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Sample records for prolonged restricted activity

  1. Exercise performance, core temperature, and metabolism after prolonged restricted activity and retraining in dogs

    Science.gov (United States)

    Nazar, K.; Greenleaf, J. E.; Pohoska, E.; Turlejska, E.; Kaciuba-Uscilko, H.; Kozlowski, S.

    1992-01-01

    Physiological effects of restricted activity (RA) and subsequent retraining have been studied. Ten male mongrel dogs performed a submaximal exercise endurance test on a treadmill during kennel control, after 8 weeks of cage confinement and after eight weeks of retraining using the same treadmill protocol 1 h/d for 6 d/week. Data obtained show that RA reduces exercise endurance, the effectiveness of exercise thermoregulation, muscle glycogen stores, and the lipolytic response to exercise and to noradrenaline stimulation.

  2. Does SIRT-1 Mediate Calorie Restriction and Prolong Life? – A Mini Review

    Directory of Open Access Journals (Sweden)

    Kordala Anna

    2014-09-01

    Full Text Available Calorie restriction is the only intervention proved to prolong both average and maximum lifespan in yeast, worms, fish, rodents and possibly primates. Not only does the regimen prolong life, but it also reduces the incident of numerous age-related diseases like diabetes, atherosclerosis or cancer and slows down ageing. Mechanisms by which that is thought to occur have not yet been elucidated, but they probably involve reactive oxygen species signaling, insulin growth factor and transcriptional factors. Here, special emphasis is given to SIRT1 - silent information regulator. There is sound evidence showing that SIRT1 is a key player in mediating physiological response to calorie restriction and that its overexpression is correlated with extended lifespan. The possible mechanism leading to its elevated levels is high NAD/NADH ratio, observed in Sir2 in yeast. SIRT1 increases glucose production, enhances fat mobilization, stimulates angiogenesis, prevents neuronal degeneration and rises insulin sensitivity. Therefore, it seems to be a very beneficial factor activated by such a simple intervention that is calorie restriction.

  3. The GOAT-ghrelin system is not essential for hypoglycemia prevention during prolonged calorie restriction.

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi

    Full Text Available Ghrelin acylation by ghrelin O-acyltransferase (GOAT has recently been reported to be essential for the prevention of hypoglycemia during prolonged negative energy balance. Using a unique set of four different genetic loss-of-function models for the GOAT/ghrelin/growth hormone secretagogue receptor (GHSR system, we thoroughly tested the hypothesis that lack-of-ghrelin activation or signaling would lead to hypoglycemia during caloric deprivation.Male and female knockout (KO mice for GOAT, ghrelin, GHSR, or both ghrelin and GHSR (dKO were subjected to prolonged calorie restriction (40% of ad libitum chow intake. Body weight, fat mass, and glucose levels were recorded daily and compared to wildtype (WT controls. Forty-eight hour blood glucose profiles were generated for each individual mouse when 2% or less body fat mass was reached. Blood samples were obtained for analysis of circulating levels of acyl- and desacyl-ghrelin, IGF-1, and insulin.Chronic calorie restriction progressively decreased body weight and body fat mass in all mice regardless of genotype. When fat mass was depleted to 2% or less of body weight for 2 consecutive days, random hypoglycemic events occurred in some mice across all genotypes. There was no increase in the incidence of hypoglycemia in any of the four loss-of-function models for ghrelin signaling including GOAT KO mice. Furthermore, no differences in insulin or IGF-1 levels were observed between genotypes.The endogenous GOAT-ghrelin-GHSR system is not essential for the maintenance of euglycemia during prolonged calorie restriction.

  4. The impact of breaking up prolonged sitting on glucose metabolism and cognitive function when sleep is restricted

    Directory of Open Access Journals (Sweden)

    Grace E. Vincent

    2018-01-01

    Conclusions: There were no observable benefits of breaking up prolonged sitting on glucose metabolism under conditions of sleep restriction. These findings have implications for behaviour change interventions. Future studies will need to include larger, less homogenous study populations and appropriate control conditions (i.e., 8–9 h sleep opportunities.

  5. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During cogenesis in Drosophila melanogaster local Egfr activation by the spatially-restricted TGFalpha-like ligand Gurken (Grk...

  6. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken (Grk...

  7. Brain activity and fatigue during prolonged exercise in the heat

    DEFF Research Database (Denmark)

    Nielsen, Bodil; Hyldig, Tino; Bidstrup, F.

    2001-01-01

    We hypothesized that fatigue due to hyperthermia during prolonged exercise in the heat is in part related to alterations in frontal cortical brain activity. The electroencephalographic activity (EEG) of the frontal cortex of the brain was measured in seven cyclists [maximal O2 uptake (VO2max) 4...... min of exercise; P

  8. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Clouse, Katherine N; Goodrich, Jennifer S

    2006-01-01

    ...) functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Sqd to produce spatially-restricted Egfr activation...

  9. EGFR Activation by Spatially Restricted Ligands

    National Research Council Canada - National Science Library

    Goodrich, Jennifer S

    2005-01-01

    ...) functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Squid to produce spatially-restricted EGFR activation...

  10. Compensatory mechanisms activated with intermittent energy restriction

    DEFF Research Database (Denmark)

    Coutinho, Sílvia Ribeiro; Halset, Eline Holli; Gåsbakk, Sigrid

    2018-01-01

    Background & aims: Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy...... restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. Methods: 35 adults (age......: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m2) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting...

  11. Prolonged REM sleep restriction induces metabolic syndrome-related changes: Mediation by pro-inflammatory cytokines.

    Science.gov (United States)

    Venancio, Daniel Paulino; Suchecki, Deborah

    2015-07-01

    Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (pmetabolic syndrome-related alterations that may be mediated by inflammation of the RPAT. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. AVS-1357 inhibits melanogenesis via prolonged ERK activation.

    Science.gov (United States)

    Kim, Dong-Seok; Lee, Hyun-Kyung; Park, Seo-Hyoung; Chae, Chong Hak; Park, Kyoung-Chan

    2009-08-01

    In this study, we demonstrated that a derivative of imidazole, AVS-1357, is a novel skin-whitening compound. AVS-1357 was found to significantly inhibit melanin production in a dose-dependent manner; however, it did not directly inhibit tyrosinase. Furthermore, we found that AVS-1357 induced prolonged activation of extracellular signal-regulated kinase (ERK) and Akt, while it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase. It has been reported that the activation of ERK and/or Akt is involved in melanogenesis. Therefore, we examined the effects of AVS-1357 on melanogenesis in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway) and/or LY294002 (a specific inhibitor of the Akt pathway). PD98059 dramatically increased melanogenesis, whereas LY294002 had no effect. Furthermore, PD98059 attenuated AVS-1357 induced ERK activation, as well as the downregulation of MITF and tyrosinase. These findings suggest that the effects of AVS-1357 occur via downregulation of MITF and tyrosinase, which is caused by AVS-1357-induced prolonged ERK activation. Taken together, our results indicate that AVS-1357 has the potential as a new skin whitening agent.

  13. Effect of pinealectomy and prolonged melatonin administration on circadian testicular function in food restricted rats

    International Nuclear Information System (INIS)

    Ostrowska, Z.; Zwirska-Korczala, K.; Kajdaniuk, D.; Gorski, J.; Buntner, B.

    1995-01-01

    The effect of pinealectomy and exogenous melatonin on the circadian testosterone variations was investigated (using the radioimmunoassay method) after 3 weeks of 50% food restriction in sexually mature male Wistar rats at 3-h intervals under 12:12 light-dark cycle. The circadian periodicity of testosterone secretion was maintained after caloric deprivation, however its mean 24-h concentration was lower and rhythm disturbances appeared in the form of acrophase shifts from 18.00 to 0.50 h. In pinealectomized animals the mean 24-h testosterone level and amplitude values were significantly increased without the rhythm disturbances. As compared to the control animals, underfed pinealectomized rats had a partial recovery of reduced testosterone levels during the 24-h cycle and showed a normalization of the rhythm acrophase. Melatonin administration was found to inhibit the testosterone mesor value in pinealectomized rats with acrophase shifts from 16.58 to 14.51 h. In comparison with the pinealectomized ones the underfed pinealectomized rats had a greater reduction of the mesor and amplitude values after the melatonin administration. These findings indicate that long-term food restriction sensitizes the circadian testicular axis to antigonadotropic action of the pineal gland. (author). 42 refs, 3 figs, 1 tab

  14. Intermittent food restriction initiated late in life prolongs lifespan and retards the onset of age-related markers in the annual fish Nothobranchius guentheri.

    Science.gov (United States)

    Wang, Xia; Du, Xiaoyuan; Zhou, Yang; Wang, Su; Su, Feng; Zhang, Shicui

    2017-06-01

    Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3.5 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We also showed that IFR reduced the accumulation of lipofuscin in the gills and the protein oxidation and lipid peroxidation levels in the muscles. Moreover, IFR was able to enhance the activities of antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the fish. Finally, IFR was also able to decelerate the decrease of SirT1 and Foxo3A, but accelerate the decrease of IGF-1. Collectively, our findings suggest that late-onset IFR can retard the onset of age-related markers, and prolong the lifespan of the aging fish, via a synergistic action of an anti-oxidant system and the IIS pathway. It also proposes that the combined assessment of anti-oxidant system and IIS pathway will contribute to providing a more comprehensive view of anti-aging process.

  15. Performance and brain electrical activity during prolonged confinement.

    Science.gov (United States)

    Lorenz, B; Lorenz, J; Manzey, D

    1996-01-01

    to be associated with an increasing demand on perceptual cue utilization required by the tracking performance. In one subject marked attenuation of alpha power occurred during the first half of the confinement period, where he also scored the highest fatigue ratings. A striking increase in fronto-central theta activity was observed in the same subject after six weeks of isolation. The change was associated with an efficient rather than a degraded task performance, and a high rating of the item "concentrated" and a low rating of the item "fatigued." This finding supports the hypothesis that the activation state associated with increased fronto-central theta activity accompanies efficient performance of demanding mental tasks. The usefulness of standardized laboratory tasks as monitoring instruments is demonstrated by the direct comparability with results of studies obtained from other relevant research applications using the same tasks. The feasibility of a self-administered integrated psychophysiological assessment of the individual state was illustrated by the nearly complete collection of data. The large number of individual data collected over the entire period permitted application of quantitative single-subject analysis, allowing reliable determination of changes in the individual state in the course of time. It thus appears that this assessment technique can be adapted for in-flight monitoring of astronauts during prolonged spaceflights. Parallel EEG recording can provide relevant supplementary information for diagnosing the individual activation state associated with task performance. The existence of large individual differences in the generation of task-sensitive EEG rhythms forms an important issue for further studies.

  16. Prolonged radioprotective activity of WR-2721 linked to dextran

    International Nuclear Information System (INIS)

    Moenig, H.; Konermann, G.; Oehlert, W.

    1990-01-01

    The radioprotective agent WR-2721 was linked to dextran and poly(glutamic acid) respectively, to obtain a prolonged radioprotective ability. Male mice were administered these water soluble polymer conjugates one to 72 hours prior to a whole body irradiation with X-rays. A prolongation of radioprotective efficiency was achieved with two dextran-(WR-2721)-conjugates. For a period of 24 hours between administration, and irradiation dose reduction factors of 1.14±0.04 and 1.10±0.03 respectively were found. After 72 hours, no protective effect was observed. Histopathological investigations of the liver for formation of tumors 200 to 600 days after irradiation seems to indicate that a protective effect is not produced by the dextran-(WR-2721)-conjugats. (orig.) [de

  17. Activity restriction among women with a short cervix.

    Science.gov (United States)

    Grobman, William A; Gilbert, Sharon A; Iams, Jay D; Spong, Catherine Y; Saade, George; Mercer, Brian M; Tita, Alan T N; Rouse, Dwight J; Sorokin, Yoram; Leveno, Kenneth J; Tolosa, Jorge E; Thorp, John M; Caritis, Steve N; Van Dorsten, J Peter

    2013-06-01

    To estimate determinants of and outcomes associated with activity restriction among women with a short cervix. This was a secondary analysis of a randomized trial of 17-α hydroxyprogesterone caproate for prevention of preterm birth among nulliparous women with singleton gestations and cervices less than 30 mm by midtrimester ultrasonography. Women were asked weekly whether they had been placed on pelvic, work, or nonwork rest. "Any activity restriction" was defined as being placed on any type of rest. Factors associated with any activity restriction were determined and the association between preterm birth and activity restriction was estimated with multivariable logistic regression. Of the 657 women in the trial, 646 (98%) responded to questions regarding activity restriction. Two hundred fifty-two (39.0%) were placed on any activity restriction at a median of 23.9 weeks (interquartile range 22.6-27.9 weeks). Women on activity restriction were older, more likely to have private insurance, less likely to be Hispanic, had a shorter cervical length, and were more likely to have funneling and intra-amniotic debris. Preterm birth at less than 37 weeks of gestation was more common among women placed on activity restriction (37% compared with 17%, Prestriction (adjusted odds ratio 2.37, 95% confidence interval 1.60-3.53). Results were similar for preterm birth at less than 34 weeks of gestation. Activity restriction did not reduce the rate of preterm birth in asymptomatic nulliparous women with a short cervix.

  18. Recommendations of activity restriction in high-risk pregnancy scenarios

    DEFF Research Database (Denmark)

    Bendix, Jane; Hegaard, Hanne Kristine; Bergholt, Thomas

    2015-01-01

    activity restriction more often than obstetricians in five of the nine scenarios, in women with preterm premature rupture of membranes, preterm labour, cervical ripening, total placenta praevia, and intrauterine growth restriction, whereas no differences were found in the remaining scenarios. Compared...... to the obstetricians, the midwives also reported that they expected the recommendation to be more effective. Most midwives and obstetricians reported that they thought strict activity restriction was associated with severe or moderate adverse effect, and recommended antithrombotic prophylaxis. Conclusions: Danish...... obstetricians and midwives prescribe activity restriction in most high-risk pregnancies. The degree of activity restriction and the presumed effect vary between clinicians. This may reflect different attitudes and lack of guidelines based on clinical studies of a possible benefit of activity restriction....

  19. Perceived risk of osteoporosis: Restricted physical activities?

    DEFF Research Database (Denmark)

    Reventlow, Susanne

    2007-01-01

    Objective. To explore elderly women's physical activity in relation to their perception of the risk of osteoporosis. Design. Qualitative study using in-depth interviews. Setting. Informants were purposely selected from a Danish population-based, age-specific cohort study conducted in the county...... of Copenhagen with people born in 1936. Subjects. Women in their sixties. Results. Women who perceived a current risk of osteoporosis tended to reduce their physical activity in an attempt to reduce the risk of bone damage. This behaviour was related to the imagined fragility of the bones (the risk inside...... the body), and the actual situations (the risk outside the body), including places and activities. Knowledge of a reduced bone mass reinforced the women's uncertainty about what their bones could endure. Experiences managing physical activity without injury resulted in reinterpretations of their risk...

  20. 45 CFR 3.42 - Restricted activities.

    Science.gov (United States)

    2010-10-01

    ... take photographs, films or audiovisuals, for personal or news purposes on the grounds of the enclave or... by appropriate signs. Photographs and similar activities for advertising or commercial purposes may...

  1. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

    Science.gov (United States)

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank

    2017-01-01

    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868

  2. Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan.

    Science.gov (United States)

    Speakman, John R; Hambly, Catherine

    2007-04-01

    Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

  3. Prolonged fasting activates Nrf2 in post-weaned elephant seals.

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Soñanez-Organis, José G; Rodriguez, Ruben; Viscarra, Jose A; Nishiyama, Akira; Crocker, Daniel E; Ortiz, Rudy M

    2013-08-01

    Elephant seals naturally experience prolonged periods of absolute food and water deprivation (fasting). In humans, rats and mice, prolonged food deprivation activates the renin-angiotensin system (RAS) and increases oxidative damage. In elephant seals, prolonged fasting activates RAS without increasing oxidative damage likely due to an increase in antioxidant defenses. The mechanism leading to the upregulation of antioxidant defenses during prolonged fasting remains elusive. Therefore, we investigated whether prolonged fasting activates the redox-sensitive transcription factor Nrf2, which controls the expression of antioxidant genes, and if such activation is potentially mediated by systemic increases in RAS. Blood and skeletal muscle samples were collected from seals fasting for 1, 3, 5 and 7 weeks. Nrf2 activity and nuclear content increased by 76% and 167% at week 7. Plasma angiotensin II (Ang II) and transforming growth factor β (TGF-β) were 5000% and 250% higher at week 7 than at week 1. Phosphorylation of Smad2, an effector of Ang II and TGF signaling, increased by 120% at week 7 and by 84% in response to intravenously infused Ang II. NADPH oxidase 4 (Nox4) mRNA expression, which is controlled by smad proteins, increased 430% at week 7, while Nox4 protein expression, which can activate Nrf2, was 170% higher at week 7 than at week 1. These results demonstrate that prolonged fasting activates Nrf2 in elephant seals and that RAS stimulation can potentially result in increased Nox4 through Smad phosphorylation. The results also suggest that Nox4 is essential to sustain the hormetic adaptive response to oxidative stress in fasting seals.

  4. Interrupting Prolonged Sitting with Regular Activity Breaks does not Acutely Influence Appetite: A Randomised Controlled Trial

    OpenAIRE

    Evelyn M. Mete; Tracy L. Perry; Jillian J. Haszard; Ashleigh R. Homer; Stephen P. Fenemor; Nancy J. Rehrer; C. Murray Skeaff; Meredith C. Peddie

    2018-01-01

    Regular activity breaks increase energy expenditure; however, this may promote compensatory eating behaviour. The present study compared the effects of regular activity breaks and prolonged sitting on appetite. In a randomised, cross-over trial, 36 healthy adults (BMI (Body Mass Index) 23.9 kg/m2 (S.D. = 3.9)) completed four, two-day interventions: two with prolonged sitting (SIT), and two with sitting and 2 min of walking every 30 min (RAB). Standardized meals were provided throughout the in...

  5. Perceived need for restrictions on activity for children with epilepsy.

    Science.gov (United States)

    Brna, Paula M; Gordon, Kevin E; Woolridge, Elaine; Dooley, Joseph M; Wood, Ellen

    2017-08-01

    Children and youth with epilepsy have long been subjected to excessive restrictions on extracurricular activities due to concerns over risk of injury. Over time physicians and medical regulatory associations have liberalized the advice given for people with epilepsy to promote independence, self-esteem and general health benefits of physical activity. Current evidence suggests that few restrictions are needed for children with epilepsy beyond water-related precautions and avoidance of very high-risk activities. However, more stringent restrictions on daily activities may be imposed by caregivers. This study was aimed at exploring current perceptions of parents regarding restrictions on activity for children with epilepsy and the child's perspective on restrictions related to the diagnosis. A self-administered questionnaire was offered to a sample of parent-child dyads of children/youth with epilepsy attending summer camp for children with epilepsy age 8-18years. A 10-item validated HARCES Parent Scale of Childhood Epilepsy was completed by the parent/guardian and a modified-HARCES completed by the child. The primary objective was to assess the degree of restrictions placed on children with epilepsy from the perspective of child and parent assessed independently. Agreement of perceived restrictions between parent-child dyads was also determined. 21 parent/guardian-child pairs were recruited with mean age of children/youth 12.7years (range 9-16years). Total HARCES scores for parents and guardians ranged from 11-26 (x=16.5; SD 4.9) while total scores for children with epilepsy similarly ranged from 10-25 (x=15.2; SD 4.9). There were no differences in total parent scores when analyzed by child's age (13years), gender, age of seizure onset, seizure frequency or seizure type. Total HARCES scores showed no agreement between parent and child pairs with correlation of 0.2798 (95% CI -0.173-0.635). Children and youth with epilepsy often face activity restrictions based on

  6. Historical space weather monitoring of prolonged aurora activities in Japan and in China

    Science.gov (United States)

    Kataoka, Ryuho; Isobe, Hiroaki; Hayakawa, Hisashi; Tamazawa, Harufumi; Kawamura, Akito Davis; Miyahara, Hiroko; Iwahashi, Kiyomi; Yamamoto, Kazuaki; Takei, Masako; Terashima, Tsuneyo; Suzuki, Hidehiko; Fujiwara, Yasunori; Nakamura, Takuji

    2017-02-01

    Great magnetic storms are recorded as aurora sightings in historical documents. The earliest known example of "prolonged" aurora sightings, with aurora persistent for two or more nights within a 7 day interval at low latitudes, in Japan was documented on 21-23 February 1204 in Meigetsuki, when a big sunspot was also recorded in China. We have searched for prolonged events over the 600 year interval since 620 in Japan based on the catalogue of Kanda and over the 700 year interval since 581 in China based on the catalogues of Tamazawa et al. (2017) and Hayakawa et al. (2015). Before the Meigetsuki event, a significant fraction of the 200 possible aurora sightings in Sòng dynasty (960-1279) of China was detected at least twice within a 7 day interval and sometimes recurred with approximately the solar rotation period of 27 days. The majority of prolonged aurora activity events occurred around the maximum phase of solar cycles rather than around the minimum, as estimated from the 14C analysis of tree rings. They were not reported during the Oort Minimum (1010-1050). We hypothesize that the prolonged aurora sightings are associated with great magnetic storms resulting from multiple coronal mass ejections from the same active region. The historical documents therefore provide useful information to support estimation of great magnetic storm frequency, which are often associated with power outages and other societal concerns.

  7. Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

    Science.gov (United States)

    Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

    2016-06-15

    Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Prolonged calorie restriction downregulates skeletal muscle mTORC1 signaling independent of dietary protein intake and associated microRNA expression

    Directory of Open Access Journals (Sweden)

    Lee M Margolis

    2016-10-01

    Full Text Available Short-term (5-10 days calorie restriction (CR downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1, however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR. 12-wk old male Sprague Dawley rats consumed ad libitum (AL or calorie restricted (CR; 40% adequate (10%, AIN-93M or high (32% protein milk-based diets for 16 weeks. Body composition was determined using dual energy X-ray absorptiometry and muscle protein content was calculated from muscle homogenate protein concentrations expressed relative to fat-free mass to estimate protein content. Western blot and RT-qPCR were used to determine mTORC1 signaling and mRNA and miR expression in fasted mixed gastrocnemius. Independent of dietary protein intake, muscle protein content was 38% lower (P < 0.05 in CR compared to AL. Phosphorylation and total Akt, mTOR, rpS6 and p70S6K were lower (P < 0.05 in CR versus AL, and total rpS6 was associated with muscle protein content (r = 0.64, r2 = 0.36. Skeletal muscle miR expression was not altered by either energy or protein intake. This study provides evidence that chronic CR attenuates muscle protein content by downregulating mTORC1 signaling. This response is independent of skeletal muscle miR and dietary protein.

  9. The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

    Science.gov (United States)

    Liu, Jie; Li, Fanfan; Shu, Kuangyi; Chen, Tao; Wang, Xiaoou; Xie, Yaoqi; Li, Shanshan; Zhang, Zhaohua; Jin, Susu; Jiang, Minghua

    2018-05-13

    To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid. © 2018 Wiley Periodicals, Inc.

  10. Interrupting Prolonged Sitting with Regular Activity Breaks does not Acutely Influence Appetite: A Randomised Controlled Trial.

    Science.gov (United States)

    Mete, Evelyn M; Perry, Tracy L; Haszard, Jillian J; Homer, Ashleigh R; Fenemor, Stephen P; Rehrer, Nancy J; Skeaff, C Murray; Peddie, Meredith C

    2018-01-26

    Regular activity breaks increase energy expenditure; however, this may promote compensatory eating behaviour. The present study compared the effects of regular activity breaks and prolonged sitting on appetite. In a randomised, cross-over trial, 36 healthy adults (BMI (Body Mass Index) 23.9 kg/m² (S.D. = 3.9)) completed four, two-day interventions: two with prolonged sitting (SIT), and two with sitting and 2 min of walking every 30 min (RAB). Standardized meals were provided throughout the intervention, with an ad libitum meal at the end of Day 2. Appetite and satiety were assessed throughout both days of each intervention using five visual analogue scales. The five responses were combined into a single appetite response at each time point. The area under the appetite response curve (AUC) was calculated for each day. Intervention effects for appetite response AUC and ad libitum meal intake were tested using linear mixed models. Appetite AUC did not differ between interventions (standardised effect of RAB compared to SIT: Day 1: 0.11; 95% CI: -0.28, 0.06; p = 0.212; Day 2: 0.04; 95% CI: -0.15, 0.24; p = 0.648). There was no significant difference in energy consumed at the ad libitum lunch meal on Day 2 between RAB and SIT. Interrupting prolonged sitting with regular activity breaks does not acutely influence appetite or volume of food consumed, despite inferred increases in energy expenditure. Longer-term investigation into the effects of regular activity breaks on energy balance is warranted.

  11. Interrupting Prolonged Sitting with Regular Activity Breaks does not Acutely Influence Appetite: A Randomised Controlled Trial

    Directory of Open Access Journals (Sweden)

    Evelyn M. Mete

    2018-01-01

    Full Text Available Regular activity breaks increase energy expenditure; however, this may promote compensatory eating behaviour. The present study compared the effects of regular activity breaks and prolonged sitting on appetite. In a randomised, cross-over trial, 36 healthy adults (BMI (Body Mass Index 23.9 kg/m2 (S.D. = 3.9 completed four, two-day interventions: two with prolonged sitting (SIT, and two with sitting and 2 min of walking every 30 min (RAB. Standardized meals were provided throughout the intervention, with an ad libitum meal at the end of Day 2. Appetite and satiety were assessed throughout both days of each intervention using five visual analogue scales. The five responses were combined into a single appetite response at each time point. The area under the appetite response curve (AUC was calculated for each day. Intervention effects for appetite response AUC and ad libitum meal intake were tested using linear mixed models. Appetite AUC did not differ between interventions (standardised effect of RAB compared to SIT: Day 1: 0.11; 95% CI: −0.28, 0.06; p = 0.212; Day 2: 0.04; 95% CI: −0.15, 0.24; p = 0.648. There was no significant difference in energy consumed at the ad libitum lunch meal on Day 2 between RAB and SIT. Interrupting prolonged sitting with regular activity breaks does not acutely influence appetite or volume of food consumed, despite inferred increases in energy expenditure. Longer-term investigation into the effects of regular activity breaks on energy balance is warranted.

  12. Influence of a prolonged fasting and mild activity on routine laboratory tests.

    Science.gov (United States)

    Šupak-Smolčić, Vesna; Antončić, Dragana; Ožanić, Doris; Vladilo, Ivana; Bilić-Zulle, Lidija

    2015-01-01

    Despite the standardization of the phlebotomy procedure, blood analysis is occasionally requested after recommended hours with the excuse that the patient is still fasting. We aimed to examine the influence of prolonged fasting and mild physical activity on routine laboratory tests. The study was conducted on 30 volunteers (27 female) median age 40y (20-59). Blood samples were taken in the morning (7:00-8:00a.m.) and early afternoon (1:00-2:00p.m.) after prolonged fasting and usual daily activities. Serum glucose (GLU), urea, creatinine, triglyceride, uric acid (UA), iron and electrolytes were analyzed on Roche cobas 6000 c501 and complete blood count on Siemens ADVIA 2120i. Statistical significance between the two measurements was tested using paired t-test or Wilcoxon test according to data distribution. Clinical significance was judged against calculated reference change values (RCV). A statistically significant decrease was found for red blood cell count, hemoglobin, hematocrit, mean corpuscular volume (MCV), GLU, urea, creatinine, triglycerides and electrolytes, whereas white blood cell count and iron were significantly increased. Judging against desirable bias derived from biological variation, a significant change was found for all the analytes except MCV, platelet count, UA and triglycerides. A clinically significant change was not found for any of the tested analytes when compared to RCV. Prolonged fasting and mild activity will not influence the medical decision for healthy subjects with normal results. Despite the present statistically significant change, the clinically significant change was not shown. However, the study did not include pathological results which have to be interpreted more carefully. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. Physical activity, energy restriction, and the risk of pancreatic cancer: Prospective study in the Netherlands

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Goldbohm, R.A.; Lumey, L.H.; Brandt, P.A. van den

    2011-01-01

    Background: Because of their influence on insulin concentrations, we hypothesized that both physical activity and energy restriction may reduce the risk of pancreatic cancer. Objective: We examined the associations between physical activity, proxies for energy restriction, and pancreatic cancer

  14. Lupus nephritis: prolonged immunoadsorption (IAS) reduces proteinuria and stabilizes global disease activity.

    Science.gov (United States)

    Stummvoll, Georg H; Schmaldienst, Sabine; Smolen, Josef S; Derfler, Kurt; Biesenbach, Peter

    2012-02-01

    Systemic lupus erythematosus (SLE) is characterized by pathogenic autoantibodies, which can be removed by extracorporeal procedures. While previous studies have shown short-term efficacy of immunoadsorption (IAS) in SLE, no information on long-term benefit and safety is available. IAS was offered to patients with highly active renal disease when conventional therapy had failed. Eleven patients entered the prolonged IAS programme and were followed for up to 10 years (mean 6.4 ± 3.5). Efficacy of IAS was determined by reduction in proteinuria (primary outcome), global disease activity [SLE Disease Activity Index (SLEDAI)] and anti-double-stranded DNA (anti-dsDNA) levels (secondary outcomes). Full/partial remission was defined as ≤ 0.5/≤ 1.0 g/day for proteinuria, ≤ 5/≤ 8 for SLEDAI and ≤ 25/≤ 50 IU/mL for anti-dsDNA levels. We further assessed flares, infections, malignancies and procedure-related adverse events. Short-term IAS (≤ 1 year) resulted in a significant reduction of proteinuria (9.2 ± 3.7 to 2.3 ± 2.4, P = 0.0001), disease activity (SLEDAI 19 ± 8 to 4 ± 2, P = 0.0004) and dsDNA levels (168 ± 205 to 45 ± 34, P = 0.001). In patients without remission after 1 year (n = 5), prolonged IAS decreased proteinuria from 4.3 ± 2.4 to 0.5 ± 0.4 g/day, P = 0.02. At the end of observation, complete remission in proteinuria was achieved in seven patients (64%) and partial remission in two (18%) additional patients. One patient flared and was discontinued; in all other patients, disease activity and anti-dsDNA stabilized at remission levels. Flares (0.28 ± 0.30) and infections (0.66 ± 0.70 per patient/year) were relatively uncommon; no malignancies, anaphylactic or orthostatic adverse events were observed. IAS is effective in short-term use but prolonged IAS can provide additional therapeutic benefit while showing an acceptable safety profile. The vast majority of initially therapy-refractory patients met the remission criteria at the end of

  15. Prolonged Intracellular Na+ Dynamics Govern Electrical Activity in Accessory Olfactory Bulb Mitral Cells.

    Directory of Open Access Journals (Sweden)

    Asaph Zylbertal

    2015-12-01

    Full Text Available Persistent activity has been reported in many brain areas and is hypothesized to mediate working memory and emotional brain states and to rely upon network or biophysical feedback. Here, we demonstrate a novel mechanism by which persistent neuronal activity can be generated without feedback, relying instead on the slow removal of Na+ from neurons following bursts of activity. We show that mitral cells in the accessory olfactory bulb (AOB, which plays a major role in mammalian social behavior, may respond to a brief sensory stimulation with persistent firing. By combining electrical recordings, Ca2+ and Na+ imaging, and realistic computational modeling, we explored the mechanisms underlying the persistent activity in AOB mitral cells. We found that the exceptionally slow inward current that underlies this activity is governed by prolonged dynamics of intracellular Na+ ([Na+]i, which affects neuronal electrical activity via several pathways. Specifically, elevated dendritic [Na+]i reverses the Na+-Ca2+ exchanger activity, thus modifying the [Ca2+]i set-point. This process, which relies on ubiquitous membrane mechanisms, is likely to play a role in other neuronal types in various brain regions.

  16. Changes in voluntary activation assessed by transcranial magnetic stimulation during prolonged cycling exercise.

    Directory of Open Access Journals (Sweden)

    Marc Jubeau

    Full Text Available Maximal central motor drive is known to decrease during prolonged exercise although it remains to be determined whether a supraspinal deficit exists, and if so, when it appears. The purpose of this study was to evaluate corticospinal excitability and muscle voluntary activation before, during and after a 4-h cycling exercise. Ten healthy subjects performed three 80-min bouts on an ergocycle at 45% of their maximal aerobic power. Before exercise and immediately after each bout, neuromuscular function was evaluated in the quadriceps femoris muscles under isometric conditions. Transcranial magnetic stimulation was used to assess voluntary activation at the cortical level (VATMS, corticospinal excitability via motor-evoked potential (MEP and intracortical inhibition by cortical silent period (CSP. Electrical stimulation of the femoral nerve was used to measure voluntary activation at the peripheral level (VAFNES and muscle contractile properties. Maximal voluntary force was significantly reduced after the first bout (13 ± 9%, P<0.01 and was further decreased (25 ± 11%, P<0.001 at the end of exercise. CSP remained unchanged throughout the protocol. Rectus femoris and vastus lateralis but not vastus medialis MEP normalized to maximal M-wave amplitude significantly increased during cycling. Finally, significant decreases in both VATMS and VAFNES (∼ 8%, P<0.05 and ∼ 14%, P<0.001 post-exercise, respectively were observed. In conclusion, reductions in VAFNES after a prolonged cycling exercise are partly explained by a deficit at the cortical level accompanied by increased corticospinal excitability and unchanged intracortical inhibition. When comparing the present results with the literature, this study highlights that changes at the cortical and/or motoneuronal levels depend not only on the type of exercise (single-joint vs. whole-body but also on exercise intensity and/or duration.

  17. Comparisons of muscular activity in males and females while walking in restricted postures

    CSIR Research Space (South Africa)

    Hodgskiss, J

    2013-07-01

    Full Text Available The purpose of this study was to examine differences in muscular activation between males and females while walking in restricted postures. Restricted postures are evident in various industries, including mining, construction and agriculture...

  18. Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins.

    Science.gov (United States)

    Chang, Jih-Chin; Chen, Chao-Huei; Fang, Li-Jung; Tsai, Chi-Ren; Chang, Yu-Chuan; Wang, Teh-Ming

    2013-12-01

    The bioactive proteins in human milk may be influenced by prolonged storage process, pasteurization, and heat treatment. This study was conducted to evaluate the effects of these procedures. Three forms of human milk - freshly expressed, frozen at -20°C for a prolonged duration, and pasteurized milk - were collected from 14 healthy lactating mothers and a milk bank. The concentrations of major bioactive proteins (secretory immunoglobulin A, lactoferrin, lysozyme, and leptin) were quantified using enzyme-linked immunosorbent assay kits. Changes in these proteins by heat treatment at 40°C or 60°C for 30 minutes were further evaluated. The mean concentrations of lactoferrin and secretory immunoglobulin A were significantly reduced by 66% and 25.9%, respectively, in pasteurized milk compared with those in freshly-expressed milk. Heat treatment at 40°C or 60°C did not cause significant changes in lactoferrin and secretory immunoglobulin A, but there was an apparent increase in lysozyme (p = 0.016). There were no significant differences in leptin level among these three forms of milk prior to (p = 0.153) or after heat treatment (p = 0.053). Various freezing/heating/pasteurization processes applied to human milk prior to delivery to neonates could affect the concentration of immunomodulatory proteins, especially lactoferrin, secretory immunoglobulin A, and lysozyme. Leptin was unaffected by the various handling processes tested. Fresh milk was found to be the best food for neonates. Further studies are warranted to evaluate the functional activity of these proteins and their effects on infants' immunological status. Copyright © 2013. Published by Elsevier B.V.

  19. Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor?

    Science.gov (United States)

    Marín-Blasco, Ignacio; Muñoz-Abellán, Cristina; Andero, Raül; Nadal, Roser; Armario, Antonio

    2018-04-01

    Despite extensive research on the impact of emotional stressors on brain function using immediate-early genes (e.g., c-fos), there are still important questions that remain unanswered such as the reason for the progressive decline of c-fos expression in response to prolonged stress and the neuronal populations activated by different stressors. This study tackles these 2 questions by evaluating c-fos expression in response to 2 different emotional stressors applied sequentially, and performing a fluorescent double labeling of c-Fos protein and c-fos mRNA on stress-related brain areas. Results were complemented with the assessment of the hypothalamic-pituitary-adrenal axis activation. We showed that the progressive decline of c-fos expression could be related to 2 differing mechanisms involving either transcriptional repression or changes in stimulatory inputs. Moreover, the neuronal populations that respond to the different stressors appear to be predominantly separated in high-level processing areas (e.g., medial prefrontal cortex). However, in low-hierarchy areas (e.g., paraventricular nucleus of the hypothalamus) neuronal populations appear to respond unspecifically. The data suggest that the distinct physiological and behavioral consequences of emotional stressors, and their implication in the development of psychopathologies, are likely to be closely associated with neuronal populations specifically activated by each stressor.

  20. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

    Directory of Open Access Journals (Sweden)

    Massimo Collino

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1 induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO. These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO activity, interleukin 1β (IL-1β production and tumor necrosis factor-α (TNFα production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  1. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

    Science.gov (United States)

    Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  2. Ancient cellular structures and modern humans: change of survival strategies before prolonged low solar activity period

    Science.gov (United States)

    Ragulskaya, Mariya; Rudenchik, Evgeniy; Gromozova, Elena; Voychuk, Sergei; Kachur, Tatiana

    The study of biotropic effects of modern space weather carries the information about the rhythms and features of adaptation of early biological systems to the outer space influence. The influence of cosmic rays, ultraviolet waves and geomagnetic field on early life has its signs in modern biosphere processes. These phenomena could be experimentally studied on present-day biological objects. Particularly inorganic polyphosphates, so-called "fossil molecules", attracts special attention as the most ancient molecules which arose in inanimate nature and have been accompanying biological objects at all stages of evolution. Polyphosphates-containing graves of yeast's cells of Saccharomyces cerevisiae strain Y-517, , from the Ukrainian Collection of Microorganisms was studied by daily measurements during 2000-2013 years. The IZMIRAN daily data base of physiological parameters dynamics during 2000-2013 years were analyzed simultaneously (25 people). The analysis showed significant simultaneous changes of the statistical parameters of the studied biological systems in 2004 -2006. The similarity of simultaneous changes of adaptation strategies of human organism and the cell structures of Saccharomyces cerevisiae during the 23-24 cycles of solar activity are discussed. This phenomenon could be due to a replacement of bio-effective parameters of space weather during the change from 23rd to 24th solar activity cycle and nonstandard geophysical peculiarities of the 24th solar activity cycle. It could be suggested that the observed similarity arose as the optimization of evolution selection of the living systems in expectation of probable prolonged period of low solar activity (4-6 cycles of solar activity).

  3. A calpain-2 selective inhibitor enhances learning & memory by prolonging ERK activation.

    Science.gov (United States)

    Liu, Yan; Wang, Yubin; Zhu, Guoqi; Sun, Jiandong; Bi, Xiaoning; Baudry, Michel

    2016-06-01

    While calpain-1 activation is required for LTP induction by theta burst stimulation (TBS), calpain-2 activation limits its magnitude during the consolidation period. A selective calpain-2 inhibitor applied either before or shortly after TBS enhanced the degree of potentiation. In the present study, we tested whether the selective calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I), could enhance learning and memory in wild-type (WT) and calpain-1 knock-out (C1KO) mice. We first showed that C2I could reestablish TBS-LTP in hippocampal slices from C1KO mice, and this effect was blocked by PD98059, an inhibitor of ERK. TBS resulted in PTEN degradation in hippocampal slices from both WT and C1KO mice, and C2I treatment blocked this effect in both mouse genotypes. Systemic injection of C2I 30 min before training in the fear-conditioning paradigm resulted in a biphasic dose-response curve, with low doses enhancing and high doses inhibiting freezing behavior. The difference between the doses needed to enhance and inhibit learning matches the difference in concentrations producing inhibition of calpain-2 and calpain-1. A low dose of C2I also restored normal learning in a novel object recognition task in C1KO mice. Levels of SCOP, a ERK phosphatase known to be cleaved by calpain-1, were decreased in dorsal hippocampus early but not late following training in WT mice; C2I treatment did not affect the early decrease in SCOP levels but prevented its recovery at the later time-point and prolonged ERK activation. The results indicate that calpain-2 activation limits the extent of learning, an effect possibly due to temporal limitation of ERK activation, as a result of SCOP synthesis induced by calpain-2-mediated PTEN degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. 15 CFR 400.33 - Restrictions on manufacturing and processing activity.

    Science.gov (United States)

    2010-01-01

    ...-TRADE ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.33 Restrictions on manufacturing and processing activity. (a) In general. In approving manufacturing or processing activity for a zone... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Restrictions on manufacturing and...

  5. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Naval Support Activity Panama City; St. Andrews Bay; restricted areas. 334.761 Section 334.761 Navigation and Navigable Waters CORPS... REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The areas—(1...

  6. Dissociation between mental fatigue and motivational state during prolonged mental activity.

    Science.gov (United States)

    Gergelyfi, Mónika; Jacob, Benvenuto; Olivier, Etienne; Zénon, Alexandre

    2015-01-01

    Mental fatigue (MF) is commonly observed following prolonged cognitive activity and can have major repercussions on the daily life of patients as well as healthy individuals. Despite its important impact, the cognitive processes involved in MF remain largely unknown. An influential hypothesis states that MF does not arise from a disruption of overused neural processes but, rather, is caused by a progressive decrease in motivation-related task engagement. Here, to test this hypothesis, we measured various neural, autonomic, psychometric and behavioral signatures of MF and motivation (EEG, ECG, pupil size, eye blinks, Skin conductance responses (SCRs), questionnaires and performance in a working memory (WM) task) in healthy volunteers, while MF was induced by Sudoku tasks performed for 120 min. Moreover extrinsic motivation was manipulated by using different levels of monetary reward. We found that, during the course of the experiment, the participants' subjective feeling of fatigue increased and their performance worsened while their blink rate and heart rate variability (HRV) increased. Conversely, reward-induced EEG, pupillometric and skin conductance signal changes, regarded as indicators of task engagement, remained constant during the experiment, and failed to correlate with the indices of MF. In addition, MF did not affect a simple reaction time task, despite the strong influence of extrinsic motivation on this task. Finally, alterations of the motivational state through monetary incentives failed to compensate the effects of MF. These findings indicate that MF in healthy subjects is not caused by an alteration of task engagement but is likely to be the consequence of a decrease in the efficiency, or availability, of cognitive resources.

  7. Dissociation between mental fatigue and motivational state during prolonged mental activity

    Directory of Open Access Journals (Sweden)

    Monika eGergelyfi

    2015-07-01

    Full Text Available Mental fatigue (MF is commonly observed following prolonged cognitive activity and can have major repercussions on the daily life of patients as well as healthy individuals. Despite its important impact, the cognitive processes involved in MF remain largely unknown. An influential hypothesis states that MF does not arise from a disruption of overused neural processes but, rather, is caused by a progressive decrease in motivation-related task engagement.Here, to test this hypothesis, we measured various neural, autonomic, psychometric and behavioral signatures of MF and motivation (EEG, ECG, pupil size, eye blinks, skin conductance responses, questionnaires and performance in a working memory task in healthy volunteers, while MF was induced by Sudoku tasks performed for 120 minutes. Moreover extrinsic motivation was manipulated by using different levels of monetary reward. We found that, during the course of the experiment, the participants’ subjective feeling of fatigue increased and their performance worsened while their blink rate and heart rate variability increased. Conversely, reward-induced EEG, pupillometric and skin conductance signal changes, regarded as indicators of task engagement, remained constant during the experiment, and failed to correlate with the indices of MF. In addition, MF did not affect a simple reaction time task, despite the strong influence of extrinsic motivation on this task. Finally, alterations of the motivational state through monetary incentives failed to compensate the effects of MF. These findings indicate that MF in healthy subjects is not caused by an alteration of task engagement but is likely to be the consequence of a decrease in the efficiency, or availability, of cognitive resources.

  8. Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity.

    Science.gov (United States)

    Sun, Lidan; Huang, Xun; Han, Jing; Cai, Xingguang; Dai, Yuxuan; Chu, Yingying; Wang, Chuandong; Huang, Wenlong; Qian, Hai

    2016-06-15

    The therapeutic utility of exenatide (Ex-4) is limited due to short plasma half-life of 2.4h and thus numerous approaches have been used to obtain a longer action time. However, such strategies often attend to one thing and lose another. The study aimed to identify a candidate with balanced glucoregulatory activity and prolonged in vivo activity. A series of fatty chain conjugates of Ex-4 were designed and synthesized. First, thirteen cysteine modified peptides (1-13) were prepared. Peptides 1, 10, and 13 showed improved glucagon-like peptide-1 (GLP-1) receptor activate potency and were thus selected for second step modifications to yield conjugates I-1-I-9. All conjugates retained significant GLP-1 receptor activate potency and more importantly exerted enhanced albumin-binding properties and in vitro plasma stability. The protracted antidiabetic effects of the most stable I-3 were further confirmed by both multiple intraperitoneal glucose tolerance test and hypoglycemic efficacies test in vivo. Furthermore, once daily injection of I-3 to streptozotocin (STZ) induced diabetic mice achieved long-term beneficial effects on hemoglobin A1C (HbA1C) lowering and glucose tolerance. Once daily injection of I-3 to diet induced obesity (DIO) mice also achieved favorable effects on food intake, body weight, and blood chemistry. Our results suggested that I-3 was a promising agent deserving further investigation to treat obesity patients with diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Glial cell activity is maintained during prolonged inflammatory challenge in rats

    Energy Technology Data Exchange (ETDEWEB)

    Borges, B.C.; Rorato, R.; Antunes-Rodrigues, J.; Elias, L.L.K. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP (Brazil)

    2012-05-04

    We evaluated the expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), ionized calcium binding adaptor protein-1 (Iba-1), and ferritin in rats after single or repeated lipopolysaccharide (LPS) treatment, which is known to induce endotoxin tolerance and glial activation. Male Wistar rats (200-250 g) received ip injections of LPS (100 µg/kg) or saline for 6 days: 6 saline (N = 5), 5 saline + 1 LPS (N = 6) and 6 LPS (N = 6). After the sixth injection, the rats were perfused and the brains were collected for immunohistochemistry. After a single LPS dose, the number of GFAP-positive cells increased in the hypothalamic arcuate nucleus (ARC; 1 LPS: 35.6 ± 1.4 vs control: 23.1 ± 2.5) and hippocampus (1 LPS: 165.0 ± 3.0 vs control: 137.5 ± 2.5), and interestingly, 6 LPS injections further increased GFAP expression in these regions (ARC = 52.5 ± 4.3; hippocampus = 182.2 ± 4.1). We found a higher GS expression only in the hippocampus of the 6 LPS injections group (56.6 ± 0.8 vs 46.7 ± 1.9). Ferritin-positive cells increased similarly in the hippocampus of rats treated with a single (49.2 ± 1.7 vs 28.1 ± 1.9) or repeated (47.6 ± 1.1 vs 28.1 ± 1.9) LPS dose. Single LPS enhanced Iba-1 in the paraventricular nucleus (PVN: 92.8 ± 4.1 vs 65.2 ± 2.2) and hippocampus (99.4 ± 4.4 vs 73.8 ± 2.1), but had no effect in the retrochiasmatic nucleus (RCA) and ARC. Interestingly, 6 LPS increased the Iba-1 expression in these hypothalamic and hippocampal regions (RCA: 57.8 ± 4.6 vs 36.6 ± 2.2; ARC: 62.4 ± 6.0 vs 37.0 ± 2.2; PVN: 100.7 ± 4.4 vs 65.2 ± 2.2; hippocampus: 123.0 ± 3.8 vs 73.8 ± 2.1). The results suggest that repeated LPS treatment stimulates the expression of glial activation markers, protecting neuronal activity during prolonged inflammatory challenges.

  10. Influence of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing.

    Science.gov (United States)

    Karimi, Zanyar; Allahyari, Teimour; Azghani, Mahmood Reza; Khalkhali, Hamidreza

    2016-03-01

    The present study was an attempt to investigate the effect of unstable footwear on lower leg muscle activity, volume change and subjective discomfort during prolonged standing. Ten healthy subjects were recruited to stand for 2 h in three footwear conditions: barefoot, flat-bottomed shoe and unstable shoe. During standing, lower leg discomfort and EMG activity of medial gastrocnemius (MG) and tibialis anterior (TA) muscles were continuously monitored. Changes in lower leg volume over standing time also were measured. Lower leg discomfort rating reduced significantly while subjects standing on unstable shoe compared to the flat-bottomed shoe and barefoot condition. For lower leg volume, less changes also were observed with unstable shoe. The activity level and variation of right MG muscle was greater with unstable shoe compared to the other footwear conditions; however regarding the left MG muscle, significant difference was found between unstable shoe and flat-bottomed shoe only for activity level. Furthermore no significant differences were observed for the activity level and variation of TA muscles (right/left) among all footwear conditions. The findings suggested that prolonged standing with unstable footwear produces changes in lower leg muscles activity and leads to less volume changes. Perceived discomfort also was lower for this type of footwear and this might mean that unstable footwear can be used as ergonomic solution for employees whose work requires prolonged standing. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  11. Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

    Directory of Open Access Journals (Sweden)

    Essam Tawfik

    2017-02-01

    Full Text Available In this study, we aimed to improve the anticancer effect of 5-FU on human colon cancer cell lines by incorporating in poly(d,l lactic-co-glycolic acid (PLGA nanoparticles (NPs. The 5-FU-PLGA NPs were prepared by nanoprecipitation technique. Prepared NPs were moderately dispersed with an average diameter of 133 ± 25.19 nm. Scanning Electron Microscope (SEM images revealed spherical structures with subtle surface irregularity. Free 5-FU dose–response curves were constructed (12.5–2000 μM using MTT assay on HCT 116 and HT-29 cell lines for 1, 3, and 5 days. The calculated IC50 on HCT 116 were 185 μM after 1 day, 11.3 μM after 3 days, and 1.48 μM after 5 days. On HT-29, IC50 was only reached after 5 days of 5-FU treatment (11.25 μM. The HCT 116 viability following treatment with 100 μM 5-FU in free or NPs forms for 3 days was 38.8% and 18.6%, respectively. Similarly, when 250 μM was applied, HCT 116 viability was 17.03% and 14.6% after treatment with free and NPs forms of 5-FU, respectively. Moreover, HT-29 cell viability after 250 μM 5-FU treatment in free or NPs forms was 55.45% and 34.01%, respectively. We also noticed that HCT 116 cells were more sensitive to 5-FU-PLGA NPs as compared to HT-29 cells. Overall, our data indicate that 5-FU activity is time dependent and the prolonged effects created by PLGA NPs may contribute, at least in part, to the noticed enhancement of the anticancer activity of 5-FU drug.

  12. No consensus on restrictions on physical activity to prevent incisional hernias after surgery

    DEFF Research Database (Denmark)

    Pommergaard, H-C; Burcharth, J; Danielsen, Anne Kjaergaard

    2014-01-01

    of restrictions on physical activity recommended for patients operated for colorectal cancer and to evaluate the agreement among surgical specialists. METHODS: A questionnaire was sent to 60 general surgeons (specialists) in Denmark and Sweden working in academic departments of surgery with a high volume......PURPOSE: In the postoperative phase after colorectal surgery, restrictions on physical activity are often recommended for patients to prevent incisional hernias. However, evidence does not support that restrictions may prevent such hernias. The purpose of this study was to evaluate the extent...... of colorectal cancer resections. The questionnaire was case based and contained questions regarding possible restrictions on physical activity recommended for patients 0-2, 2-6 and >6 weeks after resection for colorectal cancer. Agreement among the surgeon on whether restrictions should be recommended...

  13. Public Relations and Propaganda: Restrictions on Executive Agency Activities

    National Research Council Canada - National Science Library

    Kosar, Kevin R

    2005-01-01

    Controversies recently have arisen over certain executive branch agencies' expenditures of appropriated funds on public relations activities, some of which have been characterized as propagandistic...

  14. Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells.

    Science.gov (United States)

    Renteria, Lissette S; Raj, J Usha; Ibe, Basil O

    2010-12-01

    Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6) cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Exploring physical activity engagement and barriers for asylum seekers in Australia coping with prolonged uncertainty and no right to work.

    Science.gov (United States)

    Hartley, Lisa; Fleay, Caroline; Tye, Marian E

    2017-05-01

    This paper explores the engagement in physical activity as a potential coping strategy for asylum seekers living in the Australian community without the right to work and with prolonged uncertainty, and benefits or barriers to undertaking such activity. Semi-structured in-depth interviews were held with 29 asylum seekers who had arrived to Australia by boat and were living in the community in the cities of Perth, Sydney or Melbourne in July-October 2013 after their release from immigration detention. The ratio of the numbers of men and women interviewed (23 men and 6 women) was comparable to the ratio of men and women who came by boat to Australia seeking asylum in 2012-2013. Nine participants reported that they participated in physical activity as a coping strategy. Seven other participants were so worried about their future and their families that they did not have the mental or physical energy to engage in physical activity. A further six wanted to participate in physical activity but faced a number of barriers to doing so. The seven remaining participants were either not asked about their physical activity engagement because they focused their discussion on other challenges or did not elaborate on why they were not engaging in physical activity. The findings suggest that physical activity, coupled with other coping strategies, are important for some asylum seekers in trying to manage the distress of being denied the right to work and living with prolonged uncertainty. In addition, these findings highlight the critical barrier that government policy plays in disabling engagement in physical activity, which further compounds social exclusion. This includes the lack of welfare support provided, which hinders people's financial ability to access activities and support in the community. © 2017 John Wiley & Sons Ltd.

  16. Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Garcia-Leal, C; Del-Ben, C M; Leal, F M; Graeff, F G; Guimarães, F S

    2010-05-01

    Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

  17. Activity restriction induced by fear of falling and objective and subjective measures of physical function: a prospective cohort study.

    Science.gov (United States)

    Deshpande, Nandini; Metter, E Jeffrey; Lauretani, Fulvio; Bandinelli, Stefania; Guralnik, Jack; Ferrucci, Luigi

    2008-04-01

    To examine whether activity restriction specifically induced by fear of falling (FF) contributes to greater risk of disability and decline in physical function. Prospective cohort study. Population-based older cohort. Six hundred seventy-three community-living elderly (> or = 65) participants in the Invecchiare in Chianti Study who reported FF. FF, fear-induced activity restriction, cognition, depressive symptoms, comorbidities, smoking history, and demographic factors were assessed at baseline. Disability in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) and performance on the Short Performance Physical Battery (SPPB) were evaluated at baseline and at the 3-year follow-up. One-quarter (25.5%) of participants did not report any activity restriction, 59.6% reported moderate activity restriction (restriction or avoidance of or = 3 activities). The severe restriction group reported significantly higher IADL disability and worse SPPB scores than the no restriction and moderate restriction groups. Severe activity restriction was a significant independent predictor of worsening ADL disability and accelerated decline in lower extremity performance on SPPB over the 3-year follow-up. Severe and moderate activity restriction were independent predictors of worsening IADL disability. Results were consistent even after adjusting for multiple potential confounders. In an elderly population, activity restriction associated with FF is an independent predictor of decline in physical function. Future intervention studies in geriatric preventive care should directly address risk factors associated with FF and activity restriction to substantiate long-term effects on physical abilities and autonomy of older persons.

  18. Fast fracture: an adiabatic restriction on thermally activated crack propagation

    Energy Technology Data Exchange (ETDEWEB)

    Burns, S.J.

    1978-01-01

    Slow, isothermal, crack propagation is widely suspected to be rate controlled by thermally activated plastic deformation in the crack tip region. Adiabatic conditions are generally established in the fracture modified material at the tip of a crack during fast fracture. The temperature of this material is not the temperature of the specimen and is generally not measured during fast fracture. Thus, a complete thermodynamic description of adiabatic crack propagation data can not be made. When the slow, isothermal, crack propagation mechanisms are assumed to be operative during adiabatic crack propagation then certain predictions can be made. For example: the changes in the driving force due to temperature and rate are always in the opposite sense; there is no minimum in the driving force versus crack velocity without a change in mechanism; the temperature rise in the crack tip fracture modified material is determined mainly by the activation enthalpy for crack propagation; the interpretation of fast fracture structural steel data from simple plastic models is suspect since these materials have dissimilar isothermal temperature dependencies.

  19. Napping Characteristics and Restricted Participation in Valued Activities Among Older Adults.

    Science.gov (United States)

    Owusu, Jocelynn T; Ramsey, Christine M; Tzuang, Marian; Kaufmann, Christopher N; Parisi, Jeanine M; Spira, Adam P

    2018-03-02

    Napping is associated with both positive and negative health outcomes among older adults. However, the association between particular napping characteristics (eg, frequency, duration, and whether naps were intentional) and daytime function is unclear. Participants were 2,739 community-dwelling Medicare beneficiaries aged ≥65 years from the nationally representative National Health and Aging Trends Study. Participants reported napping frequency, duration, and whether naps were intentional versus unintentional. Restricted participation in valued activities was measured by self-report. After adjusting for potential confounders and nighttime sleep duration, those who took intentional and unintentional naps had a greater odds of any valued activity restriction (ie, ≥1 valued activity restriction), compared to those who rarely/never napped (unintentional odds ratio [OR] = 1.34, 95% confidence interval [CI] 1.01, 1.79, intentional OR = 1.49, 95% CI 1.09, 2.04). There was no difference between unintentional napping and intentional napping with respect to any valued activity restriction after adjustment for demographics. Compared to participants napping "some days," those napping most days/every day had a greater odds of any valued activity restriction (OR = 1.68, 95% CI 1.30, 2.16). Moreover, each 30-minute increase in average nap duration was associated with a 25% greater odds of any valued activity restriction (OR = 1.25, 95% CI 1.10, 1.43). Older adults who took more frequent or longer naps were more likely to report activity restrictions, as were those who took intentional or unintentional naps. Additional longitudinal studies with objective measures of sleep are needed to further our understanding of associations between napping characteristics and daytime dysfunction. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Noninvasive cardiac activation imaging of ventricular arrhythmias during drug-induced QT prolongation in the rabbit heart.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Killingsworth, Cheryl R; Zhou, Zhaoye; He, Bin

    2013-10-01

    Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine. To investigate the ability of a noninvasive 3-dimensional cardiac electrical imaging technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbits. Simultaneous body surface potential mapping and 3-dimensional intracardiac mapping were performed in a closed-chest condition in 8 rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during intravenous administration of clofilium and phenylephrine with combinations of various infusion rates. The drug infusion led to a significant increase in the QT interval (from 175 ± 7 to 274 ± 31 ms) and rate-corrected QT interval (from 183 ± 5 to 262 ± 21 ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at the focal site, whereas the subsequent beats were due to focal activity from different sites or 2 competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements, with a correlation coefficient of 0.65 ± 0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5 mm from the directly measured initiation sites. The 3-dimensional cardiac electrical imaging technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbits. It offers the potential to noninvasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis. © 2013 Heart Rhythm Society. All rights reserved.

