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Sample records for acute functional tolerance

  1. Cannabis and tolerance: acute drug impairment as a function of cannabis use history

    PubMed Central

    Ramaekers, J. G.; van Wel, J. H.; Spronk, D. B.; Toennes, S. W.; Kuypers, K. P. C.; Theunissen, E. L.; Verkes, R. J.

    2016-01-01

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic. PMID:27225696

  2. Cannabis and tolerance: acute drug impairment as a function of cannabis use history.

    PubMed

    Ramaekers, J G; van Wel, J H; Spronk, D B; Toennes, S W; Kuypers, K P C; Theunissen, E L; Verkes, R J

    2016-05-26

    Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 μg/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.

  3. Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

    PubMed Central

    Goodall, Stuart; Twomey, Rosie; Amann, Markus

    2015-01-01

    Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude. PMID:25593787

  4. Acute Tolerance to Alcohol in At-risk Binge Drinkers

    PubMed Central

    Fillmore, Mark T.; Weafer, Jessica

    2012-01-01

    Studies of the impairing effects of alcohol on behavior often show greater tolerance in heavy drinkers compared to light drinkers, suggesting a causal link between heavy consumption and tolerance. Tolerance also develops during the time-course of a single drinking episode, and this “acute tolerance” might play an important role in the escalation to heavy drinking. The present study examined the development of acute tolerance to the impairing effects of alcohol on motor coordination and inhibitory control in a group of at-risk, binge drinkers (N = 20) and a group of non-risk, moderate drinkers (N = 20). Participants performed the testing battery in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations (BACs): once on the ascending limb and once on the descending limb of the blood alcohol curve. Results showed marked acute tolerance to the impairing effects of alcohol on motor coordination in the at-risk drinkers. By contrast, no recovery of motor skill was observed in the non-risk drinkers. Regarding inhibitory control, both groups remained impaired on both the ascending and descending limbs, indicating no acute tolerance in either group. The findings suggest that at-risk, binge drinkers display a faster recovery in their ability to execute versus inhibit action under alcohol. Such an “activational bias” of behavior could account for their continued alcohol consumption and impulsive behaviors while intoxicated, especially as BAC begins to decline. PMID:22023021

  5. Physiological Determinants of Human Acute Hypoxia Tolerance

    DTIC Science & Technology

    2013-11-01

    variables. We chose variables that have been historically associated with both anaerobic and aerobic metabolism, as well as with responses to acute onset...carbon monoxide diffusing capacity (transfer factor): recommendations for a standard technique–1995 update. Am J Respir Crit Care Med 152: 2185–2198... Respiration . New Haven, CT: Yale University Press, 1922. Hart MC, Orzalesi MM, Cook CD. Relation between anatomic respiratory dead space and body size and

  6. Improved tolerance of acute severe hypoxic stress in chronic hypoxic diaphragm is nitric oxide-dependent.

    PubMed

    Lewis, Philip; McMorrow, Clodagh; Bradford, Aidan; O'Halloran, Ken D

    2015-09-01

    The effects of chronic hypoxia (CH) on respiratory muscle performance have hardly been investigated, despite clinical relevance. Results from recent studies are indicative of unique adaptive strategies in hypoxic diaphragm. Respiratory muscle tolerance of acute severe hypoxic stress was examined in normoxic and CH diaphragm in the presence and absence of a nitric oxide (NO) synthase inhibitor. We tested the hypothesis that improved tolerance of severe hypoxic stress in CH diaphragm is NO-dependent. Wistar rats were exposed to normoxia (sea-level, n = 6) or CH (ambient pressure = 380 mmHg, n = 6) for 6 weeks. Diaphragm muscle functional properties were determined ex vivo under severe hypoxic conditions (gassed with 95%N2/5% CO2) with and without 1 mM L-N(G)-nitroarginine (L-NNA, nNOS inhibitor). Fatigue tolerance, but not force, was significantly improved in CH diaphragm (p = 0.008). CH exposure did not affect diaphragm muscle fibre oxidative capacity determined from cluster analysis of area-density plots of muscle fibre succinate dehydrogenase activity. Acute NOS inhibition reduced diaphragm peak tetanic force (p = 0.018), irrespective of gas treatment, and completely reversed improved fatigue tolerance of the CH diaphragm. We conclude that CH exposure improves fatigue tolerance during acute severe hypoxic stress in an NO-dependent manner, independent of muscle fibre oxidative capacity.

  7. Influence of the ambient acceleration field upon acute acceleration tolerance in chickens

    NASA Technical Reports Server (NTRS)

    Smith, A. H.; Spangler, W. L.; Rhode, E. A.; Burton, R. R.

    1979-01-01

    The paper measured the acceleration tolerance of domestic fowl (Rhode Island Red cocks), acutely exposed to a 6 Gz field, as the time over which a normal heart rate can be maintained. This period of circulatory adjustment ends abruptly with pronounced bradycardia. For chickens which previously have been physiologically adapted to 2.5 -G field, the acute acceleration tolerance is greatly increased. The influence of the ambient acceleration field on the adjustment of the circulatory system appears to be a general phenomenon.

  8. Reverse of Acute and Chronic Morphine Tolerance by Lithocholic Acid via Down-Regulating UGT2B7

    PubMed Central

    Yang, Zizhao; Li, Li; Hu, Haihong; Xu, Mingcheng; Gu, Jingkai; Wang, Zaijie Jim; Yu, Lushan; Zeng, Su

    2016-01-01

    Lithocholic acid (LCA) deposited in human livers always induces drastic pains which need analgesic drug, like morphine to release. Our research showed that LCA can effectively inhibit uridine 5’-diphospho-glucuronosyltransferase 2B7 (UGT2B7) in morphine tolerance-like human normal liver cells, HL-7702, then increase μ-opioid receptor (MOR) and calcium–calmodulin dependent protein kinase IIα (CaMKIIα) expression. In vivo assay, UGT2B7 was significantly repressed in the livers of acute or chronic morphine tolerance mice pretreated with LCA (10, 50, and 100 mg/kg, p.o.). To investigate the connections between LCA function performance and change of UGT2B7 enzymatic activity in mice livers, two morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were quantified by solid phase extraction (SPE)–HPLC–MS/MS. The result indicated no matter in acute or chronic morphine tolerance, the concentrations of M3G and M6G were all decreased, the later one fell even more. Besides that, 50 mg/kg of LCA administration can prevent auto-phosphorylation of CaMKIIα at Thr286 in acute or chronic morphine tolerance mice prefrontal cortexes (mPFCs) due to synthesis increase of cyclic adenosine monophosphate. As a consequence, UGT2B7 depression mediated by LCA can affect its selective catalysis ability to morphine, that may be responsible to acute or chronic morphine tolerance alleviation. These findings might assist to modify antinociception of morphine in clinic. PMID:27847477

  9. Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice.

    PubMed

    Carlson, Scott; Prasain, Jeevan K; Peng, Ning; Dai, Yanying; Wyss, J Michael

    2014-01-01

    Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

  10. Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice

    PubMed Central

    Carlson, Scott; Prasain, Jeevan K.; Peng, Ning; Dai, Yanying; Wyss, J. Michael

    2016-01-01

    Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

  11. Abundance of Plasma Antioxidant Proteins Confers Tolerance to Acute Hypobaric Hypoxia Exposure

    PubMed Central

    Padhy, Gayatri; Sethy, Niroj Kumar; Ganju, Lilly

    2013-01-01

    Abstract Padhy, Gayatri, Niroj Kumar Sethy, Lilly Ganju, and Kalpana Bhargava. Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure. High Alt Med Biol 14:289–297, 2013—Systematic identification of molecular signatures for hypobaric hypoxia can aid in better understanding of human adaptation to high altitude. In an attempt to identify proteins promoting hypoxia tolerance during acute exposure to high altitude, we screened and identified hypoxia tolerant and susceptible rats based on hyperventilation time to a simulated altitude of 32,000 ft (9754 m). The hypoxia tolerance was further validated by estimating 8-isoprotane levels and protein carbonyls, which revealed that hypoxia tolerant rats possessed significant lower plasma levels as compared to susceptible rats. We used a comparative plasma proteome profiling approach using 2-dimensional gel electrophoresis (2-DGE) combined with MALDI TOF/TOF for both groups, along with an hypoxic control group. This resulted in the identification of 19 differentially expressed proteins. Seven proteins (TTR, GPx-3, PON1, Rab-3D, CLC11, CRP, and Hp) were upregulated in hypoxia tolerant rats, while apolipoprotein A-I (APOA1) was upregulated in hypoxia susceptible rats. We further confirmed the consistent higher expression levels of three antioxidant proteins (PON1, TTR, and GPx-3) in hypoxia-tolerant animals using ELISA and immunoblotting. Collectively, these proteomics-based results highlight the role of antioxidant enzymes in conferring hypoxia tolerance during acute hypobaric hypoxia. The expression of these antioxidant enzymes could be used as putative biomarkers for screening altitude adaptation as well as aiding in better management of altered oxygen pathophysiologies. PMID:24067188

  12. Acute alcohol tolerance on subjective intoxication and simulated driving performance in binge drinkers.

    PubMed

    Marczinski, Cecile A; Fillmore, Mark T

    2009-06-01

    High rates of binge drinking and alcohol-related problems, including drinking and driving, occur among college students. Underlying reasons for the heightened impaired driving rates in this demographic group are not known. The authors hypothesized that acute tolerance to the interoceptive cues of intoxication may contribute to these maladaptive decisions to drive in binge drinkers. Groups of binge-drinking and non-binge-drinking college students (N = 28) attended sessions during which they received a moderate dose of alcohol (0.65 g/kg) or a placebo. The development of acute tolerance to subjective ratings of intoxication and simulated driving performance was assessed by comparing measures taken during the ascending phase and descending phases of the blood alcohol curve. Compared with placebo, alcohol increased ratings of intoxication and impaired multiple aspects of simulated driving performance in both binge and non-binge drinkers. During the descending phase of the blood alcohol curve, binge drinkers showed acute tolerance to alcohol's effect on subjective intoxication, and this effect was accompanied by an increased rating of willingness to drive. By contrast, non-binge drinkers showed no acute tolerance.

  13. Effect of aging and oral tolerance on dendritic cell function.

    PubMed

    Simioni, P U; Fernandes, L G R; Gabriel, D L; Tamashiro, W M S C

    2010-01-01

    Oral tolerance can be induced in some mouse strains by gavage or spontaneous ingestion of dietary antigens. In the present study, we determined the influence of aging and oral tolerance on the secretion of co-stimulatory molecules by dendritic cells (DC), and on the ability of DC to induce proliferation and cytokine secretion by naive T cells from BALB/c and OVA transgenic (DO11.10) mice. We observed that oral tolerance could be induced in BALB/c mice (N = 5 in each group) of all ages (8, 20, 40, 60, and 80 weeks old), although a decline in specific antibody levels was observed in the sera of both tolerized and immunized mice with advancing age (40 to 80 weeks old). DC obtained from young, adult and middle-aged (8, 20, and 40 weeks old) tolerized mice were less efficient (65, 17 and 20%, respectively) than DC from immunized mice (P < 0.05) in inducing antigen-specific proliferation of naive T cells from both BALB/c and DO11.10 young mice, or in stimulating IFN-g, IL-4 and IL-10 production. However, TGF-beta levels were significantly elevated in co-cultures carried out with DC from tolerant mice (P < 0.05). DC from both immunized and tolerized old and very old (60 and 80 weeks old) mice were equally ineffective in inducing T cell proliferation and cytokine production (P < 0.05). A marked reduction in CD86+ marker expression was observed in DC isolated from both old and tolerized mice (75 and 50%, respectively). The results indicate that the aging process does not interfere with the establishment of oral tolerance in BALB/c mice, but reduces DC functions, probably due to the decline of the expression of the CD86 surface marker.

  14. Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats.

    PubMed

    Beveridge, T J R; Smith, H R; Porrino, L J

    2013-05-01

    Baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, has been used clinically to treat muscle spasticity, rigidity and pain. More recently, interest in the use of baclofen as an addiction medicine has grown, with promising preclinical cocaine and amphetamine data and demonstrated clinical benefit from alcohol and nicotine studies. Few preclinical investigations, however, have utilized chronic dosing of baclofen, which is important given that tolerance can occur to many of its effects. Thus the question of whether chronic treatment of baclofen maintains the efficacy of acute doses is imperative. The neural substrates that underlie the effects of baclofen, particularly those after chronic treatment, are also not known. In the present study, therefore, rats were treated with either a) vehicle, b) acute baclofen (5 mg/kg) or c) chronic baclofen (5 mg/kg, t.i.d. for 5 days). The effects of acute and chronic baclofen administration, compared to vehicle, were assessed using locomotor activity and changes in brain glucose metabolism (a measure of functional brain activity). Acute baclofen significantly reduced locomotor activity (horizontal and total distance traveled), while chronic baclofen failed to affect locomotor activity. Acute baclofen resulted in significantly lower rates of local cerebral glucose utilization throughout many areas of the brain, including the prefrontal cortex, caudate putamen, septum and hippocampus. The majority of these functional effects, with the exception of the caudate putamen and septum, were absent in animals chronically treated with baclofen. Despite the tolerance to the locomotor and functional effects of baclofen following repeated treatment, these persistent effects on functional activity in the caudate putamen and septum may provide insights into the way in which baclofen alters the reinforcing effects of abused substances such as cocaine, alcohol, and methamphetamine both in humans and animal models.

  15. Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance.

    PubMed

    Quanhong, Zhou; Ying, Xue; Moxi, Chen; Tao, Xu; Jing, Wang; Xin, Zhang; Li, Wang; Derong, Cui; Xiaoli, Zhang; Wei, Jiang

    2012-09-07

    Morphine is a mainstay for chronic pain treatment, but its efficacy has been hampered by physical tolerance. The underlying mechanism for chronic morphine induced tolerance is complicated and not well understood. PLC(β3) is regarded as an important factor in the morphine tolerance signal pathway. In this study, we determined intrathecal (i.t.) administration of an antisense oligodeoxynucleotide (ODN) of PLC(β3) could quicken the on-set antinociceptive efficacy of acute morphine treatment and prolong the maximum effect up to 4h. The antisense could also attenuate the development of morphine-induced tolerance and left shift the ED50 after 7 day of coadministration with morphine. These results probably were contributed by the PLC(β3) antisense ODN as they successfully knocked down protein expression levels and reduced activity of PLC(β3) in spinal cord in rats. The mismatch group had no such effects. The results confirmed the important involvement of PLC(β3) in both acute morphine efficacy and chronic morphine tolerance at spinal level in rats. This study may provide an idea for producing a novel adjuvant for morphine treatment.

  16. Polyamines function in stress tolerance: from synthesis to regulation

    PubMed Central

    Liu, Ji-Hong; Wang, Wei; Wu, Hao; Gong, Xiaoqing; Moriguchi, Takaya

    2015-01-01

    Plants are challenged by a variety of biotic or abiotic stresses, which can affect their growth and development, productivity, and geographic distribution. In order to survive adverse environmental conditions, plants have evolved various adaptive strategies, among which is the accumulation of metabolites that play protective roles. A well-established example of the metabolites that are involved in stress responses, or stress tolerance, is the low-molecular-weight aliphatic polyamines, including putrescine, spermidine, and spermine. The critical role of polyamines in stress tolerance is suggested by several lines of evidence: firstly, the transcript levels of polyamine biosynthetic genes, as well as the activities of the corresponding enzymes, are induced by stresses; secondly, elevation of endogenous polyamine levels by exogenous supply of polyamines, or overexpression of polyamine biosynthetic genes, results in enhanced stress tolerance; and thirdly, a reduction of endogenous polyamines is accompanied by compromised stress tolerance. A number of studies have demonstrated that polyamines function in stress tolerance largely by modulating the homeostasis of reactive oxygen species (ROS) due to their direct, or indirect, roles in regulating antioxidant systems or suppressing ROS production. The transcriptional regulation of polyamine synthesis by transcription factors is also reviewed here. Meanwhile, future perspectives on polyamine research are also suggested. PMID:26528300

  17. Functional Genomics of Drought Tolerance in Bioenergy Crops

    SciTech Connect

    Yin, Hengfu; Chen, Rick; Yang, Jun; Weston, David; Chen, Jay; Muchero, Wellington; Ye, Ning; Tschaplinski, Timothy J; Wullschleger, Stan D; Cheng, Zong-Ming; Tuskan, Gerald A; Yang, Xiaohan

    2014-01-01

    With the predicted trends in climate change, drought will increasingly impose a grand challenge to biomass production. Most of the bioenergy crops have some degree of drought susceptibility with low water-use efficiency (WUE). It is imperative to improve drought tolerance and WUE in bioenergy crops for sustainable biomass production in arid and semi-arid regions with minimal water input. Genetics and functional genomics can play a critical role in generating knowledge to inform and aid genetic improvement of drought tolerance in bioenergy crops. The molecular aspect of drought response has been extensively investigated in model plants like Arabidopsis, yet our understanding of the molecular mechanisms underlying drought tolerance in bioenergy crops are limited. Crops exhibit various responses to drought stress depending on species and genotype. A rational strategy for studying drought tolerance in bioenergy crops is to translate the knowledge from model plants and pinpoint the unique features associated with individual species and genotypes. In this review, we summarize the general knowledge about drought responsive pathways in plants, with a focus on the identification of commonality and specialty in drought responsive mechanisms among different species and/or genotypes. We describe the genomic resources developed for bioenergy crops and discuss genetic and epigenetic regulation of drought responses. We also examine comparative and evolutionary genomics to leverage the ever-increasing genomics resources and provide new insights beyond what has been known from studies on individual species. Finally, we outline future exploration of drought tolerance using the emerging new technologies.

  18. Neuromuscular Functions on Experimental Acute Methanol Intoxication

    PubMed Central

    Moral, Ali Reşat; Çankayalı, İlkin; Sergin, Demet; Boyacılar, Özden

    2015-01-01

    Objective The incidence of accidental or suicidal ingestion of methyl alcohol is high and methyl alcohol intoxication has high mortality. Methyl alcohol intoxication causes severe neurological sequelae and appears to be a significant problem. Methyl alcohol causes acute metabolic acidosis, optic neuropathy leading to permanent blindness, respiratory failure, circulatory failure and death. It is metabolised in the liver, and its metabolite formic acid has direct toxic effects, causing oxidative stress, mitochondrial damage and increased lipid peroxidation associated with the mechanism of neurotoxicity. Methanol is known to cause acute toxicity of the central nervous system; however, the effects on peripheral neuromuscular transmission are unknown. In our study, we aimed to investigate the electrophysiological effects of experimentally induced acute methanol intoxication on neuromuscular transmission in the early period (first 24 h). Methods After approval by the Animal Experiment Ethics Committee of Ege University, the study was carried out on 10 Wistar rats, each weighing about 200 g. During electrophysiological recordings and orogastric tube insertion, the rats were anaesthetised using intra-peritoneal (IP) injection of ketamine 100 mg kg−1 and IP injection of xylazine 10 mg kg−1. The rats were given 3 g kg−1 methyl alcohol by the orogastric tube. Electrophysiological measurements from the gastrocnemius muscle were compared with baseline. Results Latency measurements before and 24 h after methanol injection were 0.81±0.11 ms and 0.76±0.12 ms, respectively. CMAP amplitude measurements before and 24 h after methanol injection were 9.85±0.98 mV and 9.99±0.40 mV, respectively. CMAP duration measurements before and 24 h after methanol injection were 9.86±0.03 ms and 9.86±0.045 ms, respectively. Conclusion It was concluded that experimental methanol intoxication in the acute phase (first 24 h) did not affect neuromuscular function. PMID:27366524

  19. Sir2/Sirt1 Links Acute Inebriation to Presynaptic Changes and the Development of Alcohol Tolerance, Preference, and Reward

    PubMed Central

    Engel, Gregory L.; Marella, Sunanda; Kaun, Karla R.; Wu, Julia; Adhikari, Pratik; Kong, Eric C.

    2016-01-01

    Acute ethanol inebriation causes neuroadaptive changes in behavior that favor increased intake. Ethanol-induced alterations in gene expression, through epigenetic and other means, are likely to change cellular and neural circuit function. Ethanol markedly changes histone acetylation, and the sirtuin Sir2/SIRT1 that deacetylates histones and transcription factors is essential for the rewarding effects of long-term drug use. The molecular transformations leading from short-term to long-term ethanol responses mostly remain to be discovered. We find that Sir2 in the mushroom bodies of the fruit fly Drosophila promotes short-term ethanol-induced behavioral plasticity by allowing changes in the expression of presynaptic molecules. Acute inebriation strongly reduces Sir2 levels and increases histone H3 acetylation in the brain. Flies lacking Sir2 globally, in the adult nervous system, or specifically in the mushroom body α/β-lobes show reduced ethanol sensitivity and tolerance. Sir2-dependent ethanol reward is also localized to the mushroom bodies, and Sir2 mutants prefer ethanol even without a priming ethanol pre-exposure. Transcriptomic analysis reveals that specific presynaptic molecules, including the synaptic vesicle pool regulator Synapsin, depend on Sir2 to be regulated by ethanol. Synapsin is required for ethanol sensitivity and tolerance. We propose that the regulation of Sir2/SIRT1 by acute inebriation forms part of a transcriptional program in mushroom body neurons to alter presynaptic properties and neural responses to favor the development of ethanol tolerance, preference, and reward. SIGNIFICANCE STATEMENT We identify a mechanism by which acute ethanol inebriation leads to changes in nervous system function that may be an important basis for increasing ethanol intake and addiction liability. The findings are significant because they identify ethanol-driven transcriptional events that target presynaptic properties and direct behavioral plasticity. They also

  20. Acute effects of nicorandil on glucose tolerance in subjects with borderline fasting blood glucose levels.

    PubMed

    Boes, U; Wallner, S; Wascher, T C

    2001-02-15

    The acute effect of the anti-ischemic potassium channel opener nicorandil on glucose tolerance and post-challenge insulin levels was investigated in 11 subjects (6 males and 5 females, age 59 +/- 2 years) with borderline fasting blood glucose in a single blinded randomised study. All participants were submitted to two oral glucose tolerance tests in randomised order, once without any premedication and once 30 minutes after oral administration of 20 mg nicorandil. This single dose of nicorandil significantly increased blood glucose levels at 120 minutes (173 +/- 16 vs. 150 +/- 11 mg/dl, p < 0.05 by ANOVA) and 180 minutes (106 +/- 11 vs. 88 +/- 7 mg/dl, p < 0.05 by ANOVA) after ingestion of 75 mg of glucose. Serum insulin levels were not significantly altered. In conclusion we suggest that controlled studies in patients with coronary artery disease should be performed to investigate whether long term treatment with nicorandil increases progression rates from impaired glucose tolerance to type-II diabetes and/or from normal to impaired glucose tolerance with a possibly negative impact on the course of cardiovascular disease in comparison to conventional anti-anginal drugs.

  1. Exogenous IL-33 overcomes T cell tolerance in murine acute myeloid leukemia

    PubMed Central

    Qin, Lei; Dominguez, Donye; Chen, Siqi; Fan, Jie; Long, Alan; Zhang, Minghui; Fang, Deyu; Zhang, Yi; Kuzel, Timothy M.; Zhang, Bin

    2016-01-01

    Emerging studies suggest that dominant peripheral tolerance is a major mechanism of immune escape in disseminated leukemia. Using an established murine acute myeloid leukemia (AML) model, we here show that systemic administration of recombinant IL-33 dramatically inhibits the leukemia growth and prolongs the survival of leukemia-bearing mice in a CD8+ T cell dependent manner. Exogenous IL-33 treatment enhanced anti-leukemia activity by increasing the expansion and IFN-γ production of leukemia-reactive CD8+ T cells. Moreover, IL-33 promoted dendritic cell (DC) maturation and activation in favor of its cross presentation ability to evoke a vigorous anti-leukemia immune response. Finally, we found that the combination of PD-1 blockade with IL-33 further prolonged the survival, with half of the mice achieving complete regression. Our data establish a role of exogenous IL-33 in reversing T cell tolerance, and suggest its potential clinical implication into leukemia immunotherapy. PMID:27517629

  2. Modification of the development of acute opiate tolerance by increased dopamine receptor sensitivity.

    PubMed

    Martin, J R; Takemori, A E

    1987-04-01

    Earlier studies have suggested that the acute administration of an opiate can result in the development of supersensitive dopamine receptors. The present study was undertaken to determine whether the supersensitive dopamine receptors can modify the development of opiate tolerance and dependence. Administration of morphine (100 mg/kg s.c.) 6 or 24 hr before apomorphine (i.p.) potentiated apomorphine-induced climbing behavior in mice. Administration of levorphanol (12 mg/kg s.c.) 3 or 6 hr, but not 24 hr, before apomorphine also potentiated apomorphine-induced climbing behavior. Coadministration of 5 mEq/kg of LiCl with morphine or levorphanol attenuated the increased sensitivity developed to apomorphine after either opiate. Acute tolerance and dependence was induced by administration of 100 mg/kg of morphine or 12 mg/kg of levorphanol. Lithium enhanced the development of acute tolerance when coadministered with morphine 3, 6 or 24 hr before test doses of morphine, or with levorphanol 3 hr before test doses of levorphanol. Administration of apomorphine 5 min before naloxone significantly decreased the naloxone ED50 for inducing withdrawal jumping in mice that had been pretreated with morphine or levorphanol. Although coadministration of lithium with morphine or levorphanol had no significant effect on naloxone-induced withdrawal jumping, it attenuated the ability of apomorphine to decrease naloxone ED50. Morphine (100 mg/kg s.c.) increased the number of whole brain [3H]spiroperidol binding sites 3 and 6 hr after administration of morphine. This increase was no longer present 24 hr after morphine administration. Levorphanol (12 mg/kg s.c.) also increased the number of binding sites 3 hr after administration. Coadministration of lithium with morphine attenuated the increase in [3H]spiroperidol binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Dietary phosphorus acutely impairs endothelial function.

    PubMed

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  4. Effectiveness, tolerability and safety of azithromycin 1% in DuraSite® for acute bacterial conjunctivitis

    PubMed Central

    McLean, Susannah; Sheikh, Aziz

    2010-01-01

    Purpose: Bacterial eye infections are commonly treated with topical antibiotics, despite limited evidence of effectiveness. Azithromycin 1% in DuraSite® is a new formulation of azithromycin in a gel polymer designed for use in acute bacterial conjunctivitis. Methods: We conducted systematic searches of the Cochrane Database of Clinical Trials, PubMed and Google Scholar to find randomized controlled trials of “azithromycin DuraSite®”. These searches of published literature were supplemented with searches for unpublished trials and trials in progress. Results: We found six reports of randomized controlled trials investigating the role of azithromycin 1% in DuraSite® for the management of acute bacterial conjunctivitis. The quality of these trials was judged to be moderate to high. These trials assessed effectiveness, tolerability and safety outcomes, but we found no trials looking at cost-effectiveness. DuraSite® is a relatively stable formulation and so azithromycin 1% in DuraSite® has a simpler dosing schedule than other available topical antibiotics. It appears to be similar to other topical antibiotics in its effectiveness, but minor side effects are quite common. Conclusion: Acute bacterial conjunctivitis is a relatively mild, typically self-limiting, infection. Antibiotics should seldom be required. If, however, a decision to prescribe antibiotics is made, azithromycin 1% in DuraSite® is likely to be broadly comparable in its effectiveness to most other antibiotics used to treat acute bacterial conjunctivitis. Further research is needed to determine its cost-effectiveness. PMID:20517467

  5. Multimodal examination of distress tolerance and posttraumatic stress disorder symptoms in acute-care psychiatric inpatients.

    PubMed

    Vujanovic, Anka A; Dutcher, Christina D; Berenz, Erin C

    2016-09-01

    Distress tolerance (DT), the actual or perceived capacity to withstand negative internal states, has received increasing scholarly attention due to its theoretical and clinical relevance to posttraumatic stress disorder (PTSD). Past studies have indicated that lower self-reported - but not behaviorally observed - DT is associated with greater PTSD symptoms; however, studies in racially and socioeconomically diverse clinical samples are lacking. The current study evaluated associations between multiple measures of DT (self-report and behavioral) and PTSD symptoms in an urban, racially and socioeconomically diverse, acute-care psychiatric inpatient sample. It was hypothesized that lower self-reported DT (Distress Tolerance Scale [DTS]), but not behavioral DT (breath-holding task [BH]; mirror-tracing persistence task [MT]), would be associated with greater PTSD symptoms, above and beyond the variance contributed by trauma load, substance use, gender, race/ethnicity, and subjective social status. Participants were 103 (41.7% women, Mage=33.5) acute-care psychiatric inpatients who endorsed exposure to potentially traumatic events consistent with DSM-5 PTSD Criterion A. Results of hierarchical regression analyses indicated that DTS was negatively associated with PTSD symptom severity (PCL-5 Total) as well as with each of the four DSM-5 PTSD symptom clusters (p's<0.001), contributing between 5.0%-11.1% of unique variance in PTSD symptoms across models. BH duration was positively associated with PTSD arousal symptom severity (p<0.05). Covariates contributed between 21.3%-40.0% of significant variance to the models. Associations between DT and PTSD in this sample of acute-care psychiatric inpatients are largely consistent with those observed in community samples.

  6. Identification of microRNAs involved in acute rejection and spontaneous tolerance in murine hepatic allografts

    PubMed Central

    Morita, Miwa; Chen, Jiajie; Fujino, Masayuki; Kitazawa, Yusuke; Sugioka, Atsushi; Zhong, Liang; Li, Xiao-Kang

    2014-01-01

    Graft acceptance without the need for immunosuppressive drugs is the ultimate goal of transplantation therapy. In murine liver transplantation, allografts are accepted across major histocompatibility antigen complex barriers without the use of immunosuppressive drugs and constitute a suitable model for research on immunological rejection and tolerance. MicroRNA (miRNA) has been known to be involved in the immunological responses. In order to identify mRNAs in spontaneous liver allograft tolerance, miRNA expression in hepatic allografts was examined using this transplantation model. According to the graft pathological score and function, miR-146a, 15b, 223, 23a, 27a, 34a and 451 were upregulated compared with the expression observed in the syngeneic grafts. In contrast, miR-101a, 101b and 148a were downregulated. Our results demonstrated the alteration of miRNAs in the allografts and may indicate the role of miRNAs in the induction of tolerance after transplantation. Furthermore, our data suggest that monitoring the graft expression of novel miRNAs may allow clinicians to differentiate between rejection and tolerance. A better understanding of the tolerance inducing mechanism observed in murine hepatic allografts may provide a therapeutic strategy for attenuating allograft rejection. PMID:25323448

  7. Distributed Evaluation Functions for Fault Tolerant Multi-Rover Systems

    NASA Technical Reports Server (NTRS)

    Agogino, Adrian; Turner, Kagan

    2005-01-01

    The ability to evolve fault tolerant control strategies for large collections of agents is critical to the successful application of evolutionary strategies to domains where failures are common. Furthermore, while evolutionary algorithms have been highly successful in discovering single-agent control strategies, extending such algorithms to multiagent domains has proven to be difficult. In this paper we present a method for shaping evaluation functions for agents that provide control strategies that both are tolerant to different types of failures and lead to coordinated behavior in a multi-agent setting. This method neither relies of a centralized strategy (susceptible to single point of failures) nor a distributed strategy where each agent uses a system wide evaluation function (severe credit assignment problem). In a multi-rover problem, we show that agents using our agent-specific evaluation perform up to 500% better than agents using the system evaluation. In addition we show that agents are still able to maintain a high level of performance when up to 60% of the agents fail due to actuator, communication or controller faults.

  8. Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction

    PubMed Central

    Korjian, Serge; Tricoci, Pierluigi; Daaboul, Yazan; Yee, Megan; Jain, Purva; Alexander, John H.; Steg, P. Gabriel; Lincoff, A. Michael; Kastelein, John J.P.; Mehran, Roxana; D’Andrea, Denise M.; Deckelbaum, Lawrence I.; Merkely, Bela; Zarebinski, Maciej; Ophuis, Ton Oude; Harrington, Robert A.

