affects C reactive protein (CRP) values in patients with type 1 diabetes, and correlate baseline CRP levels with periodontal disease severity. Study Design: A cohort of fifty three subjects with type 1 diabetes and moderate to severe periodontitis were recruited. Periodontal parameters were measured, and blood samples were obtained to evaluate high-sensitivity C-reactive protein (hs-CRP). Group 1 was treated with scaling, root planning, and systemic administration of doxycycline. Group 2 received only scaling and root planning. Results: Hs-CRP was reduced after periodontal treatment in group 1 (-0.22 mg/l) and 2 (-0.21 mg/l ) but this reduction was not statistically significant, even in the patients with the best response to periodontal treatment. However, significant correlation appeared between hs-CRP and mean probing pocket depth (PPD) (p=0, 01) and mean clinical attachment level (CAL) (p=0,03). Conclusions: Non-surgical periodontal treatment couldn’t reduce hs-CRP values, however, it was found an association between advanced periodontitis and elevated blood hs-CRP levels in patients with type 1 diabetes. It can be speculated that periodontal disease increases production of pro-inflammatory mediators in patients with type 1 diabetes, but other producing sources of these pro-inflammatory substances may exist. Key words:Periodontal disease, periodontitis, diabetes mellitus type 1, periodontal therapy, C reactive protein. PMID:22322513

  11. Reactive astrocytosis-induced perturbation of synaptic homeostasis is restored by nerve growth factor.

    PubMed

    Cirillo, Giovanni; Bianco, Maria Rosaria; Colangelo, Anna Maria; Cavaliere, Carlo; Daniele, De Luca; Zaccaro, Laura; Alberghina, Lilia; Papa, Michele

    2011-03-01

    Reactive gliosis has been implicated in both inflammatory and neurodegenerative diseases. However, mechanisms by which astrocytic activation affects synaptic efficacy have been poorly elucidated. We have used the spared nerve injury (SNI) of the sciatic nerve to induce reactive astrocytosis in the lumbar spinal cord and investigate its potential role in disrupting the neuro-glial circuitry. Analysis of spinal cord sections revealed that SNI was associated with an increase of microglial (Iba1) and astrocytic (GFAP) markers. These changes, indicative of reactive gliosis, were paralleled by (i) a decrease of glial amino acid transporters (GLT1 and GlyT1) and increased levels of (ii) neuronal glutamate transporter EAAC1, (iii) neuronal vesicular GABA transporter (vGAT) and (iv) the GABAergic neuron marker GAD65/67. Besides the increase of Glutamate/GABA ratio, indicative of the perturbation of synaptic circuitry homeostasis, the boost of glutamate also compromised glial function in neuroprotection by up-regulating the xCT subunit of the glutamate-cystine antiport system and reducing glutathione (GSH) production. Finally, this study also shows that all these structural changes were linked to an alteration of endogenous NGF metabolism, as demonstrated by the decrease of endogenous NGF expression levels and increased activity of the NGF-degrading metalloproteinases. All the changes displayed by SNI-animals were reversed by a 7-days i.t. administration of NGF or GM6001, a generic metalloproteinase inhibitor, as compared to vehicle (ACSF)-treated animals. All together, these data strongly support the correlation between reactive astrogliosis and mechanisms underlying the perturbation of the synaptic circuitry in the SNI model of peripheral nerve injury, and the essential role of NGF in restoring both synaptic homeostasis and the neuroprotective function of glia.

  12. Effects of atorvastatin on human c reactive protein metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Statins are known to reduce plasma C-reactive protein (CRP) concentrations. Our goals were to define the mechanisms by which CRP was reduced by maximal dose atorvastatin. Eight subjects with combined hyperlipidemia (5 men and 3 postmenopausal women) were enrolled in a randomized, placebo-controlled...

  13. Administrative Costs of Education Voucher Programs.

    ERIC Educational Resources Information Center

    Hill, Paul T.

    This paper focuses on the administrative costs of vouchers programs. It considers the tasks that public and private agencies must undertake and estimates the administrative burdens and cash flow that local programs create. It assumes that all voucher programs, including those meant in part to reduce overcrowding, will be voluntary. The paper…

  14. Shear-Induced Reactive Gelation.

    PubMed

    Brand, Bastian; Morbidelli, Massimo; Soos, Miroslav

    2015-11-24

    In this work, we describe a method for the production of porous polymer materials in the form of particles characterized by narrow pore size distribution using the principle of shear-induced reactive gelation. Poly(styrene-co-divinylbenzene) primary particles with diameter ranging from 80 to 200 nm are used as building blocks, which are assembled into fractal-like clusters when exposed to high shear rates generated in a microchannel. It was found that independent of the primary particle size, it is possible to modulate the internal structure of formed fractal-like aggregates having fractal dimension ranging from 2.4 to 2.7 by varying the residence time in the microchannel. Thermally induced postpolymerization was used to increase the mechanical resilience of such formed clusters. Primary particle interpenetration was observed by SEM and confirmed by light scattering resulting in an increase of fractal dimension. Nitrogen sorption measurements and mercury porosimetry confirmed formation of a porous material with surface area ranging from 20 to 40 m(2)/g characterized by porosity of 70% and narrow pore size distribution with an average diameter around 700 nm without the presence of any micropores. The strong perfusive character of the synthesized material was confirmed by the existence of a plateau of the height equivalent to a theoretical plate measured at high reduced velocities using a chromatographic column packed with the synthesized microclusters. PMID:26488233

  15. Reactivation of Latent Viruses in Space

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.; Mehta, S. K.; Tyring, S. K.; Lugg, D. J.

    1999-01-01

    Reactivation of latent viruses is an important health risk for people working and living in physically isolated extreme environments such as Antarctica and space. Preflight quarantine does not significantly reduce the risk associated with latent viruses, however, pharmaceutical countermeasures are available for some viruses. The molecular basis of latency is not fully understood, but physical and psychosocial stresses are known to initiate the reactivation of latent viruses. Presumably, stress induced changes in selected hormones lead to alterations in the cell- mediated immune (CMI) response resulting in increased shedding of latent viruses. Limited access to space makes the use of ground-based analogs essential. The Australian Antarctic stations serve as a good stress model and simulate many aspects of space flight. Closed environmental chambers have been used to simulate space flight since the Skylab missions and have also proven to be a valuable analog of selected aspects of space flight.

  16. Physical Activity and Hemodynamic Reactivity in Chronic Kidney Disease

    PubMed Central

    Agarwal, Rajiv; Light, Robert P.

    2008-01-01

    Background and objectives: Patients with chronic kidney disease (CKD) have an elevated cardiovascular risk. This study was designed to understand better the presence and strength of the relationship between physical activity and BP and to explore determinants of hemodynamic reactivity. Design, setting, participants, & measurements: Twenty-four patients with CKD (mean age 69.5 yr; 3.1 antihypertensive drugs; estimated GFR 47 ml/min per 1.73 m2, albumin/creatinine ratio 403 mg/g) were studied on three occasions during a 6-wk period with 24-h ambulatory BP monitoring and simultaneous activity monitoring with wrist actigraphy. Results: Nondippers were found have a greater level of sleep activity compared with dippers, although the awake activity level was similar (7.06 versus 6.73) between groups (P = 0.042 for interaction). In 3587 BP activity pairs, hemodynamic reactivity was variable between individuals (systolic BP reactivity 1.06 [SD 10.50]; diastolic BP reactivity 0.89 [SD 7.80] heart rate reactivity 1.18 [SD 11.00]); those who were more sedentary had a greater increment in systolic BP compared with those who were less sedentary. Antihypertensive drugs blunted hemodynamic reactivity. Hemodynamic reactivity was greatest between 12 a.m. and 8 a.m., making this a vulnerable period for cardiovascular events. Conclusions: Greater hemodynamic reactivity in sedentary people with CKD offers a possible and thus far unrecognized mechanism of cardiovascular damage. Besides reducing BP, antihypertensive drugs reduce hemodynamic reactivity, which offers another plausible mechanism of cardiovascular protection with their use. PMID:18922983

  17. Transportation Security Administration

    MedlinePlus

    ... content Official website of the Department of Homeland Security Transportation Security Administration A - Z Index What Can I Bring? Search form Apples Main menu Administrator Travel Security Screening Special Procedures TSA Pre✓® Passenger Support Travel ...

  18. NASA, NOAA administrators nominated

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    President Ronald Reagan recently said he intended to nominate James Montgomery Beggs as NASA Administrator and John V. Byrne as NOAA Administrator. These two positions are key scientific posts that have been vacant since the start of the Reagan administration on January 20. The President also said he intends to nominate Hans Mark as NASA Deputy Administrator. At press time, Reagan had not designated his nominee for the director of the Office of Science and Technology Policy.

  19. Geotechnical techniques for the construction of reactive barriers

    PubMed

    Day; O'Hannesin; Marsden

    1999-06-30

    One of the newest and most promising remediation techniques for the treatment of contaminated groundwater and soil is the reactive barrier wall (commonly known as PRB for permeable reactive barrier or reactive barrier). Although a variety of treatment media and strategies are available, the most common technique is to bury granular iron in a trench so that contaminated groundwater passes through the reactive materials, the contaminants are removed and the water becomes 'clean'. The principal advantages of the technique are the elimination of pumping, mass excavation, off-site disposal, and a very significant reduction in costs. The use of this technology is now becoming better known and implemented. Special construction considerations need to be made when planning the installation of reactive barriers or PRBs to ensure the design life of the installation and to be cost-effective. Geotechnical techniques such as slurry trenching, deep soil mixing, and grouting can be used to simplify and improve the installation of reactive materials relative to conventional trench and fill methods. These techniques make it possible to reduce the hazards to workers during installation, reduce waste and reduce costs for most installations. To date, most PRBs have been installed to shallow depths using construction methods such as open trenching and/or shored excavations. While these methods are usable, they are limited to shallow depths and more disruptive to the site's normal use. Geotechnical techniques are more quickly installed and less disruptive to site activities and thus more effective. Recently, laboratory studies and pilot projects have demonstrated that geotechnical techniques can be used successfully to install reactive barriers. This paper describes the factors that are important in designing a reactive barrier or PRB installation and discusses some of the potential problems and pitfalls that can be avoided with careful planning and the use of geotechnical techniques

  20. Hydrothermal reactivity of saponite.

    USGS Publications Warehouse

    Whitney, G.

    1983-01-01

    The nature and extent of the reactions of synthetic Fe-free saponite have been investigated under experimental hydrothermal conditions as a first step towards understanding saponite reactivity under relatively simple conditions. Saponite crystallizes from amorphous gel of ideal saponite composition within 7 days at 300o-550oC under P = 1 kbar. Reactions subsequent to this initial crystallization depend on reaction T and interlayer cations. Saponite is found to react hydrothermally, over a period of 200 days, at T down to 400oC, at least 150oC lower than previously reported, but showed no signs of reaction below 400oC. At 450oC, a mixture of talc/saponite and saponite/phlogopite clays forms from K-saponite via intracrystalline layer transformations, while above 450oC the initial K-saponite dissolves, with talc and phlogopite forming as discrete phases. After 200 days reactions at 400-450oC were not complete, so that given sufficient time to reach equilibrium, a lower hydrothermal stability limit for saponite is possible. Further study of the Fe-bearing saponite system will be required before experimental results can be applied to natural systems.-D.F.B.

  1. A Philosophy of Administration.

    ERIC Educational Resources Information Center

    Bruening, William H.

    Justification is given for paying relatively large salaries to college administrators, specifically the president or chancellor and the chief academic officer. Three administrative task areas are discussed as criteria: management, administration per se, and leadership. It is contended that only leadership can be used as a criterion for…

  2. Antiviral Prevention of Sepsis Induced Cytomegalovirus Reactivation in Immunocompetent Mice

    PubMed Central

    Forster, Meghan R.; Trgovcich, Joanne; Zimmerman, Peter; Chang, Alexander; Miller, Cortland; Klenerman, Paul; Cook, Charles H.

    2009-01-01

    Introduction Immunocompetent patients can reactivate latent cytomegalovirus (CMV) during critical illness and reactivation is associated with significantly worse outcomes. Prior to clinical trials in humans to prove causality, we sought to determine an optimal antiviral treatment strategy. Methods Mice latently infected with murine CMV (MCMV) received a septic reactivation trigger and were randomized to receive one of four ganciclovir regimens or saline. Lungs were evaluated for viral transcriptional reactivation and fibrosis after each regimen. Influences of ganciclovir on early sepsis induced pulmonary inflammation and T-cell activation were studied after sepsis induction. Results All ganciclovir regimens reduced measurable MCMV transcriptional reactivation, and 10mg/day for 7 or 21 days was most effective. Lower dose (5mg/kg/day) or delayed therapy were associated with significant breakthrough reactivation. Higher doses of ganciclovir given early were associated with the lowest incidence of pulmonary fibrosis, and delay of therapy for 1 week was associated with significantly worse pulmonary fibrosis. Although bacterial sepsis induced activation of MCMV-specific pulmonary T-cells, this activation was not influenced by ganciclovir. Conclusion These results suggest that antiviral treatment trials in humans should use 10mg/kg/day ganciclovir administered as early as possible in at-risk patients to minimize reactivation events and associated pulmonary injury PMID:20004216

  3. Corticosterone levels determine individual vulnerability to amphetamine self-administration.

    PubMed Central

    Piazza, P V; Maccari, S; Deminière, J M; Le Moal, M; Mormède, P; Simon, H

    1991-01-01

    Individual vulnerability to the reinforcing properties of drugs appears to be an essential characteristic predisposing humans to addiction. In animals, a greater behavioral reactivity to a mild stress, such as exposure to a novel environment, is an index of the vulnerability to acquire amphetamine self-administration. Biological responses to stress as well as behavioral reactivity may predict such a vulnerability. In the present study, rats with a longer duration of corticosterone secretion after exposure to novelty showed facilitation of acquisition of amphetamine self-administration. Furthermore, corticosterone administration in nonpredisposed individuals increased the reinforcing value of the drug and facilitated the acquisition of amphetamine self-administration. These results indicate that the stress-related activity of the hypothalamic-pituitary-adrenal axis may play a role in the pathogenesis of psychostimulant addiction. PMID:2006148

  4. Reducing Dropouts.

    ERIC Educational Resources Information Center

    Timpane, Michael; And Others

    A group of three conference papers, all addressing the subject of effective programs to decrease the number of school dropouts, is presented in this document. The first paper, "Systemic Approaches to Reducing Dropouts" (Michael Timpane), asserts that dropping out is a symptom of failures in the social, economic, and educational systems. Dropping…

  5. Kinetics of reactive wetting

    SciTech Connect

    Yost, F.G.