  1. Prolonged sedentary time and physical activity in workplace and non-work contexts: a cross-sectional study of office, customer service and call centre employees.

    Science.gov (United States)

    Thorp, Alicia A; Healy, Genevieve N; Winkler, Elisabeth; Clark, Bronwyn K; Gardiner, Paul A; Owen, Neville; Dunstan, David W

    2012-10-26

    To examine sedentary time, prolonged sedentary bouts and physical activity in Australian employees from different workplace settings, within work and non-work contexts. A convenience sample of 193 employees working in offices (131), call centres (36) and customer service (26) was recruited. Actigraph GT1M accelerometers were used to derive percentages of time spent sedentary (customer service workers were typically the least sedentary and the most active at work. The workplace is a key setting for prolonged sedentary time, especially for some occupational groups, and the potential health risk burden attached requires investigation. Future workplace regulations and health promotion initiatives for sedentary occupations to reduce prolonged sitting time should be considered.

  2. The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia

    NARCIS (Netherlands)

    W.H. Tong (Wing); R. Pieters (Rob); H.A. de Groot-Kruseman (Hester A.); W.C.J. Hop (Wim); J. Boos (Joachim); W.J.E. Tissing (Wim); I.M. van der Sluis (Inge)

    2014-01-01

    textabstractWe prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of

  3. The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia

    NARCIS (Netherlands)

    Tong, Wing H.; Pieters, Rob; de Groot-Kruseman, Hester A.; Hop, Wim C. J.; Boos, Joachim; Tissing, Wim J. E.; van der Sluis, Inge M.

    2014-01-01

    We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of pancreatitis,

  4. Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

    Science.gov (United States)

    Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

    2015-02-01

    Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

  5. Cultivating Composting Culture Activities among Citizens and Its Beneficial to Prolong the Landfill Lifespan

    Science.gov (United States)

    Azura Zakarya, Irnis; Azri Jamial, Khairul; Mat Tanda, Norazlinda

    2018-03-01

    Currently, the Ministry of Housing and Local Government manage solid waste in Malaysia, with the participation of the private sector. Food waste represents almost 60% of the total municipal solid waste disposed in the landfill. Material valorisation of food waste usually conducted by biological processes such as composting. Compost, an organic amendment, is the final product of the composting process. These processes are efficient, low cost and environmentally friendly alternative for managing food waste and are used extensively worldwide. Therefore, organic solid waste management practices program for the communities in Perlis was conducted. The main objective of this program was to instilling environment awareness especially among Perlis citizens. This study was investigated the impact of food waste or kitchen waste composting to the citizens in Perlis State and the beneficial of compost fertilizer to our environment especially in plant growth. Composting method was taught to the food premises owner, individuals, teachers, and students and their responses to the composting practices were then summarized. In future, we can prolong our landfill lifespan by practicing organic waste composting and can preserving our environment.

  6. The role of C/EBPa in PD-1+ CD4+ T cells & modulation of RNR activity prolongs survival of mice with AML

    DEFF Research Database (Denmark)

    Norrie, Ida Christine

    of age-dependent PD-1+ CD4+ T cells was therefore investigated as well as its importance for development of PD-1+ CD4+ T cells during leukemic development. My results showed that loss of C/EBPα expression in the lymphoid compartment led to an increased amount of aged PD-1+ CD4+ T cells, but not of young...... PD-1+ CD4+ T cells, suggesting that C/EBPα repress the accumulation of these cells in old mice. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells during development of leukemia. M data indicates......The Ph.D. thesis comprises two projects: (1) C/EBPα is dispensable for the ontogeny of PD1+ CD4+ memory T cells, but restricts their expansion in an age-dependent manner. (2) Modulation of RNR activity prolongs survival of mice with AML. Immunosenescence is a condition of the immune system...

  7. Assessment of activity limitations and participation restrictions with persons with chronic fatigue syndrome: a systematic review.

    Science.gov (United States)

    Vergauwen, Kuni; Huijnen, Ivan P J; Kos, Daphne; Van de Velde, Dominique; van Eupen, Inge; Meeus, Mira

    2015-01-01

    To summarize measurement instruments used to evaluate activity limitations and participation restrictions in patients with chronic fatigue syndrome (CFS) and review the psychometric properties of these instruments. General information of all included measurement instruments was extracted. The methodological quality was evaluated using the COSMIN checklist. Results of the measurement properties were rated based on the quality criteria of Terwee et al. Finally, overall quality was defined per psychometric property and measurement instrument by use of the quality criteria by Schellingerhout et al. A total of 68 articles were identified of which eight evaluated the psychometric properties of a measurement instrument assessing activity limitations and participation restrictions. One disease-specific and 37 generic measurement instruments were found. Limited evidence was found for the psychometric properties and clinical usability of these instruments. However, the CFS-activities and participation questionnaire (APQ) is a disease-specific instrument with moderate content and construct validity. The psychometric properties of the reviewed measurement instruments to evaluate activity limitations and participation restrictions are not sufficiently evaluated. Future research is needed to evaluate the psychometric properties of the measurement instruments, including the other properties of the CFS-APQ. If it is necessary to use a measurement instrument, the CFS-APQ is recommended. Chronic fatigue syndrome (CFS). Chronic fatigue syndrome causes activity limitations and participation restrictions in one or more areas of life. Standardized, reliable and valid measurement instruments are necessary to identify these limitations and restrictions. Currently, no measurement instrument is sufficiently evaluated with persons with CFS. If a measurement instrument is needed to identify activity limitations and participation restrictions with persons with CFS, it is recommended to use

  8. Prolonged performance-related neuroendocrine activation and perseverative cognition in low- and high-anxious university music students.

    Science.gov (United States)

    Gomez, Patrick; Nielsen, Carole; Studer, Regina K; Hildebrandt, Horst; Klumb, Petra L; Nater, Urs M; Wild, Pascal; Danuser, Brigitta

    2018-05-14

    Music performances are social-evaluative situations that can elicit marked short-term neuroendocrine activation and anxious thoughts especially in musicians suffering from music performance anxiety (MPA). The temporal patterns of neuroendocrine activity and concert-related worry and rumination (perseverative cognition, PC) days before and after a concert in low- and high-anxious musicians are unknown. The first goal of the present study was to investigate the prolonged effects of a solo music performance and the effects of trait MPA on salivary cortisol (sC), alpha-amylase (sAA), and concert-related PC. The second goal was to investigate whether concert-related PC is associated with neuroendocrine activity and mediates the effects of measurement day and trait MPA on neuroendocrine responses. Seventy-two university music students collected saliva samples and reported their PC for seven consecutive days. On the fifth day, they performed solo. Measurement day and trait MPA were tested as main predictors of the diurnal area under the curve with respect to ground (sC AUCg, sAA AUCg), awakening responses, and PC. SC AUCg, sAA AUCg, and concert-related PC were highest on concert day. SC AUCg decreased only partially on post-concert days. SAA AUCg remained elevated on the first post-concert day among students with moderate to very high trait MPA. Throughout the assessment period, trait MPA was associated with smaller sC AUCg and higher concert-related PC. Concert-related PC showed significant positive associations with sC AUCg and sAA AUCg but did not mediate the effects of measurement day and trait MPA on these measures. These findings suggest that solo music performances have prolonged neuroendocrine effects and that trait MPA is an important factor having specific effects on university music students' hypothalamic-pituitary-adrenal axis, autonomic nervous system, and cognitive activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    International Nuclear Information System (INIS)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M.

    2013-01-01

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g -1 ·min -1 ) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g -1 ·min -1 ) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring

  10. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

    Science.gov (United States)

    Dumont, Jennifer A.; Liu, Tongyao; Low, Susan C.; Zhang, Xin; Kamphaus, George; Sakorafas, Paul; Fraley, Cara; Drager, Douglas; Reidy, Thomas; McCue, Justin; Franck, Helen W. G.; Merricks, Elizabeth P.; Nichols, Timothy C.; Bitonti, Alan J.; Pierce, Glenn F.

    2012-01-01

    Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation. PMID:22246033

  11. 'Living within your limits': activity restriction in older people experiencing chronic pain.

    Science.gov (United States)

    Mackichan, Fiona; Adamson, Joy; Gooberman-Hill, Rachael

    2013-11-01

    although maintaining activity is key to successful pain management, and important to health and wellbeing, it is known that older people in pain frequently alter or reduce activity levels. A 'fear-avoidance' model is often used to explain avoidance of activity in the face of pain. However, this model is not intended to take account of the wider context in which activity changes take place, nor older people's own explanations for their behaviour. to investigate the reasons why older people in the community adjust their activity levels when living with chronic pain. thirty-one people aged between 67 and 92 were purposively sampled from respondents to a community-based cross-sectional survey. All participants had reported long-term pain and were interviewed about this. Data were collected and analysed using a qualitative constructivist grounded theory approach. explanations for deliberative reduction or ceasing of activities reflected a desire to prevent pain exacerbation, thereby avoiding medical intervention. It also reflected a desire to safeguard autonomy in the face of pain in older age. Restrictions were often rationalised as normal in older age, although co-existing accounts of perseverance and frustration with limitation were also evident. a rational desire to avoid pain exacerbation and medical intervention motivated restrictions to activity. However, deliberative limitation of activity has the potential to compromise autonomy by increasing social isolation and de-conditioning. Supporting older people with pain to be active requires sensitivity to the function of activity restriction, especially as a means of preventing deterioration.

  12. Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

    International Nuclear Information System (INIS)

    Aoki, Shigehisa; Ikeda, Satoshi; Takezawa, Toshiaki; Kishi, Tomoya; Makino, Junichi; Uchihashi, Kazuyoshi; Matsunobu, Aki; Noguchi, Mitsuru; Sugihara, Hajime; Toda, Shuji

    2011-01-01

    Highlights: ► Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. ► Fluid streaming is a potent factor for peritoneal fibrosis in PD. ► We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. ► A history of fluid streaming exposure promoted mesothelial proliferative activity. ► We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial–mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination

  13. Minoxidil activates β-catenin pathway in human dermal papilla cells: a possible explanation for its anagen prolongation effect.

    Science.gov (United States)

    Kwack, Mi Hee; Kang, Bo Mi; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

    2011-06-01

    It is believed that the length of the actively growing phase of the anagen hair cycle mainly contributes to hair length. Recent studies showed that maintenance of β-catenin activity in the dermal papilla cells (DPCs) enables hair follicles to keep actively growing. Topical minoxidil treatment promotes hair growth in men with androgenetic alopecia, suggesting that minoxidil may prolong the actively growing phase of the anagen hair cycle. To investigate whether minoxidil prolongs the anagen hair cycle in mice and, if so, to investigate whether minoxidil activates β-catenin pathway in human DPCs. Dorsal skins of C57BL/6 mice were depilated to synchronize the hair cycle. After 10 days, 3% minoxidil were topically applied daily for 10 days. Sections of back skins were stained with hematoxylin and eosin. Hair follicles were graded and hair cycle score (HCS) was calculated. Cultured human DPCs were transiently transfected with the β-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of β-catenin signaling by minoxidil. Immunofluorescence staining and immunoblot were performed to examine the expression and localization of β-catenin in the presence or absence of minoxidil. Phosphorylation of GSK3β, PKA and PKB were also examined by immunoblot after minoxidil treatment. RT-PCR analysis and immunoblot were employed to investigate the expression of β-catenin pathway targets in DPCs, such as Axin2, Lef-1, and EP2. Modest extension of anagen phase thereby delay of catagen progression was observed by application of minoxidil in mice. Minoxidil stimulated the transcriptional activity of pTopflash but not pFopflash. Nuclear accumulation of β-catenin was also observed after minoxidil treatment. Immunoblot further showed that minoxidil treatment increases the phosphorylation of GSK3β, PKA and PKB. Moreover, minoxidil induced Axin2, Lef-1, and EP2 expression. Our results strongly suggest that

  14. Activity limitations and participation restrictions experienced by people with stroke in Musanze district in Rwanda.

    Science.gov (United States)

    Urimubenshi, Gerard

    2015-09-01

    Stroke is a major cause of long-term disability. Information regarding the limitations in activity and participation experienced by patients with stroke in a specific setting such as Musanze district in Rwanda would assist to develop the rehabilitation programmes that would take into consideration the functional challenges experienced post stroke. To explore the activity limitations and participation restrictions experienced by people with stroke in Musanze district in Rwanda. A qualitative phenomenological approach using in-depth face-to-face interviews with 10 participants was employed to gather the data that was analyzed using a qualitative thematic approach. The themes that arose as activity limitations included limitations in walking, self care, and domestic life activities. The themes related to participation restrictions as expressed by the participants were inability to return to previous occupation, decreased social interactions and inability to participate in religious activities. The current study findings highlight the need for interventions to improve the functional status of stroke survivors.

  15. Exhaustion from prolonged gambling

    Directory of Open Access Journals (Sweden)

    Fatimah Lateef

    2013-01-01

    Full Text Available Complaints of fatigue and physical exhaustion are frequently seen in the acute medical setting, especially amongst athletes, army recruits and persons involved in strenuous and exertional physical activities. Stress-induced exhaustion, on the other hand, is less often seen, but can present with very similar symptoms to physical exhaustion. Recently, three patients were seen at the Department of Emergency Medicine, presenting with exhaustion from prolonged involvement in gambling activities. The cases serve to highlight some of the physical consequences of prolonged gambling.

  16. Korean Children's Evaluation of Parental Restrictions Regarding Gender-Stereotypic Peer Activities

    Science.gov (United States)

    Park, Yoonjung; Lee-Kim, Jennie; Killen, Melanie; Park, Kyoungja; Kim, Jihyun

    2012-01-01

    Korean children's evaluations of parental restrictions of children's activities based on gender stereotypic expectations were investigated. Third and sixth grade Korean (N = 128) children evaluated scenarios in which a boy or girl desired to play ballet or soccer. Participants used stereotypes to support children's desires to play…

  17. Deletion of protease-activated receptor 2 prolongs survival of scrapie-inoculated mice

    Czech Academy of Sciences Publication Activity Database

    Matěj, R.; Olejár, Tomáš; Janoušková, O.; Holada, K.

    2012-01-01

    Roč. 93, č. 9 (2012), s. 2057-2061 ISSN 0022-1317 Institutional support: RVO:67985823 Keywords : protease-activated receptor (PAR2) * scrapie * neurodegenerative disorders Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 3.127, year: 2012

  18. Restrictive pattern on spirometry: association with cardiovascular risk and level of physical activity in asymptomatic adults

    Directory of Open Access Journals (Sweden)

    Evandro Fornias Sperandio

    2016-02-01

    Full Text Available Objective : To determine whether a restrictive pattern on spirometry is associated with the level of physical activity in daily life (PADL, as well as with cardiovascular disease (CVD risk factors, in asymptomatic adults. Methods : A total of 374 participants (mean age, 41 ± 14 years underwent spirometry, which included the determination of FVC and FEV1. A restrictive pattern on spirometry was defined as an FEV1/FVC ratio > 0.7 and an FVC < 80% of the predicted value. After conducting demographic, anthropometric, and CVD risk assessments, we evaluated body composition, muscle function, and postural balance, as well as performing cardiopulmonary exercise testing and administering the six-minute walk test. The PADL was quantified with a triaxial accelerometer. Results : A restrictive pattern on spirometry was found in 10% of the subjects. After multivariate logistic regression, adjusted for confounders (PADL and cardiorespiratory fitness, the following variables retained significance (OR; 95% CI as predictors of a restrictive pattern: systemic arterial hypertension (17.5; 1.65-184.8, smoking (11.6; 1.56-87.5, physical inactivity (8.1; 1.43-46.4, larger center-of-pressure area while standing on a force platform (1.34; 1.05-1.71; and dyslipidemia (1.89; 1.12-1.98. Conclusions : A restrictive pattern on spirometry appears to be common in asymptomatic adults. We found that CVD risk factors, especially systemic arterial hypertension, smoking, and physical inactivity, were directly associated with a restrictive pattern, even when the analysis was adjusted for PADL and cardiorespiratory fitness. Longitudinal studies are needed in order to improve understanding of the etiology of a restrictive pattern as well as to aid in the design of preventive strategies.

  19. Influence of Prolonged Storage Process, Pasteurization, and Heat Treatment on Biologically-active Human Milk Proteins

    Directory of Open Access Journals (Sweden)

    Jih-Chin Chang

    2013-12-01

    Conclusion: Various freezing/heating/pasteurization processes applied to human milk prior to delivery to neonates could affect the concentration of immunomodulatory proteins, especially lactoferrin, secretory immunoglobulin A, and lysozyme. Leptin was unaffected by the various handling processes tested. Fresh milk was found to be the best food for neonates. Further studies are warranted to evaluate the functional activity of these proteins and their effects on infants' immunological status.

  20. Active packaging from chitosan-titanium dioxide nanocomposite film for prolonging storage life of tomato fruit.

    Science.gov (United States)

    Kaewklin, Patinya; Siripatrawan, Ubonrat; Suwanagul, Anawat; Lee, Youn Suk

    2018-06-01

    The feasibility of active packaging from chitosan (CS) and chitosan containing nanosized titanium dioxide (CT) to maintain quality and extend storage life of climacteric fruit was investigated. The CT nanocomposite film and CS film were fabricated using a solution casting method and used as active packaging to delay ripening process of cherry tomatoes. Changes in firmness, weight loss, a*/b* color, lycopene content, total soluble solid, ascorbic acid, and concentration of ethylene and carbon dioxide of the tomatoes packaged in CT film, CS film, and control (without CT or CS films) were monitored during storage at 20°C. Classification of fruit quality as a function of different packaging treatments was visualized using linear discriminant analysis. Tomatoes packaged in the CT film evolved lower quality changes than those in the CS film and control. The results suggested that the CT film exhibited ethylene photodegradation activity when exposed to UV light and consequently delayed the ripening process and changes in the quality of the tomatoes. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.

    Science.gov (United States)

    Yamamoto, Tomohiro; Wolf, Hans-Gerd; Sinzobahamvya, Nicodème; Asfour, Boulos; Hraska, Victor; Schindler, Ehrenfried

    2015-08-01

    In open heart surgery, heparinization is commonly neutralized using an empirical heparin:protamine ratio ranging between 1:1 and 1:1.5. However, these ratios may result in protamine overdose that should be avoided for its negative side effects on the coagulation system. This study aimed to indicate the appropriate treatment for prolonged activated clotting time (ACT) after protamine administration following cardiopulmonary bypass (CPB) in pediatric open heart surgery by investigating the underlying reasons for it. Twenty-seven children (open heart surgery were included. Heparin was administered only before CPB (400 IU/kg) and in the pump priming volume for CPB (2,000 IU) and was neutralized by 1:1 protamine after CPB. The blood heparin concentration was measured using anti-Xa assay. ACT and blood concentrations of heparin, coagulation factors, thrombin-antithrombin complex, and prothrombin fragment 1 + 2 were assessed. A rotational thromboelastometry (ROTEM; Tem International GmbH, München, Bayern, Germany) was used to confirm the coagulation status and residual heparin after protamine administration. Anti-Xa assay showed that there is no residual heparin in the blood after 1:1 protamine administration. Nevertheless, ACT (128.89 ± 3.09 seconds before heparin administration) remained prolonged (177.14 ± 5.43 seconds at 10 minutes after protamine, 182.00 ± 5.90 seconds at 30 minutes after protamine). The blood concentrations of coagulation factors were significantly lower than those before heparin administration (p < 0.01). The low FIBTEM MCF of ROTEM (4.43 ± 0.32 mm) at 10 minutes after protamine indicated low fibrinogen concentration. Prolonged ACT after heparin neutralization by 1:1 protamine administration does not necessarily indicate residual heparin, but low blood concentrations of coagulation factors should be considered as a reason as well. Accordingly, supply of coagulation factors instead of additional protamine should be

  2. Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice

    Science.gov (United States)

    Blednov, Y.A.; Benavidez, J.M.; Geil, C.; Perra, S.; Morikawa, H.; Harris, R.A.

    2011-01-01

    Previous studies showed that mice with genetic predisposition for high alcohol consumption as well as human alcoholics show changes in brain expression of genes related to immune signaling. In addition, mutant mice lacking genes related to immune function show decreased alcohol consumption (Blednov et al., in press), suggesting that immune signaling promotes alcohol consumption. To test the possibility that activation of immune signaling will increase alcohol consumption, we treated mice with lipopolysaccaride (LPS; 1 mg/kg, i.p.) and tested alcohol consumption in the continuous two-bottle choice test. To take advantage of the long-lasting activation of brain immune signaling by LPS, we measured drinking beginning one week or one month after LPS treatment and continued the studies for several months. LPS produced persistent increases in alcohol consumption in C57/Bl6 J (B6) inbred mice, FVBxB6F1 and B6xNZBF1 hybrid mice, but not in FVB inbred mice. To determine if this effect of LPS is mediated through binding to TLR4, we tested mice lacking CD14, a key component of TLR4 signaling. These null mutants showed no increase of alcohol intake after treatment with LPS. LPS treatment decreased ethanol-conditioned taste aversion but did not alter ethanol-conditioned place preference (B6xNZBF1 mice). Electro-physiological studies of dopamine neurons in the ventral tegmental area showed that pretreatment of mice with LPS decreased the neuronal firing rate. These results suggest that activation of immune signaling promotes alcohol consumption and alters certain aspects of alcohol reward/aversion. PMID:21266194

  3. Peroxidase activity of the rat blood at prolonged intake of 137Cs

    Directory of Open Access Journals (Sweden)

    Yu. P. Grynevych

    2013-03-01

    Full Text Available Investigated peroxidase activity of blood white nonlinear rats-males by daily oral administration of 15 kBq 137Cs by chemiluminescence. Discovered oscillatory nature of the changes chemiluminescent indicators peroxi-dase oxidation of blood, the maximum deviation of the control are registered during the 4th and 60th days, and the minimum at the 1st, 7th and 135th days. Recovering kinetic parameters CL does not occur within 135 days of ob-servation (the 90th day of the completion of the introduction of radioactive cesium.

  4. Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis.

    Science.gov (United States)

    Keszthelyi, E; Karlik, S; Hyduk, S; Rice, G P; Gordon, G; Yednock, T; Horner, H

    1996-10-01

    The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

  5. The Early Time Properties of GRBs - Canonical Afterglows and the Importance of Prolonged Central Engine Activity

    International Nuclear Information System (INIS)

    Melandri, A.; Mundell, C. G.; Kobayashi, S.; Bersier, D.; Steele, I. A.; Smith, R. J.; Carter, D.; Bode, M. F.; Guidorzi, C.; Gomboc, A.

    2009-01-01

    Using a new, comprehensive multiwavelength survey of 63 Gamma Ray Bursts (GRBs) with unprecedented temporal coverage, we classify the observed afterglows into four main classes and discuss the underlying physics that can explain them. The presence or absence of temporal breaks in X-ray and optical bands is used to examine the emission in the context of the standard model; a number of GRBs are shown to deviate from the forward shock model even with the inclusion of energy injection or ambient density gradients. We show that additional emission in the early-time X-ray afterglow due to late-time central engine activity is key and may explain both GRBs whose afterglows do not fit the standard model and those GRBs that appear to be optically dark even at early times.

  6. Prolonged activation of virus-specific CD8+T cells after acute B19 infection

    DEFF Research Database (Denmark)

    Isa, Adiba; Kasprowicz, Victoria; Norbeck, Oscar

    2005-01-01

    BACKGROUND: Human parvovirus B19 (B19) is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS......: The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia......, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function...

  7. Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

    Directory of Open Access Journals (Sweden)

    Adiba Isa

    2005-12-01

    Full Text Available Human parvovirus B19 (B19 is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously.The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low.This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

  8. Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Human parvovirus B19 (B19 is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS: The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low. CONCLUSION: This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

  9. [Placental gene activity of significant angiogenetic factors in the background of intrauterine growth restriction].

    Science.gov (United States)

    Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László

    2017-04-01

    Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.

  10. Effects of long-term elevated CO2, warming, and prolonged drought on Pleurozium-associated diazotrophic activity and abundance

    Science.gov (United States)

    Dyrnum, Kristine; Priemé, Anders; Michelsen, Anders

    2014-05-01

    Nitrogen (N2) fixation is the primary natural influx of N to terrestrial ecosystems, and changes in N2 fixation may have consequences for primary productivity and thus ecosystem function. We studied the activity and abundance of diazotrophs associated with the feather moss Pleurozium schreberi in a temperate heathland, after seven years of global change manipulations, including elevated atmospheric CO2 (510 ppm), increased temperature (0.5-1.5 ° C), and prolonged pre-summer droughts (4-6 weeks /year). Acetylene reduction assay was carried out monthly to monitor N2 fixation rates throughout one year, while nif H copy abundance, serving as a diazotroph abundance estimate, was measured by quantitative polymerase chain reaction (q-PCR). Prolonged summer droughts significantly increased both N2 fixation and nif H copy abundance, contrasting previous studies that demonstrate a direct negative correlation between N2 fixation and water availability. A shift in the relative abundance of N2-fixing bacteria from the green, upper parts of the moss stem to the lower, brown parts was observed. This shift could make diazotrophs less sensitive to desiccation, enabling N2 fixation to be upheld for longer during drought and thus causing higher abundance. Increased temperature likewise had a positive effect on the diazotroph abundance, although this did not translate into increased activity. Possibly, warming protects diazotrophs during extreme cold events, while actual N2 fixation is limited by water, disregarding a rise in potential N2 fixation caused by higher abundance. Increased CO2 caused no significant diazotroph response. Our study showed that long-term increase in temperature and recurrent drought events cause higher diazotroph abundance in Pleurozium schreberi and thus enhance the potential N2 fixations rate. Furthermore, our results indicate that diazotrophs may alter colonization patterns and thereby actively remain in the moss fraction less likely affected by

  11. The Effect of Activity Restriction on Infant's Birth Weight and Gestational Age at Birth: PRAMS Data Analysis.

    Science.gov (United States)

    Omar, Abeer

    2018-01-01

    Activity restriction is extensively prescribed for pregnant women with major comorbidities despite the lack of evidence to support its effectiveness in preventing preterm birth or low birth weight. To determine the moderation effect of home activity restriction for more than a week on infant's birth weight and gestational age at birth for high-risk women with obstetrical and medical comorbidities. A secondary analysis of 2004-2008 New York Pregnancy Risk Assessment Monitoring System was conducted with 1426 high-risk women. High-risk group included 41% of women treated with activity restriction and 59% of those not treated with activity restriction. Women with preterm premature rupture of membrane (PPROM) who were treated with activity restriction had a lower infant birth weight ( b = -202.85, p = ≤.001) and gestational age at birth ( b = -.91, p = ≤.001) than those without activity restriction. However, women with preterm labor and hypertensive disorders of pregnancy who were not treated with activity restriction had lower infant gestational age at birth ( b = -96, p = ≤.01) and ( b = -92, p = ≤.001), respectively, compared to those who were treated with activity restriction. Findings suggest a contrary effect of activity restriction on infants born to women with PPROM, which is a major reason for prescribing activity restriction. The current study results may trigger the need to conduct randomized control trials to determine the effect of severity of activity restriction on maternal and infant outcomes.

  12. Maternal protein restriction affects gene expression and enzyme activity of intestinal disaccharidases in adult rat offspring

    Energy Technology Data Exchange (ETDEWEB)

    Pinheiro, D.F.; Pacheco, P.D.G.; Alvarenga, P.V.; Buratini, J. Jr; Castilho, A.C.S.; Lima, P.F.; Sartori, D.R.S.; Vicentini-Paulino, M.L.M. [Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Botucatu, SP (Brazil)

    2013-03-15

    This study investigated the consequences of intrauterine protein restriction on the gastrointestinal tract and particularly on the gene expression and activity of intestinal disaccharidases in the adult offspring. Wistar rat dams were fed isocaloric diets containing 6% protein (restricted, n = 8) or 17% protein (control, n = 8) throughout gestation. Male offspring (n = 5-8 in each group) were evaluated at 3 or 16 weeks of age. Maternal protein restriction during pregnancy produced offspring with growth restriction from birth (5.7 ± 0.1 vs 6.3 ± 0.1 g; mean ± SE) to weaning (42.4 ± 1.3 vs 49.1 ± 1.6 g), although at 16 weeks of age their body weight was similar to control (421.7 ± 8.9 and 428.5 ± 8.5 g). Maternal protein restriction also increased lactase activity in the proximal (0.23 ± 0.02 vs 0.15 ± 0.02), medial (0.30 ± 0.06 vs 0.14 ± 0.01) and distal (0.43 ± 0.07 vs 0.07 ± 0.02 U·g{sup -1}·min{sup -1}) small intestine, and mRNA lactase abundance in the proximal intestine (7.96 ± 1.11 vs 2.38 ± 0.47 relative units) of 3-week-old offspring rats. In addition, maternal protein restriction increased sucrase activity (1.20 ± 0.02 vs 0.91 ± 0.02 U·g{sup -1}·min{sup -1}) and sucrase mRNA abundance (4.48 ± 0.51 vs 1.95 ± 0.17 relative units) in the duodenum of 16-week-old rats. In conclusion, the present study shows for the first time that intrauterine protein restriction affects gene expression of intestinal enzymes in offspring.

  13. Net joint moments and muscle activation in barbell squats without and with restricted anterior leg rotation.

    Science.gov (United States)

    Chiu, Loren Z F; vonGaza, Gabriella L; Jean, Liane M Y

    2017-01-01

    Muscle utilisation in squat exercise depends on technique. The purpose of this study was to compare net joint moments (NJMs) and muscle activation during squats without and with restricted leg dorsiflexion. Experienced men (n = 5) and women (n = 4) performed full squats at 80% one repetition maximum. 3D motion analysis, force platform and (EMG) data were collected. Restricting anterior leg rotation reduced anterior leg (P = 0.001) and posterior thigh (P squat depth, ankle plantar flexor (P squats. Hip extensor NJM (P = 0.14) was not different between squat types at maximum squat depth. Vastus lateralis (P > 0.05), vastus medialis (P > 0.05) and rectus femoris (P > 0.05) EMG were not different between squat types. Unrestricted squats have higher ankle plantar flexor and knee extensor NJM than previously reported from jumping and landing. However, ankle plantar flexor and knee extensor NJM are lower in restricted squats than previous studies of jumping and landing. The high NJM in unrestricted squat exercise performed through a full range of motion suggests this squat type would be more effective to stimulate adaptations in the lower extremity musculature than restricted squats.

  14. Compensatory mechanisms activated with intermittent energy restriction: A randomized control trial.

    Science.gov (United States)

    Coutinho, Sílvia Ribeiro; Halset, Eline Holli; Gåsbakk, Sigrid; Rehfeld, Jens F; Kulseng, Bård; Truby, Helen; Martins, Cátia

    2018-06-01

    Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL. 35 adults (age: 39 ± 9 y) with obesity (BMI: 36 ± 4 kg/m 2 ) were randomized to lose a similar weight with an IER (N = 18) or a CER (N = 17) diet over a 12 week period. Macronutrient composition and overall energy restriction (33% reduction) were similar between groups. Body weight/composition, RMR, fasting respiratory quotient (RQ), ExEff (10, 25, and 50 W), subjective appetite ratings (hunger, fullness, desire to eat, and prospective food consumption (PFC)), and appetite-regulating hormones (active ghrelin (AG), cholecystokinin (CCK), total peptide YY (PYY), active glucagon-like peptide-1 (GLP-1), and insulin) were measured before and after WL. Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting RQ and ExEff at 10 W increased in both groups. Losing weight, either by IER or CER dieting, did not induce significant changes in subjective appetite ratings. RMR decreased and ExEff at 25 and 50 W increased (P intermittent, does not appear to modulate the compensatory mechanisms activated by weight loss. NCT02169778 (the study was registered in clinicaltrial.gov). Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities

    Science.gov (United States)

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi

    2016-01-01

    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.

  16. [Pathophysiology of prolonged hypokinesia].

    Science.gov (United States)

    Kovalenko, E A

    1976-01-01

    Hypokinesia is an important problem in modern medicine. In the pathogenetic effect of prolonged hypokinesia the main etiological factor is diminished motor activity; of major importance are disorders in the energy and plastic metabolism which affect the muscle system; the contributing factors are cardiovascular deconditioning and orthostatic intolerance. This is attributed to a decreased oxygen supply and eliminated hydrostatic influences during a prolonged recumbency. Blood redistribution in the vascular bed is related to the Gauer-Henry reflex and subsequent changes in the fluid-electrolyte balance. Decreased load on the bone system induces changes in the protein-phosphate-calcium metabolism, diminished bone density and increased calcium content in the blood and urine. Changes in the calcium metabolism are systemic. The activity of the higher nervous system and reflex functions is lowered. Changes in the function of the autonomic nervous system which include a noticeable decline of its adaptive-trophic role as a result of the decrease of afferent and efferent impulsation are of great importance. Changes in the hormonal function involve a peculiar stress-reaction which develops at an early stage of hypokinesia as a response to an unusual situation. Prolonged hypokinesia may result in a disturbed function of the pituitary-adrenal system. It is assumed that prolonged hypokinesia may induce a specific disease of hypokinesia during which man cannot lead a normal mode of life and work.

  17. Restriction in participation in leisure activities after joint replacement: an exploratory study.

    Science.gov (United States)

    Wylde, Vikki; Livesey, Christine; Blom, Ashley W

    2012-03-01

    currently, assessment of outcomes after joint replacement is predominantly centred on impairment and activity limitation (e.g. walking), with little consideration of participation restriction. structured telephone interviews about participation in leisure activities were conducted with 56 total hip replacement (THR) and 60 total knee replacement (TKR) patients before and 1 year after joint replacement. before surgery, THR patients participated in 209 leisure activities, with an average of four leisure activities per person. TKR patients participated in 171 leisure activities, with an average of three leisure activities per person. The leisure activities were coded into four categories: sports/exercise, hobbies, social activities and holidays. Between 89 and 95% of leisure activities were rated as important by THR and TKR patients prior to surgery. Before surgery, THR patients rated 82% of leisure activities as difficult to perform because of joint problems, which decreased to 25% of leisure activities by 1-year after surgery. TKR patients rated 86% of leisure activities as difficult to perform because of joint problems, which decreased to 32% after surgery. this research highlights that participation in leisure activities is important to patients undergoing joint replacement, but that approximately a quarter of patients are unable to perform their valued leisure activities after surgery.

  18. Calorigenic effect of adrenaline in rats under conditions of restricted motor activity

    Science.gov (United States)

    Tomaszewska, L.; Kaciuba-Uscilko, H.; Kozlowski, S.

    1980-01-01

    In previous studies, it was demonstrated that long term restricted motor activity in rats induces a decrease in body weight, an increase in release of adrenaline, and a decrease in the release of noradrenaline with the urine, as well as a reduction in activity of the thymus gland and level of thyroxin in the blood. At the same time, a decrease was found in the internal body temperature that was accompanied by an increase in the rate of metabolism in the state of rest. An investigation is presented which attempts to clarify whether the calorigenic effect of adrenaline under conditions of increased metabolism in the period of immobility is exposed to changes.

  19. Benefits for Type 2 Diabetes of Interrupting Prolonged Sitting With Brief Bouts of Light Walking or Simple Resistance Activities.

    Science.gov (United States)

    Dempsey, Paddy C; Larsen, Robyn N; Sethi, Parneet; Sacre, Julian W; Straznicky, Nora E; Cohen, Neale D; Cerin, Ester; Lambert, Gavin W; Owen, Neville; Kingwell, Bronwyn A; Dunstan, David W

    2016-06-01

    To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D). In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 ± 6 years old) underwent the following 8-h conditions on three separate days (with 6-14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h(-1)) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions. Compared with SIT, both activity-break conditions significantly attenuated iAUCs for glucose (SIT mean 24.2 mmol · h · L(-1) [95% CI 20.4-28.0] vs. LW 14.8 [11.0-18.6] and SRA 14.7 [10.9-18.5]), insulin (SIT 3,293 pmol · h · L(-1) [2,887-3,700] vs. LW 2,104 [1,696-2,511] and SRA 2,066 [1,660-2,473]), and C-peptide (SIT 15,641 pmol · h · L(-1) [14,353-16,929] vs. LW 11,504 [10,209-12,799] and SRA 11,012 [9,723-12,301]) (all P triglycerides was significantly attenuated for SRA (P triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Prolonged seizure activity leads to increased Protein Kinase A activation in the rat pilocarpine model of status epilepticus.

    Science.gov (United States)

    Bracey, James M; Kurz, Jonathan E; Low, Brian; Churn, Severn B

    2009-08-04

    Status epilepticus is a life-threatening form of seizure activity that represents a major medical emergency associated with significant morbidity and mortality. Protein Kinase A is an important regulator of synaptic strength that may play an important role in the development of status epilepticus-induced neuronal pathology. This study demonstrated an increase in PKA activity against exogenous and endogenous substrates during later stages of SE. As SE progressed, a significant increase in PKA-mediated phosphorylation of an exogenous peptide substrate was demonstrated in cortical structures. The increased activity was not due to altered expression of either regulatory or catalytic subunits of the enzyme. Through the use of phospho-specific antibodies, this study also investigated the effects of SE on the phosphorylation of the GluR1 subunit of the AMPA subtype of glutamate receptor. After the onset of continuous seizure activity, an increase in phosphorylation of the PKA site on the GluR1 subunit of the AMPA receptor was observed. These data suggest a potential mechanism by which SE may increase neuronal excitability in the cortex, potentially leading to maintenance of seizure activity or long-term neuronal pathology.

  1. Neuroimpairment, activity limitation, and participation restriction among children with cerebral palsy in Hong Kong.

    Science.gov (United States)

    Chan, H S S; Lau, P H B; Fong, K H; Poon, D; Lam, C C C

    2005-10-01

    To study children with cerebral palsy in Hong Kong, their neuroimpairment, activity limitation, and participation restriction in society. Parents' opinion on current medical and rehabilitation services was also sought. Systematic survey using questionnaires. Four associations in Hong Kong: Child Assessment Service, Hong Kong Association for Parents of Children with Physical Disabilities, Association of Parents of the Severely Mentally Handicapped, and Hong Kong Physically Handicapped and Able-Bodied Association. Parents of children with cerebral palsy. Neuroimpairment, activity limitation, and participation restriction. Information from 181 children with cerebral palsy was analysed. Among them, 56% were boys. The mean age was 7 years 6 months (standard deviation, 3 years 11 months). The most common diagnostic type was spastic cerebral palsy. Co-morbidities in children with cerebral palsy were common. Limitation in daily activities including mobility and self-care tasks was considerable and this posed great stress to parents when taking care of their children. Children's participation in both social and leisure activities was regarded as a low priority. A high percentage (70%) of parents reported difficulty in travelling. The reasons involved problems in transportation, building access (entry and exit), and attitudes of the general public. These environmental factors restricted the social participation of the children and their families. Over 75% of parents were satisfied with the current medical and rehabilitation services. Children with cerebral palsy have multiple and complex needs. The findings of this study may serve as a reference for parents, service providers, and policy makers to work in partnership to achieve a more comprehensive health-care service for children with cerebral palsy and to facilitate better integration into the community.

  2. Restrictions of physical activity participation in older adults with disability: employing keyword network analysis.

    Science.gov (United States)

    Koo, Kyo-Man; Kim, Chun-Jong; Park, Chae-Hee; Byeun, Jung-Kyun; Seo, Geon-Woo

    2016-08-01

    Older adults with disability might have been increasing due to the rapid aging of society. Many studies showed that physical activity is an essential part for improving quality of life in later lives. Regular physical activity is an efficient means that has roles of primary prevention and secondary prevention. However, there were few studies regarding older adults with disability and physical activity participation. The purpose of this current study was to investigate restriction factors to regularly participate older adults with disability in physical activity by employing keyword network analysis. Two hundred twenty-nine older adults with disability who were over 65 including aging with disability and disability with aging in type of physical disability and brain lesions defined by disabled person welfare law partook in the open questionnaire assessing barriers to participate in physical activity. The results showed that the keyword the most often used was 'Traffic' which was total of 21 times (3.47%) and the same proportion as in the 'personal' and 'economical'. Exercise was considered the most central keyword for participating in physical activity and keywords such as facility, physical activity, disabled, program, transportation, gym, discomfort, opportunity, and leisure activity were associated with exercise. In conclusion, it is necessary to educate older persons with disability about a true meaning of physical activity and providing more physical activity opportunities and decreasing inconvenience should be systematically structured in Korea.

  3. Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

    Science.gov (United States)

    Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

    2017-12-01

    Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Synthesis, anticancer activity, and inhibition of tubulin polymerization by conformationally restricted analogues of lavendustin A.

    Science.gov (United States)

    Mu, Fanrong; Hamel, Ernest; Lee, Debbie J; Pryor, Donald E; Cushman, Mark

    2003-04-24

    Compounds in the lavendustin A series have been shown to inhibit both protein-tyrosine kinases (PTKs) and tubulin polymerization. Since certain lavendustin A derivatives can exist in conformations that resemble both the trans-stilbene structure of the PTK inhibitor piceatannol and the cis-stilbene structure of the tubulin polymerization inhibitor combretastatin A-4, the possibility exists that the ratio of the two types of activities of the lavendustins could be influenced through the synthesis of conformationally restricted analogues. Accordingly, the benzylaniline structure of a series of pharmacologically active lavendustin A fragments was replaced by either their cis- or their trans-stilbene relatives, and effects on both inhibition of tubulin polymerization and cytotoxicity in cancer cell cultures were monitored. Both dihydrostilbene and 1,2-diphenylalkyne congeners were also prepared and evaluated biologically. Surprisingly, conformational restriction of the bridge between the two aromatic rings of the lavendustins had no significant effect on biological activity. On the other hand, conversion of the three phenolic hydroxyl groups of the lavendustin A derivatives to their corresponding methyl ethers consistently abolished their ability to inhibit tubulin polymerization and usually decreased cytotoxicity in cancer cell cultures as well, indicating the importance of at least one of the phenolic hydroxyl groups. Further investigation suggested that the phenolic hydroxyl group in the salicylamide ring was required for activity, while the two phenol moieties in the hydroquinone ring could be methylated with retention of activity. Two of the lavendustin A derivatives displayed IC(50) values of 1.4 microM for inhibition of tubulin polymerization, which ranks them among the most potent of the known tubulin polymerization inhibitors.

  5. Effects of fear of falling and activity restriction on normal and dual task walking in community dwelling older adults.

    Science.gov (United States)

    Donoghue, Orna A; Cronin, Hilary; Savva, George M; O'Regan, Claire; Kenny, Rose Anne

    2013-05-01

    Fear of falling (FOF) is associated with poor physical and psychosocial health and can have debilitating consequences especially when it leads to activity restriction. This study examined whether normal and dual task gait disruptions were independently associated with FOF and activity restriction or if they were fully explained by impaired health status. Data was obtained from The Irish Longitudinal Study on Ageing (TILDA). Community dwelling adults ≥65 years, with a Mini-Mental State Examination score ≥18 and who completed a gait assessment (n=1307) were divided into three groups: no FOF, FOF but no activity restriction (FOF-NAR), FOF with activity restriction (FOF-AR). Physical, psychosocial and cognitive measures were obtained and gait characteristics were assessed using a GAITRite(®) mat during normal and dual task (cognitive) walking. After adjusting for sociodemographics, physical, mental and cognitive health, FOF was associated with reduced gait speed and stride length and increased double support phase and step width in normal and dual task conditions; these changes were most pronounced in those who restrict activities as a result of FOF. These gait changes may be associated with an increased fall risk, however some changes especially increased step width may also reflect positive, compensatory adaptations to FOF. The results also highlight the importance of treating underlying health impairments and preventing the transition from FOF to activity restriction. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Activity restriction, impaired capillary function, and the development of insulin resistance in lean primates.

    Science.gov (United States)

    Chadderdon, Scott M; Belcik, J Todd; Smith, Elise; Pranger, Lindsay; Kievit, Paul; Grove, Kevin L; Lindner, Jonathan R

    2012-09-01

    Insulin produces capillary recruitment in skeletal muscle through a nitric oxide (NO)-dependent mechanism. Capillary recruitment is blunted in obese and diabetic subjects and contributes to impaired glucose uptake. This study's objective was to define whether inactivity, in the absence of obesity, leads to impaired capillary recruitment and contributes to insulin resistance (IR). A comprehensive metabolic and vascular assessment was performed on 19 adult male rhesus macaques (Macaca mulatta) after sedation with ketamine and during maintenance anesthesia with isoflurane. Thirteen normal-activity (NA) and six activity-restricted (AR) primates underwent contrast-enhanced ultrasound to determine skeletal muscle capillary blood volume (CBV) during an intravenous glucose tolerance test (IVGTT) and during contractile exercise. NO bioactivity was assessed by flow-mediated vasodilation. Although there were no differences in weight, basal glucose, basal insulin, or truncal fat, AR primates were insulin resistant compared with NA primates during an IVGTT (2,225 ± 734 vs. 5,171 ± 3,431 μg·ml⁻¹·min⁻¹, P < 0.05). Peak CBV was lower in AR compared with NA primates during IVGTT (0.06 ± 0.01 vs. 0.12 ± 0.02 ml/g, P < 0.01) and exercise (0.10 ± 0.02 vs. 0.20 ± 0.02 ml/g, P < 0.01), resulting in a lower peak skeletal muscle blood flow in both circumstances. The insulin-mediated changes in CBV correlated inversely with the degree of IR and directly with activity. Flow-mediated dilation was lower in the AR primates (4.6 ± 1.0 vs. 9.8 ± 2.3%, P = 0.01). Thus, activity restriction produces impaired skeletal muscle capillary recruitment during a carbohydrate challenge and contributes to IR in the absence of obesity. Reduced NO bioactivity may be a pathological link between inactivity and impaired capillary function.

  7. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging

    Directory of Open Access Journals (Sweden)

    Zhuoran Yin

    2018-03-01

    Full Text Available Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD or low-fat diet (LFD during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS. Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32 in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

  8. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging.

    Science.gov (United States)

    Yin, Zhuoran; Raj, Divya D; Schaafsma, Wandert; van der Heijden, Roel A; Kooistra, Susanne M; Reijne, Aaffien C; Zhang, Xiaoming; Moser, Jill; Brouwer, Nieske; Heeringa, Peter; Yi, Chun-Xia; van Dijk, Gertjan; Laman, Jon D; Boddeke, Erik W G M; Eggen, Bart J L

    2018-01-01

    Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

  9. Asymmetric hydration structure around calcium ion restricted in micropores fabricated in activated carbons

    International Nuclear Information System (INIS)

    Ohkubo, Takahiro; Kusudo, Tomoko; Kuroda, Yasushige

    2016-01-01

    The adsorbed phase and hydration structure of an aqueous solution of Ca(NO 3 ) 2 restricted in micropores fabricated in activated carbons (ACs) having different average pore widths (0.63 and 1.1 nm) were investigated with the analysis of adsorption isotherms and x-ray absorption fine structure (XAFS) spectra on Ca K -edge. The adsorbed density of Ca 2+ per unit micropore volume in the narrower pore was higher than in the wider pore, while the adsorbed amount per unit mass of carbon with the narrower pore was half of the amount of ACs with the larger pore. On the other hand, variations in the bands assigned to double-electron ( KM I ) and 1s  →  3d excitations in XAFS spectra demonstrate the formation of a distorted hydration cluster around Ca 2+ in the micropore, although the structural parameters of hydrated Ca 2+ in the micropores were almost consistent with the bulk aqueous solution, as revealed by the analysis of extended XAFS (EXAFS) spectra. In contrast to the hydration structure of monovalent ions such as Rb + , which generally presents a dehydrated structure in smaller than 1 nm micropores in ACs, the present study clearly explains that the non-spherically-symmetric structure of hydrated Ca 2+ restricted in carbon micropores whose sizes are around 1 nm is experimentally revealed where any dehydration phenomena from the first hydration shell around Ca 2+ could not be observed. (paper)

  10. Efficacy of physical activity counseling plus sleep restriction therapy on the patients with chronic insomnia

    Directory of Open Access Journals (Sweden)

    Wang J

    2015-10-01

    Full Text Available Jihui Wang, Guangxia Yin, Guanying Li, Wenjing Liang, Qinling Wei Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China Objective: Lack of physical activity (PA is common in patients with chronic insomnia. Studies to increase PA and decrease sedentary behavior in those patients are limited. Therefore, we investigated the efficacy of “PA counseling combined with sleep restriction (SR therapy (PASR” vs only SR in the patients with chronic insomnia. Methods: Seventy-one outpatients were assigned to either PASR (n=35, consisting of four weekly PA counseling sessions based on 5A model (assess, advise, agree, assist, and arrange + SR, or SR (n=36, consisting of four weekly SR. International Physical Activity Questionnaire (Chinese version and pedometer-based daily steps were evaluated as the primary endpoints. Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep Diary were evaluated as the secondary endpoints. Results: The results showed that the patients in the PASR group gained more benefits than the SR group in terms of PA level and pedometer-based daily steps (all P<0.05. Better improvements of the study group were also shown in Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep efficiency (all P<0.05. Conclusion: We conclude that PA counseling based on 5A model combined with SR cannot only effectively increase the PA levels but also improve the sleep quality for patients with chronic insomnia. Keywords: behavioral therapy, physical activity, sleep disorders, sleep restriction, counseling

  11. Muscle Shear Moduli Changes and Frequency of Alternate Muscle Activity of Plantar Flexor Synergists Induced by Prolonged Low-Level Contraction

    Directory of Open Access Journals (Sweden)

    Ryota Akagi

    2017-09-01

    Full Text Available During prolonged low-level contractions, synergist muscles are activated in an alternating pattern of activity and silence called as alternate muscle activity. Resting muscle stiffness is considered to increase due to muscle fatigue. Thus, we investigated whether the difference in the extent of fatigue of each plantar flexor synergist corresponded to the difference in the frequency of alternate muscle activity between the synergists using muscle shear modulus as an index of muscle stiffness. Nineteen young men voluntarily participated in this study. The shear moduli of the resting medial and lateral gastrocnemius muscles (MG and LG and soleus muscle (SOL were measured using shear wave ultrasound elastography before and after a 1-h sustained contraction at 10% peak torque during maximal voluntary contraction of isometric plantar flexion. One subject did not accomplish the task and the alternate muscle activity for MG was not found in 2 subjects; therefore, data for 16 subjects were used for further analyses. The magnitude of muscle activation during the fatiguing task was similar in MG and SOL. The percent change in shear modulus before and after the fatiguing task (MG: 16.7 ± 12.0%, SOL: −4.1 ± 13.9%; mean ± standard deviation and the alternate muscle activity during the fatiguing task (MG: 33 [20–51] times, SOL: 30 [17–36] times; median [25th–75th percentile] were significantly higher in MG than in SOL. The contraction-induced change in shear modulus (7.4 ± 20.3% and the alternate muscle activity (37 [20–45] times of LG with the lowest magnitude of muscle activation during the fatiguing task among the plantar flexors were not significantly different from those of the other muscles. These results suggest that the degree of increase in muscle shear modulus induced by prolonged contraction corresponds to the frequency of alternate muscle activity between MG and SOL during prolonged contraction. Thus, it is likely that, compared with

  12. Alterations of telomerase activity and terminal restriction fragment in gastric cancer and its premalignant lesions.

    Science.gov (United States)

    Yang, S M; Fang, D C; Luo, Y H; Lu, R; Battle, P D; Liu, W W

    2001-08-01

    In order to explore the role of alterations of telomerase activity and terminal restriction fragment (TRF) length in the development and progression of gastric cancer. Telomerase activity was detected in 176 specimens of gastric mucosa obtained through an operation or endoscopical biopsy by using the telomeric repeat amplification protocol (TRAP) assay. Meanwhile, the mean length of TRF was measured with the use of a Southern blot in part of those samples. Telomerase activity was detected in 14 of 57 (24.6%) chronic atrophy gastritis patients, six of 18 (33.3%) intestinal metaplasia patients, three of eight (37.5%) dysplasia patients and 60 of 65 (92.3%) gastric cancer patients, respectively. Normal gastric mucosa revealed no telomerase activity. No association was found between telomerase activity and any clinicopathological parameters. The mean TRF length was decreased gradually with age in normal mucosa and in gastric cancer tissue. Regression analysis demonstrated that the reduction rate in these tissues was 41 +/- 12 base pairs/year. Among 35 gastric cancers, TRF length was shown to be shorter in 20 cases (57.1%), similar in 12 cases (34.3%) and elongated in three cases (7.6%), compared to the corresponding adjacent tissues. The mean TRF length tended to decrease as the mucosa underwent chronic atrophy gastritis, intestinal metaplasia, dysplasia and into gastric cancer. The mean TRF length in gastric cancer was not statistically correlated with clinicopathological parameters and telomerase activity. Our results suggest that telomerase is expressed during the early stage of gastric carcinogenesis, and that the clinical significance of TRF length appears to be limited in gastric cancer.

  13. Effect of restricted motion in high temperature on enzymatic activity of the pancreas

    Science.gov (United States)

    Abdusattarov, A.; Smirnova, G. I.

    1980-01-01

    Effects of 30 day hypodynamia coupled with high temperature (35-36 C) on enzymatic activity of the pancreas of male adult rats were studied. The test animals were divided into four groups. Group one served as controls (freedom of movement and a temperature of 25-26 C, considered optimal). The remaining animals were divided into three additional groups: Group two freedom of movement but high temperature (35-36 C); group three hypodynamia but an optimal temperature; group four hypodynamia and 35-36 C. Considerable change in the enzymatic activity in the pancreas of the four groups is observed in three experimental groups (two, three, and four) as compared to the control (group one). The results indicate that adaption of the organism to the thermal factor and restricted movement is accompanied by a change in the enzymatic spectrum of the pancreas. With the combined effect of these two stresses under conditions of the adaption of the organism especially sharp shifts occur in the enzymatic activity.

  14. Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes.

    Science.gov (United States)

    Paco, Sonia; Hummel, Manuela; Plá, Virginia; Sumoy, Lauro; Aguado, Fernando

    2016-04-23

    cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown. Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes. These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.

  15. The effects of feed restriction on physical activity, body weight, physiology, haematology and immunology in female mink

    DEFF Research Database (Denmark)

    Damgaard, Birthe Marie; Dalgaard, Tina Sørensen; Larsen, Torben

    2012-01-01

    The aim of the present study was to investigate if adult mink females characterised as having a high or low residual feed intake (RFI) differed in their response to feed restriction with regard to activity, body weight loss and physiological parameters. For RFI-High, the activity was higher prior...

  16. The influence of a consumer-wearable activity tracker on sedentary time and prolonged sedentary bouts: secondary analysis of a randomized controlled trial.

    Science.gov (United States)

    Sloan, Robert A; Kim, Youngdeok; Sahasranaman, Aarti; Müller-Riemenschneider, Falk; Biddle, Stuart J H; Finkelstein, Eric A

    2018-03-22

    A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activity tracker to reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month randomized control trial where 800 employees from 13 organizations were assigned to control, activity tracker, or one of two activity tracker plus incentive groups designed to increase step count. The primary outcome was accelerometer measured moderate-to-vigorous physical activity. We conducted a secondary analysis on accelerometer measured daily ST and PSB bouts. A general linear mixed model was used to examine changes in ST and prolonged sedentary bouts, followed by between-group pairwise comparisons. Regression analyses were conducted to examine the association of changes in step counts with ST and PSB. The changes in ST and PSB were not statistically significant and not different between the groups (P consumer-wearable activity trackers as a means to reduce sedentary behavior. Trial registration NCT01855776 Registered: August 8, 2012.

  17. Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups

    Directory of Open Access Journals (Sweden)

    Emily S. Riddle

    2014-01-01

    Full Text Available Intrauterine growth restriction (IUGR programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNFα. TNFα contributes to adipocyte inflammation and impaired insulin signaling. TNFα has also been implicated in the activation of the unfolded protein response (UPR, which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNFα, TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2α, and Ddit3 prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1 increased circulating and adipose TNFα, (2 increased mRNA levels of UPR components as well as p-eIF2a, and (3 impaired glucose tolerance after observed TNFα increased and after UPR activation. We speculate that programmed dysregulation of TNFα and UPR contributed to the development of glucose intolerance in male IUGR rats.

  18. Management of prolonged pregnancy

    International Nuclear Information System (INIS)

    Iqbal, S.

    2004-01-01

    Objective: To compare two strategies for management of prolonged pregnancy (= or >294 days) i.e. induction (intervention) versus expectant management (non-intervention) and evaluate the associated feto-maternal risks. Subjects and Methods: One hundred cases of uncomplicated prolonged gestation were selected. The gestational age was confirmed by ultrasound in first trimester. One group (50 patients) was managed by intervention i.e. induction of labour (group A) and other group (50 patients) by non-intervention i.e. expectant management (group B). In group A intervention was done at 42 weeks. In expectant group, the methods of monitoring were fetal kick charting recorded daily by the patient, and ultrasound for amniotic fluid index. The biophysical profile score and NST (non stress test) were performed once a week till 42 weeks and then twice weekly. Results: The frequency of prolonged pregnancy was found to be 10.9%. There was no significant difference in the number of spontaneous vaginal deliveries between the two groups. The rate of LSCS (lower segment caesarean section) was higher in intervention group ( 30% versus 18% ). The neonatal depression at birth was more in group B ( 10% versus 4%) and at 5 minutes almost same between two groups (4% versus 2%). There were 11 cases of meconium aspiration syndrome, leading to one neonatal death. Among nine perinatal deaths two were neonatal deaths. Seven cases of intrauterine deaths in which antepartum deaths occurred because of non compliance of patients. No cause could be detected for the other three fetuses. Conclusion: There was increased LSCS rate in group A. However in expectant group B perinatal mortality was about twice more as compared to intervention group. Active early intervention at 42 weeks is warranted to reduce perinatal morbidity and mortality. (author)

  19. Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

    Science.gov (United States)

    Jakobsdottir, S; van Nieuwpoort, I C; van Bunderen, C C; de Ruiter, M B; Twisk, J W R; Deijen, J B; Veltman, D J; Drent, M L

    2016-11-01

    Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated. An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30-35 kg m -2 . The first 2 weeks subjects were on an isocaloric diet and 4 weeks on a 1000 kcal restricted diet followed by 2 weeks on an isocaloric diet. Anthropometric and laboratory analyses were performed weekly during the isocaloric diet and three times a week during the caloric-restricted diet. Functional magnetic resonance imaging scans were obtained before and after the caloric restriction in four separate sessions (fasting or sated). Generalized Estimating Equations analysis was used for data analysis. A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas. Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.