    2016-01-01

    Background: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein–mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. Methods: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). Results: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events

  9. Functionalization of perovskite thin films with moisture-tolerant molecules

    NASA Astrophysics Data System (ADS)

    Yang, Shuang; Wang, Yun; Liu, Porun; Cheng, Yi-Bing; Zhao, Hui Jun; Yang, Hua Gui

    2016-02-01

    Organic-inorganic hybrid perovskites are particularly suited as light-harvesting materials in photovoltaic devices. The power conversion efficiency of perovskite solar cells has reached certified values of over 20% in just a few years. However, one of the major hindrances for application of these materials in real-world devices is the performance degradation in humid conditions, leading to a rapid loss of photovoltaic response. Here, we demonstrate that hydrophobic tertiary and quaternary alkyl ammonium cations can be successfully assembled on the perovskite surface as efficient water-resisting layers via a facile surface functionalization technique. Such layers can protect the perovskite film under high relative humidity (90 ± 5%) over 30 days. More importantly, devices based on such films can retain the photovoltaic capacities of bulk perovskites, with power conversion efficiencies over 15%. Improving the humidity tolerance of perovskite materials is a necessary step towards large-scale production of high-performance perovskite-based devices under ambient humidity.

  10. Facilitating tolerance of delayed reinforcement during functional communication training.

    PubMed

    Fisher, W W; Thompson, R H; Hagopian, L P; Bowman, L G; Krug, A

    2000-01-01

    Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

  11. Impaired glucose tolerance in pediatric burn patients at discharge from the acute hospital stay.

    PubMed

    Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Barr, David; Herndon, David N

    2010-01-01

    Hyperglycemia, secondary to the hypermetabolic stress response, is a common occurrence after thermal injury. This stress response has been documented to persist up to 9 months postburn. The purpose of this study was to measure insulin sensitivity in severely burned children before discharge when wounds are 95% healed. Twenty-four children, aged 4 to 17 years, with burns > or = 40% TBSA underwent a 2-hour oral glucose tolerance test before discharge from the acute pediatric burn unit. Plasma glucose and insulin levels as well as the Homeostasis Model Assessment for Insulin Resistance (HOMAIR) were compared with published oral glucose tolerance test data from healthy, nonburned children. There was a significant difference between severely burned children and nonburned, healthy children with respect to the HOMAIR. Severely burned children had a HOMAIR of 3.53 +/- 1.62 compared with the value in nonburned, healthy children of 1.28 +/- 0.16 (P < .05). Insulin resistance secondary to the hypermetabolic stress response persists in severely burned children when burn wounds are at least 95% healed. The results of this study warrant future investigations into therapeutic options for the burned child during the rehabilitative phase of their care after injury.

  12. Application of acute maximal exercise to protect orthostatic tolerance after simulated microgravity

    NASA Technical Reports Server (NTRS)

    Engelke, K. A.; Doerr, D. F.; Crandall, C. G.; Convertino, V. A.

    1996-01-01

    We tested the hypothesis that one bout of maximal exercise performed at the conclusion of prolonged simulated microgravity would improve blood pressure stability during an orthostatic challenge. Heart rate (HR), mean arterial blood pressure (MAP), norepinephrine (NE), epinephrine (E), arginine vasopressin (AVP), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cardiac output (Q), forearm vascular resistance (FVR), and changes in leg volume were measured during lower body negative pressure (LBNP) to presyncope in seven subjects immediately prior to reambulation from 16 days of 6 degrees head-down tilt (HDT) under two experimental conditions: 1) after maximal supine cycle ergometry performed 24 h before returning to the upright posture (exercise) and 2) without exercise (control). After HDT, the reduction of LBNP tolerance time from pre-HDT levels was greater (P = 0.041) in the control condition (-2.0 +/- 0.2 min) compared with the exercise condition (-0.4 +/- 0.2 min). At presyncope after HDT, FVR and NE were higher (P < 0.05) after exercise compared with control, whereas MAP, HR, E, AVP, PRA, ANP, and leg volume were similar in both conditions. Plasma volume (PV) and carotid-cardiac baroreflex sensitivity were reduced after control HDT, but were restored by the exercise treatment. Maintenance of orthostatic tolerance by application of acute intense exercise after 16 days of simulated microgravity was associated with greater circulating levels of NE, vasoconstriction, Q, baroreflex sensitivity, and PV.

  13. Identification of genes associated with heat tolerance in Arctic charr exposed to acute thermal stress.

    PubMed

    Quinn, Nicole L; McGowan, Colin R; Cooper, Glenn A; Koop, Ben F; Davidson, William S

    2011-06-15

    Arctic charr is an especially attractive aquaculture species given that it features the desirable tissue traits of other salmonids and is bred and grown at inland freshwater tank farms year round. It is of interest to develop upper temperature tolerant (UTT) strains of Arctic charr to increase the robustness of the species in the face of climate change and to enable production in more southern regions. We used a genomics approach that takes advantage of the well-studied Atlantic salmon genome to identify genes that are associated with UTT in Arctic charr. Specifically, we conducted an acute temperature trial to identify temperature tolerant and intolerant Arctic charr individuals, which were subject to microarray and qPCR analysis to identify candidate UTT genes. These were compared with genes annotated in a quantitative trait locus (QTL) region that was previously identified as associated with UTT in rainbow trout and Arctic charr and that we sequenced in Atlantic salmon. Our results suggest that small heat shock proteins as well as HSP-90 genes are associated with UTT. Furthermore, hemoglobin expression was significantly downregulated in tolerant compared with intolerant fish. Finally, QTL analysis and expression profiling identified COUP-TFII as a candidate UTT gene, although its specific role is unclear given the identification of two transcripts, which appear to have different expression patterns. Our results highlight the importance of using more than one approach to identify candidate genes, particularly when examining a complicated trait such as UTT in a highly complex genome for which there is no reference genome.

  14. COGNITIVE FUNCTIONING AND TOLERANCE FOR DELAY OF GRATIFICATION.

    ERIC Educational Resources Information Center

    ZIMILES, HERBERT

    TWO EXPERIMENTS WERE CONDUCTED TO STUDY THE RELATIONSHIP BETWEEN A CHILD'S TOLERANCE FOR DELAY OF GRATIFICATION AND HIS ABILITY TO CONSERVE NUMBER AND PICTURES. OTHER MEASURES OF COGNITION ALSO WERE USED. TOLERANCE FOR DELAY OF GRATIFICATION WAS MEASURED BY THE CHILD'S DECISION TO RECEIVE A PACK OF CANDY AND A TOY ON THE DAY OF TESTING OR TO…

  15. Acute postexercise effects of concentric and eccentric exercise on glucose tolerance.

    PubMed

    Cook, Matthew David; Myers, Stephen David; Kelly, John Stephen Michael; Willems, Mark Elisabeth Theodorus

    2015-02-01

    Impaired glucose tolerance was shown to be present 48 hr following muscle-damaging eccentric exercise. We examined the acute effect of concentric and muscle-damaging eccentric exercise, matched for intensity, on the responses to a 2-hr 75-g oral glucose tolerance test (OGTT). Ten men (27 ± 9 years, 178 ± 7 cm, 75 ± 11 kg, VO₂max: 52.3 ± 7.3 ml · kg⁻¹ · min⁻¹) underwent three OGTTs after an overnight 12 hr fast: rest (control), 40-min (5 × 8-min with 2-min interbout rest) of concentric (level running, 0%, CON) or eccentric exercise (downhill running, -12%, ECC). Running intensity was matched at 60% of maximal metabolic equivalent. Maximal isometric force of m. quadriceps femoris of both legs was measured before and after the running protocols. Downhill running speed was higher (level: 9.7 ± 2.1, downhill: 13.8 ± 3.2 km · hr⁻¹, p < .01). Running protocols had similar VO₂max (p = .59), heart rates (p = .20) and respiratory exchange ratio values (p = .74) indicating matched intensity and metabolic demands. Downhill running resulted in higher isometric force deficits (level: 3.0 ± 6.7, downhill: 17.1 ± 7.3%, p < .01). During OGTTs, area-under-the-curve for plasma glucose (control: 724 ± 97, CON: 710 ± 77, ECC: 726 ± 72 mmol · L⁻¹ · 120 min, p = .86) and insulin (control: 24995 ± 11229, CON: 23319 ± 10417, ECC: 21842 ± 10171 pmol · L⁻¹ · 120 min, p = .48), peak glucose (control: 8.1 ± 1.3, CON: 7.7 ± 1.2, ECC: 7.7 ± 1.1 mmol · L⁻¹, p = .63) and peak insulin levels (control: 361 ± 188, CON: 322 ± 179, ECC: 299 ± 152 pmol · L⁻¹, p = .30) were similar. It was concluded that glucose tolerance and the insulin response to an OGTT were not changed immediately by muscle-damaging eccentric exercise.

  16. Impaired glucose tolerance in pediatric burn patients at discharge from the acute hospital stay

    PubMed Central

    Fram, Ricki Y.; Cree, Melanie G.; Wolfe, Robert R.; Barr, David; Herndon, David N.

    2013-01-01

    Objective Hyperglycemia, secondary to the hypermetabolic stress response, is a common occurrence after thermal injury. This stress response has been documented to persist up to 9 months post burn. The purpose of this study was to measure insulin sensitivity in severely burned children prior to discharge when wounds are 95% healed. Methods Twenty-four children, aged 4–17 years, with burns ≥ 40% total body surface area (TBSA) underwent a 2 hour oral glucose tolerance test (OGTT) prior to discharge from the acute pediatric burn unit. Plasma glucose and insulin levels, as well as the Homeostasis Model Assessment for Insulin Resistance (HOMAIR) were compared to published OGTT data from healthy, non-burned children. Results There was a significant difference between severely burned children and non-burned, healthy children with respect to the HOMAIR. Severely burned children had a HOMAIR of 3.53±1.62 compared to the value in non-burned healthy children was 1.28±0.16 (p<0.05). Conclusion Insulin resistance secondary to the hypermetabolic stress response persists in severely burned children when burn wounds are at least 95% healed. The results of this study warrant future investigations into therapeutic options for the burned child during the rehabilitative phase of their care after injury. PMID:20634704

  17. Functional Identification and Characterization of Genes Cloned from Halophyte Seashore Paspalum Conferring Salinity and Cadmium Tolerance

    PubMed Central

    Chen, Yu; Chen, Chuanming; Tan, Zhiqun; Liu, Jun; Zhuang, Lili; Yang, Zhimin; Huang, Bingru

    2016-01-01

    Salinity-affected and heavy metal-contaminated soils limit the growth of glycophytic plants. Identifying genes responsible for superior tolerance to salinity and heavy metals in halophytes has great potential for use in developing salinity- and Cd-tolerant glycophytes. The objective of this study was to identify salinity- and Cd-tolerance related genes in seashore paspalum (Paspalum vaginatum), a halophytic perennial grass species, using yeast cDNA expression library screening method. Based on the Gateway-compatible vector system, a high-quality entry library was constructed, which contained 9.9 × 106 clones with an average inserted fragment length of 1.48 kb representing a 100% full-length rate. The yeast expression libraries were screened in a salinity-sensitive and a Cd-sensitive yeast mutant. The screening yielded 32 salinity-tolerant clones harboring 18 salinity-tolerance genes and 20 Cd-tolerant clones, including five Cd-tolerance genes. qPCR analysis confirmed that most of the 18 salinity-tolerance and five Cd-tolerance genes were up-regulated at the transcript level in response to salinity or Cd stress in seashore paspalum. Functional analysis indicated that salinity-tolerance genes from seashore paspalum could be involved mainly in photosynthetic metabolism, antioxidant systems, protein modification, iron transport, vesicle traffic, and phospholipid biosynthesis. Cd-tolerance genes could be associated with regulating pathways that are involved in phytochelatin synthesis, HSFA4-related stress protection, CYP450 complex, and sugar metabolism. The 18 salinity-tolerance genes and five Cd-tolerance genes could be potentially used as candidate genes for genetic modification of glycophytic grass species to improve salinity and Cd tolerance and for further analysis of molecular mechanisms regulating salinity and Cd tolerance. PMID:26904068

  18. Does acute lead (Pb) contamination influence membrane fatty acid composition and freeze tolerance in intertidal blue mussels in arctic Greenland?

    PubMed

    Thyrring, Jakob; Juhl, Bodil Klein; Holmstrup, Martin; Blicher, Martin E; Sejr, Mikael K

    2015-11-01

    In their natural habitats, organisms are exposed to multiple stressors. Heavy metal contamination stresses the cell membrane due to increased peroxidation of lipids. Likewise, sub-zero air temperatures potentially reduce membrane functionality in ectothermal animals. We tested if acute lead (Pb) exposure for 7 days would influence survival in intertidal blue mussels (Mytilus edulis) after exposure to realistic sub-zero air temperatures. A full factorial experiment with five tissue Pb concentrations between 0 and 3500 μg Pb/g and six sub-zero temperatures from 0 to -17 °C were used to test the hypothesis that sub-lethal effects of Pb may increase the lethality caused by freezing in blue mussels exposed to temperatures simulating Greenland winter conditions. We found a significant effect of temperature on mortality. However, the short-term exposure to Pb did not result in any effects of Pb, nor did we find interactions between Pb and temperature. We analysed the relative abundance of major phospholipid fatty acids (PLFAs) in the gill tissue, but we found no significant effect of Pb tissue concentration on PLFA composition. Results suggest that Pb accumulation has limited effects on freeze tolerance and does not induce membrane damage in terms of persistent lipid peroxidation.

  19. Investigating the association between parental reflective functioning and distress tolerance in motherhood.

    PubMed

    Rutherford, Helena J V; Booth, Cortney R; Luyten, Patrick; Bridgett, David J; Mayes, Linda C

    2015-08-01

    Parental reflective functioning, referring to the capacity of a parent to consider their child's mental states as they relate to their behavior, may support sensitive and adaptive parenting. We investigated the relationship between parental reflective functioning and tolerance of distress in a sample of recent mothers (N=59). Participants completed self-report measures of parental reflective functioning and distress tolerance, as well as two behavioral distress tolerance tasks. We also examined blood pressure and heart rate during the laboratory session. Mothers reporting more difficulty in recognizing and understanding their child's mental states displayed decreased tolerance of distress on our behavioral and self-report measures. Further, we found evidence of a relationship between these measures and assessments of peripheral physiology. These findings are discussed in the context of reflective functioning and distress tolerance in parenthood, and their implications for parenting interventions.

  20. Effects of melatonin on gallbladder neuromuscular function in acute cholecystitis.

    PubMed

    Gomez-Pinilla, Pedro J; Camello, Pedro J; Pozo, María J

    2007-10-01

    Gallbladder stasis is associated to experimental acute cholecystitis. Impaired contractility could be, at least in part, the result of inflammation-induced alterations in the neuromuscular function. This study was designed to determine the changes in gallbladder neurotransmission evoked by acute inflammation and to evaluate the protective and therapeutic effects of melatonin. Experimental acute cholecystitis was induced in guinea pigs by common bile duct ligation for 2 days, and then the neuromuscular function was evaluated using electrical field stimulation (EFS; 5-40 Hz). In a group of animals with the bile duct ligated for 2 days, a deligation of the duct was performed, and after 2 days, the neuromuscular function was studied. The EFS-evoked isometric gallbladder contraction was significantly lower in cholecystitic tissue. In addition, inflammation changed the pharmacological profile of these contractions that were insensitive to tetrodotoxin but sensitive to atropine and omega-conotoxin, indicating that acute cholecystitis affects action potential propagation in the intrinsic nerves. Nitric oxide (NO)-mediated neurotransmission was reduced by inflammation, which also increased the reactivity of sensitive fibers. Melatonin treatment prevented qualitative changes in gallbladder neurotransmission, but it did not improve EFS-induced contractility. The hormone recovered gallbladder neuromuscular function once the biliary obstruction was resolved, even when the treatment was started after the onset of gallbladder inflammation. These findings show for the first time the therapeutic potential of melatonin in the recovery of gallbladder neuromuscular function during acute cholecystitis.

  1. Application of an alcohol clamp paradigm to examine inhibitory control, subjective responses, and acute tolerance in late adolescence.

    PubMed

    Hendershot, Christian S; Wardell, Jeffrey D; Strang, Nicole M; Markovich, Mike S D; Claus, Eric D; Ramchandani, Vijay A

    2015-06-01

    Individual differences in acute alcohol effects on cognitive control and subjective responses--and acute tolerance to these effects--are implicated in the risk for heavy drinking and alcohol-related harms. Few studies have examined these effects in drinkers under age 21. Additionally, studies of acute tolerance typically involve bolus oral alcohol administration, such that estimates of tolerance are confounded with blood alcohol concentration (BAC) limb. The current study examined cognitive control and subjective responses in young heavy drinkers (n = 88; M = 19.8 years old, SD = 0.8) during a single-session alcohol clamp protocol. Participants completed an intravenous alcohol session comprising an ascending limb (0 to 80 mg% in 20 min) and a BAC plateau (80 mg% for 80 min). Serial assessments included a cued go/no-go task and measures of stimulation, sedation, and craving. Relevant individual difference factors (attention-deficit hyperactivity disorder [ADHD] symptoms and sensation seeking) were examined as moderators. Multilevel modeling demonstrated that response inhibition worsened following initial rise in BAC and showed increasing impairment during the BAC plateau. ADHD symptoms and sensation seeking moderated this effect. Significant within-person associations between stimulation and craving were evident on the ascending limb only. Participants with higher ADHD symptoms reported steeper increases in stimulation during the ascending limb. These findings provide initial information about subjective and behavioral responses during pseudoconstant BAC, and potential moderators of these outcomes, in late adolescence. Additional studies with placebo-controlled designs are necessary to confirm these findings.

  2. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

    PubMed Central

    Shiels, H. A.; Galli, G. L. J.; Block, B. A.

    2015-01-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation–contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca2+ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation–contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

  3. Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic

    PubMed Central

    Porwal, A.; Mahajan, A. D.; Oswal, D. S.; Erram, S. S.; Sheth, D. N.; Balamurugan, S.; Kamat, V.; Enadle, R. P.; Badadare, A.; Bhatnagar, S. K.; Walvekar, R. S.; Dhorepatil, S.; Naik, R. C.; Basu, I.; Kshirsagar, S. N.; Keny, J. V.; Sengupta, S.

    2012-01-01

    Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD) injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n = 109) or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n = 108), intramuscularly. Pain intensity (PI) was self-evaluated by patients on visual analogue scale (VAS) at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID) at 8 hours, and sum of analogue of pain intensity differences (SAPID). Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P < 0.0001), PID at 8 hours (P = 0.002), and SAPID0–8 hours (P = 0.004). The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic. PMID:22577544

  4. Effect of an Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: A Preliminary Study

    PubMed Central

    GREENWALD, SAMANTHA; SEGER, EDWARD; NICHOLS, DAVID; RAY, ANDREW D.; RIDEOUT, TODD C.; GOSSELIN, LUC E.

    2016-01-01

    Impaired glucose tolerance can have significant health consequences. The purposes of this preliminary study were to examine whether a single session of kettlebell exercise improves acute post-exercise glucose tolerance in sedentary individuals, and whether it was as effective as high-intensity interval running. Six sedentary male subjects underwent a two-hour oral glucose tolerance test following three different conditions: 1) control (no exercise); 2) kettlebell exercise (2 sets of 7 exercises, 15 repetitions per exercise with 30 seconds rest between each exercise); or 3) high-intensity interval running (10 one-minute intervals at a workload corresponding to 90% VO2max interspersed with one-minute active recovery periods). Blood glucose and insulin levels were measured before (0 minutes), and 60 and 120 minutes after glucose ingestion. Both kettlebell and high-intensity interval running exercise significantly lowered blood glucose 60 minutes after glucose ingestion compared with control. However, there was no significant difference in blood glucose between the two exercise conditions at any time point. In addition, there were no significant differences in insulin concentration between high intensity interval running, kettlebell, and control conditions at all time points. Results indicate that an acute bout of kettlebell exercise is as effective as high intensity interval running at improving glucose tolerance in sedentary young men. PMID:27766136

  5. Effect of an Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: A Preliminary Study.

    PubMed

    Greenwald, Samantha; Seger, Edward; Nichols, David; Ray, Andrew D; Rideout, Todd C; Gosselin, Luc E

    2016-01-01

    Impaired glucose tolerance can have significant health consequences. The purposes of this preliminary study were to examine whether a single session of kettlebell exercise improves acute post-exercise glucose tolerance in sedentary individuals, and whether it was as effective as high-intensity interval running. Six sedentary male subjects underwent a two-hour oral glucose tolerance test following three different conditions: 1) control (no exercise); 2) kettlebell exercise (2 sets of 7 exercises, 15 repetitions per exercise with 30 seconds rest between each exercise); or 3) high-intensity interval running (10 one-minute intervals at a workload corresponding to 90% VO2max interspersed with one-minute active recovery periods). Blood glucose and insulin levels were measured before (0 minutes), and 60 and 120 minutes after glucose ingestion. Both kettlebell and high-intensity interval running exercise significantly lowered blood glucose 60 minutes after glucose ingestion compared with control. However, there was no significant difference in blood glucose between the two exercise conditions at any time point. In addition, there were no significant differences in insulin concentration between high intensity interval running, kettlebell, and control conditions at all time points. Results indicate that an acute bout of kettlebell exercise is as effective as high intensity interval running at improving glucose tolerance in sedentary young men.

  6. Three-dimensional object rotation-tolerant recognition for integral imaging using synthetic discriminant function

    NASA Astrophysics Data System (ADS)

    Hao, Jinbo; Wang, Xiaorui; Zhang, Jianqi; Xu, Yin

    2013-04-01

    This paper presents a novel approach of three-dimensional object rotation-tolerant recognition that combines the merits of Integral Imaging (II) and Synthetic Discriminant Function (SDF). SDF aims at filters and distortion-tolerant recognition, and we use it for three-dimensional (3-D) rotation-tolerant recognition with II system. Using high relevancy of elemental images of II, the approach can not only realize 3-D rotation-tolerant recognition, but also reduce computational complexity. The correctness has been validated by experimental results.

  7. Fault Tolerant Hardware/Software Architecture for Flight Critical Function

    DTIC Science & Technology

    1985-09-01

    performance demands, are becoming complex and sophisticated. Demands for higher accuracy, improved reliability /survivabiiity, all-weather operation, and more...catastrophic). Flight critical architectures are more complex than fault-tolerant computers. In addition to airborne computers, overall reliability ... reliable data communications, and multi-computer operation using the Ada language. First Day The first paper presents a description of two recent GEC

  8. Acute CO2 tolerance during the early developmental stages of four marine teleosts.

    PubMed

    Kikkawa, T; Ishimatsu, A; Kita, J

    2003-12-01

    Ocean sequestration of CO2 is proposed as a possible measure to mitigate climate changes caused by increasing atmospheric concentrations of the gas, but its impact on the marine ecosystem is unknown. We investigated the acute lethal effect of CO2 during the early developmental stages of four marine teleosts: red sea bream (Pagrus major), Japanese whiting (Sillago japonica), Japanese flounder (Paralichthys olivaceus), and eastern little tuna (Euthynnus affinis). The percentages of larvae that hatched and survived were not affected by exposure to water with a PCO2 of 1.0 kPa (= 7.5 mmHg) within 24 h. Median lethal PCO2 values for a 360-min exposure were 1.4 kPa (cleavage), 5.1 kPa (embryo), 7.3 kPa (preflexion), 4.2 kPa (flexion), 4.6 kPa (postflexion), and 2.5 kPa (juvenile) for red sea bream; 2.4 kPa (cleavage), 4.9 kPa (embryo), 5.9 kPa (preflexion), 6.1 kPa (flexion), 4.1 kPa (postflexion), and 2.7 kPa (juvenile) for Japanese whiting; 2.8 kPa (cleavage) and > 7.0 kPa (young) for Japanese flounder; and 11.8 kPa (cleavage) for eastern little tuna. Red sea bream and Japanese whiting of all ontogenetic stages had similar susceptibilities to CO2: the most susceptible stages were cleavage and juvenile, whereas the most tolerant stages were preflexion and flexion.

  9. A Comprehensive Comparison of the Efficacy and Tolerability of Racecadotril with Other Treatments of Acute Diarrhea in Adults

    PubMed Central

    Fischbach, Wolfgang; Andresen, Viola; Eberlin, Marion; Mueck, Tobias; Layer, Peter

    2016-01-01

    Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability, but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain, and meteorism; it was also consistent across countries in Africa, Asia, and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. The seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration, and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea, racecadotril is more efficacious than placebo or S. boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or S. boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together, these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults. PMID:27790616

  10. The acute temperature tolerance of green sturgeon (Acipenser medirostris) and the effect of environmental salinity.

    PubMed

    Sardella, Brian A; Sanmarti, Enio; Kültz, Dietmar

    2008-10-01

    We investigated the effect of environmental salinity on the upper thermal tolerance of green sturgeon (Acipenser medirostris), a threatened species whose natural habitat is vulnerable to temperature and salinity variation as a result of global climate change. Freshwater (FW)-reared sturgeon were gradually acclimated to salinities representing FW, estuary water (EST), or San Francisco Bay water (BAY) at 18 degrees C, and their critical thermal maximum (CTMax) was measured by increasing temperature 0.3 degrees C/min until branchial ventilation ceased. CTMax was 34.2+/-0.09 degrees C in EST-acclimated fish, with FW- and BAY-acclimated fish CTMax at 33.7+/-0.08 and 33.7+/-0.1 degrees C, respectively. Despite the higher CTMax in EST-acclimated fish, FW-acclimated sturgeon ventilation rate reached a peak that was 2 degrees C higher than EST- and BAY-acclimated groups and had a greater range of temperatures within which they exhibited normal ventilatory function as assessed by Q10 calculation. The osmoregulatory consequences of exposure to near-lethal temperatures were assessed by measuring plasma osmolality and hematocrit, as well as white muscle, brain, and heart tissue water contents. Hematocrit was increased following CTMax exposure, most likely owing to the elevated metabolic demands of temperature increase, and plasma osmolality was significantly increased in EST- and BAY-acclimated fish, which was likely the result of a greater osmotic gradient across the gill as metabolism increased. To our knowledge, this represents the first evidence for an effect of salinity on the upper thermal tolerance of sturgeon, as well as the first investigation of the osmoregulatory consequences of exposure to near-lethal temperatures.

  11. Hagfish: Champions of CO2 tolerance question the origins of vertebrate gill function

    PubMed Central

    Baker, Daniel W.; Sardella, Brian; Rummer, Jodie L.; Sackville, Michael; Brauner, Colin J.

    2015-01-01

    The gill is widely accepted to have played a key role in the adaptive radiation of early vertebrates by supplanting the skin as the dominant site of gas exchange. However, in the most basal extant craniates, the hagfishes, gills play only a minor role in gas exchange. In contrast, we found hagfish gills to be associated with a tremendous capacity for acid-base regulation. Indeed, Pacific hagfish exposed acutely to severe sustained hypercarbia tolerated among the most severe blood acidoses ever reported (1.2 pH unit reduction) and subsequently exhibited the greatest degree of acid-base compensation ever observed in an aquatic chordate. This was accomplished through an unprecedented increase in plasma [HCO3−] (>75 mM) in exchange for [Cl−]. We thus propose that the first physiological function of the ancestral gill was acid-base regulation, and that the gill was later co-opted for its central role in gas exchange in more derived aquatic vertebrates. PMID:26057989

  12. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood.

    PubMed Central

    Nysom, K.; Holm, K.; Olsen, J. H.; Hertz, H.; Hesse, B.

    1998-01-01

    The aim of this study was to examine pulmonary function after acute lymphoblastic leukaemia in childhood and identify risk factors for reduced pulmonary function. We studied a population-based cohort of 94 survivors of acute lymphoblastic leukaemia in childhood who were in first remission after treatment without spinal irradiation or bone marrow transplantation. Pulmonary function test results were compared with reference values for our laboratory, based on 348 healthy subjects who had never smoked from a local population study. A median of 8 years after cessation of therapy (range 1-18 years) the participants had a slight, subclinical, restrictive ventilatory insufficiency and reduced transfer factor and transfer coefficient. The changes in lung function were related to younger age at treatment and to more dose-intensive treatment protocols that specified more use of cranial irradiation and higher cumulative doses of anthracyclines, cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We conclude that, 8 years after treatment without bone marrow transplantation or spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first remission were without pulmonary symptoms but had signs of slight restrictive pulmonary disease including reduced transfer factor. The increased dose intensity of many recent protocols for childhood acute lymphoblastic leukaemia may lead to increased late pulmonary toxicity. PMID:9662245

  13. Lung function after acute chlorine exposure

    SciTech Connect

    Jones, R.N.; Hughes, J.M.; Glindmeyer, H.; Weill, H.

    1986-12-01

    Chlorine gas, spreading from a train derailment, caused the deaths of 8 persons and the hospitalization of 23 with sublethal respiratory injuries. Twenty-five others had at least one sign of lower respiratory abnormality but were not hospitalized. One hundred thirteen who were examined for gas effects in the forty-eight hours after exposure, including 20 of 23 of those hospitalized and 21 of 25 of those not hospitalized but with respiratory abnormality, participated in follow-up studies. Probability of admission to hospital was related to distance from the spill, but by 3 wk after exposure there was no detectable difference in lung function relating to distance or apparent severity of injury. In 60 adults tested multiple times over the following 6 yr, longitudinal change in lung function showed expected differences related to smoking but none related to distance or severity of injury. The average annual change in FEV was -34 ml/yr in current smokers and -18 ml/yr in ex and never-smokers. The lack of a discernible chlorine effect in this cohort accords with the findings in most previous studies. Without pre-exposure measurements, a single, lasting reduction in lung function cannot be excluded, but there is no evidence for a persisting abnormal rate of decline.

  14. Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes.

    PubMed

    Forsberg, Kevin J; Patel, Sanket; Witt, Evan; Wang, Bin; Ellison, Tyler D; Dantas, Gautam

    2015-11-06

    The production of fuels or chemicals from lignocellulose currently requires thermochemical pretreatment to release fermentable sugars. These harsh conditions also generate numerous small-molecule inhibitors of microbial growth and fermentation, limiting production. We applied small-insert functional metagenomic selections to discover genes that confer microbial tolerance to these inhibitors, identifying both individual genes and general biological processes associated with tolerance to multiple inhibitory compounds. Having screened over 248 Gb of DNA cloned from 16 diverse soil metagenomes, we describe gain-of-function tolerance against acid, alcohol, and aldehyde inhibitors derived from hemicellulose and lignin, demonstrating that uncultured soil microbial communities hold tremendous genetic potential to address the toxicity of pretreated lignocellulose. We recovered genes previously known to confer tolerance to lignocellulosic inhibitors as well as novel genes that confer tolerance via unknown functions. For instance, we implicated galactose metabolism in overcoming the toxicity of lignin monomers and identified a decarboxylase that confers tolerance to ferulic acid; this enzyme has been shown to catalyze the production of 4-vinyl guaiacol, a valuable precursor to vanillin production. These metagenomic tolerance genes can enable the flexible design of hardy microbial catalysts, customized to withstand inhibitors abundant in specific bioprocessing applications.

  15. Identification of Genes Conferring Tolerance to Lignocellulose-Derived Inhibitors by Functional Selections in Soil Metagenomes

    PubMed Central

    Forsberg, Kevin J.; Patel, Sanket; Witt, Evan; Wang, Bin; Ellison, Tyler D.

    2015-01-01

    The production of fuels or chemicals from lignocellulose currently requires thermochemical pretreatment to release fermentable sugars. These harsh conditions also generate numerous small-molecule inhibitors of microbial growth and fermentation, limiting production. We applied small-insert functional metagenomic selections to discover genes that confer microbial tolerance to these inhibitors, identifying both individual genes and general biological processes associated with tolerance to multiple inhibitory compounds. Having screened over 248 Gb of DNA cloned from 16 diverse soil metagenomes, we describe gain-of-function tolerance against acid, alcohol, and aldehyde inhibitors derived from hemicellulose and lignin, demonstrating that uncultured soil microbial communities hold tremendous genetic potential to address the toxicity of pretreated lignocellulose. We recovered genes previously known to confer tolerance to lignocellulosic inhibitors as well as novel genes that confer tolerance via unknown functions. For instance, we implicated galactose metabolism in overcoming the toxicity of lignin monomers and identified a decarboxylase that confers tolerance to ferulic acid; this enzyme has been shown to catalyze the production of 4-vinyl guaiacol, a valuable precursor to vanillin production. These metagenomic tolerance genes can enable the flexible design of hardy microbial catalysts, customized to withstand inhibitors abundant in specific bioprocessing applications. PMID:26546427

  16. Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation.