    2000-04-14

    The importance of interfacial processes in materials joining has a long history. A significant amount of work has suggested that processes collateral to wetting can affect the extent of wetting and moderate or retard wetting rate. Even very small additions of a constituent, known to react with the substrate, cause pronounced improvement in wetting and are exploited in braze alloys, especially those used for joining to ceramics. In the following a model will be constructed for the wetting kinetics of a small droplet of metal containing a constituent that diffuses to the wetting line and chemically reacts with a flat, smooth substrate. The model is similar to that of Voitovitch et al. and Mortensen et al. but incorporates chemical reaction kinetics such that the result contains both diffusion and reaction kinetics. The model is constructed in the circular cylinder coordinate system, satisfies the diffusion equation under conditions of slow flow, and considers diffusion and reaction at the wetting line to be processes in series. This is done by solving the diffusion equation with proper initial and boundary conditions, computing the diffusive flux at the wetting line, and equating this to both the convective flux and reaction flux. This procedure is similar to equating the current flowing in components of a series circuit. The wetting rate will be computed versus time for a variety of diffusion and reaction conditions. A transition is observed from nonlinear (diffusive) to linear (reactive) behavior as the control parameters (such as the diffusion coefficient) are modified. This is in agreement with experimental observations. The adequacy of the slow flow condition, used in this type of analysis, is discussed and an amended procedure is suggested.

  6. Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network.

    PubMed

    Hughes, Tyler B; Dang, Na Le; Miller, Grover P; Swamidass, S Joshua

    2016-08-24

    Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural network-the XenoSite reactivity model-using literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule-level, the

  7. Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network.

    PubMed

    Hughes, Tyler B; Dang, Na Le; Miller, Grover P; Swamidass, S Joshua

    2016-08-24

    Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural network-the XenoSite reactivity model-using literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule-level, the

  8. Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network

    PubMed Central

    2016-01-01

    Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural network—the XenoSite reactivity model—using literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule

  9. Modeling Reactivity to Biological Macromolecules with a Deep Multitask Network

    PubMed Central

    2016-01-01

    Most small-molecule drug candidates fail before entering the market, frequently because of unexpected toxicity. Often, toxicity is detected only late in drug development, because many types of toxicities, especially idiosyncratic adverse drug reactions (IADRs), are particularly hard to predict and detect. Moreover, drug-induced liver injury (DILI) is the most frequent reason drugs are withdrawn from the market and causes 50% of acute liver failure cases in the United States. A common mechanism often underlies many types of drug toxicities, including both DILI and IADRs. Drugs are bioactivated by drug-metabolizing enzymes into reactive metabolites, which then conjugate to sites in proteins or DNA to form adducts. DNA adducts are often mutagenic and may alter the reading and copying of genes and their regulatory elements, causing gene dysregulation and even triggering cancer. Similarly, protein adducts can disrupt their normal biological functions and induce harmful immune responses. Unfortunately, reactive metabolites are not reliably detected by experiments, and it is also expensive to test drug candidates for potential to form DNA or protein adducts during the early stages of drug development. In contrast, computational methods have the potential to quickly screen for covalent binding potential, thereby flagging problematic molecules and reducing the total number of necessary experiments. Here, we train a deep convolution neural network—the XenoSite reactivity model—using literature data to accurately predict both sites and probability of reactivity for molecules with glutathione, cyanide, protein, and DNA. On the site level, cross-validated predictions had area under the curve (AUC) performances of 89.8% for DNA and 94.4% for protein. Furthermore, the model separated molecules electrophilically reactive with DNA and protein from nonreactive molecules with cross-validated AUC performances of 78.7% and 79.8%, respectively. On both the site- and molecule

  10. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation...

  11. 21 CFR 10.90 - Food and Drug Administration regulations, recommendations, and agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE PRACTICES AND PROCEDURES General Administrative... Commissioner, e.g., model State and local ordinances, or personnel practices for reducing radiation...

  12. "Bioshrouding": a novel approach for securing reactive mineral tailings.

    PubMed

    Johnson, D Barrie; Yajie, Liu; Okibe, Naoko

    2008-03-01

    A novel technique ("bioshrouding") for safeguarding highly reactive sulfidic mineral tailings deposits is proposed. In this, freshly milled wastes are colonised with ferric iron-reducing heterotrophic acidophilic bacteria that form biofilms on reactive mineral surfaces, thereby preventing or minimising colonisation by iron sulfide-oxidising chemolithotrophs such as Acidithiobacillus ferrooxidans and Leptospirillum spp. Data from initial experiments showed that dissolution of pyrite could be reduced by between 57 and 75% by "bioshrouding" the mineral with three different species of heterotrophic acidophiles (Acidiphilium, Acidocella and Acidobacterium spp.), under conditions that were conducive to microbial oxidative dissolution of the iron sulfide. PMID:17975731

  13. Reactive Functionalized Membranes for Polychlorinated Biphenyl Degradation

    PubMed Central

    Gui, Minghui; Ormsbee, Lindell E.; Bhattacharyya, Dibakar

    2014-01-01

    Membranes have been widely used in water remediation (e.g. desalination and heavy metal removal) because of the ability to control membrane pore size and surface charge. The incorporation of nanomaterials into the membranes provides added benefits through increased reactivity with different functionality. In this study, we report the dechlorination of 2-chlorobiphenyl in the aqueous phase by a reactive membrane system. Fe/Pd bimetallic nanoparticles (NPs) were synthesized (in-situ) within polyacrylic acid (PAA) functionalized polyvinylidene fluoride (PVDF) membranes for degradation of polychlorinated biphenyls (PCBs). Biphenyl formed in the reduction was further oxidized into hydroxylated biphenyls and benzoic acid by an iron-catalyzed hydroxyl radical (OH•) reaction. The formation of magnetite on Fe surface was observed. This combined pathway (reductive/oxidative) could reduce the toxicity of PCBs effectively while eliminating the formation of chlorinated degradation byproducts. The successful manufacturing of full-scale functionalized membranes demonstrates the possibility of applying reactive membranes in practical water treatment. PMID:24954974

  14. Love alters autonomic reactivity to emotions.

    PubMed

    Schneiderman, Inna; Zilberstein-Kra, Yael; Leckman, James F; Feldman, Ruth

    2011-12-01

    Periods of bond formation are accompanied by physiological and emotional changes, yet, little is known about the effects of falling in love on the individual's physiological response to emotions. We examined autonomic reactivity to the presentation of negative and positive films in 112 young adults, including 57 singles and 55 new lovers who began a romantic relationship 2.5 months prior to the experiment Autonomic reactivity was measured by Respiratory Sinus Arrhythmia (RSA) to two baseline emotionally neutral films, two negative films, and two positive films. Results demonstrated that RSA in singles decreased during the presentation of negative emotions, indicating physiological stress response. However, no such decrease was found among new lovers, pointing to more optimal vagal regulation during the period of falling in love. Autonomic reactivity, indexed by RSA decrease from the positive to the negative films, was greater among singles as compared to lovers, suggesting that love buffers against autonomic stress and facilitates emotion regulation. Findings suggest that vagal regulation may be one mechanism through which love and attachment reduce stress and promote well-being and health.

  15. Recent changes in anthropogenic reactive nitrogen compounds

    NASA Astrophysics Data System (ADS)

    Andronache, Constantin

    2014-05-01

    Significant anthropogenic perturbations of the nitrogen cycle are the result of rapid population growth, with mounting need for food and energy production. The increase of reactive nitrogen compounds (such as NOx, HNO3, NH3, and N2O) has a significant impact on human health, environment, and climate. NOx emissions contribute to O3 chemistry, aerosol formation and acidic precipitation. Ammonia is a notable atmospheric pollutant that may deteriorate ecosystems and contribute to respiratory problems. It reacts with acidic gases to form aerosols or is deposited back to ecosystems. The application of fertilizers accounts for most of the N2O production, adding to greenhouse gas emissions. We analyze the change of some reactive nitrogen compounds based on observations, in eastern United States. Results show that the control of NOx and SO2 emissions over the last decades caused a significant decrease of acidic deposition. The nitrate deposition is highest in eastern US, while the ammonium ion concentration is highest in central US regions. Overall, the inorganic nitrogen wet deposition from nitrate and ammonium is enhanced in central, and eastern US. Research shows that sensitive ecosystems in northeastern regions exhibit a slow recovery from the accumulated effects of acidic deposition. Given the growing demand for nitrogen in agriculture and industry, we discuss possible pathways to reduce the impact of excess reactive nitrogen on the environment.

  16. Aerobic fitness, psychological characteristics, and cardiovascular reactivity to stress.

    PubMed

    Czajkowski, S M; Hindelang, R D; Dembroski, T M; Mayerson, S E; Parks, E B; Holland, J C

    1990-01-01

    Examined the relations among aerobic fitness (AF), psychological characteristics, and cardiovascular reactivity using 62 men divided into highly fit and less fit groups based on a maximal treadmill exercise test. Several psychological and physiological variables were measured, and subjects' cardiovascular reactivity was assessed during a mental arithmetic task and during a video game task. Highly fit subjects showed a significantly smaller increase in both diastolic blood pressure (DBP) and heart rate (HR) and reported themselves to be less anxious and less angry than less fit subjects. Furthermore, controlling for subjects' scores on a scale assessing angry temperament reduced the relationship between AF and DBP reactivity to nonsignificant levels. These results suggest that degree of dispositional anger, which covaries with increased fitness, may contribute to the apparent relationship between AF and DBP--but not HR--reactivity.

  17. Grinding methods to enhance the reactivity of olivine

    SciTech Connect

    Summers, Cathy A.; Dahlin, David C.; Rush, Gilbert E.; O'Connor, William K.; Gerdemann, Stephen J.

    2005-08-01

    The Albany Research Center (ARC) conducted studies of mechanical activation by conventional and ultrafine grinding techniques to enhance olivine reactivity in mineral carbonation reactions. Activated olivine is one of several solid feed materials used at ARC in reactions with carbon dioxide to form carbonate minerals. This paper compares grinding techniques via energy demand data and product characteristics, including particle size distributions, surface areas, full-width-at-half-maximum (FWHM) XRD analyses, and particle morphology by SEM analyses. Reactivity was calculated by percent conversion to carbonate in subsequent carbonation tests. Particle size reduction has the greatest impact on reactivity, and wet grinding is more energy efficient than dry grinding. Large additional inputs of energy to increase surface area or reduce crystallinity do not result in proportional improvements in reactivity.

  18. Reactive Orthotropic Lattice Diffuser for Noise Reduction

    NASA Technical Reports Server (NTRS)

    Khorrami, Mehdi R. (Inventor)

    2016-01-01

    An orthotropic lattice structure interconnects porous surfaces of the flap with internal lattice-structured perforations to equalize the steady pressure field on the flap surfaces adjacent to the end and to reduce the amplitude of the fluctuations in the flow field near the flap end. The global communication that exists within all of the perforations provides the mechanism to lessen the pressure gradients experienced by the end portion of the flap. In addition to having diffusive effects (diffusing the incoming flow), the three-dimensional orthogonal lattice structure is also reactive (acoustic wave phase distortion) due to the interconnection of the perforations.

  19. Preparation of reactive beta-dicalcium silicate

    DOEpatents

    Shen, Ming-Shing; Chen, James M.; Yang, Ralph T.

    1982-01-01

    This invention relates to the preparation of fine particles of reactive beta-dicalcium silicate by means of a solid state process which comprises firing a mixture of calcium sulfate, silica and a reducing additive selected from the group consisting of calcium sulfide, carbon, carbon monoxide, methane and hydrogen, at a temperature of about 850.degree.-1000.degree. C. A carrier gas such as nitrogen or carbon dioxide may also be added, if desired. A high concentration of sulfur dioxide is a by-product of this process.

  20. Preparation of reactive beta-dicalcium silicate

    DOEpatents

    Shen, M.S.; Chen, J.M.; Yang, R.T.

    1980-02-28

    This invention relates to the preparation of fine particles of reactive beta-dicalcium silicate by means of a solid state process which comprises firing a mixture of calcium sulfate, silica, and a reducing additive selected from the group consisting of calcium sulfide, carbon, carbon monoxide, methane, and hydrogen, at a temperature of about 850 to 1000/sup 0/C. A carrier gas such as nitrogen or carbon dioxide may also be added, if desired. A high concentration of sulfur dioxide is a by-product of this process.

  1. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury

    PubMed Central

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-01-01

    Background: Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. Methods: In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Results: Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Conclusion: Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice. PMID:26950150

  2. COAL SLAGGING AND REACTIVITY TESTING

    SciTech Connect

    Donald P. McCollor; Kurt E. Eylands; Jason D. Laumb

    2003-10-01

    carbon as well as slagging. A second phase of the project involved advanced analysis of the baseline coal along with an Australian coal fired at the plant. These analysis results were used in equilibrium thermodynamic modeling along with a coal quality model developed by the EERC to assess slagging, fouling, and opacity for the coals. Bench-scale carbon conversion testing was performed in a drop-tube furnace to assess the reactivity of the coals. The Australian coal had a higher mineral content with significantly more clay minerals present than the baseline coal. The presence of these clay minerals, which tend to melt at relatively low temperatures, indicated a higher potential for problematic slagging than the baseline coal. However, the pyritic minerals, comprising over 25% of the baseline mineral content, may form sticky iron sulfides, leading to severe slagging in the burner region if local areas with reducing conditions exist. Modeling results indicated that neither would present significant fouling problems. The Australian coal was expected to show slagging behavior much more severe than the baseline coal except at very high furnace temperatures. However, the baseline coal was predicted to exhibit opacity problems, as well as have a higher potential for problematic calcium sulfate-based low-temperature fouling. The baseline coal had a somewhat higher reactivity than the Australian coal, which was consistent with both the lower average activation energy for the baseline coal and the greater carbon conversion at a given temperature and residence time. The activation energy of the baseline coal showed some effect of oxygen on the activation energy, with E{sub a} increasing at the lower oxygen concentration, but may be due to the scatter in the baseline coal kinetic values at the higher oxygen level tested.