  20. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Science.gov (United States)

    2010-07-01

    ..., 085°47′29″ W; West point—30°07′55″ N, 085°51′05″ W, then northerly to point of origin. (b) The restrictions. (1) For the purposes of this section, “military security zones” are specific portion/s within any... both military and civilian personnel during exercises conducted within the restricted area by...

  1. Time-dependent restricted-active-space self-consistent-field theory for laser-driven many-electron dynamics

    DEFF Research Database (Denmark)

    Miyagi, Haruhide; Madsen, Lars Bojer

    2013-01-01

    We present the time-dependent restricted-active-space self-consistent-field (TD-RASSCF) theory as a framework for the time-dependent many-electron problem. The theory generalizes the multiconfigurational time-dependent Hartree-Fock (MCTDHF) theory by incorporating the restricted-active-space scheme...... well known in time-independent quantum chemistry. Optimization of the orbitals as well as the expansion coefficients at each time step makes it possible to construct the wave function accurately while using only a relatively small number of electronic configurations. In numerical calculations of high...

  2. Vanadium oxide based cpd. useful as a cathode active material - is used in lithium or alkali metal batteries to prolong life cycles

    DEFF Research Database (Denmark)

    1997-01-01

    A mixt. of metallic iron particles and vanadium pentoxide contg. V in its pentavalent state in a liq. is reacted to convert at least some of the pentavalent V to its tetravalent state and form a gel. The liq. phase is then sepd. from the oxide based gel to obtain a solid material(I) comprising Fe......, V and oxygen where at least some of the V is in the tetravalent state. USE-(I) is a cathode active material in electric current producing storage cells. ADVANTAGE-Use of (I) in Li or alkali metal batteries gives prolonged life cycles.Storage cells using (I) have improved capacity during charge...

  3. Time-dependent restricted-active-space self-consistent-field theory for bosonic many-body systems

    International Nuclear Information System (INIS)

    Lévêque, Camille; Madsen, Lars Bojer

    2017-01-01

    We develop an ab initio time-dependent wavefunction based theory for the description of a many-body system of cold interacting bosons. Like the multi-configurational time-dependent Hartree method for bosons (MCTDHB), the theory is based on a configurational interaction Ansatz for the many-body wavefunction with time-dependent self-consistent-field orbitals. The theory generalizes the MCTDHB method by incorporating restrictions on the active space of the orbital excitations. The restrictions are specified based on the physical situation at hand. The equations of motion of this time-dependent restricted-active-space self-consistent-field (TD-RASSCF) theory are derived. The similarity between the formal development of the theory for bosons and fermions is discussed. The restrictions on the active space allow the theory to be evaluated under conditions where other wavefunction based methods due to exponential scaling in the numerical effort cannot, and to clearly identify the excitations that are important for an accurate description, significantly beyond the mean-field approach. For ground state calculations we find it to be important to allow a few particles to have the freedom to move in many orbitals, an insight facilitated by the flexibility of the restricted-active-space Ansatz . Moreover, we find that a high accuracy can be obtained by including only even excitations in the many-body self-consistent-field wavefunction. Time-dependent simulations of harmonically trapped bosons subject to a quenching of their noncontact interaction, show failure of the mean-field Gross-Pitaevskii approach within a fraction of a harmonic oscillation period. The TD-RASSCF theory remains accurate at much reduced computational cost compared to the MCTDHB method. Exploring the effect of changes of the restricted-active-space allows us to identify that even self-consistent-field excitations are mainly responsible for the accuracy of the method. (paper)

  4. Impairments, activity limitations and participation restrictions: Prevalence and associations among persons living with HIV/AIDS in British Columbia

    Directory of Open Access Journals (Sweden)

    Braitstein Paula

    2004-09-01

    Full Text Available Abstract Background To measure the prevalence of and associations among impairments, activity limitations and participation restrictions in persons living with HIV in British Columbia to inform support and care programs, policy and research. Methods A cross-sectional population-based sample of persons living with HIV in British Columbia was obtained through an anonymous survey sent to members of the British Columbia Persons With AIDS Society. The survey addressed the experience of physical and mental impairments, and the experience and level of activity limitations and participation restrictions. Associations were measured in three ways: 1 impact of types of impairment on social restriction; 2 impact of specific limitations on social restriction; and 3 independent association of overall impairments and limitations on restriction levels. Logistic regression was used to measure associations with social restriction, while ordinal logistic regression was used to measure associations with a three-category measure of restriction level. Results The survey was returned by 762 (50.5% of the BCPWA participants. Over ninety percent of the population experienced one or more impairments, with one-third reporting over ten. Prevalence of activity limitations and participation restrictions was 80.4% and 93.2%, respectively. The presence of social restrictions was most closely associated with mental function impairments (OR: 7.0 for impairment vs. no impairment; 95% CI: 4.7 – 10.4. All limitations were associated with social restriction. Among those with ≤ 200 CD4 cells/mm3, odds of being at a higher restriction level were lower among those on antiretrovirals (OR: 0.3 for antiretrovirals vs. no antiretrovirals; 95% CI: 0.1–0.9, while odds of higher restriction were increased with higher limitation (OR: 3.6 for limitation score of 1–5 vs. no limitation, 95%CI: 0.9–14.2; OR: 24.7 for limitation score > 5 vs. no limitation, 95%CI: 4.9–125.0. Among those

  5. Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

    Science.gov (United States)

    Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

    2018-01-01

    Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

  6. Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Fangyun Tian

    2018-02-01

    Full Text Available Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG and electroencephalogram (EEG signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

  7. Acute and short-term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women

    NARCIS (Netherlands)

    Jakobsdottir, S.; van Nieuwpoort, I. C.; van Bunderen, C. C.; de Ruiter, M. B.; Twisk, J. W. R.; Deijen, J. B.; Veltman, D. J.; Drent, M. L.

    2016-01-01

    Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated. An 8-week prospective intervention study of 18

  8. Acute and short term effects of caloric restriction on metabolic profile and brain activation in obese, postmenopausal women.

    NARCIS (Netherlands)

    Jakobsdottir, S.; van Nieuwpoort, I.C.; van Bunderen, C.C.; de Ruiter, M.B.; Twisk, J.W.R.; Deijen, J.B.; Veltman, D.J.; Drent, M.L.

    2016-01-01

    OBJECTIVE:Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated.SUBJECTS AND METHODS:An 8-week prospective

  9. Prolonged fasting activates hypoxia inducible factors-1α, -2α and -3α in a tissue-specific manner in northern elephant seal pups.

    Science.gov (United States)

    Soñanez-Organis, José G; Vázquez-Medina, José P; Crocker, Daniel E; Ortiz, Rudy M

    2013-09-10

    Hypoxia inducible factors (HIFs) are important regulators of energy homeostasis and cellular adaptation to low oxygen conditions. Northern elephant seals are naturally adapted to prolonged periods (1-2 months) of food deprivation (fasting) which result in metabolic changes that may activate HIF-1. However, the effects of prolonged fasting on HIFs are not well defined. We obtained the full-length cDNAs of HIF-1α and HIF-2α, and partial cDNA of HIF-3α in northern elephant seal pups. We also measured mRNA and nuclear protein content of HIF-1α, -2α, -3α in muscle and adipose during prolonged fasting (1, 3, 5 & 7 weeks), along with mRNA expression of HIF-mediated genes, LDH and VEGF. HIF-1α, -2α and -3α are 2595, 2852 and 1842 bp and encode proteins of 823, 864 and 586 amino acid residues with conserved domains needed for their function (bHLH and PAS) and regulation (ODD and TAD). HIF-1α and -2α mRNA expression increased 3- to 5-fold after 7 weeks of fasting in adipose and muscle, whereas HIF-3α increased 5-fold after 7 weeks of fasting in adipose. HIF-2α protein expression was detected in nuclear fractions from adipose and muscle, increasing approximately 2-fold, respectively with fasting. Expression of VEGF increased 3-fold after 7 weeks in adipose and muscle, whereas LDH mRNA expression increased 12-fold after 7 weeks in adipose. While the 3 HIFα genes are expressed in muscle and adipose, only HIF-2α protein was detectable in the nucleus suggesting that HIF-2α may contribute more significantly in the up-regulation of genes involved in the metabolic adaptation during fasting in the elephant seal. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Acute Right Ventricular Dysfunction Complicating Prolonged ...

    African Journals Online (AJOL)

    We report a case of transient right ventricular dysfunction associated with prolonged cardiac tamponade, an unusual complication of uncertain etiology. We believe that in this case dynamic coronary flow restriction resulted in ischemic injury and stunning of the right ventricle. Other possible causes are briefly reviewed. Right ...

  11. Activity restriction increases deoxypyridinoline excretion in hospitalized high-risk pregnant women.

    Science.gov (United States)

    Vanderspank, Dana; Bernier, Suzanne M; Sopper, Maggie M; Watson, Patricia; Mottola, Michelle F

    2014-01-01

    Activity restriction (AR), one of the most common interventions used in high-risk pregnancies, may exacerbate loss of bone mass. The purpose of this study was to determine changes over time in bone resorption in hospitalized AR women during late pregnancy. This was a short-term prospective study conducted in two tertiary-care obstetric hospitals. We measured urinary deoxypyridinoline (Dpd) excretion, a marker of bone resorption, once per week in a convenience sample of 14 hospitalized AR women in the third trimester and compared values at 28-31 and 34-36 weeks' gestation to those of 11 ambulatory control women. Both groups completed a bone-loading questionnaire, 3-day food intake record, and pedometer step counts at the same gestational age. Urinary Dpd excretion increased from Days 1-7 (2.60 ± 0.32 nmol/mmol creatinine) to Days 22-28 (5.36 ± 0.83 nmol/mmol creatinine; p ≤ .05). Dpd excretion was higher in AR women (4.51 ± 0.31 nmol/mmol creatinine) than ambulatory women (2.72 ± 0.39 nmol/mmol creatinine) at 34-36 weeks' gestation (p ≤ .05). Energy intake between ambulatory and AR women was not different (p ≥ .05). All women met the daily requirements for calcium and vitamin D intake during pregnancy. Average daily pedometer steps for the AR women were significantly less compared to controls (1,329 ± 936 and 8,024 ± 1,890 steps/day, respectively; p ≤ .05). AR leads to increased bone resorption in hospitalized pregnant women, which may impact future risk of developing osteopenia and osteoporosis.

  12. Oxycodone is associated with dose-dependent QTc prolongation in patients and low-affinity inhibiting of hERG activity in vitro

    DEFF Research Database (Denmark)

    Fanoe, Søren; Jensen, Gorm Boje; Sjøgren, Per

    2008-01-01

    with the use of these drugs. WHAT THIS PAPER ADDS: This study is the first to show that oxycodone dose is associated with QT prolongation and in vitro blockade of hERG channels expressed in HEK293. Neither morphine nor tramadol doses are associated with the QT interval length. AIMS: During recent years some...... and TdP could be a more general problem associated with the use of these drugs. The aims of this study were to evaluate the association between different opioids and the QTc among patients and measure hERG activity under influence by opioids in vitro. METHODS: One hundred chronic nonmalignant pain...... patients treated with methadone, oxycodone, morphine or tramadol were recruited in a cross-sectional study. The QTc was estimated from a 12-lead ECG. To examine hERG activity in the presence of oxycodone, electrophysiological testing was conducted using Xenopus laevis oocytes and HEK293 cells expressing h...

  13. Fear of falling and activity restriction{ in older adults from the urban community of Londrina: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Fabiana Satiko Fucahori

    Full Text Available Objective The objective of this study was to assess the fear of falling and restriction of activities in the elderly of the city of Londrina (PR. Materials and method A cross-sectional study was conducted with individuals over 60 years old of both sexes. They were interviewed at their home with the Falls Efficacy Scale International - Brazil the Survey of Activities and Fear of Falling in the Elderly a socio-demographic and health perception questionnaire. Results The participants were 38 elderly people (mean age 71.6 ± 6.1 years with a prevalence of women (68.4%. The occurrence of a fall in the last year was reported by 44.7% of the elderly, and the prevalence of the fear of falling again by 56.3%. In the evaluation of the Falls Efficacy Scale, 97.4% of participants reported fear of falling in at least one of the activities while 55.3% had score ≥ 23 points showing high risk for falls. Fifty two percent of the elders restricted their activity due the fear of falling. Conclusion These results show a high frequency of fear of falling associated with restriction of activities and individuals with a high risk potential for falls. The evaluation of this data contributes to establishing indicators and development of preventive strategies and specific interventions for the elderly with fear of falling.

  14. Influence of Restrictive Ventilation Impairment on Physical Function and Activities of Homebound Elderly Persons

    Directory of Open Access Journals (Sweden)

    Jun Horie

    2011-06-01

    Conclusions: Although patients with restrictive ventilation impairment were unlikely to be aware of their disorder, degradation in systemic stamina had already commenced. It appears that maintaining exercise habits prevented degradation of not only instantaneous walking ability but also of systemic stamina.

  15. DNA-tension dependence of restriction enzyme activity reveals mechanochemical properties of the reaction pathway

    NARCIS (Netherlands)

    van den Broek, B.; Noom, M.C.; Wuite, G.J.L.

    2005-01-01

    Type II restriction endonucleases protect bacteria against phage infections by cleaving recognition sites on foreign double-stranded DNA (dsDNA) with extraordinary specificity. This capability arises primarily from large conformational changes in enzyme and/or DNA upon target sequence recognition.

  16. Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34.

    Science.gov (United States)

    Strother, Douglas R; Lafay-Cousin, Lucie; Boyett, James M; Burger, Peter; Aronin, Patricia; Constine, Louis; Duffner, Patricia; Kocak, Mehmet; Kun, Larry E; Horowitz, Marc E; Gajjar, Amar

    2014-03-01

    The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion. Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm. Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma.

  17. Effect of prolonged gamma irradiation (6.7 Gy) on monoamine oxidase activity in ewe hypothalamus in anestral period

    International Nuclear Information System (INIS)

    Pastorova, B.; Arendarcik, J.

    1988-01-01

    Changes were studied of monoamine oxidase (MAO) activity in the hypothalamus and hypophysis of ewes in the anestral period following whole-body 60 Co irradiation for 7 days with a dose of 6.7 Gy. The gamma radiation exposure rate was 0.039 Gy/h. The activity of MAO was determined using the radiochemical method. 14 C-tryptamine was used as the substrate. The highest activity was determined in the rostral hypothalamus (1100 pmol.mg -1 .min -1 ). MAO activity was at its lowest in the caudal region of the hypothalamus (550 pmol). The results show that whole-body exposure to gamma radiation with a total dose of 6.7 Gy makes a statistically significant increase (P<0.001) in MAO activity in the caudal hypothalamus of ewes while remaining at the level of the control group or increasing insignificantly in the rostral and medial hypothalamus. A significant decrease (P<0.05) was recorded in the hypophysis. It may be assumed that the increased degradation of catecholamines caused by MAO is one of the mechanisms responsible for the decreased concentration of catecholamines in the hypothalamus of ewes after irradiation. (author). 1 fig., 22 refs

  18. Impact of prolonged storm activity on the Ecological Status of intertidal benthic habitats within oyster (Crassostrea gigas) trestle cultivation sites.

    Science.gov (United States)

    O'Carroll, Jack P J; Quinn, Christina; Forde, James; Patterson, Adrian; O'Beirn, Francis X; Kennedy, Robert

    2016-09-15

    The Ecological Status (ES; sensu the Water Framework Directive) of intertidal benthic communities within six oyster trestle cultivation sites was found to be negatively impacted along the access routes to trestles in a 2013 study. All cultivation sites occur within Natura 2000 sites. The current study revisited four of the 2013 cultivation sites in February 2014 one month after the storm activity of winter 2013/14 to test if the compaction effect along access routes persisted after the storms. Three levels of the fixed factor treatment were sampled; immediately below the trestles, along the access route and 300m away from any anthropogenic activity. The compaction effect at the Access treatment persisted in spite of the major storm activity. The current study showed the IQI to be effective for assessing the impacts of aquaculture and highlights the IQI as a tool for monitoring Conservation Status of intertidal communities under the Habitats Directive. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Restricted active space spin-flip configuration interaction: theory and examples for multiple spin flips with odd numbers of electrons.

    Science.gov (United States)

    Zimmerman, Paul M; Bell, Franziska; Goldey, Matthew; Bell, Alexis T; Head-Gordon, Martin

    2012-10-28

    The restricted active space spin flip (RAS-SF) method is extended to allow ground and excited states of molecular radicals to be described at low cost (for small numbers of spin flips). RAS-SF allows for any number of spin flips and a flexible active space while maintaining pure spin eigenfunctions for all states by maintaining a spin complete set of determinants and using spin-restricted orbitals. The implementation supports both even and odd numbers of electrons, while use of resolution of the identity integrals and a shared memory parallel implementation allow for fast computation. Examples of multiple-bond dissociation, excited states in triradicals, spin conversions in organic multi-radicals, and mixed-valence metal coordination complexes demonstrate the broad usefulness of RAS-SF.

  20. Concomitant active tuberculosis prolongs survival in non-small cell lung cancer: a study in a tuberculosis-endemic country.

    Directory of Open Access Journals (Sweden)

    Chih-Hsi Kuo

    Full Text Available BACKGROUND: Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. METHODS: Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. RESULTS: A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01. Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48 ~ 0.97. Squamous cell carcinoma (SCC (55.8 vs. 31.7%, p<0.01 is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05. Active tuberculosis in SCC increases the expression of CD3 (46.4 ± 24.8 vs. 24.0 ± 16.0, p<0.05, CXCR3 (35.1 ± 16.4 vs. 19.2 ± 13.3, p<0.01 and IP-10 (63.5 ± 21.9 vs. 35.5 ± 21.0, p<0.01, while expression of FOXP3 is decreased (3.5 ± 0.5 vs. 13.3 ± 3.7 p<0.05, p<0.05. Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05 and CXCR3 (12.1 vs. 4.4 month, p<0.05 is longer than that with low expression. CONCLUSIONS: Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches.

  1. Prolonged activated prothromboplastin time and breed specific variation in haemostatic analytes in healthy adult Bernese Mountain dogs

    DEFF Research Database (Denmark)

    Nielsen, Lise; Wiinberg, Bo; Kjelgaard-Hansen, Mads

    2011-01-01

    Coagulation tests are often performed in dogs suspected of haemostatic dysfunction and are interpreted according to validated laboratory reference intervals (RIs). Breed specific RIs for haematological and biochemical analytes have previously been identified in Bernese Mountain dogs, but it remains...... to be determined if breed specific RIs are necessary for haemostasis tests. Activated prothromboplastin time (aPTT), prothrombin time (PT), selected coagulation factors, D-dimers, fibrinogen, von Willebrand factor and thromboelastography (TEG) were analyzed in healthy Bernese Mountain dogs using the CLSI model...

  2. Prolonged activation of S6K1 does not suppress IRS or PI-3 kinase signaling during muscle cell differentiation

    Directory of Open Access Journals (Sweden)

    MacKenzie Matthew G

    2010-05-01

    Full Text Available Abstract Background Myogenesis in C2C12 cells requires the activation of the PI3K/mTOR signaling pathways. Since mTOR signaling can feedback through S6K1 to inhibit the activation of PI3K, the aim of this work was to assess whether feedback from S6K1 played a role in myogenesis and determine whether siRNA mediated knockdown of S6K1 would lead to an increased rate of myotube formation. Results S6K1 activity increased in a linear fashion following plating and was more than 3-fold higher after Day 3 of differentiation (subconfluent = 11.09 ± 3.05, Day 3 = 29.34 ± 3.58. IRS-1 levels tended to increase upon serum withdrawal but decreased approximately 2-fold (subconfluent = 0.88 ± 0.10, Day 3 = 0.42 ± 0.06 3 days following differentiation whereas IRS-2 protein remained stable. IRS-1 associated p85 was significantly reduced upon serum withdrawal (subconfluent = 0.86 ± 0.07, Day 0 = 0.31 ± 0.05, remaining low through day 1. IRS-2 associated p85 decreased following serum withdrawal (subconfluent = 0.96 ± 0.05, Day 1 = 0.56 ± 0.08 and remained suppressed up to Day 3 following differentiation (0.56 ± 0.05. Phospho-tyrosine associated p85 increased significantly from subconfluent to Day 0 and remained elevated throughout differentiation. siRNA directed against S6K1 and S6K2 did not result in changes in IRS-1 levels after either 48 or 96 hrs. Furthermore, neither 48 nor 96 hrs of S6K1 knockdown caused a change in myotube formation. Conclusions Even though S6K1 activity increases throughout muscle cell differentiation and IRS-1 levels decrease over this period, siRNA suggests that S6K1 is not mediating the decrease in IRS-1. The decrease in IRS-1/2 associated p85 together with the increase in phospho-tyrosine associated p85 suggests that PI3K associates primarily with scaffolds other than IRS-1/2 during muscle cell differentiation.

  3. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Salgado Maria

    2011-12-01

    Full Text Available Abstract Background While initiation of highly active antiretroviral therapy (HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of + T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL mediated suppression that has been reported in many elite suppressors.

  4. Peripheral innate immune challenge exaggerated microglia activation, increased the number of inflammatory CNS macrophages, and prolonged social withdrawal in socially defeated mice.

    Science.gov (United States)

    Wohleb, Eric S; Fenn, Ashley M; Pacenta, Ann M; Powell, Nicole D; Sheridan, John F; Godbout, Jonathan P

    2012-09-01

    Repeated social defeat (RSD) activates neuroendocrine pathways that have a significant influence on immunity and behavior. Previous studies from our lab indicate that RSD enhances the inflammatory capacity of CD11b⁺ cells in the brain and promotes anxiety-like behavior in an interleukin (IL)-1 and β-adrenergic receptor-dependent manner. The purpose of this study was to determine the degree to which mice subjected to RSD were more responsive to a secondary immune challenge. Therefore, RSD or control (HCC) mice were injected with saline or lipopolysaccharide (LPS) and activation of brain CD11b⁺ cells and behavioral responses were determined. Peripheral LPS (0.5 mg/kg) injection caused an extended sickness response with exaggerated weight loss and prolonged social withdrawal in socially defeated mice. LPS injection also amplified mRNA expression of IL-1β, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD14 in enriched CD11b⁺ cells isolated from socially defeated mice. In addition, IL-1β mRNA levels in enriched CD11b⁺ cells remained elevated in socially defeated mice 24 h and 72 h after LPS. Moreover, microglia and CNS macrophages isolated from socially defeated mice had the highest CD14 expression after LPS injection. Both social defeat and LPS injection increased the percentage of CD11b⁺/CD45(high) macrophages in the brain and the number of inflammatory macrophages (CD11b⁺/CD45(high)/CCR2⁺) was highest in RSD-LPS mice. Anxiety-like behavior was increased by social defeat, but was not exacerbated by the LPS challenge. Nonetheless, reduced locomotor activity and increased social withdrawal were still present in socially defeated mice 72 h after LPS. Last, LPS-induced microglia activation was most evident in the hippocampus of socially defeated mice. Taken together, these findings demonstrate that repeated social defeat enhanced the neuroinflammatory response and caused prolonged sickness following innate immune challenge

  5. A second wave of Salmonella T3SS1 activity prolongs the lifespan of infected epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ciaran E Finn

    2017-04-01

    Full Text Available Type III secretion system 1 (T3SS1 is used by the enteropathogen Salmonella enterica serovar Typhimurium to establish infection in the gut. Effector proteins translocated by this system across the plasma membrane facilitate invasion of intestinal epithelial cells. One such effector, the inositol phosphatase SopB, contributes to invasion and mediates activation of the pro-survival kinase Akt. Following internalization, some bacteria escape from the Salmonella-containing vacuole into the cytosol and there is evidence suggesting that T3SS1 is expressed in this subpopulation. Here, we investigated the post-invasion role of T3SS1, using SopB as a model effector. In cultured epithelial cells, SopB-dependent Akt phosphorylation was observed at two distinct stages of infection: during and immediately after invasion, and later during peak cytosolic replication. Single cell analysis revealed that cytosolic Salmonella deliver SopB via T3SS1. Although intracellular replication was unaffected in a SopB deletion mutant, cells infected with ΔsopB demonstrated a lack of Akt phosphorylation, earlier time to death, and increased lysis. When SopB expression was induced specifically in cytosolic Salmonella, these effects were restored to levels observed in WT infected cells, indicating that the second wave of SopB protects this infected population against cell death via Akt activation. Thus, T3SS1 has two, temporally distinct roles during epithelial cell colonization. Additionally, we found that delivery of SopB by cytosolic bacteria was translocon-independent, in contrast to canonical effector translocation across eukaryotic membranes, which requires formation of a translocon pore. This mechanism was also observed for another T3SS1 effector, SipA. These findings reveal the functional and mechanistic adaptability of a T3SS that can be harnessed in different microenvironments.

  6. Prolonged duration of isoflurane anesthesia impairs spatial recognition memory through the activation of JNK1/2 in the hippocampus of mice.

    Science.gov (United States)

    Jiang, Shan; Miao, Bei; Chen, Ying

    2017-05-03

    Postoperative cognitive dysfunction is a frequent complication with surgery and anesthesia, and the underlying mechanism is unclear. Our aim was to investigate the effect of different durations of isoflurane anesthesia on spatial recognition memory and activation of JNK1/2 in the hippocampus of mice. In the present study, adult male mice were anesthetized with isoflurane for different durations (1.5% isoflurane for 1, 2, and 4 h). Spatial recognition memory was determined using spontaneous alternation and two-trial recognition memory in Y-maze at 24 h after anesthesia. The activation of JNK1/2 in the hippocampus was tested using western blot. Mice treated with isoflurane for 4 h showed significantly decreased spontaneous alternations and decreased exploration parameters compared with the no anesthesia group, but this was not observed in mice treated with isoflurane for 1 or 2 h. The protein levels of p-JNK1/2 in the hippocampus were significantly increased at 10 min after isoflurane anesthesia for 1, 2, and 4 h compared with no anesthesia. However, only isoflurane anesthesia for 4 h still increased JNK1/2 and p-JNK1/2 levels at 24 h after anesthesia. We concluded that prolonged duration of isoflurane anesthesia maintained the activation of JNK1/2, which led to memory impairment at 24 h after anesthesia.

  7. Antidepressant-like activity of venlafaxine and clonidine in mice exposed to single prolonged stress - A model of post-traumatic stress disorder. Pharmacodynamic and molecular docking studies.

    Science.gov (United States)

    Malikowska, Natalia; Fijałkowski, Łukasz; Nowaczyk, Alicja; Popik, Piotr; Sałat, Kinga

    2017-10-15

    Post-traumatic stress disorder (PTSD) is a growing issue worldwide characterized by stress and anxiety in response to re-experiencing traumatic events which strongly impair patient's quality of life and social functions. Available antidepressant and anxiolytic drugs are not efficacious in the majority of treated individuals. This necessitates a significant medical demand to develop novel therapeutic strategies for PTSD. Animal model of PTSD was induced using a mouse single prolonged stress protocol (mSPS). To assess the activity of venlafaxine and clonidine, the forced swim test (FST) was used repeatedly 24h, 3days, 8days, 15days and 25days after mSPS. To get insight into a possible mechanism of anti-PTSD action, molecular docking procedure was utilized for the most active drug. This in silico part comprised molecular docking of enantiomers of venlafaxine to human transporters for serotonin (hSERT), norepinephrine (hNET) and dopamine (hDAT). In mSPS-subjected mice FST revealed the effectiveness of venlafaxine, however in non SPS-subjected mice both venlafaxine and clonidine were active. Molecular docking studies indicated that the affinity of venlafaxine to monoamine transporters is growing in the following rank order: hDATPTSD. Its mechanism of action, i.e., SERT, NET and DAT inhibition indicates potential drug targets for PTSD treatment. We expect that these results will contribute to a broader application of VLX in PTSD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Differential diagnosis between obsessive compulsive disorder and restrictive and repetitive behavioural patterns, activities and interests in autism spectrum disorders.

    Science.gov (United States)

    Paula-Pérez, Isabel

    2013-01-01

    The obsessive compulsive disorder (OCD) and the restricted and repetitive patterns of behavior, interests and activities inherent to autism spectrum disorders (ASD) share a number of features that can make the differential diagnosis between them extremely difficult and lead to erroneous overdiagnosis of OCD in people with autism. In both cases there may appear to have a fixation on routine, ritualized patterns of verbal and nonverbal behavior, resistance to change, and highly restrictive interests, which becomes a real challenge for differentiating rituals, stereotypes and adherence to routines in ASD from obsessions and compulsions in OCD. This article provides key points to clarify this differential diagnosis through the analysis of emotional valence, content, function and psychological theories that explain the obsessions and compulsions in OCD, and the desire for sameness, stereotyped movements and limited interest in autism. The terms "obsession" and "compulsion" should no longer be used when referring to patterns of behavior, interests or restricted and repetitive activities in autism due to syntonic characteristics, low perception of personal responsibility and low neutralizing efforts. Treatment focuses on changing the environment, the use of socio-communicative compensatory strategies and behavioral modification techniques to improve cognitive and behavioral flexibility. When there is comorbidity between, exposure behavioral and response prevention techniques are then used, followed by others of more cognitive orientation if necessary. Copyright © 2012 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  9. Abortion as empowerment: reproductive rights activism in a legally restricted context.

    Science.gov (United States)

    McReynolds-Pérez, Julia

    2017-11-08

    This paper analyzes the strategies used by activist health professionals in Argentina who justify providing abortion despite legal restrictions on the procedure. These "insider activists" make a case for abortion rights by linking pregnancy termination to a woman's ability to exert agency at a key point in her reproductive life, and argue that refusing women access to the procedure constitutes a grievous health risk. This argument frames pregnancy termination as an issue of empowerment and also as a medical necessity. This article is based on ethnographic research conducted in Argentina in 2013 and 2015, which includes in-depth interviews with abortion activists and health professionals and ethnographic observation at activist events and in clinics. During the period of my field research, the medical staff in one clinic shifted from abortion counseling, based on a harm reduction model, to legal pregnancy termination, a new mode of abortion provision where they directly provided abortions based on the legal health exception. These insider activists formalized the latter approach by creating a diagnostic instrument that frames women's "bio-psycho-social" reasons for wishing to terminate a pregnancy as medically justified. The clinical practice analyzed in this article raises important questions about the potential for health professionals to take on an activist role by making safe abortion accessible, even in a context where the procedure is highly restricted.

  10. mTOR inhibition in macrophages of asymptomatic HIV+ persons reverses the decrease in TLR4-mediated TNFα release through prolongation of MAPK pathway activation1

    Science.gov (United States)

    Li, Xin; Han, Xinbing; Llano, Juliana; Bole, Medhavi; Zhou, Xiuqin; Swan, Katharine; Anandaiah, Asha; Nelson, Benjamin; Patel, Naimish R.; Reinach, Peter S.; Koziel, Henry; Tachado, Souvenir D.

    2011-01-01

    Toll-like receptor 4 (TLR4) mediated signaling is significantly impaired in macrophages from HIV+ persons predominantly due to altered MyD88-dependent pathway signaling caused in part by constitutive activation of PI3K. Here we assessed in these macrophages if the blunted increase in TLR4-mediated TNFα release induced by lipid A are associated with PI3K-induced upregulation of mammalian target of rapamycin (mTOR) activity. mTOR inhibition with rapamycin enhanced TLR4-mediated TNFα release, but instead suppressed anti-inflammatory IL-10 release. Targeted gene silencing of mTOR in macrophages resulted in lipid A-induced TNFα and IL-10 release patterns similar to those induced by rapamycin. Rapamycin restored MyD88-IRAK interaction in a dose-dependent manner. Targeted gene silencing of MyD88 (shRNA) and mTOR (RNAi) inhibition resulted in TLR4-mediated p70s6K activation and enhanced TNFα release, whereas IL-10 release was inhibited in both silenced and non-silenced HIV+ macrophages. Furthermore, mTOR inhibition augmented lipid A-induced TNFα release through enhanced and prolonged phosphorylation of ERK1/2 and JNK1/2 MAP kinases, which was associated with time-dependent MKP-1 destabilization. Taken together, impaired TLR4-mediated TNFα release in HIV+ macrophages is attributable in part to mTOR activation by constitutive PI3K expression in a MyD88-dependent signaling pathway. These changes result in MKP-1 stabilization, which shortens and blunts MAP kinase activation. mTOR inhibition may serve as a potential therapeutic target to upregulate macrophage innate immune host defense responsiveness in HIV+ persons. PMID:22025552

  11. 9. Nuclear power plant service life prolongation

    International Nuclear Information System (INIS)

    Evropin, S.V.

    1998-01-01

    The problem of prolongation of nuclear power plant service life duration is discussed. A schematic diagram of the program developed in the course of activities dealing with NPP service time prolongation is shown and analyzed in details. It is shown that the basic moment when determining the strategy for NPP service time prolongation is the positive confirmation of the agreement between the NPP safety provisions and modern safety requirements. The other very important aspect of the problem is engineering substantiation of the measures assuring the reactor operation prolongation. The conclusion is made that available methods of recovering reactor materials properties, main components repair and replacement, the modern techniques for nondestructive testing of metals and NPP pipelines, as well as the developed approaches to reactor facility safety improvements make the prolongation of the Russian NPP service lifetimes possible from engineering viewpoint and economically desirable

  12. Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes.

    Science.gov (United States)

    Dempsey, Paddy C; Sacre, Julian W; Larsen, Robyn N; Straznicky, Nora E; Sethi, Parneet; Cohen, Neale D; Cerin, Ester; Lambert, Gavin W; Owen, Neville; Kingwell, Bronwyn A; Dunstan, David W

    2016-12-01

    Prolonged sitting is increasingly recognized as a ubiquitous cardiometabolic risk factor, possibly distinct from lack of physical exercise. We examined whether interrupting prolonged sitting with brief bouts of light-intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2 diabetes (T2D). In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men; mean ± SD; 62 ± 6 years) consumed standardized meals during 3 × 8 h conditions: uninterrupted sitting (SIT); sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity walking); and sitting + half-hourly bouts of simple resistance activities for 3 min (SRAs), each separated by 6-14 days washout. Resting seated BP was measured hourly (mean of three recordings, ≥20-min postactivity). Plasma noradrenaline was measured at 30-min intervals for the first hour after meals and hourly thereafter. Compared with SIT, mean resting SBP and DBP were significantly reduced (P light-intensity walking (mean ± SEM; -14 ± 1/-8 ± 1 mmHg) and SRA (-16 ± 1/-10 ± 1 mmHg), with a more pronounced effect for SRA (P light-intensity walking). Similarly, mean plasma noradrenaline was significantly reduced for both light-intensity walking (-0.3 ± 0.1 nmol/l) and SRA (-0.6 ± 0.1 nmol/l) versus SIT, with SRA lower than light-intensity walking (P light-intensity walking (-3 ± 1 bpm; P light-intensity walking or SRA reduces resting BP and plasma noradrenaline in adults with T2D, with SRA being more effective. Given the ubiquity of sedentary behaviors and poor adherence to structured exercise, this approach may have important implications for BP management in patients with T2D.

  13. Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress.

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R; Staib, Jennifer M; David, Nina P; DePietro, Thomas; Chamness, Marisa; Schneider, Elizabeth K; Keller, Samantha M; Lawless, Caroline

    2018-04-02

    Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. RD50 Prolongation Request 2018

    CERN Document Server

    Casse, Gianluigi

    2018-01-01

    With this document, we request the prolongation of the CERN RD50 research program for 5 years. A very brief historical review of the RD50 research program since the RD50 project approval by the Research Board in the year 2002 is presented and the biggest RD50 achievements are highlighted. The present composition of the collaboration, its organizational structure, and the research methodology are described. The role of RD50 in the present various upgrade and research programs of the LHC Experiments community is given and the overall work plan explained. Finally, a detailed 5-years work program with precise milestones and deliverables for the various research activities is presented. We conclude with our prolongation request towards the LHCC.

  15. Long-term dietary restriction up-regulates activity and expression of renal arginase II in aging mice.

    Science.gov (United States)

    Majaw, T; Sharma, R

    2017-06-01

    Arginase II is a mitochondrial enzyme that catalyses the hydrolysis of L-arginine into urea and ornithine. It is present in other extra-hepatic tissues that lack urea cycle. Therefore, it is plausible that arginase II has a physiological role other than urea cycle which includes polyamine, proline, glutamate synthesis and regulation of nitric oxide production. The high expression of arginase II in kidney, among extrahepatic tissues, might have an important role associated with kidney functions. The present study is aimed to determine the age-associated alteration in the activity and expression of arginase II in the kidney of mice of different ages. The effect of dietary restriction to modulate the agedependent changes of arginase II was also studied. Results showed that renal arginase II activity declines significantly with the progression of age (p less than 0.01 and p less than 0.001 in 6- and 18-month-old mice, respectively as compared to 2-month old mice) and is due to the reduction in its protein as well as the mRNA level (p less than 0.001 in both 6- and 18-month-old mice as compared to 2-month-old mice). Long-term dietary restriction for three months has significantly up-regulated arginase II activity and expression level in both 2- and 18-month-old mice (p less than 0.01 and p less than 0.001, respectively as compared to AL group). These findings clearly indicate that the reducing level of arginase II during aging might have an impact on the declining renal functions. This age-dependent down-regulation of arginase II in the kidney can be attenuated by dietary restriction which may help in the maintenance of such functions.

  16. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

    Directory of Open Access Journals (Sweden)

    Sachin Gupta

    Full Text Available Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG, including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1. Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5 expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration.

  17. Physical activity and psychological well-being in obese pregnant and postpartum women attending a weight-gain restriction programme.

    Science.gov (United States)

    Claesson, Ing-Marie; Klein, Sofia; Sydsjö, Gunilla; Josefsson, Ann

    2014-01-01

    the objective of the study was to compare the differences in psychological well-being and quality of life during pregnancy and post partum of obese physically active women and obese physically inactive women enroled in a weight gain restriction programme. We also wanted to explore whether physical activity influences weight change or health status during pregnancy. a prospective intervention study. antenatal care clinic. a total of 74 obese pregnant women in a physically active group and 79 obese women in a physically inactive group. the women kept diaries of their physical activity during pregnancy and answered the Beck Anxiety Inventory, the Edinburgh Postnatal Depression Scale and Medical Study Short-Form Health Survey in gestational weeks 15 and 35 and 11 weeks post partum. Physical activity was measured in metabolic equivalents. the physically active women experienced fewer depressive symptoms and estimated an improved quality of life during their pregnancies as measured by physical functioning, bodily pain, social functioning, role limitations due to emotional problems and general mental health as compared with the physically inactive women. There were no differences between the groups in gestational weight gain or weight change from early pregnancy to post partum or in prevalence of complications. physical activity among obese pregnant women provides better psychological well-being and improved quality of life, but does not prevent weight change. staff at Antenatal Care Clinics that face obese pregnant women, should encourage and emphasise the benefits of being physically active throughout pregnancy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. cAMP-response Element-binding Protein (CREB) and NF-κB Transcription Factors Are Activated during Prolonged Hypoxia and Cooperatively Regulate the Induction of Matrix Metalloproteinase MMP1*

    Science.gov (United States)

    Nakayama, Koh

    2013-01-01

    Responses to low levels of oxygen (hypoxia) are essential to maintain homeostasis. During the hypoxic response, gene expression is altered by various transcription factors. The transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxic response. The α subunit of HIF, which is actively degraded during normoxia, becomes stabilized during hypoxia, which leads to HIF activation. A microarray analysis of HeLa cells showed that expression of matrix metalloproteinase 1 (MMP1) was markedly induced during prolonged hypoxia. CREB and NF-κB binding sites were identified in the MMP1 promoter region between 1945 and 1896 nucleotides upstream of the transcription start site. Assays with luciferase reporters demonstrated that HIF activity was induced during the early phase of hypoxia, whereas CREB and NF-κB were activated during the later (prolonged) phase. Depletion of CREB and/or NF-κB reduced MMP1 induction during prolonged hypoxia both at the mRNA and protein levels. A chromatin immunoprecipitation assay demonstrated binding of CREB and NF-κB to the MMP1 promoter. Finally, cell migration and invasion on a collagen matrix and pulmonary metastasis in nude mice were inhibited after depletion of CREB and NF-κB in MDA-MB-231 cells. Taken together, these results suggest that the cooperative action of CREB and NF-κB plays an important role to induce MMP1 expression during prolonged hypoxia and regulates cell migration and invasion in cancer cells. PMID:23775082

  19. Prevalence and Stability of Active Play, Restricted Movement and Television Viewing in Infants

    Science.gov (United States)

    Hesketh, Kylie D.; Crawford, David A.; Abbott, Gavin; Campbell, Karen J.; Salmon, Jo

    2015-01-01

    This study describes engagement in and stability of physical activity and sedentary behaviours in early life, and assesses associations with sex, maternal education and developmental stage. Maternal-report data at child age 4, 9 and 20 months were collected from 542 families in the Melbourne Infant Feeding Activity and Nutrition Trial Program.…

  20. Sodium restriction potentiates the renoprotective effects of combined vitamin D receptor activation and angiotensin-converting enzyme inhibition in established proteinuric nephropathy.

    NARCIS (Netherlands)

    Mirkovic, K.; Frenay, A.S.; Born, J. van den; Goor, H van; Navis, G.; Borst, M.H. de; Bindels, R.J.M.; Hoenderop, J.G.J.; Hillebrands, J.L.

    2017-01-01

    BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade provides renoprotective effects in chronic kidney disease (CKD); yet progressive renal function loss remains common. Dietary sodium restriction potentiates the renoprotective effects of RAAS blockade. Vitamin D receptor activator

  1. [Intra-rater Reliability for the Questionnaire on Activity Limitations and Participation Restrictions of Children With ADHD].

    Science.gov (United States)

    Salamanca Duque, Luisa Matilde; Naranjo Aristizábal, María Mercedes; Gutiérrez Ríos, Gladys Helena; Prieto, Jaime Bayona

    2014-03-01

    Questionnaires for evaluating activity limitations and participation restrictions in children with ADHD (CLARP-TDAH) has recently been developed in Colombia, based on the suggestions made by the WHO from the International Classification of Functioning, Disability and Health (ICF), allowing clinical evaluation beyond an evaluation of the functionality and functioning of children in their family and school environments. Previous research with the questionnaire proved useful in the multidisciplinary approach of Colombian children with ADHD. This study determines the level of intra-rater reliability for questionnaires CLARP-TDAH Parents and Teachers. The study included a non-random sample of 203 Colombian children attending school and diagnosed with ADHD. Intra-rater reliability and the reproducibility of the results was determined using the Kappa index. The informants were parents and teachers. Kappa values >0.7 were obtained for the intra-rater reliability of the questionnaire domains of CLARP-TDAH Parents, while for CLARP-TDAH Teachers domains these values were >0.8. CLARP-TDAH questionnaires are a tool with a good level of intra-rater reliability, which allows a reliable assessment of activity limitations and participation restrictions in order to determine the level of functioning at home and school. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  2. Glucocorticoid receptor activation is involved in producing abnormal phenotypes of single-prolonged stress rats: a putative post-traumatic stress disorder model.

    Science.gov (United States)

    Kohda, K; Harada, K; Kato, K; Hoshino, A; Motohashi, J; Yamaji, T; Morinobu, S; Matsuoka, N; Kato, N

    2007-08-10

    Post-traumatic stress disorder (PTSD) is a stress-related mental disorder caused by traumatic experience, and presents with characteristic symptoms, such as intrusive memories, a state of hyperarousal, and avoidance, that endure for years. Single-prolonged stress (SPS) is one of the animal models proposed for PTSD. Rats exposed to SPS showed enhanced inhibition of the hypothalamo-pituitary-adrenal (HPA) axis, which has been reliably reproduced in patients with PTSD, and increased expression of glucocorticoid receptor (GR) in the hippocampus. In this study, we characterized further neuroendocrinologic, behavioral and electrophysiological alterations in SPS rats. Plasma corticosterone recovered from an initial increase within a week, and gross histological changes and neuronal cell death were not observed in the hippocampus of the SPS rats. Behavioral analyses revealed that the SPS rats presented enhanced acoustic startle and impaired spatial memory that paralleled the deficits in hippocampal long-term potentiation (LTP) and depression. Contextual fear memory was enhanced in the rats 1 week after SPS exposure, whereas LTP in the amygdala was blunted. Interestingly, blockade of GR activation by administering 17-beta-hydroxy-11-beta-/4-/[methyl]-[1-methylethyl]aminophenyl/-17-alpha-[prop-1-ynyl]estra-4-9-diene-3-one (RU40555), a GR antagonist, prior to SPS exposure prevented potentiation of fear conditioning and impairment of LTP in the CA1 region. Altogether, SPS caused a number of behavioral changes similar to those described in PTSD, which marks SPS as a putative PTSD model. The preventive effects of a GR antagonist suggested that GR activation might play a critical role in producing the altered behavior and neuronal function of SPS rats.

  3. Effect of restricted suckling upon post-partum reproductive activity in sheep

    International Nuclear Information System (INIS)

    Lopez Barbella, S.F.; Martinez Guillen, N.D.; Combellas, J.B. de; Rondon Morales, Z.

    1990-01-01

    The post-partum reproductive performance of adult West African ewes of proven fertility was studied to assess the beneficial effect of both 14 and 18 h restricted nursing or early weaning (35 days post-lambing) on the resumption of ovarian function and conception rate at first oestrus. Although the interval from lambing to first oestrus and/or conception in the 14 h nursing (55.13±11.03 days), 18 h nursing (65.00±15.65 days) and control (59.00±13.48 days) groups did not differ, the percentage of ewes that showed oestrus (90, 60 and 50% respectively) favoured the treatment with the shortest nursing time. When lambs were weaned early, the interval from lambing to oestrus (61.40±16.50 days) did not differ significantly from that for the 14 h nursing ewes (70.10±19.37 days) but tended to be lower than for the controls (94.25±62.38 days). Since differences in response were assumed to be dependent on body condition of the individual ewes at the time of lambing, and body weight changes of the dams after lambing were correlated with progesterone hormone, plasma proteins, glucose and free fatty acids, it was assumed that the beneficial effects of the treatments on the reproductive parameters were due to the partition of nutrients towards restoration of body reserves and subsequently to the secretion of progesterone. (author). 27 refs, 2 figs, 3 tabs

  4. Repetitive and retinotopically restricted activation of the dorsal lateral geniculate nucleus with optogenetics.

    Directory of Open Access Journals (Sweden)

    Alexandre Castonguay

    Full Text Available Optogenetics allows the control of cellular activity using focused delivery of light pulses. In neuroscience, optogenetic protocols have been shown to efficiently inhibit or stimulate neuronal activity with a high temporal resolution. Among the technical challenges associated with the use of optogenetics, one is the ability to target a spatially specific population of neurons in a given brain structure. To address this issue, we developed a side-illuminating optical fiber capable of delivering light to specific sites in a target nucleus with added flexibility through rotation and translation of the fiber and by varying the output light power. The designed optical fiber was tested in vivo in visual structures of ChR2-expressing transgenic mice. To assess the spatial extent of neuronal activity modulation, we took advantage of the hallmark of the visual system: its retinotopic organization. Indeed, the relative position of ganglion cells in the retina is transposed in the cellular topography of both the dorsal lateral geniculate nucleus (LGN in the thalamus and the primary visual cortex (V1. The optical fiber was inserted in the LGN and by rotating it with a motor, it was possible to sequentially activate different neuronal populations within this structure. The activation of V1 neurons by LGN projections was recorded using intrinsic optical imaging. Increasing light intensity (from 1.4 to 8.9 mW/mm² led to increasing activation surfaces in V1. Optogenetic stimulation of the LGN at different translational and rotational positions was associated with different activation maps in V1. The position and/or orientation of the fiber inevitably varied across experiments, thus limiting the capacity to pool data. With the optogenetic design presented here, we demonstrate for the first time a transitory and spatially-concise activation of a deep neuronal structure. The optogenetic design presented here thus opens a promising avenue for studying the function

  5. Francisella tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel Activity.

    Science.gov (United States)

    Shakerley, Nicole L; Chandrasekaran, Akshaya; Trebak, Mohamed; Miller, Barbara A; Melendez, J Andrés

    2016-02-19

    As an innate defense mechanism, macrophages produce reactive oxygen species that weaken pathogens and serve as secondary messengers involved in immune function. The Gram-negative bacterium Francisella tularensis utilizes its antioxidant armature to limit the host immune response, but the mechanism behind this suppression is not defined. Here we establish that F. tularensis limits Ca(2+) entry in macrophages, thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild type (live vaccine strain) or catalase-deficient F. tularensis (ΔkatG) show distinct profiles in their H2O2 scavenging rates, 1 and 0.015 pm/s, respectively. Murine alveolar macrophages infected with ΔkatG display abnormally high basal intracellular Ca(2+) concentration that did not increase further in response to H2O2. Additionally, ΔkatG-infected macrophages displayed limited Ca(2+) influx in response to ionomycin, as a result of ionophore H2O2 sensitivity. Exogenously added H2O2 or H2O2 generated by ΔkatG likely oxidizes ionomycin and alters its ability to transport Ca(2+). Basal increases in cytosolic Ca(2+) and insensitivity to H2O2-mediated Ca(2+) entry in ΔkatG-infected cells are reversed by the Ca(2+) channel inhibitors 2-aminoethyl diphenylborinate and SKF-96365. 2-Aminoethyl diphenylborinate but not SKF-96365 abrogated ΔkatG-dependent increases in macrophage actin remodeling and IL-6 secretion, suggesting a role for H2O2-mediated Ca(2+) entry through the transient receptor potential melastatin 2 (TRPM2) channel in macrophages. Indeed, increases in basal Ca(2+), actin polymerization, and IL-6 production are reversed in TRPM2-null macrophages infected with ΔkatG. Together, our findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species to temper macrophage TRPM2-mediated Ca(2+) signaling and limit host immune function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity

    Directory of Open Access Journals (Sweden)

    Suhong Qian

    2015-03-01

    Full Text Available Foot-and-mouth disease (FMD is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV. FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i apigenin inhibits FMDV infection at the viral post-entry stage; (ii apigenin does not exhibit direct extracellular virucidal activity; and (iii apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection.

  7. Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity.

    Science.gov (United States)

    Qian, Suhong; Fan, Wenchun; Qian, Ping; Zhang, Dong; Wei, Yurong; Chen, Huanchun; Li, Xiangmin

    2015-03-31

    Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection.

  8. The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function.

    Science.gov (United States)

    Wan, Lixin; Chen, Ming; Cao, Juxiang; Dai, Xiangpeng; Yin, Qing; Zhang, Jinfang; Song, Su-Jung; Lu, Ying; Liu, Jing; Inuzuka, Hiroyuki; Katon, Jesse M; Berry, Kelsey; Fung, Jacqueline; Ng, Christopher; Liu, Pengda; Song, Min Sup; Xue, Lian; Bronson, Roderick T; Kirschner, Marc W; Cui, Rutao; Pandolfi, Pier Paolo; Wei, Wenyi

    2017-04-01

    BRAF drives tumorigenesis by coordinating the activation of the RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathways governing BRAF kinase activity and protein stability remain undefined. Here, we report that in primary cells with active APC FZR1 , APC FZR1 earmarks BRAF for ubiquitination-mediated proteolysis, whereas in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases. Phosphorylation of FZR1 inhibits APC FZR1 , leading to elevation of a cohort of oncogenic APC FZR1 substrates to facilitate melanomagenesis. Importantly, CDK4 and/or BRAF/MEK inhibitors restore APC FZR1 E3 ligase activity, which might be critical for their clinical effects. Furthermore, FZR1 depletion cooperates with AKT hyperactivation to transform primary melanocytes, whereas genetic ablation of Fzr1 synergizes with Pten loss, leading to aberrant coactivation of BRAF/ERK and AKT signaling in mice. Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis. Significance: FZR1 inhibits BRAF oncogenic functions via both APC-dependent proteolysis and APC-independent disruption of BRAF dimers, whereas hyperactivated ERK and CDK4 reciprocally suppress APC FZR1 E3 ligase activity. Aberrancies in this newly defined signaling network might account for BRAF hyperactivation in human cancers, suggesting that targeting CYCLIN D1/CDK4, alone or in combination with BRAF/MEK inhibition, can be an effective anti-melanoma therapy. Cancer Discov; 7(4); 424-41. ©2017 AACR. See related commentary by Zhang and Bollag, p. 356 This article is highlighted in the In This Issue feature, p. 339 . ©2017 American Association for Cancer Research.

  9. Water restriction and heat effects on thyroid activity in ad libitium and force-fed cattle exposed to 180C and 320C

    International Nuclear Information System (INIS)

    Kamal, T.H.; Johnson, H.D.

    1976-01-01

    Seven non-lactating Holstein cows were maintained in a climatic laboratory for two weeks at 18 0 C and 50% relative humidity, followed by two weeks at 32 0 C and 50% relative humidity. Water was provided ad libitum in the first week and restricted 50% of the ad libitum level in the second week. Thyroid activity, determined by the 125 I-triiodothyronine uptake with coated charcoal, decreased 10.9% (P 0 C. Water restriction at 32 0 C did not depress thyroid activity because environmental heat had already decreased thyroid activity to a low level. High ambient temperature depressed thyroid activity 14.7% in ad libitum cows (P<0.01) and a further 1.8% in water-restricted cows. Similar effects of water restriction and heat were obtained when the same experiment was repeated on four non-lactating rumen-fistulated cows, in which the refused feed during the water restriction periods was put into the rumen to maintain the feed levels for each temperature exposure. This indicated that forced feeding did not prevent the adverse effect of water restriction or heat on thyroid activity. (author)

  10. In utero exposure to heat stress during late gestation has prolonged effects on the activity patterns and growth of dairy calves.

    Science.gov (United States)

    Laporta, J; Fabris, T F; Skibiel, A L; Powell, J L; Hayen, M J; Horvath, K; Miller-Cushon, E K; Dahl, G E

    2017-04-01

    Exposure to heat stress during late gestation exerts negative carryover effects on the postnatal performance of the calf. In this study, we evaluated the health, growth, and activity patterns of calves born to cows exposed to heat stress (HT, provided only shade, n = 31) or cooling (CL, fans, soakers, and shade, n = 29) during late gestation (∼46 d, maternal dry period). Calves' body weight, rectal temperature, suckling reflex, and movement scores were recorded at birth, and calves were fed 6.6 L of maternal colostrum in 2 meals. Blood samples were collected at birth (before feeding), 24 h after birth, and at d 10 and 28 of age. Calves were housed in individual pens, fed pasteurized milk (6 L/d), and had ad libitum access to grain and water until weaning (49 d). Activity was assessed during the first week of life (wk 1), at weaning (wk 7), and in the first week postweaning (wk 8) using electronic data loggers. Health and body weight were monitored weekly. At birth, calves born to CL cows were heavier (41.9 vs. 39.1 ± 0.8 kg), their temperature was lower (38.9 vs. 39.3 ± 0.08°C), and they were more efficient at absorbing IgG than HT calves. Suckling reflex and movement score at birth were not different between groups, but calves born to CL cows spent more time (50 min/d) standing in the first week of life as a result of longer standing bouts. In wk 7 and 8, calves born to CL cows had less frequent standing bouts than HT heifers, but CL heifers maintained greater total daily standing time (36 min/d) due to longer (7 min/bout) standing bouts. All calves were healthy, but HT heifers tended to have higher (looser) fecal scores on d 10. Heifers born from CL cows gained 0.2 kg/d more from birth to weaning, weighed 4 kg more at weaning, and had greater concentrations of IGF-1 than HT calves, particularly on d 28. In utero heat stress during late gestation had immediate and prolonged effects on passive immunity, growth, and activity patterns in dairy calves. Copyright

  11. Immigration Restrictions as Active Labor Market Policy: Evidence from the Mexican Bracero Exclusion

    OpenAIRE

    Clemens, Michael A.; Lewis, Ethan Gatewood; Postel, Hannah M.

    2017-01-01

    An important class of active labor market policy has received little rigorous impact evaluation: immigration barriers intended to improve the terms of employment for domestic workers by deliberately shrinking the workforce. Recent advances in the theory of endogenous technical change suggest that such policies could have limited or even perverse labor-market effects, but empirical tests are scarce. We study a natural experiment that excluded almost half a million Mexican 'bracero' seasonal ag...

  12. Restricted expression of recombination activating gene (RAG-1) in mouse lymphoid tissues

    International Nuclear Information System (INIS)

    Yamamoto, Akihito; Fujinaga, Hiroyuki; Hamatani, Kiyohiro; Atsuta, Mitsuru.

    1993-03-01

    In an attempt to determine the distribution of recombinase activity in the mouse thymus, spleen, and lymph nodes, we used the in situ hybridization method to examine the expression of the recombination activating genes RAG-1 and RAG-2. Expression of RAG-1 was found in most cortical thymocytes but not in the majority of medullary thymocytes. Although hybridization signals of RAG-2 were not as intense as those of RAG-1, the localization of RAG-2 transcripts was similar to that of RAG-1. In the spleen, expression of RAG-1 was found only in limited cells near the splenic sinus, and the majority of the cells within the follicle were negative for RAG-1 transcript. In nude mice, RAG-1-expressing cells were detected in the same regions, which suggests that in situ hybridization signals of RAG-1 in the spleen are due to the cells of B-cell origin. In the lymph nodes, expression of RAG-1 was found only in the medullary region. Expression of RAG-2 transcript in the spleen and the lymph nodes, if any, was too faint to allow determination of the specific localization. These results suggest that most of the cortical thymocytes and some cells in the spleen are capable of rearranging T-cell receptor genes and immunoglobulin genes, respectively, but the possible involvement of the RAG-1 transcript in RAG-1-positive cells of the spleen and the lymph nodes in functions other than the rearrangement of genes could not be ruled out. (author)

  13. Caloric restriction counteracts age-related changes in the activities of sorbitol metabolizing enzymes from mouse liver

    Science.gov (United States)

    Hagopian, Kevork; Ramsey, Jon J.; Weindruch, Richard

    2009-01-01

    The influence of caloric restriction (CR) on hepatic sorbitol-metabolizing enzyme activities was investigated in young and old mice. Aldose reductase and sorbitol dehydrogenase activities were significantly lower in old CR mice than in old controls. Young CR mice showed decreased aldose reductase activity and a trend towards decreased sorbitol dehydrogenase when compared to controls. Metabolites of the pathway, namely sorbitol, glucose and fructose were decreased by CR in young and old mice. Pyruvate levels were decreased by CR in both young and old mice, while lactate decreased only in old CR. Malate levels increased in old CR but remained unchanged in young CR, when compared with controls. Accordingly, the lactae/pyruvate and malate/pyruvate ratios in young and old CR mice were increased, indicating increased NADH/NAD and NADPH/NADP redox couples, respectively. The results indicate that decreased glucose levels under CR conditions lead to decreased sorbitol pathway enzyme activities and metabolite levels, and could contribute to the beneficial effects of long-term CR through decreased sorbitol levels and NADPH sparing. PMID:18953666

  14. Pain and symptoms of depression in older adults living in community and in nursing homes: the role of activity restriction as a potential mediator and moderator.