    PubMed

    Hirsch, Katie R; Smith-Ryan, Abbie E; Roelofs, Erica J; Trexler, Eric T; Mock, Meredith G

    2016-07-13

    To determine the effects of a mushroom blend containing Cordyceps militaris on high-intensity exercise after 1 and 3 weeks of supplementation. Twenty-eight individuals (Mean ± standard deviation [SD]; Age = 22.7 ± 4.1 yrs; Height = 175.4 ± 8.7 cm; Weight = 71.6 ± 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (%drop) were recorded during a 3 minute maximal cycle test with resistance at 4.5% body weight. Subjects consumed 4 g·d(-1) mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks. Exercise tests were separated by at least 48 hours and repeated following supplementation periods. One week of supplementation elicited no significant time × treatment interaction for VO2max (p = 0.364), VT (p = 0.514), TTE (p = 0.540), RPP (p = 0.134), AvgP (p = 0.398), or %drop (p = 0.823). After 3 weeks, VO2max significantly improved (p = 0.042) in MR (+4.8 ml·kg(-1)·min(-1)), but not PL (+0.9 ml·kg(-1)·min(-1)). Analysis of 95% confidence intervals revealed significant improvements in TTE after 1- (+28.1 s) and 3 weeks (+69.8 s) in MR, but not PL, with additional improvements in VO2max (+4.8 ml·kg(-1)·min(-1)) and VT (+0.7 l·min(-1)) after 3 weeks. Acute supplementation with a Cordyceps militaris containing mushroom blend may improve tolerance to high-intensity exercise; greater benefits may be elicited with consistent chronic supplementation.

  17. Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms related to driving: drinking and driving on the descending limb

    PubMed Central

    Weafer, Jessica

    2015-01-01

    Rationale Alcohol effects on behavioral and cognitive mechanisms influence impaired driving performance and decisions to drive after drinking (Barry 1973; Moskowitz and Robinson 1987). To date, research has focused on the ascending limb of the blood alcohol curve, and there is little understanding of how acute tolerance to impairment of these mechanisms might influence driving behavior on the descending limb. Objectives To provide an integrated examination of the degree to which alcohol impairment of motor coordination and inhibitory control contributes to driving impairment and decisions to drive on the ascending and descending limbs of the blood alcohol curve. Methods Social-drinking adults (N=20) performed a testing battery that measured simulated driving performance and willingness to drive, as well as mechanisms related to driving: motor coordination (grooved pegboard), inhibitory control (cued go/no-go task), and subjective intoxication. Performance was tested in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations: once on the ascending limb and again on the descending limb. Results Impaired motor coordination and subjective intoxication showed acute tolerance, whereas driving performance and inhibitory control showed no recovery from impairment. Greater motor impairment was associated with poorer driving performance under alcohol, and poorer inhibitory control was associated with more willingness to drive. Conclusions Findings suggest that acute tolerance to impairment of motor coordination is insufficient to promote recovery of driving performance and that the persistence of alcohol-induced disinhibition might contribute to risky decisions to drive on the descending limb. PMID:21960182

  18. Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance

    PubMed Central

    Mackern-Oberti, Juan P.; Vega, Fabián; Llanos, Carolina; Bueno, Susan M.; Kalergis, Alexis M.

    2014-01-01

    Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders. PMID:25229821

  19. Yeast functional screen to identify genes conferring salt stress tolerance in Salicornia europaea

    PubMed Central

    Nakahara, Yoshiki; Sawabe, Shogo; Kainuma, Kenta; Katsuhara, Maki; Shibasaka, Mineo; Suzuki, Masanori; Yamamoto, Kosuke; Oguri, Suguru; Sakamoto, Hikaru

    2015-01-01

    Salinity is a critical environmental factor that adversely affects crop productivity. Halophytes have evolved various mechanisms to adapt to saline environments. Salicornia europaea L. is one of the most salt-tolerant plant species. It does not have special salt-secreting structures like a salt gland or salt bladder, and is therefore a good model for studying the common mechanisms underlying plant salt tolerance. To identify candidate genes encoding key proteins in the mediation of salt tolerance in S. europaea, we performed a functional screen of a cDNA library in yeast. The library was screened for genes that allowed the yeast to grow in the presence of 1.3 M NaCl. We obtained three full-length S. europaea genes that confer salt tolerance. The genes are predicted to encode (1) a novel protein highly homologous to thaumatin-like proteins, (2) a novel coiled-coil protein of unknown function, and (3) a novel short peptide of 32 residues. Exogenous application of a synthetic peptide corresponding to the 32 residues improved salt tolerance of Arabidopsis. The approach described in this report provides a rapid assay system for large-scale screening of S. europaea genes involved in salt stress tolerance and supports the identification of genes responsible for such mechanisms. These genes may be useful candidates for improving crop salt tolerance by genetic transformation. PMID:26579166

  20. Correlation between the dose and development of acute tolerance to the hypothermic effect of THC.

    PubMed

    Uran, B; Tulunay, F C; Ayhan, I H; Ulkü, E; Kaymakçalan, S

    1980-01-01

    The administration of 0.3-40 mg/kg delta 9-tetrahydrocannabinol (THC) produced a dose-dependent hypothermia in rats. The maximal hypothermic effect was obtained with the dose of 2.5 mg/kg of THC. When the same doses of THC were repeated on days 2 and 3, tolerance to the hypothermic effect of THC was apparent. Doses of THC higher than 2.5 mg/kg induced a significant and dose-dependent tolerance after the first administration whereas with the lower doses, tolerance was only apparent after the second injection. The possible mechanism of these effects of THC is discussed.

  1. CO2-O2 interactions in extension of tolerance to acute hypoxia

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.

    1995-01-01

    Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).

  2. Facilitating Tolerance of Delayed Reinforcement during Functional Communication Training.

    ERIC Educational Resources Information Center

    Fisher, Wayne W.; Thompson, Rachel H.; Hagopian, Louis P.; Bowman, Lynn G.; Krug, Amy

    2000-01-01

    Three individuals with severe behavior disorders and mental retardation, whose destructive behaviors were being maintained by positive reinforcement, were treated using functional communication training with extinction. The case studies investigated techniques used to increase effectiveness of delayed reinforcement and to teach individuals with…

  3. From Genetics to Functional Genomics: Improvement in Drought Signaling and Tolerance in Wheat

    PubMed Central

    Budak, Hikmet; Hussain, Babar; Khan, Zaeema; Ozturk, Neslihan Z.; Ullah, Naimat

    2015-01-01

    Drought being a yield limiting factor has become a major threat to international food security. It is a complex trait and drought tolerance response is carried out by various genes, transcription factors (TFs), microRNAs (miRNAs), hormones, proteins, co-factors, ions, and metabolites. This complexity has limited the development of wheat cultivars for drought tolerance by classical breeding. However, attempts have been made to fill the lost genetic diversity by crossing wheat with wild wheat relatives. In recent years, several molecular markers including single nucleotide polymorphisms (SNPs) and quantitative trait loci (QTLs) associated with genes for drought signaling pathways have been reported. Screening of large wheat collections by marker assisted selection (MAS) and transformation of wheat with different genes/TFs has improved drought signaling pathways and tolerance. Several miRNAs also provide drought tolerance to wheat by regulating various TFs/genes. Emergence of OMICS techniques including transcriptomics, proteomics, metabolomics, and ionomics has helped to identify and characterize the genes, proteins, metabolites, and ions involved in drought signaling pathways. Together, all these efforts helped in understanding the complex drought tolerance mechanism. Here, we have reviewed the advances in wide hybridization, MAS, QTL mapping, miRNAs, transgenic technique, genome editing system, and above mentioned functional genomics tools for identification and utility of signaling molecules for improvement in wheat drought tolerance. PMID:26635838

  4. Diacylglycerol Kinases in T Cell Tolerance and Effector Function

    PubMed Central

    Chen, Shelley S.; Hu, Zhiming; Zhong, Xiao-Ping

    2016-01-01

    Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by phosphorylating DAG to produce PA. Both DAG and PA are important second messengers cascading T cell receptor (TCR) signal by recruiting multiple effector molecules, such as RasGRP1, PKCθ, and mTOR. Studies have revealed important physiological functions of DGKs in the regulation of receptor signaling and the development and activation of immune cells. In this review, we will focus on recent progresses in our understanding of two DGK isoforms, α and ζ, in CD8 T effector and memory cell differentiation, regulatory T cell development and function, and invariant NKT cell development and effector lineage differentiation. PMID:27891502

  5. Safety and tolerability of intrathecal liposomal cytarabine as central nervous system prophylaxis in patients with acute lymphoblastic leukemia.

    PubMed

    Valentin, Angelika; Troppan, Katharina; Pfeilstöcker, Michael; Nösslinger, Thomas; Linkesch, Werner; Neumeister, Peter

    2014-08-01

    Central nervous system recurrence in acute lymphoblastic leukemia (ALL) occurs in up to 15% of patients and is frequently associated with poor outcome. The purpose of our study was to evaluate the efficacy and safety of a slow-release liposomal formulation of cytarabine for intrathecal (IT) meningeal prophylaxis in patients suffering from ALL. Forty patients aged 20-77 years (median 36) were preventively treated with a total of 96 (range 1-6) single doses containing 50 mg of liposomal cytarabine on a compassionate use basis. After a median observation period of 23 months (range 2-118) only two patients experienced a combined medullary-leptomeningeal disease recurrence after primary diagnosis. Except for headache grade 2 in two patients, no specific toxicity attributable to IT liposomal cytarabine application was noted. Long-term neurological side effects were not observed. IT liposomal cytarabine therapy with concomitant dexamethasone appears to be feasible and well tolerated.

  6. Senescence marker protein-30/gluconolactonase deletion worsens glucose tolerance through impairment of acute insulin secretion.

    PubMed

    Hasegawa, Goji; Yamasaki, Masahiro; Kadono, Mayuko; Tanaka, Muhei; Asano, Mai; Senmaru, Takafumi; Kondo, Yoshitaka; Fukui, Michiaki; Obayashi, Hiroshi; Maruyama, Naoki; Nakamura, Naoto; Ishigami, Akihito

    2010-02-01

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout (KO) mice treated with L-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wild-type (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in beta-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mm glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mm in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging.

  7. Atomoxetine and Methylphenidate Treatment in Children with ADHD: The Efficacy, Tolerability and Effects on Executive Functions

    ERIC Educational Resources Information Center

    Yildiz, Ozlem; Sismanlar, Sahika G.; Memik, Nursu Cakin; Karakaya, Isik; Agaoglu, Belma

    2011-01-01

    The aim of this study was to compare the safety, efficacy, tolerability, and the effects of atomoxetine and OROS-MPH on executive functions in children with ADHD. This study was an open-label study that only included two medication groups. Children were randomized to open-label atomoxetine or OROS-MPH for 12 weeks. Primary efficacy measures were…

  8. RH-01THE SIGNIFICANCE OF ACUTE INPATIENT REHABILITATION FOR GLIOMA PATIENTS: IMPROVING THE PHYSICAL FUNCTION, QUALITY OF LIFE AND SURVIVAL

    PubMed Central

    Beverly Fu, D.; Bota, Daniela A.

    2014-01-01

    OBJECTIVE: To assess the effects of inpatient acute rehabilitation on overall function, quality of life and overall survival for glioma patients. DESIGN: A retrospective study of glioma patients treated at UCI Neuro-Oncology Program. PARTICIPANTS: We have identified 12 patients with glioma diagnosis who underwent inpatient acute rehabilitation program using our IRB approved neuro-oncology database. OUTCOME ASSESSMENT TOOLS: Functional status based upon Karnofsky performance scale (KPS), quality of life as assessed by Functional Assessment of Cancer Therapy Brain (FACT-Br) and overall survival. RESULTS: We identified on our study 3 patients with glioblastoma, 7 patients with anaplastic gliomas, and 2 patients with low grade gliomas. All of them had radiation and chemotherapy, except 2 patients with low grade gliomas who had radiation treatment only. The age range is from 26 to 77 and the mean age is 49-year-old. All the patients who underwent the acute inpatient rehabilitation program at our institution, not only improved their KPS scale significantly, but also enhanced their social and emotional well-being. The median KPS improvement is 30 points from a 3-6 weeks stay. Functional Assessment of Cancer Therapy Brain (FACT-Br) is obtained from 4 patients at this time (further information will be presented at SNO conference). The mean FACT-Br TOI is 60.8, and the total FACT0Br Score is 119.6. Survival data are still collected. CONCLUSIONS: The patients who underwent acute inpatient rehabilitation program, showed significant improvements in their functional status and quality of life. The observation from this pilot study warrants further research and demonstrates the acute inpatient rehabilitation may be beneficial to glioma patients with good physical functions and tolerance for 3 hours a day of physical, occupation and speech therapies.

  9. Cyanine dyes as contrast agents for near-infrared imaging in vivo: acute tolerance, pharmacokinetics, and fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Ebert, Bernd; Riefke, Björn; Sukowski, Uwe; Licha, Kai

    2011-06-01

    We compare pharmacokinetic, tolerance, and imaging properties of two near-IR contrast agents, indocyanine green (ICG) and 1,1'-bis-(4-sulfobutyl) indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium salt (SIDAG). ICG is a clinically approved imaging agent, and its derivative SIDAG is a more hydrophilic counterpart that has recently shown promising imaging properties in preclinical studies. The rather lipophilic ICG has a very short plasma half-life, thus limiting the time available to image body regions during its vascular circulation (e.g., the breast in optical mammography where scanning over several minutes is required). In order to change the physicochemical properties of the indotricarbocyanine dye backbone, several derivatives were synthesized with increasing hydrophilicity. The most hydrophilic dye SIDAG is selected for further biological characterization. The acute tolerance of SIDAG in mice is increased up to 60-fold compared to ICG. Contrary to ICG, the pharmacokinetic properties of SIDAG are shifted toward renal elimination, caused by the high hydrophilicity of the molecule. N-Nitrosomethylurea (NMU)-induced rat breast carcinomas are clearly demarcated, both immediately and 24 h after intravenous administration of SIDAG, whereas ICG shows a weak tumor contrast under the same conditions. Our findings demonstrate that SIDAG is a high potential contrast agent for optical imaging, which could increase the sensitivity for detection of inflamed regions and tumors.

  10. Practical Guide to the Management of Acute and Chronic Pain in the Presence of Drug Tolerance for the Healthcare Practitioner

    PubMed Central

    Vadivelu, Nalini; Singh-Gill, Harman; Kodumudi, Gopal; Kaye, Aaron Joshua; Urman, Richard D.; Kaye, Alan David

    2014-01-01

    Background Drug tolerance has been on the rise in recent years worldwide, and consequently, pain management in our population has become challenging. Methods Discussed in this review are commonly abused drugs and considerations for treating acute and chronic pain states in patients with substance disorders. Results After marijuana, alcohol, and tobacco, the most widely abused substances are oxycodone (Oxycontin), diazepam (Valium), and methylphenidate (Ritalin). Urine testing can detect metabolites of drugs used by patients and is useful for assessing drug abuse, medication diversion, and drug interactions. The comprehensive treatment of pain in a patient with addictive disorder or tolerance must address 3 issues: the patient's addiction, any associated psychiatric conditions, and the patient's pain. Eliciting a detailed history of drug abuse—illicit drugs as well as prescription drugs—and ascertaining if the patient is currently enrolled in a methadone maintenance program for the treatment of drug addiction is vital. Conclusion Medical observation, supportive care, multidisciplinary pain management, and timely interventions as necessary are the keys to safe outcomes in these patients. PMID:25249810

  11. Acute toxicity of lead on tolerance, oxygen consumption, ammonia-N excretion, and metal accumulation in Penaeus indicus postlarvae.

    PubMed

    Chinni, Satyavathi; Khan, Ritindra N; Yallapragada, Prabhakara Rao

    2002-02-01

    The estuaries and backwaters that are the potential breeding grounds of penaeid shrimps are subject to heavy metal pollution through industrial effluents and domestic sewage. In the present investigation, laboratory experiments were conducted to study the acute toxicity of lead on tolerance, oxygen consumption, ammonia-N excretion, and metal accumulation in Penaeus indicus postlarvae. Static bioassay tests were employed to determine tolerance limits. Oxygen consumption, ammonia-N excretion, and metal accumulation were determined in postlarvae by exposing them to different concentrations of lead for a period of 48 h. Oxygen consumption measurements were made by using a respiratory chamber equipped with an oxygen electrode and ammonia-N was determined with trione (dichloro-S-triamine 2,4,6(1H,3H,5H-trione)). Accumulation of metal was estimated by wet-ash method. The LC50 value for 96 h was 7.223 ppm and the regression equation Y=4.1638+0.9738X with correlation coefficient of 0.9613 was obtained by probit method. A decrease in oxygen consumption and ammonia-N excretion was observed in postlarvae with increasing concentration of lead. A concentration-dependent accumulation of metal was noticed in these postlarvae. Modifications in O:N ratios of postlarvae suggest that lead accumulation might have altered utilization patterns.

  12. Clinical Comparative Study: Efficacy and Tolerability of Tolperisone and Thiocolchicoside in Acute Low Back Pain and Spinal Muscle Spasticity

    PubMed Central

    Rao, Rajeev; Panghate, Atul; Chandanwale, Ajay; Sardar, Indrajeet; Ghosh, Mriganka; Roy, Modan; Banerjee, Bireswar; Goswami, Ankur

    2012-01-01

    Study Design We performed a multicentric, randomized, comparative clinical trial. Eligible patients were randomly assigned to receive 150 mg of Tolperisone thrice daily or 8 mg of Thiocolchicoside twice daily for 7 days. Purpose To assess the efficacy and tolerability of Tolperisone in comparison with Thiocolchicoside in the treatment of acute low back pain with spasm of spinal muscles. Overview of Literature No head on clinical trial of Tolperisone with Thiocolchicoside is available and so this study is done. Methods The assessment of muscle spasm was made by measuring the finger-to-floor distance (FFD), articular excursion in degrees on performing Lasegue's maneuver and modified Schober's test. Assessment of pain on movement and spontaneous pain (pain at rest) of the lumbar spine was made with the help of visual analogue scale score. Results The improvement in articular excursion on Lasegue's maneuver was significantly greater on day 3 (p = 0.017) and day 7 (p = 0.0001) with Tolperisone as compared to Thiocolchicoside. The reduction in FFD score was greater on day 7 (p = 0.0001) with Tolperisone. However there was no significant difference in improvement in Schober's test score on day 3 (p = 0.664) and day 7 (p = 0.192). The improvement in pain score at rest and on movement was significantly greater with Tolperisone (p = 0.0001). Conclusions Tolperisone is an effective and well tolerated option for treatment of patients with skeletal muscle spasm associated with pain. PMID:22708015

  13. Shade tolerance and herbivory are associated with RGR of tree species via different functional traits.

    PubMed

    Salgado-Luarte, C; Gianoli, E

    2016-12-20

    Relative growth rate (RGR) plays an important role in plant adaptation to the light environment through the growth potential/survival trade-off. RGR is a complex trait with physiological and biomass allocation components. It has been argued that herbivory may influence the evolution of plant strategies to cope with the light environment, but little is known about the relation between susceptibility to herbivores and growth-related functional traits. Here, we examined in 11 evergreen tree species from a temperate rainforest the association between growth-related functional traits and (i) species' shade-tolerance, and (ii) herbivory rate in the field. We aimed at elucidating the differential linkage of shade and herbivory with RGR via growth-related functional traits. We found that RGR was associated negatively with shade-tolerance and positively with herbivory rate. However, herbivory rate and shade-tolerance were not significantly related. RGR was determined mainly by photosynthetic rate (Amax ) and specific leaf area (SLA). Results suggest that shade tolerance and herbivore resistance do not covary with the same functional traits. Whereas shade-tolerance was strongly related to Amax and to a lesser extent to leaf mass ratio (LMR) and dark respiration (Rd ), herbivory rate was closely related to allocation traits (SLA and LMR) and slightly associated with protein content. The effects of low light on RGR would be mediated by Amax , while the effects of herbivory on RGR would be mediated by SLA. Our findings suggest that shade and herbivores may differentially contribute to shape RGR of tree species through their effects on different resource-uptake functional traits.

  14. Evidence for PTZ-like cues as a function of time following treatment with chlordiazepoxide: implications for understanding tolerance and withdrawal.

    PubMed

    Barrett, R J; Smith, R L

    2005-05-01

    The present study used a two-lever, drug-discrimination procedure to train rats to discriminate between the cues associated with 5 mg/kg of the anxiolytic, chlordiazepoxide (CDP) and 15 mg/kg of the anxiogenic, pentylenetetrazol (PTZ), to investigate the relationship between withdrawal and acute tolerance. Training doses of the two drugs were chosen so that rats responded about equally on both levers when tested on saline (SAL). Following acquisition of the discrimination, rats were injected with 10 mg/kg CDP and tested for lever choice at various intervals from 6 h to 192 h. These tests revealed that cues associated with CDP withdrawal lasted approximately three times longer than the cues associated with the drug's primary effects. At the shortest retest interval (6 h) after treatment with 10 mg/kg CDP, rats responded primarily on the CDP lever, followed by a shift to predominant responding on the PTZ lever at the 16 h and 24 h intervals before returning to predrug, baseline levels at the longer intervals (48-192 h). In order to investigate the relationship between tolerance and withdrawal to the cue properties of CDP, CDP dose-response curves were determined 24 h following treatment with SAL or 10 mg/kg CDP. Acute tolerance, as defined by a rightward, parallel shift in the dose-response function, was observed in the rats pretreated with CDP. Furthermore, it was evident that the baseline shift associated with CDP withdrawal, rather than a weaker drug cue, accounted for acute tolerance. The results from this study are relevant to evaluating the role positive and negative reinforcement play in motivating compulsive drug use.

  15. The Acute and Residual Effect of a Single Exercise Session on Meal Glucose Tolerance in Sedentary Young Adults

    PubMed Central

    Short, Kevin R.; Pratt, Lauren V.; Teague, April M.

    2012-01-01

    The study goals were to (1) establish the variability in postprandial glucose control in healthy young people consuming a mixed meal and, then (2) determine the acute and residual impact of a single exercise bout on postprandial glucose control. In study 1, 18 people completed two similar mixed meal trials and an intravenous glucose tolerance test (IVGTT). There were strong test-retest correlations for the post-meal area under the curve (AUC) for glucose, insulin, and Cpeptide (r = 0.73–0.83) and the Matsuda insulin sensitivity index (ISI, r = 0.76), and between meal and IVGTT-derived ISI (r = 0.83). In study 2, 11 untrained young adults completed 3 trials. One trial (No Ex) was completed after refraining from vigorous activity for ≥3 days. On the other 2 trials, a 45-min aerobic exercise bout was performed either 17-hours (Prior Day Ex) or 1-hour (Same Day Ex) before consuming the test meal. Compared to No Ex and Prior Day Ex, which did not differ from one another, there were lower AUCs on the Same Day Ex trial for glucose (6%), insulin (20%) and C-peptide (14%). Thus, a single moderate intensity exercise session can acutely improve glycemic control but the effect is modest and short-lived. PMID:22666560

  16. The impact of microbial immune enteral nutrition on the patients with acute radiation enteritis in bowel function and immune status.

    PubMed

    Shao, Feng; Xin, Fu-Ze; Yang, Cheng-Gang; Yang, Dao-Gui; Mi, Yue-Tang; Yu, Jun-Xiu; Li, Guo-Yong

    2014-06-01

    The aim of the study was to investigate the effect of microbial immune enteral nutrition by microecopharmaceutics and deep sea fish oil and glutamine and Peptisorb on the patients with acute radiation enteritis in bowel function and immune status. From June 2010 to January 2013, 46 acute radiation enteritis patients in Liaocheng People's Hospital were randomized into the microbial immune enteral nutrition group and the control group: 24 patients in treatment group and 22 patients in control group. The immune microbial nutrition was given to the study group, but not to the control group. The concentration of serum albumin and prealbumin and the number of CD3 (+) T cell, CD4 (+) T cell, CD8 (+) T cell, CD4 (+)/CD8 (+) and natural killer cell of the two groups were detected on the 1, 7 and 14 days after treatment. The arm muscle circumference and triceps skinfold thickness (TSF) were recorded, and the tolerance of the two groups for enteral nutrition and intestinal symptoms was collected and then comparing the two indicators and get results. The tolerance of microbial immune enteral nutrition group about abdominal pain, bloating and diarrhea was better than the control group (P values were 0.018, 0.04 and 0.008 after 7 days; P values were 0.018, 0.015 and 0.002 after 14 days); and the cellular immune parameters were better than the control group((△) P = 0.008,([Symbol: see text]) P = 0.039, (☆) P = 0.032); No difference was found in nutrition indicators. To the patients with acute radiation enteritis, microbial immune enteral nutrition could improve the patient's immune status, and the tolerance of enteral nutrition could be better for the bowel function and the patients' rehabilitation.

  17. Functional diversity supports the physiological tolerance hypothesis for plant species richness along climatic gradients

    USGS Publications Warehouse

    Spasojevic, Marko J.; Grace, James B.; Harrison, Susan; Damschen, Ellen Ingman

    2013-01-01

    1. The physiological tolerance hypothesis proposes that plant species richness is highest in warm and/or wet climates because a wider range of functional strategies can persist under such conditions. Functional diversity metrics, combined with statistical modeling, offer new ways to test whether diversity-environment relationships are consistent with this hypothesis. 2. In a classic study by R. H. Whittaker (1960), herb species richness declined from mesic (cool, moist, northerly) slopes to xeric (hot, dry, southerly) slopes. Building on this dataset, we measured four plant functional traits (plant height, specific leaf area, leaf water content and foliar C:N) and used them to calculate three functional diversity metrics (functional richness, evenness, and dispersion). We then used a structural equation model to ask if ‘functional diversity’ (modeled as the joint responses of richness, evenness, and dispersion) could explain the observed relationship of topographic climate gradients to species richness. We then repeated our model examining the functional diversity of each of the four traits individually. 3. Consistent with the physiological tolerance hypothesis, we found that functional diversity was higher in more favorable climatic conditions (mesic slopes), and that multivariate functional diversity mediated the relationship of the topographic climate gradient to plant species richness. We found similar patterns for models focusing on individual trait functional diversity of leaf water content and foliar C:N. 4. Synthesis. Our results provide trait-based support for the physiological tolerance hypothesis, suggesting that benign climates support more species because they allow for a wider range of functional strategies.

  18. The role of recovery of mitochondrial structure and function in desiccation tolerance of pea seeds.

    PubMed

    Wang, Wei-Qing; Cheng, Hong-Yan; Møller, Ian M; Song, Song-Quan

    2012-01-01

    Mitochondrial repair is of fundamental importance for seed germination. When mature orthodox seeds are imbibed and germinated, they lose their desiccation tolerance in parallel. To gain a better understanding of this process, we studied the recovery of mitochondrial structure and function in pea (Pisum sativum cv. Jizhuang) seeds with different tolerance to desiccation. Mitochondria were isolated and purified from the embryo axes of control and imbibed-dehydrated pea seeds after (re-)imbibition for various times. Recovery of mitochondrial structure and function occurred both in control and imbibed-dehydrated seed embryo axes, but at different rates and to different maximum levels. The integrity of the outer mitochondrial membrane reached 96% in all treatments. However, only the seeds imbibed for 12 h and then dehydrated recovered the integrity of the inner mitochondrial membrane (IMM) and State 3 (respiratory state in which substrate and ADP are present) respiration (with NADH and succinate as substrate) to the control level after re-imbibition. With increasing imbibition time, the degree to which each parameter recovered decreased in parallel with the decrease in desiccation tolerance. The tolerance of imbibed seeds to desiccation increased and decreased when imbibed in CaCl(2) and methylviologen solution, respectively, and the recovery of the IMM integrity similarly improved and weakened in these two treatments, respectively. Survival of seeds after imbibition-dehydration linearly increased with the increase in ability to recover the integrity of IMM and State 3 respiration, which indicates that recovery of mitochondrial structure and function during germination has an important role in seed desiccation tolerance.

  19. Dynamic alteration in splenic function during acute falciparum malaria

    SciTech Connect

    Looareesuwan, S.; Ho, M.; Wattanagoon, Y.; White, N.J.; Warrell, D.A.; Bunnag, D.; Harinasuta, T.; Wyler, D.J.

    1987-09-10

    Plasmodium-infected erythrocytes lose their normal deformability and become susceptible to splenic filtration. In animal models, this is one mechanism of antimalarial defense. To assess the effect of acute falciparum malaria on splenic filtration, we measured the clearance of heated /sup 51/Cr-labeled autologous erythrocytes in 25 patients with acute falciparum malaria and in 10 uninfected controls. Two groups of patients could be distinguished. Sixteen patients had splenomegaly, markedly accelerated clearance of the labeled erythrocytes (clearance half-time, 8.4 +/- 4.4 minutes (mean +/- SD) vs. 62.5 +/- 36.5 minutes in controls; P less than 0.001), and a lower mean hematocrit than did the patients without splenomegaly (P less than 0.001). In the nine patients without splenomegaly, clearance was normal. After institution of antimalarial chemotherapy, however, the clearance in this group accelerated to supernormal rates similar to those in the patients with splenomegaly, but without the development of detectable splenomegaly. Clearance was not significantly altered by treatment in the group with splenomegaly. Six weeks later, normal clearance rates were reestablished in most patients in both groups. We conclude that splenic clearance of labeled erythrocytes is enhanced in patients with malaria if splenomegaly is present and is enhanced only after treatment if splenomegaly is absent. Whether this enhanced splenic function applies to parasite-infected erythrocytes in patients with malaria and has any clinical benefit will require further studies.

  20. Functional associations between the metabolome and manganese tolerance in Vigna unguiculata.

    PubMed

    Führs, Hendrik; Specht, André; Erban, Alexander; Kopka, Joachim; Horst, Walter J

    2012-01-01

    Genotypic- and silicon (Si)-mediated differences in manganese (Mn) tolerance of cowpea (Vigna unguiculata) arise from a combination of symplastic and apoplastic traits. A detailed metabolomic inspection could help to identify functional associations between genotype- and Si-mediated Mn tolerance and metabolism. Two cowpea genotypes differing in Mn tolerance (TVu 91, Mn sensitive; TVu 1987, Mn tolerant) were subjected to differential Mn and Si treatments. Gas chromatography-mass spectrometry (GC-MS)-based metabolite profiling of leaf material was performed. Detailed evaluation of the response of metabolites was combined with gene expression and physiological analyses. After 2 d of 50 μM Mn supply TVu 91 expressed toxicity symptoms first in the form of brown spots on the second oldest trifoliate leaves. Silicon treatment suppressed symptom development in TVu 91. Despite higher concentrations of Mn in leaves of TVu 1987 compared with TVu 91, the tolerant genotype did not show symptoms. From sample cluster formation as identified by independent component analysis (ICA) of metabolite profiles it is concluded that genotypic differences accounted for the highest impact on variation in metabolite pools, followed by Mn and Si treatments in one of two experiments. Analysis of individual metabolites corroborated a comparable minor role for Mn and Si treatments in the modulation of individual metabolites. Mapping individual metabolites differing significantly between genotypes onto biosynthetic pathways and gene expression studies on the corresponding pathways suggest that genotypic Mn tolerance is a consequence of differences (i) in the apoplastic binding capacity; (ii) in the capability to maintain a high antioxidative state; and (iii) in the activity of shikimate and phenylpropanoid metabolism.

  1. Methamphetamine Self-Administration Acutely Decreases Monoaminergic Transporter Function

    PubMed Central

    McFadden, Lisa M.; Stout, Kristen A.; Vieira-Brock, Paula L.; Allen, Scott C.; Nielsen, Shannon M.; Wilkins, Diana G.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Numerous pre-clinical studies have demonstrated that non-contingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of non-contingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence. PMID:22120988

  2. Methamphetamine self-administration acutely decreases monoaminergic transporter function.

    PubMed

    McFadden, Lisa M; Stout, Kristen A; Vieira-Brock, Paula L; Allen, Scott C; Nielsen, Shannon M; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2012-03-01

    Numerous preclinical studies have demonstrated that noncontingent methamphetamine (METH) administration rapidly decreases both dopamine (DA) transporter (DAT) and vesicular monoamine-2 transporter (VMAT-2) function. Because of the importance of transporter function to the abuse and neurotoxic liabilities of METH, and previous research indicating that the effects of noncontingent METH treatment do not necessarily predict effects of contingent exposure, the present study examined the acute impact of METH self-administration on these transporters. Results revealed that five days of METH self-administration (4 h/session; 0.06 mg/infusion) decreased DAT and VMAT-2 activity, as assessed in synaptosomes and vesicles, respectively, prepared from striatal tissue 1 h after the final self-administration session. METH self-administration increased core body temperatures as well. Brain METH and amphetamine (AMPH) levels, assessed 1 h after the final self-administration session, were approximately twice greater in high-pressing rats compared to low-pressing rats despite similar changes in DAT function. In conclusion, the present manuscript is the first to describe transporter function and METH/AMPH levels after self-administration in rodents. These data provide a foundation to investigate complex questions including how the response of dopaminergic systems to METH self-administration contributes to contingent-related processes such as dependence.