  3. Hepatitis B Reactivation with Novel Agents in Non-Hodgkin’s Lymphoma and Prevention Strategies

    PubMed Central

    Ozoya, Oluwatobi O.; Sokol, Lubomir; Dalia, Samir

    2016-01-01

    Abstract Hepatitis B virus (HBV) infection remains an endemic disease in most parts of the world despite available prophylactic vaccines. Non-Hodgkin’s lymphoma is the most common hematological malignancy, and certain patients undergoing therapy are at increased risk of HBV reactivation. Rituximab, a monoclonal antibody, is well studied in HBV reactivation, but newer agents have been implicated as well. Here, we review novel agents suspected in HBV reactivation and effective strategies to prevent HBV reactivation. Fifteen years of literature were reviewed in order to better understand the reactivation rates of hepatitis B in patients with non-Hodgkin’s lymphoma. Anti-CD20 antibodies continue to be the main medications that can lead to HBV reactivation, and HBV reactivation rates have decreased with increased awareness. HBV reactivation is uncommon when using other novel agents. Entecavir and lamivudine remain the agents of choice to prevent HBV reactivation in high risk patients. In conclusion, the immunosuppressive effect of NHL and its therapy provide a pathway for HBV reactivation, especially in patients treated with anti-CD20 antibody. Since many HBV positive patients are often excluded from clinical trials of novel agents in NHL, more aggressive post-market surveillance of new agents, well-designed best practice advisories, and timely case reports are needed to reduce the incidence of HBV reactivation. Lastly, large prospective investigations coupled with well-utilized best practice advisories need to be conducted to understand the impact of more potent novel NHL therapy on HBV reactivation. PMID:27350944

  4. A comparison of reactivating and therapeutic efficacy of bispyridinium acetylcholinesterase reactivator KR-22934 with the oxime K203 and commonly used oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice.

    PubMed

    Kassa, Jiri; Karasova, Jana Zdarova; Pavlikova, Ruzena; Musilek, Kamil; Kuca, Kamil; Bajgar, Jiri; Jung, Young-Sik

    2011-03-01

    The potency of bispyridinium acetylcholinesterase reactivator KR-22934 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with the oxime K203 and commonly used oximes. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of KR-22934 was slightly higher than the reactivating efficacy of K203 and roughly corresponded to the reactivating efficacy of obidoxime and trimedoxime in blood and diaphragm. On the other hand, the oxime KR-22934 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied approximately corresponded to their reactivating efficacy. Based on the results, one can conclude that the oxime KR-22934 is not suitable for the replacement of commonly used oximes for the antidotal treatment of tabun poisoning in spite of its potency to reactivate tabun-inhibited acetylcholinesterase in the peripheral compartment (blood, diaphragm).

  5. [Effect of antipsychotic amisulpride on immune reactivity].

    PubMed

    Idova, G V; Al'perina, E L; Lobacheva, O A; Zhukova, E N; Cheĭdo, M A; Meniavtseva, T A; Vetlugina, T P

    2013-01-01

    The effect of atypical antipsychotic solian (amisulpride), binding predominantly to dopamine D2/D3-receptors, on the immune reactivity has been studied in mice of the CBA strain with different psychoemotional states (aggressive and submissive behavior). In addition, the effect of solian on the expression of various CD-markers of lymphocytes in has been analyzed in vitro for patients with schizophrenia diagnosis. Chronic (10 days) administration of solian in mice at a dose of 5.0 mg/kg resulted in a significant suppression of the immune response to T-dependent antigen (sheep red blood cells). This effect was manifested in animals with both psychoemotional states, but was more expressed in aggressive animals. In the in vitro system, solian produced opposite effects on the expression of surface CD receptors in lymphocytes of patients with schizophrenia. It is suggested that solian does not only affects immune function through D2 receptors of the brain, but also directly influences immunocompetent cells.

  6. Reactive Collision Avoidance Algorithm

    NASA Technical Reports Server (NTRS)

    Scharf, Daniel; Acikmese, Behcet; Ploen, Scott; Hadaegh, Fred

    2010-01-01

    The reactive collision avoidance (RCA) algorithm allows a spacecraft to find a fuel-optimal trajectory for avoiding an arbitrary number of colliding spacecraft in real time while accounting for acceleration limits. In addition to spacecraft, the technology can be used for vehicles that can accelerate in any direction, such as helicopters and submersibles. In contrast to existing, passive algorithms that simultaneously design trajectories for a cluster of vehicles working to achieve a common goal, RCA is implemented onboard spacecraft only when an imminent collision is detected, and then plans a collision avoidance maneuver for only that host vehicle, thus preventing a collision in an off-nominal situation for which passive algorithms cannot. An example scenario for such a situation might be when a spacecraft in the cluster is approaching another one, but enters safe mode and begins to drift. Functionally, the RCA detects colliding spacecraft, plans an evasion trajectory by solving the Evasion Trajectory Problem (ETP), and then recovers after the collision is avoided. A direct optimization approach was used to develop the algorithm so it can run in real time. In this innovation, a parameterized class of avoidance trajectories is specified, and then the optimal trajectory is found by searching over the parameters. The class of trajectories is selected as bang-off-bang as motivated by optimal control theory. That is, an avoiding spacecraft first applies full acceleration in a constant direction, then coasts, and finally applies full acceleration to stop. The parameter optimization problem can be solved offline and stored as a look-up table of values. Using a look-up table allows the algorithm to run in real time. Given a colliding spacecraft, the properties of the collision geometry serve as indices of the look-up table that gives the optimal trajectory. For multiple colliding spacecraft, the set of trajectories that avoid all spacecraft is rapidly searched on

  7. Kinetics of Reactive Wetting

    SciTech Connect

    YOST, FREDERICK G.

    1999-09-09

    for a variety of diffusion and reaction conditions. A transition is observed from nonlinear (diffusive) to linear (reactive) behavior as the control parameters (such as the diffusion coefficient) are modified. This is in agreement with experimental observations. The adequacy of the slow flow condition, used in this type of analysis, is discussed and an amended procedure is suggested.

  8. Fuel Temperature Coefficient of Reactivity

    SciTech Connect

    Loewe, W.E.

    2001-07-31

    A method for measuring the fuel temperature coefficient of reactivity in a heterogeneous nuclear reactor is presented. The method, which is used during normal operation, requires that calibrated control rods be oscillated in a special way at a high reactor power level. The value of the fuel temperature coefficient of reactivity is found from the measured flux responses to these oscillations. Application of the method in a Savannah River reactor charged with natural uranium is discussed.

  9. Syzigium cumini seed extracts reduce tissue damage in diabetic rat brain.

    PubMed

    Stanely Mainzen Prince, P; Kamalakkannan, N; Menon, Venugopal P

    2003-02-01

    Syzigium cumini commonly known as Jamun, is widely used in different parts of India for the treatment of diabetes mellitus. Oral administration of an aqueous Jamun seed extract (JSEt) for 6 weeks caused a significant decrease in lipids, thiobarbituric acid reactive substances (TBARS) and an increase in catalase and superoxide dismutase in the brain of alloxan induced diabetic rats. Oral administration of an alcoholic JSEt for 6 weeks brought back all the parameters to near normal. The effect of alcoholic JSEt (100 mg/kg) was better than aqueous JSEt (5 g/kg). The effect of both these extracts was better than glibenclamide (600 microg/kg). Thus, our study shows that S. cumini seed extracts reduce tissue damage in diabetic rat brain. PMID:12648817

  10. Synchronous reactive programming in Ptolemy

    SciTech Connect

    Boulanger, F.; Vidal-Naquet, G.

    1996-12-31

    Synchronous reactive languages allow a high level deterministic description of reactive systems such as control-command systems. Their well defined mathematical semantics makes it possible to check formal properties on the control of a system. In previous work, we developed an object-oriented execution model for synchronous reactive modules. This model is implemented as a set of tools and a C++ class library, and allows us to use object-oriented methodologies and tools for the design of complex applications with both transformational and reactive parts. Among these design tools, the Ptolemy system stands as an object-oriented framework that supports various execution models, or {open_quotes}domains{close_quotes}. We are currently working on a translator from the output format of the Lustre and Esterel compilers to the Ptolemy language. Since no existing domain matches the reactive synchronous execution model, we also plan to develop a SEC (Synchronous Execution and Communication) domain. Such a domain will provide support for the execution of synchronous modules in Ptolemy. One of the most interesting features of Ptolemy is the communication between domains. Therefore we discuss the interface of the SEC domain to other domains to determine the meaning of communications between them. The main goal is to allow the use of synchronous reactive modules for the control of the behavior of data-flow or discrete event processes.

  11. Veterans Administration Databases

    Cancer.gov

    The Veterans Administration Information Resource Center provides database and informatics experts, customer service, expert advice, information products, and web technology to VA researchers and others.

  12. MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

    EPA Science Inventory

    Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

  13. Pre-pregnancy stress reactivity and pregnancy outcome.

    PubMed

    Harville, Emily W; Gunderson, Erica P; Matthews, Karen A; Lewis, Cora E; Carnethon, Mercedes

    2010-11-01

    Stress has been proposed as a cause of preterm birth (PTB) and small-for-gestational age (SGA), but stress does not have the same effects on all women. It may be that a woman's reaction to stress relates to her pregnancy health, and previous studies indicate that higher reactivity is associated with reduced birthweight and gestational age. The objective of this study was to examine the relationship between pre-pregnancy cardiovascular reactivity to stress and pregnancy outcome. The sample included 917 women in the Coronary Artery Risk Development in Young Adults Study who had cardiovascular reactivity measured in 1987-88 and at least one subsequent singleton livebirth within an 18-year period. Cardiovascular reactivity was measured using a video game, star tracing and cold pressor test. Gestational age and birthweight were based on the women's self-report, with PTB defined as birth <37 weeks' gestation and SGA as weight <10th percentile for gestational age. Linear and Poisson regression and generalised estimating equations were used to model the relationship between reactivity to stress and birth outcomes with control for confounders. Few associations were seen between reactivity and pregnancy outcomes. Higher pre-pregnancy diastolic blood pressure (adjusted relative risk 1.14; 95% confidence interval [CI] 0.98, 1.34) and mean arterial pressure reactivity (1.15; 0.98, 1.36) were associated with risk of PTB at first pregnancy, while SGA was associated with lower systolic blood pressure reactivity (0.76; 0.60, 0.95). No associations were seen with other measures of reactivity. Contrary to hypothesis, the association between heart rate reactivity and PTB in first pregnancy was stronger in whites (adjusted relative risk 1.39; 1.03, 1.88) than in blacks (1.00; 0.83, 1.20; P for interaction = 0.08). Similar results were found for mean arterial pressure. No strong associations were found between higher pre-pregnancy stress reactivity and SGA or PTB, and stress reactivity

  14. 78 FR 63177 - Order on Voluntary Remand and Clarifying Policy on Filing of Reactive Power Service Rate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... Generation Sources Service (reactive power) to the Bonneville Power Administration (Bonneville or BPA) is a....'' \\5\\ The Commission stated that ``Chehalis has been providing reactive power to BPA pursuant to an... interconnection agreement between Chehalis and BPA was required to be filed prior to May 2005, even though it...

  15. The Administrative Power Grab

    ERIC Educational Resources Information Center

    Sorenson, Richard D.

    2007-01-01

    Administrative power for some school teachers can be an aphrodisiac that can be applied negatively, especially when a leader has devastating instinct for the weaknesses of others. A leader's intellect and heart closes shop and ceases to function when drunk on power. In this article, the author describes how the use of administrative power can be…

  16. Innovation in Administrator Preparation.

    ERIC Educational Resources Information Center

    Coleman, Don

    An innovative administrator preparation program based on guidelines established by national boards and commissions is described in this paper. The California State University, Fresno, administrator education curriculum was reorganized by faculty and an advisory committee of 11 superintendents to meet the needs of local school districts. The…

  17. Migrant Education Administrative Guide.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Div. of Compensatory Education.

    Relating specifically to the North Carolina migrant education program's administrative responsibilities, this guide is designed to aid administrators in program management, monitoring project activities, project evaluation, self-assessment, determining needs for training and staff development, site-visit preparation, policy development, and…

  18. Administration of Computer Resources.

    ERIC Educational Resources Information Center

    Franklin, Gene F.

    Computing at Stanford University has, until recently, been performed at one of five facilities. The Stanford hospital operates an IBM 370/135 mainly for administrative use. The university business office has an IBM 370/145 for its administrative needs and support of the medical clinic. Under the supervision of the Stanford Computation Center are…

  19. Issues in Educational Administration.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    School administrators need to study and analyze the pros and cons of issues before making decisions. Ultimately, decisions need to be made by administrators as to which philosophies of education to implement in resolving conflicting points of view. More research studies would lead to an increased number of syntheses of the pros and cons of certain…

  20. Justifying Educational Administration.

    ERIC Educational Resources Information Center

    Evers, Colin; Lakomski, Gabriele

    1993-01-01

    The traditional conceptions of science dominating educational administration are mistaken. Unacceptable epistemologies, like those implicit in logical positivism, justify knowledge solely in terms of empirical adequacy. An improved science of educational administration embraces a coherent global theory accounting for all the phenomena of human…

  1. Test Administration Models

    ERIC Educational Resources Information Center

    Becker, Kirk A.; Bergstrom, Betty A.

    2013-01-01

    The need for increased exam security, improved test formats, more flexible scheduling, better measurement, and more efficient administrative processes has caused testing agencies to consider converting the administration of their exams from paper-and-pencil to computer-based testing (CBT). Many decisions must be made in order to provide an optimal…

  2. Champions of Children. Administrators . . .

    ERIC Educational Resources Information Center

    Chaffee, John; Olds, H. Robert

    Today, in an era of taxpayer revolts, lack of clarity in values, and changing family structure, children need advocates in the political arena as well as in the schools. This pamphlet suggests that administrators are in an excellent position to defend the rights of children on all fronts. It focuses on what administrators have done and specific…

  3. The School Personnel Administrator.

    ERIC Educational Resources Information Center

    Knox, Rodney F.

    This paper provides an overview of the development of the school-personnel administrator role. It first describes the influence of the science-management and human-relations movements and the behavioral sciences on personnel administration and human resource management. It next discusses the role of the personnel-performance-appraisal system and…

  4. Tenure for Administrators?

    ERIC Educational Resources Information Center

    Holyer, Robert

    2004-01-01

    The practice of granting tenure to academic administrators, especially presidents and academic deans, seems fairly prevalent. However, it is important to consider the possible advantages and disadvantages carefully before making such an offer. Boards interested in attracting talented administrators empowered to do what is in the best interest of…

  5. 47 CFR 54.715 - Administrative expenses of the Administrator.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Administrative expenses of the Administrator. 54.715 Section 54.715 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) UNIVERSAL SERVICE Administration § 54.715 Administrative expenses of the Administrator. (a) The annual administrative expenses...