    Science.gov (United States)

    López-Lopez, Almudena; González, José L; Alonso-Fernández, Miriam; Cuidad, Noelia; Matías, Borja

    2014-10-01

    Chronic pain is likely to lead to depressive symptoms, but the nature of this relationship is not completely clear. The aim of the present study is to analyze the role of activity restriction in the pain-depression relationship in older people, and to test the hypothesis that this role is more relevant in community-dwelling older people than in nursing home residents. Depressive symptoms, pain intensity, and activity restriction were measured in a sample of 208 older adults with osteoarthritis, 102 living in nursing homes (NH), and 106 in the community. Analyses were carried out using moderation and moderated mediation analyses approach, treating activity restriction as a confounder. RESULTS showed a significant confounding effect of activity restriction, interaction effect between pain intensity and activity restriction on depression, and modifying effect of pain intensity on depression by adding activity restriction into the model. These results suggest a potential mediating and moderating effects of activity restriction. Moreover, analyses suggest that, surprisingly, the strength of the mediation could be higher in nursing homes. Overall, it may be that what is really important to emotional well-being is not so much pain itself, but rather the way in which the pain alters older people's lives. The greater strength of the mediation in NH might be understood within the scope of self-determination theory. Generally speaking, the NH context has been considered as a coercive setting, promoting non-autonomous orientation. In this context, when events are objectively coercive, people may lack perceived autonomy and hence be at greater risk of depression.

  15. Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    2009-05-01

    Full Text Available Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host-cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIV(smm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIV(mac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIV(smm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts.

  16. Effect of ionizing radiation on the activity of restriction nucleases PvuII and HindIII

    International Nuclear Information System (INIS)

    Luzova, M.; Michaelidesova, A.; Davidkova, M.

    2014-01-01

    The research is focused on the influence of the ionizing radiation on the activity of the restriction enzymes PvuII and HindIII. Enzymes PvuII and HindIII are restriction endonucleases of type II. These enzymes can be found in bacteria and they have a significant role in defense mechanisms of bacteria against viruses. They cleave DNA double helix at specific recognition palindromic sequences in the presence of cofactor Mg 2+ . PvuII cleaves the sequence CAG↓CTG and HindIII cleaves the sequence A↓AGCTT in marked places. Plasmid pcDNA3 has been used as the DNA substrate for the whole experimental study. It is 5446 base pairs (bp) long, circular DNA molecule and it contains three recognition sites for enzyme PvuII and one recognition site for enzyme HindIII. After the correct interaction of pcDNA3 with PvuII, we thus have three plasmid fragments with lengths 1069, 1097 and 3280 bp. When HindIII is incubated with this plasmid, we shall obtain the linear form of the DNA plasmid.The method for processing the cleaved DNA samples is the agarose gel electrophoresis. The activity of the irradiated enzymes decreases with increasing dose of radiation, because a part of the enzymes is deactivated due to induced radiation damage. To determine effect of radiation quality, samples were irradiated using proton and gamma sources. The results of our experimental study will be presented and discussed with respect to molecular structure of both enzymes and particular sites of radical damage influencing their function. (authors)

  17. Polycomb repressive complex 2 (PRC2 restricts hematopoietic stem cell activity.

    Directory of Open Access Journals (Sweden)

    Ian J Majewski

    2008-04-01

    Full Text Available Polycomb group proteins are transcriptional repressors that play a central role in the establishment and maintenance of gene expression patterns during development. Using mice with an N-ethyl-N-nitrosourea (ENU-induced mutation in Suppressor of Zeste 12 (Suz12, a core component of Polycomb Repressive Complex 2 (PRC2, we show here that loss of Suz12 function enhances hematopoietic stem cell (HSC activity. In addition to these effects on a wild-type genetic background, mutations in Suz12 are sufficient to ameliorate the stem cell defect and thrombocytopenia present in mice that lack the thrombopoietin receptor (c-Mpl. To investigate the molecular targets of the PRC2 complex in the HSC compartment, we examined changes in global patterns of gene expression in cells deficient in Suz12. We identified a distinct set of genes that are regulated by Suz12 in hematopoietic cells, including eight genes that appear to be highly responsive to PRC2 function within this compartment. These data suggest that PRC2 is required to maintain a specific gene expression pattern in hematopoiesis that is indispensable to normal stem cell function.

  18. Restrictive cardiomyopathy

    Science.gov (United States)

    ... People with restrictive cardiomyopathy may be heart transplant candidates. The outlook depends on the cause of the ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  19. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice

    DEFF Research Database (Denmark)

    Liu, Yawei; Teige, Anna; Mondoc, Emma

    2011-01-01

    NKT cells in the mouse recognize antigen in the context of the MHC class I-like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition...... in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707-721), was not associated...... with either MHC class I or II. Activation of CD1d-restricted mCII707-721-specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707-721-specific NKT cells induced T cell death through Fas/FasL, in an IL-17A-independent fashion. Moreover, mCII707-721-specific NKT cells...

  20. Effect of calorie restriction on spontaneous physical activity and body mass in mice divergently selected for basal metabolic rate (BMR).

    Science.gov (United States)

    Brzęk, Paweł; Gębczyński, Andrzej K; Książek, Aneta; Konarzewski, Marek

    2016-07-01

    Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass ('thrifty genotype hypothesis'). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Mutagenesis of the redox-active disulfide in mercuric ion reductase: Catalysis by mutant enzymes restricted to flavin redox chemistry

    International Nuclear Information System (INIS)

    Distefano, M.D.; Au, K.G.; Walsh, C.T.

    1989-01-01

    Mercuric reductase, a flavoenzyme that possesses a redox-active cystine, Cys 135 Cys 140 , catalyzes the reduction of Hg(II) to Hg(0) by NADPH. As a probe of mechanism, the authors have constructed mutants lacking a redox-active disulfide by eliminating Cys 135 (Ala 135 Cys 140 ), Cys 14 (Cys 135 Ala 140 ), or both (Ala 135 Ala 140 ). Additionally, they have made double mutants that lack Cys 135 (Ala 135 Cys 139 Cys 140 ) or Cys 140 (Cys 135 Cys 139 Ala 140 ) but introduce a new Cys in place of Gly 139 with the aim of constructing dithiol pairs in the active site that do not form a redox-active disulfide. The resulting mutant enzymes all lack redox-active disulfides and are hence restricted to FAD/FADH 2 redox chemistry. Each mutant enzyme possesses unique physical and spectroscopic properties that reflect subtle differences in the FAD microenvironment. Preliminary evidence for the Ala 135 Cys 139 Cys 14 mutant enzyme suggests that this protein forms a disulfide between the two adjacent Cys residues. Hg(II) titration experiments that correlate the extent of charge-transfer quenching with Hg(II) binding indicate that the Ala 135 Cys 140 protein binds Hg(II) with substantially less avidity than does the wild-type enzyme. All mutant mercuric reductases catalyze transhydrogenation and oxygen reduction reactions through obligatory reduced flavin intermediates at rates comparable to or greater than that of the wild-type enzyme. In multiple-turnover assays which monitored the production of Hg(0), two of the mutant enzymes were observed to proceed through at least 30 turnovers at rates ca. 1000-fold slower than that of wild-type mercuric reductase. They conclude that the Cys 135 and Cys 140 thiols serve as Hg(II) ligands that orient the Hg(II) for subsequent reduction by a reduced flavin intermediate

  2. Cost and sensitivity of restricted active-space calculations of metal L-edge X-ray absorption spectra.

    Science.gov (United States)

    Pinjari, Rahul V; Delcey, Mickaël G; Guo, Meiyuan; Odelius, Michael; Lundberg, Marcus

    2016-02-15

    The restricted active-space (RAS) approach can accurately simulate metal L-edge X-ray absorption spectra of first-row transition metal complexes without the use of any fitting parameters. These characteristics provide a unique capability to identify unknown chemical species and to analyze their electronic structure. To find the best balance between cost and accuracy, the sensitivity of the simulated spectra with respect to the method variables has been tested for two models, [FeCl6 ](3-) and [Fe(CN)6 ](3-) . For these systems, the reference calculations give deviations, when compared with experiment, of ≤1 eV in peak positions, ≤30% for the relative intensity of major peaks, and ≤50% for minor peaks. When compared with these deviations, the simulated spectra are sensitive to the number of final states, the inclusion of dynamical correlation, and the ionization potential electron affinity shift, in addition to the selection of the active space. The spectra are less sensitive to the quality of the basis set and even a double-ζ basis gives reasonable results. The inclusion of dynamical correlation through second-order perturbation theory can be done efficiently using the state-specific formalism without correlating the core orbitals. Although these observations are not directly transferable to other systems, they can, together with a cost analysis, aid in the design of RAS models and help to extend the use of this powerful approach to a wider range of transition metal systems. © 2015 Wiley Periodicals, Inc.

  3. Restricted active space calculations of L-edge X-ray absorption spectra: from molecular orbitals to multiplet states.

    Science.gov (United States)

    Pinjari, Rahul V; Delcey, Mickaël G; Guo, Meiyuan; Odelius, Michael; Lundberg, Marcus

    2014-09-28

    The metal L-edge (2p → 3d) X-ray absorption spectra are affected by a number of different interactions: electron-electron repulsion, spin-orbit coupling, and charge transfer between metal and ligands, which makes the simulation of spectra challenging. The core restricted active space (RAS) method is an accurate and flexible approach that can be used to calculate X-ray spectra of a wide range of medium-sized systems without any symmetry constraints. Here, the applicability of the method is tested in detail by simulating three ferric (3d(5)) model systems with well-known electronic structure, viz., atomic Fe(3+), high-spin [FeCl6](3-) with ligand donor bonding, and low-spin [Fe(CN)6](3-) that also has metal backbonding. For these systems, the performance of the core RAS method, which does not require any system-dependent parameters, is comparable to that of the commonly used semi-empirical charge-transfer multiplet model. It handles orbitally degenerate ground states, accurately describes metal-ligand interactions, and includes both single and multiple excitations. The results are sensitive to the choice of orbitals in the active space and this sensitivity can be used to assign spectral features. A method has also been developed to analyze the calculated X-ray spectra using a chemically intuitive molecular orbital picture.

  4. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    Science.gov (United States)

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. © 2013 John Wiley & Sons Ltd.

  5. Endogenous collagen peptide activation of CD1d-restricted NKT cells ameliorates tissue-specific inflammation in mice.

    Science.gov (United States)

    Liu, Yawei; Teige, Anna; Mondoc, Emma; Ibrahim, Saleh; Holmdahl, Rikard; Issazadeh-Navikas, Shohreh

    2011-01-01

    NKT cells in the mouse recognize antigen in the context of the MHC class I-like molecule CD1d and play an important role in peripheral tolerance and protection against autoimmune and other diseases. NKT cells are usually activated by CD1d-presented lipid antigens. However, peptide recognition in the context of CD1 has also been documented, although no self-peptide ligands have been reported to date. Here, we have identified an endogenous peptide that is presented by CD1d to activate mouse NKT cells. This peptide, the immunodominant epitope from mouse collagen type II (mCII707-721), was not associated with either MHC class I or II. Activation of CD1d-restricted mCII707-721-specific NKT cells was induced via TCR signaling and classical costimulation. In addition, mCII707-721-specific NKT cells induced T cell death through Fas/FasL, in an IL-17A-independent fashion. Moreover, mCII707-721-specific NKT cells suppressed a range of in vivo inflammatory conditions, including delayed-type hypersensitivity, antigen-induced airway inflammation, collagen-induced arthritis, and EAE, which were all ameliorated by mCII707-721 vaccination. The findings presented here offer new insight into the intrinsic roles of NKT cells in health and disease. Given the results, endogenous collagen peptide activators of NKT cells may offer promise as novel therapeutics in tissue-specific autoimmune and inflammatory diseases.

  6. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes.

    Science.gov (United States)

    Xu, Lei; Zhou, Xinying; Wang, Wenshi; Wang, Yijin; Yin, Yuebang; Laan, Luc J W van der; Sprengers, Dave; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2016-10-01

    IFN regulatory factor 1 (IRF1) is one of the most important IFN-stimulated genes (ISGs) in cellular antiviral immunity. Although hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide, how ISGs counteract HEV infection is largely unknown. This study was conducted to investigate the effect of IRF1 on HEV replication. Multiple cell lines were used in 2 models that harbor HEV. In different HEV cell culture systems, IRF1 effectively inhibited HEV replication. IRF1 did not trigger IFN production, and chromatin immunoprecipitation sequencing data analysis revealed that IRF1 bound to the promoter region of signal transducers and activators of transcription 1 (STAT1). Functional assay confirmed that IRF1 could drive the transcription of STAT1, resulting in elevation of total and phosphorylated STAT1 proteins and further activating the transcription of a panel of downstream antiviral ISGs. By pharmacological inhibitors and RNAi-mediated gene-silencing approaches, we revealed that antiviral function of IRF1 is dependent on the JAK-STAT cascade. Furthermore, induction of ISGs and the anti-HEV effect of IRF1 overlapped that of IFNα, but was potentiated by ribavirin. We demonstrated that IRF1 effectively inhibits HEV replication through the activation of the JAK-STAT pathway, and the subsequent transcription of antiviral ISGs, but independent of IFN production.-Xu, L., Zhou, X., Wang, W., Wang, Y., Yin, Y., van der Laan, L. J. W., Sprengers, D., Metselaar, H. J., Peppelenbosch, M. P., Pan, Q. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes. © FASEB.

  7. Hypoxia activates muscle-restricted coiled-coil protein (MURC) expression via transforming growth factor-β in cardiac myocytes.

    Science.gov (United States)

    Shyu, Kou-Gi; Cheng, Wen-Pin; Wang, Bao-Wei; Chang, Hang

    2014-03-01

    The expression of MURC (muscle-restricted coiled-coil protein), a hypertrophy-regulated gene, increases during pressure overload. Hypoxia can cause myocardial hypertrophy; however, how hypoxia affects the regulation of MURC in cardiomyocytes undergoing hypertrophy is still unknown. The aim of the present study was to test the hypothesis that hypoxia induces MURC expression in cardiomyocytes during hypertrophy. The expression of MURC was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia and in an in vivo model of AMI (acute myocardial infarction) to induce myocardial hypoxia in adult rats. MURC protein and mRNA expression were significantly enhanced by hypoxia. MURC proteins induced by hypoxia were significantly blocked after the addition of PD98059 or ERK (extracellular-signal-regulated kinase) siRNA 30 min before hypoxia. Gel-shift assay showed increased DNA-binding activity of SRF (serum response factor) after hypoxia. PD98059, ERK siRNA and an anti-TGF-β (transforming growth factor-β) antibody abolished the SRF-binding activity enhanced by hypoxia or exogenous administration of TGF-β. A luciferase promoter assay demonstrated increased transcriptional activity of SRF in cardiomyocytes by hypoxia. Increased βMHC (β-myosin heavy chain) and BNP (B-type natriuretic peptide) protein expression and increased protein synthesis was identified after hypoxia with the presence of MURC in hypertrophic cardiomyocytes. MURC siRNA inhibited the hypertrophic marker protein expression and protein synthesis induced by hypoxia. AMI in adult rats also demonstrated increased MURC protein expression in the left ventricular myocardium. In conclusion, hypoxia in cultured rat neonatal cardiomyocytes increased MURC expression via the induction of TGF-β, SRF and the ERK pathway. These findings suggest that MURC plays a role in hypoxia-induced hypertrophy in cardiomyocytes.

  8. Restrictive Cardiomyopathy

    Science.gov (United States)

    ... up in the circulatory system. In time, the heart fails. What causes it? Restrictive cardiomyopathy is often caused by diseases in other parts of the body. One known cause is cardiac ... build up in the heart tissue, making the tissue stiff and thickened. Cardiac ...

  9. Effects of Blood-Flow Restriction Combined With Postactivation Potentiation Stimuli on Jump Performance in Recreationally Active Men.

    Science.gov (United States)

    Miller, Ryan M; Keeter, Victoria M; Freitas, Eduardo D S; Heishman, Aaron D; Knehans, Allen W; Bemben, Debra A; Bemben, Michael G

    2018-07-01

    Miller, RM, Keeter, VM, Freitas, EDS, Heishman, AD, Knehans, AW, Bemben, DA, and Bemben, MG. Effects of blood-flow restriction combined with postactivation potentiation stimuli on jump performance in recreationally active men. J Strength Cond Res 32(7): 1869-1874, 2018-Whole-body vibration (WBV) and maximum voluntary contractions (MVCs) combined with blood-flow restriction (BFR) to augment postactivation potentiation have yet to be examined. Therefore, the purpose of this investigation was to examine the augmented effects of postactivation potentiation when WBV and MVC are combined with BFR. Twenty men (21.8 ± 2.6 years, 180.5 ± 6.2 cm and 84.5 ± 12.1 kg) completed the study. Participants completed 3 testing sessions in a randomized design that included one of the following: (a) control (CON), (b) WBV and WBV combined with BFR (WBV + BFR), or (c) MVC and MVC combined with BFR (MVC + BFR). Jump height and power were recorded for 3 trials, PRE and POST jump height (cm) mean ± SD for each were as follows: CON 58.9 ± 8.6 and 57.9 ± 8.6, WBV 58.2 ± 8.1 and 59.9 ± 8.1, WBV + BFR 58.7 ± 7.6 and 60.2 ± 8.1, MVC 59.7 ± 7.4 and 60.2 ± 8.6, and MVC + BFR 57.7 ± 7.9 and 59.4 ± 8.1. PRE and POST jump power (W) mean ± SD for each were as follows: CON 1,224.3 ± 221.5 and 1,234.3 ± 189.2, WBV 1,251.1 ± 230.4 and 1,266.1 ± 215.7, WBV + BFR 1,265.8 ± 207.9 and 1,259 ± 223.3, MVC 1,264.7 ± 211.9 and 1,263.5 ± 236.5, and MVC + BFR 1,252.3 ± 222.0 and 1,294.6 ± 256.6. Significant differences were revealed in jump height between the 5 interventions (p jump power. In conclusion, the results of this study indicate that WBV, WBV + BFR, and MVC + BFR significantly improve jump height and time in air but not jump power.

  10. Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

    Science.gov (United States)

    Yamamoto, Tsunehisa; Tamaki, Kayoko; Shirakawa, Kohsuke; Ito, Kentaro; Yan, Xiaoxiang; Katsumata, Yoshinori; Anzai, Atsushi; Matsuhashi, Tomohiro; Endo, Jin; Inaba, Takaaki; Tsubota, Kazuo; Sano, Motoaki; Fukuda, Keiichi; Shinmura, Ken

    2016-04-15

    Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting

  11. Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

    Directory of Open Access Journals (Sweden)

    Arun Kapoor

    Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

  12. Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera: Calliphoridae.

    Directory of Open Access Journals (Sweden)

    Paul C Coleman

    Full Text Available Virtually all temperate insects survive the winter by entering a physiological state of reduced metabolic activity termed diapause. However, there is increasing evidence that climate change is disrupting the diapause response resulting in non-diapause life stages encountering periods of winter cold. This is a significant problem for adult life stages in particular, as they must remain mobile, periodically feed, and potentially initiate reproductive development at a time when resources should be diverted to enhance stress tolerance. Here we present the first evidence of protein/meat feeding restricting rapid cold hardening (RCH ability and increasing low temperature activity thresholds. No RCH response was noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy fed a sugar, water and liver (SWL diet, while a strong RCH response was seen in females fed a diet of sugar and water (SW only. The RCH response in SW flies was induced at temperatures as high as 10°C, but was strongest following 3h at 0°C. The CTmin (loss of coordinated movement and chill coma (final appendage twitch temperature of SWL females (-0.3 ± 0.5°C and -4.9 ± 0.5°C, respectively was significantly higher than for SW females (-3.2 ± 0.8°C and -8.5 ± 0.6°C. We confirmed this was not directly the result of altered extracellular K+, as activity thresholds of alanine-fed adults were not significantly different from SW flies. Instead we suggest the loss of cold tolerance is more likely the result of diverting resource allocation to egg development. Between 2009 and 2013 winter air temperatures in Birmingham, UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively, suggesting differential exposure to chill injury depending on whether adults had access to meat or not. We conclude that disruption of diapause could significantly impact on winter survival through loss of synchrony in the timing of active feeding and reproductive development with

  13. Time-dependent restricted-active-space self-consistent eld theory: Formulation and application to laser-driven many-electron dynamics

    DEFF Research Database (Denmark)

    Miyagi, Haruhide; Madsen, Lars Bojer

    We have developed a new theoretical framework for time-dependent many-electron problems named time-dependent restricted-active-space self-consistent field (TD-RASSCF) theory. The theory generalizes the multicongurational time-dependent Hartree-Fock (MCTDHF) theory by truncating the expansion...

  14. Factors associated with fear of falling and associated activity restriction in community-dwelling older adults: a systematic review.

    Science.gov (United States)

    Denkinger, Michael D; Lukas, Albert; Nikolaus, Thorsten; Hauer, Klaus

    2015-01-01

    Fear of falling (FOF) is an important threat to autonomy. Current interventions to reduce FOF have yielded conflicting results. A possible reason for this discrepancy could be its multicausality. Some risk factors may not have been identified and addressed in recent studies. The last systematic review included studies until 2006. To identify additional risk factors for FOF and to test those mentioned previously, we conducted a systematic literature review. Studies examining FOF in community-dwelling older adults between 2006 and October 2013 were screened. Outcomes are summarized with respect to different constructs such as FOF, fall-related self-efficacy/balance confidence, and FOF-related activity restriction. Odds ratios and p values are reported. There is no clear pattern with regard to the different FOF-related constructs studied. The only parameters robustly associated across all constructs were female gender, performance-based and questionnaire-based physical function, the use of a walking aid, and, less robust, a history of falls and poor self-rated health. Conflicting results were identified for depression and anxiety, multiple drugs, and psychotropic drugs. Other potentially modifiable risk factors were only mentioned in one or two studies and warrant further investigation. Parameters with mainly negative results are also presented. Only few risk factors identified were robustly associated across all FOF-related constructs and should be included in future studies on FOF. Some newer factors have to be tested again in different cohorts. The comprehensive overview might assist in the conceptualization of future studies. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Simulations of iron K pre-edge X-ray absorption spectra using the restricted active space method.

    Science.gov (United States)

    Guo, Meiyuan; Sørensen, Lasse Kragh; Delcey, Mickaël G; Pinjari, Rahul V; Lundberg, Marcus

    2016-01-28

    The intensities and relative energies of metal K pre-edge features are sensitive to both geometric and electronic structures. With the possibility to collect high-resolution spectral data it is important to find theoretical methods that include all important spectral effects: ligand-field splitting, multiplet structures, 3d-4p orbital hybridization, and charge-transfer excitations. Here the restricted active space (RAS) method is used for the first time to calculate metal K pre-edge spectra of open-shell systems, and its performance is tested against on six iron complexes: [FeCl6](n-), [FeCl4](n-), and [Fe(CN)6](n-) in ferrous and ferric oxidation states. The method gives good descriptions of the spectral shapes for all six systems. The mean absolute deviation for the relative energies of different peaks is only 0.1 eV. For the two systems that lack centrosymmetry [FeCl4](2-/1-), the ratios between dipole and quadrupole intensity contributions are reproduced with an error of 10%, which leads to good descriptions of the integrated pre-edge intensities. To gain further chemical insight, the origins of the pre-edge features have been analyzed with a chemically intuitive molecular orbital picture that serves as a bridge between the spectra and the electronic structures. The pre-edges contain information about both ligand-field strengths and orbital covalencies, which can be understood by analyzing the RAS wavefunction. The RAS method can thus be used to predict and rationalize the effects of changes in both the oxidation state and ligand environment in a number of hard X-ray studies of small and medium-sized molecular systems.

  16. Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

    DEFF Research Database (Denmark)

    Blomqvist, Maria; Rhost, Sara; Teneberg, Susann

    2009-01-01

    The glycosphingolipid sulfatide (SO(3)-3Galbeta1Cer) is a demonstrated ligand for a subset of CD1d-restricted NKT cells, which could regulate experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as tumor immunity and experimental hepatitis. Native sulfatide...

  17. Restricted Mobilities

    DEFF Research Database (Denmark)

    Nielsen, Mette; Lassen, Claus

    2012-01-01

    communities and shopping centres through mobility lenses. The article shows how different mobility systems enable and restrict the public access to private-public spaces, and it points out that proprietary communities create an unequal potential for human movement and access in the city. The main argument......Privatisation of public spaces in the contemporary city has increased during the last decades but only few studies have approached this field from a mobility perspective. Therefore the article seeks to rectify this by exploring two Australian examples of private spaces in the city; gated...... and stratification mechanisms. In conclusion the article therefore suggests that future urban research and planning also needs a mobile understanding of spaces in the cities and how different mobility systems play an important role to sustain the exclusiveness that often characterises the private/public spaces...

  18. Acute and transient activation of pituitary-thyroid axis during unforced restriction in rats: component of nonshivering thermogenesis in conscious animals?

    Science.gov (United States)

    Langer, P; Földes, O; Macho, L; Kvetnanský, R

    1983-01-01

    Groups of 6-8 male Wistar Olac SPF rats weighing about 300 g were subjected to unforced restriction (UR) in small cages with a metallic bottom and a Plexiglas cover for various intervals from 2 min to 72 h. An acute activation of the pituitary-thyroid axis was found which was manifested by an increase of thyrotropin (TSH) and thyroxine (T4) levels at 2-5 min of UR. This was presumably due to the emotional effect of a rapid transfer and to the placing of the animals into restriction cages. Later, between 3 and 6 h of UR, another, and more pronounced period of activation of the pituitary-thyroid axis and of the peripheral thyroid hormone metabolism was repeatedly observed which lasted until about 36-48 h and was manifested by a highly significant increase of TSH, T4, 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) levels. It was concluded that this phenomenon presumably may be a component of nonshivering thermogenesis resulting from a decreased muscular activity and resembling the conditions occurring under cold stress. Such a view was supported by findings of highly increased nonesterified fatty acid levels in plasma in restricted animals, by unchanged levels of TSH and thyroid hormones found in unrestricted animals kept individually in regular group cages and, finally, by a preventive effect of ambient temperature of 32 degrees C on the pituitary-thyroid activation at 6 h of UR. In some experiments, no substantial differences in hormone levels were found between the animals kept in Plexiglas or stainless wire-mesh restriction cages. Finally, a multifold increase of prolactin level in plasma was found as early as 2 min of UR, the peak being observed between 5 and 20 min and a decrease to about the initial level at about 360 min.

  19. Prolongation of islet allograft survival

    International Nuclear Information System (INIS)

    Lacy, P.E.; Davie, J.M.; Finke, E.H.; Scharp, D.W.

    1979-01-01

    Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if hand-picked, clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier

  20. Genetic influence on prolonged gestation

    DEFF Research Database (Denmark)

    Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

    2004-01-01

    OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

  1. Beta-lactam antibiotic-induced platelet dysfunction: Evidence for irreversible inhibition of platelet activation in vitro and in vivo after prolonged exposure to penicillin

    International Nuclear Information System (INIS)

    Burroughs, S.F.; Johnson, G.J.

    1990-01-01

    beta-Lactam antibiotics cause platelet dysfunction with bleeding complications. Previous in vitro studies documented reversible inhibition of agonist-receptor interaction. This mechanism is inadequate to explain the effect of beta-lactam antibiotics in vivo. Platelet function does not return to normal immediately after drug treatment, implying irreversible inhibition of platelet function. We report here evidence of irreversible platelet functional and biochemical abnormalities after in vitro and in vivo exposure to beta-lactam antibiotics. Irreversible binding of [14C]-penicillin (Pen) occurred in vitro. After 24 hours' in vitro incubation with 10 to 20 mmol/L Pen, or ex vivo after antibiotic treatment, irreversible functional impairment occurred; but no irreversible inhibition of alpha 2 adrenergic receptors, measured with [3H]-yohimbine, or high-affinity thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors, measured with agonist [3H]-U46619 and antagonist [3H]-SQ29548, occurred. However, low-affinity platelet TXA2/PGH2 receptors were decreased 40% after Pen exposure in vitro or in vivo, indicating irreversible membrane alteration. Two postreceptor biochemical events were irreversibly inhibited in platelets incubated with Pen for 24 hours in vitro or ex vivo after antibiotic treatment. Thromboxane synthesis was inhibited 28.3% to 81.7%. Agonist-induced rises in cytosolic calcium ([Ca2+]i) were inhibited 40.1% to 67.5% in vitro and 26.6% to 52.2% ex vivo. Therefore, Pen binds to platelets after prolonged exposure, resulting in irreversible dysfunction attributable to inhibition of TXA2 synthesis and impairment of the rise in [Ca2+]i. The loss of low-affinity TXA2/PGH2 receptors suggests that the primary site of action of these drugs is on the platelet membrane

  2. The life span-prolonging effect of sirtuin-1 is mediated by autophagy.

    Science.gov (United States)

    Morselli, Eugenia; Maiuri, Maria Chiara; Markaki, Maria; Megalou, Evgenia; Pasparaki, Angela; Palikaras, Konstantinos; Criollo, Alfredo; Galluzzi, Lorenzo; Malik, Shoaib Ahmad; Vitale, Ilio; Michaud, Mickael; Madeo, Frank; Tavernarakis, Nektarios; Kroemer, Guido

    2010-01-01

    The life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. Life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase Sirtuin-1. Intrigued by these observations and by the established link between caloric restriction and Sirtuin-1 activation, we decided to investigate the putative implication of Sirtuin-1 in the response of human cancer cells and Caenorhabditis elegans to multiple triggers of autophagy. Our data indicate that the activation of Sirtuin-1 (by the pharmacological agent resveratrol and/or genetic means) per se ignites autophagy, and that Sirtuin-1 is required for the autophagic response to nutrient deprivation, in both human and nematode cells, but not for autophagy triggered by downstream signals such as the inhibition of mTOR or p53. Since the life spanextending effects of Sirtuin-1 activators are lost in autophagy-deficient C. elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy.

  3. Transient impairments in single muscle fibre contractile function after prolonged cycling in elite endurance athletes

    DEFF Research Database (Denmark)

    Hvid, L G; Gejl, Kasper Degn; Bech, R D

    2013-01-01

    Prolonged muscle activity impairs whole-muscle performance and function. However, little is known about the effects of prolonged muscle activity on the contractile function of human single muscle fibres. The purpose of this study was to investigate the effects of prolonged exercise and subsequent...... recovery on the contractile function of single muscle fibres obtained from elite athletes....

  4. Prolonged QRS Widening After Aripiprazole Overdose.

    Science.gov (United States)

    Mazer-Amirshahi, Maryann; Porter, Robert; Dewey, Kayla

    2018-05-05

    Aripiprazole is an atypical antipsychotic with a long half-life. Overdose can result in protracted somnolence and cardiac disturbances, particularly QT interval prolongation. This is a single case report of a 14-year-old boy who took an overdose of aripiprazole and developed QRS widening. A 14-year-old boy intentionally ingested 20 tablets of aripiprazole (5 mg). He was brought to the emergency department when his ingestion was discovered. The patient's vital signs were as follows: temperature, 37.7°C; heart rate, 108 beats/min; blood pressure, 138/98 mm Hg; and respirations, 16 breaths/min. Activated charcoal was administered within 90 minutes of ingestion. Initial electrocardiogram (EKG) showed sinus tachycardia, with a QRS of 138 ms and QT interval of 444 ms. QRS duration was 90 ms on an EKG performed 3 months earlier. A bolus of sodium bicarbonate was administered, and the patient was transferred to the pediatric intensive care unit. Repeat EKG demonstrated a QRS of 156 ms, and a sodium bicarbonate infusion was initiated. The patient continued to have QRS prolongation for the next 8 days, reaching a peak of 172 ms 3 days postingestion. Despite aggressive treatment with sodium bicarbonate, there was persistent QRS prolongation; however, the patient did not have any dysrhythmias and remained hemodynamically stable. The patient was discharged 9 days postingestion when the QRS duration normalized to 82 ms. Genetic testing revealed that the patient was a CYP2D6 poor metabolizer. This case suggests that aripiprazole toxicity may possibly be associated with QRS prolongation without associated dysrhythmias or cardiovascular compromise. In addition, toxicity may be prolonged in patients who are CYP2D6 poor metabolizers.

  5. Property Rights, Restrictions and Responsibilities

    DEFF Research Database (Denmark)

    Enemark, Stig

    more to a social, ethical commitment or attitude to environmental sustainability and good husbandry. This paper provides an overall understanding of the concept of land administration systems for dealing with rights, restrictions and responsibilities in future spatially enabled government. Finally......Land Administration Systems are the basis for conceptualizing rights, restrictions and responsibilities related to people, policies and places. Property rights are normally concerned with ownership and tenure whereas restrictions usually control use and activities on land. Responsibilities relate...

  6. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury: Effect of duty cycle

    NARCIS (Netherlands)

    MSc Karin J.A. Legemate; MD Christof A. J. Smit; MSc Anja de Koning; PhD Sonja de Groot; MD, PhD Janneke M. Stolwijk-Swuste; PhD Thomas W.H. Janssen

    2013-01-01

    Abstract—Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation

  7. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury : Effect of duty cycle

    NARCIS (Netherlands)

    Smit, Christof A. J.; Legemate, Karin J. A.; de Koning, Anja; de Groot, Sonja; Stolwijk-Swuste, Janneke M.; Janssen, Thomas W. J.

    2013-01-01

    Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation on

  8. Evaluating an intervention to reduce fear of falling and associated activity restriction in elderly persons: design of a randomised controlled trial [ISRCTN43792817

    Directory of Open Access Journals (Sweden)

    van Eijk JThM

    2005-03-01

    Full Text Available Abstract Background Fear of falling and associated activity restriction is common in older persons living in the community. Adverse consequences of fear of falling and associated activity restriction, like functional decline and falls, may have a major impact on physical, mental and social functioning of these persons. This paper presents the design of a trial evaluating a cognitive behavioural group intervention to reduce fear of falling and associated activity restriction in older persons living in the community. Methods/design A two-group randomised controlled trial was developed to evaluate the intervention. Persons 70 years of age or over and still living in the community were eligible for study if they experienced at least some fear of falling and associated activity restriction. A random community sample of elderly people was screened for eligibility; those eligible for study were measured at baseline and were subsequently allocated to the intervention or control group. Follow-up measurements were carried out directly after the intervention period, and then at six months and 12 months after the intervention. People allocated to the intervention group were invited to participate in eight weekly sessions of two hours each and a booster session. This booster session was conducted before the follow-up measurement at six months after the intervention. People allocated to the control group received no intervention as a result of this trial. Both an effect evaluation and a process evaluation were performed. The primary outcome measures of the effect evaluation are fear of falling, avoidance of activity due to fear of falling, and daily activity. The secondary outcome measures are perceived general health, self-rated life satisfaction, activities of daily life, feelings of anxiety, symptoms of depression, social support interactions, feelings of loneliness, falls, perceived consequences of falling, and perceived risk of falling. The outcomes of

  9. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury: Effect of duty cycle

    OpenAIRE

    Christof A. J. Smit, MD; Karin J. A. Legemate, MSc; Anja de Koning, MSc; Sonja de Groot, PhD; Janneke M. Stolwijk-Swuste, MD, PhD; Thomas W. J. Janssen, PhD

    2013-01-01

    Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation on interface pressure distribution in sitting individuals with SCI and study the usability of a newly developed electrode garment (ES shorts). Ten individuals with SCI participated in this study, in which t...

  10. The effects of chronic food restriction on hypothalamic-pituitary-adrenal activity depend on morning versus evening availability of food.

    Science.gov (United States)

    Belda, Xavier; Ons, Sheila; Carrasco, Javier; Armario, Antonio

    2005-05-01

    Partial food restriction (FR) protocols have been used not only to study behavioral and physiological consequences of decrease food intake, but as a necessary treatment of the animals in some operant learning tasks. It is well-established in rodents that restricting food availability to a few hours in the morning causes an alteration of the daily rhythm of corticosterone, thus making it difficult to evaluate whether or not such treatments are stressful. In the present experiment adult male Sprague-Dawley rats were subjected to two different FR schedules: food availability after 1100 h (LFR) or after 1900 h (DFR). After 14 days, animals from both groups, together with corresponding controls, were killed under resting conditions, either in the morning or in the evening, just before daily access to food in FR rats. Both FR schedules reduced body weight gain to the same extent, but their impact on the hypothalamic-pituitary-adrenal (HPA) axis was different: DFR increased relative, but not absolute, adrenal weight and morning and evening levels of corticosterone, whereas LFR increased both absolute and relative adrenal weights and increased morning corticosterone levels to a greater extent than DFR rats. Neither serum ACTH nor corticotropin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus were altered by DFR or LFR protocols, suggesting that factors other than CRF and ACTH are involved in the control of adrenocortical secretion under FR. It appears that LFR caused more alterations in the HPA axis than DFR and, therefore, the latter FR schedule should be used in those protocols necessarily involving partial FR.

  11. Robust photosystem I activity by Cyanothece sp. (Cyanobacteria) and its role in prolonged bloom persistence in lake St Lucia, South Africa.

    Science.gov (United States)

    du Plooy, Schalk J; Anandraj, Akash; White, Sarah; Perissinotto, Renzo; du Preez, Derek R

    2018-04-12

    Worldwide, cyanobacterial blooms are becoming more frequent, exacerbated by eutrophication, anthropogenic effects, and global climate change. Environmental factors play a direct role in photosynthesis of cyanobacteria and subsequent cellular changes, growth, and bloom dynamics. This study investigated the photosynthetic functioning of a persistent bloom-forming (18 months) cyanobacterium, Cyanothece sp., isolated from Lake St Lucia, South Africa. DUAL-PAM fluorometric methods were used to observe physiological responses in Cyanothece sp. photosystems I and II. Results show that photosystem I activity was maintained under all environmental conditions tested, while photosystem II activity was not observed at all. Out of the environmental factors tested (temperature, salinity, and nitrogen presence), only temperature significantly influenced photosystem I activity. In particular, high temperature (40 °C) facilitated faster electron transport rates, while effects of salinity and nitrogen were variable. Cyanothece sp. has shown to sustain bloom status for long periods largely because of the essential role of photosystem I activity during highly dynamic and even extreme (e.g., salinities higher than 200) environmental conditions. This ensures the continual supply of cellular energy (e.g. ATP) to important processes such as nitrogen assimilation, which is essential for protein synthesis, cell growth and, therefore, bloom maintenance.

  12. Women's experiences of becoming a mother after prolonged labour.

    Science.gov (United States)

    Nystedt, Astrid; Högberg, Ulf; Lundman, Berit

    2008-08-01

    This paper is a report of a study to explore women's experiences of becoming a mother after prolonged labour. The negativity associated with a complicated labour such as prolonged labour can lead to a struggle to become a healthy mother and could restrict the process of becoming a mother. Interviews were conducted in 2004 with 10 mothers who had been through a prolonged labour with assisted vaginal or caesarean delivery 1-3 months previously. Thematic content analysis was used. Three themes were formulated, describing women's experiences as fumbling in the dark, struggling for motherhood and achieving confidence in being a mother. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like 'fumbling in the dark'. Women experienced bodily fatigue, accompanied by feelings of illness and detachment from the child. Having the child when in this condition entailed a struggle to become a mother. In spite of these experiences and the desire to achieve confidence in being a mother, the reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged interaction and relationship with the child, and contributed to their adaptation to motherhood. Women experiencing prolonged labour may be comparable with the experience of and recovery from illness, which could contribute to difficulties transitioning to motherhood and limit a woman's ability to be emotionally available for the child.

  13. Synthesis of tritium labeled Ac-[Nle4, D-Phe7]-α-MSH/sub 4-11/-NH2: a superpotent melanotropin with prolonged biological activity

    International Nuclear Information System (INIS)

    Wilkes, B.D.; Hruby, V.J.; Yamamura, H.I.; Akiyama, K.; Castrucci, A.M. de; Hadley, M.E.; Andrews, J.R.; Wan, Y.P.

    1984-01-01

    Ac-[Nle 4 , D-Phe 7 ]-α-MSH/sub 4-11/-NH 2 an octapeptide, is a melanotropin analogue (Ac-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-NH 2 ), which is a superpotent agonist of frog and lizard skin melanocytes and mouse S 91 (Cloudman) melanoma cells. This melanotropin possesses ultraprolonged activity on melanocytes, both in vitro and in vivo, and the peptide is resistant to inactivation by serum enzymes. The tritium-labeled congener was prepared by direct incorporation of [ 3 H]-labeled norleucine into the peptide. The melanotropic activity of the labeled peptide is identical to the unlabeled analogue. This labeled peptide should be useful for studies on the localization and characterization of melanotropin receptors

  14. Prolonged unexplained fatigue in paediatrics

    NARCIS (Netherlands)

    Bakker, R.J.

    2010-01-01

    Prolonged Unexplained Fatigue in Paediatrics. Fatigue, as the result of mental or physical exertion, will disappear after rest, drinks and food. Fatigue as a symptom of illness will recover with the recovering of the illness. But when fatigue is ongoing for a long time, and not the result of

  15. Physiology Of Prolonged Bed Rest

    Science.gov (United States)

    Greenleaf, John E.

    1991-01-01

    Report describes physiological effects of prolonged bed rest. Rest for periods of 24 hours or longer deconditions body to some extent; healing proceeds simultaneously with deconditioning. Report provides details on shifts in fluid electrolytes and loss of lean body mass, which comprises everything in body besides fat - that is, water, muscle, and bone. Based on published research.

  16. Prolonged sulforaphane treatment activates survival signaling in nontumorigenic NCM460 colon cells but apoptotic signaling in tumorigenic HCT116 colon cells.

    Science.gov (United States)

    Zeng, Huawei; Trujillo, Olivia N; Moyer, Mary P; Botnen, James H

    2011-01-01

    Sulforaphane (SFN) is a naturally occurring chemopreventive agent; the induction of cell cycle arrest and apoptosis is a key mechanism by which SFN exerts its colon cancer prevention. However, little is known about the differential effects of SFN on colon cancer and normal cells. In this study, we demonstrated that SFN (15 μmol/L) exposure (72 h) inhibited cell proliferation by up to 95% in colon cancer cells (HCT116) and by 52% in normal colon mucosa-derived (NCM460) cells. Our data also showed that SFN exposure (5 and 10 μmol/L) led to the reduction of G1 phase cell distribution and an induction of apoptosis in HCT116 cells, but to a much lesser extent in NCM460 cells. Furthermore, the examination of mitogen-activated protein kinase (MAPK) signaling status revealed that SFN upregulated the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. In contrast, SFN enhanced the phosphorylation of stress-activated protein kinase (SAPK) and decreased cellular myelocytomatosis oncogene (c-Myc) expression in HCT116 cells but not NCM460 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may play a critical role in SFN's stronger potential of inhibiting cell proliferation in colon cancer cells than in normal colon cells. Copyright © 2011, Taylor & Francis Group, LLC

  17. Transfer of in vitro expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with EL4 tumor cells.

    Science.gov (United States)

    Li, Jinhua; Theofanous, Leigh; Stickel, Sara; Bouton-Verville, Hilary; Burgin, Kelly E; Jakubchak, Susan; Wagner, Thomas E; Wei, Yanzhang

    2007-07-01

    Adoptive T cell transfer after in vitro expansion represents an attractive cancer immunotherapy. The majority of studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naïve T cells can be primed with dendritomas and expanded in vitro to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from lymph nodes of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The in vitro primed and expanded T cells showed tumor cell specific CTL activity and increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of the mice that received the adoptive transfer therapy.

  18. Is willingness to exercise programmed in utero? Reviewing sedentary behavior and the benefits of physical activity in intrauterine growth restricted individuals.

    Science.gov (United States)

    Bischoff, Adrianne Rahde; Cunha, Fábio da Silva; Dalle Molle, Roberta; Maróstica, Paulo José Cauduro; Silveira, Patrícia Pelufo

    2018-02-22

    The literature suggests that a fetus will adapt to surrounding adversities by optimizing its use of energy to improve survival, ultimately leading to the programming of the individual's energy intake and expenditure. While recent reviews focused on the fetal programming of energy intake and food preferences, there is also some evidence that fetal adversity is associated with diminished physical activity levels. Therefore, we aimed to review (a) the evidence for an association between being born with intrauterine growth restriction and sedentarism over the life-course and (b) the potential benefits of physical activity over cardiometabolic risk factors for this population. PubMed, Scielo, Scopus and Embase. Most clinical studies that used objective measures found no association between intrauterine growth restriction and physical activity levels, while most studies that used self-reported questionnaires revealed such relationships, particularly leisure time physical activity. Experimental studies support the existence of fetal programming of physical activity, and show that exposure to exercise during IUGR individuals' life improves metabolic outcomes but less effect was seen on muscle architecture or function. Alterations in muscle strength and metabolism, as well as altered aerobic performance, may predispose IUGR individuals to be spontaneously less physically active, suggesting that this population may be an important target for preventive interventions. Although very heterogeneous, the different studies allow us to infer that physical activity may have beneficial effects especially for individuals that are more vulnerable to metabolic modifications such as those with IUGR. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Engagement in community activities and trust in local leaders as concomitants of psychological distress among Israeli civilians exposed to prolonged rocket attacks.

    Science.gov (United States)

    Zanbar, Lea; Kaniasty, Krzysztof; Ben-Tzur, Navit

    2018-07-01

    Present study, conducted in the aftermath of the 2014 Israel-Gaza conflict, investigated psychological toll of exposure to rockets attacks in a sample of residents of central and southern Israel. Analyses focused on the distress-protective functions of collectively grounded resources: engagement in community activities and trust in local leadership. This cross-sectional study was conducted between 2 and 3 months after the hostilities. Participants (N = 764) were recruited by an online survey company that distributed a questionnaire assessing, in addition to focal predictors, sociodemographic factors and prior exposure to trauma. The outcome variables were post-traumatic stress disorder (PTSD) and nonspecific distress symptoms. Conservative regression analyses revealed that greater exposure to rocket attacks was predictive of higher levels of posttraumatic stress symptoms. Higher engagement in community activities exhibited a partial trauma-buffering function. However, higher levels of trust in local leaders appeared to exacerbate, rather than diminish, negative impact of rocket exposure on PTSD. Symptoms of psychological distress were not influenced neither by trauma exposure nor by stressor interactions with resources. Trust in local leadership exerted a beneficial main effect on distress. Collectively based resources are important for coping in times of community-wide stressors, yet their role is complex.

  20. Hydrolysate from a mixture of legume flours with antifungal activity as an ingredient for prolonging the shelf-life of wheat bread.

    Science.gov (United States)

    Rizzello, Carlo Giuseppe; Verni, Michela; Bordignon, Stefano; Gramaglia, Valerio; Gobbetti, Marco

    2017-06-01

    Aiming at identifying antifungal compounds from plant matrices to be used as ingredients in the bakery industry, a water/salt-soluble extract (WSE) was produced from a legume enzyme hydrolysate, consisting of a mixture of pea, lentil, and faba bean flours, and assayed towards Penicillium roqueforti DPPMAF1. Agar diffusion assays allowed the selection of the optimal processing conditions for hydrolysis. As shown by hyphal radial growth rate, the inhibition was observed towards several fungi, including Aspergillus parasiticus CBS971.97, Penicillium carneum CBS 112297, Penicillium paneum CBS 101032, Penicillium polonicum 112490. A multi-step purification was carried out to identify the active compounds. The antifungal activity was attributed to native proteins (nsLTP, ubiquitin, lectin alpha-1 chain, wound-induced basic protein, defensin-1, defensin-2) and a mixture of peptides, which were released during hydrolysis. Nine peptides were purified and identified as sequences encrypted in legume vicilins, lectins and chitinases. WSE was used as ingredient for making bread under pilot plant conditions. Chemical, structural and sensory characterization of bread showed the lack of significant changes compared to control. The bread made with the legume hydrolysate had a longer shelf-life than that of the control. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Measurement of activity limitations and participation restrictions: examination of ICF-linked content and scale properties of the FIM and PC-PART instruments.

    Science.gov (United States)

    Darzins, Susan W; Imms, Christine; Di Stefano, Marilyn

    2017-05-01

    To explore the operationalization of activity and participation-related measurement constructs through comparison of item phrasing, item response categories and scoring (scale properties) for two separate instruments targeting activities of daily living. Personal Care Participation Assessment and Resource Tool (PC-PART) item content was linked to ICF categories using established linking rules. Previously reported ICF-linked FIM content categories and ICF-linked PC-PART content categories were compared to identify common ICF categories between the instruments. Scale properties of both instruments were compared using a patient scenario to explore the instruments' separate measurement constructs. The PC-PART and FIM shared 15 of the 53 level two ICF-linked categories identified across both instruments. Examination of the instruments' scale properties for items with overlapping ICF content, and exploration through a patient scenario, provided supportive evidence that the instruments measure different constructs. While the PC-PART and FIM share common ICF-linked content, they measure separate constructs. Measurement construct was influenced by the instruments' scale properties. The FIM was observed to measure activity limitations and the PC-PART measured participation restrictions. Scrutiny of instruments' scale properties in addition to item content is critical in the operationalization of activity and participation-related measurement constructs. Implications for Rehabilitation When selecting outcome measures for use in rehabilitation it is necessary to examine both the content of the instruments' items and item phrasing, response categories and scoring, to clarify the construct being measured. Measurement of activity limitations as well as participation restrictions in activities of daily living required for community life provides a more comprehensive measurement of rehabilitation outcomes than measurement of either construct alone. To measure the effects of

  2. The effect of prolonged flooding of an oil deposit on the special composition and the activity of hydrocarbon-oxidizing microflora

    Energy Technology Data Exchange (ETDEWEB)

    Berdichevskaya, M V

    1982-07-01

    The special composition of hydrocarbon-oxidizing bacteria was studied in terrigenous and carbonate oil-bearing strata from several deposits of the Permian Cis-Ural region. We isolated 43 strains and assigned them to the following genera: Mycobacterium, Micrococcus, Brevibacterium, Corynebacterium, Flavobacterium, Achromobacter and Pseudomonas. The special composition of the hydrocarbon-oxidizing microflora was shown to depend on the flooding of an oil stratum, as a result of which the ecological environment in a deposit changed. Gram-positive coryneform bacteria were found in stratal salinized waters and in diluted stratal waters. Gram-negative hydrocarbon-oxidizing bacteria were isolated from pumped-in river waters and from stratal waters diluted by 70-100% as the result of flooding. The metabolic activity of Corynebacterium fascians (2 strains), Mycobacterium rubrum (1 strain), Pseudomonas mira (1 strain) and Flavobacterium perigrinum (1 strain) was assayed in stratal waters with different concentrations of salts. The coryneform hydrocarbon-oxidizing bacteria were shown to be very halotolerant as the result of adaptation; that is why the incidence of these microorganisms is very great in highly mineralized stratal water of oil deposits.

  3. Activity of R(+) limonene on the maximum growth rate of fish spoilage organisms and related effects on shelf-life prolongation of fresh gilthead sea bream fillets.

    Science.gov (United States)

    Giarratana, Filippo; Muscolino, Daniele; Beninati, Chiara; Ziino, Graziella; Giuffrida, Alessandro; Panebianco, Antonio

    2016-11-21

    R(+)limonene (LMN) is the major aromatic compound in essential oils obtained from oranges, grapefruits, and lemons. The improvement of preservation techniques to reduce the growth and activity of spoilage microorganisms in foods is crucial to increase their shelf life and to reduce the losses due to spoilage. The aim of this work is to evaluate the effect of LMN on the shelf life of fish fillets. Its effectiveness was preliminarily investigated in vitro against 60 strains of Specific Spoilage Organisms (SSOs) and then on gilt-head sea bream fillets stored at 2±0.5°C for 15days under vacuum. LMN showed a good inhibitory effect against tested SSOs strains. On gilt-head sea bream fillets, LMN inhibited the growth SSOs effectively, and its use resulted in a shelf-life extension of ca. 6-9days of treated fillets, compared to the control samples. The LMN addition in Sparus aurata fillets giving a distinctive smell and like-lemon taste to fish fillets that resulted pleasant to panellists. Its use contributed to a considerable reduction of fish spoilage given that the fillets treated with LMN were still sensory acceptable after 15days of storage. LMN may be used as an effective antimicrobial system to reduce the microbial growth and to improve the shelf life of fresh gilt-head sea bream fillets. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. What Is the Effect on Obesity Indicators from Replacing Prolonged Sedentary Time with Brief Sedentary Bouts, Standing and Different Types of Physical Activity during Working Days?

    DEFF Research Database (Denmark)

    Gupta, Nidhi; Heiden, Marina; Aadahl, Mette

    2016-01-01

    ) across the day during work period and 5.5 hours (~62% of the measured time, SD = 1.5 hours) during non-work period. Most of the sedentary time was accrued in moderate bouts [work = 1.40 (SD = 1.09) hours] during work and in long bouts during non-work [2.7 (SD = 1.4) hours], while least in long sedentary...... bouts during work [work = 0.5 (SD = 0.9)] and in brief sedentary bouts [0.5 hours (SD = 0.3)] during non-work. Significant associations with all obesity indicators were found when 30 min of total sedentary time or long sedentary bouts were replaced with standing time (~1–2% lower) or MVPA (~4–9% lower...... physical activity (MVPA) time on working days was computed using validated Acti4 software. The total sedentary time and uninterrupted sedentary time spent in brief (≤5 mins), moderate (>5 and ≤30 mins), and long (>30mins) bouts, were determined for the whole day and during work and non-work time separately...

  5. Fasting or caloric restriction for healthy aging.

    Science.gov (United States)

    Anton, Stephen; Leeuwenburgh, Christiaan

    2013-10-01

    Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prolonged caloric restriction, which has led to a search for alternative approaches that can produce similar to benefits as caloric restriction. A growing body of evidence indicates that fasting periods and intermittent fasting regimens in particular can trigger similar biological pathways as caloric restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting periods, as well as whether long-term compliance may be improved by this type of dietary approach. This special will highlight the latest scientific findings related to the effects of both caloric restriction and intermittent fasting across various species including yeast, fruit flies, worms, rodents, primates, and humans. A specific emphasis is placed on translational research with findings from basic bench to bedside reviewed and practical clinical implications discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The Effects of Montmorency Tart Cherry Concentrate Supplementation on Recovery Following Prolonged, Intermittent Exercise

    Directory of Open Access Journals (Sweden)

    Phillip G. Bell

    2016-07-01

    Full Text Available This study investigated Montmorency tart cherry concentrate (MC supplementation on markers of recovery following prolonged, intermittent sprint activity. Sixteen semi-professional, male soccer players, who had dietary restrictions imposed for the duration of the study, were divided into two equal groups and consumed either MC or placebo (PLA supplementation for eight consecutive days (30 mL twice per day. On day 5, participants completed an adapted version of the Loughborough Intermittent Shuttle Test (LISTADAPT. Maximal voluntary isometric contraction (MVIC, 20 m Sprint, counter movement jump (CMJ, agility and muscle soreness (DOMS were assessed at baseline, and 24, 48 and 72 h post-exercise. Measures of inflammation (IL-1-β, IL-6, IL-8, TNF-α, hsCRP, muscle damage (CK and oxidative stress (LOOH were analysed at baseline and 1, 3, 5, 24, 48 and 72 h post-exercise. Performance indices (MVIC, CMJ and agility recovered faster and muscle soreness (DOMS ratings were lower in the MC group (p < 0.05. Additionally, the acute inflammatory response (IL-6 was attenuated in the MC group. There were no effects for LOOH and CK. These findings suggest MC is efficacious in accelerating recovery following prolonged, repeat sprint activity, such as soccer and rugby, and lends further evidence that polyphenol-rich foods like MC are effective in accelerating recovery following various types of strenuous exercise.

  7. Chromic phosphate synoviortheses without age restriction, as a firsts option for treatment of chronic active haemophilic synovitis

    International Nuclear Information System (INIS)

    Llinas, Adolfo; Silva, Mauricio; Duarte, Monica; Cuervo, Pilar; Ninno, Dora; Ucros, Gonzalo; Cerquera, Angela Maria; Bernal, Patricia

    2003-01-01

    The aim of the work was to demonstrate that clinical results obtained with synovectomies using active chromic phosphate without receiving dose of prophylactic factor concentrate before or after procedure are comparable to those obtained by a 3-month of post procedure prohylasis. the effectiveness of the synovectomy using chromic phosphate (32P) in the control of chronic hemarthroses in haemophilic patients to prevent the evolution of the arthropathy and its complications was also assessed

  8. Low accessibility and chemical activity of PAHs restrict bioremediation and risk of exposure in a manufactured gas plant soil

    International Nuclear Information System (INIS)

    Reichenberg, Fredrik; Karlson, Ulrich Gosewinkel; Gustafsson, Orjan; Long, Sara M.; Pritchard, Parmely H.; Mayer, Philipp

    2010-01-01

    Composting of manufactured gas plant soil by a commercial enterprise had removed most of its polycyclic aromatic hydrocarbons (PAHs), but concentrations remained above regulatory threshold levels. Several amendments and treatments were first tested to restart the PAH degradation, albeit with little success. The working hypothesis was then that PAHs were 'stuck' due to strong sorption to black carbon. Accessibility was measured with cyclodextrin extractions and on average only 4% of the PAHs were accessible. Chemical activity of the PAHs was measured by equilibrium sampling, which confirmed a low exposure level. These results are consistent with strong sorption to black carbon (BC), which constituted 59% of the total organic carbon. Composting failed to remove the PAHs, but it succeeded to minimize PAH accessibility and chemical activity. This adds to accumulating evidence that current regulatory thresholds based on bulk concentrations are questionable and alternative approaches probing actual risk should be considered. - Bioremediation of MGP soil failed to eliminate PAHs but it succeeded to limit their accessibility, chemical activity and the remaining risk of biological exposure.