  3. Amino acid mixture acutely improves the glucose tolerance of healthy overweight adults.

    PubMed

    Wang, Bei; Kammer, Lynne M; Ding, Zhenping; Lassiter, David G; Hwang, Jungyun; Nelson, Jeffrey L; Ivy, John L

    2012-01-01

    Certain amino acids have been reported to influence carbohydrate metabolism and blood glucose clearance, as well as improve the glucose tolerance in animal models. We hypothesized that an amino acid mixture consisting of isoleucine and 4 additional amino acids would improve the glucose response of healthy overweight men and women to an oral glucose tolerance test (OGTT). Twenty-two overweight healthy subjects completed 2 OGTTs after consuming 2 different test beverages. The amino acid mixture beverage (CHO/AA) consisted of 0.088 g cystine 2HCl, 0.043 g methionine, 0.086 g valine, 12.094 g isoleucine, 0.084 g leucine, and 100 g dextrose. The control beverage (CHO) consisted of 100 g dextrose only. Venous blood samples were drawn 10 minutes before the start of ingesting the drinks and 15, 30, 60, 120, and 180 minutes after the completion of the drinks. During the OGTT, the plasma glucose response for the CHO/AA treatment was significantly lower than that of the CHO treatment (P < .01), as was the plasma glucose area under the curve (CHO/AA 806 ± 31 mmol/L·3 hours vs CHO 942 ± 40 mmol/L·3 hours). Differences in plasma glucose between treatments occurred at 30, 60, 120, and 180 minutes after supplement ingestion. Plasma glucagon during the CHO/AA treatment was significantly higher than during the CHO treatment. However, there were no significant differences in plasma insulin or C-peptide responses between treatments. These results suggest that the amino acid mixture lowers the glucose response to an OGTT in healthy overweight subjects in an insulin-independent manner.

  4. Leukoaraiosis, intracerebral hemorrhage, and functional outcome after acute stroke thrombolysis

    PubMed Central

    Kongbunkiat, Kannikar; Wilson, Duncan; Kasemsap, Narongrit; Tiamkao, Somsak; Jichi, Fatima; Palumbo, Vanessa; Hill, Michael D.; Buchan, Alastair M.; Jung, Simon; Mattle, Heinrich P.; Henninger, Nils

    2017-01-01

    Objective: To perform a systematic review and pooled meta-analysis of published studies to assess whether the presence of leukoaraiosis on neuroimaging before treatment with thrombolysis (IV or intra-arterial) is associated with an increased risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome. Methods: We included studies of patients with acute ischemic stroke, treated with IV or intra-arterial thrombolysis, which assessed functional outcome (3-month modified Rankin Scale [mRS]) or sICH in relation to leukoaraiosis on pretreatment neuroimaging (CT or MRI). We used random-effects models to calculate pooled relative risks (RR) of sICH and poor functional outcome (mRS ≥ 2) for any vs no leukoaraiosis (using any rating scale) and for no to mild vs moderate to severe leukoaraiosis (using the Van Swieten or Fazekas Schmidt scale). Results: We identified 15 studies (total n = 6,967). For sICH outcome, the RR was 1.65 (n = 5,551; 95% confidence interval [CI] 1.26–2.16, p = 0.001) with an absolute risk (AR) increase of 2.5% for any leukoaraiosis vs none. The RR was 2.4 (n = 4,192; 95% CI 1.83–3.14, p = 0.001) with an AR increase of 6.2% for moderate to severe vs no to mild leukoaraiosis. For poor functional outcome; the RR was 1.30 (n = 3,401; 95% CI 1.19–1.42, p = 0.001) with an AR increase of 15.4% for any leukoaraiosis vs none. The RR was 1.31 (n = 3,659; 95% CI 1.22–1.42, p = 0.001) with an AR increase of 17.5% for moderate to severe vs no to mild leukoaraiosis. No statistical heterogeneity was noted for any of the analyses. Conclusions: Leukoaraiosis presence and severity are consistently associated with an increased risk of sICH and poor functional outcome after IV or intra-arterial thrombolysis for acute ischemic stroke. PMID:28130468

  5. Yin-Yang of costimulation: crucial controls of immune tolerance and function

    PubMed Central

    Nurieva, Roza I.; Liu, Xikui; Dong, Chen

    2010-01-01

    Summary In addition to signals from the T cell receptor complex, it has been recognized for many years that a “second” signal, most notably from CD28, is also important in T cell activation. In the recent years, many new members of CD28 family as well as the molecules that are share structural homology to CD28 ligands CD80 and CD86 have been discovered. Interestingly, some of these proteins function to dampen T cell activation and regulate the induction of T cell tolerance. Therefore, positive and negative costimulation are the two sides of the coin to fine tune T cell receptor signaling to determine the outcome of T cell receptor engagement- tolerance vs. function. PMID:19426216

  6. Integrating metabolic performance, thermal tolerance, and plasticity enables for more accurate predictions on species vulnerability to acute and chronic effects of global warming.

    PubMed

    Magozzi, Sarah; Calosi, Piero

    2015-01-01

    Predicting species vulnerability to global warming requires a comprehensive, mechanistic understanding of sublethal and lethal thermal tolerances. To date, however, most studies investigating species physiological responses to increasing temperature have focused on the underlying physiological traits of either acute or chronic tolerance in isolation. Here we propose an integrative, synthetic approach including the investigation of multiple physiological traits (metabolic performance and thermal tolerance), and their plasticity, to provide more accurate and balanced predictions on species and assemblage vulnerability to both acute and chronic effects of global warming. We applied this approach to more accurately elucidate relative species vulnerability to warming within an assemblage of six caridean prawns occurring in the same geographic, hence macroclimatic, region, but living in different thermal habitats. Prawns were exposed to four incubation temperatures (10, 15, 20 and 25 °C) for 7 days, their metabolic rates and upper thermal limits were measured, and plasticity was calculated according to the concept of Reaction Norms, as well as Q10 for metabolism. Compared to species occupying narrower/more stable thermal niches, species inhabiting broader/more variable thermal environments (including the invasive Palaemon macrodactylus) are likely to be less vulnerable to extreme acute thermal events as a result of their higher upper thermal limits. Nevertheless, they may be at greater risk from chronic exposure to warming due to the greater metabolic costs they incur. Indeed, a trade-off between acute and chronic tolerance was apparent in the assemblage investigated. However, the invasive species P. macrodactylus represents an exception to this pattern, showing elevated thermal limits and plasticity of these limits, as well as a high metabolic control. In general, integrating multiple proxies for species physiological acute and chronic responses to increasing

  7. Switch Function and Pathological Dissociation in Acute Psychiatric Inpatients

    PubMed Central

    Chiu, Chui-De; Tseng, Mei-Chih Meg; Chien, Yi-Ling; Liao, Shih-Cheng; Liu, Chih-Min; Yeh, Yei-Yu; Hwu, Hai-Gwo

    2016-01-01

    Swift switching, along with atypical ability on updating and inhibition, has been found in non-clinical dissociators. However, whether swift switching is a cognitive endophenotype that intertwines with traumatisation and pathological dissociation remains unknown. Unspecified acute psychiatric patients were recruited to verify a hypothesis that pathological dissociation is associated with swift switching and traumatisation may explain this relationship. Behavioural measures of intellectual function and three executive functions including updating, switching and inhibition were administered, together with standardised scales to evaluate pathological dissociation and traumatisation. Our results showed superior control ability on switching and updating in inpatients who displayed more symptoms of pathological dissociation. When all three executive functions were entered as predictors, in addition to intellectual quotient and demographic variables to regress upon pathological dissociation, switching rather than updating remained the significant predictor. Importantly, the relationship between pathological dissociation and switching became non-significant when the effect of childhood trauma were controlled. The results support a trauma-related switching hypothesis which postulates swift switching as a cognitive endophenotype of pathological dissociation; traumatisation in childhood may explain the importance of swift switching. PMID:27123578

  8. Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging.

    PubMed

    Thambisetty, Madhav; Beason-Held, Lori L; An, Yang; Kraut, Michael; Metter, Jeffrey; Egan, Josephine; Ferrucci, Luigi; O'Brien, Richard; Resnick, Susan M

    2013-10-01

    We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent serial (15)O-water positron emission tomography scans (age at first scan, 69.6 ± 7.5 years) and oral glucose tolerance tests 12 years earlier (age at first oral glucose tolerance test, 57.2 ± 11.1 years). Using voxel-based analysis, we compared changes in rCBF over an 8-year period between 15 participants with IGT in midlife and 49 with NGT. Significant differences were observed in longitudinal change in rCBF between the IGT and NGT groups. The predominant pattern was greater rCBF decline in the IGT group in the frontal, parietal, and temporal cortices. Some brain regions in the frontal and temporal cortices also showed greater longitudinal increments in rCBF in the IGT group. Our findings suggest that IGT in midlife is associated with subsequent longitudinal changes in brain function during aging even in cognitively normal older individuals.

  9. Advances in functional genomics for investigating salinity stress tolerance mechanisms in cereals

    PubMed Central

    Shelden, Megan C.; Roessner, Ute

    2013-01-01

    Abiotic stresses such as low water availability and high salinity are major causes of cereal crop yield losses and significantly impact on sustainability. Wheat and barley are two of the most important cereal crops (after maize and rice) and are grown in increasingly hostile environments with soil salinity and drought both expected to increase this century, reducing the availability of arable land. Barley and wheat are classified as glycophytes (salt-sensitive), yet they are more salt-tolerant than other cereal crops such as rice and so are good models for studying salt tolerance in cereals. The exploitation of genetic variation of phenotypic traits through plant breeding could significantly improve growth of cereals in salinity-affected regions, thus leading to improved crop yields. Genetic variation in phenotypic traits for abiotic stress tolerance have been identified in land races and wild germplasm but the molecular basis of these differences is often difficult to determine due to the complex genetic nature of these species. High-throughput functional genomics technologies, such as transcriptomics, metabolomics, proteomics, and ionomics are powerful tools for investigating the molecular responses of plants to abiotic stress. The advancement of these technologies has allowed for the identification and quantification of transcript/metabolites in specific cell types and/or tissues. Using these new technologies on plants will provide a powerful tool to uncovering genetic traits in more complex species such as wheat and barley and provide novel insights into the molecular mechanisms of salinity stress tolerance. PMID:23717314

  10. Effects of acute NH3 air pollution on N-sensitive and N-tolerant lichen species.

    PubMed

    Paoli, Luca; Maslaňáková, Ivana; Grassi, Alice; Bačkor, Martin; Loppi, Stefano

    2015-12-01

    Lichens are sensitive to the presence of ammonia (NH3) in the environment. However, in order to use them as reliable indicators in biomonitoring studies, it is necessary to establish unequivocally the occurrence of certain symptoms following the exposure to NH3 in the environment. In this paper, we simulated an episode of acute air pollution due to the release of NH3. The biological effects of acute air pollution by atmospheric NH3 have been investigated using N-sensitive (Flavoparmelia caperata) and N-tolerant (Xanthoria parietina) species. Lichen samples were exposed to ecologically relevant NH3 concentrations for 8 weeks, simulating three areas of impact: a control area (2 μg/m(3)), an area of intermediate impact (2-35 μg/m(3)) and an area of high impact (10-315 μg/m(3)), with a peak of pollution reached between the fourth and fifth week. Ammonia affected both the photobiont and the mycobiont in F. caperata, while in X. parietina only the photosynthetic performance of the photobiont was altered after exposure to the highest concentration. In the photobiont of F. caperata we recorded chlorophyll degradation as indicated by OD435/415 ratio, decrease of the photosynthetic performance (as reflected by the maximum quantum yield of primary photochemistry FV/FM and the performance index PIABS); in the mycobiont, ergosterol reduction, membrane lipid peroxidation (as reflected by the increase of thiobarbituric acid reactive substances), alteration (decrease) of the secondary metabolite usnic acid. No effects were detected on caperatic acid and dehydrogenase activity. In X. parietina, the only signal determined by NH3 was the alteration of FV/FM and the performance index PIABS. The results suggest that physiological parameters in N-sensitive lichens well reflect the effects of NH3 exposure and can be applied as early indicators in monitoring studies.

  11. Carbohydrate and carbon metabolite accumulation responses in leaves of ozone tolerant and ozone susceptible spinach plants after acute ozone exposure.

    PubMed

    Robinson, J M; Rowland, R A

    1996-11-01

    The objective of this study was to determine whether exposure of plants to ozone (O3) increased the foliar levels of glucose, glucose sources, e.g., sucrose and starch, and glucose-6-phosphate (G6P), because in leaf cells, glucose is the precursor of the antioxidant, L-ascorbate, and glucose-6-phosphate is a source of NADPH needed to support antioxidant capacity. A further objective was to establish whether the response of increased levels of glucose, sucrose, starch and G6P in leaves could be correlated with a greater degree of plant tolerance to O3. Four commercially available Spinacia oleracea varieties were screened for tolerance or susceptibility to detrimental effects of O3 employing one 6.5 hour acute exposure to 25O nL O3 L(-1) air during the light. One day after the termination of ozonation (29 d post emergence), leaves of the plants were monitored both for damage and for gas exchange characteristics. Cultivar Winter Bloomsdale (cv Winter) leaves were least damaged on a quantitative grading scale. The leaves of cv Nordic, the most susceptible, were approximately 2.5 times more damaged. Photosynthesis (Pn) rates in the ozonated mature leaves of cv Winter were 48.9% less, and in cv Nordic, 66.2% less than in comparable leaves of their non-ozonated controls. Stomatal conductance of leaves of ozonated plants was found not to be a factor in the lower Pn rates in the ozonated plants. At some time points in the light, leaves of ozonated cv Winter plants had significantly higher levels of glucose, sucrose, starch, G6P, G1P, pyruvate and malate than did leaves of ozonated cv Nordic plants. It was concluded that leaves of cv Winter displayed a higher tolerance to ozone mediated stress than those of cv Nordic, in part because they had higher levels of glucose and G6P that could be mobilized during diminished photosynthesis to generate antioxidants (e.g., ascorbate) and reductants (e.g., NADPH). Elevated levels of both pyruvate and malate in the leaves of ozonated cv

  12. Acute hypoxia up-regulates HIF-1α and VEGF mRNA levels in Amazon hypoxia-tolerant Oscar (Astronotus ocellatus).

    PubMed

    Baptista, R B; Souza-Castro, N; Almeida-Val, V M F

    2016-10-01

    Amazon fish maintain oxygen uptake through a variety of strategies considered evolutionary and adaptive responses to the low water oxygen saturation, commonly found in Amazon waters. Oscar (Astronotus ocellatus) is among the most hypoxia-tolerant fish in Amazon, considering its intriguing anaerobic capacity and ability to depress oxidative metabolism. Previous studies in hypoxia-tolerant and non-tolerant fish have shown that hypoxia-inducible factor-1α (HIF-1α) gene expression is positively regulated during low oxygen exposure, affecting vascular endothelial growth factor (VEGF) transcription and fish development or tolerance in different manners. However, whether similar isoforms exists in tolerant Amazon fish and whether they are affected similarly to others physiological responses to improve hypoxia tolerance remain unknown. Here we evaluate the hepatic HIF-1α and VEGF mRNA levels after 3 h of acute hypoxia exposure (0.5 mgO2/l) and 3 h of post-hypoxia recovery. Additionally, hematological parameters and oxidative enzyme activities of citrate synthase (CS) and malate dehydrogenase (MDH) were analyzed in muscle and liver tissues. Overall, three sets of responses were detected: (1) as expected, hematocrit, hemoglobin concentration, red blood cells, and blood glucose increased, improving oxygen carrying capacity and glycolysis potential; (2) oxidative enzymes from liver decreased, corroborating the tendency to a widespread metabolic suppression; and (3) HIF-1α and VEGF increased mRNA levels in liver, revealing their role in the oxygen homeostasis through, respectively, activation of target genes and vascularization. This is the first study to investigate a hypoxia-related transcription factor in a representative Amazon hypoxia-tolerant fish and suggests that HIF-1α and VEGF mRNA regulation have an important role in enhancing hypoxia tolerance in extreme tolerant species.

  13. CO2-O2 Interactions in Extension of Tolerance to Acute Hypoxia

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Gelfand, R.

    1996-01-01

    Advantageous and/or detrimental influences associated with purposeful deviations from atmospheric levels of O2 and CO2 are studied. Specific goals have been directed to simulating situations of emergency or accidental exposure to hypoxic (10% O2) environments. They included establishing dynamic effects of hypoxia with and without CO2 (rate of acute adaptation), and stable-state (equilibrium) effects on blood and brain oxygenation. They also included effects on the physiological parameters of respiration and blood gas composition which underlie brain oxygenation. For 10% O2, a complete experiment consisted of three identical rest-exercise phases of 32 minutes duration. Following a five minute air control period, each inspired gas was administered over the next 27 minutes. The test gases were room air control, 10% +/- 0.1% O2 with 4% +/- 0.1% CO2, and 10% +/- 0.1% O2. A minimum of 45 minutes separated each phase. Relative to inspiration of 10% O2, brain oxygenation is enhanced by addition of 4% CO2. This is accomplished by increasing the rate at which O2 in arterial blood is supplied to the brain circulation (well above even the normoxic level), and on relative improvement in the arterial pressure of O2.

  14. Suppressed neutrophil function in children with acute lymphoblastic leukemia.

    PubMed

    Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

    2009-10-01

    Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

  15. Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance

    PubMed Central

    Balza, E; Piccioli, P; Carta, S; Lavieri, R; Gattorno, M; Semino, C; Castellani, P; Rubartelli, A

    2016-01-01

    Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions. PMID:27441656

  16. Splenic CD11clowCD45RBhigh dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure

    PubMed Central

    Zhang, Sai-Nan; Yang, Nai-Bin; Ni, Shun-Lan; Dong, Jin-Zhong; Shi, Chun-Wei; Li, Shan-Shan; Zhang, Sheng-Guo; Tang, Xin-Yue; Lu, Ming-Qin

    2016-01-01

    Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF. PMID:27625297

  17. Feasibility of early functional rehabilitation in acute stroke survivors using the Balance-Bed—a technology that emulates microgravity

    PubMed Central

    Oddsson, Lars I. E.; Finkelstein, Marsha J.; Meissner, Sarah

    2015-01-01

    Evidence-based guidelines recommend early functional rehabilitation of stroke patients when risk of patient harm can be managed. Current tools do not allow balance training under load conditions sufficiently low for acute stroke patients. This single-arm pilot study tested feasibility and safety for acute stroke survivors to use “Balance-Bed”, a technology for balance exercises in supine initially developed to emulate microgravity effects on balance. Nine acute stroke patients (50–79 years) participated in 3–10 sessions over 16–46 days as part of their rehabilitation in a hospital inpatient setting. Standard inpatient measures of outcome were monitored where lack of progress from admission to discharge might indicate possible harm. Total FIM scores at admission (median 40, range 22–53) changed to (74, 50–96), Motor FIM scores from (23, 13–32) to (50, 32–68) and Berg Balance scores from (3, 0–6) to (19, 7–43) at discharge. Changes reached Minimal Clinical Important Difference for a sufficient proportion (>0.6) of the patients to indicate no harm to the patients. In addition, therapists reported the technology was safe, provided a positive experience for the patient and fit within the rehabilitation program. They reported the device should be easier to set up and exit. We conclude acute stroke patients tolerated Balance-Bed exercises such as standing on one or two legs, squats, stepping in place as well as balance perturbations provided by the therapist. We believe this is the first time it has been demonstrated that acute stroke patients can safely perform whole body balance training including balance perturbations as part of their rehabilitation program. Future studies should include a control group and compare outcomes from best practices to interventions using the Balance-Bed. In addition, the technology is relevant for countermeasure development for spaceflight and as a test-bed of balance function under microgravity-like conditions. PMID

  18. Structural and Functional Analysis of Transmembrane Segment IV of the Salt Tolerance Protein Sod2*

    PubMed Central

    Ullah, Asad; Kemp, Grant; Lee, Brian; Alves, Claudia; Young, Howard; Sykes, Brian D.; Fliegel, Larry

    2013-01-01

    Sod2 is the plasma membrane Na+/H+ exchanger of the fission yeast Schizosaccharomyces pombe. It provides salt tolerance by removing excess intracellular sodium (or lithium) in exchange for protons. We examined the role of amino acid residues of transmembrane segment IV (TM IV) (126FPQINFLGSLLIAGCITSTDPVLSALI152) in activity by using alanine scanning mutagenesis and examining salt tolerance in sod2-deficient S. pombe. Two amino acids were critical for function. Mutations T144A and V147A resulted in defective proteins that did not confer salt tolerance when reintroduced into S. pombe. Sod2 protein with other alanine mutations in TM IV had little or no effect. T144D and T144K mutant proteins were inactive; however, a T144S protein was functional and provided lithium, but not sodium, tolerance and transport. Analysis of sensitivity to trypsin indicated that the mutations caused a conformational change in the Sod2 protein. We expressed and purified TM IV (amino acids 125–154). NMR analysis yielded a model with two helical regions (amino acids 128–142 and 147–154) separated by an unwound region (amino acids 143–146). Molecular modeling of the entire Sod2 protein suggested that TM IV has a structure similar to that deduced by NMR analysis and an overall structure similar to that of Escherichia coli NhaA. TM IV of Sod2 has similarities to TM V of the Zygosaccharomyces rouxii Na+/H+ exchanger and TM VI of isoform 1 of mammalian Na+/H+ exchanger. TM IV of Sod2 is critical to transport and may be involved in cation binding or conformational changes of the protein. PMID:23836910

  19. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

    2012-01-01

    Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

  20. Development of tolerance to the inhibitory effects of ethanol in the rat isolated vas deferens: effect of acute and chronic ethanol administration in vivo.

    PubMed Central

    DeTurck, K. H.; Pohorecky, L. A.

    1986-01-01

    Contractions of the rat vas deferens elicited by the addition of noradrenaline (NA), K+-depolarizing solutions or by electrical stimulation were recorded before and after incubation with ethanol 181 mM. In tissues from untreated rats, the contractions were inhibited 40-50% by such exposure. Injection of ethanol (2 g kg-1) significantly attenuated ethanol's reduction of peak tension generated by the lowest concentration of NA (10(-4) mM). Chronic administration of ethanol, 18-14 g kg-1 daily for two weeks, resulted in significant tolerance to ethanol. Tissues of treated animals demonstrated ethanol-induced decreases of roughly one-half those of the maltose dextrin (isocaloric) and water (fluid control) groups. This tolerance persisted for at least 48 h after ethanol treatment had been terminated. Overall, the data suggest that ethanol acts both pre- and postsynaptically to produce acute inhibition of smooth muscle contractions or tolerance to these actions upon chronic exposure. PMID:3730699

  1. Plant glutathione transferase-mediated stress tolerance: functions and biotechnological applications.

    PubMed

    Nianiou-Obeidat, Irini; Madesis, Panagiotis; Kissoudis, Christos; Voulgari, Georgia; Chronopoulou, Evangelia; Tsaftaris, Athanasios; Labrou, Nikolaos E

    2017-04-08

    Plant glutathione transferases (EC 2.5.1.18, GSTs) are an ancient, multimember and diverse enzyme class. Plant GSTs have diverse roles in plant development, endogenous metabolism, stress tolerance, and xenobiotic detoxification. Their study embodies both fundamental aspects and agricultural interest, because of their ability to confer tolerance against biotic and abiotic stresses and to detoxify herbicides. Here we review the biotechnological applications of GSTs towards developing plants that are resistant to biotic and abiotic stresses. We integrate recent discoveries, highlight, and critically discuss the underlying biochemical and molecular pathways involved. We elaborate that the functions of GSTs in abiotic and biotic stress adaptation are potentially a result of both catalytic and non-catalytic functions. These include conjugation of reactive electrophile species with glutathione and the modulation of cellular redox status, biosynthesis, binding, and transport of secondary metabolites and hormones. Their major universal functions under stress underline the potential in developing climate-resilient cultivars through a combination of molecular and conventional breeding programs. We propose that future GST engineering efforts through rational and combinatorial approaches, would lead to the design of improved isoenzymes with purpose-designed catalytic activities and novel functional properties. Concurrent GST-GSH metabolic engineering can incrementally increase the effectiveness of GST biotechnological deployment.

  2. Prospective investigation of pituitary functions in patients with acute infectious meningitis: is acute meningitis induced pituitary dysfunction associated with autoimmunity?

    PubMed

    Tanriverdi, F; De Bellis, A; Teksahin, H; Alp, E; Bizzarro, A; Sinisi, A A; Bellastella, G; Paglionico, V A; Bellastella, A; Unluhizarci, K; Doganay, M; Kelestimur, F

    2012-12-01

    Previous case reports and retrospective studies suggest that pituitary dysfunction may occur after acute bacterial or viral meningitis. In this prospective study we assessed the pituitary functions, lipid profile and anthropometric measures in adults with acute bacterial or viral meningitis. Moreover, in order to investigate whether autoimmune mechanisms could play a role in the pathogenesis of acute meningitis-induced hypopituitarism we also investigated the anti-pituitary antibodies (APA) and anti-hypothalamus antibodies (AHA) prospectively. Sixteen patients (10 males, 6 females; mean ± SD age 40.9 ± 15.9) with acute infectious meningitis were included and the patients were evaluated in the acute phase, and at 6 and 12 months after the acute meningitis. In the acute phase 18.7% of the patients had GH deficiency, 12.5% had ACTH and FSH/LH deficiencies. At 12 months after acute meningitis 6 of 14 patients (42.8%) had GH deficiency, 1 of 14 patients (7.1%) had ACTH and FSH/LH deficiencies. Two of 14 patients (14.3%) had combined hormone deficiencies and four patients (28.6%) had isolated hormone deficiencies at 12 months. Four of 9 (44.4%) hormone deficiencies at 6 months were recovered at 12 months, and 3 of 8 (37.5%) hormone deficiencies at 12 months were new-onset hormone deficiencies. At 12 months there were significant negative correlations between IGF-I level vs. LDL-C, and IGF-I level vs. total cholesterol. The frequency of AHA and APA positivity was substantially high, ranging from 35 to 50% of the patients throughout the 12 months period. However there were no significant correlations between AHA or APA positivity and hypopituitarism. The risk of hypopituitarism, GH deficiency in particular, is substantially high in the acute phase, after 6 and 12 months of the acute infectious meningitis. Moreover we found that 6th month after meningitis is too early to make a decision for pituitary dysfunction and these patients should be screened for at least 12 months

  3. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts.

    PubMed

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-07-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine.

  4. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts

    PubMed Central

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-01-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine. PMID:25903472

  5. Impairment of striatal mitochondrial function by acute paraquat poisoning.

    PubMed

    Czerniczyniec, Analía; Lanza, E M; Karadayian, A G; Bustamante, J; Lores-Arnaiz, S

    2015-10-01

    Mitochondria are essential for survival. Their primary function is to support aerobic respiration and to provide energy for intracellular metabolic pathways. Paraquat is a redox cycling agent capable of generating reactive oxygen species. The aim of the present study was to evaluate changes in cortical and striatal mitochondrial function in an experimental model of acute paraquat toxicity and to compare if the brain areas and the molecular mechanisms involved were similar to those observed after chronic exposure. Sprague-Dawley rats received paraquat (25 mg/Kg i.p.) or saline and were sacrificed after 24 h. Paraquat treatment decreased complex I and IV activity by 37 and 21 % respectively in striatal mitochondria. Paraquat inhibited striatal state 4 and state 3 KCN-sensitive respiration by 80 % and 62 % respectively, indicating a direct effect on respiratory chain. An increase of 2.2 fold in state 4 and 2.3 fold in state 3 in KCN-insensitive respiration was observed in striatal mitochondria from paraquat animals, suggesting that paraquat redox cycling also consumed oxygen. Paraquat treatment increased hydrogen peroxide production (150 %), TBARS production (42 %) and cardiolipin oxidation/depletion (12 %) in striatal mitochondria. Also, changes in mitochondrial polarization was induced after paraquat treatment. However, no changes were observed in any of these parameters in cortical mitochondria from paraquat treated-animals. These results suggest that paraquat treatment induced a clear striatal mitochondrial dysfunction due to both paraquat redox cycling reactions and impairment of the mitochondrial electron transport, causing oxidative damage. As a consequence, mitochondrial dysfunction could probably lead to alterations in cellular bioenergetics.

  6. Functional interaction and cross-tolerance between ethanol and Δ9-THC: possible modulation by mouse cerebellar adenosinergic A1/GABAergic-A receptors.

    PubMed

    Dar, M Saeed

    2014-08-15

    We have previously shown a functional motor interaction between ethanol and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) that involved cerebellar adenosinergic A1 and GABAergic A receptor modulation. We now report the development of cross-tolerance between intracerebellar Δ(9)-THC and intraperitoneal ethanol using ataxia as the test response in male CD-1 mice. The drugs [Δ(9)-THC (20 μg), N(6)-cyclohexyladenosine, CHA (12 ng), muscimol (20 ng)] used in the study were directly microinfused stereotaxically via guide cannulas into the cerebellum except ethanol. Δ(9)-THC, infused once daily for 5 days followed 16 h after the last infusion by acute ethanol (2g/kg) and Rotorod evaluation, virtually abolished ethanol ataxia indicating development of cross-tolerance. The cross-tolerance was also observed when the order of ethanol and Δ(9)-THC treatment was reversed, i.e., ethanol injected once daily for 5 days followed 16 h after the last ethanol injection by Δ(9)-THC infusion. The cross-tolerance appeared within 24-48 h, lasted over 72 h and was maximal in 5-day ethanol/Δ(9)-THC-treated animals. Finally, tolerance in chronic ethanol/Δ(9)-THC/-treated animals developed not only to ethanol/Δ(9)-THC-induced ataxia, respectively, but also to the ataxia potentiating effect of CHA and muscimol, indicating modulation by cerebellar adenosinergic A1 and GABAA receptors. A practical implication of these results could be that marijuana smokers may experience little or no negative effects such as ataxia following alcohol consumption. Clinically, such antagonism of ethanol-induced ataxia can be observed in marijuana users thereby encouraging more alcohol consumption and thus may represent a risk factor for the development of alcoholism in this segment of population.

  7. Functional Characterization of a Gene in Sedum alfredii Hance Resembling Rubber Elongation Factor Endowed with Functions Associated with Cadmium Tolerance

    PubMed Central

    Liu, Mingying; Qiu, Wenming; He, Xuelian; Zheng, Liu; Song, Xixi; Han, Xiaojiao; Jiang, Jing; Qiao, Guirong; Sang, Jian; Liu, Mingqing; Zhuo, Renying

    2016-01-01

    Cadmium is a major toxic heavy-metal pollutant considering their bioaccumulation potential and persistence in the environment. The hyperaccumulating ecotype of Sedum alfredii Hance is a Zn/Cd co-hyperaccumulator inhabiting in a region of China with soils rich in Pb/Zn. Investigations into the underlying molecular regulatory mechanisms of Cd tolerance are of substantial interest. Here, library screening for genes related to cadmium tolerance identified a gene resembling the rubber elongation factor gene designated as SaREFl. The heterologous expression of SaREFl rescued the growth of a transformed Cd-sensitive strain (ycf1). Furthermore, SaREFl-expressing Arabidopsis plants were more tolerant to cadmium stress compared with wild type by measuring parameters of root length, fresh weight and physiological indexes. When under four different heavy metal treatments, we found that SaREFl responded most strongly to Cd and the root was the plant organ most sensitive to this heavy metal. Yeast two-hybrid screening of SaREFl as a bait led to the identification of five possible interacting targets in Sedum alfredii Hance. Among them, a gene annotated as prenylated Rab acceptor 1 (PRA1) domain protein was detected with a high frequency. Moreover, subcellular localization of SaREF1-GFP fusion protein revealed some patchy spots in cytosol suggesting potential association with organelles for its cellular functions. Our findings would further enrich the connotation of REF-like genes and provide theoretical assistance for the application in breeding heavy metal-tolerant plants. PMID:27446189

  8. Thioetherification of chloroheteroarenes: a binuclear catalyst promotes wide scope and high functional-group tolerance.