  6. 75 FR 64216 - Interpretation of OSHA's Provisions for Feasible Administrative or Engineering Controls of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ... Occupational Safety and Health Administration 29 CFR Parts 1910 and 1926 Interpretation of OSHA's Provisions for Feasible Administrative or Engineering Controls of Occupational Noise AGENCY: Occupational Safety... affordable engineering and administrative controls to reduce noise levels. The Occupational Safety and...

  7. Reactivity to nicotine cues over repeated cue reactivity sessions.

    PubMed

    LaRowe, Steven D; Saladin, Michael E; Carpenter, Matthew J; Upadhyaya, Himanshu P

    2007-12-01

    The present study investigated whether reactivity to nicotine-related cues would attenuate across four experimental sessions held 1 week apart. Participants were nineteen non-treatment seeking, nicotine-dependent males. Cue reactivity sessions were performed in an outpatient research center using in vivo cues consisting of standardized smoking-related paraphernalia (e.g., cigarettes) and neutral comparison paraphernalia (e.g., pencils). Craving ratings were collected before and after both cue presentations while physiological measures (heart rate, skin conductance) were collected before and during the cue presentations. Although craving levels decreased across sessions, smoking-related cues consistently evoked significantly greater increases in craving relative to neutral cues over all four experimental sessions. Skin conductance was higher in response to smoking cues, though this effect was not as robust as that observed for craving. Results suggest that, under the described experimental parameters, craving can be reliably elicited over repeated cue reactivity sessions.

  8. The diffusion-active permeable reactive barrier.

    PubMed

    Schwarz, Alex O; Rittmann, Bruce E

    2010-03-01

    Using the biogeochemical model CCBATCH, which we expanded to include transport processes, we study a novel approach for the treatment of aquifers contaminated with toxic concentrations of metals, the diffusion-active permeable reactive barrier (DAPRB), which is based on generation of sulfide by Sulfate Reducing Bacteria (SRB) as the groundwater moves through a layered treatment zone. In the DAPRB, layers of low conductivity (low-K) containing reactive materials are intercalated between layers of high conductivity (high-K) that transport the groundwater across the barrier. Because diffusion dominates transport in the reactive layers, microbial communities can take advantage there of the chemical-gradient mechanism for protection from toxicants. The ideal sulfidic DAPRB design includes particulate organic matter (POM) and solid sulfate mineral inside the reactive (low-K) layer. This leads to sulfate reduction and the formation of sulfide ligands that complex with toxic metals, such as Zn(2+) in the high-K layer. We perform a theoretical biogeochemical analysis of the ideal configuration of a DAPRB for treatment of Zn-contaminated groundwater. Our analysis using the expanded CCBATCH confirms the gradient-resistance mechanism for bio-protection, with the ZnS bio-sink forming at the intersection of the Zn and sulfide plumes inside the high-K layers of the DAPRB. The detailed DAPRB analysis also shows that total alkalinity and pH distributions are representative footprints of the two key biogeochemical processes taking place, sulfidogenesis and Zn immobilization as sulfide mineral. This is so because these two reactions consume or produce acidic hydrogen and alkalinity. Additionally, because Zn immobilization is due to ZnS mineral precipitation, the ZnS mineral distribution is a good indicator for the bio-sink. Bio-sinks are located for the most part within the high-K layers, and their exact position depends on the relative magnitude of metal and sulfide fluxes. Finally

  9. Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection

    PubMed Central

    2013-01-01

    Background Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections. Materials and methods Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated. Results The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury. Conclusions HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model. PMID:23458564

  10. Detoxification of castor meal through reactive seed crushing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Non-edible oil crops, such as castor or jatropha, contain several toxic components. Post-harvest treatments should be used to reduce the risks associated with the possible dispersion of toxic compounds in the environment. A new processing technology named Reactive Seed Crushing was developed, which ...

  11. Reactivity and Regulation in Children Prenatally Exposed to Cocaine

    ERIC Educational Resources Information Center

    Dennis, Tracy; Bendersky, Margaret; Ramsay, Douglas; Lewis, Michael

    2006-01-01

    Children prenatally exposed to cocaine may be at elevated risk for adjustment problems in early development because of greater reactivity and reduced regulation during challenging tasks. Few studies have examined whether cocaine-exposed children show such difficulties during the preschool years, a period marked by increased social and cognitive…

  12. Maternal Regulation of Infant Reactivity From 2 to 6 Months.

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Putnam, Samuel P.; Stifter, Cynthia A.

    2004-01-01

    Previous research has investigated the effect of maternal soothing behaviors on reducing infant reactivity but not the differential effects of specific maternal behaviors on infant stress responses. The present study investigated maternal regulation of 2- and 6-month-olds' responses to an inoculation and found a significant decline with age in…

  13. Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice.

    PubMed

    Hu, Hailong; Guo, Qian; Wang, Changlin; Ma, Xiao; He, Hongjuan; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2015-10-01

    There have been few reports about the possible toxic effects of titanium dioxide (TiO2 ) nanoparticles on the endocrine system. We explored the endocrine effects of oral administration to mice of anatase TiO2 nanoparticles (0, 64 and 320 mg kg(-1) body weight per day to control, low-dose and high-dose groups, respectively, 7 days per week for 14 weeks). TiO2 nanoparticles were characterized by scanning and transmission electron microscopy (TEM) and dynamic light scattering (DLS), and their physiological distribution was investigated by inductively coupled plasma. Biochemical analyzes included plasma glucose, insulin, heart blood triglycerides (TG), free fatty acid (FFA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and reactive oxygen species (ROS)-related markers (total SOD, GSH and MDA). Phosphorylation of IRS1, Akt, JNK1, and p38 MAPK were analyzed by western blotting. Increased titanium levels were found in the liver, spleen, small intestine, kidney and pancreas. Biochemical analyzes showed that plasma glucose significantly increased whereas there was no difference in plasma insulin secretion. Increased ROS levels were found in serum and the liver, as evidenced by reduced total SOD activity and GSH level and increased MDA content. Western blotting showed that oral administration of TiO2 nanoparticles induced insulin resistance (IR) in mouse liver, shown by increased phosphorylation of IRS1 (Ser307) and reduced phosphorylation of Akt (Ser473). The pathway by which TiO2 nanoparticles increase ROS-induced IR were included in the inflammatory response and phosphokinase, as shown by increased serum levels of TNF-α and IL-6 and increased phosphorylation of JNK1 and p38 MAPK in liver. These results show that oral administration of TiO2 nanoparticles increases ROS, resulting in IR and increasing plasma glucose in mice.

  14. Surface Reactivity of Quasicrystalline Materials

    NASA Astrophysics Data System (ADS)

    Jenks, Cynthia J.

    1997-03-01

    A fundamental knowledge and understanding of the reactivity of quasicrystalline materials is of great interest because of certain practical properties these materials possess, namely low coefficients of friction and oxidation resistance. A recent "hierarchical cluster" model proposed by Janot(C. Janot Phys. Rev. B 56 (1996) 181.) predicts that quasicrystal surfaces should be intrinsically inert and rough, and is useful in explaining their interesting properties. Surface structure and preparation may play a role in the applicability of this model. In this talk, we examine these factors and present experimental measurements of the surface reactivity of some Al-based quasicrystalline materials under ultra-high vacuum conditions (less than 2 x 10-10 Torr). To gain an understanding of what properties are unique to quasicrystals, we make comparisons with the surface reactivity of crystalline alloys of similar composition and pure, crystalline aluminum. note number.

  15. DETERMINATION OF SPECIFIC NEUTRONIC REACTIVITY

    DOEpatents

    Dessauer, G.

    1960-05-10

    A method is given for production-line determination of the specific neutronic reactivity of such objects as individual nuclear fuel or neutron absorber elements and is notable for rapidity and apparatus simplicity. The object is incorporated in a slightly sub-critical chain fission reactive assembly having a discrete neutron source, thereby establishing a K/sub eff/ within the crucial range of 0.95 to 0.995. The range was found to afford, uniquely, flux- transient damped response in a niatter of seconds simultaneously with acceptable analytical sensitivity. The resulting neutron flux measured at a situs spaced from both object and source within the assembly serves as a calibrable indication of said reactivity.

  16. Transformation of Reactive Iron Minerals in a Permeable Reactive Barrier (Biowall) Used to Treat TCE in Groundwater

    EPA Science Inventory

    Abstract: Iron and sulfur reducing conditions are generally created in permeable reactive barrier (PRB) systems constructed for groundwater treatment, which usually leads to formation of iron sulfide phases. Iron sulfides have been shown to play an important role in degrading ch...

  17. Environmental life cycle assessment of permeable reactive barriers: effects of construction methods, reactive materials and groundwater constituents.

    PubMed

    Mak, Mark S H; Lo, Irene M C

    2011-12-01

    The effects of the construction methods, materials of reactive media and groundwater constituents on the environmental impacts of a permeable reactive barrier (PRB) were evaluated using life cycle assessment (LCA). The PRB is assumed to be installed at a simulated site contaminated by either Cr(VI) alone or Cr(VI) and As(V). Results show that the trench-based construction method can reduce the environmental impacts of the remediation remarkably compared to the caisson-based method due to less construction material consumption by the funnel. Compared to using the zerovalent iron (Fe(0)) and quartz sand mixture, the use of the Fe(0) and iron oxide-coated sand (IOCS) mixture can reduce the environmental impacts. In the presence of natural organic matter (NOM) in groundwater, the environmental impacts generated by the reactive media were significantly increased because of the higher usage of Fe(0). The environmental impacts are lower by using the Fe(0) and IOCS mixture in the groundwater with NOM, compared with using the Fe(0) and quartz sand mixture. Since IOCS can enhance the removal efficiency of Cr(VI) and As(V), the usage of the Fe(0) can be reduced, which in turn reduces the impacts induced by the reactive media.

  18. Histamine H3 receptors modulate reactive hyperemia in rat gut.

    PubMed

    Pawlik, W W; Obuchowicz, R; Pawlik, M W; Sendur, R; Biernat, J; Brzozowski, T; Konturek, S J

    2004-09-01

    Reactive hyperemia (RH) is an abrupt blood flow increase following release from mechanical occlusion of an artery, with restoration of intra-arterial pressure. The mechanism of this postocclusion increase in blood flow in the gut is multifactorial. Relaxation of intestinal resistance vessels, observed during RH, may involve myogenic, metabolic, hormonal and neurogenic factors. Evidence exists that histamine is an important endogenous mediator of various functions of the gut, including blood flow. The vascular effects of histamine in the intestinal circulation are due its agonistic action on histamine H1, H2 and H3 receptors. In the present study the hypothesis was tested that peripheral histamine H3 receptors are involved in the mediation of RH in the intestinal circulation. In anesthetized rats, anterior mesenteric artery blood flow (MBF) was determined with ultrasonic Doppler flowmeter, and arterial pressure (AP) was determined with a transducer. The increase in the volume of blood accumulating during RH (RH-volume), the peak increase of arterial blood flow (RH-peak response) and the duration of the hyperemia (RH-duration) were used to quantify RH after occluding the anterior mesenteric artery for 30, 60 and 120 s. Hyperemia parameters were determined before and after administration of the selective histamine H3 receptor antagonist clobenpropit. Pretreatment with clobenpropit was without any effect on control MBF and AP but significantly reduced most of RH responses. These findings support the hypothesis that histamine H3 receptors do not play any role in the control of intestinal vasculature at basal conditions but these receptors participate in the intestinal hyperemic reaction in response to complete temporal intestinal ischemia.

  19. Vaccination with a recombinant protein encoding the tumor-specific antigen NY-ESO-1 elicits an A2/157-165-specific CTL repertoire structurally distinct and of reduced tumor reactivity than that elicited by spontaneous immune responses to NY-ESO-1-expressing Tumors.

    PubMed

    Bioley, Gilles; Guillaume, Philippe; Luescher, Immanuel; Bhardwaj, Nina; Mears, Gregory; Old, Lloyd; Valmori, Danila; Ayyoub, Maha

    2009-01-01

    In a recent vaccination trial assessing the immunogenicity of an NY-ESO-1 (ESO) recombinant protein administered with Montanide and CpG, we have obtained evidence that this vaccine induces specific cytolytic T lymphocytes (CTL) in half of the patients. Most vaccine-induced CTLs were directed against epitopes located in the central part of the protein, between amino acids 81 and 110. This immunodominant region, however, is distinct from another ESO CTL region, 157-165, that is a frequent target of spontaneous CTL responses in A2+ patients bearing ESO tumors. In this study, we have investigated the CTL responses to ESO 157-165 in A2+ patients vaccinated with the recombinant protein. Our data indicate that after vaccination with the protein, CTL responses to ESO 157-165 are induced in some, but not all, A2+ patients. ESO 157-165-specific CTLs induced by vaccination with the ESO protein were functionally heterogeneous in terms of tumor recognition and often displayed decreased tumor reactivity as compared with ESO 157-165-specific CTLs isolated from patients with spontaneous immune responses to ESO. Remarkably, protein-induced CTLs used T-cell receptors similar to those previously isolated from patients vaccinated with synthetic ESO peptides (Vbeta4.1) and distinct from those used by highly tumor-reactive CTLs isolated from patients with spontaneous immune responses (Vbeta1.1, Vbeta8.1, and Vbeta13.1). Together, these results demonstrate that vaccination with the ESO protein elicits a repertoire of ESO 157-165-specific CTLs bearing T-cell receptors that are structurally distinct from those of CTLs found in spontaneous immune responses to the antigen and that are heterogeneous in terms of tumor reactivity, being often poorly tumor reactive.

  20. Thoughts for New Administrators

    ERIC Educational Resources Information Center

    LaCrosse, E. Robert

    1977-01-01

    Discusses issues in program administration, with specific reference to preschool programs. Some of the issues discussed include coping with conflict, leadership, the sharing of power, and honesty. A short annotated bibliography is included. (BD)

  1. Evaluation of Administrators.

    ERIC Educational Resources Information Center

    Ryan, Edmund G.