  9. On low fertility from the aspect of the economic activity of female population: Possibilities and restrictions in encouragement of childbearing

    Directory of Open Access Journals (Sweden)

    Šobot Ankica

    2014-01-01

    Full Text Available Below replacement fertility was the outcome of changes in the education and socio-professional structure of women, as well as modifications in values and life aspirations. On the other hand, economic strengthening of women and encourage-ment of jobs which require greater dedication and more of their time are important aspects of achieving gender equality. These two circumstances gave rise to contemplations on the connection between economic activities of female population and the level of births in postindustrial societies. The aim of this article is to point out to the positive influence of female employment on the fertility level, as a capacity for encouraging births in Serbia. When observing the most developed European countries, it can be noticed that greater birth rates are noted in those countries in which there are greater economic activity and employment rates of female population. Furthermore, a series of researches and comparative analyses confirm the positive relation between female employment and fertility. The differences regarding of birth rates among European welfare states are seen as a result of the possibilities of female employment, reconciliation between work and parenthood and the division of gender roles within the family. The influence of economic activity on fertility levels is determined by an institutional framework of family support and gender equality (Engelhardt and Prskawetz, 2004, Neyer, 2006; Andersson and Scott, 2007; Rovny, A.E. 2011; Seeleib-Kaise and Toivonen, 2011. During the first decade of the 21st century, the birth rates in Serbia were by about 30% lower than in the countries which had the highest fertility within European frameworks. The traditional labor division in the household and parenthood produces conflicts between families and employment, recognized in the practices of everyday life (Blagojević, 1997; Blagojević-Hjuson, 2013 and standpoints on the relation between parenthood and employment

  10. Acute restriction impairs memory in the elevated T-maze (ETM) and modifies serotonergic activity in the dorsolateral striatum.

    Science.gov (United States)

    Cruz-Morales, Sara Eugenia; García-Saldívar, Norma Laura; González-López, María Reyes; Castillo-Roberto, Georgina; Monroy, Juana; Domínguez, Roberto

    2008-12-16

    Serotonin (5-HT) is involved in behaviors such as sleep, eating, memory, in mental disorders like anxiety and depression and plays an important role in the modulation of stress. On the other hand, exposure to stress influence learning as well as declarative and non-declarative memory. These effects are dependent on the type of stressor, their magnitude, and the type of memory. The striatum has been associated with non-declarative procedural memory, while the information about stress effects on procedural memory and their relation with striatal serotonin is scarce. The objective of this study was to evaluate the effects of stress on the modifications of the striatal serotonergic system. In Experiment 1, the effects of either 60 min of restraint (R) or exposure to the elevated T-maze (ETM) was assessed. Exposure to ETM decreased 5-HT concentration and to R increased 5-HT activity ([metabolite]/[neurotransmitter]). In Experiment 2, we evaluated the effects of restraint on ETM trained immediately, 24 or 48 h after restraint. No effects were detected in acquisition or escape latencies, while retention latencies were lower in all groups compared with the non-restrained group, although significant effects were detected immediately and 24h after restraint. The memory impairment seems to be associated with changes in striatal serotonergic system, given that 5-HT concentration increased, while serotonergic activity decreased. The differences in the activity of 5-HT detected in each experiment could be explained by the effects of different stressors on the serotonergic neurons ability to synthesize the neurotransmitter. Thus, we suggest that exposure to stress impairs procedural memory and that striatal serotonin modulates this effect.

  11. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

    Directory of Open Access Journals (Sweden)

    Matias Russo

    2016-07-01

    Full Text Available The purpose of this study was to determine whether the administration of the feruloyl esterase (FE-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group, CR diet Group (CR Group and CR diet plus L. fermentum Group (CR-Lf Group. CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020 than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025, total cholesterol (p = 0.005 and glucose (p < 0.0001 levels and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006 parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions.

  12. Decreased activation of placental mTOR family members is associated with the induction of intrauterine growth restriction by secondhand smoke in the mouse.

    Science.gov (United States)

    Mejia, Camilo; Lewis, Josh; Jordan, Clinton; Mejia, Juan; Ogden, Connor; Monson, Troy; Winden, Duane; Watson, Marc; Reynolds, Paul R; Arroyo, Juan A

    2017-02-01

    Cigarette smoke is known to be a risk for the development of intrauterine growth restriction (IUGR). Our objective was to assess the effects of secondhand smoke (SHS) during pregnancy and to what extent it regulates the activation of mTOR family members and murine trophoblast invasion. Mice were treated to SHS for 4 days. Placental and fetal weights were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of placental trophoblast invasion. Western blots were utilized to assess the activation of caspase 3, XIAP, mTOR, p70 and 4EBP1 in treated and control placental lysates. As compared to controls, treated animals showed: (1) decreased placental (1.4-fold) and fetal (2.3-fold) weights (p smoke extract (CSE). Similar to primary smoking, SHS may induce IUGR via decreased activation of the mTOR family of proteins in the placenta. Increased activation of the placental XIAP protein could be a survival mechanism for abnormal trophoblast cells during SHS exposure. Further, CSE reduced trophoblast invasion, suggesting a direct causative effect of smoke on susceptible trophoblast cells involved in IUGR progression. These results provide important insight into the physiological consequences of SHS exposure and smoke-mediated placental disease.

  13. Placental NFE2L2 is discordantly activated in monochorionic twins with selective intrauterine growth restriction and possibly regulated by hypoxia.

    Science.gov (United States)

    Wu, Jing; He, Zhiming; Gao, Yu; Zhang, Guanglan; Huang, Xuan; Fang, Qun

    2017-04-01

    Nuclear factor, erythroid 2 like 2 (NFE2L2) is an important transcription factor that protects cells from oxidative stress (OS). NFE2L2 deficiency in placentas is associated with pregnancy complications. We have demonstrated that elevated OS existed in placental shares of the smaller fetus in selective intrauterine growth restriction (sIUGR); however, the role of NFE2L2 in the development of sIUGR remains unknown. In this study, we examined the levels of NFE2L2 and heme oxygenase 1 (HMOX1), a major antioxidant regulated by NFE2L2, in sIUGR placentas. We also investigated the relationship between hypoxia and NFE2L2 activation, which may be involved in the pathogenesis of sIUGR. Real-time PCR, Western blot, and immunohistochemistry were used to detect the levels of NFE2L2 and HMOX1 in placentas from 30 monochorionic diamniotic (MCDA) twin pregnancies. The trophoblast cell line HTR-8/SVneo was cultured under severe (3%) or mild (10%) hypoxia. NFE2L2 and HMOX1 were both up-regulated in placental shares of the smaller fetus in the sIUGR group. No significant inter-twin differences in NFE2L2 and HMOX1 were detected in the normal group. In vitro, NFE2L2 was suppressed under severe hypoxia (3% O 2 ) but was clearly up-regulated under mild hypoxia (10% O 2 ). Compared with the suppression of NFE2L2 in placentas of fetal growth restriction (FGR) in singleton pregnancies, NFE2L2 was up-regulated in placental shares of the smaller fetus in sIUGR pregnancies. The asymmetrical activation of NFE2L2 in placental shares of sIUGR twins may be a compensation for hypoxia that protects the smaller fetus from OS damage.

  14. Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin

    Science.gov (United States)

    Rogers, Nicole H.; Walsh, Heidi; Alvarez-Garcia, Oscar; Park, Seongjoon; Gaylinn, Bruce; Thorner, Michael O.

    2016-01-01

    Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin−/−) or ghrelin receptor (Ghsr−/−), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin−/− and Ghsr−/− mice to metabolically adapt and avoid severe hypoglycemia. Twelve months later, plasma ghrelin, metabolic parameters, ambulatory activity, hypothalamic and liver gene expression, as well as body composition were measured. CR increased plasma ghrelin and des-acyl ghrelin concentrations in WT and Ghsr−/− mice. CR of WT, Ghsr−/−, and Ghrelin−/− mice markedly improved metabolic flexibility, enhanced ambulatory activity, and reduced adiposity. Inactivation of Ghrelin or Ghsr had no effect on AL food intake or food anticipatory behavior. In contrast to the widely held belief that endogenous ghrelin regulates food intake, CR increased expression of hypothalamic Agrp and Npy, with reduced expression of Pomc across genotypes. In the AL context, ablation of ghrelin signaling markedly inhibited liver steatosis, which correlated with reduced Pparγ expression and enhanced Irs2 expression. Although CR and administration of GH secretagogue receptor 1a agonists both benefit the aging phenotype, we conclude the benefits of chronic CR are a consequence of enhanced metabolic flexibility independent of endogenous ghrelin or des-acyl ghrelin signaling. PMID:26812158

  15. [Effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction].

    Science.gov (United States)

    Li, Xiang-Wen; Li, Fang; Liu, Jing; Wang, Yan; Fu, Wei

    2016-11-01

    To study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR. A total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups: control, FGR, and taurine (n=8 each ). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac). The FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (Ptaurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (Ptaurine group had significantly higher mRNA expression of Rac than the FGR and control groups (Ptaurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (Ptaurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.

  16. Exploring the relationships between International Classification of Functioning, Disability and Health (ICF) constructs of Impairment, Activity Limitation and Participation Restriction in people with osteoarthritis prior to joint replacement.

    Science.gov (United States)

    Pollard, Beth; Johnston, Marie; Dieppe, Paul

    2011-05-16

    The International Classification of Functioning, Disability and Health (ICF) proposes three main constructs, impairment (I), activity limitation (A) and participation restriction (P). The ICF model allows for all paths between the constructs to be explored, with significant paths likely to vary for different conditions. The relationships between I, A and P have been explored in some conditions but not previously in people with osteoarthritis prior to joint replacement. The aim of this paper is to examine these relationships using separate measures of each construct and structural equation modelling. A geographical cohort of 413 patients with osteoarthritis about to undergo hip and knee joint replacement completed the Aberdeen measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP). Confirmatory factor analysis was used to test the three factor (I, A, P) measurement model. Structural equation modelling was used to explore the I, A and P pathways in the ICF model. There was support from confirmatory factor analysis for the three factor I, A, P measurement model. The structural equation model had good fit [S-B Chi-square = 439.45, df = 149, CFI robust = 0.91, RMSEA robust = 0.07] and indicated significant pathways between I and A (standardised coefficient = 0.76 p < 0.0001) and between A and P (standardised coefficient = 0.75 p < 0.0001). However, the path between I and P was not significant (standardised coefficient = 0.01). The significant pathways suggest that treatments and interventions aimed at reducing impairment, such as joint replacement, may only affect P indirectly, through A, however, longitudinal data would be needed to establish this.

  17. Prevention of early postnatal hyperalimentation protects against activation of transforming growth factor-β/bone morphogenetic protein and interleukin-6 signaling in rat lungs after intrauterine growth restriction.

    Science.gov (United States)

    Alcázar, Miguel Angel Alejandre; Dinger, Katharina; Rother, Eva; Östreicher, Iris; Vohlen, Christina; Plank, Christian; Dötsch, Jörg

    2014-12-01

    Intrauterine growth restriction (IUGR) is intimately linked with postnatal catch-up growth, leading to impaired lung structure and function. However, the impact of catch-up growth induced by early postnatal hyperalimentation (HA) on the lung has not been addressed to date. The aim of this study was to investigate whether prevention of HA subsequent to IUGR protects the lung from 1) deregulation of the transforming growth factor-β(TGF-β)/bone morphogenetic protein (BMP) pathway, 2) activation of interleukin (IL)-6 signaling, and 3) profibrotic processes. IUGR was induced in Wistar rats by isocaloric protein restriction during gestation by feeding a control (Co) or a low-protein diet with 17% or 8% casein, respectively. On postnatal day 1 (P1), litters from both groups were randomly reduced to 6 pups per dam to induce HA or adjusted to 10 pups and fed with standard diet: Co, Co with HA (Co-HA), IUGR, and IUGR with HA (IUGR-HA). Birth weights in rats after IUGR were lower than in Co rats (P < 0.05). HA during lactation led to accelerated body weight gain from P1 to P23 (Co vs. Co-HA, IUGR vs. IUGR-HA; P < 0.05). At P70, prevention of HA after IUGR protected against the following: 1) activation of both TGF-β [phosphorylated SMAD (pSMAD) 2; plasminogen activator inhibitor 1 (Pai1)] and BMP signaling [pSMAD1; inhibitor of differentiation (Id1)] compared with Co (P < 0.05) and Co or IUGR (P < 0.05) rats, respectively; 2) greater mRNA expression of interleukin (Il) 6 and Il13 (P < 0.05) as well as activation of signal transducer and activator of transcription 3 (STAT3) signaling (P < 0.05) after IUGR-HA; and 3) greater gene expression of collagen Iα1 and osteopontin (P < 0.05) and increased deposition of bronchial subepithelial connective tissue in IUGR-HA compared with Co and IUGR rats. Moreover, HA had a significant additive effect (P < 0.05) on the increased enhanced pause (indicator of airway resistance) in the IUGR group (P < 0.05) at P70. This study demonstrates

  18. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    Directory of Open Access Journals (Sweden)

    Fábio da Silva Cunha

    Full Text Available We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib, receiving standard laboratory chow ad libitum; 50% food restricted (FR, receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF, receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels, abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females. Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters, probably through different biological mechanisms.

  19. Characterization of gut microbiota profiles by disease activity in patients with Crohn's disease using data mining analysis of terminal restriction fragment length polymorphisms.

    Science.gov (United States)

    Andoh, Akira; Kobayashi, Toshio; Kuzuoka, Hiroyuki; Tsujikawa, Tomoyuki; Suzuki, Yasuo; Hirai, Fumihito; Matsui, Toshiyuki; Nakamura, Shiro; Matsumoto, Takayuki; Fujiyama, Yoshihide

    2014-05-01

    The gut microbiota plays a significant role in the pathogenesis of Crohn's disease (CD). In this study, we analyzed the disease activity and associated fecal microbiota profiles in 160 CD patients and 121 healthy individuals. Fecal samples from the CD patients were collected during three different clinical phases, the active (n=66), remission-achieved (n=51) and remission-maintained (n=43) phases. Terminal restriction fragment length polymorphism (T-RFLP) and data mining analysis using the Classification and Regression Tree (C&RT) approach were performed. Data mining provided a decision tree that clearly identified the various subject groups (nodes). The majority of the healthy individuals were divided into Node-5 and Node-8. Healthy subjects comprised 99% of Node-5 (91 of 92) and 84% of Node-8 (21 of 25 subjects). Node-3 was characterized by CD (136 of 160 CD subjects) and was divided into Node-6 and Node-7. Node-6 (n=103) was characterized by subjects in the active phase (n=48; 46%) and remission-achieved phase (n=39; 38%) and Node-7 was characterized by the remission-maintained phase (21 of 37 subjects; 57%). Finally, Node-6 was divided into Node-9 and Node-10. Node-9 (n=78) was characterized by subjects in the active phase (n=43; 55%) and Node-10 (n=25) was characterized by subjects in the remission-maintained phase (n=16; 64%). Differences in the gut microbiota associated with disease activity of CD patients were identified. Thus, data mining analysis appears to be an ideal tool for the characterization of the gut microbiota in inflammatory bowel disease.

  20. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  1. HAART (Highly Active Anti-Retroviral Therapy : An overview

    Directory of Open Access Journals (Sweden)

    Praful Pande

    2014-01-01

    activation, restoration of lymph node architecture, clinical improvement, prolonged survival, fewer opportunistic infections and HIV - associated malignancies. Problem with therapy are pill burden, non-availability of drugs, food and storage restrictions, drug-drug interactions, severe side-effects, reduction in quality of life measures, emergence of multiple drug resistance mutations.

  2. Prolonged pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    Summary Prolonged pregnancy, defined as a pregnancy with a gestational length of 294 days or more, is a frequent condition. It is associated with an increased risk of fetal and maternal complications. Little is known about the aetiology of prolonged pregnancy. The aims of the thesis were 1......) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... the risk of recurrence of prolonged pregnancy as a function of change in male partner and social conditions (IV). The National Birth Cohort provided data for the study on prenatal risk indicators of prolonged pregnancy in a follow-up design (V). The self-reported gestational ages from this database...

  3. Impact of prolonged leucine supplementation on protein synthesis and lean growth in neonatal pigs

    Science.gov (United States)

    Most low-birth weight infants experience extrauterine growth failure due to reduced nutrient intake as a result of feeding intolerance. The objective of this study was to determine whether prolonged enteral leucine supplementation improves lean growth in neonatal pigs fed a restricted protein diet. ...

  4. [Can solar/geomagnetic activity restrict the occurrence of some shellfish poisoning outbreaks? The example of PSP caused by Gymnodinium catenatum at the Atlantic Portuguese coast].

    Science.gov (United States)

    Vale, P

    2013-01-01

    Cyclic outbreaks of accumulation of paralytic shellfish poisoning (PSP) toxins in mussels attributed to Gymnodinium catenatum blooms displayed several of the highest inter-annual maxima coincidental with minima of the 11-year solar sunspot number (SSN) cycle. The monthly distribution of PSP was associated with low levels of the solar radio flux, a more quantitative approach than SSN for fluctuations in solar activity. A comparison between monthly distribution of PSP and other common biotoxins (okadaic acid (OA), dinophysistoxin-2 (DTX2) and amnesic shellfish poisoning (ASP) toxins) demonstrated that only PSP was significantly associated with low levels of radio flux (p < 0.01). PSP occurrence suggests a prior decline in solar activity could be required to act as a trigger, in a similar manner to a photoperiodic signal. The seasonal frequency increased towards autumn during the study period, which might be related to the progressive atmospheric cut-off of deleterious radiation associated with the seasonal change in solar declination, and might play an additional role in seasonal signal-triggering. PSP distribution was also associated with low levels of the geomagnetic index Aa. A comparison between monthly distribution of PSP and other common biotoxins, also demonstrated that only PSP was significantly associated with low levels of the Aa index (p < 0.01). In some years of SSN minima no significant PSP-outbreaks in mussels were detected. This was attributed to a steady rise in geomagnetic activity that could disrupt the triggering signal. Global distribution patterns show that hotspots for G. catenatum blooms are regions with deficient crustal magnetic anomalies. In addition to the variable magnetic field mostly of solar origin, static fields related to magnetized rocks in the crust and upper mantle might play a role in restricting worldwide geographic distribution.

  5. Viral Restriction Activity of Feline BST2 Is Independent of Its N-Glycosylation and Induction of NF-κB Activation.

    Directory of Open Access Journals (Sweden)

    Weiran Wang

    Full Text Available BST2 (CD317, tetherin, HM1.24 is an interferon-inducible transmembrane protein which can directly inhibit the release of enveloped virus particles from infected cells, and its anti-viral activity is reported to be related to the specific topological arrangement of its four structural domains. The N-terminal cytoplasmic tail of feline BST2 (fBST2 is characterized by a shorter N-terminal region compared to those of other known homologs. In this study, we investigated the functional impact of modifying the cytoplasmic tail region of fBST2 and its molecular mechanism. The fBST2 protein with the addition of a peptide at the N-terminus retained anti-release activity against human immunodeficiency virus type-1 and pseudovirus based on feline immunodeficiency virus at a weaker level compared with the wild-type fBST2. However, the fBST2 protein with addition of a peptide internally in the ectodomain proximal to the GPI anchor still retained its anti-viral activity well. Notably, the N-glycosylation state and the cell surface level of the N-terminally modified variants were unlike those of the wild-type protein, while no difference was observed in their intracellular localizations. However, in contrast to human BST2, the wild-type fBST2 did not show the ability to activate NF-κB. Consistent with previous reports, our findings showed that adding a peptide in the cytoplasmic tail region of fBST2 may influence its anti-viral activity. The shorter N-terminal cytoplasmic region of fBST2 compared with human BST2 did not apparently affect its anti-viral activity, which is independent of its N-glycosylation and ability to activate NF-κB.

  6. Thermoregulatory, Cardiovascular, and Metabolic Responses to Mild Caloric Restriction in the Brown Norway Rat

    Science.gov (United States)

    Caloric restriction (CR) has been demonstrated to prolong the life span of a variety of species. CR-induced reduction in core temperature (Tc) is considered a key mechanism responsible for prolonging life span in rodents; however, little is known on the regulation of CR-induced h...

  7. Utility of circulating IGF-I as a biomarker for assessing body composition changes in men during periods of high physical activity superimposed upon energy and sleep restriction.

    Science.gov (United States)

    Nindl, Bradley C; Alemany, Joseph A; Kellogg, Mark D; Rood, Jennifer; Allison, Steven A; Young, Andrew J; Montain, Scott J

    2007-07-01

    Insulin-like growth factor (IGF)-I is a biomarker that may have greater utility than other conventional nutritional biomarkers in assessing nutritional, health, and fitness status. We hypothesized that the IGF-I system would directionally track a short-term energy deficit and would be more related to changes in body composition than other nutritional biomarkers. Thirty-five healthy men (24 +/- 0.3 yr) underwent 8 days of exercise and energy imbalance. Total and free IGF-I, IGF binding proteins-1, -2, and -3, the acid labile subunit, transferrin, ferritin, retinol binding protein, prealbumin, testosterone, triiodothyronine, thyroxine, and leptin responses were measured. Dual-energy X-ray absorptiometry assessed changes in body mass and composition. Repeated-measures ANOVA, correlation analysis, and receiver operator characteristic curves were used for statistical analyses (P losing >5% body mass. The IGF-I system is an important adjunct in the overall assessment of adaptation to stress imposed by high levels of physical activity superimposed on energy and sleep restriction and is more closely associated with losses in body mass and fat-free mass than other conventional nutritional biomarkers.

  8. TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection

    Directory of Open Access Journals (Sweden)

    Ulrike Schleicher

    2016-05-01

    Full Text Available Neutralization or deletion of tumor necrosis factor (TNF causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1 expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO synthase (NOS2 was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control.

  9. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs.

    Science.gov (United States)

    Manjarín, Rodrigo; Columbus, Daniel A; Suryawan, Agus; Nguyen, Hanh V; Hernandez-García, Adriana D; Hoang, Nguyet-Minh; Fiorotto, Marta L; Davis, Teresa

    2016-01-01

    Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants. The objective of this study was to determine if in neonates who can consume only 70 % of their protein and energy requirements for 8 days, enteral leucine supplementation will upregulate the mammalian target of rapamycin (mTOR) pathway in skeletal muscle, leading to an increase in protein synthesis and muscle anabolism. Nineteen 4-day-old piglets were fed by gastric tube 1 of 3 diets, containing (kg body weight(-1) · day(-1)) 16 g protein and 190 kcal (CON), 10.9 g protein and 132 kcal (R), or 10.8 g protein + 0.2 % leucine and 136 kcal (RL) at 4-h intervals for 8 days. On day 8, plasma AA and insulin levels were measured during 6 post-feeding intervals, and muscle protein synthesis rate and mTOR signaling proteins were determined at 120 min post-feeding. At 120 min, leucine was highest in RL (P protein synthesis, phosphorylation of S6 kinase (p-S6K1) and 4E-binding protein (p-4EBP1), and activation of eukaryotic initiation factor 4 complex (eIF4E · eIF4G). RL increased (P ≤ 0.01) p-S6K1, p-4EBP1 and eIF4E · eIF4G compared to R. In conclusion, when protein and energy intakes are restricted for 8 days, leucine supplementation increases muscle mTOR activation, but does not improve body weight gain or enhance skeletal muscle protein synthesis in neonatal pigs.

  10. Biochemical responses to dietary α-linolenic acid restriction proceed differently among brain regions in mice.

    Science.gov (United States)

    Miyazawa, Daisuke; Yasui, Yuko; Yamada, Kazuyo; Ohara, Naoki; Okuyama, Harumi

    2011-08-01

    Previously, we noted that the dietary restriction of α-linolenic acid (ALA, n-3) for 4 weeks after weaning brought about significant decreases in the BDNF content and p38 MAPK activity in the striatum of mice, but not in the other regions of the brain, compared with an ALA- and linoleic acid (LNA, n-6)-adequate diet. In this study, we examined whether a prolonged dietary manipulation induces biochemical changes in other regions of the brain as well. Mice were fed a safflower oil (SAF) diet (ALA-restricted, LNA-adequate) or a perilla oil (PER) diet (containing adequate amounts of ALA and LNA) for 8 weeks from weaning. The docosahexaenoic acid (DHA, 22:6n-3) contents and p38 MAPK activities in the cerebral cortex, striatum and hippocampus were significantly lower in the SAF group. The BDNF contents and protein kinase C (PKC) activities in the cerebral cortex as well as in the striatum, but not in the hippocampus, were significantly lower in the SAF group. These data indicate that the biochemical changes induced by the dietary restriction of ALA have a time lag in the striatum and cortex, suggesting that the signal is transmitted through decreased p38 MAPK activity and BDNF content and ultimately decreased PKC activity.

  11. Safety information on QT-interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

    2014-01-01

    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approve...

  12. Risk factors for QTc interval prolongation

    NARCIS (Netherlands)

    Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

    2018-01-01

    Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

  13. Prenatal risk indicators of a prolonged pregnancy

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Westergaard, Jes Grabow; Olsen, Jørn

    2006-01-01

    BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from...

  14. The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH can measure the impairment, activity limitations and participation restriction constructs from the International Classification of Functioning, Disability and Health (ICF

    Directory of Open Access Journals (Sweden)

    McQueen Margaret

    2008-08-01

    Full Text Available Abstract Background The International Classification of Functioning, Disability and Health (ICF model of the consequences of disease identifies three health outcomes, impairment, activity limitations and participation restrictions. However, few orthopaedic health outcome measures were developed with reference to the ICF. This study examined the ability of a valid and frequently used measure of upper limb function, namely the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH, to operationalise the ICF. Methods Twenty-four judges used the method of Discriminant Content Validation to allocate the 38 items of the DASH to the theoretical definition of one or more ICF outcome. One-sample t-tests classified each item as measuring, impairment, activity limitations, participation restrictions, or a combination thereof. Results The DASH contains items able to measure each of the three ICF outcomes with discriminant validity. The DASH contains five pure impairment items, 19 pure activity limitations items and three participation restriction items. In addition, seven items measured both activity limitations and participation restrictions. Conclusion The DASH can measure the three health outcomes identified by the ICF. Consequently the DASH could be used to examine the impact of trauma and subsequent interventions on each health outcome in the absence of measurement confound.

  15. [Brain function recovery after prolonged posttraumatic coma].

    Science.gov (United States)

    Klimash, A V; Zhanaidarov, Z S

    2016-01-01

    To explore the characteristics of brain function recovery in patients after prolonged posttraumatic coma and with long-unconscious states. Eighty-seven patients after prolonged posttraumatic coma were followed-up for two years. An analysis of a clinical/neurological picture after a prolonged episode of coma was based on the dynamics of vital functions, neurological status and patient's reactions to external stimuli. Based on the dynamics of the clinical/neurological picture that shows the recovery of functions of the certain brain areas, three stages of brain function recovery after a prolonged episode of coma were singled out: brain stem areas, diencephalic areas and telencephalic areas. These functional/anatomic areas of brain function recovery after prolonged coma were compared to the present classifications.

  16. Telomere Restriction Fragment (TRF) Analysis.

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al. , 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al. , 1990; Ouellette et al. , 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  17. Hormone supply of the organism in prolonged emotional stress

    Science.gov (United States)

    Amiragova, M. G.; Stulnikov, B. V.; Svirskaya, R. I.

    1980-01-01

    The effect of prolonged emotional stress of varying genesis on the hormonal function of the pancreas, thyroid gland, and adrenal cortex was studied. The amount of the hormonal secretion was found to depend on the type of adaptation activity and its duration. High secretion of the hormones observed outside the adaptation activity was examined as an index of the phase transition of defense reactions to the phase of overstress.

  18. Restrictions and Proportionality

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2009-01-01

    The article discusses three central aspects of the freedoms under European Community law, namely 1) the prohibition against restrictions as an important extension of the prohibition against discrimination, 2) a prohibition against exit restrictions which is just as important as the prohibition...... against host country restrictions, but which is often not recognised to the same extent by national law, and 3) the importance of also identifying and recognising an exit restriction, so that it is possible to achieve the required test of appropriateness and proportionality in relation to the rule...

  19. Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2–Signal Transducer and Activator of Transcription 3 Pathway

    Directory of Open Access Journals (Sweden)

    Kai Hu

    2018-03-01

    Full Text Available Inflammation is an energy-intensive process, and caloric restriction (CR could provide anti-inflammatory benefits. CR mimetics (CRM, such as the glycolytic inhibitor 2-deoxyglucose (2-DG, mimic the beneficial effects of CR without inducing CR-related physiologic disturbance. This study investigated the potential anti-inflammatory benefits of 2-DG and the underlying mechanisms in mice with lipopolysaccharide (LPS-induced lethal endotoxemia. The results indicated that pretreatment with 2-DG suppressed LPS-induced elevation of tumor necrosis factor alpha and interleukin 6. It also suppressed the upregulation of myeloperoxidase, attenuated Evans blue leakage, alleviated histological abnormalities in the lung, and improved the survival of LPS-challenged mice. Treatment with 2-DG had no obvious effects on the total level of pyruvate kinase M2 (PKM2, but it significantly suppressed LPS-induced elevation of PKM2 in the nuclei. Prevention of PKM2 nuclear accumulation by ML265 mimicked the anti-inflammatory benefits of 2-DG. In addition, treatment with 2-DG or ML265 suppressed the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3. Inhibition of STAT3 by stattic suppressed LPS-induced inflammatory injury. Interestingly, posttreatment with 2-DG at the early stage post-LPS challenge also improved the survival of the experimental animals. This study found that treatment with 2-DG, a representative CRM, provided anti-inflammatory benefits in lethal inflammation. The underlying mechanisms included suppressed nuclear PKM2-STAT3 pathway. These data suggest that 2-DG might have potential value in the early intervention of lethal inflammation.

  20. Caloric Restriction Mimetic 2-Deoxyglucose Alleviated Inflammatory Lung Injury via Suppressing Nuclear Pyruvate Kinase M2-Signal Transducer and Activator of Transcription 3 Pathway.

    Science.gov (United States)

    Hu, Kai; Yang, Yongqiang; Lin, Ling; Ai, Qing; Dai, Jie; Fan, Kerui; Ge, Pu; Jiang, Rong; Wan, Jingyuan; Zhang, Li

    2018-01-01

    Inflammation is an energy-intensive process, and caloric restriction (CR) could provide anti-inflammatory benefits. CR mimetics (CRM), such as the glycolytic inhibitor 2-deoxyglucose (2-DG), mimic the beneficial effects of CR without inducing CR-related physiologic disturbance. This study investigated the potential anti-inflammatory benefits of 2-DG and the underlying mechanisms in mice with lipopolysaccharide (LPS)-induced lethal endotoxemia. The results indicated that pretreatment with 2-DG suppressed LPS-induced elevation of tumor necrosis factor alpha and interleukin 6. It also suppressed the upregulation of myeloperoxidase, attenuated Evans blue leakage, alleviated histological abnormalities in the lung, and improved the survival of LPS-challenged mice. Treatment with 2-DG had no obvious effects on the total level of pyruvate kinase M2 (PKM2), but it significantly suppressed LPS-induced elevation of PKM2 in the nuclei. Prevention of PKM2 nuclear accumulation by ML265 mimicked the anti-inflammatory benefits of 2-DG. In addition, treatment with 2-DG or ML265 suppressed the phosphorylation of nuclear signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 by stattic suppressed LPS-induced inflammatory injury. Interestingly, posttreatment with 2-DG at the early stage post-LPS challenge also improved the survival of the experimental animals. This study found that treatment with 2-DG, a representative CRM, provided anti-inflammatory benefits in lethal inflammation. The underlying mechanisms included suppressed nuclear PKM2-STAT3 pathway. These data suggest that 2-DG might have potential value in the early intervention of lethal inflammation.

  1. Prolonged CT urography in duplex kidney.

    Science.gov (United States)

    Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

    2016-05-13

    Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

  2. Restricting wolves risks escape

    Science.gov (United States)

    Mech, L. David; Ballard, Warren; Bangs, Ed; Ream, Bob

    2010-01-01

    Implementing the proposal set forth by Licht and colleagues (BioScience 60: 147–153) requires restricting wolves to tiny "islands," areas that are magnitudes smaller than the ranges of most wolf populations. Wolves naturally have large ranges; restricting their spatial needs increases the risk of wolves escaping, exacerbating public relations and political and legal problems.

  3. Exogenous progesterone exacerbates running response of adolescent female mice to repeated food restriction stress by changing α4-GABAA receptor activity of hippocampal pyramidal cells.

    Science.gov (United States)

    Wable, G S; Chen, Y-W; Rashid, S; Aoki, C

    2015-12-03

    Adolescent females are particularly vulnerable to mental illnesses with co-morbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel-running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain resistance

  4. Avoided crossings, conical intersections, and low-lying excited states with a single reference method: the restricted active space spin-flip configuration interaction approach.

    Science.gov (United States)

    Casanova, David

    2012-08-28

    The restricted active space spin-flip CI (RASCI-SF) performance is tested in the electronic structure computation of the ground and the lowest electronically excited states in the presence of near-degeneracies. The feasibility of the method is demonstrated by analyzing the avoided crossing between the ionic and neutral singlet states of LiF along the molecular dissociation. The two potential energy surfaces (PESs) are explored by means of the energies of computed adiabatic and approximated diabatic states, dipole moments, and natural orbital electronic occupancies of both states. The RASCI-SF methodology is also used to study the ground and first excited singlet surface crossing involved in the double bond isomerization of ethylene, as a model case. The two-dimensional PESs of the ground (S(0)) and excited (S(1)) states are calculated for the complete configuration space of torsion and pyramidalization molecular distortions. The parameters that define the state energetics in the vicinity of the S(0)/S(1) conical intersection region are compared to complete active space self-consistent field (CASSCF) results. These examples show that it is possible to describe strongly correlated electronic states using a single reference methodology without the need to expand the wavefunction to high levels of collective excitations. Finally, RASCI is also examined in the electronic structure characterization of the ground and 2(1)A(g)(-), 1(1)B(u)(+), 1(1)B(u)(-), and 1(3)B(u)(-) states of all-trans polyenes with two to seven double bonds and beyond. Transition energies are compared to configuration interaction singles, time-dependent density functional theory (TDDFT), CASSCF, and its second-order perturbation correction calculations, and to experimental data. The capability of RASCI-SF to describe the nature and properties of each electronic state is discussed in detail. This example is also used to expose the properties of different truncations of the RASCI wavefunction and to

  5. Licence prolongations of US nuclear power plants

    International Nuclear Information System (INIS)

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  6. Prolonged delirium misdiagnosed as a mood disorder.

    Science.gov (United States)

    Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

    2017-01-01

    Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

  7. QT Prolongation due to Graves’ Disease

    Directory of Open Access Journals (Sweden)

    Zain Kulairi

    2017-01-01

    Full Text Available Hyperthyroidism is a highly prevalent disease affecting over 4 million people in the US. The disease is associated with many cardiac complications including atrial fibrillation and also less commonly with ventricular tachycardia and fibrillation. Many cardiac pathologies have been extensively studied; however, the relationship between hyperthyroidism and rate of ventricular repolarization manifesting as a prolonged QTc interval is not well known. Prolonged QTc interval regardless of thyroid status is a risk factor for cardiovascular mortality and life-threatening ventricular arrhythmia. The mechanism regarding the prolongation of the QT interval in a hyperthyroid patient has not been extensively investigated although its clinical implications are relevant. Herein, we describe a case of prolonged QTc in a patient who presented with signs of hyperthyroidism that was corrected with return to euthyroid status.

  8. Prolonged parenteral nutrition after neonatal gastrointestinal surgery

    DEFF Research Database (Denmark)

    Estmann, Anne; Qvist, Niels; Husby, Steffen

    2002-01-01

    to diagnosis and clinical course. METHODOLOGY: This study reviews the clinical course of infants with gastrointestinal disease (gastroschisis, intestinal atresia, omphalocele, volvulus, Hirschsprung's disease and necrotizing enterocolitis) with a prolonged need for parenteral nutrition in the Western part...

  9. Prolonged Pregnancy: Methods, Causal Determinants and Outcome

    DEFF Research Database (Denmark)

    Olesen, Annette Wind

    ) to study the incidence of prolonged pregnancy as a function of methods for determining gestational age; 2) to determine the risk of obstetrical and fetal complications in prolonged pregnancy; 3) to validate the self-reported gestational age in the National Birth Cohort; 4) to determine whether...... an ultrasound scan in the first or second trimester, or menstrual history was best at predicting the day of delivery; 5) to study the risk of recurrence of prolonged pregnancy as a function of change in male partner, social status and municipality; and 6) to detect prenatal risk indicators of prolonged...... of perinatal and obstetrical complications was high in post-term delivery compared to term delivery (OR between 1.2 and 3.1). The risk of perinatal death (OR=1.36 (1.08-1.72)) was also higher in the post-term group (I). The self-reported gestational ages in the National Birth Cohort correlated well with data...

  10. QT interval prolongation associated with sibutramine treatment

    Science.gov (United States)

    Harrison-Woolrych, Mira; Clark, David W J; Hill, Geraldine R; Rees, Mark I; Skinner, Jonathan R

    2006-01-01

    Aims To investigate a possible association of sibutramine with QT interval prolongation. Methods Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. Results The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QTc at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. Conclusions This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval. PMID:16542208

  11. Stress-induced activation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is restricted to telencephalic areas in the rat brain: relationship to c-fos mRNA.

    Science.gov (United States)

    Ons, Sheila; Martí, Octavi; Armario, Antonio

    2004-06-01

    Arc is an effector immediate early gene whose expression is induced in situations of increased neuronal activity. However, there is no report on the influence of stress on Arc expression. Here, we compared the induction of both c-fos and Arc mRNAs in the brain of rats exposed to one of three different stressful situations: novel environment, forced swimming and immobilization. An absent or weak c-fos mRNA signal was observed in control rats, whereas those exposed to one of three stressors showed enhanced c-fos expression in a wide range of brain areas. Constitutive Arc expression was observed in some areas such as cortex, striatum, hippocampus, reticular thalamic nucleus and cerebellar cortex. In response to stressors, a strong induction of Arc was observed, but the pattern was different from that of c-fos. For instance, activation of Arc but not c-fos was observed in the nucleus accumbens after immobilization and in the hippocampus after novel environment. No Arc induction was observed in diencephalic and brainstem areas. The present data show that Arc has a neuroanatomically restricted pattern of induction in the brain after emotional stress. Telencephalic activation suggests that a more intense induction of synaptic plasticity is occurring in this area after exposure to emotional stressors.

  12. Quality of drug label information on QT interval prolongation

    DEFF Research Database (Denmark)

    Warnier, Miriam J; Holtkamp, Frank A; Rutten, Frans H

    2014-01-01

    BACKGROUND: Information regarding QT-prolongation in the drug label may vary between products. This could lead to suboptimal risk minimization strategies. OBJECTIVE: To systematically assess the variation in the extent and content of information on QT prolongation in the summary of product......-prolongation'/'QT-prolongation') and the advice on cautionary measures pertaining to QT-prolongation in the label were examined, as well as their association. RESULTS: Of the 175 screened products, 44 contained information on QT in the SPC ('no QT-prolongation': 23%, 'unclear drug-QT association': 43%, 'possibly QT-prolongation': 16%, 'QT......-prolongation': 18%). 62% contained advices to act with caution in patients with additional risk factors for QT-prolongation. Products that more likely to have QT-prolonging properties according to the SPC provided more information on QT-prolongation in the SPC ('no prolongation': 10% and for the category 'QT...

  13. Peptide-loaded dendritic cells prime and activate MHC-class I-restricted T cells more efficiently than protein-loaded cross-presenting DC

    DEFF Research Database (Denmark)

    Met, Ozcan; Buus, Søren; Claesson, Mogens H

    2003-01-01

    -pulsed DC. Moreover, SIINFEKL-loaded DC were up to 50 times more efficient than DC-pulsed with OVA-protein for generation of an H-2K(b)-restricted response. Immunization of mice with SIINFEKL-loaded DC resulted in a much stronger H-2K(b)-restricted response than immunization with OVA-pulsed DC. These data......Undifferentiated and differentiated dendritic cells (uDC and dDC, respectively), derived from the bone marrow, were studied in vitro and in vivo. Ovalbumin (OVA) and two OVA-derived peptides binding to H-2K(b) and I-A(b), respectively, were used. Two IL-2 secreting T cell hybridomas specific...... for the OVA-derived epitopes were used in the in vitro read-out. The ability to cross-present the H-2K(b) binding OVA(257-264)-peptide (SIINFEKL) was restricted to dDC, which express CD11c(+), CD86(+), and MHC-II(+). In vitro, the antigenicity of SIINFEKL-loaded DC declined at a slower rate than that of OVA...

  14. Prolonged non-metabolic heart rate variability reduction as a physiological marker of psychological stress in daily life

    NARCIS (Netherlands)

    Verkuil, B.; Brosschot, J.F.; Tollenaar, M.S.; Lane, R.D.; Thayer, J.F.

    2016-01-01

    BACKGROUND Prolonged cardiac activity that exceeds metabolic needs can be detrimental for somatic health. Psychological stress could result in such "additional cardiac activity." PURPOSE In this study, we examined whether prolonged additional reductions in heart rate variability (AddHRVr) can be

  15. Protein restriction and cancer.

    Science.gov (United States)

    Yin, Jie; Ren, Wenkai; Huang, Xingguo; Li, Tiejun; Yin, Yulong

    2018-03-26

    Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. BAHAN PENYERAP KMnO4 DAN ASAM L-ASKORBAT DALAM PENGEMASAN AKTIF (ACTIVE PACKAGING UNTUK MEMPERPANJANG MASA SIMPAN DAN MEMPERTAHANKAN MUTU BUAH DUKU (Lansium domesticum Corr. [Adsorbers for KMnO4 and L-Ascorbic Acid in the Active Packaging to Prolong the Shelve-Life and Maintain the Quality of Lanzone (Lansium domesticum Corr. Fruits

    Directory of Open Access Journals (Sweden)

    Soesiladi E Widodo

    2005-08-01

    Full Text Available To develop an active packaging of lanzone (Lansium domisticum Corr. Fruits, KmnO4 as an ethylene scavenger and L-ascorbic acid as an oxygent scavenger were inserted into packaging. As direct contact of KmnO4 with agricultural product was not recommended and due to the liquid characteristic of both scavenger was carried out. This research was aimed at finding out the best adsorbers for KmnO4, L-ascorbic acid, and their combination in an active packaging to prolog the shelve-life and to maintain the quality of lanzone fruits. The result showed that 1 among the four adsorbers tested, pumice could was the best alternative as a KmnO4 or L-ascorbic acid adsorbers, and 2 spon and pumice were the best alternative adsorber for the combination of KmnO4 or L-ascorbic acid. Both adsorber were effective in prolonging the shelve-live (8-11 days longer than with out packaging and as good as using silica gel and vermiculite and maintaining the quality of lanzone fruits.

  17. Prolonged minor allograft survival in intravenously primed mice--a test of the veto hypothesis

    International Nuclear Information System (INIS)

    Johnson, L.L.

    1987-01-01

    Experiments were performed to test the hypothesis that veto cells are responsible for the prolonged survival of minor allografts of skin that is observed in recipients primed intravenously with spleen cells from mice syngeneic with the skin donors. This prolonged survival was observed for each of several minor histocompatibility (H) antigens and is antigen-specific. Gamma radiation (3300 rads) abolished the ability of male spleen cells infused i.v. to delay the rejection of male skin grafts (H-Y antigen) on female recipients. However, depletion of Thy-1+ cells from the i.v. infusion failed to abolish the ability to prolong male skin graft survival. Furthermore, the prolonged survival accorded to B6 (H-2b) male skin grafts on CB6F1 (H-2b/H-2d) female recipients given i.v. infusions of B6 male spleen cells extended to BALB/c (H-2d) male skin grafts as well, indicating a lack of MHC restriction. Thus, prolongation of minor allograft survival by i.v. infusion of minor H antigen-bearing spleen cells appears not to depend on veto T cells that others have found to be responsible for the suppression of CTL generation

  18. Intrauterine growth restriction

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-07-01

    Full Text Available It is estimated that the true prevalence of intrauterine growth restriction is 3-10% of all pregnancies, making this fetal condition one of the most frequent obstetric problems, together with premature labor and premature rupture of membranes. The article stresses the importance of early diagnosis because of the associated risks.

  19. Late gestational nutrient restriction

    DEFF Research Database (Denmark)

    Tygesen, Malin Plumhoff; Nielsen, Mette Olaf; Nørgaard, Peder

    2008-01-01

    We investigated the effect of 50% nutrient restriction during the last 6 weeks of gestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, ß-hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb birth weight and ewes' lactation performance. Plasma...

  20. Restricted Variance Interaction Effects

    DEFF Research Database (Denmark)

    Cortina, Jose M.; Köhler, Tine; Keeler, Kathleen R.

    2018-01-01

    Although interaction hypotheses are increasingly common in our field, many recent articles point out that authors often have difficulty justifying them. The purpose of this article is to describe a particular type of interaction: the restricted variance (RV) interaction. The essence of the RV int...

  1. SALIVARY ANTIMICROBIAL PROTEIN RESPONSE TO PROLONGED RUNNING

    Directory of Open Access Journals (Sweden)

    Suzanne Schneider

    2013-01-01

    Full Text Available Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs. Salivary IgA (IgA has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys and lactoferrin (Lac. Objective: To determine the effect of a 50-km trail race on salivary cortisol (Cort, IgA, Lys, and Lac. Methods: 14 subjects: (6 females, 8 males completed a 50km ultramarathon. Saliva was collected pre, immediately after (post and 1.5 hrs post race ( 1.5. Results: Lac concentration was higher at 1.5 hrs post race compared to post exercise (p0.05. IgA concentration, secretion rate, and IgA/Osm were lower 1.5 hrs post compared to pre race (p<0.05. Cort concentration was higher at post compared to 1.5 (p<0.05, but was unaltered from pre race levels. Subjects finished in 7.81 ± 1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p<0.05 compared to pre race. Conclusions: The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

  2. Prolonged displacement may compromise resilience in Eritrean ...

    African Journals Online (AJOL)

    Objective: to assess the impact of prolonged displacement on the resilience of Eritrean mothers. Methods: an adapted SOC scale (short form) was administered. Complementary qualitative data were gathered from study participants' spontaneous reactions to and commentaries on the SOC scale. Results: Displaced ...

  3. Prolonged Cholestatic Jaundice Associated With Flurbiprofen.

    Science.gov (United States)

    Dogan, Serkan; Celikbilek, Mehmet; Demirkan, Kutay; Yilmaz, Semih; Deniz, Kemal; Gursoy, Sebnem; Yucesoy, Mehmet

    2014-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia. © The Author(s) 2013.

  4. Hippocampal Abnormalities after Prolonged Febrile Convulsions

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available Hippocampal volume and T2 relaxation times were determined in an MRI study of 14 children with prolonged febrile convulsions (PFC who were investigated, 1 within 5 days of a PFC, and 2 at follow-up 4-8 months after the acute study, at the Institute of Child Health, University College, and Great Ormond Street Hospital, London, UK.

  5. Translating QT interval prolongation from conscious dogs to humans.

    Science.gov (United States)

    Dubois, Vincent F S; Smania, Giovanni; Yu, Huixin; Graf, Ramona; Chain, Anne S Y; Danhof, Meindert; Della Pasqua, Oscar

    2017-02-01

    In spite of screening procedures in early drug development, uncertainty remains about the propensity of new chemical entities (NCEs) to prolong the QT/QTc interval. The evaluation of proarrhythmic activity using a comprehensive in vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences in vivo. In the present study, we evaluated the correlation between drug-specific parameters describing QT interval prolongation in dogs and in humans. Using estimates of the drug-specific parameter, data on the slopes of the PKPD relationships of nine compounds with varying QT-prolonging effects (cisapride, sotalol, moxifloxacin, carabersat, GSK945237, SB237376 and GSK618334, and two anonymized NCEs) were analysed. Mean slope estimates varied between -0.98 ms μM -1 and 6.1 ms μM -1 in dogs and -10 ms μM -1 and 90 ms μM -1 in humans, indicating a wide range of effects on the QT interval. Linear regression techniques were then applied to characterize the correlation between the parameter estimates across species. For compounds without a mixed ion channel block, a correlation was observed between the drug-specific parameter in dogs and humans (y = -1.709 + 11.6x; R 2  = 0.989). These results show that per unit concentration, the drug effect on the QT interval in humans is 11.6-fold larger than in dogs. Together with information about the expected therapeutic exposure, the evidence of a correlation between the compound-specific parameter in dogs and in humans represents an opportunity for translating preclinical safety data before progression into the clinic. Whereas further investigation is required to establish the generalizability of our findings, this approach can be used with clinical trial simulations to predict the probability of QT prolongation in humans. © 2016 The British Pharmacological Society.

  6. Muscular soreness following prolonged intermittent high-intensity shuttle running.

    Science.gov (United States)

    Thompson, D; Nicholas, C W; Williams, C

    1999-05-01

    The aim of this study was to examine the impact of prolonged intermittent high-intensity shuttle running on soreness and markers of muscle damage. Sixteen males took part in the study, half of whom were assigned to a running group and half to a resting control group. The exercise protocol involved 90 min of intermittent shuttle running and walking (Loughborough Intermittent Shuttle Test: LIST), reflecting the activity pattern found in multiple-sprint sports such as soccer. Immediately after exercise, there was a significant increase (P < 0.05) in serum activities of creatine kinase and aspartate aminotransferase, and values remained above baseline for 48 h (P < 0.05). Median peak activities of creatine kinase and aspartate aminotransferase occurred 24 h post-exercise and were 774 and 43 U x l(-1), respectively. The intensity of general muscle soreness, and in the specific muscles investigated, was greater than baseline for 72 h after the shuttle test (P < 0.05), peaking 24-48 h post-exercise (P < 0.05). Muscle soreness was not correlated with either creatine kinase or aspartate aminotransferase activity. Soreness was most frequently reported in the hamstrings. Neither soreness nor serum enzyme activity changed in the controls over the 4 day observation period. It appears that unaccustomed performance of prolonged intermittent shuttle running produces a significant increase in both soreness and markers of muscle damage.

  7. Rurality study of restricted areas

    Directory of Open Access Journals (Sweden)

    Sergio Rivaroli

    2011-02-01

    Full Text Available Two main perspectives of investigation emerge from the study of a territory’s rurality: a geographical approach and a sociological approach. The research examines the sub-regional study case of ‘Nuovo circondario imolese’. The analysis shows that the combination of traditional institutional criteria with detailed informations about the territory, generates more accurate results which determine a better comprehension of the characteristics of restricted areas’ rurality. Over the period 1991-2001, the study highlights an increase in rural areas. This result could be interpreted as an effect of urban sprawl’s intensification, that increases the competition between non-farm residences and agricultural activities.

  8. Patients with prolonged effect of succinylcholine or mivacurium had novel mutations in the butyrylcholinesterase gene

    DEFF Research Database (Denmark)

    Wichmann, Sine; Færk, Gitte; Bundgaard, Jens R.

    2016-01-01

    with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used......Introduction Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general...... anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. Methods The Danish Cholinesterase Research Unit registers patients...

  9. Licence prolongations of US nuclear power plants; Les prolongations de licence des centrales nucleaires americaines

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-04-01

    Licences of US nuclear reactors were initially attributed for a 40 years duration. However, the vast majority of the reactors can benefit of a licence prolongation for a period of 20 years maximum. This article recalls first the procedure to follow for the licence prolongation demands (safety analysis, components aging, environmental impact statement), and then it makes a status of the accepted prolongations, of the demands under examination, and of the demands that should be presented in the next 5 years. (J.S.)

  10. Sidestep and crossover lower limb kinematics during a prolonged sport-like agility test.

    Science.gov (United States)

    Potter, Danielle; Reidinger, Kellie; Szymialowicz, Rebecca; Martin, Thomas; Dione, Donald; Feinn, Richard; Wallace, David; Garbalosa, Juan C

    2014-10-01

    Non-contact anterior cruciate ligament (ACL) injuries in athletes occur more often towards the end of athletic competitions. However, the exact mechanisms of how prolonged activity increases the risk for ACL injuries are not clear. To determine the effect of prolonged activity on the hip and knee kinematics observed during self-selected cutting maneuvers performed in a timed agility test. Nineteen female Division I collegiate soccer players completed a self-selected cutting agility test until they were unable to meet a set performance time (one standard deviation of the average baseline trial). Using the 3D dimensional coordinate data the cut type was identified by the principle investigators. The 3D hip and knee angles at 32ms post heel strike were analyzed using a two-factor, linear mixed model to assess the effect of prolonged activity and cut type on the recorded mean hip and knee angles. Athletes performed either sidestep or crossover cuts. An effect of cut type and prolonged activity was seen at the hip and knee. During the prolonged activity trials, the knee was relatively more adducted and both the hip and knee were less flexed than during the baseline trials regardless of cut type. Regardless of activity status, during sidestep cuts, the hip was more internally rotated and abducted, and less flexed than during crossover cuts while the knee was more abducted and less flexed during the sidestep than crossover cuts. During a sport-like agility test, prolonged activity appears to predispose the athlete to position their knee in a more extended and abducted posture and their hip in a more extended posture. This position has been suggested to place stress on the ACL and potentially increase the risk for injury. Clinicians may want to consider the effects of prolonged activity on biomechanical risk factors for sustaining ACL injuries in the design of intervention strategies to prevent ACL injuries. Level 4.

  11. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity

    Science.gov (United States)

    Park, J.-W.; Moon, C.H.; Harmache, A.; Wargo, A.R.; Purcell, M.K.; Bremont, M.; Kurath, G.

    2011-01-01

    Previously, we demonstrated that a representative M genogroup type strain of infectious haematopoietic necrosis virus (IHNV) from rainbow trout grows well in rainbow trout-derived RTG-2 cells, but a U genogroup type strain from sockeye salmon has restricted growth, associated with reduced genome replication and mRNA transcription. Here, we analysed further the mechanisms for this growth restriction of U-type IHNV in RTG-2 cells, using strategies that assessed differences in viral genes, host immune regulation and phosphorylation. To determine whether the viral glycoprotein (G) or non-virion (NV) protein was responsible for the growth restriction, four recombinant IHNV viruses were generated in which the G gene of an infectious IHNV clone was replaced by the G gene of U- or M-type IHNV and the NV gene was replaced by NV of U- or M-type IHNV. There was no significant difference in the growth of these recombinants in RTG-2 cells, indicating that G and NV proteins are not major factors responsible for the differential growth of the U- and M-type strains. Poly I:C pretreatment of RTG-2 cells suppressed the growth of both U- and M-type IHNV, although the M virus continued to replicate at a reduced level. Both viruses induced type 1 interferon (IFN1) and the IFN1 stimulated gene Mx1, but the expression levels in M-infected cells were significantly higher than in U-infected cells and an inhibitor of the IFN1-inducible protein kinase PKR, 2-aminopurine (2-AP), did not affect the growth of U- or M-type IHNV in RTG-2 cells. These data did not indicate a role for the IFN1 system in the restricted growth of U-type IHNV in RTG-2 cells. Prediction of kinase-specific phosphorylation sites in the viral phosphoprotein (P) using the NetPhosK program revealed differences between U- and M-type P genes at five phosphorylation sites. Pretreatment of RTG-2 cells with a PKC inhibitor or a p38MAPK inhibitor did not affect the growth of the U- and M-type viruses. However, 100 μm of the

  12. Prdm1a and miR-499 act sequentially to restrict Sox6 activity to the fast-twitch muscle lineage in the zebrafish embryo.

    Science.gov (United States)

    Wang, XinGang; Ono, Yosuke; Tan, Swee Chuan; Chai, Ruth JinFen; Parkin, Caroline; Ingham, Philip W

    2011-10-01

    Sox6 has been proposed to play a conserved role in vertebrate skeletal muscle fibre type specification. In zebrafish, sox6 transcription is repressed in slow-twitch progenitors by the Prdm1a transcription factor. Here we identify sox6 cis-regulatory sequences that drive fast-twitch-specific expression in a Prdm1a-dependent manner. We show that sox6 transcription subsequently becomes derepressed in slow-twitch fibres, whereas Sox6 protein remains restricted to fast-twitch fibres. We find that translational repression of sox6 is mediated by miR-499, the slow-twitch-specific expression of which is in turn controlled by Prdm1a, forming a regulatory loop that initiates and maintains the slow-twitch muscle lineage.

  13. Sleep restriction may lead to disruption in physiological attention and reaction time

    Directory of Open Access Journals (Sweden)

    Arbind Kumar Choudhary

    2016-07-01

    Full Text Available Sleepiness is the condition where for some reason fails to go into a sleep state and will have difficulty in remaining awake even while carrying out activities. Sleep restriction occurs when an individual fails to get enough sleep due to high work demands. The mechanism between sleep restriction and underlying brain physiology deficits is not well assumed. The objective of the present study was to investigate the mental attention (P300 and reaction time [visual (VRT and auditory (ART] among night watchmen, at subsequent; first (1st day, fourth (4th day and seventh (7th day of restricted sleep period. After exclusion and inclusion criteria, the study was performed among 50 watchmen (age=18–35 years (n=50 after providing written informed consent and divided into two group. Group I-(Normal sleep (n=28 working in day time and used to have normal sleep in night (≥8 h; Group II-(Restricted sleep (n=22 - working in night time and used to have less sleep in night (≤3 h. Statistical significance between the different groups was determined by the independent student ʻtʼ test and the significance level was fixed at p≤0.05. We observed that among all normal and restricted sleep watchmen there was not any significant variation in Karolinska Sleepiness Scale (KSS score, VRT and ART, along with latency and amplitude of P300 on 1st day of restricted sleep. However at subsequent on 4th day and 7th day of restricted sleep, there was significant increase in (KSSscore, and prolongation of VRT and ART as well as alteration in latency and amplitude of P300 wave in restricted sleep watchmen when compare to normal sleep watchmen. The present finding concludes that loss of sleep has major impact in dynamic change in mental attention and reaction time among watchmen employed in night shift. Professional regulations and work schedules should integrate sleep schedules before and during the work period as an essential dimension for their healthy life.