    PubMed

    Platon, Mélanie; Wijaya, Novi; Rampazzi, Vincent; Cui, Luchao; Rousselin, Yoann; Saeys, Mark; Hierso, Jean-Cyrille

    2014-09-22

    A constrained binuclear palladium catalyst system affords selective thioetherification of a wide range of functionalized arenethiols with chloroheteroaromatic partners with the highest turnover numbers (TONs) reported to date and tolerates a large variety of reactive functions. The scope of this system includes the coupling of thiophenols with six- and five-membered 2-chloroheteroarenes (i.e., functionalized pyridine, pyrazine, quinoline, pyrimidine, furane, and thiazole) and 3-bromoheteroarenes (i.e., pyridine and furane). Electron-rich congested thiophenols and fluorinated thiophenols are also suitable partners. The coupling of unprotected amino-2-chloropyridines with thiophenol and the successful employment of synthetically valuable chlorothiophenols are described with the same catalyst system. DFT studies attribute the high performance of this binuclear palladium catalyst to the decreased stability of thiolate-containing resting states. Palladium loading was as low as 0.2 mol %, which is important for industrial application and is a step forward in solving catalyst activation/deactivation problems.

  9. Preliminary data on ASP2215: tolerability and efficacy in acute myeloid leukemia patients.

    PubMed

    Thom, Claire

    2015-09-01

    Claire Thom speaks to Gemma Westcott, Commissioning Editor: Claire Thom joined Astellas in 2013 as the Therapeutic Area Head for Oncology in Global Development. In that role, she also serves as the STAR leader for Oncology for Astellas. Prior to Astellas, she spent 12 years with Takeda. Her last position was Senior Vice President, Portfolio Management, Drug Development Management and Medical Informatics and Strategic Operations within the Medical Division (the Division within Millennium responsible for oncology clinical drug development within Takeda). During her 4 years at Millennium, at various times, she had responsibility within the Medical Division for leading portfolio management, business operations (medical finance, annual and mid-range financial planning, space planning and operations, headcount resourcing, development goals process), clinical development operations (clinical operations, programming, data management, statistics, medical writing, clinical outsourcing), drug development management (project management), medical informatics (technology support for the division) and the strategic project management office for the division. Prior to joining Millennium, Claire Thom spent 18 months working in Osaka, Japan, during which she was responsible for developing the oncology strategy for Takeda that culminated in the acquisition of Millennium. Before going to Japan, she held positions of varying responsibility within the Takeda US development organization including the management of regulatory affairs, safety, biometrics and data management, clinical research and quality assurance. Claire Thom has particular expertise in organizational design and efficiency; she has successfully worked through integrations across multiple functions and redesigned business processes. She has a PharmD from University of Illinois (IL, USA) and over 20 years of pharmaceutical experience including positions in medical affairs and new product planning (over 11 years at Searle

  10. Functional Definition and Characterisation of Acute Traumatic Coagulopathy

    PubMed Central

    Davenport, Ross; Manson, Joanna; De’Ath, Henry; Platton, Sean; Coates, Amy; Allard, Shubha; Hart, Daniel; Pearse, Rupert; Pasi, K. John; MacCallum, Peter; Stanworth, Simon; Brohi, Karim

    2011-01-01

    Objective To identify an appropriate diagnostic tool for the early diagnosis of Acute Traumatic Coagulopathy (ATC) and validate this modality through prediction of transfusion requirements in trauma hemorrhage. Design Prospective observational cohort study Setting Level 1 trauma centre Patients Adult trauma patients who met the local criteria for full trauma team activation. Exclusion criteria included emergency department (ED) arrival >2 hours after injury, >2000ml of intravenous fluid before ED arrival or transfer from another hospital. Interventions None Measurements Blood was collected on arrival in ED and analysed with laboratory prothrombin time (PT), point of care (PoC) PT and rotational thromboelastometry (ROTEM). Prothrombin ratio (PTr) was calculated and ATC defined as laboratory PTr>1.2. Transfusion requirements were recorded for the first 12 hours following admission. Main Results 300 patients were included in the study. Laboratory PT results were available at median 78 (62-103) minutes. PoC PTr had reduced agreement with laboratory PTr in patients with ATC, with 29% false negative results. In ATC the ROTEM Clot Amplitude at 5 minutes (CA5) was diminished by 42% and this persisted throughout clot maturation. ROTEM clotting time was not significantly prolonged. A CA5 threshold ≤35mm had a detection rate of 77% for ATC with a false positive rate of 13%. Patients with CA5 ≤35mm were more likely to receive red cell (46% vs 17%, p<0.001) and plasma (37% vs 11%, p<0.001) transfusions. The CA5 could identify patients who would require massive transfusion (detection rate of 71%, vs 43% for PTr >1.2, p<0.001). Conclusions In trauma hemorrhage PTr is not rapidly available from the laboratory and PoC devices can be inaccurate. ATC is functionally characterised by a reduction in clot strength. With a threshold of CA5 ≤35mm ROTEM can identify ATC at 5 minutes and predict the need for massive transfusion. PMID:21765358

  11. Acute Toluene Exposure alters expression of genes associated with synaptic structure and function

    EPA Science Inventory

    Toluene (TOL), a volatile organic compound, is a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several potential modes of action in the CNS have been proposed. Therefore, the genomic response to acute TOL...

  12. Acute functional reactivation of the language network during awake intraoperative brain mapping.

    PubMed

    Spena, Giannantonio; Costi, Emanuele; Panciani, Pier Paolo; Roca, Elena; Migliorati, Karol; Fontanella, Marco Maria

    2015-01-01

    Acute brain plasticity during resection of central lesions has been recently described. In the cases reported, perilesional latent networks, useful to preserve the neurological functions, were detected in asymptomatic patients. In this paper, we presented a case of acute functional reactivation (AFR) of the language network in a symptomatic patient. Tumor resection allowed to acutely restore the neurological deficit. Intraoperative direct cortical stimulation (DCS) and functional neuroimaging showed new epicentres of activation of the language network after tumor excision. DCS in awake surgery is mandatory to reveal AFR needful to improve the extent of resection preserving the quality of life.

  13. Hyperlipidemia Alters Regulatory T Cell Function and Promotes Resistance to Tolerance Induction Through Costimulatory Molecule Blockade

    PubMed Central

    Bagley, J.; Yuan, J.; Chandrakar, A.; Iacomini, J.

    2016-01-01

    Recent work from our laboratory has shown that hyperlipidemia promotes accelerated rejection of vascularized cardiac allografts in mice by inducing anti-donor Th17 reactivity and production of IL-17. Here, we show that hyperlipidemia also affects FoxP3+ regulatory T cells (Tregs). Hyperlipidemia promotes the development of Tregs that express low levels of CD25. Hyperlipidemia also promotes a decrease in central Tregs and an increase in effector Tregs that appears to account for the increase in the frequency of CD25low Tregs. Alterations in Treg subsets also appear to lead to alterations in Treg function. The ability of FoxP3+, CD25high, CD4+ Tregs from hyperlipidemic mice to inhibit proliferation of effector T cells stimulated with anti-CD3 and CD28 was reduced when compared with Tregs from control mice. Regulatory T cells isolated from hyperlipidemic recipients exhibit increased activation of Akt, and a reduction in Bim levels that permits the expansion of FoxP3+CD25lowCD4+ T cells. Hyperlipidemic mice were also resistant to tolerance induction using costimulatory molecule blockade consisting of anti-CD154 and CTLA4Ig, a strategy that requires Tregs. Together, our data suggest that hyperlipidemia profoundly affects Treg subsets and function as well as the ability to induce tolerance. PMID:26079467

  14. Change in functional selectivity of morphine with the development of antinociceptive tolerance

    PubMed Central

    Macey, T A; Bobeck, E N; Suchland, K L; Morgan, M M; Ingram, S L

    2015-01-01

    BACKGROUND AND PURPOSE Opioids, such as morphine, are the most effective treatment for pain but their efficacy is diminished with the development of tolerance following repeated administration. Recently, we found that morphine activated ERK in opioid-tolerant but not in naïve rats, suggesting that morphine activation of μ-opioid receptors is altered following repeated morphine administration. Here, we have tested the hypothesis that μ-opioid receptor activation of ERK in the ventrolateral periaqueductal gray (vlPAG) is dependent on dynamin, a protein implicated in receptor endocytosis. EXPERIMENTAL APPROACH Rats were made tolerant to repeated microinjections of morphine into the vlPAG. The effects of dynamin on ERK activation and antinociception were assessed by microinjecting myristoylated dominant-negative dynamin peptide (Dyn-DN) or a scrambled control peptide into the vlPAG. Microinjection of a fluorescent dermorphin analogue (DERM-A594) into the vlPAG was used to monitor μ-opioid receptor internalization. KEY RESULTS Morphine did not activate ERK and Dyn-DN administration had no effect on morphine-induced antinociception in saline-pretreated rats. In contrast, morphine-induced ERK activation in morphine-pretreated rats that was blocked by Dyn-DN administration. Dyn-DN also inhibited morphine antinociception. Finally, morphine reduced DERM-A594 internalization only in morphine-tolerant rats indicating that μ-opioid receptors were internalized and unavailable to bind DERM-A594. CONCLUSIONS AND IMPLICATIONS Repeated morphine administration increased μ-opioid receptor activation of ERK signalling via a dynamin-dependent mechanism. These results demonstrate that the balance of agonist signalling to G-protein and dynamin-dependent pathways is altered, effectively changing the functional selectivity of the agonist-receptor complex. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other

  15. Diabetes, impaired glucose tolerance, and metabolic biomarkers in individuals with normal glucose tolerance are inversely associated with lung function: the Jackson Heart Study.

    PubMed

    Hickson, DeMarc A; Burchfiel, Cecil M; Liu, Jiankang; Petrini, Marcy F; Harrison, Kimystian; White, Wendy B; Sarpong, Daniel F

    2011-08-01

    The objectives of this study were to test the hypothesis that diabetes and impaired glucose tolerance (IGT), diabetes control and diabetes duration, and metabolic biomarkers in adults with normal glucose tolerance (NGT) are inversely associated with spirometry-measured lung function. We conducted a cross-sectional observational cohort study that included nonsmoking African American adults (n = 2,945; mean age = 52.5 ± 12.6 years; 69.2% female), who were free of cardiovascular disease, from the Jackson Heart Study. The interventions were diabetes, metabolic biomarkers and lung function. We measured the associations of glycemia with forced expiratory volume (FEV) in 1 s, FEV in 6 s, and vital capacity. Multivariable adjusted mean lung function values were lower among adults with diabetes and IGT (in women only, but not after adjustment for waist circumference) than adults with NGT. Among adults with diabetes, no associations were observed between lung function and diabetes control or duration. In women with NGT, lower lung function was consistently associated with higher glucose levels and less consistently with higher insulin levels and insulin resistance. Lower lung function was consistently associated with higher insulin levels and insulin resistance and less consistently associated with insulin and hemoglobin A1c in men with NGT. Overall, our findings generally support the hypothesis that diabetes, IGT, and increased levels of metabolic biomarkers in individuals with NGT are inversely associated with lung function in African Americans, independent of adiposity.

  16. The expressed protein in glyphosate-tolerant soybean, 5-enolpyruvylshikimate-3-phosphate synthase from Agrobacterium sp. strain CP4, is rapidly digested in vitro and is not toxic to acutely gavaged mice.

    PubMed

    Harrison, L A; Bailey, M R; Naylor, M W; Ream, J E; Hammond, B G; Nida, D L; Burnette, B L; Nickson, T E; Mitsky, T A; Taylor, M L; Fuchs, R L; Padgette, S R

    1996-03-01

    The safety of 5-enolpyruvylshikimate-3-phosphate synthase enzyme derived from Agrobacterium sp. strain CP4 (CP4 EPSPS) was assessed. CP4 EPSPS is the only protein introduced by genetic manipulation that is expressed in glyphosate-tolerant soybeans, which are being developed to provide new weed-control options for farmers. Expression of this protein in plants imparts high levels of glyphosate tolerance. The safety of CP4 EPSPS was ascertained by evaluating both physical and functional characteristics. CP4 EPSPS degrades readily in simulated gastric and intestinal fluids, suggesting that this protein will be degraded in the mammalian digestive tract upon ingestion as a component of food or feed, There were no deleterious effects due to the acute administration of CP4 EPSPS to mice by gavage at a high dosage of 572 mg/kg body wt, which exceeds 1000-fold tha anticipated consumption level of food products potentially containing CP4 EPSPS protein. CP4 EPSPS does not pose any important allergen concerns because this protein does not possess characteristics typical of allergenic proteins. These data, in combination with seed compositional analysis and animal feeding studies, support the conclusion that glyphosate-tolerant soybean are as safe and nutritious as traditional soybeans currently being marketed.

  17. Echo derived variables predicting exercise tolerance in patients with dilated and poorly functioning left ventricle

    PubMed Central

    Webb-Peploe, K; Henein, M; Coats, A; Gibson, D

    1998-01-01

    Objective—To determine whether resting echo derived measurements predict exercise tolerance and its interrelation with heart rate response and ventilation drive in patients with systolic left ventricular disease.
Design—Prospective echocardiographic examination followed by cardiopulmonary exercise testing.
Setting—A tertiary referral centre for cardiac diseases.
Subjects—21 patients (11 with coronary artery disease, 10 with idiopathic dilated cardiomyopathy) with end diastolic dimension > 6.4 cm, shortening fraction< 25%, and in sinus rhythm. There were 11 age matched normal controls.
Results—In the patients, peak oxygen consumption (mV̇O2) correlated with right ventricular long axis excursion (r = 0.62); 65% of the variance in mV̇O2 was predictable using a multivariate model with right ventricular long axis excursion and peak lengthening rate, and peak mitral atrial filling velocity as independent variables. Aetiology was not an independent predictor, although the right ventricular long axis excursion (mean (SD)) was greater in patients with idiopathic dilated cardiomyopathy than in those with coronary artery disease (2.4 (0.5) cm v 1.6 (0.5) cm, p < 0.001). Peak heart rate correlated with duration of mitral regurgitation (r = −0.52) and the slope of ventilation against CO2 production correlated with M mode isovolumic relaxation time (r = 0.61).
Conclusions—In patients with systolic left ventricular dysfunction, more than half the variance in exercise tolerance can be predicted by factors measured on echocardiography at rest, particularly right ventricular long axis excursion.

 Keywords: left ventricular function;  heart failure;  exercise tolerance;  echocardiography PMID:10065024

  18. Tissue-specific expression and functional role of dehydrins in heat tolerance of sugarcane (Saccharum officinarum).

    PubMed

    Galani, Saddia; Wahid, Abdul; Arshad, Muhammad

    2013-04-01

    Studies on the functional roles of dehydrins (DHNs) in heat tolerance of plants are scarce. This study was conducted to immunohistolocalize DHNs in leaves of heat-tolerant (CP-4333) and heat-sensitive (HSF-240) sugarcane (Saccharum officinarum L.) clones at three phenological stages in order to elucidate their putative roles under heat stress. CP-4333 indicated greater amounts of heat-stable proteins than HSF-240 under heat stress. Western blotting revealed the expression of three DHNs in CP-4333 (13- and 15-kDa peptides at 48 h and an additional 18-kDa band at 72 h) and two (13 and 15 kDa at 48 h) in HSF-240 at formative stage; two DHNs in CP-4333 (20 and 25 kDa) and one in HSF-240 (20 kDa) at grand growth stage, while two DHNs in CP-4333 (20 and 22 kDa) and one in HSF-240 (20 kDa) at maturity stage. Tissue-specific immunohistolocalization showed that DHNs were expressed in stele particularly the phloem and the cells intervening bundle sheath and vascular bundles. Furthermore, DHNs were also found scattered along the epidermal and parenchymatous cells. Recovery of sugarcane from heat stress manifested a gradual disappearance of DHNs in both the clones, being quicker in sensitive clone (HSF-240). Results suggested specific implications for DHNs synthesis. Their synthesis in epidermis appears to protect the mesophyll tissues from heat injury. When associated to vascular tissue, they tend to ensure the normal photoassimilate loading into the sieve element-companion cell complex. DHNs diminution during recovery suggested that their expression was transitory. However, prolonged retention of DHNs by tolerant clone appears to be an adaptive advantage of sugarcane to withstand heat stress.

  19. Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer.

    PubMed

    Labidi-Galy, Sana Intidhar; Sisirak, Vanja; Meeus, Pierre; Gobert, Michael; Treilleux, Isabelle; Bajard, Agathe; Combes, Jean-Damien; Faget, Julien; Mithieux, François; Cassignol, Alexandre; Tredan, Olivier; Durand, Isabelle; Ménétrier-Caux, Christine; Caux, Christophe; Blay, Jean-Yves; Ray-Coquard, Isabelle; Bendriss-Vermare, Nathalie

    2011-08-15

    In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patients. In the tumor and malignant ascites, CD4(+)CD123(+)BDCA2(+) pDC were the most abundant dendritic cell subset; however, they were profoundly depleted in peripheral blood. The presence of pDC in primary ovarian cancer, but not ascites, was an independent prognostic factor associated with early relapse. Following chemotherapy, we observed a partial restoration of blood pDC levels in patients in complete remission. These findings show preferential recruitment of pDC into tumors where they express a partially mature phenotype that may reflect an in situ activation. Importantly, compared with pDC found in ascites or blood, tumor-associated pDC (TApDC) produced less IFN-α, TNF-α, IL-6, macrophage inflammatory protein-1β, and RANTES in response to toll-like receptor stimulation, and alterations in pDC functions were mainly mediated through tumor-derived TNF-α and TGF-β. Unlike ascites-derived pDC, TApDC induced IL-10 production from allogeneic naive CD4(+) T lymphocytes, suggesting the existence of a paracrine immunosuppressive loop. Taken together, our findings indicate that both local and systemic dysfunction of pDC play a critical role in the progression of ovarian cancer via induction of immune tolerance.

  20. Acute presentations of renal artery stenosis in three patients with a solitary functioning kidney.

    PubMed

    Pun, E; Dowling, R J; Mitchell, P J

    2004-12-01

    Renal artery stenosis can present uncommonly in the acute state as flash pulmonary oedema and hypertensive encephalopathy. We present three such cases in patients with a solitary functioning kidney, with successful management via renal artery angioplasty and stent insertion.

  1. Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function

    SciTech Connect

    Taylor, A. Jr.; Akiya, F.; Gregory, M.C.

    1986-03-01

    A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A (99mTc)dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.

  2. The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster.

    PubMed

    Ogueta, Maite; Cibik, Osman; Eltrop, Rouven; Schneider, Andrea; Scholz, Henrike

    2010-11-01

    Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

  3. Percutaneous Access: Acute Effects on Renal Function and Structure in a Porcine Model

    NASA Astrophysics Data System (ADS)

    Handa, Rajash K.; Willis, Lynn R.; Evan, Andrew P.; Connors, Bret A.; Ying, Jun; Fat-Anthony, William; Wind, Kelli R.; Johnson, Cynthia D.; Blomgren, Philip M.; Estrada, Mark C.; Paterson, Ryan F.; Kuo, Ramsay L.; Kim, Samuel C.; Matlaga, Brian R.; Miller, Nicole L.; Watkins, Stephanie L.; Handa, Shelly E.; Lingeman, James E.

    2007-04-01

    Percutaneous nephrolithotomy (PCNL) involves gaining access into the urinary collecting system to remove kidney stones. Animal studies demonstrated that a reduction in renal filtration and perfusion in both kidneys, and a decline in tubular organic anion transport in the treated kidney characterizes the acute (hours) functional response to unilateral percutaneous access. The acute morphologic and histological changes in the treated kidney were consistent with blunt trauma and ischemia. Only tubular organic anion transport remained depressed during the late (3-day) response to the access procedure. Human studies revealed an acute decline in glomerular function and bilateral renal vasoconstriction following unilateral PCNL. Therefore, percutaneous access is not a benign procedure, but is associated with acute functional and structural derangements.

  4. Cardiac function and tolerance to ischemia–reperfusion injury in chronic kidney disease

    PubMed Central

    Kuczmarski, James M.; Martens, Christopher R.; Lennon-Edwards, Shannon L.; Edwards, David G.

    2014-01-01

    Background Cardiac dysfunction is an independent risk factor of ischemic heart disease and mortality in chronic kidney disease (CKD) patients, yet the relationship between impaired cardiac function and tolerance to ischemia–reperfusion (IR) injury in experimental CKD remains unclear. Methods Cardiac function was assessed in 5/6 ablation–infarction (AI) and sham male Sprague–Dawley rats at 20 weeks of age, 8 weeks post-surgery using an isolated working heart system. This included measures taken during manipulation of preload and afterload to produce left ventricular (LV) function curves as well as during reperfusion following a 15-min ischemic bout. In addition, LV tissue was used for biochemical tissue analysis. Results Cardiac function was impaired in AI animals during preload and afterload manipulations. Cardiac functional impairments persisted post-ischemia in the AI animals, and 36% of AI animals did not recover sufficiently to achieve aortic overflow following ischemia (versus 0% of sham animals). However, for those animals able to withstand the ischemic perturbation, no difference was observed in percent recovery of post-ischemic cardiac function between groups. Urinary NOx (nitrite + nitrate) excretion was lower in AI animals and accompanied by reduced LV endothelial nitric oxide synthase and NOx. LV antioxidants superoxide dismutase-1 and -2 were reduced in AI animals, whereas glutathione peroxidase-1/2 as well as NADPH-oxidase-4 and H2O2 were increased in these animals. Conclusions Impaired cardiac function appears to predispose AI rats to poor outcomes following short-duration ischemic insult. These findings could be, in part, mediated by increased oxidative stress via nitric oxide-dependent and -independent mechanisms. PMID:24151020

  5. Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels

    PubMed Central

    Laursen, Willem J.; Merriman, Dana K.; Bagriantsev, Sviatoslav N.; Gracheva, Elena O.

    2016-01-01

    The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40 °C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by primary afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV1 orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV1 as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV1 orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV1, supporting functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV1-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV1 molecule, which can undergo profound tuning at the minimal cost of a single amino acid change. PMID:27638213

  6. Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels.

    PubMed

    Laursen, Willem J; Schneider, Eve R; Merriman, Dana K; Bagriantsev, Sviatoslav N; Gracheva, Elena O

    2016-10-04

    The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40 °C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by primary afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV1 orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV1 as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV1 orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV1, supporting functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV1-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV1 molecule, which can undergo profound tuning at the minimal cost of a single amino acid change.

  7. IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV infection

    PubMed Central

    Depla, Marion; Pelletier, Sandy; Bédard, Nathalie; Brunaud, Camille; Bruneau, Julie

    2016-01-01

    Abstract Introduction Polymorphisms in the type III interferon IFN‐λ3 and the killer cell immunoglobulin‐like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN‐λ3 polymorphism may modulate NK cell function during acute HCV. Methods We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes. Results Early acute HCV was associated with high variability in type III IFNs plasma levels and the favorable IFN‐λ3 CC genotype was associated with higher viral loads. Reduced expression of Natural Killer Group Protein 2A (NKG2A) was associated with lower IFN‐λ3 plasma levels and the CC genotype. IFN‐γ production by NK cells was higher in individuals with the CC genotype during acute infection but this did not prevent viral persistence. IFN‐λ3 plasma levels did not correlate with function of NK cells and IFN‐λ3 prestimulation did not affect NK cell activation and function. Conclusions These results suggest that IFN‐λ3 polymorphism indirectly influences NK cell phenotype and function during acute HCV but other factors may act in concert to determine the outcome of the infection. PMID:27621819

  8. Effects of Acute Exposures to Carbon Dioxide upon Cognitive Functions

    NASA Technical Reports Server (NTRS)

    Ryder, V. E.; Scully, R. R.; Alexander, D. J.; Lam, C. W.; Young, M.; Satish, U.; Basner, M.

    2017-01-01

    Carbon dioxide (CO2) originates from human metabolism and typically remains about 10-fold higher in concentration on the International Space Station (ISS) than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the ISS that associates CO2 levels with reports of headaches by crewmembers. Consequently, flight rules have been employed to control CO2 below 3 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached, and there is evidence that CO2 has effects at levels below the threshold for headaches. This concern appears to be substantiated in reports that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. Therefore, we set out to determine if decision-making under volatile, uncertain, confusing and ambiguous circumstances, where feedback is delayed or absent, is correlated with low levels of CO2 during acute exposures (several hours) in crew-like subjects and to determine if additional cognitive domains are sensitive to concentrations of CO2 at, or below, current ISS levels by using a test battery that is currently available onboard ISS. We enrolled 22 volunteers (8 females, 14 males) between the ages of 30-55 (38.8 +/- 7.0) years whose training and professional experience reflect that of the astronaut corps. Subjects were divided among 4 study

  9. Increased analgesic tolerance to acute morphine in fosB knock-out mice: a gender study.

    PubMed

    Solecki, Wojciech; Krowka, Tomasz; Kubik, Jakub; Kaczmarek, Leszek; Przewlocki, Ryszard

    2008-10-01

    The proteins of Fos family are a potential candidate to link molecular mechanisms of morphine action with behavioural effects such as morphine-induced reward, dependence and tolerance. We used both male and female mice lacking fosB gene to study its contribution to morphine effects. Morphine analgesia (tail-flick test) and hypothermia were studied using morphine at cumulative doses in morphine-naive and morphine-tolerant (tolerance induced by 24 h prior 100 mg/kg morphine administration) mice. FosB -/- mice, as compared to fosB +/+ mice, developed enhanced tolerance to morphine-induced analgesia. No effects of genotype or gender on tolerance to morphine-induced hypothermia were observed. These results suggest that fosB may be involved in the development of tolerance to morphine analgesia but not hypothermia. The gender study implicates that lack of FosB proteins in female fosB -/- mice enhanced morphine analgesic potency. In conclusion, we show that fosB gene is important to analgesia but not hypothermia phenotype indicating its role in morphine effects.

  10. Safety and tolerance data from the Belgian multicentre study of anisoylated plasminogen streptokinase activator complex versus heparin in acute myocardial infarction.

    PubMed

    Bossaert, L L

    1987-01-01

    In the European Multicentre Study (EMS), the safety and efficacy of a single 30U intravenous injection of anisoylated plasminogen streptokinase activator complex (APSAC) was studied in patients with acute myocardial infarction. The present study discusses the Belgian data on safety and tolerance from the EMS study. 87 patients were randomised to treatment with APSAC or heparin. The reperfusion rate was 60.5% (APSAC) versus 20.5% (heparin control), and reocclusion occurred in 21% of the reperfused APSAC patients. Drug-related adverse events consisted of bleeding problems (7 events in patients on APSAC and 1 event in a patient on heparin and moderate allergic reactions (12 events in 9 patients on APSAC and 1 event in a heparin patient). There was 1 drug-related death in the APSAC group (hypovolaemic shock due to central vein puncture during lytic state) which could have been avoided. It is concluded that thrombolytic treatment of acute myocardial infarction with APSAC is effective and safe, as long as the standard precautions for thrombolytic treatment are respected. Bleeding and allergic-type events are infrequent, usually well tolerated and easily treated.

  11. Exercise tolerance, lung function abnormalities, anemia, and cardiothoracic ratio in sickle cell patients.

    PubMed

    van Beers, Eduard J; van der Plas, Mart N; Nur, Erfan; Bogaard, Harm-Jan; van Steenwijk, Reindert P; Biemond, Bart J; Bresser, Paul

    2014-08-01

    Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty-four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS-beta thalassemia) with a median age (interquartile range) of 26 (21-41) years underwent pulmonary function tests, CPET, chest x-ray, and echocardiography to further characterize exercise limitation in SCD. Peak oxygen uptake (V'O2 -peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V'O2 -peak correlated with hemoglobin levels (R = 0.440, P = 0.005), forced vital capacity (FVC) (R = 0.717, P < 0.0001). Cardiothoracic ratio on chest x-ray inversely correlated with FVC (R = -0.637, P < 0.001). According to criteria for exercise limitation, the patients were limited in exercise capacity due to anemia (n = 17), cardiovascular dysfunction (n = 2), musculoskeletal function (n = 10), pulmonary ventilatory abnormalities (n = 1), pulmonary vascular exercise limitation (n = 1), and poor effort (n = 3). In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, that is, reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better.

  12. Pharmacologic strategies to preserve renal function in acute decompensated heart failure.

    PubMed

    Kumar, Sachin; Taylor, David O

    2015-02-01

    Over a million patients get hospitalized with the diagnosis of acute decompensated heart failure which poses an insurmountable financial burden on the health care system. Heart failure alone incurs over 30 billion dollars with half the cost spent towards acute hospitalizations. Majority of the treatment strategies have focused towards decongesting patients which often comes with the cost of worsening renal function. Renal dysfunction in the setting of acute decompensated heart failure portends worse morbidity and mortality. Recently, there has been a change in the focus with shift towards therapies attempting to conserve renal function. In the past decade, we have witnessed several large randomized controlled trials testing the established as well as emerging therapies in this subset of population with mixed results. This review intends to provide a comprehensive overview of the pharmacologic therapies commonly utilized in the management of acute decompensated heart failure and the body of evidence supporting these strategies.

  13. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity.

    PubMed

    Gonzalez-Martin, Alicia; Adams, Brian D; Lai, Maoyi; Shepherd, Jovan; Salvador-Bernaldez, Maria; Salvador, Jesus M; Lu, Jun; Nemazee, David; Xiao, Changchun

    2016-04-01

    Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Elevated miR-148a expression impaired B cell tolerance by promoting the survival of immature B cells after engagement of the B cell antigen receptor by suppressing the expression of the autoimmune suppressor Gadd45α, the tumor suppressor PTEN and the pro-apoptotic protein Bim. Furthermore, increased expression of miR-148a, which occurs frequently in patients with lupus and lupus-prone mice, facilitated the development of lethal autoimmune disease in a mouse model of lupus. Our studies demonstrate a function for miR-148a as a regulator of B cell tolerance and autoimmunity.

  14. Isolation of high salinity stress tolerant genes from Pisum sativum by random overexpression in Escherichia coli and their functional validation.

    PubMed

    Joshi, Amita; Dang, Hung Quang; Vaid, Neha; Tuteja, Narendra

    2009-05-01

    Salinity stress is one of the major factors which reduce crop plants growth and productivity resulting in significant economic losses worldwide. Therefore, it would be fruitful to isolate and functionally identify new salinity stress-induced genes for understanding the mechanism and developing salinity stress tolerant plants. Based on functional gene screening assay, we have isolated few salinity tolerant genes out of one million Escherichia coli (SOLR) transformants containing pea cDNAs. Sequence analysis of three of these genes revealed homology to Ribosomal-L30E (RPL30E), Chlorophyll-a/b-binding protein (Chla/bBP) and FIDDLEHEAD (FDH). The salinity tolerance of these genes in bacteria was further confirmed by using another strain of E. coli (DH5alpha) transformants. The homology based computational modeling of these proteins suggested the high degree of conservation with the conserved domains of their homologous partners. The reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that the expression of these cDNAs (except the FDH) was upregulated in pea plants in response to NaCl stress. We observed that there was no significant effect of Li(+) ion on the expression level of these genes, while an increase in response to K(+) ion was observed. Overall, this study provides an evidence for a novel function of these genes in high salinity stress tolerance. The PsFDH showed constitutive expression in planta suggesting that it can be used as constitutively expressed marker gene for salinity stress tolerance in plants. This study brings new direction in identifying novel function of unidentified genes in abiotic stress tolerance without previous knowledge of the genome sequence.