    1979-01-01

    Guidelines are presented for the evaluation of college administrators: (1) purposes of the evaluation; (2) approaches to evaluation; (3) criteria for evaluation; (4) participants or evaluators in the process; and (5) evaluation results and use of results. (GDC)

  2. Serving the Space Administration

    ERIC Educational Resources Information Center

    Campbell, Jack E.; Thompson, Arthur W.

    1974-01-01

    The purpose of the current program was to establish an upward mobility program that afforded employees an opportunity to improve their credibility in job opportunity selection under the directives of the National Aeronautics and Space Administration. (Author/RK)

  3. Goldstone (GDSCC) administrative computing

    NASA Technical Reports Server (NTRS)

    Martin, H.

    1981-01-01

    The GDSCC Data Processing Unit provides various administrative computing services for Goldstone. Those activities, including finance, manpower and station utilization, deep-space station scheduling and engineering change order (ECO) control are discussed.

  4. Administrators Speak Out

    ERIC Educational Resources Information Center

    Miner, Fred V.

    1976-01-01

    A summary is presented of the issues and concerns discussed and the recommendations made by the American Vocational Association's (AVA) Administration Policy Committee during its meeting at the 1975 AVA Convention. (AJ)

  5. Metabolic syndrome reduces the contribution of K+ channels to ischemic coronary vasodilation.

    PubMed

    Borbouse, Léna; Dick, Gregory M; Payne, Gregory A; Berwick, Zachary C; Neeb, Zachary P; Alloosh, Mouhamad; Bratz, Ian N; Sturek, Michael; Tune, Johnathan D

    2010-04-01

    This investigation tested the hypothesis that metabolic syndrome decreases the relative contribution of specific K(+) channels to coronary reactive hyperemia. Ca(2+)-activated (BK(Ca)), voltage-activated (K(V)), and ATP-dependent (K(ATP)) K(+) channels were investigated. Studies were conducted in anesthetized miniature Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) for 20 wk. The latter diet induces metabolic syndrome, increasing body weight, fasting glucose, total cholesterol, and triglyceride levels. Ischemic vasodilation was determined by the coronary flow response to a 15-s occlusion before and after cumulative administration of antagonists for BK(Ca) (penitrem A; 10 microg/kg iv), K(V) (4-aminopyridine; 0.3 mg/kg iv) and K(ATP) (glibenclamide; 1 mg/kg iv) channels. Coronary reactive hyperemia was diminished by metabolic syndrome as the repayment of flow debt was reduced approximately 30% compared with lean swine. Inhibition of BK(Ca) channels had no effect on reactive hyperemia in either lean or metabolic syndrome swine. Subsequent inhibition of K(V) channels significantly reduced the repayment of flow debt ( approximately 25%) in both lean and metabolic syndrome swine. Additional blockade of K(ATP) channels further diminished ( approximately 45%) the repayment of flow debt in lean but not metabolic syndrome swine. These data indicate that the metabolic syndrome impairs coronary vasodilation in response to cardiac ischemia via reductions in the contribution of K(+) channels to reactive hyperemia. PMID:20118408

  6. Formation and Reactivity of Biogenic Iron Minerals

    SciTech Connect

    Ferris, F. Grant

    2002-06-01

    Dissimilatory iron-reducing bacteria (DIRB) play an important role in regulating the aqueous geochemistry of iron and other metals in anaerobic, non-sulfidogenic groundwater environments; however, little work has directly assessed the cell surface electrochemistry of DIRB, or the nature of the interfacial environment around individual cells. The electrochemical properties of particulate solids are often inferred from titrations in which net surface charge is determined, assuming electroneutrality, as the difference between known added amounts of acid and base and measured proton concentration. The resultant titration curve can then be fit to a speciation model for the system to determine pKa values and site densities of reactive surface sites. Moreover, with the development of non-contact electrostatic force microscopy (EFM), it is now possible to directly inspect and quantify charge development on surfaces. A combination of acid-base titrations and EFM are being used to assess the electrochemical surface properties of the groundwater DIRB, Shewanella putrefaciens. The pKa spectra and EFM data show together that a high degree of electrochemical heterogeneity exists within the cell wall and at the cell surface of S. putrefaciens. Recognition of variations in the nature and spatial distribution of reactive sites that contribute to charge development on these bacteria implies further that the cell surface of these Fe(III)-reducing bacteria functions as a highly differentiated interfacial system capable of supporting multiple intermolecular interactions with both solutes and solids. These include surface complexation reactions involving dissolved metals, as well as adherence to mineral substrates such as hydrous ferric oxide through longer-range electrostatic interactions, and surface precipitation of secondary reduced-iron minerals.

  7. Systemic Administration of Epothilone B Promotes Axon Regeneration and Functional Recovery after Spinal Cord Injury

    PubMed Central

    Ruschel, Jörg; Hellal, Farida; Flynn, Kevin C.; Dupraz, Sebastian; Elliot, David A.; Tedeschi, Andrea; Bates, Margaret; Sliwinski, Christopher; Brook, Gary; Dobrint, Kristina; Peitz, Michael; Brüstle, Oliver; Norenberg, Michael D.; Blesch, Armin; Weidner, Norbert; Bunge, Mary Bartlett; Bixby, John L.; Bradke, Frank

    2015-01-01

    After central nervous system (CNS) injury, inhibitory factors in the lesion scar and a poor axon growth potential prevent axon regeneration. Microtubule stabilization reduces scarring and promotes axon growth. However, the cellular mechanisms of this dual effect remain unclear. Here, delayed systemic administration of a blood-brain barrier permeable microtubule stabilizing drug, epothilone B, decreased scarring after rodent spinal cord injury (SCI) by abrogating polarization and directed migration of scar-forming fibroblasts. Conversely, epothilone B reactivated neuronal polarization by inducing concerted microtubule polymerization into the axon tip, which propelled axon growth through an inhibitory environment. Together, these drug elicited effects promoted axon regeneration and improved motor function after SCI. With recent clinical approval, epothilones hold promise for clinical use after CNS injury. PMID:25765066

  8. Transport equations for partially ionized reactive plasma in magnetic field

    NASA Astrophysics Data System (ADS)

    Zhdanov, V. M.; Stepanenko, A. A.

    2016-06-01

    Transport equations for partially ionized reactive plasma in magnetic field taking into account the internal degrees of freedom and electronic excitation of plasma particles are derived. As a starting point of analysis the kinetic equation with a binary collision operator written in the Wang-Chang and Uhlenbeck form and with a reactive collision integral allowing for arbitrary chemical reactions is used. The linearized variant of Grad's moment method is applied to deduce the systems of moment equations for plasma and also full and reduced transport equations for plasma species nonequilibrium parameters.

  9. A synchronous paradigm for modeling stable reactive systems

    SciTech Connect

    Winter, V.L.

    1998-12-01

    This paper describes a modeling technique for single-agent reactive systems, that is influenced by the modeling paradigm of Parnas as well as by the synchronous paradigms of LUSTRE and ESTEREL. In this paradigm, single-agent reactive systems are modeled in a universe having a discrete clock. This discretization of time greatly reduces the temporal complexity of the model. He believes that the advantage of this reduction in temporal complexity is that the resulting model is in many ways better suited to automated software construction and analysis techniques (e.g., deductive synthesis, transformation, and verification) than models that are based on continuous representations of time.

  10. Use of reactive materials to bind phosphorus.

    PubMed

    Chardon, Wim J; Groenenberg, Jan E; Temminghoff, Erwin J M; Koopmans, Gerwin F

    2012-01-01

    Phosphorus (P) losses from agricultural soils have caused surface water quality impairment in many regions of the world, including The Netherlands. Due to the large amounts of P accumulated in Dutch soils, the generic fertilizer and manure policy will not be sufficient to reach in time the surface water quality standards of the European Water Framework Directive. Additional measures must be considered to further reduce P enrichment of surface waters. One option is to immobilize P in soils or manure or to trap P when it moves through the landscape by using reactive materials with a large capacity to retain P. We characterized and tested two byproducts of the process of purification of deep groundwater for drinking water that could be used as reactive materials: iron sludge and iron-coated sand. Both materials contain low amounts of inorganic contaminants, which also have a low (bio)availability, and bound a large amount of P. We could describe sorption of P to the iron sludge in batch experiments well with the kinetic Freundlich equation (Q = × t (m) × C(n)). Kinetics had a large influence on P sorption in batch and column experiments and should be taken into account when iron-containing materials are tested for their capability to immobilize or trap P. A negative aspect of the iron sludge is its low hydraulic conductivity; even when mixed with pure sand to a mixture containing 20% sludge, the conductivity was very low, and only 10% sludge may be needed before application is possible in filters or barriers for removing P from groundwater. Due to its much higher hydraulic conductivity, iron-coated sand has greater potential for use under field conditions. Immobilizing P could be an option for using iron sludge as a reactive material. PMID:22565245

  11. Heparin-protamine complexes and C-reactive protein induce activation of the classical complement pathway: studies in patients undergoing cardiac surgery and in vitro.

    PubMed

    Bruins, P; te Velthuis, H; Eerenberg-Belmer, A J; Yazdanbakhsh, A P; de Beaumont, E M; Eijsman, L; Trouwborst, A; Hack, C E

    2000-08-01

    The administration of protamine to patients undergoing cardiopulmonary bypass (CPB) to neutralize heparin and to reduce the risk of bleeding, induces activation of the classical complement pathway mainly by heparin-protamine complexes. We investigated whether C-reactive protein (CRP) contributes to protamine-induced complement activation. In 24 patients during myocardial revascularization, we measured complement, CRP, and complement-CRP complexes, reflecting CRP-mediated complement activation in vivo. We also incubated plasma from healthy volunteers and patients with heparin and protamine in vitro to study CRP-mediated complement activation. During CPB, CRP levels remained unchanged while C3 activation products increased. C4 activation occurred after protamine administration. CRP-complement complexes increased at the end of CPB and upon protamine administration. Incubation of plasma with heparin and protamine in vitro generated complement-CRP complexes, which was blocked by phosphorylcholine and stimulated by exogenous CRP. C4d-CRP complex formation after protamine administration correlated clinically with the incidence of postoperative arrhythmia. Protamine administration during cardiac surgery induces complement activation which in part is CRP-dependent, and correlates with postoperative arrhythmia.

  12. Neurological Complications of VZV Reactivation

    PubMed Central

    Nagel, Maria A.

    2014-01-01

    Purpose of the review Varicella zoster virus (VZV) reactivation results in zoster, which may be complicated by postherpetic neuralgia, myelitis, meningoencephalitis and VZV vasculopathy. This review highlights the clinical features, laboratory abnormalities, imaging changes and optimal treatment of each of those conditions. Because all of these neurological disorders produced by VZV reactivation can occur in the absence of rash, the virological tests proving that VZV caused disease are discussed. Recent findings After primary infection, VZV becomes latent in ganglionic neurons along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity, VZV reactivates from ganglia and travels anterograde to the skin to cause zoster, which is often complicated by postherpetic neuralgia. VZV can also travel retrograde to produce meningoencephaltis, myelitis and stroke. When these complications occur without rash, VZV-induced disease can be diagnosed by detection of VZV DNA or anti-VZV antibody in CSF and treated with intravenous acyclovir. Summary Awareness of the expanding spectrum of neurological complications caused by VZV reactivation with and without rash will improve diagnosis and treatment. PMID:24792344

  13. PROCEEDINGS: MULTIPOLLUTANT SORBENT REACTIVITY WORKSHOP

    EPA Science Inventory

    The report is a compilation of technical papers and visual aids presented by representatives of industry, academia, and government agencies at a workshop on multipollutant sorbent reactivity that was held at EPA's Environmental Research Center in Research Triangle Park, NC, on Ju...

  14. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5375 Iron reduced. (a) Product. Iron reduced. (b) Conditions of use. This substance...

  15. 21 CFR 582.5375 - Iron reduced.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Iron reduced. 582.5375 Section 582.5375 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5375 Iron reduced. (a) Product. Iron reduced. (b) Conditions of use. This substance...

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2007-01-01

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

  18. Effect of superbanana diffusion on fusion reactivity in stellarators

    SciTech Connect

    Hinton, Fred L.

    2012-08-15

    Fusion reactivity is usually obtained using a Maxwellian distribution. However, energy-dependent radial diffusion can modify the energy distribution. Superbanana diffusion is energy-dependent and occurs in nonaxisymmetric magnetic confinement devices, such as stellarators, because of ripple-trapped particles which can take large steps between collisions. In this paper, the D-T fusion reactivity is calculated using a non-Maxwellian energy distribution obtained by solving the Fokker-Planck equation numerically, including radial superbanana diffusion as well as energy scattering. The ions in the tail of the distribution, with energies larger than thermal, which are most needed for fusion, are depleted by superbanana diffusion. In this paper, it is shown that the D-T fusion reactivity is reduced by tail ion depletion due to superbanana diffusion, by roughly a factor of 0.5 for the parameters used in the calculation.

  19. Reactivated memories compete for expression after Pavlovian extinction.

    PubMed

    Laborda, Mario A; Miller, Ralph R

    2012-05-01

    We view the response decrement resulting from extinction treatment as an interference effect, in which the reactivated memory from acquisition competes with the reactivated memory from extinction for behavioral expression. For each of these memories, reactivation is proportional to both the strength of the stimulus-outcome association and the quality of the facilitatory cues for that association which are present at test. Here we review basic extinction and recovery-from-extinction phenomena, showing how these effects are explicable in this associative interference framework. Moreover, this orientation has and continues to dictate efficient manipulations for minimizing recovery from extinction. This in turn suggests procedures that might reduce relapse from exposure therapy for a number of psychological disorders. Some of these manipulations enhance the facilitatory cues from extinction that are present at test, others strengthen the extinction association (i.e., CS-no outcome), and yet others seem to work by a combination of these two processes.