  14. Sleep restriction may lead to disruption in physiological attention and reaction time.

    Science.gov (United States)

    Choudhary, Arbind Kumar; Kishanrao, Sadawarte Sahebrao; Dadarao Dhanvijay, Anup Kumar; Alam, Tanwir

    2016-01-01

    Sleepiness is the condition where for some reason fails to go into a sleep state and will have difficulty in remaining awake even while carrying out activities. Sleep restriction occurs when an individual fails to get enough sleep due to high work demands. The mechanism between sleep restriction and underlying brain physiology deficits is not well assumed. The objective of the present study was to investigate the mental attention (P300) and reaction time [visual (VRT) and auditory (ART)] among night watchmen, at subsequent; first (1st) day, fourth (4th) day and seventh (7th) day of restricted sleep period. After exclusion and inclusion criteria, the study was performed among 50 watchmen (age=18-35 years) (n=50) after providing written informed consent and divided into two group. Group I-(Normal sleep) (n=28) working in day time and used to have normal sleep in night (≥8 h); Group II-(Restricted sleep) (n=22) - working in night time and used to have less sleep in night (≤3 h). Statistical significance between the different groups was determined by the independent student ' t ' test and the significance level was fixed at p≤0.05. We observed that among all normal and restricted sleep watchmen there was not any significant variation in Karolinska Sleepiness Scale (KSS) score, VRT and ART, along with latency and amplitude of P300 on 1st day of restricted sleep. However at subsequent on 4th day and 7th day of restricted sleep, there was significant increase in (KSS)score, and prolongation of VRT and ART as well as alteration in latency and amplitude of P300 wave in restricted sleep watchmen when compare to normal sleep watchmen. The present finding concludes that loss of sleep has major impact in dynamic change in mental attention and reaction time among watchmen employed in night shift. Professional regulations and work schedules should integrate sleep schedules before and during the work period as an essential dimension for their healthy life.

  15. Safety and efficacy of prolonged epidural analgesia after oncologic colorectal surgery

    Directory of Open Access Journals (Sweden)

    R. V. Garyaev

    2012-01-01

    Full Text Available This study demonstrates effective thoracic epidural analgesia by ropivacain 0.2 %, phentanyl 2 mkg/ml, adrenaline 2 mkg/ml in single-use infusion pumps in 124 patients, who underwent surgery for colorectal cancer. Safe, effective and controllable analgesia was observed during surgery and postoperative period. Prolonged analgesia facilitates early rehabilitation and improves gastrointestinal peristaltic activity.  Prolonged epidural analgesia is the recommended method of analgesia in this group of patients.

  16. Prolonged ketamine exposure induces increased activity of the GluN2B-containing N-methyl-d-aspartate receptor in the anterior cingulate cortex of neonatal rats.

    Science.gov (United States)

    Kokane, Saurabh S; Gong, Kerui; Jin, Jianhui; Lin, Qing

    2017-09-01

    Ketamine is a commonly used anesthetic among pediatric patients due to its high efficacy. However, it has been demonstrated by several preclinical studies that, widespread accelerated programmed death of neurons (neuroapoptosis) occurs due to prolonged or repeated exposure to ketamine specifically in the neonatal brain. Therefore, an emphasis on understanding the molecular mechanisms underlying this selective vulnerability of the neonatal brain to ketamine-induced neuroapoptosis becomes important in order to identify potential therapeutic targets, which would help prevent or at least ameliorate this neuroapoptosis. In this study, we demonstrated that repeated ketamine administration (6 injections of 20mg/kg dose given over 12h time period) in neonatal (postnatal day 7; PND 7) Sprague-Dawley rats induced a progressive increase in N-methyl-d-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents (EPSCs) in the neurons of the anterior cingulate cortex (ACC) for up to 6h after the last ketamine dose. Specifically, we observed that the increased EPSCs were largely mediated by GluN2B-containing NMDARs in the neurons of the ACC. Along with increased synaptic transmission, there was also a significant increase in the expression of the GluN2B-containing NMDARs as well. Taken together, these results showed that after repeated exposure to ketamine, the synaptic transmission mediated by GluN2B-containing NMDARs was significantly increased in the neonatal brain. This was significant as it showed for the first time that ketamine had subunit-specific effects on GluN2B-containing NMDARs, potentially implicating the involvement of these subunits in the increased vulnerability of immature neurons of the neonatal brain to ketamine-induced neuroapoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Health Benefits of Fasting and Caloric Restriction.

    Science.gov (United States)

    Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

    2017-10-23

    Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

  18. Evolutionary genomics and HIV restriction factors.

    Science.gov (United States)

    Pyndiah, Nitisha; Telenti, Amalio; Rausell, Antonio

    2015-03-01

    To provide updated insights into innate antiviral immunity and highlight prototypical evolutionary features of well characterized HIV restriction factors. Recently, a new HIV restriction factor, Myxovirus resistance 2, has been discovered and the region/residue responsible for its activity identified using an evolutionary approach. Furthermore, IFI16, an innate immunity protein known to sense several viruses, has been shown to contribute to the defense to HIV-1 by causing cell death upon sensing HIV-1 DNA. Restriction factors against HIV show characteristic signatures of positive selection. Different patterns of accelerated sequence evolution can distinguish antiviral strategies--offense or defence--as well as the level of specificity of the antiviral properties. Sequence analysis of primate orthologs of restriction factors serves to localize functional domains and sites responsible for antiviral action. We use recent discoveries to illustrate how evolutionary genomic analyses help identify new antiviral genes and their mechanisms of action.

  19. Severe bradycardia and prolonged hypotension in ciguatera.

    Science.gov (United States)

    Chan, Thomas Yan Keung

    2013-06-01

    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  20. The Significance of Prolonged and Saddleback Fever in Hospitalised Adult Dengue.

    Directory of Open Access Journals (Sweden)

    Deborah Hl Ng

    Full Text Available Dengue fever is gaining importance in Singapore with an increase in the number of cases and mortality in recent years. Although prolonged and saddleback fever have been reported in dengue fever, there are no specific studies on their significance in dengue. This study aims to examine the prevalence of prolonged and saddleback fever in dengue as well as their associations with dengue severity. A total of 2843 polymerase-chain reaction (PCR confirmed dengue patients admitted to Tan Tock Seng Hospital from 2004 to 2008 were included in the study. Sixty-nine percent of them were male with a median age of 34 years. Prolonged fever (fever > 7 days duration was present in 572 (20.1% of patients. Dengue hemorrhagic fever (DHF, dengue shock syndrome (DSS and severe dengue (SD were significantly more likely to occur in patients with prolonged fever. Mucosal bleeding, anorexia, diarrhea, abdominal pain, nausea or vomiting, lethargy, rash, clinical fluid accumulation, hepatomegaly, nosocomial infection, leukopenia, higher neutrophil count, higher hematocrit, higher alanine transaminase (ALT and aspartate transaminase (AST, higher creatinine, lower protein and prolonged activated partial thromboplastin time (APTT were significantly associated with prolonged fever but not platelet count or prothrombin time (PT. Saddleback fever was present in 165 (5.8%. Although DHF and SD were more likely to occur in patients in those with saddleback fever, DSS was not. Compared with prolonged fever, saddleback fever did not show many significant associations except for diarrhea, abdominal pain, clinical fluid accumulation, hematocrit and platelet change, and lower systolic blood pressure. This study demonstrates that prolonged fever may be associated with various warning signs and more severe forms of dengue (SD, DSS, DHF, while saddleback fever showed associations with DHF and SD but not DSS. The presence of prolonged or saddleback fever in dengue patients should therefore

  1. Variation in Definition of Prolonged Mechanical Ventilation.

    Science.gov (United States)

    Rose, Louise; McGinlay, Michael; Amin, Reshma; Burns, Karen Ea; Connolly, Bronwen; Hart, Nicholas; Jouvet, Philippe; Katz, Sherri; Leasa, David; Mawdsley, Cathy; McAuley, Danny F; Schultz, Marcus J; Blackwood, Bronagh

    2017-10-01

    Consistency of definitional criteria for terminology applied to describe subject cohorts receiving mechanical ventilation within ICU and post-acute care settings is important for understanding prevalence, risk stratification, effectiveness of interventions, and projections for resource allocation. Our objective was to quantify the application and definition of terms for prolonged mechanical ventilation. We conducted a scoping review of studies (all designs except single-case study) reporting a study population (adult and pediatric) using the term prolonged mechanical ventilation or a synonym. We screened 5,331 references, reviewed 539 full-text references, and excluded 120. Of the 419 studies (representing 38 countries) meeting inclusion criteria, 297 (71%) reported data on a heterogeneous subject cohort, and 66 (16%) included surgical subjects only (46 of those 66, 70% cardiac surgery). Other studies described COPD (16, 4%), trauma (22, 5%), neuromuscular (17, 4%), and sepsis (1, 0.2%) cohorts. A total of 741 terms were used to refer to the 419 study cohorts. The most common terms were: prolonged mechanical ventilation (253, 60%), admission to specialized unit (107, 26%), and long-term mechanical ventilation (79, 19%). Some authors (282, 67%) defined their cohorts based on duration of mechanical ventilation, with 154 studies (55%) using this as the sole criterion. We identified 37 different durations of ventilation ranging from 5 h to 1 y, with > 21 d being the most common (28 of 282, 7%). For studies describing a surgical cohort, minimum ventilation duration required for inclusion was ≥ 24 h for 20 of 66 studies (30%). More than half of all studies (237, 57%) did not provide a reason/rationale for definitional criteria used, with only 28 studies (7%) referring to a consensus definition. We conclude that substantial variation exists in the terminology and definitional criteria for cohorts of subjects receiving prolonged mechanical ventilation. Standardization of

  2. Prolonged Exposure: a Rapid Treatment for Phobias

    Science.gov (United States)

    Watson, J. P.; Gaind, R.; Marks, I. M.

    1971-01-01

    Ten adult patients with long-standing specific phobias were treated by prolonged continuous exposure to their phobic objects in fantasy and reality without avoidance. All patients were greatly helped by four to five hours' treatment in two or three sessions, and all improved more after practice than after imaginal sessions. The treatment method is more economical and efficient than other methods described so far. PMID:5539135

  3. The association between the social and communication elements of autism, and repetitive/restrictive behaviours and activities: a review of the literature.

    Science.gov (United States)

    Kuenssberg, Renate; McKenzie, Karen; Jones, Jill

    2011-01-01

    Research continues to try and pinpoint the etiological role of particular genes and brain structure in autistic spectrum disorder (ASD), but despite a host of biological, genetic and neuropsychological research, the symptom profile of pervasive developmental disorders (PDDs) are not yet linked to etiological theory. Debate continues around whether or not there is one single dimension that incorporates the three criteria domains of social difficulties, communication deficits and repetitive or restrictive interests and behaviours as a unitary 'ASD' concept, or whether PDD as they are currently described represent the co-occurrence of separate sub-domains of developmental difficulties. Although the three criteria need to be met for a diagnosis of PDD to be made, the association between them remains unclear. This review highlights that the majority of the literature that looks at the triad of impairments suggests the symptom structure does not match that proposed by diagnostic manuals, and that the triad may no longer fit as the best way to conceptualize ASD. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Prolonged fasting impairs neural reactivity to visual stimulation.

    Science.gov (United States)

    Kohn, N; Wassenberg, A; Toygar, T; Kellermann, T; Weidenfeld, C; Berthold-Losleben, M; Chechko, N; Orfanos, S; Vocke, S; Laoutidis, Z G; Schneider, F; Karges, W; Habel, U

    2016-01-01

    Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

  5. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

    Directory of Open Access Journals (Sweden)

    Raphael Johannes Morscher

    Full Text Available Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system.Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content.Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention.Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens

  6. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

    Science.gov (United States)

    Morscher, Raphael Johannes; Aminzadeh-Gohari, Sepideh; Feichtinger, René Gunther; Mayr, Johannes Adalbert; Lang, Roland; Neureiter, Daniel; Sperl, Wolfgang; Kofler, Barbara

    2015-01-01

    Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system. Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content). Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention. Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens. Therefore, we propose

  7. Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation.

    Science.gov (United States)

    Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

    2016-12-20

    Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ERβ largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ERβ-dependent manner. Moreover, arctigenin was recognized to be an agonist of ERβ, which could bind to ERβ with a moderate affinity, promote dissociation of ERβ/HSP90 complex and nuclear translocation and phosphorylation of ERβ, and increase the transcription activity. Following activation of ERβ, arctigenin inhibited the activity of mTORC1 by disruption of ERβ-raptor-mTOR complex assembly. Deficiency of ERβ markedly abolished arctigenin-mediated inhibition of Th17 cell differentiation. In colitis mice, the activation of ERβ, inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by PHTPP treatment. In conclusion, ERβ might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development.

  8. Breaking Up Sitting with Light-Intensity Physical Activity: Implications for Shift-Workers

    Directory of Open Access Journals (Sweden)

    Grace E. Vincent

    2017-10-01

    Full Text Available Prolonged sitting, restricted sleep, and circadian disruption are all independent risk factors for non-communicable diseases. Previous research has demonstrated that breaking up sitting with light-intensity physical activity has clear benefits for the health of day workers, but these findings may not apply in the presence of sleep restriction and/or circadian disruption—both of which are commonly experienced by shift-workers. Specifically, sleep restriction, and circadian disruption result in acute physiological changes that may offset the benefits of breaking up sitting. This commentary will explore the potential benefits of breaking up sitting for health, work performance, and subsequent sleep in shift-workers. Future areas of research designed to understand the mechanisms by which prolonged sitting and shift work impact worker health and safety and to support the design of effective occupational health and safety interventions are proposed.

  9. Cellular plasticity in the supraoptic and paraventricular nuclei after prolonged dehydration in the desert rodent Meriones shawi: Vasopressin and GFAP immunohistochemical study.

    Science.gov (United States)

    Gamrani, Halima; Elgot, Abdeljalil; El Hiba, Omar; Fèvre-Montange, Michelle

    2011-02-23

    Supraoptic (SON) and paraventricular (PVN) nuclei are part of the hypothalamic-neurohypophysial system, they constitute the main source for vasopressin and they represent also obvious examples of activity-dependent neuroglial plasticity. Certain physiological conditions such as dehydration are accompanied by a structural remodeling of the neurons, their synaptic inputs and their surrounding glia. In the present work, an adult Meriones shawi (a rodent adapted to desert life) is used as an animal model. Using GFAP and vasopressin expressions as indicators successively of astrocytes and neuronal activations, the effect of a prolonged episode of water deprivation on the SON and PVN, hypothalamus nuclei were examined. We studied the immunoreactivity of GFAP and vasopressin in various hydration states (total deprivation of drinking water for 1 and 2months compared to hydrated animals). Prolonged dehydration produces an important decrease of GFAP immunoreactivity in both SON and PVN after 1 and 2months of water restriction. This decrease is accompanied by increased vasopressin immunoreactivity following the same periods of water deprivation. These findings may explain a real communication between vasopressin neurons and their surrounding astrocytes, thus the retraction of astrocytes and their processes is accompanied by an enhancement of vasopressin neuron density and their projecting fibers in response to this osmotic stress situation. Furthermore, these data could open further investigations concerning the possible involvement of the communication between astrocytes and vasopressin neurons in both PVN and SON in the regulation of Meriones hydrous balance and resistance to dehydration. Copyright © 2010. Published by Elsevier B.V.

  10. Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks

    Science.gov (United States)

    Kitaysky, A.S.; Kitaiskaia, E.V.; Wingfield, J.C.; Piatt, John F.

    2001-01-01

    Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone.

  11. Prolonged labour as indication for emergency caesarean section

    DEFF Research Database (Denmark)

    Maaløe, Nanna; Sorensen, B L; Onesmo, R

    2012-01-01

    To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour.......To audit the quality of obstetric management preceding emergency caesarean sections for prolonged labour....

  12. Repeated Sleep Restriction in Adolescent Rats Altered Sleep Patterns and Impaired Spatial Learning/Memory Ability

    Science.gov (United States)

    Yang, Su-Rong; Sun, Hui; Huang, Zhi-Li; Yao, Ming-Hui; Qu, Wei-Min

    2012-01-01

    Study Objectives: To investigate possible differences in the effect of repeated sleep restriction (RSR) during adolescence and adulthood on sleep homeostasis and spatial learning and memory ability. Design: The authors examined electroencephalograms of rats as they were subjected to 4-h daily sleep deprivation that continued for 7 consecutive days and assessed the spatial learning and memory by Morris water maze test (WMT). Participants: Adolescent and adult rats. Measurements and Results: Adolescent rats exhibited a similar amount of rapid eye movement (REM) and nonrapid eye movement (NREM) sleep with higher slow wave activity (SWA, 0.5-4 Hz) and fewer episodes and conversions with prolonged durations, indicating they have better sleep quality than adult rats. After RSR, adult rats showed strong rebound of REM sleep by 31% on sleep deprivation day 1; this value was 37% on sleep deprivation day 7 in adolescents compared with 20-h baseline level. On sleep deprivation day 7, SWA in adult and adolescent rats increased by 47% and 33%, and such elevation lasted for 5 h and 7 h, respectively. Furthermore, the authors investigated the effects of 4-h daily sleep deprivation immediately after the water maze training sessions on spatial cognitive performance. Adolescent rats sleep-restricted for 7 days traveled a longer distance to find the hidden platform during the acquisition training and had fewer numbers of platform crossings in the probe trial than those in the control group, something that did not occur in the sleep-deprived adult rats. Conclusions: Repeated sleep restriction (RSR) altered sleep profiles and mildly impaired spatial learning and memory capability in adolescent rats. Citation: Yang SR; Sun H; Huang ZL; Yao MH; Qu WM. Repeated sleep restriction in adolescent rats altered sleep patterns and impaired spatial learning/memory ability. SLEEP 2012;35(6):849-859. PMID:22654204

  13. Laryngotracheal Injury following Prolonged Endotracheal Intubation

    Directory of Open Access Journals (Sweden)

    J. Mehdizadeh

    2006-07-01

    Full Text Available Background: Prolonged endotracheal intubation is a growing method for supporting ventilation in patients who require intensive care. Despite considerable advancement in endotracheal intubation, this method still has some complications; the most important is laryngo-tracheal injuries. Methods: Over a 2-year period, this retrospective study was conducted on 57 patients with history of prolonged intubation who were referred to the ENT Department of Amir Alam Hospital. For each patient, a complete evaluation including history, physical examination, and direct laryngoscopy and bronchoscopy was done under general anesthesia. Results: Fifty-seven patients (44 male; mean age, 23.014.7 years were studied. Mean intubation period was 15.88 days. The most common presenting symptom was dyspnea (62%. Head trauma was responsible for most cases of intubation (72.4%. The most common types of tracheal and laryngeal lesions were tracheal (56.9% and subglottic (55.2% stenosis, respectively. Mean length of tracheal stenosis was 0.810.83 cm. There was a statistically significant relationship between length of tracheal stenosis and intubation period (P=0.0001 but no relation was observed between tracheal stenosis and age, sex, and etiology of intubation (All P=NS. Among the glottic lesions, inter- arytenoids adhesion was the most common lesion (25.9%. No statistically significant relation was found between glottic and subglottic lesions and age, sex and intubation period (all P=NS. Length of stenosis and intubation period was significantly greater in tracheal/ subglottic lesions than those in glottic/ supraglottic lesions (all P=NS. Conclusion: After prolonged endotracheal intubation, laryngo-tracheal lesions had no relation with patient’s age, sex, and cause of intubation.There was direct relation between length of tracheal stenosis and intubation period. Glottic lesions were more commonly observed in head trauma patients. Lesion length and intubation

  14. Arctigenin functions as a selective agonist of estrogen receptor ? to restrict mTORC1 activation and consequent Th17 differentiation

    OpenAIRE

    Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

    2016-01-01

    Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ER? largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condit...

  15. The N terminus of cGAS de-oligomerizes the cGAS:DNA complex and lifts the DNA size restriction of core-cGAS activity.

    Science.gov (United States)

    Lee, Arum; Park, Eun-Byeol; Lee, Janghyun; Choi, Byong-Seok; Kang, Suk-Jo

    2017-03-01

    Cyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme in the innate immune system. Recent studies using core-cGAS lacking the N terminus investigated the mechanism for binding of double-stranded (ds) DNA and synthesis of 2',3'-cyclic GMP-AMP (cGAMP), a secondary messenger that ultimately induces type I interferons. However, the function of the N terminus of cGAS remains largely unknown. Here, we found that the N terminus enhanced the activity of core-cGAS in vivo. Importantly, the catalytic activity of core-cGAS decreased as the length of double-stranded DNA (dsDNA) increased, but the diminished activity was restored by addition of the N terminus. Furthermore, the N terminus de-oligomerized the 2 : 2 complex of core-cGAS and dsDNA into a 1 : 1 complex, suggesting that the N terminus enhanced the activity of core-cGAS by facilitating formation of a monomeric complex of cGAS and DNA. © 2017 Federation of European Biochemical Societies.

  16. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity.

    Science.gov (United States)

    Hall, Kevin D; Bemis, Thomas; Brychta, Robert; Chen, Kong Y; Courville, Amber; Crayner, Emma J; Goodwin, Stephanie; Guo, Juen; Howard, Lilian; Knuth, Nicolas D; Miller, Bernard V; Prado, Carla M; Siervo, Mario; Skarulis, Monica C; Walter, Mary; Walter, Peter J; Yannai, Laura

    2015-09-01

    Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Training Restricted Boltzmann Machines

    DEFF Research Database (Denmark)

    Fischer, Asja

    relies on sampling based approximations of the log-likelihood gradient. I will present an empirical and theoretical analysis of the bias of these approximations and show that the approximation error can lead to a distortion of the learning process. The bias decreases with increasing mixing rate......Restricted Boltzmann machines (RBMs) are probabilistic graphical models that can also be interpreted as stochastic neural networks. Training RBMs is known to be challenging. Computing the likelihood of the model parameters or its gradient is in general computationally intensive. Thus, training...... of the applied sampling procedure and I will introduce a transition operator that leads to faster mixing. Finally, a different parametrisation of RBMs will be discussed that leads to better learning results and more robustness against changes in the data representation....

  18. Topical Drug Formulations for Prolonged Corneal Anesthesia

    Science.gov (United States)

    Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.

    2013-01-01

    Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270

  19. What Is the Effect on Obesity Indicators from Replacing Prolonged Sedentary Time with Brief Sedentary Bouts, Standing and Different Types of Physical Activity during Working Days? A Cross-Sectional Accelerometer-Based Study among Blue-Collar Workers

    OpenAIRE

    Gupta, Nidhi; Heiden, Marina; Aadahl, Mette; Korsh?j, Mette; J?rgensen, Marie Birk; Holtermann, Andreas

    2016-01-01

    INTRODUCTION: The aim of the study was to investigate if (a) substituting total sedentary time or long sedentary bouts with standing or various types of physical activity and (b) substituting long sedentary bouts with brief sedentary bouts; is associated with obesity indicators using a cross sectional isotemporal substitution approach among blue-collar workers.METHODS: A total of 692 workers from transportation, manufacturing and cleaning sectors wore an Actigraph GT3X+ accelerometer on the t...

  20. Transcription Factors Synergistically Activated at the Crossing of the Restriction Point between G1 and S Cell Cycle Phases. Pathologic Gate Opening during Multi-Hit Malignant Transformation

    Directory of Open Access Journals (Sweden)

    Nicoletta Castagnino

    2016-12-01

    Full Text Available Transcription factors (TFs represent key regulators of gene-expression patterns controlling cell behavior. TFs are active at nuclear – chromatin levels. TFs do not act in isolation; small sets of TFs cooperate toward the transcription of sets of mRNAs and consequently the translation of new proteins (the molecular phenotypes of a cell. Most TFs are activated through a cascade of biochemical reactions mediated by receptors expressed on the target cell surface. Nuclear Receptors (NRs are transcription factors activated instead by small hydrophobic molecules capable of crossing the plasma membrane. The convergence of different pathways on TFs and their posttranslational modifications ensure that the external stimuli generate appropriate and integrated responses. The reconstruction of the molecular anatomy of these pathways through Molecular Interactions Maps (MIMs can depict these intricate interactions. A mathematical modeling approach simulates/mimics their mechanism of action in normal and pathological conditions. We can simulate the effect of virtual hits in neoplastic transformation as mutations/alterations in these pathways. We can also simulate the effect of targeted inhibitors on these deregulated pathways. This strategy can help to guide an appropriate combination of targeted drugs in the treatment of a cancer patient, a major innovative perspective of incoming years.

  1. A Conserved RhoGAP Limits M-phase Contractility and Coordinates with Microtubule Asters to Restrict Active RhoA to the Cell Equator During Cytokinesis

    Science.gov (United States)

    Zanin, Esther; Desai, Arshad; Poser, Ina; Toyoda, Yusuke; Andree, Cordula; Moebius, Claudia; Bickle, Marc; Conradt, Barbara; Piekny, Alisa; Oegema, Karen

    2014-01-01

    SUMMARY During animal cell cytokinesis, the spindle directs contractile ring assembly by activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone dimensions. Testing the significance of RhoA flux has been hampered by the fact that the GAP targeting RhoA is not known. Here, we identify M-phase GAP (MP-GAP) as the primary GAP targeting RhoA during mitosis/cytokinesis. MP-GAP inhibition caused excessive RhoA activation in M-phase leading to the uncontrolled formation of large cortical protrusions and late cytokinesis failure. RhoA zone width was broadened by attenuation of the centrosomal asters but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery. These results identify the major GAP restraining RhoA during cell division and delineate the relative contributions of RhoA flux and centrosomal asters in controlling RhoA zone dimensions. PMID:24012485

  2. Nek2A destruction marks APC/C activation at the prophase-to-prometaphase transition by spindle-checkpoint-restricted Cdc20.

    Science.gov (United States)

    Boekhout, Michiel; Wolthuis, Rob

    2015-04-15

    Nek2 isoform A (Nek2A) is a presumed substrate of the anaphase-promoting complex/cyclosome containing Cdc20 (APC/C(Cdc20)). Nek2A, like cyclin A, is degraded in mitosis while the spindle checkpoint is active. Cyclin A prevents spindle checkpoint proteins from binding to Cdc20 and is recruited to the APC/C in prometaphase. We found that Nek2A and cyclin A avoid being stabilized by the spindle checkpoint in different ways. First, enhancing mitotic checkpoint complex (MCC) formation by nocodazole treatment inhibited the degradation of geminin and cyclin A, whereas Nek2A disappeared at a normal rate. Second, depleting Cdc20 effectively stabilized cyclin A but not Nek2A. Nevertheless, Nek2A destruction crucially depended on Cdc20 binding to the APC/C. Third, in contrast to cyclin A, Nek2A was recruited to the APC/C before the start of mitosis. Interestingly, the spindle checkpoint very effectively stabilized an APC/C-binding mutant of Nek2A, which required the Nek2A KEN box. Apparently, in cells, the spindle checkpoint primarily prevents Cdc20 from binding destruction motifs. Nek2A disappearance marks the prophase-to-prometaphase transition, when Cdc20, regardless of the spindle checkpoint, activates the APC/C. However, Mad2 depletion accelerated Nek2A destruction, showing that spindle checkpoint release further increases APC/C(Cdc20) catalytic activity. © 2015. Published by The Company of Biologists Ltd.

  3. 32 CFR 701.44 - Restrictions.

    Science.gov (United States)

    2010-07-01

    ... OFFICIAL RECORDS AVAILABILITY OF DEPARTMENT OF THE NAVY RECORDS AND PUBLICATION OF DEPARTMENT OF THE NAVY DOCUMENTS AFFECTING THE PUBLIC FOIA Fees § 701.44 Restrictions. (a) No fees may be charged by any DON activity if the costs of routine collection and processing of the fee are likely to equal or exceed the...

  4. Prolonged fasting increases glutathione biosynthesis in postweaned northern elephant seals

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Forman, Henry Jay; Crocker, Daniel E.; Ortiz, Rudy M.

    2011-01-01

    SUMMARY Northern elephant seals experience prolonged periods of absolute food and water deprivation (fasting) while breeding, molting or weaning. The postweaning fast in elephant seals is characterized by increases in the renin–angiotensin system, expression of the oxidant-producing protein Nox4, and NADPH oxidase activity; however, these increases are not correlated with increased oxidative damage or inflammation. Glutathione (GSH) is a potent reductant and a cofactor for glutathione peroxidases (GPx), glutathione-S transferases (GST) and 1-cys peroxiredoxin (PrxVI) and thus contributes to the removal of hydroperoxides, preventing oxidative damage. The effects of prolonged food deprivation on the GSH system are not well described in mammals. To test our hypothesis that GSH biosynthesis increases with fasting in postweaned elephant seals, we measured circulating and muscle GSH content at the early and late phases of the postweaning fast in elephant seals along with the activity/protein content of glutamate-cysteine ligase [GCL; catalytic (GCLc) and modulatory (GCLm) subunits], γ-glutamyl transpeptidase (GGT), glutathione disulphide reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), GST and PrxVI, as well as plasma changes in γ-glutamyl amino acids, glutamate and glutamine. GSH increased two- to four-fold with fasting along with a 40–50% increase in the content of GCLm and GCLc, a 75% increase in GGT activity, a two- to 2.5-fold increase in GR, G6PDH and GST activities and a 30% increase in PrxVI content. Plasma γ-glutamyl glutamine, γ-glutamyl isoleucine and γ-glutamyl methionine also increased with fasting whereas glutamate and glutamine decreased. Results indicate that GSH biosynthesis increases with fasting and that GSH contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals. PMID:21430206

  5. Effect of prolonged exposure to low antigen concentration for sensitization

    International Nuclear Information System (INIS)

    Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

    2003-01-01

    The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

  6. Mast cell-restricted, tetramer-forming tryptases induce aggrecanolysis in articular cartilage by activating matrix metalloproteinase-3 and -13 zymogens.

    Science.gov (United States)

    Magarinos, Natalia J; Bryant, Katherine J; Fosang, Amanda J; Adachi, Roberto; Stevens, Richard L; McNeil, H Patrick

    2013-08-01

    Mouse mast cell protease (mMCP)-6-null C57BL/6 mice lost less aggrecan proteoglycan from the extracellular matrix of their articular cartilage during inflammatory arthritis than wild-type (WT) C57BL/6 mice, suggesting that this mast cell (MC)-specific mouse tryptase plays prominent roles in articular cartilage catabolism. We used ex vivo mouse femoral head explants to determine how mMCP-6 and its human ortholog hTryptase-β mediate aggrecanolysis. Exposure of the explants to recombinant hTryptase-β, recombinant mMCP-6, or lysates harvested from WT mouse peritoneal MCs (PMCs) significantly increased the levels of enzymatically active matrix metalloproteinases (MMP) in cartilage and significantly induced aggrecan loss into the conditioned media, relative to replicate explants exposed to medium alone or lysates collected from mMCP-6-null PMCs. Treatment of cartilage explants with tetramer-forming tryptases generated aggrecan fragments that contained C-terminal DIPEN and N-terminal FFGVG neoepitopes, consistent with MMP-dependent aggrecanolysis. In support of these data, hTryptase-β was unable to induce aggrecan release from the femoral head explants obtained from Chloe mice that resist MMP cleavage at the DIPEN↓FFGVG site in the interglobular domain of aggrecan. In addition, the abilities of mMCP-6-containing lysates from WT PMCs to induce aggrecanolysis were prevented by inhibitors of MMP-3 and MMP-13. Finally, recombinant hTryptase-β was able to activate latent pro-MMP-3 and pro-MMP-13 in vitro. The accumulated data suggest that human and mouse tetramer-forming tryptases are MMP convertases that mediate cartilage damage and the proteolytic loss of aggrecan proteoglycans in arthritis, in part, by activating the zymogen forms of MMP-3 and MMP-13, which are constitutively present in articular cartilage.

  7. Fluorescence quenching of graphene oxide combined with the site-specific cleavage of restriction endonuclease for deoxyribonucleic acid demethylase activity assay

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Lijuan; Qian, Yingdan; Wu, Ping; Zhang, Hui; Cai, Chenxin, E-mail: cxcai@njnu.edu.cn

    2015-04-15

    Highlights: • An approach for sensitive and selective DNA demethylase activity assay is reported. • This assay is based on the fluorescence quenching of GO and site-specific cleavage of endonuclease. • It can determine as low as 0.05 ng mL{sup −1} of MBD2 with a linear range of 0.2–300 ng mL{sup −1}. • It has an ability to recognize MBD2 from other possibly coexisting proteins and cancer cell extracts. • It can avoid false signals, requiring no bisulfite conversion, PCR amplification, radioisotope-labeling. - Abstract: We report on the development of a sensitive and selective deoxyribonucleic acid (DNA) demethylase (using MBD2 as an example) activity assay by coupling the fluorescence quenching of graphene oxide (GO) with the site-specific cleavage of HpaII endonuclease to improve the selectivity. This approach was developed by designing a single-stranded probe (P1) that carries a binding region to facilitate the interaction with GO, which induces fluorescence quenching of the labeled fluorophore (FAM, 6-carboxyfluorescein), and a sensing region, which contains a hemi-methylated site of 5′-CmCGG-3′, to specifically recognize the target (T1, a 32-mer DNA from the promoter region of p53 gene) and hybridize with it to form a P1/T1 duplex. After demethylation with MBD2, the duplex can be specifically cleaved using HpaII, which releases the labeled FAM from the GO surface and results in the recovery of fluorescence. However, this cleavage is blocked by the hemi-methylation of this site. Thus, the magnitude of the recovered fluorescence signal is related to the MBD2 activity, which establishes the basis of the DNA demethylase activity assay. This assay can determine as low as ∼(0.05 ± 0.01) ng mL{sup −1} (at a signal/noise of 3) of MBD2 with a linear range of 0.2–300 ng mL{sup −1} and recognize MBD2 from other possibly coexisting proteins and cancer cell extracts. The advantage of this assay is its ability to avoid false signals and no

  8. Caloric restriction lowers endocannabinoid tonus and improves cardiac function in type 2 diabetes

    NARCIS (Netherlands)

    Eyk, van H.J.; Schinkel, van L.D.; Kantae, V.; Dronkers, C.E.A.; Westenberg, J.J.M.; Roos, de A.; Lamb, H.J.; Jukema, J.W.; Harms, A.C.; Hankemeier, T.; Stelt, van der M.; Jazet, I.M.; Rensen, P.C.N.; Smit, J.W.A.

    2018-01-01

    Background/ObjectivesEndocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac

  9. Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.

    Directory of Open Access Journals (Sweden)

    Hui Qun Fu

    Full Text Available Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001 and up to 6 hours (p<0.001 following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG, IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.

  10. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Michael Gysel

    2014-01-01

    Full Text Available A 71-year-old woman collapsed while working as a grocery store cashier. CPR was performed and an AED revealed torsades de pointes (TdP. She was subsequently defibrillated resulting in restoration of sinus rhythm with a QTc interval of 544 msec. Further evaluation revealed a diagnosis of Takotsubo Cardiomyopathy (TCM contributing to the development of a multifactorial acquired long QT syndrome (LQTS. The case highlights the role of TCM as a cause of LQTS in the setting of multiple risk factors including old age, female gender, hypokalemia, and treatment with QT prolonging medications. It also highlights the multifactorial nature of acquired LQTS and lends support to growing evidence of an association with TCM.

  11. Prolonged toxicity from Kambo cleansing ritual.

    Science.gov (United States)

    Li, Kai; Horng, Howard; Lynch, Kara; Smollin, Craig G

    2018-04-02

    Kambo cleanse is a purification, cleansing ritual traditionally performed by South American shaman to confer luck and health to hunters. We report a patient who presented to the emergency department with prolonged symptoms of vomiting, flushing, facial swelling, altered mental status, and agitation requiring chemical restraints, 22 h after a Kambo cleanse. The patient was found with four small, circular, superficial burns to the ankle at the site where the resin was introduced. The cleanse consists of rubbing resin obtained from the secretions of the giant leaf frog (Phyllomedusa bicolor) into superficial wounds to produce intense gastrointestinal symptoms followed by a sensation of increased stamina and strength. The cleanse is now being increasingly performed in Europe and USA.

  12. Bywalled plasma formation in vacuum prolonged channels

    International Nuclear Information System (INIS)

    Korenev, S.A.; Rubin, N.B.

    1982-01-01

    To produce homogeneous along the channel length plasma the application of incomplete rate-in surface dielectric discharge for generating the bywalled plasma in prolonged cylindrical channels at a pressure of the residual gas of P approximately 10 -5 Torr is proposed. Experimental set-up consisted of a pulse voltage generator and a plasma channel. The plasma channel was a coaxial system of three tubes inserted into each other. The first outer tube is made of a stainless steel, the second - of a dielectric material, the third - of smallsized stainless steel greed. It is demonstrated that the plasma being formed in the process is sufficiently homogeneous by concentration of the components, by the channel length and azimuth. The length of the experimental channel under investigation was 1.6 m, its diameter amounted 0.05 m. The maximum concentration of electron component was 10 17 m -3

  13. Neurohumoral responses during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Nielsen, Bodil; Blomstrand, Eva

    2003-01-01

    This study examined neurohumoral alterations during prolonged exercise with and without hyperthermia. The cerebral oxygen-to-carbohydrate uptake ratio (O2/CHO = arteriovenous oxygen difference divided by arteriovenous glucose difference plus one-half lactate), the cerebral balances of dopamine......, and the metabolic precursor of serotonin, tryptophan, were evaluated in eight endurance-trained subjects during exercise randomized to be with or without hyperthermia. The core temperature stabilized at 37.9 +/- 0.1 degrees C (mean +/- SE) in the control trial, whereas it increased to 39.7 +/- 0.2 degrees C...... in the hyperthermic trial, with a concomitant increase in perceived exertion (P exercise trials. Both the arterial and jugular venous dopamine levels...

  14. High frequency components of tracheal sound are emphasized during prolonged flow limitation

    International Nuclear Information System (INIS)

    Tenhunen, M; Huupponen, E; Saastamoinen, A; Kulkas, A; Himanen, S-L; Rauhala, E

    2009-01-01

    A nasal pressure transducer, which is used to study nocturnal airflow, also provides information about the inspiratory flow waveform. A round flow shape is presented during normal breathing. A flattened, non-round shape is found during hypopneas and it can also appear in prolonged episodes. The significance of this prolonged flow limitation is still not established. A tracheal sound spectrum has been analyzed further in order to achieve additional information about breathing during sleep. Increased sound frequencies over 500 Hz have been connected to obstruction of the upper airway. The aim of the present study was to examine the tracheal sound signal content of prolonged flow limitation and to find out whether prolonged flow limitation would consist of abundant high frequency activity. Sleep recordings of 36 consecutive patients were examined. The tracheal sound spectral analysis was performed on 10 min episodes of prolonged flow limitation, normal breathing and periodic apnea-hypopnea breathing. The highest total spectral amplitude, implicating loudest sounds, occurred during flow-limited breathing which also presented loudest sounds in all frequency bands above 100 Hz. In addition, the tracheal sound signal during flow-limited breathing constituted proportionally more high frequency activities compared to normal breathing and even periodic apnea-hypopnea breathing

  15. Prolonged grieving after abortion: a descriptive study.

    Science.gov (United States)

    Brown, D; Elkins, T E; Larson, D B

    1993-01-01

    Although flawed by methodological problems, the research literature tends to provide support for the assumption that induced abortion in the 1st trimester is not accompanied by enduring negative psychological sequelae. In cases where such sequelae are reported, the morbidity is attributed to a pre-existing psychiatric condition or circumstances precipitating the choice of abortion. However, detailed descriptive letters from 45 women prepared in response to a request by a pastor of an upper-middle-class Protestant congregation in Florida indicate that prolonged grieving after abortion may be more widespread phenomenon than previously believed. Letter writers ranged in age from 25-60 years; 75% were unmarried at the time of the procedure and 29% aborted before the legalization of abortion in the US. The most frequently cited long-term sequela, especially among those who felt coerced to abort, was a continued feeling of guilt. Fantasies about the aborted fetus was the next most frequently mentioned experience. Half of the letter writers referred to their abortions, as "murder" and 44% voiced regret about their decision to abort. Other long-term effects included depression (44%), feelings of loss (31%), shame (27%), and phobic responses to infants (13%). For 42% of these women, the adverse psychological effects of abortion endured over 10 years. Since letter-writers came from a self-selected population group with a known bias against abortion and only negative experiences were solicited, these experiences must be regarded as subjectives and anecdotal. However, they draw attention to the need for methodologically sound studies of a possible prolonged grief syndrome among a small percentage of women who have abortions, especially when coercion is involved.

  16. About 'restriction', 'justified' and 'necessary'

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2016-01-01

    The article is an academic fairy tale about why and how all national corporate tax protection legislation should undergo a 3-part test to ensure its consistency with EU law. Each Member State introduce a compulsory 3-step test for each new (corporate) tax provision. The test is simple: (1) Does...... the tax provision constitute a restriction in the sense of EU law? (2) If the answer is yes: Is the restriction justified? (3) If the answer is yes: Is the restriction necessary?"...

  17. Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

    Science.gov (United States)

    Markowitz, Geoffrey J; Yang, Pengyuan; Fu, Jing; Michelotti, Gregory A; Chen, Rui; Sui, Jianhua; Yang, Bin; Qin, Wen-Hao; Zhang, Zheng; Wang, Fu-Sheng; Diehl, Anna Mae; Li, Qi-Jing; Wang, Hongyang; Wang, Xiao-Fan

    2016-04-15

    Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. What Is the Effect on Obesity Indicators from Replacing Prolonged Sedentary Time with Brief Sedentary Bouts, Standing and Different Types of Physical Activity during Working Days? A Cross-Sectional Accelerometer-Based Study among Blue-Collar Workers.

    Science.gov (United States)

    Gupta, Nidhi; Heiden, Marina; Aadahl, Mette; Korshøj, Mette; Jørgensen, Marie Birk; Holtermann, Andreas

    2016-01-01

    The aim of the study was to investigate if (a) substituting total sedentary time or long sedentary bouts with standing or various types of physical activity and (b) substituting long sedentary bouts with brief sedentary bouts; is associated with obesity indicators using a cross sectional isotemporal substitution approach among blue-collar workers. A total of 692 workers from transportation, manufacturing and cleaning sectors wore an Actigraph GT3X+ accelerometer on the thigh for 1-4 working days. The sedentary (sit and lie), standing, walking, and moderate to vigorous physical activity (MVPA) time on working days was computed using validated Acti4 software. The total sedentary time and uninterrupted sedentary time spent in brief (≤5 mins), moderate (>5 and ≤30 mins), and long (>30mins) bouts, were determined for the whole day and during work and non-work time separately. The obesity indicators, BMI (kg/m2), waist circumference (cm) and fat percentage were objectively measured. Isotemporal substitution modelling was utilized to determine the linear association with obesity indicators of replacing 30 min of total sedentary time or long sedentary bouts with standing, walking or MVPA and separately replacing 30 min of long sedentary bouts with brief sedentary bouts. Workers [mean (standard deviation, SD); age = 45.1 (9.9) years, BMI = 27.5 (4.9) kg/m2, %BF = 29.6 (9.5), waist circumference = 94.4 (13.0) cm] sat for 2.4 hours (~32% of the measured time, SD = 1.8 hours) across the day during work period and 5.5 hours (~62% of the measured time, SD = 1.5 hours) during non-work period. Most of the sedentary time was accrued in moderate bouts [work = 1.40 (SD = 1.09) hours] during work and in long bouts during non-work [2.7 (SD = 1.4) hours], while least in long sedentary bouts during work [work = 0.5 (SD = 0.9)] and in brief sedentary bouts [0.5 hours (SD = 0.3)] during non-work. Significant associations with all obesity indicators were found when 30 min of total

  19. A solid-phase microextraction GC/MS/MS method for rapid quantitative analysis of food and beverages for the presence of legally restricted biologically active flavorings.

    Science.gov (United States)

    Bousova, Katerina; Mittendorf, Klaus; Senyuva, Hamide

    2011-01-01

    A method was developed using automated headspace solid-phase microextraction coupled with GC/MS/MS to simultaneously determine the presence of seven biologically active flavoring substances whose levels of use in processed foods is controlled by statutory limits. The method can be applied to identify and quantify the presence of 1,2-benzopyrone (coumarin), beta-asarone, 1-allyl-4-methoxybenzene (estragole), menthofuran, 4-allyl-1 ,2-dimethoxybenzene (methyl eugenol), pulegone, and thujone at levels ranging from 0.5 to 3000 mg/kg. The method has been optimized and validated for three different generic food types categorized on the basis of composition and anticipated use levels of flavorings and food ingredients. The food categories are alcoholic and nonalcoholic beverages; semisolid processed foods (e.g., soups, sauces, confectionary, etc.); and solid foods (muesli, bakery products, etc.). The method is simple, inexpensive, and rapid, and eliminates the use of flammable and toxic solvents. There is no sample preparation, and using MSIMS, unequivocal confirmation of identification is achieved even in highly complex matrixes containing many potential interfering volatiles. The method precision for spiked samples ranged from 2 to 21%, with the greatest variability associated with solid matrixes. The LOD and LOQ values were well below 0.1 and 0.5 mg/kg, respectively, in all cases for individual substances, fulfilling requirements for enforcement purposes. The robustness of the method was demonstrated in a small survey of retail samples of four spirits, five flavored milks, three energy drinks, five liqueurs, five soups, 10 sauces, five herbal teas, and three breakfast cereals.

  20. Prolonged pain and disability are common after rib fractures.

    Science.gov (United States)

    Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

    2013-05-01

    The contribution of rib fractures to prolonged pain and disability may be underappreciated and undertreated. Clinicians are traditionally taught that the pain and disability of rib fractures resolves in 6 to 8 weeks. This study was a prospective observation of 203 patients with rib fractures at a level 1 trauma center. Chest wall pain was evaluated by the McGill Pain Questionnaire (MPQ) pain rating index (PRI) and present pain intensity (PPI). Prolonged pain was defined as a PRI of 8 or more at 2 months after injury. Prolonged disability was defined as a decrease in 1 or more levels of work or functional status at 2 months after injury. Predictors of prolonged pain and disability were determined by multivariate analysis. One hundred forty-five male patients and 58 female patients with a mean injury severity score (ISS) of 20 (range, 1 to 59) had a mean of 5.4 rib fractures (range, 1 to 29). Forty-four (22%) patients had bilateral fractures, 15 (7%) had flail chest, and 92 (45%) had associated injury. One hundred eighty-seven patients were followed 2 months or more. One hundred ten (59%) patients had prolonged chest wall pain and 142 (76%) had prolonged disability. Among 111 patients with isolated rib fractures, 67 (64%) had prolonged chest wall pain and 69 (66%) had prolonged disability. MPQ PPI was predictive of prolonged pain (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.4 to 2.5), and prolonged disability (OR, 2.2; 95% CI, 1.5 to 3.4). The presence of significant associated injuries was predictive of prolonged disability (OR, 5.9; 95% CI, 1.4 to 29). Prolonged chest wall pain is common, and the contribution of rib fractures to disability is greater than traditionally expected. Further investigation into more effective therapies that prevent prolonged pain and disability after rib fractures is needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Naloxone fails to prolong seizure length in ECT.

    Science.gov (United States)

    Rasmussen, K G; Pandurangi, A K

    1999-12-01

    Electroconvulsive shock (ECS) in animals has been shown to enhance endogenous opiate systems. The anticonvulsant effects of ECS are also partially blocked by the opiate receptor antagonist naloxone, leading some investigators to postulate that the anticonvulsant effects of ECS are mediated by activation of endogenous opiates. If such a phenomenon occurs in humans, then naloxone might prolong seizure length in electroconvulsive therapy (ECT). In the present study, nine patients were given 2.0 mg intravenous (i.v.) naloxone 2 minutes prior to one-half of their ECT treatments. Motor seizure length was measured via the cuff technique. EEG tracings were read by an investigator blind to naloxone status. There was no difference between the two groups in either EEG or nonblindly evaluated motor seizure length. It is concluded that a dose of 2 mg naloxone does not effectively increase seizure length in ECT.

  2. CNS fatigue provoked by prolonged exercise in the heat

    DEFF Research Database (Denmark)

    Nybo, Lars

    2010-01-01

    to the brain. However, exercise with superimposed hyperthermia is not only a challenge to the brain it also provides an excellent model for studying factors of importance for central fatigue. Excessive heat storage within the brain appears to be the primary cause for the central fatigue during exercise......Exercise-induced hyperthermia is associated with central fatigue as indicated by an impaired ability to sustain maximal motor activation during prolonged voluntary efforts. Therefore, exercise in hot environments challenges not only to the cardiorespiratory and locomotive systems but also...... to aggravate central fatigue and degrade exercise performance. Hyperthermia mediated central fatigue may include other cerebral perturbations such as reduced perfusion of the brain, accumulation of ammonia or depletion of neuronal energy stores, but further research is needed to elucidate their possible...

  3. Effect of prolonged continuous irradiation of humoral immunity of mice

    International Nuclear Information System (INIS)

    Kirillova, E.N.; Muksinova, K.N.; Skukovskaya, T.L.

    1988-01-01

    Changes in the content and function of cell populations and subpopulations involved in the humoral response of mice to the thymus-dependent antigen were investigated. The effect was followed during a prolonged continuous exposure to 137 C gamma-emitter (total dose - 5 Gy and daily dose - 12 cGy for 22 hours) and after its termination. The data obtained give evidence for a decrease of the pool of polypotent lymphocyte precursors (CFUs), stable moderate hypoplasia of central and peripheral organs of the immune system, distinct inhibition of antibody production at the expense of reduced activity of precursors of lymphocytes, B-lymphocytes and T-helpers. In the remote post-irradiation period residual radiation damage was seen in polypotent and committed precursors of lymphocytes and T-helpers, which was responsible for the trend towards the decline of antibody production, hypoplasia in the spleen and lymph nodes being persistent

  4. Marked QTc prolongation and Torsades de Pointes in patients with chronic inflammatory arthritis

    Directory of Open Access Journals (Sweden)

    Pietro Enea Lazzerini

    2016-09-01

    Full Text Available Mounting evidence indicates that in chronic inflammatory arthritis (CIA, QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration (APD, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in RA patients the risk of SCD is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about Torsades de Pointes (TdP prevalence in CIA, and the few case reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development.We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24h from TdP/marked QTc prolongation occurrence and levels of IL-6, TNF-alpha and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNF-alpha and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other classical risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This observation should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required.

  5. Does UTI cause prolonged jaundice in otherwise well infants?

    Science.gov (United States)

    Chowdhury, Tanzila; Kisat, Hamudi; Tullus, Kjell

    2015-07-01

    The symptoms of urinary tract infections in infants are very non-specific and have historically included prolonged hyperbilirubinaemia. We studied the results of routine urine samples in 319 infants with prolonged jaundice. Convincing findings of UTI was not found in any of these children even if one of them was treated with antibiotics after four consecutive urine cultures with different bacteria. A urine culture might thus not be an appropriate investigation in a child with prolonged jaundice without any other symptoms of UTI. • The symptoms of UTI in infancy are very non-specific. • Old studies suggest that prolonged hyperbilirubinaemia is one such symptom; more modern studies give more conflicting results. What is New: • Our study could not confirm that children with prolonged jaundice have an increased risk of UTI. • Routine urine testing is thus not needed in otherwise healthy infants with prolonged jaundice.

  6. Molecular motion in restricted geometries

    Indian Academy of Sciences (India)

    Molecular dynamics in restricted geometries is known to exhibit anomalous behaviour. Diffusion, translational or rotational, of molecules is altered significantly on confinement in restricted geometries. Quasielastic neutron scattering (QENS) offers a unique possibility of studying molecular motion in such systems. Both time ...

  7. Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

    Science.gov (United States)

    Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

    2010-01-01

    Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

  8. Fermionic covariant prolongation structure theory for supernonlinear evolution equation

    International Nuclear Information System (INIS)

    Cheng Jipeng; Wang Shikun; Wu Ke; Zhao Weizhong

    2010-01-01

    We investigate the superprincipal bundle and its associated superbundle. The super(nonlinear)connection on the superfiber bundle is constructed. Then by means of the connection theory, we establish the fermionic covariant prolongation structure theory of the supernonlinear evolution equation. In this geometry theory, the fermionic covariant fundamental equations determining the prolongation structure are presented. As an example, the supernonlinear Schroedinger equation is analyzed in the framework of this fermionic covariant prolongation structure theory. We obtain its Lax pairs and Baecklund transformation.

  9. A study of immunological reactions in dogs exposed to prolonged chronic radiation

    Science.gov (United States)

    Konstantinova, I. V.; Grigoryev, Y. G.; Markelov, B. A.; Skryabin, A. S.; Zemskov, V. M.; Vasilyev, I. S.; Veysfeyler, Y. K.; Iokai, I.

    1974-01-01

    Immunomorphological studies on dog tissues exposed to long term gamma irradiation show that the number of cells containing antibodies increased and that the blast transformation reaction was activated. Prolonged radiation did not cause a reliable change in the synthesis of nucleic acids in spleen cells.

  10. Impact of Father Absence: III. Problems of Family Reintegrating Following Prolonged Father Absence.

    Science.gov (United States)

    Baker, Stewart L.; and others

    A three-phase, longitudinal study at Walter Reed Hospital in Washington, D.C., of family problems with prolonged father absence indicates that there is (1) continuing family growth beyond the situational crisis, (2) active re-examination of roles and values, and (3) heightened awareness of family strength and resourcefulness during the…

  11. Neural Circuits via Which Single Prolonged Stress Exposure Leads to Fear Extinction Retention Deficits

    Science.gov (United States)

    Knox, Dayan; Stanfield, Briana R.; Staib, Jennifer M.; David, Nina P.; Keller, Samantha M.; DePietro, Thomas

    2016-01-01

    Single prolonged stress (SPS) has been used to examine mechanisms via which stress exposure leads to post-traumatic stress disorder symptoms. SPS induces fear extinction retention deficits, but neural circuits critical for mediating these deficits are unknown. To address this gap, we examined the effect of SPS on neural activity in brain regions…

  12. Hydroelectrolytic and hormonal modifications related to prolonged bedrest in antiorthostatic position

    Science.gov (United States)

    Güell, A.; Dupui, Ph.; Fanjaud, G.; Bes, A.; Moatti, J. P.; Gharrib, Cl.

    The effects of prolonged bedrest in antiorthostatic position (-4° head down) on electrolyte balance were studied in 4 young volunteers. An increase was noted in sodium excretion during the first 4 days. Plasma renin activity and plasma aldosterone varied in parallel manner during the same period. Potassium balance and creatinine clearance were not significantly modified. In light of these data we feel that prolonged bedrest in antiorthostatic position constitutes an effective way to simulate on earth metabolic and hormonal modifications occurring in man under weightlessness conditions.

  13. Aging, adiposity, and calorie restriction.

    Science.gov (United States)

    Fontana, Luigi; Klein, Samuel

    2007-03-07

    Excessive calorie intake and subsequent obesity increases the risk of developing chronic disease and decreases life expectancy. In rodent models, calorie restriction with adequate nutrient intake decreases the risk of developing chronic disease and extends maximum life span. To evaluate the physiological and clinical implications of calorie restriction with adequate nutrient intake. Search of PubMed (1966-December 2006) using terms encompassing various aspects of calorie restriction, dietary restriction, aging, longevity, life span, adiposity, and obesity; hand search of journals that focus on obesity, geriatrics, or aging; and search of reference lists of pertinent research and review articles and books. Reviewed reports (both basic science and clinical) included epidemiologic studies, case-control studies, and randomized controlled trials, with quality of data assessed by taking into account publication in a peer-reviewed journal, number of animals or individuals studied, objectivity of measurements, and techniques used to minimize bias. It is not known whether calorie restriction extends maximum life span or life expectancy in lean humans. However, calorie restriction in adult men and women causes many of the same metabolic adaptations that occur in calorie-restricted rodents and monkeys, including decreased metabolic, hormonal, and inflammatory risk factors for diabetes, cardiovascular disease, and possibly cancer. Excessive calorie restriction causes malnutrition and has adverse clinical effects. Calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes, but the precise amount of calorie intake or body fat mass associated with optimal health and maximum longevity in humans is not known. In addition, it is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat.

  14. Protection of Dentate Hilar Cells from Prolonged Stimulation by Intracellular Calcium Chelation

    Science.gov (United States)

    Scharfman, Helen E.; Schwartzkroin, Philip A.

    1989-10-01

    Prolonged afferent stimulation of the rat dentate gyrus in vivo leads to degeneration only of those cells that lack immunoreactivity for the calcium binding proteins parvalbumin and calbindin. In order to test the hypothesis that calcium binding proteins protect against the effects of prolonged stimulation, intracellular recordings were made in hippocampal slices from cells that lack immunoreactivity for calcium binding proteins. Calcium binding protein--negative cells showed electrophysiological signs of deterioration during prolonged stimulation; cells containing calcium binding protein did not. When neurons without calcium binding proteins were impaled with microelectrodes containing the calcium chelator BAPTA, and BAPTA was allowed to diffuse into the cells, these cells showed no deterioration. These results indicate that, in a complex tissue of the central nervous system, an activity-induced increase in intracellular calcium can trigger processes leading to cell deterioration, and that increasing the calcium binding capacity of a cell decreases its vulnerability to damage.

  15. Ageing is associated with a prolonged fever response in human endotoxemia

    DEFF Research Database (Denmark)

    Krabbe, Karen S.; Kemp Bruunsgaard, Helle; Hansen, Christian Muff

    2017-01-01

    The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2......-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein...... levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response....

  16. Nickel on the market: a baseline survey of articles in 'prolonged contact' with skin.

    Science.gov (United States)

    Ringborg, Evelina; Lidén, Carola; Julander, Anneli

    2016-08-01

    In April 2014, the European Chemicals Agency defined the concept of 'prolonged contact with skin' as used in the EU nickel restriction. To establish a baseline of nickel-releasing items on the Swedish market conforming with the EU nickel restriction according to the definition of 'prolonged contact' with the skin. We performed a limited market survey in Stockholm, Sweden. Items with metallic parts that come into contact with the skin, except those explicitly mentioned in the legal text, were chosen. The dimethylglyoxime (DMG) test was used to evaluate nickel release. One hundred and forty-one items belonging to one of three categories - accessories, utensils for needlework, painting and writing (called utensils), and electronic devices - were tested in the study. Forty-four percent of all items were DMG test-positive (releasing nickel), and 9% gave a doubtful DMG test result. The large proportion of nickel-releasing items in the present study shows clearly that broader parts of industry need to take action to prevent nickel allergy. The high proportion of DMG test-positive items indicates that there is still much work to be done to reduce the nickel exposure of the population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Carbohydrate Dependence During Prolonged, Intense Endurance Exercise.