  15. Repeated Applications of Thoracic Spine Thrust Manipulation do not Lead to Tolerance in Patients Presenting with Acute Mechanical Neck Pain: A Secondary Analysis

    PubMed Central

    Fernández-De-Las-Peñas, Cesar; Cleland, Joshua A; Huijbregts, Peter; Palomeque-Del-Cerro, Luis; González-Iglesias, Javier

    2009-01-01

    It has been demonstrated that patients receiving mobilization techniques do not exhibit tolerance to repeated applications. However, this phenomenon has not been investigated for thoracic manipulation. Our aim was to determine if patients receiving thoracic thrust manipulation exhibit tolerance to repeated applications in acute mechanical neck pain. Forty-five patients were randomly assigned to two groups. The control group received electro- and thermotherapy for 5 sessions, and the experimental group received the same program and also received a thoracic thrust manipulation once a week for 3 consecutive weeks. Outcome measures included neck pain and cervical mobility. Within-session change scores for pain and mobility during treatment sessions #1, 3, and 5 were examined with a one-way repeated measured ANOVA. A 2-way ANOVA with session as within-subject variable and group as between-subject variable was used to compare change scores for each visit between groups to ascertain if there were significant between-group differences in within-session changes for the experimental versus the control group. The ANOVA showed that for either group the 3 within-session change scores were not significantly different (P > 0.1). The 2-way ANOVA revealed significant differences between groups for both pain and neck mobility in within-session change scores (all, P < 0.001). Change scores in each session were superior in the experimental group as compared to those in the control group. The results suggest that patients receiving thoracic manipulation do not exhibit tolerance to repeated applications with regard to pain and mobility measures in acute mechanical neck pain. Further studies should investigate the dose-response relationship of thoracic thrust manipulation in this population. PMID:20046622

  16. Assessment of Patients with Intellectual Disability using the International Classification of Functioning, Disability and Health to Evaluate Dental Treatment Tolerability

    ERIC Educational Resources Information Center

    Maeda, S.; Kita, F.; Miyawaki, T.; Takeuchi, K.; Ishida, R.; Egusa, M.; Shimada, M.

    2005-01-01

    Patients with serious intellectual disability (ID) are occasionally unable to tolerate dental treatment when intravenous sedation or general anaesthesia (IVSGA) is involved. In order to make a decision regarding the application of IVSGA, the International Classification of Functioning, Disability and Health (ICF) is useful. Therefore, in this…

  17. Chronic hyperglycemia is related to poor functional outcome after acute ischemic stroke.

    PubMed

    Luitse, Merel Ja; Velthuis, Birgitta K; Kappelle, L Jaap; van der Graaf, Yolanda; Biessels, Geert Jan

    2017-02-01

    Background Acute hyperglycemia is associated with poor functional outcome after ischemic stroke, but the association between chronic antecedent hyperglycemia and outcome is unclear. Aim We assessed the association between chronic hyperglycemia, measured by hemoglobin A1c, and functional outcome in patients with acute ischemic stroke. Methods We included 812 patients with acute ischemic stroke (mean age 66 ± 14 years; 61.5% male). Patients were categorized per hemoglobin A1c level: no (<39 mmol/mol), moderate (39-42 mmol/mol), or severe chronic hyperglycemia (>42 mmol/mol). Poor functional outcome was defined as modified Rankin Scale score > 2 after 3 months. The relation between chronic hyperglycemia and functional outcome was assessed with a Poisson regression analysis and expressed as risk ratios with 95% confidence intervals with no chronic hyperglycemia as the reference. Results Moderate chronic hyperglycemia was present in 234 (28.8%) patients and severe chronic hyperglycemia in 183 (22.5%) patients. Acute hyperglycemia on admission was present in 338 (41.6%) patients. Severe chronic hyperglycemia was associated with poor outcome (risk ratios 1.40; 95% confidence interval 1.09-1.79). After adjustment for age, sex, stroke severity, vascular risk factors, and acute hyperglycemia on admission the risk ratios was 1.35 (95% confidence interval 1.04-1.76). Moderate chronic hyperglycemia was not associated with poor outcome (risk ratios 1.12; 95% confidence interval 0.87-1.44). Conclusion Severe chronic hyperglycemia is associated with poor functional outcome in patients with acute ischemic stroke. This association is independent of hyperglycemia in the acute stage of stroke and of an unfavorable vascular risk factor profile.

  18. Predicting acute recovery of physical function following total knee joint arthroplasty.

    PubMed

    Robbins, Shawn M; Rastogi, Ravi; McLaughlin, Terry-Lyne

    2014-02-01

    The objective was to explore predictors of physical function during acute in-patient rehabilitation within a few days after TKA. Physical function status of participants (n = 72) three days after total knee arthroplasty (TKA) was measured using the Timed Up and Go Test (TUG) and the function subscale of the Western Ontario McMaster Universities Index of Osteoarthritis (WOMAC-function). Potential predictors of physical function were measured day one post-TKA. Their relationship with physical function was examined using backward elimination, multiple regression analyses. Older age and increased comorbidity were associated (R(2) = 0.20) with worse TUG times. Increased pain severity was associated (R(2) = 0.08) with worse WOMAC-function scores. Age, comorbidity, and pain severity should be considered when predicting which patients will struggle with acute recovery post-TKA.

  19. siRNA capsulated brain-targeted nanoparticles specifically knock down OATP2B1 in mice: a mechanism for acute morphine tolerance suppression

    PubMed Central

    Yang, Zi-Zhao; Li, Li; Wang, Lu; Xu, Ming-Cheng; An, Sai; Jiang, Chen; Gu, Jing-Kai; Wang, Zai-Jie Jim; Yu, Lu-Shan; Zeng, Su

    2016-01-01

    Regulating main brain-uptake transporter of morphine may restrict its tolerance generation, then modify its antinociception. In this study, more than 2 fold higher intracellular uptake concentrations for morphine and morphine-6-glucuronide (M6G) were observed in stable expression cells, HEK293-hOATP2B1 than HEK293-MOCK. Specifically, the Km value of morphine to OATP2B1 (57.58 ± 8.90 μM) is 1.4-time more than that of M6G (80.31 ± 21.75 μM); Cyclosporine A (CsA), an inhibitor of OATP2B1, can inhibit their intracellular accumulations with IC50 = 3.90 ± 0.50 μM for morphine and IC50 = 6.04 ± 0.86 μM for M6G, respectively. To further investigate the role of OATP2B1 in morphine brain transport and tolerance, the novel nanoparticles of DGL-PEG/dermorphin capsulated siRNA (OATP2B1) were applied to deliver siRNA into mouse brain. Along with OATP2B1 depressed, a main reduction was found for each of morphine or M6G in cerebrums or epencephalons of acute morphine tolerance mice. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) in mouse prefrontal cortex (mPFC) underwent dephosphorylation at Thr286. In conclusion, OATP2B1 downregulation in mouse brain can suppress tolerance via blocking morphine and M6G brain transport. These findings might help to improve the pharmacological effects of morphine. PMID:27629937

  20. Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

    PubMed

    Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G

    2017-01-01

    Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P < 0.01). Taken together, these data suggest that acute lower limb heating improves both macro- and microvascular dilator function in an age dependent manner.

  1. Highland mountain hiking and coronary artery disease: exercise tolerance and effects on left ventricular function.

    PubMed

    Huonker, M; Schmidt-Trucksäss, A; Sorichter, S; Irmer, M; Dürr, H; Lehmann, M; Keul, J

    1997-12-01

    Physical exercise has become a well-established concept in the secondary prevention of coronary artery disease. We investigated the exercise requirements of extensive highland mountain hiking (8.7 km, 470 m to 1220 m over sea level, average incline 8.5%, mean walking velocity < 3 km x h-1) in 11 regularly exercising male patients with history of MI and stable coronary artery disease (CAD; mean age +/- SD:61.0 +/- 3.9 yr) and 9 age-matched male healthy controls (CO; mean age +/- SD:61.2 +/- 5.0 yr). All subjects underwent continuous ECG monitoring; arterial blood pressure and blood lactate concentrations were measured several times during mountain hiking. Before and after exercise, cardiac dimensions and functions were assessed by two-dimensional echocardiography and Doppler echocardiography. The mean exercise levels for heart rate and blood lactate were compared with the corresponding data of a multistage upright cycle ergometry. Clinical manifestations of coronary insufficiency, left ventricular myocardial dysfunction, or cardiac arrhythmias > Lown IIIb were not observed in any case. No significant differences in left atrial and left ventricular dimensions and no changes in systolic left ventricular function compared with the preexercise values were found after the mountain hike tour. Doppler echocardiography demonstrated significant changes in diastolic left ventricular function in CAD, but not in CO. The peak exercise intensity during mountain hiking was equivalent to a workload of 100-125 W (1.25-1.5 W x kg-1 body weight) in a multistage upright cycle ergometry. Extensive highland mountain hiking may be a low risk alternative within the outpatient rehabilitation program for secondary prevention of CAD for MI patients with a cycle ergometric exercise tolerance > 1.5 W x kg-1 body weight.

  2. Structurally Integrated, Damage Tolerant Thermal Spray Coatings: Processing Effects on Surface and System Functionalities

    NASA Astrophysics Data System (ADS)

    Vackel, Andrew

    Thermal Spray (TS) coatings have seen extensive application as protective surfaces to enhance the service life of substrates prone to damage in their operating environment (wear, corrosion, heat etc.). With the advent of high velocity TS processes, the ability to deposit highly dense (>99%) metallic and cermet coatings has further enhanced the protective ability of these coatings. In addition to surface functionality, the influence of the coating application on the mechanical performance of a coated component is of great concern when such a component will experience either static or cyclic loading during service. Using a process mapping methodology, the processing-property interplay between coating materials meant to provide damage tolerant surface or for structural restoration are explored in terms of relevant mechanical properties. Most importantly, the residual stresses inherent in TS deposited coatings are shown to play a significant role in the integrated mechanical performance of these coatings. Unique to high velocity TS processes is the ability to produce compressive stresses within the deposit from the cold working induced by the high kinetic energy particles upon impact. The extent of these formation stresses are explored with different coating materials, as well as processing influence. The ability of dense TS coatings to carry significant structural load and synergistically strengthen coated tensile specimens is demonstrated as a function of coating material, processing, and thickness. The sharing of load between the substrate and otherwise brittle coating enables higher loads before yield for the bi-material specimens, offering a methodology to improve the tensile performance of coated components for structural repair or multi-functionality (surface and structure). The concern of cyclic fatigue damage in coated components is explored, since the majority of service application are designed for loading to be well below the yield point. The role of

  3. Using stable isotopes and functional wood anatomy to identify underlying mechanisms of drought tolerance in different provenances of lodgepole pine

    NASA Astrophysics Data System (ADS)

    Isaac-Renton, Miriam; Montwé, David; Hamann, Andreas; Spiecker, Heinrich; Cherubini, Paolo; Treydte, Kerstin

    2016-04-01

    Choosing drought-tolerant seed sources for reforestation may help adapt forests to climate change. By combining dendroecological growth analysis with a long-term provenance trial, we assessed growth and drought tolerance of different populations of a wide-ranging conifer, lodgepole pine (Pinus contorta). This experimental design simulated a climate warming scenario through southward seed transfer, and an exceptional drought also occurred in 2002. We felled over 500 trees, representing 23 seed sources, which were grown for 32 years at three warm, dry sites in southern British Columbia, Canada. Northern populations showed poor growth and drought tolerance. These seed sources therefore appear to be especially at risk under climate change. Before recommending assisted migration of southern seeds towards the north, however, it is important to understand the physiological mechanisms underlying these responses. We combine functional wood anatomy with a dual-isotope approach to evaluate these mechanisms to drought response.

  4. Silicon application increases drought tolerance of kentucky bluegrass by improving plant water relations and morphophysiological functions.

    PubMed

    Saud, Shah; Li, Xin; Chen, Yang; Zhang, Lu; Fahad, Shah; Hussain, Saddam; Sadiq, Arooj; Chen, Yajun

    2014-01-01

    Drought stress encumbers the growth of turfgrass principally by disrupting the plant-water relations and physiological functions. The present study was carried out to appraise the role of silicon (Si) in improving the drought tolerance in Kentucky bluegrass (Poa pratensis L.). Drought stress and four levels (0, 200, 400, and 800 mg L(-1)) of Si (Na2SiO3·9H2O) were imposed after 2 months old plants cultured under glasshouse conditions. Drought stress was found to decrease the photosynthesis, transpiration rate, stomatal conductance, leaf water content, relative growth rate, water use efficiency, and turf quality, but to increase in the root/shoot and leaf carbon/nitrogen ratio. Such physiological interferences, disturbances in plant water relations, and visually noticeable growth reductions in Kentucky bluegrass were significantly alleviated by the addition of Si after drought stress. For example, Si application at 400 mg L(-1) significantly increased the net photosynthesis by 44%, leaf water contents by 33%, leaf green color by 42%, and turf quality by 44% after 20 days of drought stress. Si application proved beneficial in improving the performance of Kentucky bluegrass in the present study suggesting that manipulation of endogenous Si through genetic or biotechnological means may result in the development of drought resistance in grasses.

  5. SIRT1 enhances glucose tolerance by potentiating brown adipose tissue function

    PubMed Central

    Boutant, Marie; Joffraud, Magali; Kulkarni, Sameer S.; García-Casarrubios, Ester; García-Roves, Pablo M.; Ratajczak, Joanna; Fernández-Marcos, Pablo J.; Valverde, Angela M.; Serrano, Manuel; Cantó, Carles

    2014-01-01

    Objective SIRT1 has been proposed to be a key signaling node linking changes in energy metabolism to transcriptional adaptations. Although SIRT1 overexpression is protective against diverse metabolic complications, especially in response to high-fat diets, studies aiming to understand the etiology of such benefits are scarce. Here, we aimed to identify the key tissues and mechanisms implicated in the beneficial effects of SIRT1 on glucose homeostasis. Methods We have used a mouse model of moderate SIRT1 overexpression, under the control of its natural promoter, to evaluate glucose homeostasis and thoroughly characterize how different tissues could influence insulin sensitivity. Results Mice with moderate overexpression of SIRT1 exhibit better glucose tolerance and insulin sensitivity even on a low fat diet. Euglycemic-hyperinsulinemic clamps and in-depth tissue analyses revealed that enhanced insulin sensitivity was achieved through a higher brown adipose tissue activity and was fully reversed by housing the mice at thermoneutrality. SIRT1 did not influence brown adipocyte differentiation, but dramatically enhanced the metabolic transcriptional responses to β3-adrenergic stimuli in differentiated adipocytes. Conclusions Our work demonstrates that SIRT1 improves glucose homeostasis by enhancing BAT function. This is not consequent to an alteration in the brown adipocyte differentiation process, but as a result of potentiating the response to β3-adrenergic stimuli. PMID:25685699

  6. Error analysis of overlay compensation methodologies and proposed functional tolerances for EUV photomask flatness

    NASA Astrophysics Data System (ADS)

    Ballman, Katherine; Lee, Christopher; Dunn, Thomas; Bean, Alexander

    2016-05-01

    Due to the impact on image placement and overlay errors inherent in all reflective lithography systems, EUV reticles will need to adhere to flatness specifications below 10nm for 2018 production. These single value metrics are near impossible to meet using current tooling infrastructure (current state of the art reticles report P-V flatness ~60nm). In order to focus innovation on areas which lack capability for flatness compensation or correction, this paper redefines flatness metrics as being "correctable" vs. "non-correctable" based on the surface topography's contributions to the final IP budget at wafer, as well as whether data driven corrections (write compensation or at scanner) are available for the reticle's specific shape. To better understand and define the limitations of write compensation and scanner corrections, an error budget for processes contributing to these two methods is presented. Photomask flatness measurement tools are now targeting 6σ reproducibility <1nm (previous 3σ reproducibility ~3nm) in order to drive down error contributions and provide more accurate data for correction techniques. Taking advantage of the high order measurement capabilities of improved metrology tooling, as well as computational capabilities which enable fast measurements and analysis of sophisticated shapes, we propose a methodology for the industry to create functional tolerances focused on the flatness errors that are not correctable with compensation.

  7. [Advances in functional genomics studies underlying acetic acid tolerance of Saccharomyces cerevisiae].

    PubMed

    Zhao, Xinqing; Zhang, Mingming; Xu, Guihong; Xu, Jianren; Bai, Fengwu

    2014-03-01

    Industrial microorganisms are subject to various stress conditions, including products and substrates inhibitions. Therefore, improvement of stress tolerance is of great importance for industrial microbial production. Acetic acid is one of the major inhibitors in the cellulosic hydrolysates, which affects seriously on cell growth and metabolism of Saccharomyces cerevisiae. Studies on the molecular mechanisms underlying adaptive response and tolerance of acetic acid of S. cerevisiae benefit breeding of robust strains of industrial yeast for more efficient production. In recent years, more insights into the molecular mechanisms underlying acetic acid tolerance have been revealed through analysis of global gene expression and metabolomics analysis, as well as phenomics analysis by single gene deletion libraries. Novel genes related to response to acetic acid and improvement of acetic acid tolerance have been identified, and novel strains with improved acetic acid tolerance were constructed by modifying key genes. Metal ions including potassium and zinc play important roles in acetic acid tolerance in S. cerevisiae, and the effect of zinc was first discovered in our previous studies on flocculating yeast. Genes involved in cell wall remodeling, membrane transport, energy metabolism, amino acid biosynthesis and transport, as well as global transcription regulation were discussed. Exploration and modification of the molecular mechanisms of yeast acetic acid tolerance will be done further on levels such as post-translational modifications and synthetic biology and engineering; and the knowledge obtained will pave the way for breeding robust strains for more efficient bioconversion of cellulosic materials to produce biofuels and bio-based chemicals.

  8. Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas' disease in rats.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Chiari, E; Machado, C R; Teixeira, M M; Camargos, E R

    2001-06-20

    Severe cardiac autonomic denervation occurs in the acute Chagas' disease in rats. The present study aims at verifying whether this denervation was accompanied by impairment of heart function. Scorpionic (Tityus serrulatus) crude venom was used for neurotransmitter release in isolated hearts (Langendorff's preparation). In control hearts, the venom induced significant bradycardia followed by tachycardia. In infected animals, despite the severe (sympathetic) or moderate (parasympathetic) cardiac denervation, the venom provoked similar bradycardia but the tachycardia was higher. The hearts of infected animals beat at significantly lower rate. Atropine prevented this lower rate. Our results demonstrated sympathetic dysfunction during the acute phase of Trypanosoma cruzi infection in rats, the parasympathetic function being spared.

  9. Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

  10. More Daytime Sleeping Predicts Less Functional Recovery Among Older People Undergoing Inpatient Post-Acute Rehabilitation

    PubMed Central

    Alessi, Cathy A.; Martin, Jennifer L.; Webber, Adam P.; Alam, Tarannum; Littner, Michael R.; Harker, Judith O.; Josephson, Karen R.

    2008-01-01

    Study Objectives: To study the association between sleep/wake patterns among older adults during inpatient post-acute rehabilitation and their immediate and long-term functional recovery Design: Prospective, observational cohort study Setting: Two inpatient post-acute rehabilitation sites (one community and one Veterans Administration) Participants: Older patients (aged ≥ 65 years, N = 245) admitted for inpatient post-acute rehabilitation Interventions: None Measurements and Results: Based on 7-day wrist actigraphy during the rehabilitation stay, mean nighttime percent sleep was only 52.2% and mean daytime percent sleep was 15.8% (16.3% based on structured behavioral observations). Using the Pittsburgh Sleep Quality Index (PSQI), participants reported their sleep was worse during rehabilitation compared to their premorbid sleep. Functional recovery between admission and discharge from rehabilitation (measured by the motor component of the Functional Independence Measure) was not significantly associated with reported sleep quality (PSQI scores) or actigraphically measured nighttime sleep. However, more daytime percent sleep (estimated by actigraphy and observations) during the rehabilitation stay was associated with less functional recovery from admission to discharge, even after adjusting for other significant predictors of functional recovery (mental status, hours of rehabilitation therapy received, rehospitalization, and reason for admission; adjusted R2 = 0.267, P < 0.0001). More daytime sleeping during rehabilitation remained a significant predictor of less functional recovery in adjusted analyses at 3-month follow-up. Conclusions: Sleep disturbance is common among older people undergoing inpatient post-acute rehabilitation. These data suggest that more daytime sleeping during the rehabilitation stay is associated with less functional recovery for up to three months after admission for rehabilitation. Citation: Alessi CA; Martin JL; Webber AP; Alam T

  11. Effects of Acute Laboratory Stress on Executive Functions

    PubMed Central

    Starcke, Katrin; Wiesen, Carina; Trotzke, Patrick; Brand, Matthias

    2016-01-01

    Recent research indicates that stress can affect executive functioning. However, previous results are mixed with respect to the direction and size of effects, especially when considering different subcomponents of executive functions. The current study systematically investigates the effects of stress on the five components of executive functions proposed by Smith and Jonides (1999): attention and inhibition; task management; planning; monitoring; and coding. Healthy participants (N = 40) were either exposed to the computerized version of the Paced Auditory Serial Addition Test as a stressor (N = 20), or to a rest condition (N = 20). Stress reactions were assessed with heart rate and subjective measures. After the experimental manipulation, all participants performed tasks that measure the different executive functions. The manipulation check indicates that stress induction was successful (i.e., the stress group showed a higher heart rate and higher subjective responses than the control group). The main results demonstrate that stressed participants show a poorer performance compared with unstressed participants in all executive subcomponents, with the exception of monitoring. Effect sizes for the tasks that reveal differences between stressed and unstressed participants are high. We conclude that the laboratory stressor used here overall reduced executive functioning. PMID:27065926

  12. Effects of Acute Laboratory Stress on Executive Functions.

    PubMed

    Starcke, Katrin; Wiesen, Carina; Trotzke, Patrick; Brand, Matthias

    2016-01-01

    Recent research indicates that stress can affect executive functioning. However, previous results are mixed with respect to the direction and size of effects, especially when considering different subcomponents of executive functions. The current study systematically investigates the effects of stress on the five components of executive functions proposed by Smith and Jonides (1999): attention and inhibition; task management; planning; monitoring; and coding. Healthy participants (N = 40) were either exposed to the computerized version of the Paced Auditory Serial Addition Test as a stressor (N = 20), or to a rest condition (N = 20). Stress reactions were assessed with heart rate and subjective measures. After the experimental manipulation, all participants performed tasks that measure the different executive functions. The manipulation check indicates that stress induction was successful (i.e., the stress group showed a higher heart rate and higher subjective responses than the control group). The main results demonstrate that stressed participants show a poorer performance compared with unstressed participants in all executive subcomponents, with the exception of monitoring. Effect sizes for the tasks that reveal differences between stressed and unstressed participants are high. We conclude that the laboratory stressor used here overall reduced executive functioning.

  13. Acute Exercise Improves Prefrontal Cortex but not Hippocampal Function in Healthy Adults.

    PubMed

    Basso, Julia C; Shang, Andrea; Elman, Meredith; Karmouta, Ryan; Suzuki, Wendy A

    2015-11-01

    The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise.

  14. Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

    PubMed Central

    Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

    2016-01-01

    Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

  15. PREDICTING THE ACUTE BEHAVIORAL EFFECTS OF TOLUENE INHALED FOR 24 HRS IN RATS: DOSE METRICS, METABOLISM AND BEHAVIORAL TOLERANCE

    EPA Science Inventory

    Purpose: Recent research on the acute effects of volatile organic compounds (VOCs) suggests that extrapolation from short (~ 1 h) to long durations (up to 4 h) is improved by using estimates of brain toluene concentration ( Br[ToI)] instead of cumulative inhaled dose (C x t) as a...

  16. An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men.

    PubMed

    Beaudoin, Marie-Soleil; Robinson, Lindsay E; Graham, Terry E

    2011-04-01

    Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine. The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Ten young, healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 0.05) after a subsequent OGTT. At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 0.05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 0.05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 6.25 h (P < 0.05), whereas only caffeinated coffee increased GIP secretion (P < 0.05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part this impaired glucose homeostasis.

  17. The Effect of Vigorous Intensity Acute Exercise on Executive Function

    ERIC Educational Resources Information Center

    Phillips, David Spencer

    2012-01-01

    The effect of physical activity (PA) and consequent influence on cognition within adult seniors has been widely published. However, there is a paucity of causal research relating PA and cognition to schoolchildren within an authentic setting. Also, little is known about the required intensity and dosage of PA to effect executive function (EF)…

  18. Does acute exposure to aldehydes impair pulmonary function and structure?

    PubMed

    Abreu, Mariana de; Neto, Alcendino Cândido; Carvalho, Giovanna; Casquillo, Natalia Vasconcelos; Carvalho, Niedja; Okuro, Renata; Ribeiro, Gabriel C Motta; Machado, Mariana; Cardozo, Aléxia; Silva, Aline Santos E; Barboza, Thiago; Vasconcellos, Luiz Ricardo; Rodrigues, Danielle Araujo; Camilo, Luciana; Carneiro, Leticia de A M; Jandre, Frederico; Pino, Alexandre V; Giannella-Neto, Antonio; Zin, Walter A; Corrêa, Leonardo Holanda Travassos; Souza, Marcio Nogueira de; Carvalho, Alysson R

    2016-07-15

    Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

  19. Metabolic status, gonadotropin secretion, and ovarian function during acute nutrient restriction of beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of acute nutritional restriction on metabolic status, gonadotropin secretion, and ovarian function of heifers was determined in 2 experiments. In Exp. 1, 14-mo-old heifers were fed a diet supplying 1.2 × maintenance energy requirements (1.2M). After 10 d, heifers were fed 1.2M or were res...

  20. Renal functional reserve and renal recovery after acute kidney injury.

    PubMed

    Sharma, Aashish; Mucino, Marìa Jimena; Ronco, Claudio

    2014-01-01

    Renal functional reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions. Once baseline GFR is determined, RFR can be assessed clinically after an oral protein load or intravenous amino acid infusion. In clinical practice, baseline GFR displays variable levels due to diet or other factors. RFR is the difference between peak 'stress' GFR induced by the test (p.o. or i.v.) and the baseline GFR. In clinical scenarios where hyperfiltration is present (high baseline GFR due to pregnancy, hypertension or diabetic nephropathy, in solitary kidney or kidney donors), RFR may be fully or partially used to achieve normal or supranormal renal function. Since commonly used renal function markers, such as GFR, may remain within normal ranges until 50% of nephrons are lost or in patients with a single remnant kidney, the RFR test may represent a sensitive and early way to assess the functional decline in the kidney. RFR assessment may become an important tool to evaluate the ability of the kidney to recover completely or partially after a kidney attack. In case of healing with a defect and progressive fibrosis, recovery may appear complete clinically, but a reduced RFR may be a sign of a maladaptive repair or subclinical loss of renal mass. Thus, a reduction in RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios, and future perspective for its use.

  1. Structural and functional changes in acute liver injury.

    PubMed Central

    Smuckler, E A

    1976-01-01

    Carbon tetrachloride produces liver cell injury in a variety of animal species. The first structurally recognizable changes occur in the endoplasmic reticulum, with alteration in ribosome-membrane interactions. Later there is an increase in intracellular fat, and the formation of tangled nets of the ergastoplasm. At no time are there changes in mitochondria or single membrane limited bodies in cells with intact plasmalemma, although a relative increase in cell sap may appear. In dead cells (those with plasmalemma discontinuties) crystalline deposits of calcium phosphatase may be noted. Functional changes are related to the endoplasmic reticulum and the plasma membrane. An early decrease in protein synthesis takes place; an accumulation of neutral lipid is related to this change. Later alterations in the ergastoplasmic functions (e.g., mixed function oxidation) occurs. Carbon tetrachloride is not the active agent; rather, a product of its metabolism, probably the CC1, free radical, is. The mechanisms of injury include macromolecular adduction and peroxide propagation. A third possibility includes a cascade effect with the production of secondary and tertiary products, also toxic in nature, with the ability to produce more widespread damage to intracellular structures. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 11. PMID:1001290

  2. Factors Affecting Recovery Time of Pulmonary Function in Hospitalized Patients With Acute Asthma Exacerbations

    PubMed Central

    Kim, Hyo-Jung; Lee, Jaemoon; Kim, Jung-Hyun; Park, So-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom

    2016-01-01

    Purpose Prolonged recovery time of pulmonary function after an asthma exacerbation is a significant burden on asthmatics, and management of these patients needs to be improved. The aim of this study was to evaluate factors associated with a longer recovery time of pulmonary function among asthmatic patients hospitalized due to a severe asthma exacerbation. Methods We retrospectively reviewed the medical records of 89 patients who were admitted for the management of acute asthma exacerbations. The recovery time of pulmonary function was defined as the time from the date each patient initially received treatment for asthma exacerbations to the date the patient reached his or her previous best FEV1% value. We investigated the influence of various clinical and laboratory factors on the recovery time. Results The median recovery time of the patients was 1.7 weeks. Multiple linear regression analysis revealed that using regular inhaled corticosteroids (ICS) before an acute exacerbation of asthma and concurrent with viral infection at admission were associated with the prolonged recovery time of pulmonary function. Conclusions The prolonged recovery time of pulmonary function after a severe asthma exacerbation was not shown to be directly associated with poor adherence to ICS. Therefore the results indicate that an unknown subtype of asthma may be associated with the prolonged recovery of pulmonary function time after an acute exacerbation of asthma despite regular ICS use. Further prospective studies to investigate factors affecting the recovery time of pulmonary function after an asthma exacerbation are warranted. PMID:27582400

  3. Effects of acute electromagnetic fields exposure on the interhemispheric homotopic functional connectivity during resting state.

    PubMed

    Lv, Bin; Shao, Qing; Chen, Zhiye; Ma, Lin; Wu, Tongning

    2015-08-01

    In this paper, we aimed to investigate the possible effects of acute radiofrequency electromagnetic fields (EMF) on the interhemispheric homotopic functional connectivity with resting state functional magnetic resonance imaging (fMRI) technique. We designed a controllable LTE-related EMF exposure environment at 2.573 GHz and performed the 30 min real/sham exposure experiments on human brain under the safety limits. The resting state fMRI signals were collected before and after EMF exposure. Then voxel-mirrored homotopic connectivity method was utilized to evaluate the acute effects of LTE EMF exposure on the homotopic functional connectivity between two human hemispheres. Based on our previous research, we further demonstrated that the 30 min short-term LTE EMF exposure would modulate the interhemispheric homotopic functional connectivity in resting state around the medial frontal gyrus and the paracentral lobule during the real exposure.

  4. Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles

    PubMed Central

    Reichstetter, Sandra; Castillo, Gerardo M.; Rubinstein, Israel; Nishimoto-Ashfield, Akiko; Lai, ManShun; Jones, Cynthia C.; Banjeree, Aryamitra; Lyubimov, Alex; Bloedow, Duane C.; Bogdanov, Alexei; Bolotin, Elijah M.

    2013-01-01

    Purpose To determine and compare pharmacokinetics and toxicity of two nanoformulations of Vasoactive Intestinal Peptide (VIP). Methods VIP was formulated using a micellar (Sterically Stabilized Micelles, SSM) and a polymer-based (Protected Graft Copolymer, PGC) nanocarrier at various loading percentages. VIP binding to the nanocarriers, pharmacokinetics, blood pressure, blood chemistry, and acute maximum tolerated dose (MTD) of the formulations after injection into BALB/c mice were determined. Results Both formulations significantly extend in vivo residence time compared to unformulated VIP. Formulation toxicity is dependent on loading percentage, showing major differences between the two carrier types. Both formulations increase in vivo potency of unformulated VIP and show acute MTDs at least 140 times lower than unformulated VIP, but still at least 100 times higher than the anticipated highest human dose, 1–5 μg/kg. These nanocarriers prevented a significant drop in arterial blood pressure compared to unformulated VIP. Conclusions While both carriers enhance in vivo residence time compared to unformulated VIP and reduce the drop in blood pressure immediately after injection, PGC is the excipient of choice to extend residence time and improve the safety of potent therapeutic peptides such as VIP. PMID:23224976

  5. A comparison of acute and chronic toxicity tests used to examine the temporal stability of a gradient in copper tolerance of Hediste diversicolor from the Fal estuary, Cornwall, UK.