  20. Printing Stretchable Spiral Interconnects Using Reactive Ink Chemistries.

    PubMed

    Mamidanna, Avinash; Song, Zeming; Lv, Cheng; Lefky, Christopher S; Jiang, Hanqing; Hildreth, Owen J

    2016-05-25

    Stretchable electronics have important applications in health monitoring and integrated lab-on-a-chip devices. This paper discusses the performance of serpentine stretchable interconnects printed using self-reducing, silver reactive inks. It details process optimization, device fabrication, and device characterization, while demonstrating the potential applications for reactive inks and new design strategies in stretchable electronics. Devices were printed with an ethanol stabilized silver diamine reactive ink and cycled to stretch ratios of 140 and 160% over 1000 cycles with less than 2.5% variation in electrical resistance. Maximum deformation before failure was measured at 180% elongation. Additionally, interconnect deformation was compared to finite element analysis (FEA) simulations to show that FEA can be used to accurately model the deformation of low-strain printed interconnects. Overall, this paper demonstrates a simple and affordable route toward stretchable electrical interconnects. PMID:27158736

  1. Reactivated memories compete for expression after Pavlovian extinction.

    PubMed

    Laborda, Mario A; Miller, Ralph R

    2012-05-01

    We view the response decrement resulting from extinction treatment as an interference effect, in which the reactivated memory from acquisition competes with the reactivated memory from extinction for behavioral expression. For each of these memories, reactivation is proportional to both the strength of the stimulus-outcome association and the quality of the facilitatory cues for that association which are present at test. Here we review basic extinction and recovery-from-extinction phenomena, showing how these effects are explicable in this associative interference framework. Moreover, this orientation has and continues to dictate efficient manipulations for minimizing recovery from extinction. This in turn suggests procedures that might reduce relapse from exposure therapy for a number of psychological disorders. Some of these manipulations enhance the facilitatory cues from extinction that are present at test, others strengthen the extinction association (i.e., CS-no outcome), and yet others seem to work by a combination of these two processes. PMID:22326812

  2. Generation of reactive oxygen species by the faecal matrix

    PubMed Central

    Owen, R; Spiegelhalder, B; Bartsch, H

    2000-01-01

    BACKGROUND—Reactive oxygen species are implicated in the aetiology of a range of human diseases and there is increasing interest in their role in the development of cancer.
AIM—To develop a suitable method for the detection of reactive oxygen species produced by the faecal matrix.
METHODS—A refined high performance liquid chromatography system for the detection of reactive oxygen species is described.
RESULTS—The method allows baseline separation of the products of hydroxyl radical attack on salicylic acid in the hypoxanthine/xanthine oxidase system, namely 2,5-dihydroxybenzoic acid, 2,3-dihydroxybenzoic acid, and catechol. The increased efficiency and precision of the method has allowed a detailed evaluation of the dynamics of reactive oxygen species generation in the faecal matrix. The data show that the faecal matrix is capable of generating reactive oxygen species in abundance. This ability cannot be attributed to the bacteria present, but rather to a soluble component within the matrix. As yet, the nature of this soluble factor is not entirely clear but is likely to be a reducing agent.
CONCLUSIONS—The soluble nature of the promoting factor renders it amenable to absorption, and circumstances may exist in which either it comes into contact with either free or chelated iron in the colonocyte, leading to direct attack on cellular DNA, or else it initiates lipid peroxidation processes whereby membrane polyunsaturated fatty acids are attacked by reactive oxygen species propagating chain reactions leading to the generation of promutagenic lesions such as etheno based DNA adducts.


Keywords: colorectal cancer; faecal matrix; hypoxanthine; phytic acid; reactive oxygen species; xanthine oxidase PMID:10644317

  3. 49 CFR 609.23 - Reduced fare.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TRANSPORTATION TRANSPORTATION FOR ELDERLY AND HANDICAPPED PERSONS § 609.23 Reduced fare. Applicants for financial... Administrator may prescribe, that the rates charged elderly and handicapped persons during non-peak hours...

  4. 49 CFR 609.23 - Reduced fare.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... TRANSPORTATION TRANSPORTATION FOR ELDERLY AND HANDICAPPED PERSONS § 609.23 Reduced fare. Applicants for financial... Administrator may prescribe, that the rates charged elderly and handicapped persons during non-peak hours...

  5. Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives' allergenicity.

    PubMed

    Mbiya, Wilbes; Chipinda, Itai; Simoyi, Reuben H; Siegel, Paul D

    2016-01-01

    Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile known to covalently modify proteins via Michael Addition (MA) reaction whilst halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism onto amine and thiol moieties on proteins, the allergenic effects of adding substituents on BQ have not been reported. The effects of inserting substituents on the BQ ring has not been studied in animal assays. However, mandated reduction/elimination of animals used in cosmetics testing in Europe has led to an increased need for alternatives for the prediction of skin sensitization potential. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT binding studies demonstrated that addition of EWG to BQ as exemplified by the chlorine substituted BQDs increased reactivity while addition of EDG as in the methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was evaluated in the murine local lymph node assay (LLNA). BQD with electron withdrawing groups had the highest chemical potency followed by unsubstituted BQ and the least potent were the BQD with electron donating groups. The BQD results demonstrate the impact of inductive effects on both BQ reactivity and allergenicity, and suggest the potential utility of chemical reactivity data for electrophilic allergen identification and potency ranking. PMID:26612505

  6. MCS Systems Administration Toolkit

    2001-09-30

    This package contains a number of systems administration utilities to assist a team of system administrators in managing a computer environment by automating routine tasks and centralizing information. Included are utilities to help install software on a network of computers and programs to make an image of a disk drive, to manage and distribute configuration files for a number of systems, and to run self-testss on systems, as well as an example of using amore » database to manage host information and various utilities.« less

  7. Computer hardware fault administration

    DOEpatents

    Archer, Charles J.; Megerian, Mark G.; Ratterman, Joseph D.; Smith, Brian E.

    2010-09-14

    Computer hardware fault administration carried out in a parallel computer, where the parallel computer includes a plurality of compute nodes. The compute nodes are coupled for data communications by at least two independent data communications networks, where each data communications network includes data communications links connected to the compute nodes. Typical embodiments carry out hardware fault administration by identifying a location of a defective link in the first data communications network of the parallel computer and routing communications data around the defective link through the second data communications network of the parallel computer.

  8. River basin administration

    NASA Astrophysics Data System (ADS)

    Management of international rivers and their basins is the focus of the Centre for Comparative Studies on (International) River Basin Administration, recently established at Delft University of Technology in the Netherlands. Water pollution, sludge, and conflicting interests in the use of water in upstream and downstream parts of a river basin will be addressed by studying groundwater and consumption of water in the whole catchment area of a river.Important aspects of river management are administrative and policy aspects. The Centre will focus on policy, law, planning, and organization, including transboundary cooperation, posing standards, integrated environmental planning on regional scale and environmental impact assessments.

  9. C-Reactive Protein (CRP) Test

    MedlinePlus

    ... Home Visit Global Sites Search Help? C-Reactive Protein Share this page: Was this page helpful? Also known as: CRP Formal name: C-Reactive Protein Related tests: ESR , Complement , Procalcitonin , ANA , Rheumatoid Factor ...

  10. Engine combustion control via fuel reactivity stratification

    DOEpatents

    Reitz, Rolf Deneys; Hanson, Reed M; Splitter, Derek A; Kokjohn, Sage L

    2013-12-31

    A compression ignition engine uses two or more fuel charges having two or more reactivities to control the timing and duration of combustion. In a preferred implementation, a lower-reactivity fuel charge is injected or otherwise introduced into the combustion chamber, preferably sufficiently early that it becomes at least substantially homogeneously dispersed within the chamber before a subsequent injection is made. One or more subsequent injections of higher-reactivity fuel charges are then made, and these preferably distribute the higher-reactivity matter within the lower-reactivity chamber space such that combustion begins in the higher-reactivity regions, and with the lower-reactivity regions following thereafter. By appropriately choose the reactivities of the charges, their relative amounts, and their timing, combustion can be tailored to achieve optimal power output (and thus fuel efficiency), at controlled temperatures (and thus controlled NOx), and with controlled equivalence ratios (and thus controlled soot).

  11. Engine combustion control via fuel reactivity stratification

    DOEpatents

    Reitz, Rolf Deneys; Hanson, Reed M.; Splitter, Derek A.; Kokjohn, Sage L.

    2015-07-14

    A compression ignition engine uses two or more fuel charges having two or more reactivities to control the timing and duration of combustion. In a preferred implementation, a lower-reactivity fuel charge is injected or otherwise introduced into the combustion chamber, preferably sufficiently early that it becomes at least substantially homogeneously dispersed within the chamber before a subsequent injection is made. One or more subsequent injections of higher-reactivity fuel charges are then made, and these preferably distribute the higher-reactivity matter within the lower-reactivity chamber space such that combustion begins in the higher-reactivity regions, and with the lower-reactivity regions following thereafter. By appropriately choosing the reactivities of the charges, their relative amounts, and their timing, combustion can be tailored to achieve optimal power output (and thus fuel efficiency), at controlled temperatures (and thus controlled NOx), and with controlled equivalence ratios (and thus controlled soot).

  12. Engine combustion control via fuel reactivity stratification

    DOEpatents

    Reitz, Rolf Deneys; Hanson, Reed M.; Splitter, Derek A.; Kokjohn, Sage L.

    2016-06-28

    A compression ignition engine uses two or more fuel charges having two or more reactivities to control the timing and duration of combustion. In a preferred implementation, a lower-reactivity fuel charge is injected or otherwise introduced into the combustion chamber, preferably sufficiently early that it becomes at least substantially homogeneously dispersed within the chamber before a subsequent injection is made. One or more subsequent injections of higher-reactivity fuel charges are then made, and these preferably distribute the higher-reactivity matter within the lower-reactivity chamber space such that combustion begins in the higher-reactivity regions, and with the lower-reactivity regions following thereafter. By appropriately choosing the reactivities of the charges, their relative amounts, and their timing, combustion can be tailored to achieve optimal power output (and thus fuel efficiency), at controlled temperatures (and thus controlled NOx), and with controlled equivalence ratios (and thus controlled soot).

  13. Perceptual basis for reactive teleoperation.

    SciTech Connect

    Park, Y. S.; Ewing, T. F.; Boyle, J. M.; Yule, T. J.

    2001-08-28

    To enhance task performance in partially structured environment, enhancement of teleoperation was proposed by introducing autonomous behaviors. Such autonomy is implemented based on reactive robotic architecture, where reactive motor agents that directly couples sensory inputs and motor actions become the building blocks. To this end, presented in this paper is a perceptual basis for the motor agents. The perceptual basis consists of perceptual agents that extracts environmental information from a structured light vision system and provide action oriented perception for the corresponding motor agents. Rather than performing general scene reconstruction, a perceptual agent directly provides the motion reference for the motor behavior. Various sensory mechanisms--sensor fission, fusion, and fashion--becomes basic building blocks of the perception process. Since perception is a process deeply intertwined with the motor actions, active perception may also incorporate motor behaviors as an integral perceptual process.

  14. Melioidosis: reactivation during radiation therapy

    SciTech Connect

    Jegasothy, B.V.; Goslen, J.B.; Salvatore, M.A.

    1980-05-01

    Melioidosis is caused by Pseudomonas pseudomallei, a gram-negative, motile bacillus which is a naturally occurring soil saprophyte. The organism is endemic in Southeast Asia, the Philippines, Australia, and parts of Central and South America. Most human disease occurs from infection acquired in these countries. Infection with P pseudomallei may produce no apparent clinical disease. Acute pneumonitis or septicemia may result from inhalation of the organism, and inoculation into sites of trauma may cause localized skin abscesses, or the disease may remain latent and be reactivated months or years later by trauma, burns, or pneumococcal pneumonia, diabetic ketoacidosis, influenza, or bronchogenic carcinoma. The last is probably the commonest form of melioidosis seen in the United States. We present the first case of reactivation of melioidosis after radiation therapy for carcinoma of the lung, again emphasizing the need to consider melioidosis in a septic patient with a history of travel, especially to Southeast Asia.

  15. Functional Reactive Polymer Electrospun Matrix.

    PubMed

    Agarwal, Vipul; Ho, Dominic; Ho, Diwei; Galabura, Yuriy; Yasin, Faizah; Gong, Peijun; Ye, Weike; Singh, Ruhani; Munshi, Alaa; Saunders, Martin; Woodward, Robert C; St Pierre, Timothy; Wood, Fiona M; Fear, Mark; Lorenser, Dirk; Sampson, David D; Zdyrko, Bogdan; Luzinov, Igor; Smith, Nicole M; Iyer, K Swaminathan

    2016-02-01

    Synthetic multifunctional electrospun composites are a new class of hybrid materials with many potential applications. However, the lack of an efficient, reactive large-area substrate has been one of the major limitations in the development of these materials as advanced functional platforms. Herein, we demonstrate the utility of electrospun poly(glycidyl methacrylate) films as a highly versatile platform for the development of functional nanostructured materials anchored to a surface. The utility of this platform as a reactive substrate is demonstrated by grafting poly(N-isopropylacrylamide) to incorporate stimuli-responsive properties. Additionally, we demonstrate that functional nanocomposites can be fabricated using this platform with properties for sensing, fluorescence imaging, and magneto-responsiveness. PMID:26780245

  16. Integrating planning and reactive control

    NASA Technical Reports Server (NTRS)

    Rosenschein, Stanley J.; Kaelbling, Leslie Pack

    1989-01-01

    Artificial intelligence research on planning is concerned with designing control systems that choose actions by manipulating explicit descriptions of the world state, the goal to be achieved, and the effects of elementary operations available to the system. Because planning shifts much of the burden of reasoning to the machine, it holds great appeal as a high-level programming method. Experience shows, however, that it cannot be used indiscriminately because even moderately rich languages for describing goals, states, and the elementary operators lead to computational inefficiencies that render the approach unsuitable for realistic applications. This inadequacy has spawned a recent wave of research on reactive control or situated activity in which control systems are modeled as reacting directly to the current situation rather than as reasoning about the future effects of alternative action sequences. While this research has confronted the issue of run-time tractability head on, in many cases it has done so by sacrificing the advantages of declarative planning techniques. Ways in which the two approaches can be unified are discussed. The authors begin by modeling reactive control systems as state machines that map a stream of sensory inputs to a stream of control outputs. These machines can be decomposed into two continuously active subsystems: the planner and the execution module. The planner computes a plan, which can be seen as a set of bits that control the behavior of the execution module. An important element of this work is the formulation of a precise semantic interpretation for the inputs and outputs of the planning system. They show that the distinction between planned and reactive behavior is largely in the eye of the beholder: systems that seem to compute explicit plans can be redescribed in situation-action terms and vice versa. They also discuss practical programming techniques that allow the advantages of declarative programming and guaranteed

  17. Synthesis and processing of composites by reactive metal penetration

    SciTech Connect

    Loehman, R.E.; Ewsuk, K.G.; Tomsia, A.P.