    Science.gov (United States)

    Hawley, John A; Leckey, Jill J

    2015-11-01

    A major goal of training to improve the performance of prolonged, continuous, endurance events lasting up to 3 h is to promote a range of physiological and metabolic adaptations that permit an athlete to work at both higher absolute and relative power outputs/speeds and delay the onset of fatigue (i.e., a decline in exercise intensity). To meet these goals, competitive endurance athletes undertake a prodigious volume of training, with a large proportion performed at intensities that are close to or faster than race pace and highly dependent on carbohydrate (CHO)-based fuels to sustain rates of muscle energy production [i.e., match rates of adenosine triphosphate (ATP) hydrolysis with rates of resynthesis]. Consequently, to sustain muscle energy reserves and meet the daily demands of training sessions, competitive athletes freely select CHO-rich diets. Despite renewed interest in high-fat, low-CHO diets for endurance sport, fat-rich diets do not improve training capacity or performance, but directly impair rates of muscle glycogenolysis and energy flux, limiting high-intensity ATP production. When highly trained athletes compete in endurance events lasting up to 3 h, CHO-, not fat-based fuels are the predominant fuel for the working muscles and CHO, not fat, availability becomes rate limiting for performance.

  18. Prolonged disengagement from distractors near the hands

    Directory of Open Access Journals (Sweden)

    Daniel B Vatterott

    2013-08-01

    Full Text Available Because items near our hands are often more important than items far from our hands, the brain processes visual items near our hands differently than items far from our hands. Multiple experiments have attributed this processing difference to spatial attention, but the exact mechanism behind how spatial attention near our hands changes is still under investigation. The current experiments sought to differentiate between two of the proposed mechanisms: a prioritization of the space near the hands and a prolonged disengagement of spatial attention near the hands. To differentiate between these two accounts, we used the additional singleton paradigm in which observers searched for a shape singleton among homogenously shaped distractors. On half the trials, one of the distractors was a different color. Both the prioritization and disengagement accounts predict differently colored distractors near the hands will slow target responses more than differently colored distractors far from the hands, but the prioritization account also predicts faster responses to targets near the hands than far from the hands. The disengagement account does not make this prediction, because attention does not need to be disengaged when the target appears near the hand. We found support for the disengagement account: Salient distractors near the hands slowed responses more than those far from the hands, yet observers did not respond faster to targets near the hands.

  19. EGFR Activation by Spatially Restricted Ligands

    Science.gov (United States)

    2006-06-01

    the level of ligand production, that result in human breast cancer. We have integrated genetic and biochemical methods to study (1) the effects of a...and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev 12, 2711-2723...findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision

  20. Activity limitations and participation restrictions experienced by ...

    African Journals Online (AJOL)

    a discharge without accurate assessment of the domes- tic environment, and the establishment of networks ..... children were helping me, and now they are working alone… I cannot do anything” (P5). ''… I am always at ... ven grounds or stones could be barriers for those who could walk independently. Independent walking ...

  1. Effects of low dose rate irradiation on life span prolongation of human premature-aging syndrome model mice

    International Nuclear Information System (INIS)

    Nomura, Takaharu

    2006-01-01

    We previously showed that Type II diabetes model mice prolonged of their life span by life long low dose rate irradiation. We also found that antioxidant function in variety tissues of some strain of mice were enhancement after low dose/low dose rate irradiation. The prolongation of life span might depend on certain damaged level of reactive oxygen species. We thought the effect of the prolongation was due to the enhancement of the antioxidant activities after irradiation. We investigated whether the enhancement of antioxidant activities after low dose rate irradiation had an effect on life span prolongation. Four-week-old female human premature-aging syndrome model mice, kl/kl (klotho) mice, which the life span of this model mouse is about 65 days, were irradiated with gamma rays at 0.35, 0.70 or 1.2 mGy/hr. The 0.70 mGy/hr-irradiated group remarkably effected on the prolongation of their life span. Some mice of the group were extremely survived for about and more 100 days. Antioxidant activities in the irradiated groups were enhancement by low dose rate irradiation, however the dependence of the dose rates were not clearly difference. These results suggest that the antioxidant activities in this model mouse were enhanced by the low dose rate irradiation, and may make it possible to prolong the life span of this mouse. (author)

  2. Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery in Children.

    Science.gov (United States)

    Master, Christina L; Master, Stephen R; Wiebe, Douglas J; Storey, Eileen P; Lockyer, Julia E; Podolak, Olivia E; Grady, Matthew F

    2018-03-01

    Up to one-third of children with concussion have prolonged symptoms lasting beyond 4 weeks. Vision and vestibular dysfunction is common after concussion. It is unknown whether such dysfunction predicts prolonged recovery. We sought to determine which vision or vestibular problems predict prolonged recovery in children. A retrospective cohort of pediatric patients with concussion. A subspecialty pediatric concussion program. Four hundred thirty-two patient records were abstracted. Presence of vision or vestibular dysfunction upon presentation to the subspecialty concussion program. The main outcome of interest was time to clinical recovery, defined by discharge from clinical follow-up, including resolution of acute symptoms, resumption of normal physical and cognitive activity, and normalization of physical examination findings to functional levels. Study subjects were 5 to 18 years (median = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular problems. A history of motion sickness was associated with vestibular dysfunction. Younger age, public insurance, and presence of headache were associated with later presentation for subspecialty concussion care. Vision and vestibular problems were associated within distinct clusters. Provocable symptoms with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and accommodative amplitude (AA) predicted prolonged recovery time. Vision and vestibular problems predict prolonged concussion recovery in children. A history of motion sickness may be an important premorbid factor. Public insurance status may represent problems with disparities in access to concussion care. Vision assessments in concussion must include smooth pursuits, saccades, near point of convergence (NPC), and accommodative amplitude (AA). A comprehensive, multidomain assessment is essential to predict prolonged recovery time and enable active intervention with specific school accommodations and targeted rehabilitation.

  3. Cyclic AMP system in muscle tissue during prolonged hypokinesia

    Science.gov (United States)

    Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

    1980-01-01

    Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

  4. Nutrigenetics and nutrigenomics of caloric restriction.

    Science.gov (United States)

    Abete, Itziar; Navas-Carretero, Santiago; Marti, Amelia; Martinez, J Alfredo

    2012-01-01

    Obesity is a complex disease resulting from a chronic and long-term positive energy balance in which both genetic and environmental factors are involved. Weight-reduction methods are mainly focused on dietary changes and increased physical activity. However, responses to nutritional intervention programs show a wide range of interindividual variation, which is importantly influenced by genetic determinants. In this sense, subjects carrying several obesity-related single-nucleotide polymorphisms (SNPs) show differences in the response to calorie-restriction programs. Furthermore, there is evidence indicating that dietary components not only fuel the body but also participate in the modulation of gene expression. Thus, the expression pattern and nutritional regulation of several obesity-related genes have been studied, as well as those that are differentially expressed by caloric restriction. The responses to caloric restriction linked to the presence of SNPs in obesity-related genes are reviewed in this chapter. Also, the influence of energy restriction on gene expression pattern in different tissues is addressed. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. How Harmful are Adaptation Restrictions

    OpenAIRE

    Bruin, de, K.C.; Dellink, R.B.

    2009-01-01

    The dominant assumption in economic models of climate policy remains that adaptation will be implemented in an optimal manner. There are, however, several reasons why optimal levels of adaptation may not be attainable. This paper investigates the effects of suboptimal levels of adaptation, i.e. adaptation restrictions, on the composition and level of climate change costs and on welfare. Several adaptation restrictions are identified and then simulated in a revised DICE model, extended with ad...

  6. Mitigating prolonged QT interval in cancer nanodrug development for accelerated clinical translation.

    Science.gov (United States)

    Ranjan, Amalendu P; Mukerjee, Anindita; Helson, Lawrence; Vishwanatha, Jamboor K

    2013-12-14

    Cardiac toxicity is the foremost reason for drug discontinuation from development to clinical evaluation and post market surveillance [Fung 35:293-317, 2001; Piccini 158:317-326 2009]. The Food and Drug Administration (FDA) has rejected many potential pharmaceutical agents due to QT prolongation effects. Since drug development and FDA approval takes an enormous amount of time, money and effort with high failure rates, there is an increased focus on rescuing drugs that cause QT prolongation. If these otherwise safe and potent drugs were formulated in a unique way so as to mitigate the QT prolongation associated with them, these potent drugs may get FDA approval for clinical use. Rescuing these compounds not only benefit the patients who need them but also require much less time and money thus leading to faster clinical translation. In this study, we chose curcumin as our drug of choice since it has been shown to posses anti-tumor properties against various cancers with limited toxicity. The major limitations with this pharmacologically active drug are (a) its ability to prolong QT by inhibiting the hERG channel and (b) its low bioavailability. In our previous studies, we found that lipids have protective actions against hERG channel inhibition and therefore QT prolongation. Results of the manual patch clamp assay of HEK 293 cells clearly illustrated that our hybrid nanocurcumin formulation prevented the curcumin induced inhibition of hERG K+ channel at concentrations higher than the therapeutic concentrations of curcumin. Comparing the percent inhibition, the hybrid nanocurcumin limited inhibition to 24.8% at a high curcumin equivalent concentration of 18 μM. Liposomal curcumin could only decrease this inhibition upto 30% only at lower curcumin concentration of 6 μM but not at 18 μM concentration. Here we show a curcumin encapsulated lipopolymeric hybrid nanoparticle formulation which could protect against QT prolongation and also render increased

  7. Superimposition of postnatal calorie restriction protects the aging male intrauterine growth- restricted offspring from metabolic maladaptations.

    Science.gov (United States)

    Dai, Yun; Thamotharan, Shanthie; Garg, Meena; Shin, Bo-Chul; Devaskar, Sherin U

    2012-09-01

    Intrauterine growth restriction (IUGR) results in dysregulated glucose homeostasis and adiposity in the adult. We hypothesized that with aging, these perturbations will wane, and superimposition of postnatal growth restriction (PNGR) on IUGR [intrauterine and postnatal growth restriction (IPGR)] will reverse the residual IUGR phenotype. We therefore undertook hyperinsulinemic-euglycemic clamp, energy balance, and physical activity studies during fed, fasted, and refed states, in light and dark cycles, on postweaned chow diet-fed more than 17-month aging male IUGR, PNGR, and IPGR vs. control (CON) rat offspring. Hyperinsulinemic-euglycemic clamp revealed similar whole-body insulin sensitivity and physical activity in the nonobese IUGR vs. CON, despite reduced heat production and energy expenditure. Compared with CON and IUGR, IPGR mimicking PNGR was lean and growth restricted with increased physical activity, O(2) consumption (VO(2)), energy intake, and expenditure. Although insulin sensitivity was no different in IPGR and PNGR, skeletal muscle insulin-induced glucose uptake was enhanced. This presentation proved protective against the chronologically earlier (5.5 months) development of obesity and dysregulated energy homeostasis after 19 wk on a postweaned high-fat diet. This protective role of PNGR on the metabolic IUGR phenotype needs future fine tuning aimed at minimizing unintended consequences.

  8. Response of Escherichia coli to Prolonged Berberine Exposure.

    Science.gov (United States)

    Budeyri Gokgoz, Nilay; Avci, Fatma Gizem; Yoneten, Kubra Karaosmanoglu; Alaybeyoglu, Begum; Ozkirimli, Elif; Sayar, Nihat Alpagu; Kazan, Dilek; Sariyar Akbulut, Berna

    2017-07-01

    Berberine is a plant-derived alkaloid possessing antimicrobial activity; unfortunately, its efflux through multidrug resistance pumps reduces its efficacy. Cellular life span of Escherichia coli is generally shorter with prolonged berberine exposure; nevertheless, about 30% of the cells still remain robust following this treatment. To elucidate its mechanism of action and to identify proteins that could be involved in development of antimicrobial resistance, protein profiles of E. coli cells treated with berberine for 4.5 and 8 hours were compared with control cells. A total of 42 proteins were differentially expressed in cells treated with berberine for 8 hours when compared to control cells. In both 4.5 and 8 hours of berberine-treated cells, carbohydrate and peptide uptake regimens remained unchanged, although amino acid maintenance regimen switched from transport to synthesis. Defect in cell division persisted and this condition was confirmed by images obtained from scanning electron microscopy. Universal stress proteins were not involved in stress response. The significant increase in the abundance of elongation factors could suggest the involvement of these proteins in protection by exhibiting chaperone activities. Furthermore, the involvement of the outer membrane protein OmpW could receive special attention as a protein involved in response to antimicrobial agents, since the expression of only this porin protein was upregulated after 8 hours of exposure.

  9. Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

    Science.gov (United States)

    Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

    2018-05-01

    Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

  10. Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.

    Science.gov (United States)

    Andersson, I M; Lorentzen, J C; Ericsson-Dahlstrand, A

    2000-11-01

    Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine-immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation-susceptible Dark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1-30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, beta-glucan-challenged DA rats responded with an aggravated arthritic process, indicating an anti-inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan-challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone-independent mechanisms. In conclusion, the hypothalamic-pituitary-adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal

  11. Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism.

    Science.gov (United States)

    Niu, Congrong; Li, Li; Daffis, Stephane; Lucifora, Julie; Bonnin, Marc; Maadadi, Sarah; Salas, Eduardo; Chu, Ruth; Ramos, Hilario; Livingston, Christine M; Beran, Rudolf K; Garg, Abhishek V; Balsitis, Scott; Durantel, David; Zoulim, Fabien; Delaney, William E; Fletcher, Simon P

    2018-05-01

    GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined. GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH. Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB. GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic

  12. Prolonged sexual abstinence after childbirth: gendered norms and perceived family health risks. Focus group discussions in a Tanzanian suburb.

    Science.gov (United States)

    Mbekenga, Columba K; Pembe, Andrea B; Darj, Elisabeth; Christensson, Kyllike; Olsson, Pia

    2013-01-15

    Prolonged sexual abstinence after childbirth is a socio-cultural practice with health implications, and is described in several African countries, including Tanzania. This study explored discourses on prolonged postpartum sexual abstinence in relation to family health after childbirth in low-income suburbs of Dar es Salaam, Tanzania. Data for the discourse analysis were collected through focus group discussions with first-time mothers and fathers and their support people in Ilala, Dar es Salaam, Tanzania. In this setting, prolonged sexual abstinence intended at promoting child health was the dominant discourse in the period after childbirth. Sexual relations after childbirth involved the control of sexuality for ensuring family health and avoiding the social implications of non-adherence to sexual abstinence norms. Both abstinence and control were emphasised more with regard to women than to men. Although the traditional discourse on prolonged sexual abstinence for protecting child health was reproduced in Ilala, some modern aspects such as the use of condoms and other contraceptives prevailed in the discussion. Discourses on sexuality after childbirth are instrumental in reproducing gender-power inequalities, with women being subjected to more restrictions and control than men are. Thus, interventions that create openness in discussing sexual relations and health-related matters after childbirth and mitigate gendered norms suppressing women and perpetuating harmful behaviours are needed. The involvement of males in the interventions would benefit men, women, and children through improving the gender relations that promote family health.

  13. Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats

    NARCIS (Netherlands)

    Meng, Li; Rijntjes, Eddy; Swarts, Hans J.M.; Keijer, Jaap; Teerds, Katja J.

    2017-01-01

    Background: There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The

  14. Predictive factors associated with prolonged chest drain production after esophagectomy

    NARCIS (Netherlands)

    Lagarde, S. M.; Omloo, J. M. T.; Ubbink, D. T.; Busch, O. R. C.; Obertop, H.; van Lanschot, J. J. B.

    2007-01-01

    After esophagectomy, pleural drainage is performed to ensure complete drainage of the pleural cavities. The aim of this study was to detect predisposing factors for prolonged drainage. Patients who underwent transhiatal or extended transthoracic esophagectomy for adenocarcinoma of the distal

  15. Prolongation of rapacuronium neuromuscular blockade by clindamycin and magnesium.

    Science.gov (United States)

    Sloan, Paul A; Rasul, Mazhar

    2002-01-01

    We report a prolonged neuromuscular block with the nondepolarizing muscle relaxant rapacuronium in the presence of clindamycin. Even when using "short-acting" muscle relaxants, the anesthesiologist must routinely monitor the neuromuscular function.

  16. Host Cell Restriction Factors that Limit Influenza A Infection

    Directory of Open Access Journals (Sweden)

    Fernando Villalón-Letelier

    2017-12-01

    Full Text Available Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors” can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.

  17. Effects of dietary caffeine on mood when rested and sleep restricted.

    Science.gov (United States)

    James, Jack E; Gregg, M Elizabeth

    2004-07-01

    Prolonged use of caffeine can lead to physical dependence evidenced by characteristic withdrawal symptoms during abstinence. Debate exists as to whether mood enhancement by caffeine represents a net effect or merely the restoration of abstinence-induced mood decrements. One aim of this study was to determine the net effects on mood of dietary caffeine compared with prolonged abstinence. In addition, the study aimed to determine whether caffeine restores mood degraded by a non-caffeine source, namely, sleep restriction. A double-blind placebo-controlled cross-over design was employed in which 48 male and female volunteers alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Mood was assessed using a computerized version of the profile of mood states (POMS), giving scores for overall mood and six mood dimensions. Gender had small effects on mood, whereas all mood dimensions were markedly adversely affected by sleep restriction. Caffeine had no significant net enhancing effects on mood when participants were rested, and produced no net restorative effects when mood was degraded by sleep restriction. On the contrary, caffeine-induced decrements in mood were observed during both conditions of rest and sleep restriction. Copyright 2004 John Wiley & Sons, Ltd.

  18. Ways to Optimize Therapy of Prolonged Conjugation Jaundice in Infants

    Directory of Open Access Journals (Sweden)

    O.G. Shadrin

    2015-09-01

    Full Text Available The article is devoted to the optimization of the treatment of prolonged conjugation jaundice. Inclusion of ursodeoxycholic acid in the treatment of neonatal prolonged conjugation jaundice in a dose of 15–20 mg/kg of body mass per day increases the terms of regression of clinical and paraclinical signs of jaundice as much as 2 times and leads to cytolysis normalization. The preparation has a sufficient level of safety, there were not revealed side effects whilst its application.

  19. Human cellular restriction factors that target HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh

    2009-09-01

    Full Text Available Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, bone marrow stromal cell antigen 2 (BST-2, cyclophilin A, tripartite motif protein 5 alpha (Trim5α, and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.

  20. Gentile statistics and restricted partitions

    Indian Academy of Sciences (India)

    In a recent paper (Tran et al, Ann. Phys. 311, 204 (2004)), some asymptotic number theoretical results on the partitioning of an integer were derived exploiting its connection to the quantum density of states of a many-particle system. We generalise these results to obtain an asymptotic formula for the restricted or coloured ...

  1. Yerba Mat? (Ilex paraguariensis) Metabolic, Satiety, and Mood State Effects at Rest and during Prolonged Exercise

    OpenAIRE

    Alkhatib, Ahmad; Atcheson, Roisin

    2017-01-01

    Yerba Mat? (YM), has become a popular herb ingested for enhancing metabolic health and weight-loss outcomes. No studies have tested the combined metabolic, satiety, and psychomotor effects of YM during exercise. We tested whether YM ingestion affects fatty acid oxidation (FAO), profile of mood state score (POMS), and subjective appetite scale (VAS), during prolonged moderate exercise. Twelve healthy active females were randomized to ingest either 2 g of YM or placebo (PLC) in a repeated-measu...

  2. Long-Term Effect of Mediterranean-Style Diet and Calorie Restriction on Biomarkers of Longevity and Oxidative Stress in Overweight Men

    Directory of Open Access Journals (Sweden)

    Katherine Esposito

    2011-01-01

    Full Text Available We report the effects of a Mediterranean-style diet, with or without calorie restriction, on biomarkers of aging and oxidative stress in overweight men. 192 men were randomly assigned to either a Mediterranean-style diet or a conventional diet. The intervention program was based on implementation of a Mediterranean dietary pattern in the overweight group (MED diet group, associated with calorie restriction and increased physical activity in the obese group (lifestyle group. Both groups were compared with participants in two matched control groups (advice groups. After 2 years, there was a significant difference in weight loss between groups, which was −14 kg (95% CI −20 to −8 in lifestyle groups and −2.0 kg (−4.4 to 0 in the advice groups, with a difference of −11.9 kg (CI −19 to −4.7 kg, <.001; moreover, there was a significant difference between groups at 2 years for insulin (=.04, 8-iso-PGF2α (=.037, glucose (=.04, and adiponectin (=.01. Prolonged adherence to a Mediterranean-style diet, with or without caloric restriction, in overweight or obese men is associated with significant amelioration of multiple risk factors, including a better cardiovascular risk profile, reduced oxidative stress, and improved insulin sensitivity.

  3. The impact of prolonged violent video-gaming on adolescent sleep: an experimental study.

    Science.gov (United States)

    King, Daniel L; Gradisar, Michael; Drummond, Aaron; Lovato, Nicole; Wessel, Jason; Micic, Gorica; Douglas, Paul; Delfabbro, Paul

    2013-04-01

    Video-gaming is an increasingly prevalent activity among children and adolescents that is known to influence several areas of emotional, cognitive and behavioural functioning. Currently there is insufficient experimental evidence about how extended video-game play may affect adolescents' sleep. The aim of this study was to investigate the short-term impact of adolescents' prolonged exposure to violent video-gaming on sleep. Seventeen male adolescents (mean age = 16 ± 1 years) with no current sleep difficulties played a novel, fast-paced, violent video-game (50 or 150 min) before their usual bedtime on two different testing nights in a sleep laboratory. Objective (polysomnography-measured sleep and heart rate) and subjective (single-night sleep diary) measures were obtained to assess the arousing effects of prolonged gaming. Compared with regular gaming, prolonged gaming produced decreases in objective sleep efficiency (by 7 ± 2%, falling below 85%) and total sleep time (by 27 ± 12 min) that was contributed by a near-moderate reduction in rapid eye movement sleep (Cohen's d = 0.48). Subjective sleep-onset latency significantly increased by 17 ± 8 min, and there was a moderate reduction in self-reported sleep quality after prolonged gaming (Cohen's d = 0.53). Heart rate did not differ significantly between video-gaming conditions during pre-sleep game-play or the sleep-onset phase. Results provide evidence that prolonged video-gaming may cause clinically significant disruption to adolescent sleep, even when sleep after video-gaming is initiated at normal bedtime. However, physiological arousal may not necessarily be the mechanism by which technology use affects sleep. © 2012 European Sleep Research Society.

  4. 49 CFR 215.203 - Restricted cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Restricted cars. 215.203 Section 215.203..., DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Restricted Equipment § 215.203 Restricted cars. (a) This section restricts the operation of any railroad freight car that is— (1) More than 50...

  5. Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

    Science.gov (United States)

    Snel, Marieke; Wijngaarden, Marjolein A; Bizino, Maurice B; van der Grond, Jeroen; Teeuwisse, Wouter M; van Buchem, Mark A; Jazet, Ingrid M; Pijl, Hanno

    2012-01-01

    Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation. Copyright © 2012 S. Karger AG, Basel.

  6. Effects of drought and prolonged winter on Townsend's ground squirrel demography in shrubsteppe habitats

    Science.gov (United States)

    Van Horne, Beatrice; Olson, Gail S.; Schooley, Robert L.; Corn, Janelle G.; Burnham, Kenneth P.

    1997-01-01

    During a mark–recapture study of Townsend's ground squirrels (Spermophilus townsendii) on 20 sites in the Snake River Birds of Prey National Conservation Area, Idaho, in 1991 through 1994, 4407 animals were marked in 17639 capture events. This study of differences in population dynamics of Townsend's ground squirrels among habitats spanned a drought near the extreme of the 130-yr record, followed by prolonged winter conditions.Townsend's ground squirrels have a short active season (≈4 mo) in which to reproduce and store fat for overwintering. Their food consists largely of succulent grasses and forbs in this dry shrubsteppe and grassland habitat. The drought in the latter half of the 1992 active season produced early drying of Sandberg's bluegrass (Poa secunda) and was associated with low adult and juvenile body masses prior to immergence into estivation/hibernation. The following prolonged winter was associated with late emergence of females in 1993. Early-season body masses of adults were low in 1993 relative to 1992, whereas percentage of body fat in males was relatively high. These weather patterns in spring 1992 and winter 1993 also resulted in reduced adult persistence through the ≈7-mo inactive period, especially for adult females, and near-zero persistence of >1200 juveniles. Consequently, densities of Townsend's ground squirrels across the 20 livetrap sites declined.The demographic effects of drought and prolonged winter lasted at least through the subsequent breeding season. Adult females that survived these weather extremes produced fewer emergent young per female than did adult females prior to the event. Prior to the drought/prolonged winter, yearling female body masses were higher than, or indistinguishable from, those of adults. Females produced in 1993 had lower body masses as yearlings than did adult females.Demographic response to the drought and prolonged winter varied with habitat; ground squirrels in sagebrush habitat showed less decline

  7. Pharmacometabolomic approach to predict QT prolongation in guinea pigs.

    Directory of Open Access Journals (Sweden)

    Jeonghyeon Park

    Full Text Available Drug-induced torsades de pointes (TdP, a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r = 0.93. From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5 were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP, deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.

  8. Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

    Science.gov (United States)

    Martin, Bronwen; Mattson, Mark P.; Maudsley, Stuart

    2008-01-01

    The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. PMID:16899414

  9. Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia

    DEFF Research Database (Denmark)

    Gätke, Mona R; Bundgaard, Jens R; Viby-Mogensen, Jørgen

    2007-01-01

    Butyrylcholinesterase (BChE) hydrolyses the neuromuscular blocking agents, succinylcholine and mivacurium used during general anaesthesia. Hereditary low BChE activity may result in an extensively prolonged duration of action of these drugs, especially in patients who are homozygous for the atypi......Butyrylcholinesterase (BChE) hydrolyses the neuromuscular blocking agents, succinylcholine and mivacurium used during general anaesthesia. Hereditary low BChE activity may result in an extensively prolonged duration of action of these drugs, especially in patients who are homozygous...... for the atypical or silent variants. We present three novel mutations in the butyrylcholinesterase gene (BCHE) identified in three families in which a member had experienced severely prolonged duration of action of succinylcholine....

  10. Fellatio by fruit bats prolongs copulation time.

    Directory of Open Access Journals (Sweden)

    Min Tan

    Full Text Available Oral sex is widely used in human foreplay, but rarely documented in other animals. Fellatio has been recorded in bonobos Pan paniscus, but even then functions largely as play behaviour among juvenile males. The short-nosed fruit bat Cynopterus sphinx exhibits resource defence polygyny and one sexually active male often roosts with groups of females in tents made from leaves. Female bats often lick their mate's penis during dorsoventral copulation. The female lowers her head to lick the shaft or the base of the male's penis but does not lick the glans penis which has already penetrated the vagina. Males never withdrew their penis when it was licked by the mating partner. A positive relationship exists between the length of time that the female licked the male's penis during copulation and the duration of copulation. Furthermore, mating pairs spent significantly more time in copulation if the female licked her mate's penis than if fellatio was absent. Males also show postcopulatory genital grooming after intromission. At present, we do not know why genital licking occurs, and we present four non-mutually exclusive hypotheses that may explain the function of fellatio in C. sphinx.

  11. THE ROLE OF WORK AND LABOUR MARKET FLEXIBILITY IN WORKING LIFE PROLONGATION: CASE SLOVENIA

    Directory of Open Access Journals (Sweden)

    Klemen, SIROK

    2014-11-01

    Full Text Available Building upon the premise that the prolongation of working life presents an adequate approach to address the fast approaching challenges of population ageing, the paper presents labour market outcomes of older workers in Slovenia in order to explore the role of social system and labour market flexibility in retirement behaviour. By applying bivariate graphic analysis and series of logistic models, paper finds that decisions of older workers (aged 50 - 69 of whether to retire or to continue working up to legal retirement age is being predominately shaped by the pension system parameters. Economic activity beyond this age (or when retired on the other hand predominately correlates with flexible work arrangements and work motivation. Thus, the future policies in Slovenia aiming to prolong working careers within formal or informal sector should simultaneously do both; change pension system parameters and significantly expand the system flexibility stimulating willing and capable elderly to continue working within the formal sector.

  12. Psidium guajava and Piper betle leaf extracts prolong vase life of cut carnation (Dianthus caryophyllus) flowers.

    Science.gov (United States)

    Rahman, M M; Ahmad, S H; Lgu, K S

    2012-01-01

    The effect of leaf extracts of Psidium guajava and Piper betle on prolonging vase life of cut carnation flowers was studied. "Carola" and "Pallas Orange" carnation flowers, at bud stage, were pulsed 24 hours with a floral preservative. Then, flowers were placed in a vase solution containing sprite and a "germicide" (leaf extracts of P. guajava and P. betle, 8-HQC, or a copper coin). Flowers treated with 8-HQC, copper coin, and leaf extracts had longer vase life, larger flower diameter, and higher rate of water uptake compared to control (tap water). The leaf extracts of P. guajava and P. betle showed highest antibacterial and antifungal activities compared to the other treatments. Both showed similar effects on flower quality as the synthetic germicide, 8-HQC. Therefore, these extracts are likely natural germicides to prolong vase life of cut flowers.

  13. Psidium guajava and Piper betle Leaf Extracts Prolong Vase Life of Cut Carnation (Dianthus caryophyllus Flowers

    Directory of Open Access Journals (Sweden)

    M. M. Rahman

    2012-01-01

    Full Text Available The effect of leaf extracts of Psidium guajava and Piper betle on prolonging vase life of cut carnation flowers was studied. “Carola” and “Pallas Orange” carnation flowers, at bud stage, were pulsed 24 hours with a floral preservative. Then, flowers were placed in a vase solution containing sprite and a “germicide” (leaf extracts of P. guajava and P. betle, 8-HQC, or a copper coin. Flowers treated with 8-HQC, copper coin, and leaf extracts had longer vase life, larger flower diameter, and higher rate of water uptake compared to control (tap water. The leaf extracts of P. guajava and P. betle showed highest antibacterial and antifungal activities compared to the other treatments. Both showed similar effects on flower quality as the synthetic germicide, 8-HQC. Therefore, these extracts are likely natural germicides to prolong vase life of cut flowers.

  14. Development of prolonged standing strain index to quantify risk levels of standing jobs.

    Science.gov (United States)

    Halim, Isa; Omar, Abdul Rahman

    2012-01-01

    Many occupations in industry such as metal stamping workers, electronics parts assembly operators, automotive industry welders, and lathe operators require working in a standing posture for a long time. Prolonged standing can contribute to discomfort and muscle fatigue particularly in the back and legs. This study developed the prolonged standing strain index (PSSI) to quantify the risk levels caused by standing jobs, and proposed recommendations to minimize the risk levels. Risk factors associated with standing jobs, such as working posture, muscles activity, standing duration, holding time, whole-body vibration, and indoor air quality, were the basis for developing the PSSI. All risk factors were assigned multipliers, and the PSSI was the product of those multipliers. Recommendations for improvement are based on the PSSI; however, extensive studies are required to validate their effectiveness. multipliers, and the PSSI was the product of those multipliers. Recommendations for improvement are based on the PSSI; however, extensive studies are required to validate their effectiveness.

  15. Prolonged peritoneal gene expression using a helper-dependent adenovirus.

    Science.gov (United States)

    Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

    2009-01-01

    Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

  16. Correcting magnesium deficiencies may prolong life

    Directory of Open Access Journals (Sweden)

    Rowe WJ

    2012-02-01

    Full Text Available William J RoweFormer Assistant Clinical Professor of Medicine, Medical University of Ohio at Toledo, Ohio, USAAbstract: The International Space Station provides an extraordinary facility to study the accelerated aging process in microgravity, which could be triggered by significant reductions in magnesium (Mg ion levels with, in turn, elevations of catecholamines and vicious cycles between the two. With space flight there are significant reductions of serum Mg (P < 0.0001 that have been shown in large studies of astronauts and cosmonauts. The loss of the functional capacity of the cardiovascular system with space flight is over ten times faster than the course of aging on Earth. Mg is an antioxidant and calcium blocker and in space there is oxidative stress, insulin resistance, and inflammatory conditions with evidence in experimental animals of significant endothelial injuries and damage to mitochondria. The aging process is associated with progressive shortening of telomeres, repetitive DNA sequences, and proteins that cap and protect the ends of chromosomes. Telomerase can elongate pre-existing telomeres to maintain length and chromosome stability. Low telomerase triggers increased catecholamines while the sensitivity of telomere synthesis to Mg ions is primarily seen for the longer elongation products. Mg stabilizes DNA and promotes DNA replication and transcription, whereas low Mg might accelerate cellular senescence by reducing DNA stability, protein synthesis, and function of mitochondria. Telomerase, in binding to short DNAs, is Mg dependent. On Earth, in humans, a year might be required to detect changes in telomeres, but in space there is a predictably much shorter duration required for detection, which is therefore more reasonable in time and cost. Before and after a space mission, telomere lengths and telomerase enzyme activity can be determined and compared with age-matched control rats on Earth. The effect of Mg supplementation

  17. Prolonged social withdrawal disorder: a hikikomori case in Spain.

    Science.gov (United States)

    Ovejero, Santiago; Caro-Cañizares, Irene; de León-Martínez, Victoria; Baca-Garcia, Enrique

    2014-09-01

    The Japanese term hikikomori means literally 'to be confined'. Social withdrawal can be present in severe psychiatric disorders; however, in Japan, hikikomori is a defined nosologic entity. There have been only a few reported cases in occidental culture. We present a case report of a Spanish man with prolonged social withdrawal lasting for 4 years. This is a case of prolonged social withdrawal not bound to culture, as well as the second case of hikikomori reported in Spain. We propose prolonged social withdrawal disorder as a disorder not linked to culture, in contrast to hikikomori. Further documentation of this disorder is still needed to encompass all cases reported in Japan and around the world. © The Author(s) 2013.

  18. Left Ventricular Function After Prolonged Exercise in Equine Endurance Athletes

    DEFF Research Database (Denmark)

    Flethøj, M.; Schwarzwald, C. C.; Haugaard, M. M.

    2016-01-01

    Doppler imaging, and two-dimensional speckle tracking. Correlation between echocardiographic variables and cardiac troponin I was evaluated. Results: Early diastolic myocardial velocities decreased significantly in longitudinal (baseline: −17.4 ± 2.4cm/s; end of ride: −15.8 ± 3.2cm/s (P = .013); morning......Background: Prolonged exercise in human athletes is associated with transient impairment of left ventricular (LV) function, known as cardiac fatigue. Cardiac effects of prolonged exercise in horses remain unknown. Objectives :To investigate the effects of prolonged exercise on LV systolic...... and diastolic function in horses. Animals: Twenty-six horses competing in 120–160 km endurance rides. Methods: Cross-sectional field study. Echocardiography was performed before and after rides, and the following morning, and included two-dimensional echocardiography, anatomical M-mode, pulsed-wave tissue...

  19. Enlargement of Axo-Somatic Contacts Formed by GAD-Immunoreactive Axon Terminals onto Layer V Pyramidal Neurons in the Medial Prefrontal Cortex of Adolescent Female Mice Is Associated with Suppression of Food Restriction-Evoked Hyperactivity and Resilience to Activity-Based Anorexia

    OpenAIRE

    Chen, Yi-Wen; Wable, Gauri Satish; Chowdhury, Tara Gunkali; Aoki, Chiye

    2015-01-01

    Many, but not all, adolescent female mice that are exposed to a running wheel while food restricted (FR) become excessive wheel runners, choosing to run even during the hours of food availability, to the point of death. This phenomenon is called activity-based anorexia (ABA). We used electron microscopic immunocytochemistry to ask whether individual differences in ABA resilience may correlate with the lengths of axo-somatic contacts made by GABAergic axon terminals onto layer 5 pyramidal neur...

  20. Prolonged fasting increases purine recycling in post-weaned northern elephant seals.

    Science.gov (United States)

    Soñanez-Organis, José Guadalupe; Vázquez-Medina, José Pablo; Zenteno-Savín, Tania; Aguilar, Andres; Crocker, Daniel E; Ortiz, Rudy M

    2012-05-01

    Northern elephant seals are naturally adapted to prolonged periods (1-2 months) of absolute food and water deprivation (fasting). In terrestrial mammals, food deprivation stimulates ATP degradation and decreases ATP synthesis, resulting in the accumulation of purines (ATP degradation byproducts). Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) salvages ATP by recycling the purine degradation products derived from xanthine oxidase (XO) metabolism, which also promotes oxidant production. The contributions of HGPRT to purine recycling during prolonged food deprivation in marine mammals are not well defined. In the present study we cloned and characterized the complete and partial cDNA sequences that encode for HGPRT and xanthine oxidoreductase (XOR) in northern elephant seals. We also measured XO protein expression and circulating activity, along with xanthine and hypoxanthine plasma content in fasting northern elephant seal pups. Blood, adipose and muscle tissue samples were collected from animals after 1, 3, 5 and 7 weeks of their natural post-weaning fast. The complete HGPRT and partial XOR cDNA sequences are 771 and 345 bp long and encode proteins of 218 and 115 amino acids, respectively, with conserved domains important for their function and regulation. XOR mRNA and XO protein expression increased 3-fold and 1.7-fold with fasting, respectively, whereas HGPRT mRNA (4-fold) and protein (2-fold) expression increased after 7 weeks in adipose tissue and muscle. Plasma xanthine (3-fold) and hypoxanthine (2.5-fold) levels, and XO (1.7- to 20-fold) and HGPRT (1.5- to 1.7-fold) activities increased during the last 2 weeks of fasting. Results suggest that prolonged fasting in elephant seal pups is associated with increased capacity to recycle purines, which may contribute to ameliorating oxidant production and enhancing the supply of ATP, both of which would be beneficial during prolonged food deprivation and appear to be adaptive in this species.

  1. Cerebral ammonia uptake and accumulation during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam

    2005-01-01

    We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebral...... blood flow; n = 5) and the ammonia concentration in the cerebrospinal fluid (CSF; n = 8) at rest and immediately following prolonged exercise either with or without glucose supplementation. There was a net balance of ammonia across the brain at rest and at 30 min of exercise, whereas 3 h of exercise...... exercise with glucose, and further to 16.1 ± 3.3 µM after the placebo trial (P

  2. Brain mapping after prolonged cycling and during recovery in the heat.

    Science.gov (United States)

    De Pauw, Kevin; Roelands, Bart; Marusic, Uros; Tellez, Helio Fernandez; Knaepen, Kristel; Meeusen, Romain

    2013-11-01

    The aim of this study was to determine the effect of prolonged intensive cycling and postexercise recovery in the heat on brain sources of altered brain oscillations. After a max test and familiarization trial, nine trained male subjects (23 ± 3 yr; maximal oxygen uptake = 62.1 ± 5.3 ml·min(-1)·kg(-1)) performed three experimental trials in the heat (30°C; relative humidity 43.7 ± 5.6%). Each trial consisted of two exercise tasks separated by 1 h. The first was a 60-min constant-load trial, followed by a 30-min simulated time trial (TT1). The second comprised a 12-min simulated time trial (TT2). After TT1, active recovery (AR), passive rest (PR), or cold water immersion (CWI) was applied for 15 min. Electroencephalography was measured at baseline and during postexercise recovery. Standardized low-resolution brain electromagnetic tomography was applied to accurately pinpoint and localize altered electrical neuronal activity. After CWI, PR and AR subjects completed TT2 in 761 ± 42, 791 ± 76, and 794 ± 62 s, respectively. A prolonged intensive cycling performance in the heat decreased β activity across the whole brain. Postexercise AR and PR elicited no significant electrocortical differences, whereas CWI induced significantly increased β3 activity in Brodmann areas (BA) 13 (posterior margin of insular cortex) and BA 40 (supramarginal gyrus). Self-paced prolonged exercise in the heat seems to decrease β activity, hence representing decreased arousal. Postexercise CWI increased β3 activity at BA 13 and 40, brain areas involved in somatosensory information processing.

  3. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP.

    Directory of Open Access Journals (Sweden)

    Wessel M A van Leeuwen

    Full Text Available BACKGROUND: Sleep restriction, leading to deprivation of sleep, is common in modern 24-h societies and is associated with the development of health problems including cardiovascular diseases. Our objective was to investigate the immunological effects of prolonged sleep restriction and subsequent recovery sleep, by simulating a working week and following recovery weekend in a laboratory environment. METHODS AND FINDINGS: After 2 baseline nights of 8 hours time in bed (TIB, 13 healthy young men had only 4 hours TIB per night for 5 nights, followed by 2 recovery nights with 8 hours TIB. 6 control subjects had 8 hours TIB per night throughout the experiment. Heart rate, blood pressure, salivary cortisol and serum C-reactive protein (CRP were measured after the baseline (BL, sleep restriction (SR and recovery (REC period. Peripheral blood mononuclear cells (PBMC were collected at these time points, counted and stimulated with PHA. Cell proliferation was analyzed by thymidine incorporation and cytokine production by ELISA and RT-PCR. CRP was increased after SR (145% of BL; p<0.05, and continued to increase after REC (231% of BL; p<0.05. Heart rate was increased after REC (108% of BL; p<0.05. The amount of circulating NK-cells decreased (65% of BL; p<0.005 and the amount of B-cells increased (121% of BL; p<0.005 after SR, but these cell numbers recovered almost completely during REC. Proliferation of stimulated PBMC increased after SR (233% of BL; p<0.05, accompanied by increased production of IL-1beta (137% of BL; p<0.05, IL-6 (163% of BL; p<0.05 and IL-17 (138% of BL; p<0.05 at mRNA level. After REC, IL-17 was still increased at the protein level (119% of BL; p<0.05. CONCLUSIONS: 5 nights of sleep restriction increased lymphocyte activation and the production of proinflammatory cytokines including IL-1beta IL-6 and IL-17; they remained elevated after 2 nights of recovery sleep, accompanied by increased heart rate and serum CRP, 2 important risk

  4. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  5. Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients.

    Science.gov (United States)

    Goossens, Chloë; Vander Perre, Sarah; Van den Berghe, Greet; Langouche, Lies

    2017-12-01

    In prolonged non-obese critically ill patients, preservation of adipose tissue is prioritized over that of the skeletal muscle and coincides with increased adipogenesis. However, we recently demonstrated that in obese critically ill mice, this priority was switched. In the obese, the use of abundantly available adipose tissue-derived energy substrates was preferred and counteracted muscle wasting. These observations suggest that different processes are ongoing in adipose tissue of lean vs. overweight/obese critically ill patients. We hypothesize that to preserve adipose tissue mass during critical illness, adipogenesis is increased in prolonged lean critically ill patients, but not in overweight/obese critically ill patients, who enter the ICU with excess adipose tissue. To test this, we studied markers of adipogenesis in subcutaneous and visceral biopsies of matched lean (n = 24) and overweight/obese (n = 24) prolonged critically ill patients. Secondly, to further unravel the underlying mechanism of critical illness-induced adipogenesis, local production of eicosanoid PPARγ agonists was explored, as well as the adipogenic potential of serum from matched lean (n = 20) and overweight/obese (n = 20) critically ill patients. The number of small adipocytes, PPARγ protein, and CEBPB expression were equally upregulated (p ≤ 0.05) in subcutaneous and visceral adipose tissue biopsies of lean and overweight/obese prolonged critically ill patients. Gene expression of key enzymes involved in eicosanoid production was reduced (COX1, HPGDS, LPGDS, ALOX15, all p ≤ 0.05) or unaltered (COX2, ALOX5) during critical illness, irrespective of obesity. Gene expression of PLA2G2A and ALOX15B was upregulated in lean and overweight/obese patients (p ≤ 0.05), whereas their end products, the PPARγ-activating metabolites 15s-HETE and 9-HODE, were not increased in the adipose tissue. In vitro, serum of lean and overweight/obese prolonged critically ill

  6. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    International Nuclear Information System (INIS)

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-01-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I Na ) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I Na , this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E max 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three

  7. Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days

    NARCIS (Netherlands)

    Starokozhko, Viktoriia; Vatakuti, Suresh; Schievink, Bauke; Merema, Marjolijn T.; Asplund, Annika; Synnergren, Jane; Aspegren, Anders; Groothuis, Geny M. M.

    Human precision-cut liver slices (hPCLS) are a valuable ex vivo model that can be used in acute toxicity studies. However, a rapid decline in metabolic enzyme activity limits their use in studies that require a prolonged xenobiotic exposure. The aim of the study was to extend the viability and

  8. Neural changes in extinction recall following prolonged exposure treatment for PTSD: A longitudinal fMRI study

    Directory of Open Access Journals (Sweden)

    Liat Helpman, PhD

    2016-01-01

    Conclusions: Prolonged exposure treatment appears to alter neural activation in PTSD patients during recall of fear extinction, and change in extinction recall (measured by SCR is associated with symptom reduction. We discuss results in the context of neural systems involved in response to affective stimuli.

  9. Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia

    DEFF Research Database (Denmark)

    Gätke, Mona R; Bundgaard, Jens R; Viby-Mogensen, Jørgen

    2007-01-01

    Butyrylcholinesterase (BChE) hydrolyses the neuromuscular blocking agents, succinylcholine and mivacurium used during general anaesthesia. Hereditary low BChE activity may result in an extensively prolonged duration of action of these drugs, especially in patients who are homozygous for the atypi...

  10. Experimental and theoretical study of the transport of silver nanoparticles at their prolonged administration into a mammal organism

    Science.gov (United States)

    Antsiferova, A. A.; Buzulukov, Yu. P.; Kashkarov, P. K.; Kovalchuk, M. V.

    2016-11-01

    The transport of silver nanoparticles in the organism of laboratory animals has been investigated. A mathematical model of the biokinetics of prolonged administration of nonmetabolizable and nonaglomerating pharmaceutical preparations is proposed, and its analytical solution is found. Based on the experimental data on the prolonged introduction and excretion of colloidal silver nanoparticles and the numerical approximation of the solutions to the equations for the proposed model, time dependences of the silver mass content in brain and blood are obtained and some other important biokinetic parameters are determined. It is concluded that both chronic1 and subchronic2 peroral application of these nanoparticles as an biologically active additive or antiseptic is potentially dangerous.

  11. The effect of medial arch support over the plantar pressure and triceps surae muscle strength after prolonged standing

    OpenAIRE

    Hindun Saadah; Deswaty Furqonita; Angela Tulaar

    2015-01-01

    Background: The activity with prolonged standing position is one of the causes of abnormalities in the lower leg and foot. The aim of this study is to discover the effect of medial arch support over the distribution of plantar pressure when standing and walking.Methods: This was an experimental study with pre- and post-design the strength of triceps surae muscle after prolonged standing, was also evaluated in an experimental study with pre- and post-design. Variables of plantar pressure measu...

  12. Parenting and restrictions in childhood epilepsy

    NARCIS (Netherlands)

    Rodenburg, R.; Meijer, A.M.; Scherphof, C.; Carpay, J.A.; Augustijn, P.; Aldenkamp, A.P.; Deković, M.

    2013-01-01

    Purpose: From the overprotection literature, the predictive and interactional (moderation) effects of controlling and indulgent parenting on restrictions in children with epilepsy were examined. Methods: Parents of 73 children with epilepsy completed questionnaires on parenting, restrictions, and

  13. Public stigma of prolonged grief disorder : An experimental study

    NARCIS (Netherlands)

    Eisma, Maarten C.

    Prolonged grief disorder (PGD), characterized by severe, persistent and disabling grief, is being considered for inclusion in the International Classification of Diseases’ 11 (ICD-11) and a related disorder, Persistent Complex Bereavement Disorder (PCBD), is included for further investigation in the

  14. Prolonged use of indwelling urinary catheter following acute urinary ...

    African Journals Online (AJOL)

    J.O. Bello

    prolonged use of urinary catheters following acute urinary retention secondary to benign prostate enlarge- ment (BPE) and urethral ... indwelling urinary catheter for >3 months following acute urinary retention due to BPE or USD. The study .... the major health-care financing strategy in Nigeria and accounts for more than ...

  15. Assessing QT interval prolongation and its associated risks with antipsychotics

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Graff, Claus; Kanters, Jørgen K.

    2011-01-01

    markers for TdP have been developed but none of them is clinically implemented yet and QT interval prolongation is still considered the most valid surrogate marker. Although automated QT interval determination may offer some assistance, QT interval determination is best performed by a cardiologist skilled...

  16. MRI findings of prolonged post-traumatic sternal pain

    International Nuclear Information System (INIS)

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne; Steinbach, Lynne

    2007-01-01

    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  17. Diet-consumer nitrogen isotope fractionation for prolonged fasting arthropods.

    Science.gov (United States)

    Mizota, Chitoshi; Yamanaka, Toshiro

    2011-12-01

    Nitrogen acquisition for cellular metabolism during diapause is a primary concern for herbivorous arthropods. Analyses of naturally occurring stable isotopes of nitrogen help elucidate the mechanism. Relevant articles have cited (58 times up to mid-June 2011) anomalously elevated δ(15)N (per mil deviation of (15)N/(14)N, relative to atmospheric nitrogen=0 ‰) values (diet-consumer nitrogen isotope fractionation; up to 12 ‰) for a prolonged fasting raspberry beetle (Byturus tomentosus Degeer (Coleoptera: Byturidae)), which feeds on red raspberries (Rubus idaeus: δ(15)N= ~ +2 ‰). Biologists have hypothesised that extensive recycling of amino acid nitrogen is responsible for the prolonged fasting. Since this hypothesis was proposed in 1995, scientists have integrated biochemical and molecular knowledge to support the mechanism of prolonged diapausing of animals. To test the validity of the recycling hypothesis, we analysed tissue nitrogen isotope ratios for four Japanese arthropods: the shield bug Parastrachia japonensis Scott (Hemiptera: Cydnidae), the burrower bug Canthophorus niveimarginatus Scott (Hemiptera: Cydnidae), leaf beetle Gastrophysa atrocyanea Motschulsky (Coleoptera: Chrysomelidae) and the Japanese oak silkworm Antheraea yamamai (Lepidoptera: Saturniidae), all of which fast for more than 6 months as part of their life-history strategy. Resulting diet-consumer nitrogen isotope discrimination during fasting ranged from 0 to 7‰, as in many commonly known terrestrial arthropods. We conclude that prolonged fasting of arthropods does not always result in anomalous diet-consumer nitrogen isotope fractionation, since the recycling process is closed or nearly closed with respect to nitrogen isotopes.

  18. Prolonged Intrauterine Retention of Foetal Bones after Midtrimester ...

    African Journals Online (AJOL)

    Prolonged retention of foetal bones in the uterus is a rare complication of induced abortion. We present the case of a 37 year old nullipara with retained foetal bones following a second trimester induced abortion. Accurate diagnosis and removal of the bony fragments led to restoration of fertility and subsequent delivery of a ...

  19. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    NARCIS (Netherlands)

    De Bruin, ML; Hoes, AW; Leufkens, HGM

    2003-01-01

    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and

  20. The Prolonged Neonatal Admission: Implications for our National Children's Hospital

    LENUS (Irish Health Repository)

    McGlacken-Byrne, SM

    2016-06-01

    A significant number of neonates are admitted to tertiary paediatric units for prolonged stays annually, despite limited availability of neonatal beds. As the three Dublin paediatric hospitals merge, this pressure will be transferred to our new National Children’s Hospital.\\r\

  1. The Importance of Prolonged Provocation in Drug Allergy

    DEFF Research Database (Denmark)

    Fransson, Sara; Mosbech, Holger; Kappel, Mogens

    2017-01-01

    BACKGROUND: Drug provocation is the "Gold Standard" in drug allergy investigation. Recent studies suggest that a negative drug provocation on first dose should be followed by a prolonged provocation over several days. OBJECTIVE: To evaluate drug allergy investigations on the basis of drug...

  2. Influence of prolonged cold ischemia in renal transplantation.

    NARCIS (Netherlands)

    Vliet, J.A. van der; Warle, M.C.; Cheung, C.L.; Teerenstra, S.; Hoitsma, A.J.

    2011-01-01

    van der Vliet JA, Warle MC, Cheung CLS, Teerenstra S, Hoitsma AJ. Influence of prolonged cold ischemia in renal transplantation. Clin Transplant 2011: 25: E612-E616. (c) 2011 John Wiley & Sons A/S. Abstract: Aim: To determine to what extent current cold ischemia times (CITs) affect the results of

  3. The impact of obesity on physiological responses during prolonged exercise

    NARCIS (Netherlands)

    Eijsvogels, T.M.H.; Veltmeijer, M.T.; Schreuder, T.H.A.; Poelkens, F.; Thijssen, D.H.J.; Hopman, M.T.E.

    2011-01-01

    Background:Prolonged, moderate-intensity exercise training is routinely prescribed to subjects with obesity. In the general population, this type of exercise can lead to fluid and sodium imbalance. However, little is known whether obesity alters the risk of fluid and sodium imbalances.Objective:This

  4. Physiological response of rabbit bucks to prolonged feeding of ...

    African Journals Online (AJOL)

    Sixty-four (64) weanling rabbit bucks, 5 to 6 weeks old, were involved in a 2 x 4 factorial experiment to evaluate the effects of prolonged feeding of cottonseed cake (CSC) – based diets with or without vitamin E supplementation on the physiological response of the bucks. There were eight treatment combinations comprising ...

  5. Single Prolonged Stress Disrupts Retention of Extinguished Fear in Rats

    Science.gov (United States)

    Knox, Dayan; George, Sophie A.; Fitzpatrick, Christopher J.; Rabinak, Christine A.; Maren, Stephen; Liberzon, Israel

    2012-01-01

    Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress…

  6. Internalized stigma in adults with early phase versus prolonged psychosis.

    Science.gov (United States)

    Firmin, Ruth L; Lysaker, Paul H; Luther, Lauren; Yanos, Philip T; Leonhardt, Bethany; Breier, Alan; Vohs, Jenifer L

    2018-03-30

    Although internalized stigma is associated with negative outcomes among those with prolonged psychosis, surprisingly little work has focused on when in the course of one's illness stigma is internalized and the impact of internalization on symptoms or social functioning over the course of the illness. Therefore, this study investigated whether (1) internalized stigma is greater among those later in the course of psychosis and (2) whether internalized stigma has a stronger negative relationship with social functioning or symptoms among those with prolonged compared to early phase psychosis. Individuals with early phase (n = 40) and prolonged psychosis (n = 71) who were receiving outpatient services at an early-intervention clinic and a VA medical center, respectively, completed self-report measures of internalized stigma and interview-rated measures of symptoms and social functioning. Controlling for education, race and sex differences, internalized stigma was significantly greater among those with prolonged psychosis compared to early phase. Internalized stigma was negatively related to social functioning and positively related to symptoms in both groups. Furthermore, the magnitude of the relationship between cognitive symptoms and internalized stigma was significantly greater among those with early phase. Stereotype endorsement, discrimination experiences and social withdrawal also differentially related to symptoms and social functioning across the 2 samples. Findings suggest that internalized stigma is an important variable to incorporate into models of early psychosis. Furthermore, internalized stigma may be a possible treatment target among those with early phase psychosis. © 2018 John Wiley & Sons Australia, Ltd.

  7. Streptococcus suis meningitis can require a prolonged treatment course

    Directory of Open Access Journals (Sweden)

    Jean Dejace

    2017-12-01

    Full Text Available We report a case of recrudescent Streptococcus suis meningitis requiring a prolonged treatment course. A few similar cases can be found in the burgeoning literature on what remains a relatively uncommon disease in humans, and these patients should be monitored carefully upon completion of therapy. Keywords: Meningitis, Relapse, Duration, Streptococcus suis

  8. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    Science.gov (United States)

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  9. Intrinsic motivation and amotivation in first episode and prolonged psychosis.

    Science.gov (United States)

    Luther, Lauren; Lysaker, Paul H; Firmin, Ruth L; Breier, Alan; Vohs, Jenifer L

    2015-12-01

    The deleterious functional implications of motivation deficits in psychosis have generated interest in examining dimensions of the construct. However, there remains a paucity of data regarding whether dimensions of motivation differ over the course of psychosis. Therefore, this study examined two motivation dimensions, trait-like intrinsic motivation, and the negative symptom of amotivation, and tested the impact of illness phase on the 1) levels of these dimensions and 2) relationship between these dimensions. Participants with first episode psychosis (FEP; n=40) and prolonged psychosis (n=66) completed clinician-rated measures of intrinsic motivation and amotivation. Analyses revealed that when controlling for group differences in gender and education, the FEP group had significantly more intrinsic motivation and lower amotivation than the prolonged psychosis group. Moreover, intrinsic motivation was negatively correlated with amotivation in both FEP and prolonged psychosis, but the magnitude of the relationship did not statistically differ between groups. These findings suggest that motivation deficits are more severe later in the course of psychosis and that low intrinsic motivation may be partially independent of amotivation in both first episode and prolonged psychosis. Clinically, these results highlight the importance of targeting motivation in early intervention services. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Prognostic Significance Of QT Interval Prolongation In Adult ...

    African Journals Online (AJOL)

    Prognostic survival studies for heart-rate corrected QT interval in patients with chronic heart failure are few; although these patients are known to have a high risk of sudden cardiac death. This study was aimed at determining the mortality risk associated with prolonged QTc in Nigerians with heart failure. Ninety-six ...

  11. Competing for Consciousness: Prolonged Mask Exposure Reduces Object Substitution Masking

    Science.gov (United States)

    Goodhew, Stephanie C.; Visser, Troy A. W.; Lipp, Ottmar V.; Dux, Paul E.

    2011-01-01

    In object substitution masking (OSM) a sparse, temporally trailing 4-dot mask impairs target identification, even though it has different contours from, and does not spatially overlap with the target. Here, we demonstrate a previously unknown characteristic of OSM: Observers show reduced masking at prolonged (e.g., 640 ms) relative to intermediate…

  12. Prolonged multifocal electroretinographic implicit times in the ocular ischemic syndrome

    DEFF Research Database (Denmark)

    Kofoed, Peter Kristian; Munch, Inger Christine; Sander, Birgit

    2010-01-01

    .4 +/- 1.7 mm Hg, respectively. Summed mfERG implicit times (N1, P1, N2) were prolonged in eyes with OIS, by 7.6%, 6.2%, and 7.5%, respectively, compared with fellow eyes (P macula, whereas the assessment of responses from...

  13. Prolongation Structure of Semi-discrete Nonlinear Evolution Equations

    International Nuclear Information System (INIS)

    Bai Yongqiang; Wu Ke; Zhao Weizhong; Guo Hanying

    2007-01-01

    Based on noncommutative differential calculus, we present a theory of prolongation structure for semi-discrete nonlinear evolution equations. As an illustrative example, a semi-discrete model of the nonlinear Schroedinger equation is discussed in terms of this theory and the corresponding Lax pairs are also given.