    PubMed

    Burlinson, F C; Lawrence, A J

    2007-01-01

    The aim of this study was to use two different toxicity tests to verify the existence of a gradient in tolerance along Rostronguet Creek. Hediste diversicolor was collected from five populations in the Fal estuary previously shown to vary in copper tolerance. Exposure to 4 mgL(-1) of copper in an acute assay demonstrated that Mylor Creek worms were sensitive (LT(50) 86 h) and the tolerance of Rostronguet Creek worms increased moving upstream from the mouth of the creek (LT(50)s 100-258 h). There was no significant difference in tolerance between Mylor worms and worms from the mouth of Rostronguet Creek. This is in agreement with a previous study [Grant, A., Hateley, J.G., Jones, N.V., 1989. Mapping the ecological impact of heavy metals on the estuarine polychaete Nereis diversicolor using inherited metal tolerance. Marine Pollution Bulletin 20, 235-238] and demonstrates temporal stability of the gradient. Copper tolerance was also measured using a chronic toxicity test run for 90 d using step-wise increases in challenge concentration. A significant difference in tolerance was shown between populations from Mylor Creek and those at the mouth of Rostronguet Creek, which has not been reported previously. Experimental protocol was therefore an important factor in detecting population variation in tolerance.

  6. Investigation of the applicability of a functional programming model to fault-tolerant parallel processing for knowledge-based systems

    NASA Technical Reports Server (NTRS)

    Harper, Richard

    1989-01-01

    In a fault-tolerant parallel computer, a functional programming model can facilitate distributed checkpointing, error recovery, load balancing, and graceful degradation. Such a model has been implemented on the Draper Fault-Tolerant Parallel Processor (FTPP). When used in conjunction with the FTPP's fault detection and masking capabilities, this implementation results in a graceful degradation of system performance after faults. Three graceful degradation algorithms have been implemented and are presented. A user interface has been implemented which requires minimal cognitive overhead by the application programmer, masking such complexities as the system's redundancy, distributed nature, variable complement of processing resources, load balancing, fault occurrence and recovery. This user interface is described and its use demonstrated. The applicability of the functional programming style to the Activation Framework, a paradigm for intelligent systems, is then briefly described.

  7. Physiological Function of Alcohol Dehydrogenases and Long-Chain (C30) Fatty Acids in Alcohol Tolerance of Thermoanaerobacter ethanolicus

    PubMed Central

    Burdette, D. S.; Jung, S.-H.; Shen, G.-J.; Hollingsworth, R. I.; Zeikus, J. G.

    2002-01-01

    A mutant strain (39E H8) of Thermoanaerobacter ethanolicus that displayed high (8% [vol/vol]) ethanol tolerance for growth was developed and characterized in comparison to the wild-type strain (39E), which lacks alcohol tolerance (<1.5% [vol/vol]). The mutant strain, unlike the wild type, lacked primary alcohol dehydrogenase and was able to increase the percentage of transmembrane fatty acids (i.e., long-chain C30 fatty acids) in response to increasing levels of ethanol. The data support the hypothesis that primary alcohol dehydrogenase functions primarily in ethanol consumption, whereas secondary alcohol dehydrogenase functions in ethanol production. These results suggest that improved thermophilic ethanol fermentations at high alcohol levels can be developed by altering both cell membrane composition (e.g., increasing transmembrane fatty acids) and the metabolic machinery (e.g., altering primary alcohol dehydrogenase and lactate dehydrogenase activities). PMID:11916712

  8. [Efficacy and tolerability of morniflumate in acute otitis in infants: results of a randomized study versus placebos].

    PubMed

    Portmann, M; Portmann, D; Rohou, S; Pollet, M; Colson, J; Cuvelier, A; Fournier, J L; Jeannerot, F; Marx, J; Menet, V

    1990-01-01

    In a randomized double-blind placebo-controlled, parallel group study, 79 infants with acute otitis media received treatment with suppositories containing either Nifluril (400 mg daily, morniflumate) or placebo for five days. Both groups of patients also received amoxicilline (50 mg/kg daily) for eight days. The combination of Nifluril with antibiotic therapy gave significantly greater relief from abnormalities of the tympanic membrane (after two days treatment), inflammation of the throat and nasal congestion than did antibiotic therapy alone. Overall clinical assessment confirmed a significantly greater recover rate in the Nifluril group compared with the placebo group. Very few side effects were recorded, limited to diarrhoea, without any drug interruption. Nifluril may be recommended as an effective safe adjuvant to the antibiotic treatment of acute otitis media in infants.

  9. Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies.

    PubMed

    Bossong, Matthijs G; Jager, Gerry; Bhattacharyya, Sagnik; Allen, Paul

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease, and may also be related to endocannabinoid dysfunction in these disorders. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of psychiatric disorders. Here we review neuroimaging studies that investigated acute and non-acute effects of cannabis on human learning and memory function, both in adults and in adolescents. Overall, results of these studies show that cannabis use is associated with a pattern of increased activity and a higher level of deactivation in different memory-related areas. This could reflect either increased neural effort ('neurophysiological inefficiency') or a change in strategy to maintain good task performance. However, the interpretation of these findings is significantly hampered by large differences between study populations in cannabis use in terms of frequency, age of onset, and time that subjects were abstinent from cannabis. Future neuroimaging studies should take these limitations into account, and should focus on the potential of cannabinoid compounds for treatment of cognitive symptoms in psychiatric disorders.

  10. Abdominal Functional Electrical Stimulation to Assist Ventilator Weaning in Acute Tetraplegia: A Cohort Study

    PubMed Central

    McCaughey, Euan J.; Berry, Helen R.; McLean, Alan N.; Allan, David B.; Gollee, Henrik

    2015-01-01

    Background Severe impairment of the major respiratory muscles resulting from tetraplegia reduces respiratory function, causing many people with tetraplegia to require mechanical ventilation during the acute stage of injury. Abdominal Functional Electrical Stimulation (AFES) can improve respiratory function in non-ventilated patients with sub-acute and chronic tetraplegia. The aim of this study was to investigate the clinical feasibility of using an AFES training program to improve respiratory function and assist ventilator weaning in acute tetraplegia. Methods AFES was applied for between 20 and 40 minutes per day, five times per week on four alternate weeks, with 10 acute ventilator dependent tetraplegic participants. Each participant was matched retrospectively with a ventilator dependent tetraplegic control, based on injury level, age and sex. Tidal Volume (VT) and Vital Capacity (VC) were measured weekly, with weaning progress compared to the controls. Results Compliance to training sessions was 96.7%. Stimulated VT was significantly greater than unstimulated VT. VT and VC increased throughout the study, with mean VC increasing significantly (VT: 6.2 mL/kg to 7.8 mL/kg VC: 12.6 mL/kg to 18.7 mL/kg). Intervention participants weaned from mechanical ventilation on average 11 (sd: ± 23) days faster than their matched controls. Conclusion The results of this study indicate that AFES is a clinically feasible technique for acute ventilator dependent tetraplegic patients and that this intervention may improve respiratory function and enable faster weaning from mechanical ventilation. Trial Registration ClinicalTrials.gov NCT02200393 PMID:26047468

  11. Palladium-catalyzed Br/D exchange of arenes: Selective deuterium incorporation with versatile functional group tolerance and high efficiency

    DOE PAGES

    Zhang, Honghai -Hai; Bonnesen, Peter V.; Hong, Kunlun

    2015-01-01

    There is a facile method for introducing one or more deuterium atoms onto an aromatic nucleus via Br/D exchange with high functional group tolerance and high incorporation efficiency is disclosed. Deuterium-labeled aryl chlorides and aryl borates which could be used as substrates in cross-coupling reactions to construct more complicated deuterium-labeled compounds can also be synthesized by this method.

  12. Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

    PubMed Central

    Fischer, M. Dominik; Willmann, Gabriel; Schatz, Andreas; Schommer, Kai; Zhour, Ahmad; Zrenner, Eberhart; Bartz-Schmidt, Karl U.; Gekeler, Florian

    2012-01-01

    Background This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.80±1.00 μm; mean change±95%CI). This change was inverted towards the inner four subfields (TRTinner = −1.89±0.97 μm) with significant reduction of TRT in the fovea (TRTfoveal = −6.62±0.90 μm) at altitude. BCVA revealed no significant difference compared to baseline (0.06±0.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = −1.12±0.68 dB). At baseline recordings before and >2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance During acute exposure to high altitude central retinal thickness is subject to minor, yet statistically significant changes. These alterations describe a function of eccentricity with an increase in regions with relatively higher retinal nerve fiber content and vascular arcades. However, these changes did not correlate with measures of central retinal function or acute mountain sickness. For the first time a quantitative approach has been used to assess these changes during acute, non

  13. Effects of Acute Aerobic Exercise on Executive Function in Older Women.

    PubMed

    Peiffer, Roseann; Darby, Lynn A; Fullenkamp, Adam; Morgan, Amy L

    2015-09-01

    Acute aerobic exercise may increase cognitive processing speed among tasks demanding a substantial degree of executive function. Few studies have investigated executive function after acute exercise in older adults across various exercise intensities. Healthy females 60-75 years of age (n = 11) who were not on medications completed 20-min exercise sessions at a moderate (50%VO2max) exercise intensity and a vigorous (75%VO2max) exercise intensity. Modified flanker tasks (reaction times) and d2 tests of sustained and selective attention (components of executive function) were completed before, immediately after, and 30-min post-exercise. Results indicated that older adult females had improved scores on the modified flanker task reaction times (RTT, RTI, RTC) and d2 tests immediately after both moderate and vigorous intensity aerobic exercise. Some of these effects were maintained 30 min post-exercise. These findings suggest that an acute bout of exercise, regardless of intensity, can improve performance on tests of executive function in older women. Key pointsFew studies have investigated the effects of the intensity of exercise on executive function in older womenExecutive function improved after 20-min of aerobic exercise regardless of exercise intensity in older womenFindings from the study were not confounded by prescribed medications; all participants who were older women were not taking any medications.

  14. Relationship between the chest radiograph, regional lung function studies, exercise tolerance, and clinical condition in cystic fibrosis.

    PubMed Central

    Coates, A L; Boyce, P; Shaw, D G; Godfrey, S; Mearns, M

    1981-01-01

    This study evaluated the accuracy of the interpretation of the chest film in delineating localised abnormalities of ventilation and perfusion, as well as the overall severity of airways obstruction, exercise tolerance, and clinical condition in children with cystic fibrosis. Radiographic findings in various regions of the chest film were compared with the functional values obtained with regional lung function tests which evaluated the arrival and disappearance of boluses of radioactive nitrogen given by inhalation and infusion. While the more severely affected areas on the chest radiograph were found to correlate with similar regions on the lung function tests, as did overall scores, errors occurred in some cases if the x-ray film alone was used as a judge of regional physiological derangement. In addition the degree of airways obstruction, the exercise tolerance on a cycle ergometer, and clinical grading, each correlated significantly with the radiographic score. We conclude that the chest radiograph is a good indicator of the overall severity of the lung disease and that it correlates well with exercise tolerance and clinical condition in cystic fibrosis. PMID:7469460

  15. The use of Functional Consequences Theory in acutely confused hospitalized elderly.

    PubMed

    Kozak-Campbell, C; Hughes, A M

    1996-01-01

    Acute confusion is a common complication of hospitalization in the elderly that impacts on both the use of health care resources and the functional status of individuals. Providing optimum nursing care for these patients depends on three factors: 1) the nurse's ability to differentiate acute confusion from other common conditions in the hospitalized elderly, chiefly dementia or depression, 2) the nurse's ability to identify factors contributing to this condition, and 3) the implementation of interventions to minimize the effects of these factors on the patient. This article differentiates the clinical features of acute confusion from those of depression and dementia, and discusses the use of the Functional Consequences Theory, developed by Miller (1990), as a framework for nursing assessment and management of care for elderly patients with this condition. The functional consequences theory framework assists the nurse to identify risk factors associated with the development of acute confusion in the hospitalized elderly. Further it guides the development of interventions to minimize the effects of this condition in this population. The use of this framework in the clinical setting is illustrated through a case study.

  16. Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers.

    PubMed

    Rooks, Cherie R; McCully, Kevin K; Dishman, Rod K

    2011-09-01

    The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color-Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (∼50% VO₂ peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress.

  17. Enhanced muscle shortening and impaired Ca2+ channel function in an acute septic myopathy model.

    PubMed

    Friedrich, Oliver; Hund, Ernst; von Wegner, Frederic

    2010-04-01

    Myopathies in critically ill patients are increasingly documented. Various animal models of chronic sepsis have been employed to investigate reduced membrane excitability or altered isometric contractility of skeletal muscle. In contrast, immediate changes occurring during acute sepsis are significantly under-characterised; L-type Ca(2+) channel function or isotonic shortening are examples. We recorded slowly activating L-type Ca(2+) currents (I (Ca)) in voltage-clamped single intact mouse skeletal muscle fibres and tested the effects of acute challenge with serum fractions from critical illness myopathy patients (CIM). Using a high-speed camera system, we simultaneously recorded unloaded fibre shortening during isotonic contractions with unprecedented temporal resolution (approximately 1,600 frames/s). Time courses of fibre lengths and shortening velocity were determined from automated imaging algorithms. CIM fractions acutely induced depression of I (Ca) amplitudes with no shifts in I (Ca)-V-relations. Voltage-dependent inactivation was unaltered and I (Ca) activation and inactivation kinetics were prolonged compared to controls. Unexpectedly, maximum unloaded speed of shortening was slightly faster following CIM serum applications, suggesting a direct action of CIM serum on weak-binding-state cross-bridges. Our results are compatible with a model where CIM serum might acutely reduce a fraction of functional L-type Ca(2+) channels and could account for reduced SR Ca(2+) release and force production in CIM patients. Acute increase in isotonic shortening velocity might be an early diagnostic feature suitable for testing in clinical studies. The acute challenge model is also robust against atrophy or fibre type changes that ordinarily would have to be considered in chronic sepsis models.

  18. Acute effects of aerobic exercise on cognitive function in older adults.

    PubMed

    Kamijo, Keita; Hayashi, Yoichi; Sakai, Tomoaki; Yahiro, Tatsuhisa; Tanaka, Kiyoji; Nishihira, Yoshiaki

    2009-05-01

    The present study investigated the effects of acute aerobic exercise on cognitive brain functions of older adults. Twenty-four males (12 older and 12 younger adults) performed a modified flanker task during a baseline session (no exercise) and after light and moderate cycling exercise in counterbalanced order on different days while measures of task performance and the P3 component of an event-related brain potential were collected. The results indicated that, for both age groups, reaction time following moderate exercise was shorter relative to the other sessions, and P3 latencies following both light and moderate exercise were shorter compared with the baseline session. In contrast, P3 amplitude increased only following moderate exercise in younger adults. These findings suggest that light and moderate exercises improve cognitive function across the adult lifespan, although the mechanisms underlying the effects of observed acute aerobic exercise on cognitive function may be age dependent.

  19. Acute pulmonary function response to ozone in young adults as a function of body mass index

    EPA Science Inventory

    Recent studies have shown enhanced responsiveness to ozone in obese mice. Adiposity has not been examined as a possible modulator of ozone response in humans. We therefore examined the relationship between body mass index and the acute spirometric response to ozone (O(3)) exposur...

  20. Protective effects of flavanol-rich dark chocolate on endothelial function and wave reflection during acute hyperglycemia.

    PubMed

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Ruggieri, Fabrizio; Blumberg, Jeffrey B; Stornello, Michele; Ferri, Claudio

    2012-09-01

    Nitric oxide plays a pivotal role in regulating vascular tone. Different studies show endothelial function is impaired during hyperglycemia. Dark chocolate increases flow-mediated dilation in healthy and hypertensive subjects with and without glucose intolerance; however, the effect of pretreatment with dark chocolate on endothelial function and other vascular responses to hyperglycemia has not been examined. Therefore, we aimed to investigate the effects of flavanol-rich dark chocolate administration on (1) flow-mediated dilation and wave reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males, 28.2±2.7 years) randomly received either 100 g/d dark chocolate or flavanol-free white chocolate for 3 days. After 7 days washout period, volunteers were switched to the other treatment. Flow-mediated dilation, stiffness index, reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso-PGF(2α) were evaluated after each treatment phase and OGTT. Compared with white chocolate, dark chocolate ingestion improved flow-mediated dilation (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2α) (P<0.05). After white chocolate ingestion, flow-mediated dilation was reduced after OGTT from 7.88±0.68 to 6.07±0.76 (P=0.027), 6.74±0.51 (P=0.046) at 1 and 2 h after the glucose load, respectively. Similarly, after white chocolate but not after dark chocolate, wave reflections, blood pressure, and endothelin-1 and 8-iso-PGF(2α) increased after OGTT. OGTT causes acute, transient impairment of endothelial function and oxidative stress, which is attenuated by flavanol-rich dark chocolate. These results suggest cocoa flavanols may contribute to vascular health by reducing the postprandial impairment of arterial function associated with the pathogenesis of atherosclerosis.

  1. Understanding Vegetative Desiccation Tolerance using Integrated Functional Genomics Approaches within a Comparative Evolutionary Framework

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Desiccation tolerance (DT) is defined as the equilibration of protoplasmic water potential with that of the surrounding air (generally dry) without loss of viability upon rehydration. Vegetative DT is widespread amongst mosses and lichens, but is relatively rare in vascular plants (0.15%). Recent st...

  2. Diurnal Cortisol and Functional Outcomes in Post-Acute Rehabilitation Patients

    PubMed Central

    Fiorentino, Lavinia; Saxbe, Darby; Alessi, Cathy A.; Woods, Diana Lynn

    2012-01-01

    Background. Cortisol is a stress-related hormone with a robust circadian rhythm where levels typically peak in the morning hours and decline across the day. Although acute cortisol increases resulting from stressors are adaptive, chronic elevated cortisol levels are associated with poor functioning. Studies have shown age-related changes in cortisol levels. The present study investigated the relationship between salivary diurnal cortisol and functional outcomes among older adults undergoing inpatient post-acute rehabilitation. Methods. Thirty-two older adults (mean age 78 years; 84% men) in a Veterans Administration inpatient post-acute rehabilitation unit were studied. Functional outcomes were assessed with the motor component of the Functional Independence Measure (mFIM; where mFIM change = discharge − admission score). Saliva samples were collected on 1 day at wake time, 45 minutes later, 11:30 AM, 2 PM, 4:30 PM, and bedtime. We analyzed the relationship between cortisol measures and functional outcomes, demographics, and health measures. Results. The analyses consistently showed that greater functional improvement (mFIM change) from admission to discharge was associated with lower comorbidity scores and higher cortisol levels at 2 PM, 4:30 PM, and bedtime. A morning cortisol rise was also associated with greater mFIM change. Conclusions. Measurement of cortisol in saliva may be a useful biological marker for identification of patients who are “at risk” of lower benefits from inpatient rehabilitation services and who may require additional assistance or intervention during their post-acute care stay. PMID:22219521

  3. Antigen-Specific Immune Modulation Targets mTORC1 Function To Drive Chemokine Receptor-Mediated T Cell Tolerance.

    PubMed

    Chen, Weirong; Wan, Xiaoxiao; Ukah, Tobechukwu K; Miller, Mindy M; Barik, Subhasis; Cattin-Roy, Alexis N; Zaghouani, Habib

    2016-11-01

    To contain autoimmunity, pathogenic T cells must be eliminated or diverted from reaching the target organ. Recently, we defined a novel form of T cell tolerance whereby treatment with Ag downregulates expression of the chemokine receptor CXCR3 and prevents diabetogenic Th1 cells from reaching the pancreas, leading to suppression of type 1 diabetes (T1D). This report defines the signaling events underlying Ag-induced chemokine receptor-mediated tolerance. Specifically, we show that the mammalian target of rapamycin complex 1 (mTORC1) is a major target for induction of CXCR3 downregulation and crippling of Th1 cells. Indeed, Ag administration induces upregulation of programmed death-ligand 1 on dendritic cells in a T cell-dependent manner. In return, programmed death-ligand 1 interacts with the constitutively expressed programmed death-1 on the target T cells and stimulates docking of Src homology 2 domain-containing tyrosine phosphatase 2 phosphatase to the cytoplasmic tail of programmed death-1. Active Src homology 2 domain-containing tyrosine phosphatase 2 impairs the signaling function of the PI3K/protein kinase B (AKT) pathway, leading to functional defect of mTORC1, downregulation of CXCR3 expression, and suppression of T1D. Thus, mTORC1 component of the metabolic pathway serves as a target for chemokine receptor-mediated T cell tolerance and suppression of T1D.

  4. Parental reflective functioning is associated with tolerance of infant distress but not general distress: evidence for a specific relationship using a simulated baby paradigm.

    PubMed

    Rutherford, Helena J V; Goldberg, Benjamin; Luyten, Patrick; Bridgett, David J; Mayes, Linda C

    2013-12-01

    Parental reflective functioning represents the capacity of a parent to think about their own and their child's mental states and how these mental states may influence behavior. Here we examined whether this capacity as measured by the Parental Reflective Functioning Questionnaire relates to tolerance of infant distress by asking mothers (N = 21) to soothe a life-like baby simulator (BSIM) that was inconsolable, crying for a fixed time period unless the mother chose to stop the interaction. Increasing maternal interest and curiosity in their child's mental states, a key feature of parental reflective functioning, was associated with longer persistence times with the BSIM. Importantly, on a non-parent distress tolerance task, parental reflective functioning was not related to persistence times. These findings suggest that parental reflective functioning may be related to tolerance of infant distress, but not distress tolerance more generally, and thus may reflect specificity to persistence behaviors in parenting contexts.

  5. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  6. Preinduction of HSP70 promotes hypoxic tolerance and facilitates acclimatization to acute hypobaric hypoxia in mouse brain

    PubMed Central

    Zhang, Kuan; Zhao, Tong; Huang, Xin; Liu, Zhao-hui; Xiong, Lei; Li, Ming-ming; Wu, Li-ying; Zhao, Yong-qi

    2008-01-01

    It has been shown that induction of HSP70 by administration of geranylgeranylacetone (GGA) leads to protection against ischemia/reperfusion injury. The present study was performed to determine the effect of GGA on the survival of mice and on brain damage under acute hypobaric hypoxia. The data showed that the mice injected with GGA survived significantly longer than control animals (survival time of 9.55 ± 3.12 min, n = 16 vs. controls at 4.28 ± 4.29 min, n = 15, P < 0.005). Accordingly, the cellular necrosis or degeneration of the hippocampus and the cortex induced by sublethal hypoxia for 6 h could be attenuated by preinjection with GGA, especially in the CA2 and CA3 regions of the hippocampus. In addition, the activity of nitric oxide synthase (NOS) of the hippocampus and the cortex was increased after exposure to sublethal hypoxia for 6 h but could be inhibited by the preinjection of GGA. Furthermore, the expression of HSP70 was significantly increased at 1 h after GGA injection. These results suggest that administration of GGA improved survival rate and prevented acute hypoxic damage to the brain and that the underlying mechanism involved induction of HSP70 and inhibition of NOS activity. PMID:19105051

  7. Pollution-induced community tolerance and functional redundancy in a decomposer food web in metal-stressed soil.

    PubMed

    Salminen, J; van Gestel, C A; Oksanen, J

    2001-10-01

    Pollution may lead to the development of pollution-induced community tolerance (PICT) in a stressed community. We studied the presence of PICT in soil food webs using soil microcosms. Soil microcosms containing soil invertebrates and microbes were collected from polluted and unpolluted areas and exposed to a range of soil zinc concentrations. A pine seedling was planted in each microcosm to measure the effects of the origin of the community and Zn pollution on above-ground plant production. The effects of the treatments on nutrient content in the soil were also measured. The diversity of soil microarthropods and the soil's mineral nutrient content were low at the Zn-polluted site. We did not observe an increasing Zn tolerance among the soil organisms in the polluted soil. However, low population growth rates of soil invertebrates from the polluted site may indicate the deleterious effects on fitness of long-lasting pollution. In the soil from the nonpolluted site, Zn additions caused changes in the invertebrate food web structure. These changes were explained by the good physiological condition of the animals and their insensitivity to Zn. The fact that the food web structure in soil from the polluted site did not change can be used as a rough indicator of PICT. Structural stability is presumed by the lack of Zn-sensitive species at this site and the inability of populations to acclimate by altering their growth or reproduction patterns in response to changing soil conditions. Although microbial-based soil decomposer systems may have a high functional redundancy, our results indicate that metal stress at the polluted site exceeds the tolerance limits of the system. As a consequence, ecosystem function at this site is endangered. This study also shows that the evolution of metal tolerance by soil decomposer organisms may not be a common reaction to soil pollution, although changes of population and community structure indicated severe metal stress on organisms.

  8. Morphine Tolerance as a Function of Ratio Schedule: Response Requirement or Unit Price?

    ERIC Educational Resources Information Center

    Hughes, Christine; Sigmon, Stacey C.; Pitts, Raymond C.; Dykstra, Linda A.

    2005-01-01

    Key pecking by 3 pigeons was maintained by a multiple fixed-ratio 10, fixed-ratio 30, fixed-ratio 90 schedule of food presentation. Components differed with respect to amount of reinforcement, such that the unit price was 10 responses per 1-s access to food. Acute administration of morphine, "l"-methadone, and cocaine dose-dependently decreased…

  9. [Post-infectious functional gastrointestinal disorders: from the acute episode to chronicity].

    PubMed

    Mearin, Fermín; Balboa, Agustín

    2011-01-01

    Functional gastrointestinal disorders (FGID) form a major part of gastroenterology practice. Several studies have reported the development of post-infectious irritable bowel syndrome (PI-IBS) after acute gastroenteritis (AGE). Non-gastrointestinal (GI) infections may increase the risk of developing IBS. There are also data showing that a GI infection may trigger functional dyspepsia (PI-FD). The possible development of PI-IBS or PI-FD depends on factors related to both the infection and the host. Microinflammation has been found in patients with post-infectious FGID. Studies performed in animal models show that infection and acute inflammation permanently change gastrointestinal motility and sensitivity. The role of AGE in the development of FGID is important not only because this entity provides an excellent natural model for pathogenic study but also because it provides an opportunity for preventive action.

  10. Functional characterization of aroA from Rhizobium leguminosarum with significant glyphosate tolerance in transgenic Arabidopsis.

    PubMed

    Han, Jing; Tian, Yong-Sheng; Xu, Jing; Wang, Li-Juan; Wang, Bo; Peng, Ri-He; Yao, Quan-Hong

    2014-09-01

    Glyphosate is the active component of the top-selling herbicide, the phytotoxicity of which is due to its inhibition of the shikimic acid pathway. 5-Enolpyruvylshikimate-3-phosphate synthase (EPSPS) is a key enzyme in the shikimic acid pathway. Glyphosate tolerance in plants can be achieved by the expression of a glyphosate-insensitive aroA gene (EPSPS). In this study, we used a PCR-based two-step DNA synthesis method to synthesize a new aroA gene (aroAR. leguminosarum) from Rhizobium leguminosarum. In vitro glyphosate sensitivity assays showed that aroAR. leguminosarum is glyphosate tolerant. The new gene was then expressed in E. coli and key kinetic values of the purified enzyme were determined. Furthermore, we transformed the aroA gene into Arabidopsis thaliana by the floral dip method. Transgenic Arabidopsis with the aroAR. leguminosarum gene was obtained to prove its potential use in developing glyphosate-resistant crops.

  11. Norepinephrine transporter function and tolerance to hypergravitational stress: A pilot study

    NASA Astrophysics Data System (ADS)

    Schroeder, Christoph; Strempel, Sebastian; Boese, Andrea; Hemmersbach, Ruth; Tank, Jens; Luft, Friedrich C.; Jordan, Jens

    Pharmacological norepinephrine transporter (NET) inhibition improves orthostatic tolerance on a tilt table while increasing heart rate. We tested the cardiovascular response to NET inhibition during a graded human centrifuge run in seven healthy men. g-Load was increased in 0.5 g steps with 3 g maximal g-load. On two separate days, patients were tested after selective NET inhibition with reboxetine or with placebo in a double-blind, randomized, crossover fashion. Resting diastolic blood pressure increased moderately with NET inhibition. Resting heart rate was profoundly increased by NET inhibition. NET inhibition augmented the heart rate response while attenuating the increase in blood pressure during hypergravitation. NET inhibition could be tested for its potential to improve cardiovascular g-tolerance.

  12. Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function

    PubMed Central

    Mackroth, Maria Sophia; Abel, Annemieke; Steeg, Christiane; Schulze zur Wiesch, Julian; Jacobs, Thomas

    2016-01-01

    In acute Plasmodium falciparum (P. falciparum) malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections. PMID:27802341

  13. Allopregnanolone Preclinical Acute Pharmacokinetic and Pharmacodynamic Studies to Predict Tolerability and Efficacy for Alzheimer’s Disease

    PubMed Central

    Irwin, Ronald W.; Solinsky, Christine M.; Loya, Carlos M.; Salituro, Francesco G.; Rodgers, Kathleen E.; Bauer, Gerhard; Rogawski, Michael A.; Brinton, Roberta Diaz

    2015-01-01

    To develop allopregnanolone as a therapeutic for Alzheimer’s disease, we investigated multiple formulations and routes of administration in translationally relevant animal models of both sexes. Subcutaneous, topical (transdermal and intranasal), intramuscular, and intravenous allopregnanolone were bolus-administered. Pharmacokinetic analyses of intravenous allopregnanolone in rabbit and mouse indicated that peak plasma and brain levels (3-fold brain/plasma ratios) at 5min were sufficient to activate neuroregenerative responses at sub-sedative doses. Slow-release subcutaneous suspension of allopregnanolone displayed 5-fold brain/plasma ratio at Cmax at 30min. At therapeutic doses by either subcutaneous or intravenous routes, allopregnanolone mouse plasma levels ranged between 34-51ng/ml by 30min, comparable to published endogenous human level in the third trimester of pregnancy. Exposure to subcutaneous, topical, intramuscular, and intravenous allopregnanolone, at safe and tolerable doses, increased hippocampal markers of neurogenesis including BrdU and PCNA in young 3xTgAD and aged wildtype mice. Intravenous allopregnanolone transiently and robustly phosphorylated CREB within 5min and increased levels of neuronal differentiation transcription factor NeuroD within 4h. Neurogenic efficacy was achieved with allopregnanolone brain exposure of 300-500hr*ng/g. Formulations were tested to determine the no observable adverse effect level (NOAEL) and maximally tolerated doses (MTD) in male and female rats by sedation behavior time course. Sex differences were apparent, males exhibited ≥40% more sedation time compared to females. Allopregnanolone formulated in sulfobutyl-ether-beta-cyclodextrin at optimized complexation ratio maximized allopregnanolone delivery and neurogenic efficacy. To establish the NOAEL and MTD for Allo-induced sedation using a once-per-week intravenous regenerative treatment regimen: In female rats the NOAEL was 0.5mg/kg and MTD 2mg/kg. The

  14. Endogenous Small-Noncoding RNAs and Potential Functions in Desiccation Tolerance in Physcomitrella Patens

    PubMed Central

    Xia, Jing; Wang, Xiaoqin; Perroud, Pierre-François; He, Yikun; Quatrano, Ralph; Zhang, Weixiong

    2016-01-01

    Early land plants like moss Physcomitrella patens have developed remarkable drought tolerance. Phytohormone abscisic acid (ABA) protects seeds during water stress by activating genes through transcription factors such as ABSCISIC ACID INSENSITIVE (ABI3). Small noncoding RNA (sncRNA), including microRNAs (miRNAs) and endogenous small-interfering RNAs (endo-siRNAs), are key gene regulators in eukaryotes, playing critical roles in stress tolerance in plants. Combining next-generation sequencing and computational analysis, we profiled and characterized sncRNA species from two ABI3 deletion mutants and the wild type P. patens that were subject to ABA treatment in dehydration and rehydration stages. Small RNA profiling using deep sequencing helped identify 22 novel miRNAs and 6 genomic loci producing trans-acting siRNAs (ta-siRNAs) including TAS3a to TAS3e and TAS6. Data from degradome profiling showed that ABI3 genes (ABI3a/b/c) are potentially regulated by the plant-specific miR536 and that other ABA-relevant genes are regulated by miRNAs and ta-siRNAs. We also observed broad variations of miRNAs and ta-siRNAs expression across different stages, suggesting that they could potentially influence desiccation tolerance. This study provided evidence on the potential roles of sncRNA in mediating desiccation-responsive pathways in early land plants. PMID:27443635

  15. Phosphoproteomic Analysis of Paper Mulberry Reveals Phosphorylation Functions in Chilling Tolerance.

    PubMed

    Pi, Zhi; Zhao, Mei-Ling; Peng, Xian-Jun; Shen, Shi-Hua

    2017-04-13

    Paper mulberry is a valuable woody species with a good chilling tolerance. In this study, phosphoproteomic analysis, physiological measurement, and mRNA quantification were employed to explore the molecular mechanism of chilling (4 °C) tolerance in paper mulberry. After chilling for 6 h, 427 significantly changed phosphoproteins were detected in paper mulberry seedlings without obvious physiological injury. When obvious physiological injury occurred after chilling for 48 h, a total of 611 phosphoproteins were found to be significantly changed at the phosphorylation level. Several protein kinases, especially CKII, were possibly responsible for these changes according to conserved sequence analysis. The results of Gene Ontology analysis showed that phosphoproteins were mainly responsible for signal transduction, protein modification, and translation during chilling. Additionally, transport and cellular component organization were enriched after chilling for 6 and 48 h, respectively. On the basis of the protein-protein interaction network analysis, a protein kinase and phosphatases hub protein (P1959) were found to be involved in cross-talk between Ca(2+), BR, ABA, and ethylene-mediated signaling pathways. We also highlighted the phosphorylation of BpSIZ1 and BpICE1 possibly impacted on the CBF/DREB-responsive pathway. From these results, we developed a schematic for the chilling tolerance mechanism at phosphorylation level.