    1995-05-01

    Ceramic-metal composites are being developed because their high stiffness-to weight ratios, good fracture toughness, and variable electrical and thermal properties give them advantages over more conventional materials. However, because ceramic-metal composite components presently are more expensive than monolithic materials, improvements in processing are required to reduce manufacturing costs. Reactive metal penetration is a promising new method for making ceramic- and metal-matrix composites that has the advantage of being inherently a net-shape process. This technique, once fully developed, will provide another capability for manufacturing the advanced ceramic composites that are needed for many light-weight structural and wear applications. The lower densities of these composites lead directly to energy savings in use. Near-net-shape fabrication of composite parts should lead to additional savings because costly and energy intensive grinding and machining operations are significantly reduced, and the waste generated from such finishing operations is minimized. The goals of this research program are: (1) to identify feasible compositional systems for making composites by reactive metal penetration; (2) to understand the mechanism(s) of composite formation by reactive metal penetration; and (3) to learn how to control and optimize reactive metal penetration for economical production of composites and composite coatings.

  18. Urban School Administration.

    ERIC Educational Resources Information Center

    McKelvey, Troy V., Ed.; Swanson, Austin D., Ed.

    This document contains 12 papers presented at an institute for urban school administrators designed to deal with the contemporary urban educational problems incident to school desegregation, social integration, and the equality of educational opportunity. The authors of the papers relate recent research findings to practical field experience, and…

  19. Telecommunications administration standard

    SciTech Connect

    Gustwiller, K.D.

    1996-05-01

    The administration of telecommunications is critical to proper maintenance and operation. The intent is to be able to properly support telecommunications for the distribution of all information within a building/campus. This standard will provide a uniform administration scheme that is independent of applications, and will establish guidelines for owners, installers, designers and contractors. This standard will accommodate existing building wiring, new building wiring and outside plant wiring. Existing buildings may not readily adapt to all applications of this standard, but the requirement for telecommunications administration is applicable to all buildings. Administration of the telecommunications infrastructure includes documentation (labels, records, drawings, reports, and work orders) of cables, termination hardware, patching and cross-connect facilities, telecommunications rooms, and other telecommunications spaces (conduits, grounding, and cable pathways are documented by Facilities Engineering). The investment in properly documenting telecommunications is a worthwhile effort. It is necessary to adhere to these standards to ensure quality and efficiency for the operation and maintenance of the telecommunications infrastructure for Sandia National Laboratories.

  20. Hospital Library Administration.

    ERIC Educational Resources Information Center

    Cramer, Anne

    The objectives of a hospital are to improve patient care, while the objectives of a hospital library are to improve services to the staff which will support their efforts. This handbook dealing with hospital administration is designed to aid the librarian in either implementing a hospital library, or improving services in an existing medical…

  1. Administrative Salary Summary Data.

    ERIC Educational Resources Information Center

    Colorado Commission on Higher Education, Denver.

    This report presents salary data on selected administrative positions from all public higher education institutions, governing boards, and other higher education state-level agencies in Colorado. Table 1 presents, by institutional type, the median and mean salaries for 1994-95, as well as the frequency and range of salaries, for the following…

  2. A Treatise on Administration.

    ERIC Educational Resources Information Center

    Moore, Thomas R.

    1988-01-01

    Expands Henri Fayol's definition of the administrative process to include a humanistic approach involving planning, organizing, implementing, controlling, evaluating, and satisfying functions. This empirical definition differs from some theoretical approaches by looking beyond resource consumption to consider ecological effects on the environment…

  3. Guidebook for School Administrators.

    ERIC Educational Resources Information Center

    Hess, Fritz, Ed.

    To provide guidance and advice regarding day-to-day responsibilities of new and experienced school administrators and superintendents in New York State, this compendium of knowledge and advice submitted by practitioners is presented with emphasis on all major aspects of superintendency. The section on general aspects of superintendency includes…

  4. Administrators Confront Student "Sexting"

    ERIC Educational Resources Information Center

    Manzo, Kathleen Kennedy

    2009-01-01

    Cellphone-savvy students have created instructional and disciplinary challenges for educators for years. But the recent emergence of "sexting" by adolescents over their mobile phones caught many school administrators off guard, and the practice is prompting efforts around the country to craft policy responses. Students' sharing of nude or…

  5. IVA: Improving Vocational Administration.

    ERIC Educational Resources Information Center

    EPD Consortium D, Richardson, TX.

    These six instructional units are intended to provide instructors of vocational education administration with a systematic package of materials for their programs of preservice and/or inservice instruction and to provide materials which could be reproduced for learner use. These units cover the following subject matter: (1) federal legislation…

  6. Administrative Utility Analysis: Appendices.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., San Juan, Puerto Rico.

    Appendixes to a study on administrative utility analysis and vocational education programs for the Area of Vocational and Technical Education (AVTE) in the Puerto Rico Department of Education contain the planning and budgeting system elements, position descriptions, and information on the growth of vocational education in Puerto Rico. The elements…

  7. Standards and Administration.

    ERIC Educational Resources Information Center

    Gross, S. P.

    1978-01-01

    Presents a literature review of water quality standards and administration, covering publications of 1976-77. Consideration is given to municipal facilities, National Pollutant Discharge Elimination Systems, regional and international water quality management, and effluent standards. A list of 99 references is also presented. (HM)

  8. Research Administration: Lessons Learned.

    ERIC Educational Resources Information Center

    Dummer, George H.

    1995-01-01

    The ways in which accountability issues have affected federal-university relationships, particularly in the area of academic research, are examined. Lessons university administrators have learned since issuance of Office of Management and Budget Circular A-21 in 1958, Congressional hearings on the operations of the National Institutes of Health…

  9. Educational Administration's Weber.

    ERIC Educational Resources Information Center

    Gronn, Peter

    1994-01-01

    Discusses Max Weber's importance in Greenfield's work, particularly in Greenfield and Ribbins'"Greenfield on Educational Administration" (1993). In concentrating on human actors' subjective understanding, Greenfield was a faithful Weberian. However, he deviated from Weber by disavowing structural explanations of social and organizational…

  10. Administrative Uses of Microcomputers.

    ERIC Educational Resources Information Center

    Crawford, Chase

    1987-01-01

    This paper examines the administrative uses of the microcomputer, stating that high performance educational managers are likely to have microcomputers in their organizations. Four situations that would justify the use of a computer are: (1) when massive amounts of data are processed through well-defined operations; (2) when data processing is…

  11. Educator Effectiveness Administrative Manual

    ERIC Educational Resources Information Center

    Pennsylvania Department of Education, 2014

    2014-01-01

    The goal of this manual is to provide guidance in the evaluation of educators, highlight critical components of effectiveness training, and offer opportunities for professional growth. The term "educator" includes teachers, all professional and temporary professional employees, education specialists, and school administrators/principals.…

  12. Discretionary Grants Administration Manual.

    ERIC Educational Resources Information Center

    Office of Human Development Services (DHHS), Washington, DC.

    This manual sets forth applicable administrative policies and procedures to recipients of discretionary project grants or cooperative agreements awarded by program offices in the Office of Human Development Services (HDS). It is intended to serve as a basic reference for project directors and business officers of recipient organizations who are…

  13. Study Shows Administrative Shortage.

    ERIC Educational Resources Information Center

    Sullivan, John R., Jr.

    1989-01-01

    Summarizes "Administrative Shortage in New England: The Evidence, the Causes, the Recommendations." High pressure, long hours, low salaries, and high housing costs are among the reasons cited for the shortage. Recommendations are centered on role identity, staff support, training, and recruitment. (SI)

  14. Professionalism in Educational Administration.

    ERIC Educational Resources Information Center

    Silver, Paula F.

    That the quest for a general theory of educational administration has been a misdirection of effort and that the advancement of professionalism within this field would represent a more sensible endeavor for the production of useful knowledge is the focus of this essay. The advancement of professionalism would entail a reorientation of research…

  15. Public Relations for Administrators.

    ERIC Educational Resources Information Center

    Bagin, Don; And Others

    This volume provides information and recommendations about public relations to assist school administrators in developing effective communication. The document contains 15 chapters. "The Scope of Public Relations," chapter 1, specifies characteristics of and individuals responsible for an effective program. Chapter 2, "Personal Public Relations,"…

  16. Championing the Latino Administrator

    ERIC Educational Resources Information Center

    Garcia, Carlos A.

    2011-01-01

    When the author worked as a vice principal at a K-8 school in Watsonville, California, a school predominantly filled with migrant workers' children, he felt a lack of support as a Latino as he began moving up into school administration. He also continued to see what he had seen as a teacher--which was how underserved minority students were. These…

  17. Indicators of Administrative Effectiveness.

    ERIC Educational Resources Information Center

    Skipper, Charles E.; Hofmann, Richard J.

    Ten personal characteristics and seven administrative skills that differentiated effective from ineffective university leaders were assessed by multiple discriminate analysis. The personal characteristics identified by previous research (Skipper, 1975, 1977) are: responsibility, integrity, self-control, intellectual efficiency, flexibility,…

  18. Migrant Education Administrative Handbook.

    ERIC Educational Resources Information Center

    Louisiana State Dept. of Education, Baton Rouge. Bureau of Migrant Education.

    Intended to provide information pertaining to the administration of migrant education projects in Louisiana, the handbook is divided into two sections: basic guidelines for program operations and support services--nursing. Section I covers the Federal and State migrant program, local migrant projects, project personnel and staff development, and…

  19. Redis database administration tool

    SciTech Connect

    Martinez, J. J.

    2013-02-13

    MyRedis is a product of the Lorenz subproject under the ASC Scirntific Data Management effort. MyRedis is a web based utility designed to allow easy administration of instances of Redis databases. It can be usedd to view and manipulate data as well as run commands directly against a variety of different Redis hosts.

  20. Renaissance Administrator, Spring 1998.

    ERIC Educational Resources Information Center

    Dowdy, June P., Ed.

    1998-01-01

    This spring 1998 issue of Renaissance Administrator features the following articles: (1) "Servant Leadership and Higher Education--What is Leadership?" (Richard E. Hasselbach); (2) "Teaching Writing in the 90's--Carnivorous Printers and Dying Grandmothers" (Helen Ruggieri); (3) Assignment--Journal Writing" (Lynn Muscato); and (4) "A Business…

  1. Oxytocin Attenuates Neural Reactivity to Masked Threat Cues from the Eyes

    PubMed Central

    Kanat, Manuela; Heinrichs, Markus; Schwarzwald, Ralf; Domes, Gregor

    2015-01-01

    The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention to the eye vs the mouth region. Intranasal oxytocin administration reduced amygdala reactivity to masked emotions when attending to salient facial features, ie, the eyes of angry faces and the mouth of happy faces. In addition, oxytocin decreased neural responses within the fusiform gyrus and brain stem areas, as well as functional coupling between the amygdala and the fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on brain activity were not attributable to differences in behavioral performance, as oxytocin had no impact on mere emotion detection. Our results suggest that oxytocin attenuates neural correlates of early arousal by threat signals from the eye region. As reduced threat sensitivity may increase the likelihood of engaging in social interactions, our findings may have important implications for clinical states of social anxiety. PMID:25047745

  2. Intravenous Medication Administration in Intensive Care: Opportunities for Technological Solutions

    PubMed Central

    Moss, Jacqueline; Berner, Eta; Bothe, Olaf; Rymarchuk, Irina

    2008-01-01

    Medication administration errors have been shown to be frequent and serious. Error is particularly prevalent in highly technical specialties such as critical care. The purpose of this study was to describe the characteristics of intravenous medication administration in five intensive care units. These data were used within the context of a larger study to design information system decision support to decrease medication administration errors in these settings. Nurses were observed during the course of their work and their intravenous medication administration process, medication order source, references used, calculation method, number of medications prepared simultaneously, and any interruptions occurring during the preparation and delivery phases of the administration event were recorded. In addition, chart reviews of medication administration records were completed and nurses were asked to complete an anonymous drop-box questionnaire regarding their experiences with medication administration error. The results of this study are discussed in terms of potential informatics solutions for reducing medication administration error. PMID:18998790

  3. Reactive nitrogen species reactivities with nitrones: theoretical and experimental studies.

    PubMed

    Nash, Kevin M; Rockenbauer, Antal; Villamena, Frederick A

    2012-08-20

    Reactive nitrogen species (RNS) such as nitrogen dioxide ((•)NO(2)), peroxynitrite (ONOO(-)), and nitrosoperoxycarbonate (ONOOCO(2)(-)) are among the most damaging species present in biological systems due to their ability to cause modification of key biomolecular systems through oxidation, nitrosylation, and nitration. Nitrone spin traps are known to react with free radicals and nonradicals via electrophilic and nucleophilic addition reactions and have been employed as reagents to detect radicals using electron paramagnetic resonance (EPR) spectroscopy and as pharmacological agents against oxidative stress-mediated injury. This study examines the reactivity of cyclic nitrones such as 5,5-dimethylpyrroline N-oxide (DMPO) with (•)NO(2), ONOO(-), ONOOCO(2)(-), SNAP, and SIN-1 using EPR. The thermochemistries of nitrone reactivity with RNS and isotropic hfsc's of the addition products were also calculated at the PCM(water)/B3LYP/6-31+G**//B3LYP/6-31G* level of theory with and without explicit water molecules to rationalize the nature of the observed EPR spectra. Spin trapping of other RNS such as azide ((•)N(3)), nitrogen trioxide ((•)NO(3)), amino ((•)NH(2)) radicals and nitroxyl (HNO) were also theoretically and experimentally investigated by EPR spin trapping and mass spectrometry. This study also shows that other spin traps such as 5-carbamoyl-5-methyl-pyrroline N-oxide, 5-ethoxycarbonyl-5-methyl-pyrroline N-oxide, and 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide can react with radical and nonradical RNS, thus making spin traps suitable probes as well as antioxidants against RNS-mediated oxidative damage. PMID:22775566

  4. [Risk Management of HBV Reactivation: Construction of Check System].