  14. Inclusion rate and physiological effects of prolonged feeding of ...

    African Journals Online (AJOL)

    The effect of incluusion of cocoa bean cake (CBC) on productive performance and physiological response of Isa Brown pullets to prolonged feeding of CBC were investigated. Dietary Inclusions or CBC (0, 50, 100 and 200g/ kg-1 diet) were monitored in typical poultry diets from day old to 51 weeks of age. Sexual maturity ...

  15. Preferences for Prolonging Life: A Prospect Theory Approach

    Science.gov (United States)

    Winter, Laraine; Lawton, M. Powell; Ruckdeschel, Katy

    2003-01-01

    Kahneman and Tversky's (1979) Prospect theory was tested as a model of preferences for prolonging life under various hypothetical health statuses. A sample of 384 elderly people living in congregate housing (263 healthy, 131 frail) indicated how long (if at all) they would want to live under each of nine hypothetical health conditions (e.g.,…

  16. Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress

    Science.gov (United States)

    2014-10-01

    Post - traumatic stress disorder ( PTSD ) is a chronic, debilitating psychiatric disorder that can...SPS animals. Post - traumatic stress disorder ( PTSD ) is associated with neurocognitive impairments that have been attributed to functional deficits...and resilience. 2. KEYWORDS Post - traumatic stress disorder , Single Prolonged Stress , Neurobiological Mechanisms 5 3. ACCOMPLISHMENTS

  17. Effect Of Prolonged Monocular Occlusion On Latent Nystagms

    NARCIS (Netherlands)

    H.J. Simonsz (Huib); G. Kommerell (Guntram)

    1992-01-01

    textabstractThe authors recorded nystagmus during seeing with one eye in eight patients with latent nystagmus (LN) before and after two or three days of prolonged occlusion of the better eye (POBE). Before POBE, the slow-phase speed of the nystagmus (SPS) was usually higher when the better eye was

  18. Effects of strict prolonged bed rest on cardiorespiratory fitness

    DEFF Research Database (Denmark)

    Ried-Larsen, Mathias; Aarts, Hugo M; Joyner, Michael J

    2017-01-01

    The aim of this systematic review and meta-analysis [International Prospective Register of Systematic Reviews (PROSPERO) CRD42017055619] was to assess the effects of strict prolonged bed rest (without countermeasures) on maximal oxygen uptake (V̇o2max) and to explore sources of variation therein....

  19. Cardiorespiratory effects of inelastic chest wall restriction.

    Science.gov (United States)

    Miller, Jordan D; Beck, Kenneth C; Joyner, Michael J; Brice, A Glenn; Johnson, Bruce D

    2002-06-01

    We examined the effects of chest wall restriction (CWR) on cardiorespiratory function at rest and during exercise in healthy subjects in an attempt to approximate the cardiorespiratory interactions observed in clinical conditions that result in restrictive lung and/or chest wall changes and a reduced intrathoracic space. Canvas straps were applied around the thorax and abdomen so that vital capacity was reduced by >35%. Data were acquired at rest and during cycle ergometry at 25 and 45% of peak workloads. CWR elicited significant increases in the flow-resistive work performed on the lung (160%) and the gastric pressure-time integral (>400%) at the higher workload, but it resulted in a decrease in the elastic work performed on the lung (56%) compared with control conditions. With CWR, heart rate increased and stroke volume (SV) fell, resulting in >10% fall in cardiac output at rest and during exercise at matched workloads (P < 0.05). Blood pressure and catecholamines were significantly elevated during CWR exercise conditions (P < 0.05). We conclude that CWR significantly impairs SV during exercise and that a compensatory increase in heart rate does not prevent a significant reduction in cardiac output. O(2) consumption appears to be maintained via increased extraction and a redistribution of blood flow via sympathetic activation.

  20. Does unconscious stress play a role in prolonged cardiovascular stress recovery?

    Science.gov (United States)

    Brosschot, J F; Geurts, S A E; Kruizinga, I; Radstaak, M; Verkuil, B; Quirin, M; Kompier, M A J

    2014-08-01

    According to recent insights, humans might not be aware of a substantial part of their cognitive stress representations while these still have prolonged physiological effects. 'Unconscious stress' can be measured by implicit affect (IA) tests. It was shown that IA predicts physiological stress responses, in fact better than explicit ('conscious') affect. It is not known yet whether IA is associated with concurrent prolonged stress responses. In two studies (n = 62 and 123), anger harassment was used to induce stress. Blood pressure (BP) and heart rate (HR) were measured continuously. During BP and HR recovery, IA was measured by an 'anger' version of the implicit association test (IAT) or the implicit positive and negative affect test (IPANAT). Blood pressure and HR increased during anger harassment and recovery afterwards. When using the IPANAT BP recovery levels were lower when positive IA was high and higher when negative IA was high, independent of explicit affect and rumination. These results were not found using the IAT. These results provide preliminary evidence that physiological stress recovery is associated with IA. This is in line with the theory that unconscious stress is responsible for a-possibly considerable-part of unhealthy prolonged stress-related physiological activity. Copyright © 2014 John Wiley & Sons, Ltd.

  1. Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

    Directory of Open Access Journals (Sweden)

    Marta Herranz

    2018-01-01

    Full Text Available Background:Mycobacterium tuberculosis (MTB has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs between isolates.Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts.Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission.Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed.Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.

  2. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Directory of Open Access Journals (Sweden)

    Raimundo M. G. del Moral

    2013-01-01

    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  3. 49 CFR 383.95 - Restrictions.

    Science.gov (United States)

    2010-10-01

    ... the skills test and the restriction, air brakes shall include any braking system operating fully or...; REQUIREMENTS AND PENALTIES Vehicle Groups and Endorsements § 383.95 Restrictions. (a) Air brake restrictions... skills test in a vehicle not equipped with air brakes, the State must indicate on the CDL, if issued...

  4. 9 CFR 92.3 - Movement restrictions.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Movement restrictions. 92.3 Section 92... ANIMAL PRODUCTS: PROCEDURES FOR REQUESTING RECOGNITION OF REGIONS § 92.3 Movement restrictions. Whenever... exist and the EC imposes prohibitions or other restrictions on the movement of animals or animal...

  5. 21 CFR 203.20 - Sales restrictions.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sales restrictions. 203.20 Section 203.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL PRESCRIPTION DRUG MARKETING Sales Restrictions § 203.20 Sales restrictions. Except as provided in § 203.22 or...

  6. Food restriction reduces neurogenesis in the avian hippocampal formation.

    Directory of Open Access Journals (Sweden)

    Barbara-Anne Robertson

    Full Text Available The mammalian hippocampus is particularly vulnerable to chronic stress. Adult neurogenesis in the dentate gyrus is suppressed by chronic stress and by administration of glucocorticoid hormones. Post-natal and adult neurogenesis are present in the avian hippocampal formation as well, but much less is known about its sensitivity to chronic stressors. In this study, we investigate this question in a commercial bird model: the broiler breeder chicken. Commercial broiler breeders are food restricted during development to manipulate their growth curve and to avoid negative health outcomes, including obesity and poor reproductive performance. Beyond knowing that these chickens are healthier than fully-fed birds and that they have a high motivation to eat, little is known about how food restriction impacts the animals' physiology. Chickens were kept on a commercial food-restricted diet during the first 12 weeks of life, or released from this restriction by feeding them ad libitum from weeks 7-12 of life. To test the hypothesis that chronic food restriction decreases the production of new neurons (neurogenesis in the hippocampal formation, the cell proliferation marker bromodeoxyuridine was injected one week prior to tissue collection. Corticosterone levels in blood plasma were elevated during food restriction, even though molecular markers of hypothalamic-pituitary-adrenal axis activation did not differ between the treatments. The density of new hippocampal neurons was significantly reduced in the food-restricted condition, as compared to chickens fed ad libitum, similar to findings in rats at a similar developmental stage. Food restriction did not affect hippocampal volume or the total number of neurons. These findings indicate that in birds, like in mammals, reduction in hippocampal neurogenesis is associated with chronically elevated corticosterone levels, and therefore potentially with chronic stress in general. This finding is consistent with the

  7. Novel host restriction factors implicated in HIV-1 replication.

    Science.gov (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

    2018-04-01

    Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

  8. Potentiation of ghrelin signaling attenuates cancer anorexia–cachexia and prolongs survival

    Science.gov (United States)

    Fujitsuka, N; Asakawa, A; Uezono, Y; Minami, K; Yamaguchi, T; Niijima, A; Yada, T; Maejima, Y; Sedbazar, U; Sakai, T; Hattori, T; Kase, Y; Inui, A

    2011-01-01

    Cancer anorexia–cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut–brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia–cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia–cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia–cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia–cachexia. PMID:22832525

  9. Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

    Directory of Open Access Journals (Sweden)

    Wei-Hua Tang

    Full Text Available Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD. In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

  10. Strategies to reduce the risk of drug-induced QT interval prolongation: a pharmaceutical company perspective.

    Science.gov (United States)

    Pollard, C E; Valentin, J-P; Hammond, T G

    2008-08-01

    Drug-induced prolongation of the QT interval is having a significant impact on the ability of the pharmaceutical industry to develop new drugs. The development implications for a compound causing a significant effect in the 'Thorough QT/QTc Study' -- as defined in the clinical regulatory guidance (ICH E14) -- are substantial. In view of this, and the fact that QT interval prolongation is linked to direct inhibition of the hERG channel, in the early stages of drug discovery the focus is on testing for and screening out hERG activity. This has led to understanding of how to produce low potency hERG blockers whilst retaining desirable properties. Despite this, a number of factors mean that when an integrated risk assessment is generated towards the end of the discovery phase (by conducting at least an in vivo QT assessment) a QT interval prolongation risk is still often apparent; inhibition of hERG channel trafficking and partitioning into cardiac tissue are just two confounding factors. However, emerging information suggests that hERG safety margins have high predictive value and that when hERG and in vivo non-clinical data are combined, their predictive value to man, whilst not perfect, is >80%. Although understanding the anomalies is important and is being addressed, of greater importance is developing a better understanding of TdP, with the aim of being able to predict TdP rather than using an imperfect surrogate marker (QT interval prolongation). Without an understanding of how to predict TdP risk, high-benefit drugs for serious indications may never be marketed.

  11. Prolonged hemodynamic response during incidental facial emotion processing in inter-episode bipolar I disorder.

    Science.gov (United States)

    Rosenfeld, Ethan S; Pearlson, Godfrey D; Sweeney, John A; Tamminga, Carol A; Keshavan, Matcheri S; Nonterah, Camilla; Stevens, Michael C

    2014-03-01

    This fMRI study examined whether hemodynamic responses to affectively-salient stimuli were abnormally prolonged in remitted bipolar disorder, possibly representing a novel illness biomarker. A group of 18 DSM-IV bipolar I-diagnosed adults in remission and a demographically-matched control group performed an event-related fMRI gender-discrimination task in which face stimuli had task-irrelevant neutral, happy or angry expressions designed to elicit incidental emotional processing. Participants' brain activation was modeled using a "fully informed" SPM5 basis set. Mixed-model ANOVA tested for diagnostic group differences in BOLD response amplitude and shape within brain regions-of-interest selected from ALE meta-analysis of previous comparable fMRI studies. Bipolar-diagnosed patients had a generally longer duration and/or later-peaking hemodynamic response in amygdala and numerous prefrontal cortex brain regions. Data are consistent with existing models of bipolar limbic hyperactivity, but the prolonged frontolimbic response more precisely details abnormalities recognized in previous studies. Prolonged hemodynamic responses were unrelated to stimulus type, task performance, or degree of residual mood symptoms, suggesting an important novel trait vulnerability brain dysfunction in bipolar disorder. Bipolar patients also failed to engage pregenual cingulate and left orbitofrontal cortex-regions important to models of automatic emotion regulation-while engaging a delayed dorsolateral prefrontal cortex response not seen in controls. These results raise questions about whether there are meaningful relationships between bipolar dysfunction of specific ventromedial prefrontal cortex regions believed to automatically regulate emotional reactions and the prolonged responses in more lateral aspects of prefrontal cortex.

  12. A simple method to prolong the service life of radioactive sources for external radiotherapy.

    Science.gov (United States)

    Xu, Yingjie; Tian, Yuan; Dai, Jianrong

    2014-07-08

    A radioactive source is usually replaced and disposed after being used for a certain amount of time (usually a half-life). In this study, a simple method is proposed to prolong its service life. Instead of replacing the used source with a new source of full activity, a new source of less activity is added in the source holder in front of the used one, so that the total activity of two sources is equal to the initial activity of the used source or even higher. Similarly, more sources can be added to the previous ones. Attenuation of front source(s) to the back source(s) was evaluated with exponential attenuation equation, and variation of source-focus distance (SFD) with inverse square law for Leksell 4C Gamma Knife, which served as an example of external radiotherapy units. When the number of front sources increased from 1 to 3, the relative air kerma decreased from 36.5% to 5.0%. Both the attenuation effect and SFD variation contributed to the decrease in air kerma, with the former being the major factor. If the height of the source can be decreased in some way, such as increasing the specific activity of sources, the sources can be used more efficiently. The method prolongs the service life of sources by several factors, and reduces the expense of source exchange and reclamation.

  13. The efficacy of antipsychotics for prolonged delirium with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Asano S

    2017-11-01

    Full Text Available Satoko Asano, Yasuto Kunii, Hiroshi Hoshino, Yusuke Osakabe, Tetsuya Shiga, Shuntaro Itagaki, Itaru Miura, Hirooki Yabe Department of Neuropsychiatry, School of Medicine Fukushima Medical University, Fukushima, Japan Aim: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization.Methods: We extracted all new inpatients (n=523 consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an “early improvement group” in which delirium resolved in ≤3 days after starting psychiatric medication, and a “prolonged group” with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2, we defined an “early improvement group with renal dysfunction” in which delirium resolved in ≤3 days after starting psychiatric medication and a “prolonged group with renal dysfunction” with delirium lasting for >3 days. We then examined differences between groups for different categorical variables.Results: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction.Conclusion: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction. Keywords: antipsychotic, prolonged delirium, chronic kidney disease, pharmacokinetics 

  14. The ability of multimerized cyclophilin A to restrict retrovirus infection

    International Nuclear Information System (INIS)

    Javanbakht, Hassan; Diaz-Griffero, Felipe; Yuan Wen; Yeung, Darwin F.; Li Xing; Song Byeongwoon; Sodroski, Joseph

    2007-01-01

    In owl monkeys, the typical retroviral restriction factor of primates, TRIM5α, is replaced by TRIMCyp. TRIMCyp consists of the TRIM5 RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIM5 coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIM5 RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection

  15. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Energy budget, behavior and leptin in striped hamsters subjected to food restriction and refeeding.

    Directory of Open Access Journals (Sweden)

    Zhi-Jun Zhao

    Full Text Available Food restriction induces a loss of body mass that is often followed by rapid regaining of the lost weight when the restriction ends, consequently increasing a risk of development of obesity. To determine the physiological and behavioral mechanisms underlining the regaining, striped hamsters were restricted to 85% of initial food intake for 4 weeks and refed ad libitum for another 4 weeks. Changes in body mass, energy budget, activity, body composition and serum leptin level were measured. Body mass, body fat mass and serum leptin level significantly decreased in food-restricted hamsters, and increased when the restriction ended, showing a short "compensatory growth" rather than over-weight or obesity compared with ad libitum controls. During restriction, the time spent on activity increased significantly, which was opposite to the changes in serum leptin level. Food intake increased shortly during refeeding, which perhaps contributed to the rapid regaining of body mass. No correlation was observed between serum leptin and energy intake, while negative correlations were found in hamsters that were refed for 7 and 28 days. Exogenous leptin significantly decreased the time spent on activity during food restriction and attenuated the increase in food intake during refeeding. This suggests that low leptin in restricted animals may function as a starvation signal to induce an increase in activity behavior, and high leptin likely serves as a satiety signal to prevent activity during refeeding. Leptin may play a crucial role in controlling food intake when the restriction ends, and consequently preventing overweight.

  17. Effectiveness of prolonged use of continuous passive motion (CPM as an adjunct to physiotherapy following total knee arthroplasty: Design of a randomised controlled trial [ISRCTN85759656

    Directory of Open Access Journals (Sweden)

    Geesink Ruud JT

    2006-02-01

    . Discussion Because restricted knee ROM affects functional activities, knee ROM and knee function are regarded as the primary indicators of successful TKA. Potential effects of the intervention under study include rapid return of knee flexion accompanied by earlier return to functional activities of daily life. If patients benefit significantly from prolonged CPM use, this treatment should be added to the standard PT treatment at home. We expect the additional home CPM programme to be more effective than the usual physiotherapy programme, resulting in a difference in ROM of at least 5°, 17 days after surgery. This clinically important difference, with a possible flexion ROM of about 100°, is expected to lead to better functioning in activities of daily life, like walking, and earlier ability to cycle. These advantages should result in earlier and increasing independence.

  18. Effectiveness of prolonged use of continuous passive motion (CPM) as an adjunct to physiotherapy following total knee arthroplasty: Design of a randomised controlled trial [ISRCTN85759656

    Science.gov (United States)

    Lenssen, Anton F; Crijns, Yvonne HF; Waltjé, Eddie MH; Roox, George M; van Steyn, Mike JA; Geesink, Ruud JT; van den Brandt, Piet A; de Bie, Rob A

    2006-01-01

    restricted knee ROM affects functional activities, knee ROM and knee function are regarded as the primary indicators of successful TKA. Potential effects of the intervention under study include rapid return of knee flexion accompanied by earlier return to functional activities of daily life. If patients benefit significantly from prolonged CPM use, this treatment should be added to the standard PT treatment at home. We expect the additional home CPM programme to be more effective than the usual physiotherapy programme, resulting in a difference in ROM of at least 5°, 17 days after surgery. This clinically important difference, with a possible flexion ROM of about 100°, is expected to lead to better functioning in activities of daily life, like walking, and earlier ability to cycle. These advantages should result in earlier and increasing independence. PMID:16504087

  19. Effectiveness of prolonged use of continuous passive motion (CPM) as an adjunct to physiotherapy following total knee arthroplasty: design of a randomised controlled trial [ISRCTN85759656].

    Science.gov (United States)

    Lenssen, Anton F; Crijns, Yvonne H F; Waltjé, Eddie M H; Roox, George M; van Steyn, Mike J A; Geesink, Ruud J T; van den Brandt, Piet A; de Bie, Rob A

    2006-02-23

    Adequate and intensive rehabilitation is an important requirement for successful Total Knee Arthroplasty. The primary focus of early rehabilitation is ambulation of patients and regaining range of motion in the knee. Although research suggests that Continuous Passive Motion should be implemented in the first rehabilitation phase following surgery, there is substantial debate about the duration of each session and the total period of CPM application and. A Cochrane review on this topic concluded that short-term use of CPM leads to greater short-term range of motion. It also suggested, however, that future research should concentrate on the treatment period during which CPM should be administered. In a randomised controlled trial we intend to investigate the efficacy of prolonged use of a continuous passive motion (CPM) device in the home situation as an adjunct to standardised physical therapy. The experimental treatment is compared to standardised physical therapy, in patients with osteoarthritis of the knee undergoing Total Knee Arthroplasty (TKA). Efficacy will be assessed in terms of faster improvements in range of motion and functional recovery. Seventy patients with knee osteoarthritis undergoing TKA and experiencing early postoperative flexion impairment (less than 80 degrees of knee flexion at the time of discharge) will be randomised over two treatment groups, a usual care group and an experimental group. The experimental group will receive CPM + physiotherapy for 17 consecutive days after surgery, whereas the usual care group will receive the same treatment during the in-hospital phase (i.e. about four days), followed by physical therapy alone (usual care) in the first two weeks after hospital discharge. From 18 days to three months after discharge, both groups will receive standardised PT. The primary focus of rehabilitation will be functional recovery (e.g. ambulation) and regaining range of motion (ROM) in the knee. Because restricted knee ROM affects

  20. Correlates of prolonged television viewing time in older Japanese men and women.

    Science.gov (United States)

    Kikuchi, Hiroyuki; Inoue, Shigeru; Sugiyama, Takemi; Owen, Neville; Oka, Koichiro; Shimomitsu, Teruichi

    2013-03-09

    In addition to insufficient moderate-to-vigorous physical activity (MVPA), prolonged sitting time is also a health risk for older adults. An understanding of population subgroups who have prolonged television viewing (TV) time, a predominant sedentary behavior, can aid in the development of relevant health promotion initiatives; however, few such studies have focused on older adults, the most sedentary segment of the population as a whole. The aim of this study is to examine the socio-demographic attributes associated with TV time among community-dwelling Japanese older men and women. A population-based, cross-sectional mail survey was used to collect data on TV time, MVPA, and socio-demographic characteristics. The survey was conducted from February through March 2010. Participants were 2700 community-dwelling older adults (aged 65-74 years, 50% men) who were randomly selected from the registry of residential addresses of three cities in Japan. Data from 1665 participants (mean age: 69.5 years, 52% men) who completed all variables for the present study were analyzed. Multivariate logistic regression analyses were used to calculate the odds ratios (ORs) of prolonged TV time (>2 hours/day) for each socio-demographic attribute, stratified by gender. Of the 1665 participants, 810 (48.6%) watched TV for more than 2 hours/day. The median television viewing time (25th, 75th percentile) was 2.00 (1.07, 3.50) hours/day. Prolonged TV time was associated with not in full-time employment, lower educational attainment, weight status, living in regional areas and low MVPA for the whole sample. For men, prolonged TV time was associated with lower educational attainment; (OR = 1.53, 95% CI: 1.12-2.07), underweight (OR = 1.63, 95% CI: 1.02-2.60), overweight (OR = 1.57, 95% CI: 1.11-2.21), and low MVPA (OR = 1.43, 95% CI: 1.02-2.02). For women, living in regional areas (OR = 2.02, 95% CI: 1.33-3.08), living alone (OR = 1.61, 95% CI: 1.03-2.49), not driving

  1. Restricted Predicates for Hypothetical Datalog

    Directory of Open Access Journals (Sweden)

    Fernando Sáenz-Pérez

    2015-12-01

    Full Text Available Hypothetical Datalog is based on an intuitionistic semantics rather than on a classical logic semantics, and embedded implications are allowed in rule bodies. While the usual implication (i.e., the neck of a Horn clause stands for inferring facts, an embedded implication plays the role of assuming its premise for deriving its consequence. A former work introduced both a formal framework and a goal-oriented tabled implementation, allowing negation in rule bodies. While in that work positive assumptions for both facts and rules can occur in the premise, negative assumptions are not allowed. In this work, we cover this subject by introducing a new concept: a restricted predicate, which allows negative assumptions by pruning the usual semantics of a predicate. This new setting has been implemented in the deductive system DES.

  2. Effects of hydrogen rich water on prolonged intermittent exercise.

    Science.gov (United States)

    Da Ponte, Alessandro; Giovanelli, Nicola; Nigris, Daniele; Lazzer, Stefano

    2018-05-01

    Recent studies showed a positive effect of hydrogen rich water (HRW) intake on acid-base homeostasis at rest. We investigated 2-weeks of HRW intake on repeated sprint performance and acid-base status during prolonged intermittent cycling exercise. In a cross over single-blind protocol, 8 trained male cyclists (age [mean±SD] 41±7 years, body mass 72.3±4.4 kg, height 1.77±0.04 m, maximal oxygen uptake [V̇O2max] 52.6±4.4 mL·kg-1·min-1) were provided daily with 2 liters of placebo normal water (PLA, pH 7.6, oxidation/reduction potential [ORP] +230 mV, free hydrogen content 0 ppb) or HRW (pH 9.8, ORP -180 mV, free Hydrogen 450 ppb). Tests were performed at baseline and after each period of 2 weeks of treatment. The treatments were counter-balanced and the sequence randomized. The 30-minute intermittent cycling trial consisted in 10 3-minute blocks, each one composed by 90 seconds at 40% V̇O2max, 60 seconds at 60% V̇O2max, 16 seconds all out sprint, and 14 seconds active recovery. Oxygen uptake (V̇O2), heart rate and power output were measured during the whole test, while mean and peak power output (PPO), time to peak power and Fatigue Index (FI) were determined during all the 16 seconds sprints. Lactate, pH and bicarbonate (HCO3-) concentrations were determined at rest and after each sprint on blood obtained by an antecubital vein indwelling catheter. In the PLA group, PPO in absolute values decreased significantly at the 8th and 9th of 10 sprints and in relative values, ΔPPO, decreased significantly at 6th, 8th and 9th of 10 sprints (by mean: -12±5%, Pmay help to maintain PPO in repetitive sprints to exhaustion over 30 minutes.

  3. A Traffic Restriction Scheme for Enhancing Carpooling

    Directory of Open Access Journals (Sweden)

    Dong Ding

    2017-01-01

    Full Text Available For the purpose of alleviating traffic congestion, this paper proposes a scheme to encourage travelers to carpool by traffic restriction. By a variational inequity we describe travelers’ mode (solo driving and carpooling and route choice under user equilibrium principle in the context of fixed demand and detect the performance of a simple network with various restriction links, restriction proportions, and carpooling costs. Then the optimal traffic restriction scheme aiming at minimal total travel cost is designed through a bilevel program and applied to a Sioux Fall network example with genetic algorithm. According to various requirements, optimal restriction regions and proportions for restricted automobiles are captured. From the results it is found that traffic restriction scheme is possible to enhance carpooling and alleviate congestion. However, higher carpooling demand is not always helpful to the whole network. The topology of network, OD demand, and carpooling cost are included in the factors influencing the performance of the traffic system.

  4. Changes in Lumbopelvic Movement and Muscle Recruitment Associated with Prolonged Deep Squatting: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Tim K. S. Lui

    2018-05-01

    Full Text Available This study examined the changes in spinal kinematics and muscle recruitment of the lumbopelvic region associated with prolonged squatting. Eight subjects with chronic nonspecific low back pain (LBP and eight asymptomatic subjects (AS performed squat-to-stand and reverse movements, before and immediately after 15 min deep-squatting. Within-group and between-group differences in lumbopelvic kinematics and electromyographic activity acquired in lumbar erector spinae (ES, gluteus maximus (GM, and vastus lateralis (VL were analyzed. During squat-to-stand after squatting, the LBP group showed slower then faster lumbar movement in the second and third quartiles, respectively. In the second quartile, the AS group moved with a significantly greater lumbar angle. However, significantly greater bilateral GM activity (+4–4.5% was found in the LBP group only. A more profound decrease in bilateral ES activity (−10% was also shown in the LBP group, yet this was nonsignificant compared to the AS group (−4%. In the third quartile, only the LBP group moved with a significantly greater lumbar angle, together with a significant increase in bilateral ES (+6–8% and GM muscle (+2–3% activity. The findings of the altered pattern of joint kinematics and recruitment of the key lumbopelvic muscles displayed in the LBP group inform on the possible mechanisms that may contribute to the increased risk of developing lumbar dysfunctions for people who work in prolonged squatting postures.

  5. Restricted Interval Valued Neutrosophic Sets and Restricted Interval Valued Neutrosophic Topological Spaces

    Directory of Open Access Journals (Sweden)

    Anjan Mukherjee

    2016-08-01

    Full Text Available In this paper we introduce the concept of restricted interval valued neutrosophic sets (RIVNS in short. Some basic operations and properties of RIVNS are discussed. The concept of restricted interval valued neutrosophic topology is also introduced together with restricted interval valued neutrosophic finer and restricted interval valued neutrosophic coarser topology. We also define restricted interval valued neutrosophic interior and closer of a restricted interval valued neutrosophic set. Some theorems and examples are cites. Restricted interval valued neutrosophic subspace topology is also studied.

  6. Restriction Inhibition Assay: A Qualitative and Quantitative Method to ...

    African Journals Online (AJOL)

    rich fractions (PRFs) with high affinity for EcoRI and HindIII restriction sequences and correlate their interaction to an anticancer activity. Methods: pBR322 linear plasmid DNA was used as a template to screen the sequence-selective inhibition of ...

  7. Restrictions in social participation of young adults with spina bifida

    NARCIS (Netherlands)

    Barf, H. A.; Post, M. W. M.; Verhoef, M.; Jennekens-Schinkel, A.; Gooskens, R. H. J. M.; Prevo, A. J. H.

    2009-01-01

    Purpose. To determine participation restrictions of young adults with spina bifida (SB) in relation to health condition and activity limitations. Method. A total of 179 persons aged 16-25 years and born with SB participated in a cross-sectional study. The main outcome on four domains of

  8. A topological insight into restricted Boltzmann machines (extented abstract)

    NARCIS (Netherlands)

    Mocanu, D.C.; Mocanu, E.; Nguyen, H.P.; Gibescu, M.; Liotta, A.

    2016-01-01

    Restricted Boltzmann Machines (RBMs) and models derived from them have been successfully used as basic building blocks in deep neural networks for automatic features extraction, unsupervised weights initialization, but also as standalone models for density estimation, activity recognition and so on.

  9. Anticonvulsant effect of time-restricted feeding in a pilocarpine-induced seizure model: Metabolic and epigenetic implications.

    Directory of Open Access Journals (Sweden)

    Jorge eLandgrave-Gómez

    2016-01-01

    Full Text Available A new generation of antiepileptic drugs has emerged; however, one-third of epilepsy patients do not properly respond to pharmacological treatments. The purpose of the present study was to investigate whether time-restricted feeding has an anticonvulsant effect and whether this restrictive diet promotes changes in energy metabolism and epigenetic modifications in a pilocarpine-induced seizure model. To resolve our hypothesis, one group of rats had free access to food and water ad libitum (AL and a second group underwent a time-restricted feeding (TRF schedule. We used the lithium-pilocarpine model to induce status epilepticus (SE, and behavioral seizure monitoring was analyzed. Additionally, an electroencephalography (EEG recording was performed to verify the effect of TRF on cortical electrical activity after a pilocarpine injection. For biochemical analysis, animals were sacrificed 24 hours after SE and hippocampal homogenates were used to evaluate the proteins related to metabolism and chromatin structure. Our results showed that TRF had an anticonvulsant effect as measured by the prolonged latency of forelimb clonus seizure, a decrease in the seizure severity score and fewer animals reaching SE. Additionally, the power of the late phase EEG recordings in the AL group was significantly higher than the TRF group. Moreover, we found that TRF is capable of inducing alterations in signaling pathways that regulate energy metabolism, including an increase in the phosphorylation of AMP dependent kinase (AMPK and a decrease in the phosphorylation of Akt kinase. Furthermore, we found that TRF was able to significantly increase the beta hydroxybutyrate (β-HB concentration, an endogenous inhibitor of histone deacetylases (HDACs. Finally, we found a significant decrease in HDAC activity as well as an increase in acetylation on histone 3 (H3 in hippocampal homogenates from the TRF group. These findings suggest that alterations in energy metabolism and the

  10. Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups.

    Science.gov (United States)

    Vázquez-Medina, José Pablo; Crocker, Daniel E; Forman, Henry Jay; Ortiz, Rudy M

    2010-07-15

    Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

  11. Effects of flooring and restricted freestall access on behavior and claw health of dairy heifers.

    Science.gov (United States)

    Ouweltjes, W; van der Werf, J T N; Frankena, K; van Leeuwen, J L

    2011-02-01

    Claw health, locomotion, feed intake, milk yield, body weight, activity, and lying and standing behavior of dairy heifers were monitored in a single dairy herd during the first 3 mo after calving. During the first 8 wk after calving, 2 treatments were applied: restricted freestall access by closing the stalls between 2300 h and 0500 h (yes or no) and alley flooring (concrete or rubber topped slatted floors). Apart from treatments, housing was identical. The animals were kept in small groups (n=4 to 6) in adjacent barn pens. Thereafter, the animals were kept in 1 group in a freestall section with concrete slatted floor and unrestricted access to the stalls for 5 wk. All animals were fed the same partial mixed ration. We hypothesized that (1) hard flooring causes high mechanical load of the claws and (2) restricted freestall access causes prolonged standing bouts and reinforced effects of hard flooring on claws. The heifers had only minor claw lesions before first calving, and the prevalence and severity of sole hemorrhages increased during the first 3 mo after calving (from 0.24 ± 0.08 to 1.18 ± 0.14 and from 0.04 ± 0.01 to 0.24 ± 0.02, respectively), particularly in the outer hind claws. Animals kept on rubber alley flooring had lower average hemorrhage scores in wk 9 (0.13 ± 0.03 vs. 0.21 ± 0.03) and wk 14 (0.20 ± 0.03 vs. 0.27 ± 0.03) after calving, had a slower feed intake (3.05 ± 0.14 vs. 3.46 ± 0.14 g/s) and spent more time feeding (7.3 ± 0.3 vs. 6.6 ± 0.3 min/h) than animals kept on hard concrete alley floors. Restricted freestall access resulted in fewer standing bouts per day (14.4 ± 1.0 vs. 17.9 ± 1.0) and more strides per hour (99.8 ± 5.4 vs. 87.2 ± 5.4) without changing overall standing time (15.0 ± 0.3 vs. 14.7 ± 0.3 h/d) and did not affect the occurrence of sole hemorrhages. The animals with no overnight freestall access spent more time standing (55.9 ± 0.9 vs. 35.8 ± 0.9 min/h) and feeding (7.8 ± 0.3 vs. 4.3 ± 0.3 min/h) between

  12. Prolonged pharmacological inhibition of cathepsin C results in elimination of neutrophil serine proteases

    DEFF Research Database (Denmark)

    Guarino, Carla; Hamon, Yveline; Croix, Cécile

    2017-01-01

    cyclopropyl nitrile CatC inhibitor almost totally lack elastase. We confirmed the elimination of neutrophil elastase-like proteases by prolonged inhibition of CatC in a non-human primate. We also showed that neutrophils lacking elastase-like protease activities were still recruited to inflammatory sites....... These preclinical results demonstrate that the disappearance of neutrophil elastase-like proteases as observed in PLS patients can be achieved by pharmacological inhibition of bone marrow CatC. Such a transitory inhibition of CatC might thus help to rebalance the protease load during chronic inflammatory diseases...

  13. Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

    DEFF Research Database (Denmark)

    Mourtzakis, Marina; Saltin, B.; Graham, T.

    2006-01-01

    During prolonged exercise, carbohydrate oxidation may result from decreased pyruvate production and increased fatty acid supply and ultimately lead to reduced pyruvate dehydrogenase (PDH) activity. Pyruvate also interacts with the amino acids alanine, glutamine, and glutamate, whereby the decline...... amino acid taken up during exercise and recovery. Alanine and glutamine were also associated...... with pyruvate metabolism, and they comprised 68% of total amino-acid release during exercise and recovery. Thus reduced pyruvate production was primarily associated with reduced carbohydrate oxidation, whereas the greatest production of pyruvate was related to glutamate, glutamine, and alanine metabolism...

  14. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

    2003-01-01

    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice......, and subsequently focused on several specific groups of patients who could be extremely vulnerable for drug-induced arrhythmias. We performed a case-control study in which patients (cases), hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998, were compared with their matched controls regarding current...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

  15. Prolonged Remission in Neuromyelitis Optica Following Cessation of Rituximab Treatment.

    Science.gov (United States)

    Weinfurtner, Kelley; Graves, Jennifer; Ness, Jayne; Krupp, Lauren; Milazzo, Maria; Waubant, Emmanuelle

    2015-09-01

    Neuromyelitis optica is an autoimmune disease characterized by acute episodes of transverse myelitis and optic neuritis. Several small, open-label studies suggest rituximab, a monoclonal antibody against CD20, prevents relapses in neuromyelitis optica; however, there is little consensus on timing or duration of treatment. Here we report four patients with severe relapsing neuromyelitis optica who were stabilized on rituximab and, after discontinuing treatment, continued to experience prolonged remission of their disease. Remission ranged from 4.5 to 10.5 years total, including 3 to 9 years off all therapies. The patients had sustained clinical responses despite normal B-lymphocyte levels and, in at least 2 patients, continued seropositivity for aquaporin-4 antibodies. These cases suggest that rituximab may induce prolonged remission in certain neuromyelitis optica patients, and they highlight the need for further elucidation of rituximab's mechanism in neuromyelitis optica. © The Author(s) 2014.

  16. Smoking prolongs the infectivity of patients with tuberculosis.

    LENUS (Irish Health Repository)

    Siddiqui, U A

    2010-10-01

    We sought to establish if smokers on anti-tuberculosis treatment are more likely to have a prolonged period of infectivity, compared to non-smoking tuberculosis patients, in a low tuberculosis prevalence country. We conducted a cross-sectional, retrospective study in Ireland that recruited 53 microbiologically confirmed cases of pulmonary tuberculosis (PTB). The age-sex adjusted odds ratios (AOR) suggest that the infectivity status of PTB on treatment was four times more likely to be prolonged beyond 6-8 weeks, if the cases had a smoking history (AOR: 4.42; 95% CI: 1.23; 15.9). Smoking was associated with delayed sputum smear conversion in PTB patients on treatment.

  17. Atraumatic femoral neck fracture secondary to prolonged lactation induced osteomalacia

    Directory of Open Access Journals (Sweden)

    Dhammapal Sahebrao Bhamare

    2013-01-01

    Full Text Available Presenting a case of atraumatic fracture neck femur secondary to 2 years of prolonged lactation. A 26-year-old lactating mother presented with pain in left hip from last 12 months. She was apparently alright before and during pregnancy. Plain radiograph showed a complete undisplaced fracture of femoral neck. Osteomalacia was diagnosed by radiological and serological investigations. The fracture was fixed using AO type cannulated cancellous screws. The fracture showed good clinical and radiological union at 3 months. Literature review shows that this is a first case of atraumatic fracture of neck femur due to prolonged lactational osteomalacia. It showed that even apparently healthy Indians are susceptible to osteomalacia, more so during pregnancy and lactation and can be presented as atraumatic fracture. Although considered relatively stable, a compression type incomplete fracture neck femur may progress to a complete fracture if not treated in time.

  18. Tetrodotoxin-Bupivacaine-Epinephrine Combinations for Prolonged Local Anesthesia

    Directory of Open Access Journals (Sweden)

    Christina Bognet

    2011-12-01

    Full Text Available Currently available local anesthetics have analgesic durations in humans generally less than 12 hours. Prolonged-duration local anesthetics will be useful for postoperative analgesia. Previous studies showed that in rats, combinations of tetrodotoxin (TTX with bupivacaine had supra-additive effects on sciatic block durations. In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity. TTX, formulated as Tectin, is in phase III clinical trials as an injectable systemic analgesic for chronic cancer pain. Here, we examine dose-duration relationships and sciatic nerve histology following local nerve blocks with combinations of Tectin with bupivacaine 0.25% (2.5 mg/mL solutions, with or without epinephrine 5 µg/mL (1:200,000 in rats. Percutaneous sciatic blockade was performed in Sprague-Dawley rats, and intensity and duration of sensory blockade was tested blindly with different Tectin-bupivacaine-epinephrine combinations. Between-group comparisons were analyzed using ANOVA and post-hoc Sidak tests. Nerves were examined blindly for signs of injury. Blocks containing bupivacaine 0.25% with Tectin 10 µM and epinephrine 5 µg/mL were prolonged by roughly 3-fold compared to blocks with bupivacaine 0.25% plain (P < 0.001 or bupivacaine 0.25% with epinephrine 5 µg/mL (P < 0.001. Nerve histology was benign for all groups. Combinations of Tectin in bupivacaine 0.25% with epinephrine 5 µg/mL appear promising for prolonged duration of local anesthesia.

  19. A Case of QT Prolongation Associated with Panhypopituitarism

    Directory of Open Access Journals (Sweden)

    Dilek Arpaci

    2013-01-01

    Full Text Available We describe a 37-year-old patient with panhypopituitarism who experienced symptoms and signs of hormonal insufficiency and QT prolongation on electrocardiogram without electrolyte disturbances. After hormonal (steroidal and thyroid replacement therapy electrocardiographic findings were normalized. Hormonal disorders should be considered as a cause of long QT intervals which may lead to torsade de pointes, even if plasma electrolyte levels are normal, because life-threatening arrhythmia is treatable by supplementation of the hormone that is lacking.

  20. MRI findings of prolonged post-traumatic sternal pain

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, Alexandra; Grosse, Claudia; Anderson, Suzanne [University Hospital of Berne, Department of Diagnostic, Pediatric and Interventional Radiology, Berne (Switzerland); Steinbach, Lynne [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)

    2007-05-15

    The objective of this study was to characterize the different causes of prolonged sternal pain following thoracic trauma with involvement of the sternum and to define criteria for sternal nonunion diagnosis using MRI. Five patients with abnormalities of the sternum were evaluated for prolonged sternal pain following thoracic trauma using MRI. MR images were evaluated by two radiologists in consensus. The patients were selected from the radiology database, which included 8 patients with post-traumatic prolonged sternal pain. Two patients (n = 2) revealed a sternal nonunion after sternal fracture. One patient had a sternal fracture with delayed union and minor displacement of the sternal halves. Abnormal signal intensity alterations adjacent to and within the manubrio-sternal joint were evident in 2 patients and considered due to trauma-related changes in the manubrio-sternal joint. The 3 patients who were not included in the study had no abnormalities of the sternum: 1 of them proved to have a well-healed sternal fracture and nonunion of a rib fracture, 1 had subtle Tietze's syndrome, and 1 patient revealed no pathological findings on imaging. Various factors may be responsible for prolonged sternal pain following thoracic trauma, and these can be viewed with MRI. In cases of sternal nonunion there was common fluid-like signal in the fracture interspace between the bony edges, and the bone marrow adjacent to the nonunion showed altered signal intensity. MRI identified sternal nonunion and other trauma-related abnormalities of the sternum following chest trauma. (orig.)

  1. The effects of sodium bicarbonate during prolonged cardiopulmonary resuscitation.

    Science.gov (United States)

    Weng, Yi-Ming; Wu, Shih-Hao; Li, Wen-Cheng; Kuo, Chan-Wei; Chen, Shou-Yen; Chen, Jih-Chang

    2013-03-01

    This study was performed to determine the effects of sodium bicarbonate injection during prolonged cardiopulmonary resuscitation (for >15 minutes). The retrospective cohort study consisted of adult patients who presented to the emergency department (ED) with the diagnosis of cardiac arrest in 2009. Data were retrieved from the institutional database. A total of 92 patients were enrolled in the study. Patients were divided into 2 groups based on whether they were treated (group1, n = 30) or not treated (group 2, n = 62) with sodium bicarbonate. There were no significant differences in demographic characteristics between groups. The median time interval between the administration of CPR and sodium bicarbonate injection was 36.0 minutes (IQR: 30.5-41.8 minutes). The median amount of bicarbonate injection was 100.2 mEq (IQR: 66.8-104.4). Patients who received a sodium bicarbonate injection during prolonged CPR had a higher percentage of return of spontaneous circulation, but not statistical significant (ROSC, 40.0% vs. 32.3%; P = .465). Sustained ROSC was achieved by 2 (6.7%) patients in the sodium bicarbonate treatment group, with no survival to discharge. No significant differences in vital signs after ROSC were detected between the 2 groups (heart rate, P = .124; systolic blood pressure, P = .094). Sodium bicarbonate injection during prolonged CPR was not associated with ROSC after adjust for variables by regression analysis (Table 3; P = .615; odds ratio, 1.270; 95% confidence interval: 0.501-3.219) The administration of sodium bicarbonate during prolonged CPR did not significantly improve the rate of ROSC in out-of-hospital cardiac arrest. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.

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    Attila Kristóf

    Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.

  3. Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve

    Science.gov (United States)

    Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László

    2012-01-01

    Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901

  4. Prolonged fever in peritoneal tuberculosis: A case report

    Science.gov (United States)

    Zein, U.; Irwandi, S.; Habib, H.; Lim, H.; Pasha, M.; Janis, I.; Saragih, R. H.; Ginting, Y.; Effendy-Y S, R.

    2018-03-01

    Peritoneal tuberculosis may lead to delayed diagnosis because of the nonspecific features such as fever, abdominal distension, abdominal tenderness, ascites, and weight loss. Here, wereported a case of prolonged fever and abdominal pain which was due to peritoneal tuberculosis. Initial examinations including acomplete blood test and serologic tests did not lead to the diagnosis. A final diagnosis was made by abdominal CT-scan and laparoscopy combined with histopathological studies. Antituberculous medications provided a good clinical response in this patient.

  5. The incidence of hyponatremia during prolonged ultraendurance exercise.

    Science.gov (United States)

    Noakes, T D; Norman, R J; Buck, R H; Godlonton, J; Stevenson, K; Pittaway, D

    1990-04-01

    Recent studies have shown that potentially fatal hyponatremia can develop during prolonged exercise. To determine the incidence of hyponatremia in athletes competing in ultradistance events, we measured serum sodium levels in 315 of 626 (50%) runners who were treated for collapse after two 90 km ultramarathon footraces (total starters 20,335; total finishers 18,031) and in 101 of 147 (69%) finishers in a 186 km ultratriathlon. In both races the athletes drank fluids with low sodium chloride content (less than 6.8 mmol.l-1). Hyponatremia (serum sodium level less than 130 mmol.l-1) was identified in 27 of 315 (9%) collapsed runners in the 90 km races and in none of the triathletes. In response to diuretic therapy, the runner with the most severe hyponatremia (serum sodium level = 112 mmol.l-1) excreted in excess of 7.5 l dilute urine during the first 17 h of hospitalization. These data suggest that, although symptomatic hyponatremia occurs in less than 0.3% of competitors during prolonged exercise even when they ingest little sodium chloride, it is found in a significant proportion (9%) of collapsed runners. A regulated contraction of the extracellular fluid volume would explain why the majority of athletes maintain normal serum sodium levels even though they develop a significant sodium chloride deficit during prolonged exercise. Alternatively, sodium chloride losses during prolonged exercise may be substantially less than are currently believed. Physicians treating collapsed ultradistance athletes need to be aware that as many as 10% or more of such patients may be hyponatremic.

  6. Risk Factors of Prolonged Hospitalization in Patients with Hyperemesis Gravidarum

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    Hasan Onur Topcu

    2015-03-01

    Conclusion: Number of vomiting per day and maternal serum TSH levels could help physicians to estimate the risk of prolonged hospitalization; however further investigations are needed in large population studies. Identifying the high risk patients is important both for prevention of HEG and beginning appropriate antiemetic treatment to avoid complications to reduce the economic costs. [Cukurova Med J 2015; 40(1.000: 113-118

  7. Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome.

    Science.gov (United States)

    Ohtsuka, Hokuto; Takinami, Masahiro; Shimasaki, Takafumi; Hibi, Takahide; Murakami, Hiroshi; Aiba, Hirofumi

    2017-07-01

    Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1 + gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner. © 2017 John Wiley & Sons Ltd.

  8. Hypercaloric diet prevents sexual impairment induced by maternal food restriction.

    Science.gov (United States)

    Bernardi, M M; Macrini, D J; Teodorov, E; Bonamin, L V; Dalboni, L C; Coelho, C P; Chaves-Kirsten, G P; Florio, J C; Queiroz-Hazarbassanov, N; Bondan, E F; Kirsten, T B

    2017-05-01

    Prenatal undernutrition impairs copulatory behavior and increases the tendency to become obese/overweight, which also reduces sexual behavior. Re-feeding rats prenatally undernourished with a normocaloric diet can restore their physiological conditions and copulatory behavior. Thus, the present study investigated whether a hypercaloric diet that is administered in rats during the juvenile period prevents sexual impairments that are caused by maternal food restriction and the tendency to become overweight/obese. Female rats were prenatally fed a 40% restricted diet from gestational day 2 to 18. The pups received a hypercaloric diet from postnatal day (PND) 23 to PND65 (food restricted hypercaloric [FRH] group) or laboratory chow (food restricted control [FRC] group). Pups from non-food-restricted dams received laboratory chow during the entire experiment (non-food-restricted [NFR] group). During the juvenile period and adulthood, body weight gain was evaluated weekly. The day of balanopreputial separation, sexual behavior, sexual organ weight, hypodermal adiposity, striatal dopamine and serotonin, serum testosterone, and tumor necrosis factor α (TNF-α) were evaluated. The FRH group exhibited an increase in body weight on PND58 and PND65. The FRC group exhibited an increase in the latency to the first mount and intromission and an increase in serum TNF-α levels but a reduction of dopaminergic activity. The hypercaloric diet reversed all of these effects but increased adiposity. We concluded that the hypercaloric diet administered during the juvenile period attenuated reproductive impairments that were induced by maternal food restriction through increases in the energy expenditure but not the tendency to become overweight/obese. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Secondary bacteraemia in adult patients with prolonged dengue fever.

    Science.gov (United States)

    Premaratna, R; Dissanayake, D; Silva, F H D S; Dassanayake, M; de Silva, H J

    2015-03-01

    Although dengue management guidelines do not advice on use of antibiotics in dengue shock syndrome, unrecognised bactraemia is likely to contribute to morbidity and mortality. To assess the occurance of secondary bacteraemia in adult patients with prolonged dengue fever. A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days). Two sets of blood cultures were taken in such patients prior to institution of antibiotic therapy. Demographic, clinical, haematological and biochemical parameters were recorded. Development of ascites and pleural effusions were detected using ultrasonography. Fourty patients (52.5% males) with a mean age of 29.8 years (SD 13.6) were studied. The average duration of fever was 7.9 days (SD 1.8). Ten patients (25%) had bacterial isolates in their blood cultures; Staphylococcus aureus (n=2), coliforms (n=3), pseudomonas (n=1) and 4 had mixed growths. The culture positive group had severe body aches at admission and higher fever, third space fluid accumulation, a significant drop in platelets and a higher CRP. A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture positive patients appeared more ill with body aches and had higher degrees of fever during the latter part of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia, low platelet count and elevation of CRP seem to be helpful.

  10. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇÝGÝL

    2012-08-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies. [JCBPR 2012; 1(2.000: 98-104

  11. Prolonged Exposure Therapy For Post Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Levent SÜTÇİGİL

    2012-07-01

    Full Text Available Post-traumatic Stress Disorder (PTSD is a psychiatric illness that usually develops after an event that threatens one’s life and body integrity and it affects quality of life and impairs social functioning significantly. Many studies have shown therapeutic effect of cognitive behavioral therapies on posttraumatic stress disorder, so that these therapies take part in the first step of treatment guides. Exposure is a practice that is generally used to reduce pathological fear and related emotions common in posttraumatic stress disorder (PTSD and other anxiety disorders. During exposure, patients intentionally confront with feared objects, situations, thoughts and similar stimuli in order to reduce anxiety level. Exposure can be divided into two main techniques as in vivo exposure and imaginal exposure. Prolonged exposure therapy is a specialized treatment program configured for the treatment of posttraumatic stress disorder and it is based on emotional processing theory. Program is comprised of four main components: (a Psycho-education about trauma and posttraumatic disorders, (b Training for breathing exercises, (c repeated facing with objects, persons, situations and thoughts which causes re-experience about trauma, (d Patient are instructed for telling repeatedly and loudly about traumatic experiences . Prolonged exposure usually involves 9 to 12 sessions, each lasting about 60-90 minutes, administered once or twice a week. Prolonged exposure therapy was started to be implemented since the 1980s, during this period the effectiveness of the therapy has been shown in various empirical studies.

  12. Dynamics of heterogeneous liners with prolonged plasma creation

    International Nuclear Information System (INIS)

    Aleksandrov, V.V.; Branitskii, A.V.; Volkov, G.S.; Grabovskii, E.V.; Zurin, M.V.; Nedoseev, S.L.; Oleinik, G.M.; Samokhin, A.A.; Smirnov, V.P.; Fedulov, M.V.; Frolov, I.N.; Sasorov, P.V.

    2001-01-01

    Prolonged plasma creation in heterogeneous liners, in which the liner substance is separated into two phase states (a hot plasma and a cold skeleton), is investigated both experimentally and theoretically. This situation is typical of multiwire, foam, and even gas liners in high-current high-voltage facilities. The main mechanisms governing the rate at which the plasma is created are investigated, and the simplest estimates of the creation rate are presented. It is found that, during prolonged plasma creation, the electric current flows through the entire cross section of the produced plasma shell, whose thickness is comparable with the liner radius; in other words, a current skin layer does not form. During compression, such a shell is fairly stable because of its relatively high resilience. It is shown that, under certain conditions, even a thick plasma shell can be highly compressed toward the discharge axis. A simplified numerical simulation of the compression of a plasma shell in a liner with prolonged plasma creation is employed in order to determine the conditions for achieving regimes of fairly compact and relatively stable radial compression of the shell

  13. Cardiovascular drugs inducing QT prolongation: facts and evidence.

    Science.gov (United States)

    Taira, Carlos A; Opezzo, Javier A W; Mayer, Marcos A; Höcht, Christian

    2010-01-01

    Acquired QT syndrome is mainly caused by the administration of drugs that prolong ventricular repolarization. On the other hand, the risk of drug-induced torsades de pointes is increased by numerous predisposing factors, such as genetic predisposition, female sex, hypokalemia and cardiac dysfunction. This adverse reaction is induced by different chemical compounds used for the treatment of a variety of pathologies, including arrhythmias. As it is known, antiarrhythmic agents and other cardiovascular drugs can prolong the QT interval, causing this adverse reaction. Of the 20 most commonly reported drugs, 10 were cardiovascular agents and these appeared in 348 of the reports (46%). Class Ia antiarrhythmic agents have frequently been linked to inducing arrhythmia, including torsades de pointes. Sotalol and amiodarone, class III antiarrhythmics, are known to prolong the QT interval by blocking I(Kr). Due to the severity of events caused by the therapeutic use of these drugs, in this work of revision the cardiovascular drugs that present this property and the factors and evidence will be mentioned.

  14. Truncation studies of alpha-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity.

    Science.gov (United States)

    Haskell-Luevano, C; Sawyer, T K; Hendrata, S; North, C; Panahinia, L; Stum, M; Staples, D J; Castrucci, A M; Hadley, M F; Hruby, V J

    1996-01-01

    Truncation studies of alpha-melanotropin peptides identify tripeptide analogues exhibiting prolonged agonist bioactivity: PEPTIDES 17(6) 995-1002, 1996.-Systematic analysis of fragment derivatives of the superpotent alpha-MSH analogue. Ac-Ser.Tyr-Ser-Nle4-Glu- His-DPhe7-Arg-Trp-Gly-Lys-Pro-Val-NH2(NDP-MSH), led to the discovery of tripeptide agonists possessing prolonged bioactivity in the frog skin assay. Of particular significance to this discovery was Ac-DPhe-Arg-DTrp-NH2, which was the most potent tripeptide in this series exhibiting sustained melanotropic activity. Different pharmacophore models appear to exist that are dependent on the substructure and stereochemistry of the MSH(6-9) "active site." The tripeptides Ac-DPhe-Arg-Trp-NH2, Ac-DPhe-Arg-DTrp-NH2, and Ac-DPhe-DArg-Trp-NH2 stereo-chemical combinations require only Phe7-Xaa8-Trp9, whereas Ac-DPhe-DArg-DTrp-NH2, Ac-Phe-Arg-DTrp-NH2, and Ac-Phe-Arg-Trp-NH2 additionally require His4 for minimal biological activity. Ac-DPhe-Arg-DTrp-NH2 represents a novel prototype lead for the development of MSH-based peptidomimetic agonists.

  15. Effects of prolonged agmatine treatment in aged male Sprague-Dawley rats.

    Science.gov (United States)

    Rushaidhi, M; Zhang, H; Liu, P

    2013-03-27

    Increasing evidence suggests that altered arginine metabolism contributes to cognitive decline during ageing. Agmatine, decarboxylated arginine, has a variety of pharmacological effects, including the modulation of behavioural function. A recent study demonstrated the beneficial effects of short-term agmatine treatment in aged rats. The present study investigated how intraperitoneal administration of agmatine (40mg/kg, once daily) over 4-6weeks affected behavioural function and neurochemistry in aged Sprague-Dawley rats. Aged rats treated with saline displayed significantly reduced exploratory activity in the open field, impaired spatial learning and memory in the water maze and object recognition memory relative to young rats. Prolonged agmatine treatment improved animals' performance in the reversal test of the water maze and object recognition memory test, and significantly suppressed age-related elevation in nitric oxide synthase activity in the dentate gyrus of the hippocampus and prefrontal cortex. However, this prolonged supplementation was unable to improve exploratory activity and spatial reference learning and memory in aged rats. These findings further demonstrate that exogenous agmatine selectively improves behavioural function in aged rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Prolonged cardiac effects of momentary assessed stressful events and worry episodes.

    Science.gov (United States)

    Pieper, Suzanne; Brosschot, Jos F; van der Leeden, Rien; Thayer, Julian F

    2010-07-01

    To test the hypothesize that increased heart rate (HR) and decreased heart rate variability (HRV) are not only due to concurrent stressful events and worries but also to stressors and worries occurring in the preceding hours or stressors anticipated to occur in the next hour. Worry was expected to mediate at least part of the prolonged effects of stressors. Ambulatory HR and HRV of 73 teachers were recorded for 4 days, during which the participants reported occurrence and duration of worry episodes and stressful events on an hourly basis, using computerized diaries. Multilevel regression models were used, accounting for effects of several biobehavioral variables. Stressful events were not associated with changes in HR or HRV. However, worry episodes had effects on concurrent HR and HRV (2.55 beats/minute; -5.76 milliseconds) and HR and HRV in the succeeding hour (3.05 beats/minute; -5.80 milliseconds) and 2 hours later (1.52 beats/minute; -3.14 milliseconds). These findings were independent of emotions, physical activity, posture, and other biobehavioral factors. Worry has effects on cardiac activity, and these effects were still visible after 2 hours. The latter finding suggests that a considerable part of prolonged activation may be induced by unconscious stress-related cognition.

  17. Restrictions of process machine retooling at machine-building enterprises

    Directory of Open Access Journals (Sweden)

    Kuznetsova Elena

    2017-01-01

    Full Text Available The competitiveness of the national economy depends on the technological level of the machine-building enterprises production equipment. Today in Russia there are objective and subjective restrictions for the optimum policy formation of the manufacturing equipment renewal. The analysis of the manufacturing equipment age structure dynamics in the Russian machine-building complex indicates the negative tendencies intensification: increase in the equipment service life, reduction in the share of up-to-date equipment, and drop in its use efficiency. The article investigates and classifies the main restrictions of the manufacturi