    PubMed

    Tanaka, Yasuhito

    2015-09-01

    In recent years, reactivation of HBV in patients receiving cancer chemotherapy or immunosuppressive therapy has been a problem. Generally, HBV-DNA levels are elevated prior to HBsAg concentration, and then hepatic dysfunction is observed in the process of hepatitis by HBV reactivation. Therefore, the monitoring of HBV-DNA is useful for the prediction of hepatic dysfunction, and nucleoside/nucleoside analogue (NA) administration is able to prevent this HBV reactivation. According to these facts, "Guidelines for the Prevention of HBV Reactivation in Patients Receiving Immunosuppressive Therapy or Chemotherapy", 2009 (revised as "JSH Guidelines for the Management of Hepatitis B Virus Infection", 2013) is established, and the diagnostic algorithm of HBsAg, anti-HBc, anti-HBs, and HBV-DNA has relevant descriptions. Combination therapy with rituximab and steroid for malignant lymphoma has a high risk of leading to fulminant hepatitis and, consequently, the guidelines are widely followed in such cases. We introduced the improvement of electronic medical recording and ordering systems in collaboration with hepatologists, and such a system has been widely used. Although the monitoring of HBV-DNA levels is required every 1-3 months, the guidelines are not followed strictly in cases such as rheumatoid disease and solid tumors only with chemotherapy or steroid treatment. Since a DNA assay is complicated and expensive, cost-effective, time-saving, and highly sensitive/specific measurements are required as well. Therefore, Lumipulse HBsAg-HQ (CLIA method) with high sensitivity is expected to be used for the monitoring of HBV reactivation.

  5. Lymphoproliferative Disease and Hepatitis B Reactivation: Challenges in the Era of Rapidly Evolving Targeted Therapy.

    PubMed

    Phipps, Colin; Chen, Yunxin; Tan, Daryl

    2016-01-01

    Reactivation of hepatitis B virus (HBV) is a known complication that occurs in patients receiving chemotherapy especially for malignant lymphoma. The increased risk in lymphoma patients parallels the potency of the immunosuppressive treatment regimens that are provided. B-cell-depleting therapy such as anti-CD20 monoclonal antibodies, especially when combined with conventional chemotherapy, significantly increases the risk of HBV reactivation, even in patients with resolved HBV infection. The first reports of HBV reactivation with anti-CD20 therapy emerged only 4 years after its US Food and Drug Administration approval. Today, these drugs carry alert warnings on the risk of hepatic dysfunction and reactivation of HBV infection. Many other new/novel agents active against lymphoma have emerged since then, targeting the different pathways involved in lymphoma pathogenesis, including histone deacetylase inhibitors, antibody-drug conjugates, and proteasome inhibitors. These various drugs have differing depths and mechanisms of immunosuppression, necessitating due diligence when administrating these compounds to prevent infective complications such as HBV reactivation, which can lead to liver failure and death. This review focuses on HBV reactivation with non-Hodgkin lymphoma treatment, in particular with the various approved novel agents. We also discuss the current recommendations for screening non-Hodgkin lymphoma patients for HBV and the role of prophylactic antiviral therapy during and after immunosuppressive treatment.

  6. Piperlongumine Blocks JAK2-STAT3 to Inhibit Collagen-Induced Platelet Reactivity Independent of Reactive Oxygen Species†

    PubMed Central

    Yuan, Hengjie; Houck, Katie L.; Tian, Ye; Bharadwaj, Uddalak; Hull, Ken; Zhou, Zhou; Zhou, Mingzhao; Wu, Xiaoping; Tweardy, David J.; Romo, Daniel; Fu, Xiaoyun; Zhang, Yanjun; Zhang, Jianning; Dong, Jing-fei

    2015-01-01

    Background Piperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known. Objective We conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen. Results PL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect. Conclusions PL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals. PMID:26645674

  7. Hyper-reactivity of cerebral arteries from ovariectomized rats: therapeutic benefit of tamoxifen.

    PubMed

    Thorin, Eric; Pham-Dang, Mylan; Clement, Robert; Mercier, Isabelle; Calderone, Angelino

    2003-12-01

    isolated from the OVX rat was associated with an exaggerated vasoconstrictor response to phenylephrine, and altered NO-dependent vascular reactivity. The administration of tamoxifen to OVX rats normalized cerebral artery reactivity to phenylephrine. These findings provide the impetus to examine the potential therapeutic benefit of the partial estrogen receptor agonist tamoxifen to reduce the incidence of cerebrovascular stroke in postmenopausal women.

  8. Reactive composite compositions and mat barriers

    DOEpatents

    Langton, Christine A.; Narasimhan, Rajendran; Karraker, David G.

    2001-01-01

    A hazardous material storage area has a reactive multi-layer composite mat which lines an opening into which a reactive backfill and hazardous material are placed. A water-inhibiting cap may cover the hazardous material storage area. The reactive multi-layer composite mat has a backing onto which is placed an active layer which will neutralize or stabilize hazardous waste and a fronting layer so that the active layer is between the fronting and backing layers. The reactive backfill has a reactive agent which can stabilize or neutralize hazardous material and inhibit the movement of the hazardous material through the hazardous material storage area.

  9. Integrated reactive absorption process for synthesis of fatty esters.

    PubMed

    Kiss, Anton Alexandru; Bildea, Costin Sorin

    2011-01-01

    Reactive separations using green catalysts offer great opportunities for manufacturing fatty esters, involved in specialty chemicals and biodiesel production. Integrating reaction and separation into one unit provides key benefits such as: simplified operation, no waste, reduced capital investment and low operating costs. This work presents a novel heat-integrated reactive absorption process that eliminates all conventional catalyst related operations, efficiently uses the raw materials and equipment, and considerably reduces the energy requirements for biodiesel production--85% lower as compared to the base case. Rigorous simulations based on experimental results were carried out using Aspen Plus and Dynamics. Despite the high degree of integration, the process is well controllable using an efficient control structure proposed in this work. The main results are provided for a plant producing 10 ktpy fatty acid methyl esters from methanol and waste vegetable oil with high free fatty acids content, using sulfated zirconia as solid acid catalyst.

  10. Sensing and Tactile Artificial Muscles from Reactive Materials

    PubMed Central

    Conzuelo, Laura Valero; Arias-Pardilla, Joaquín; Cauich-Rodríguez, Juan V.; Smit, Mascha Afra; Otero, Toribio Fernández

    2010-01-01

    Films of conducting polymers can be oxidized and reduced in a reversible way. Any intermediate oxidation state determines an electrochemical equilibrium. Chemical or physical variables acting on the film may modify the equilibrium potential, so that the film acts as a sensor of the variable. The working potential of polypyrrole/DBSA (Dodecylbenzenesulfonic acid) films, oxidized or reduced under constant currents, changes as a function of the working conditions: electrolyte concentration, temperature or mechanical stress. During oxidation, the reactive material is a sensor of the ambient, the consumed electrical energy being the sensing magnitude. Devices based on any of the electrochemical properties of conducting polymers must act simultaneously as sensors of the working conditions. Artificial muscles, as electrochemical actuators constituted by reactive materials, respond to the ambient conditions during actuation. In this way, they can be used as actuators, sensing the surrounding conditions during actuation. Actuating and sensing signals are simultaneously included by the same two connecting wires. PMID:22319265

  11. Catalytic destruction of groundwater contaminants in reactive extraction wells

    DOEpatents

    McNab, Jr., Walt W.; Reinhard, Martin

    2002-01-01

    A system for remediating groundwater contaminated with halogenated solvents, certain metals and other inorganic species based on catalytic reduction reactions within reactive well bores. The groundwater treatment uses dissolved hydrogen as a reducing agent in the presence of a metal catalyst, such a palladium, to reduce halogenated solvents (as well as other substituted organic compounds) to harmless species (e.g., ethane or methane) and immobilize certain metals to low valence states. The reactive wells function by removing water from a contaminated water-bearing zone, treating contaminants with a well bore using catalytic reduction, and then reinjecting the treated effluent into an adjacent water-bearing zone. This system offers the advantages of a compact design with a minimal surface footprint (surface facilities) and the destruction of a broad suite of contaminants without generating secondary waste streams.

  12. 21 CFR 866.5270 - C-reactive protein immuno-logical test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-reactive protein immuno-logical test system. 866.5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  13. 21 CFR 866.5270 - C-reactive protein immuno-logical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false C-reactive protein immuno-logical test system. 866.5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  14. 21 CFR 866.5270 - C-reactive protein immuno-logical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false C-reactive protein immuno-logical test system. 866.5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  15. 21 CFR 866.5270 - C-reactive protein immuno-logical test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false C-reactive protein immuno-logical test system. 866.5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  16. Reactive nitrogen species in cellular signaling

    PubMed Central

    Adams, Levi; Franco, Maria C

    2015-01-01

    The transduction of cellular signals occurs through the modification of target molecules. Most of these modifications are transitory, thus the signal transduction pathways can be tightly regulated. Reactive nitrogen species are a group of compounds with different properties and reactivity. Some reactive nitrogen species are highly reactive and their interaction with macromolecules can lead to permanent modifications, which suggested they were lacking the specificity needed to participate in cell signaling events. However, the perception of reactive nitrogen species as oxidizers of macromolecules leading to general oxidative damage has recently evolved. The concept of redox signaling is now well established for a number of reactive oxygen and nitrogen species. In this context, the post-translational modifications introduced by reactive nitrogen species can be very specific and are active participants in signal transduction pathways. This review addresses the role of these oxidative modifications in the regulation of cell signaling events. PMID:25888647

  17. Streamlining administration at the University of Minnesota Medical School.

    PubMed

    Mitsch, Peter; Jensen, Allison Campbell

    2007-03-01

    The authors describe the events and restructuring efforts of the 1990s that led the University of Minnesota Medical School leadership to advocate a new administrative model for its clinical departments. This new streamlined model established six administrative centers, each serving a cluster of two to four clinical departments. Each administrative center was charged with managing functions of finance, human resources, information technology, clinical service unit operations, research support, and education support for its departments. These centers, first proposed in 1993 when an outside firm analyzed the medical school's administration, were initially seen by most medical school department heads as too radical. Yet, after a campaign of one-on-one persuasion by medical school dean's office leadership, combined with a successful example of clustering that occurred spontaneously among three medical school departments, the administrative centers were launched in late 1998 to serve clustered clinical departments. The administrative centers were intended to improve departmental responsiveness to the dean of the medical school; improve internal medical school controls; improve on administrative services traditionally provided by outside units, such as grants management and information systems; and reduce administrative costs. Since their establishment, these administrative centers have evolved into a flexible, efficient system of administration. In a 2005 evaluation, ECG Management Consultants found the administrative center model appropriate and effective in managing the school's clinical departments. In addition, the consultants estimated that if the medical school still had stand-alone departmental administrative units, annual administrative costs would be $3 million higher.

  18. 7. Administrative structures.

    PubMed

    2014-05-01

    The basic systems of any society rarely can operate independently. Instead, they are dependent and often interdependent upon other entities. Such entities control the resources within their respective systems. Thus, coordination and control agencies require contracts or memoranda of understanding with these entities in order to assure access to the resources required during a crisis. These administrative structures include: (1) governmental institutions and agencies, including the military; (2) intergovernmental organisations; (3) nongovernmental organisations; (4) commercial private sector organisations; and (5) academic institutions. These dependencies create potential barriers to the provision of coordination and control including: (1) the complexity of the administrative structures with which coordination and control must interact; (2) the location of resources; (3) finding responsible person(s); (4) the competence and compatibility; (5) methods of access; (6) payment; (7) contracts and memoranda of understanding; (8) inventories of accessible resources; (9) competition for the mandate, power, and resources; and (10) jealousy. The need for potential interactions between administrative structures requires that agreements for the sharing of resources during crises be reached as part of planning and preparedness. Gaining an understanding of these relationships is an important area for research.

  19. Acute effects of corticosterone on LiCl-induced rapid gustatory conditioning in rats: a taste reactivity analysis.

    PubMed

    Kent, W D; Cross-Mellor, S K; Kavaliers, M; Ossenkopp, K P

    2000-11-27

    Previous research has shown that acute corticosterone treatment can have rapid effects on learning and memory. Using the taste reactivity test (TRT), the present study examined the effect of acute administration of corticosterone on sucrose palatability and the development of LiCl-induced rapid gustatory conditioning. On each of two conditioning days rats were injected with either a low dose of lithium chloride (LiCl; 0.75 mEq, i.p.) or saline (NaCl; 0.9%, i.p.) and 10 min later, received a second injection of either corticosterone (5 mg/kg, i.p.) or cyclodextrin vehicle. Rats were then placed in the TRT chamber, where 1 min intraoral infusions of sucrose (0.3 M) were delivered every 10 min. Taste reactivity responses were videotaped and later analyzed for frequency of occurrence. Rats treated with both LiCl and corticosterone showed enhanced aversive responding and reduced ingestive responding relative to control rats treated with LiCl and vehicle. The implication that corticosterone may have a rapid enhancing effect on gustatory conditioning is discussed.

  20. Reducing Methyl Halide Emissions from Soils

    NASA Astrophysics Data System (ADS)

    Yates, S. R.; Xuan, R.; Ashworth, D.; Luo, L.

    2011-12-01

    Volatilization and soil transformation are major pathways by which pesticides dissipate from treated agricultural soil. Methyl bromide (MeBr) emissions from agricultural fumigation can lead to depletion of the stratospheric ozone layer. This has led to a gradual phase-out of MeBr and replacement by other halogenated chemicals. However, MeBr continues to be widely used under Critical Use Exemptions and development of emission-reduction strategies remains important. Several methods to reduce emissions of MeBr, and other halogenated soil fumigants, have been developed and are currently being tested under field conditions. In this paper, several approaches for reducing fumigant emissions to the atmosphere are described and include the use of virtually impermeable films, the creation of reactive soil barriers and a recently developed reactive film which was designed to limit loss of MeBr from soil without adding any material to the soil surface. Ammonium thiosulfate (ATS) was used to create a reactive layer. For a reactive soil layer, ATS was sprayed on the soil surface or incorporated to a depth of 1-2 cm. For the reactive film, ATS was placed between two layers of plastic film. The lower plastic layer was a high-density polyethylene film (HDPE), which is readily permeable to MeBr. The upper layer was a virtually impermeable film (VIF) and limits MeBr diffusion. MeBr diffusion and transformation through VIFs and reactive layers were tested in laboratory and field experiments. Although ineffective when dry, when sufficient water was present, reactive barriers substantially depleted halogenated fumigants, including MeBr. When ATS was activated in laboratory experiments, MeBr half-life was about 9.0 h (20C) in a reactive film barrier, and half life decreased with increasing temperature. When the soil was covered with VIF, less than 10% of the added MeBr diffused through the film and the remainder was transformed within the soil. This compares with 60 to 90% emission