  16. Acute Effect of High-Intensity Eccentric Exercise on Vascular Endothelial Function in Young Men.

    PubMed

    Choi, Youngju; Akazawa, Nobuhiko; Zempo-Miyaki, Asako; Ra, Song-Gyu; Shiraki, Hitoshi; Ajisaka, Ryuichi; Maeda, Seiji

    2016-08-01

    Choi, Y, Akazawa, N, Zempo-Miyaki, A, Ra, S-G, Shiraki, H, Ajisaka, R, and Maeda, S. Acute effect of high-intensity eccentric exercise on vascular endothelial function in young men. J Strength Cond Res 30(8): 2279-2285, 2016-Increased central arterial stiffness is as an independent risk factor for cardiovascular disease. Evidence regarding the effects of high-intensity resistance exercise on vascular endothelial function and central arterial stiffness is conflicting. The purpose of this study was to examine the effects of acute high-intensity eccentric exercise on vascular endothelial function and central arterial stiffness. We evaluated the acute changes in endothelium-dependent flow-mediated dilation (FMD), low-flow-mediated constriction (L-FMC), and arterial stiffness after high-intensity eccentric exercise. Seven healthy, sedentary men (age, 24 ± 1 year) performed maximal eccentric elbow flexor exercise using their nondominant arm. Before and 45 minutes after eccentric exercise, carotid arterial compliance and brachial artery FMD and L-FMC in the nonexercised arm were measured. Carotid arterial compliance was significantly decreased, and β-stiffness index significantly increased after eccentric exercise. Brachial FMD was significantly reduced after eccentric exercise, whereas there was no significant difference in brachial L-FMC before and after eccentric exercise. A positive correlation was detected between change in arterial compliance and change in FMD (r = 0.779; p ≤ 0.05), and a negative correlation was detected between change in β-stiffness index and change in FMD (r = -0.891; p < 0.01) with eccentric exercise. In this study, acute high-intensity eccentric exercise increased central arterial stiffness; this increase was accompanied by a decrease in endothelial function caused by reduced endothelium-dependent vasodilation but not by a change in endothelium-dependent vasoconstriction.

  17. Chronic and acute inspiratory muscle loading augment the effect of a 6-week interval program on tolerance of high-intensity intermittent bouts of running.

    PubMed

    Tong, Tom K; Fu, Frank H; Eston, Roger; Chung, Pak-Kwong; Quach, Binh; Lu, Kui

    2010-11-01

    This study examined the hypothesis that chronic (training) and acute (warm-up) loaded ventilatory activities applied to the inspiratory muscles (IM) in an integrated manner would augment the training volume of an interval running program. This in turn would result in additional improvement in the maximum performance of the Yo-Yo intermittent recovery test in comparison with interval training alone. Eighteen male nonprofessional athletes were allocated to either an inspiratory muscle loading (IML) group or control group. Both groups participated in a 6-week interval running program consisting of 3-4 workouts (1-3 sets of various repetitions of selected distance [100-2,400 m] per workout) per week. For the IML group, 4-week IM training (30 inspiratory efforts at 50% maximal static inspiratory pressure [P0] per set, 2 sets·d-1, 6 d·wk-1) was applied before the interval program. Specific IM warm-up (2 sets of 30 inspiratory efforts at 40% P0) was performed before each workout of the program. For the control group, neither IML was applied. In comparison with the control group, the interval training volume as indicated by the repeatability of running bouts at high intensity was approximately 27% greater in the IML group. Greater increase in the maximum performance of the Yo-Yo test (control: 16.9 ± 5.5%; IML: 30.7 ± 4.7% baseline value) was also observed after training. The enhanced exercise performance was partly attributable to the greater reductions in the sensation of breathlessness and whole-body metabolic stress during the Yo-Yo test. These findings show that the combination of chronic and acute IML into a high-intensity interval running program is a beneficial training strategy for enhancing the tolerance to high-intensity intermittent bouts of running.

  18. Molecular cloning of glucose transporter 1 in grouper Epinephelus coioides and effects of an acute hyperglycemia stress on its expression and glucose tolerance.

    PubMed

    Liu, Hongyu; Dong, Xiaohui; Chi, Shuyan; Yang, Qihui; Zhang, Shuang; Chen, Liqiao; Tan, Beiping

    2017-02-01

    The glucose transporter family proteins play pivotal roles in glucose metabolism. In this study, we successfully cloned the orange spotted grouper (Epinephelus coioides) glucose transporter 1 (EcGlut1) gene (GenBank accession: JQ623903). The full-length EcGlut1 cDNA was 2126 bp with a 1476 bp ORF, a 437bp5'-UTR and 223bp3'-UTR. EcGlut1 is predicted to encode a 491 amino acid protein with a MW of 53.9 kDa, a pI of 8.66 and a Pfam domain. Bioinformatics analysis revealed that EcGlut1 was evolutionally conserved between fishes with 80-89 % amino acid identities. EcGlut1 was expressed predominantly in heart and liver and at lower levels in muscle, intestine, stomach and brain. We also investigated the effect of acute hyperglycemia stress on EcGlut1 expression. In glucose tolerance test, changes in EcGlut1 mRNA expression in response to glucose injection and glucose metabolism-related indictors were assessed at the same time. Glucose injection significantly suppressed EcGlut1 mRNA expression in liver at 12 h and in brain at 24 h postinjection (P < 0.05). EcGlut1 mRNA levels in heart were increased at 6 h (P < 0.05). Plasma glucose level increased significantly and reached its maximum at 3 h postinjection (P < 0.05). The spatiotemporal expression of EcGlut1 and glucose metabolism suggested that orange spotted grouper might rely on fat anabolism to reduce acute hyperglycemia stress and the delayed transcription of EcGlut1 gene might be one reason for glucose intolerance in E. coioides.

  19. RIFLE criteria and hepatic function in the assessment of acute renal failure in liver transplantation.

    PubMed

    Tinti, F; Umbro, I; Meçule, A; Rossi, M; Merli, M; Nofroni, I; Corradini, S Ginanni; Poli, L; Pugliese, F; Ruberto, F; Berloco, P B; Mitterhofer, A P

    2010-05-01

    Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.

  20. Functional outcome in acute stroke patients with oropharyngeal Dysphagia after swallowing therapy.

    PubMed

    Huang, Kun-Ling; Liu, Ting-Yuan; Huang, Yu-Chi; Leong, Chau-Peng; Lin, Wei-Che; Pong, Ya-Ping

    2014-01-01

    Dysphagia after stroke is associated with mortality and increased pulmonary complications. Swallowing therapies may decrease pulmonary complications and improve patients' quality of life after stroke. This study used clinical swallowing assessments and videofluoroscopy (VFS) to assess the functional recovery of acute stroke patients with dysphagia after different swallowing therapies. We enrolled 29 acute stroke patients with dysphagia and randomly divided them into 3 therapy groups: traditional swallowing (TS), oropharyngeal neuromuscular electrical stimulation (NMES), and combined NMES/TS. All patients were assessed using the clinical functional oral intake scale (FOIS), 8-point penetration-aspiration scale (PAS), and functional dysphagia scale (FDS) of VFS before and after treatment. There were no differences in the clinical parameters and swallowing results of the FOIS and VFS before swallowing treatment among the 3 groups (P > .05). TS therapy and combined therapy both had significant swallowing improvement after therapy according to the FOIS and 8-point PAS (P < .05). When comparing the results of the VFS among the 3 groups, we found significant improvements in patients eating cookies and thick liquid after combined NMES/TS therapy (P < .05). In acute stroke patients with dysphagia, combined NMES/TS therapy is the most effective swallowing therapy in taking solid diets and thick liquids.

  1. The rice thylakoid membrane-bound ascorbate peroxidase OsAPX8 functions in tolerance to bacterial blight

    PubMed Central

    Jiang, Guanghuai; Yin, Dedong; Zhao, Jiying; Chen, Honglin; Guo, Lequn; Zhu, Lihuang; Zhai, Wenxue

    2016-01-01

    Thylakoid membrane-bound ascorbate peroxidase (tAPX) is a major H2O2-scavenging enzyme. To clarify its functions in tolerance to rice bacterial blight, we produced rice lines overexpressing and suppressing tAPX (OsAPX8). The overexpressing lines exhibited increased tolerance to bacterial pathogen. The RNA interference (RNAi) lines were considerably more sensitive than the control plant. Further analysis of the H2O2 content in these transgenic plants indicated that the H2O2 accumulation of OsAPX8-overexpressing plants was considerably less than that of wild-type and RNAi plants upon challenge with bacterial pathogen. Interestingly, H2O2 was the most important factor for the serious leaf dehydration and withering of rice without major resistance genes and was not the cause of hypersensitivity. It addition, wall tightening or loosening can occur according to the level of H2O2. In addition, OsAPX8 interacted with the susceptibility protein Os8N3/Xa13, and their binding repressed the reaction of OsAPX8 in tolerance to bacterial blight. PMID:27185545

  2. The rice thylakoid membrane-bound ascorbate peroxidase OsAPX8 functions in tolerance to bacterial blight.

    PubMed

    Jiang, Guanghuai; Yin, Dedong; Zhao, Jiying; Chen, Honglin; Guo, Lequn; Zhu, Lihuang; Zhai, Wenxue

    2016-05-17

    Thylakoid membrane-bound ascorbate peroxidase (tAPX) is a major H2O2-scavenging enzyme. To clarify its functions in tolerance to rice bacterial blight, we produced rice lines overexpressing and suppressing tAPX (OsAPX8). The overexpressing lines exhibited increased tolerance to bacterial pathogen. The RNA interference (RNAi) lines were considerably more sensitive than the control plant. Further analysis of the H2O2 content in these transgenic plants indicated that the H2O2 accumulation of OsAPX8-overexpressing plants was considerably less than that of wild-type and RNAi plants upon challenge with bacterial pathogen. Interestingly, H2O2 was the most important factor for the serious leaf dehydration and withering of rice without major resistance genes and was not the cause of hypersensitivity. It addition, wall tightening or loosening can occur according to the level of H2O2. In addition, OsAPX8 interacted with the susceptibility protein Os8N3/Xa13, and their binding repressed the reaction of OsAPX8 in tolerance to bacterial blight.

  3. Functional analyses of a putative plasma membrane Na+/H+ antiporter gene isolated from salt tolerant Helianthus tuberosus.

    PubMed

    Li, Qing; Tang, Zhong; Hu, Yibing; Yu, Ling; Liu, Zhaopu; Xu, Guohua

    2014-08-01

    Jerusalem artichokes (Helianthus tuberosus L.) can tolerate relatively higher salinity, drought and heat stress. In this paper, we report the cloning of a Salt Overly Sensitive 1 (SOS1) gene encoding a plasma membrane Na(+)/H(+) antiporter from a highly salt-tolerant genotype of H. tuberosus, NY1, named HtSOS1 and characterization of its function in yeast and rice. The amino acid sequence of HtSOS1 showed 83.4% identity with the previously isolated SOS1 gene from the Chrysanthemum crassum. The mRNA level in the leaves of H. tuberosus was significantly up-regulated by presence of high concentrations of NaCl. Localization analysis using rice protoplast expression showed that the protein encoded by HtSOS1 was located in the plasma membrane. HtSOS1 partially suppressed the salt sensitive phenotypes of a salt sensitive yeast strain. In comparison with wild type (Oryza sativa L., ssp. Japonica. cv. Nipponbare), the transgenic rice expressed with HtSOS1 could exclude more Na(+) and accumulate more K(+). Expression of HtSOS1 decreased Na(+) content much larger in the shoot than in the roots, resulting in more water content in the transgenic rice than WT. These data suggested that HtSOS1 may be useful in transgenic approaches to improving the salinity tolerance of glycophyte.

  4. Isolation of a low-sulfur tolerance gene from Eichhornia crassipes using a functional gene-mining approach.

    PubMed

    Liu, Xiao; Chen, Xi; Oliver, David J; Xiang, Cheng-Bin

    2009-12-01

    Genes enhancing nutrient utilization efficiency are needed for crop improvement. Here, we report the isolation of a gene conferring low-sulfur tolerance from water hyacinth (Eichhornia crassipes) using a functional gene-mining method. In doing this, an entry cDNA library was constructed from the roots of nutrient-starved water hyacinth using recombination cloning and subsequently shuttled into the plant transformation- and expression-ready vector. The plant transformation- and expression-ready library was transferred into Arabidopsis and a seed library of 50,000 independent transgenic lines was generated. Three transgenic lines with enhanced low-sulfur tolerance were isolated from the seed library. One of the transgenic lines, shl143-1, with improved tolerance to sulfate deficiency and an improved root system was further analyzed. It was found that a water hyacinth jacalin-related lectin gene (EcJRL-1) was overexpressed in shl143-1. Recapitulation analysis confirmed that the overexpression of the EcJRL-1 cDNA caused the phenotype. Therefore, this study demonstrates that a jacalin-related lectin is involved in root elongation under sulfur-deficient conditions.

  5. Acute effects of caffeine and cigarette smoking on ventricular long-axis function in healthy subjects

    PubMed Central

    Giacomin, Elisa; Palmerini, Elisabetta; Ballo, Piercarlo; Zacà, Valerio; Bova, Giovanni; Mondillo, Sergio

    2008-01-01

    Background Few data exist regarding the direct effects of caffeine and smoking on cardiac function. We sought to explore the acute effects of caffeine assumption, cigarette smoking, or both on left ventricular (LV) and right ventricular (RV) function in a population of young normal subjects. Methods Forty-five healthy subjects aged 25 ± 2 years underwent echocardiography. Fifteen of them were non-smokers and habitual coffee consumers (group 1), 15 were smokers and not habitual coffee consumers (group 2), and 15 were smokers and habitual coffee consumers (group 3). Peak systolic (Sa), early diastolic Ea, and late diastolic (Aa) velocity of mitral annulus were measured by pulsed Tissue Doppler, and left atrioventricular plane displacement was determined by M-mode. Tricuspid annular velocities and systolic excursion (TAPSE) were also determined. Measurements were performed at baseline and after oral assumption of caffeine 100 mg in group 1, one cigarette smoking in group 2, and both in group 3. Results No changes in ventricular function were observed in group 1 after caffeine administration. In group 2, cigarette smoking yielded an acute increase in mitral Aa (+12.1%, p = 0.0026), tricuspid Sa (+9.8%, p = 0.012) and TAPSE (+7.9%, p = 0.017), and a decrease in the mitral Ea/Aa ratio (-8.5%, p = 0.0084). Sequential caffeine assumption and cigarette smoking in group 3 was associated with an acute increase in mitral Aa (+13.0%, p = 0.015) and tricuspid Aa (+11.6%, p < 0.0001) and a reduction in mitral Ea/Aa ratio (-8.5%, p = 0.0084) tricuspid Ea (-6.6%, p = 0.048) and tricuspid Ea/Aa ratio (-9.6%, p = 0.0003). In a two-way ANOVA model controlling for hemodynamic confounding factors, changes in the overall population remained significant for mitral Aa and Ea/Aa ratio, and for tricuspid Aa and Ea/Aa ratio. Conclusion In young healthy subjects, one cigarette smoking is associated to an acute impairment in LV diastolic function and a hyperdynamic RV systolic response

  6. Decline in Executive Control during Acute Bouts of Exercise as a Function of Exercise Intensity and Fitness Level

    ERIC Educational Resources Information Center

    Labelle, Veronique; Bosquet, Laurent; Mekary, Said; Bherer, Louis

    2013-01-01

    Studies on the effects of acute bouts of cardiovascular exercise on cognitive performances show contradictory findings due to methodological differences (e.g., exercise intensity, cognitive function assessed, participants' aerobic fitness level, etc.). The present study assessed the acute effect of exercise intensity on cognition while controlling…

  7. Functional Status Predicts Acute Care Readmissions from Inpatient Rehabilitation in the Stroke Population

    PubMed Central

    Slocum, Chloe; Gerrard, Paul; Black-Schaffer, Randie; Goldstein, Richard; Singhal, Aneesh; DiVita, Margaret A.; Ryan, Colleen M.; Mix, Jacqueline; Purohit, Maulik; Niewczyk, Paulette; Kazis, Lewis; Zafonte, Ross; Schneider, Jeffrey C.

    2015-01-01

    Objective Acute care readmission risk is an increasingly recognized problem that has garnered significant attention, yet the reasons for acute care readmission in the inpatient rehabilitation population are complex and likely multifactorial. Information on both medical comorbidities and functional status is routinely collected for stroke patients participating in inpatient rehabilitation. We sought to determine whether functional status is a more robust predictor of acute care readmissions in the inpatient rehabilitation stroke population compared with medical comorbidities using a large, administrative data set. Methods A retrospective analysis of data from the Uniform Data System for Medical Rehabilitation from the years 2002 to 2011 was performed examining stroke patients admitted to inpatient rehabilitation facilities. A Basic Model for predicting acute care readmission risk based on age and functional status was compared with models incorporating functional status and medical comorbidities (Basic-Plus) or models including age and medical comorbidities alone (Age-Comorbidity). C-statistics were compared to evaluate model performance. Findings There were a total of 803,124 patients: 88,187 (11%) patients were transferred back to an acute hospital: 22,247 (2.8%) within 3 days, 43,481 (5.4%) within 7 days, and 85,431 (10.6%) within 30 days. The C-statistics for the Basic Model were 0.701, 0.672, and 0.682 at days 3, 7, and 30 respectively. As compared to the Basic Model, the best-performing Basic-Plus model was the Basic+Elixhauser model with C-statistics differences of +0.011, +0.011, and + 0.012, and the best-performing Age-Comorbidity model was the Age+Elixhauser model with C-statistic differences of -0.124, -0.098, and -0.098 at days 3, 7, and 30 respectively. Conclusions Readmission models for the inpatient rehabilitation stroke population based on functional status and age showed better predictive ability than models based on medical comorbidities. PMID

  8. Gonadal function after 12-Gy testicular irradiation in childhood acute lymphoblastic leukemia

    SciTech Connect

    Castillo, L.A.; Craft, A.W.; Kernahan, J.; Evans, R.G.; Aynsley-Green, A. )

    1990-01-01

    Gonadal function was assessed in 15 boys with acute lymphoblastic leukemia (ALL) who had received testicular irradiation. The dose to the testes was 12 Gy in 12, 15 Gy in 1, and 24 Gy in 2 cases. All of those who had received 12 or 15 Gy had normal Leydig cell function, although high levels of gonadotropins suggest subclinical Leydig cell damage. The 2 who had 24 Gy had Leydig cell failure. All who were old enough to produce a semen specimen were azoospermic.

  9. The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

    PubMed Central

    Jeddi, Sajad; Asl, Amir Nezami; Asgari, Alireza; Ghasemi, Asghar

    2016-01-01

    Background Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. Objective To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. Method SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. Results In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p < 0.05) lower, and HR (32%) was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. Conclusion Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR. PMID:26559853

  10. The inhibition and potentiation of procarbazine on hepatic mixed-function oxidases in phenobarbital tolerant and nontolerant mice.

    PubMed

    Onoda, K; Ho, I K

    1980-01-01

    The effect of procarbazine on mixed-function oxidases was investigated in naive and pentobarbital tolerant mice. In mice receiving procarbazine, 200 mg/kg, i.p. 1 hr earlier, metabolisms of pentobarbital, aniline and ethylmorphine in vitro and cytochrome P-450 content of hepatic microsomes were significantly decreased. The drug binding of either aniline or pentobarbital to cytochrome P-450 was also decreased. However, procarbazine failed to exert this effect after the enzymes had been induced by continuous administration of pentobarbital. Interestingly, procarbazine enhanced the barbiturate induced hepatic microsomal mixed-function oxidase activities when it was administered before the implantation of pentobarbital pellet. Both cytochrome P-450 and cytochrome b5 content after pentobarbital pellet implantation were further increased by pretreatment with procarbazine. This finding was further substantiated by the increase in pentobarbital and aniline binding to cytochrome P-450. The present studies may provide another model for studying the nature of hepatic mixed-function oxidase induction process.

  11. Per capita interactions and stress tolerance drive stress-induced changes in biodiversity effects on ecosystem functions

    PubMed Central

    Baert, Jan M.; Janssen, Colin R.; Sabbe, Koen; De Laender, Frederik

    2016-01-01

    Environmental stress changes the relationship between biodiversity and ecosystem functions, but the underlying mechanisms are poorly understood. Because species interactions shape biodiversity–ecosystem functioning relationships, changes in per capita interactions under stress (as predicted by the stress gradient hypothesis) can be an important driver of stress-induced changes in these relationships. To test this hypothesis, we measure productivity in microalgae communities along a diversity and herbicide gradient. On the basis of additive partitioning and a mechanistic community model, we demonstrate that changes in per capita interactions do not explain effects of herbicide stress on the biodiversity–productivity relationship. Instead, assuming that the per capita interactions remain unaffected by stress, causing species densities to only change through differences in stress tolerance, suffices to predict the stress-induced changes in the biodiversity–productivity relationship and community composition. We discuss how our findings set the stage for developing theory on how environmental stress changes biodiversity effects on ecosystem functions. PMID:27534986

  12. Per capita interactions and stress tolerance drive stress-induced changes in biodiversity effects on ecosystem functions.

    PubMed

    Baert, Jan M; Janssen, Colin R; Sabbe, Koen; De Laender, Frederik

    2016-08-18

    Environmental stress changes the relationship between biodiversity and ecosystem functions, but the underlying mechanisms are poorly understood. Because species interactions shape biodiversity-ecosystem functioning relationships, changes in per capita interactions under stress (as predicted by the stress gradient hypothesis) can be an important driver of stress-induced changes in these relationships. To test this hypothesis, we measure productivity in microalgae communities along a diversity and herbicide gradient. On the basis of additive partitioning and a mechanistic community model, we demonstrate that changes in per capita interactions do not explain effects of herbicide stress on the biodiversity-productivity relationship. Instead, assuming that the per capita interactions remain unaffected by stress, causing species densities to only change through differences in stress tolerance, suffices to predict the stress-induced changes in the biodiversity-productivity relationship and community composition. We discuss how our findings set the stage for developing theory on how environmental stress changes biodiversity effects on ecosystem functions.

  13. Dynamic functional cerebral blood volume responses to normobaric hyperoxia in acute ischemic stroke

    PubMed Central

    Wu, Ona; Lu, Jie; Mandeville, Joseph B; Murata, Yoshihiro; Egi, Yasu; Dai, Guangping; Marota, John J; Diwan, Izzuddin; Dijkhuizen, Rick M; Kwong, Kenneth K; Lo, Eng H; Singhal, Aneesh B

    2012-01-01

    Studies suggest that neuroprotective effects of normobaric oxygen (NBO) therapy in acute stroke are partly mediated by hemodynamic alterations. We investigated cerebral hemodynamic effects of repeated NBO exposures. Serial magnetic resonance imaging (MRI) was performed in Wistar rats subjected to focal ischemic stroke. Normobaric oxygen-induced functional cerebral blood volume (fCBV) responses were analyzed. All rats had diffusion-weighted MRI (DWI) lesions within larger perfusion deficits, with DWI lesion expansion after 3 hours. Functional cerebral blood volume responses to NBO were spatially and temporally heterogeneous. Contralateral healthy tissue responded consistently with vasoconstriction that increased with time. No significant responses were evident in the acute DWI lesion. In hypoperfused regions surrounding the acute DWI lesion, tissue that remained viable until the end of the experiment showed relative preservation of mean fCBV at early time points, with some rats showing increased fCBV (vasodilation); however, these regions later exhibited significantly decreased fCBV (vasoconstriction). Tissue that became DWI abnormal by study-end initially showed marginal fCBV changes that later became moderate fCBV reductions. Our results suggest that a reverse-steal hemodynamic effect may occur in peripheral ischemic zones during NBO treatment of focal stroke. In addition, CBV responses to NBO challenge may have potential as an imaging marker to distinguish ischemic core from salvageable tissues. PMID:22739619

  14. Molecular and Functional Characterization of Wheat ARGOS Genes Influencing Plant Growth and Stress Tolerance.

    PubMed

    Zhao, Yue; Tian, Xuejun; Li, Yuanyuan; Zhang, Liyuan; Guan, Panfeng; Kou, Xiaoxia; Wang, Xiaobo; Xin, Mingming; Hu, Zhaorong; Yao, Yingyin; Ni, Zhongfu; Sun, Qixin; Peng, Huiru

    2017-01-01

    Auxin Regulated Gene involved in Organ Size (ARGOS) is significantly and positively associated with organ size and is involved in abiotic stress responses in plants. However, no studies on wheat ARGOS genes have been reported to date. In the present study, three TaARGOS homoeologous genes were isolated and located on chromosomes 4A, 4B, and 4D of bread wheat, all of which are highly conserved in wheat and its wild relatives. Comparisons of gene expression in different tissues demonstrated that the TaARGOSs were mainly expressed in the stem. Furthermore, the TaARGOS transcripts were significantly induced by drought, salinity, and various phytohormones. Transient expression of the TaARGOS-D protein in wheat protoplasts showed that TaARGOS-D localized to the endoplasmic reticulum. Moreover, overexpression of TaARGOS-D in Arabidopsis resulted in an enhanced germination rate, larger rosette diameter, increased rosette leaf area, and higher silique number than in wild-type (WT) plants. The roles of TaARGOS-D in the control of plant growth were further studied via RNA-seq, and it was found that 105 genes were differentially expressed; most of these genes were involved in 'developmental processes.' Interestingly, we also found that overexpression of TaARGOS-D in Arabidopsis improved drought and salinity tolerance and insensitivity to ABA relative to that in WT plants. Taken together, these results demonstrate that the TaARGOSs are involved in seed germination, seedling growth, and abiotic stress tolerance.

  15. A novel Azotobacter vinellandii (SRIAz3) functions in salinity stress tolerance in rice.

    PubMed

    Sahoo, Ranjan Kumar; Ansari, Mohammad Wahid; Pradhan, Madhusmita; Dangar, Tushar K; Mohanty, Santanu; Tuteja, Narendra

    2014-01-01

    The plant growth promoting rhizobacteria (PGPRs) as a biofertilizer provide agricultural benefits to advance various crops productivity. Recently, we discovered a novel Azotobacter vinellandii (SRIAz3) from rice rhizosphere, which is well competent to improve rice productivity. In this study, we investigated a role of A. vinellandii to confer salinity tolerance in rice (var. IR64). A. vinellandii inoculated rice plants showed higher proline and malondialdehyde content under 200 mM NaCl stress as compared with uninoculated one. The endogenous level of plant hormones viz., indole-3 acetic acid (IAA), gibberellins (GA3), zeatint (Zt) was higher in A. vinellandii inoculated plants under high salinity. The fresh biomass of root and shoot were relatively elevated in A. vinellandii inoculated rice. Further, the macronutrient profile was superior in A. vinellandii inoculated plants under salinity as compared with non-inoculated plants. The present findings further suggest that A. vinellandii, a potent biofertilzer, potentially confer salinity stress tolerance in rice via sustaining growth and improving compatible solutes and nutrients profile and thereby crop improvement.

  16. Tolerability and toxicity of prophylactic cranial irradiation in patients with non-small cell lung cancer – Results of a phase II study (with estimation of hematological toxicity, pituitary function and magnetic resonance spectra changes)

    PubMed Central

    Marzena, Gawkowska-Suwińska; Sławomir, Blamek; Alicja, Heyda; Łukasz, Boguszewicz; Anna, Cichoń; Łukasz, Zarudzki; Elżbieta, Nowicka; Katarzyna, Behrendt; Beata, Smolska-Ciszewska; Grzegorz, Plewicki; Aleksander, Zajusz; Rafał, Tarnawski

    2014-01-01

    Aim To evaluate the tolerability and toxicity of PCI in patients with NSCLC. Background Prophylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment. Materials and methods From 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30 Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with 1H nuclear magnetic resonance spectra, and estimation of pituitary function. Results During follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease (p = 0.062). Visual-motor function deteriorated after treatment (p < 0.059). Performance IQ decreased (p < 0.025) and the difference between performance IQ and verbal IQ increased (p < 0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI. Conclusion PCI in the current series was well tolerated and associated with a relatively low toxicity. PMID:25337408

  17. Tolerating Zero Tolerance?

    ERIC Educational Resources Information Center

    Moore, Brian N.

    2010-01-01

    The concept of zero tolerance dates back to the mid-1990s when New Jersey was creating laws to address nuisance crimes in communities. The main goal of these neighborhood crime policies was to have zero tolerance for petty crime such as graffiti or littering so as to keep more serious crimes from occurring. Next came the war on drugs. In federal…

  18. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

    PubMed Central

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

  19. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

    PubMed

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-03-24

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

  20. Changes in executive function after acute bouts of passive cycling in Parkinson's disease.

    PubMed

    Ridgel, Angela L; Kim, Chul-Ho; Fickes, Emily J; Muller, Matthew D; Alberts, Jay L

    2011-04-01

    Individuals with Parkinson's disease (PD) often experience cognitive declines. Although pharmacologic therapies are helpful in treating motor deficits in PD, they do not appear to be effective for cognitive complications. Acute bouts of moderate aerobic exercise have been shown to improve cognitive function in healthy adults. However, individuals with PD often have difficulty with exercise. This study examined the effects of passive leg cycling on executive function in PD. Executive function was assessed with Trail-Making Test (TMT) A and B before and after passive leg cycling. Significant improvements on the TMT-B test occurred after passive leg cycling. Furthermore, the difference between times to complete the TMT-B and TMT-A significantly decreased from precycling to postcycling. Improved executive function after passive cycling may be a result of increases in cerebral blood flow. These findings suggest that passive exercise could be a concurrent therapy for cognitive decline in PD.

  1. Functional abnormalities of sinusoidal endothelial cells in rats with acute liver rejection.

    PubMed

    Yokoi, Y; Nakamura, S; Muro, H; Baba, S

    1994-01-01

    The purpose of this study was to determine the changes of hepatic sinusoidal endothelial cell (SEC) function in acute liver rejection with respect to receptor-mediated endocytosis. Orthotopic rat liver transplantation was performed in Lewis rats grafted with DA livers and in Lewis rats grafted with Lewis livers as rejectors and controls, respectively. Animals were killed at 1, 3, 5, 7, and 10 days after the operation. Fc receptors (FcRs) were histochemically stained on frozen liver sections by applying peroxidase-antiperoxidase IgG complex as a ligand, and the FcR activity, i.e., capacity of binding the ligands represented by the FcR staining intensity, was semiquantitatively analyzed as an indicator of SEC function. The serum level of hyaluronic acid, which is specifically cleared from the circulation by receptor-mediated SEC endocytosis, was also assayed, along with the total serum bilirubin. Three days after the operation, the SECs of rejectors showed a significantly weaker FcR staining intensity of about half the value of that seen in the controls (P < 0.05), and staining disappeared after 5 days (P < 0.01). The decrease of FcR staining intensity, i.e., FcR activity, showed a correlation with elevation of the serum hyaluronic acid level (r = -0.77; P < 0.001). Histological evidence of endothelialitis and a significant elevation of total serum bilirubin (P < 0.01) were also present at 3 and 5 days, respectively. These results suggest that impairment of the endocytic function of SECs occurs at an earlier phase of acute liver rejection when compared with development of abnormalities of traditional indicators. Determination of receptor-mediated SEC endocytic functions may thus provide useful information for the early diagnosis of acute rejection.

  2. Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise.

    PubMed

    Decroix, Lieselot; Tonoli, Cajsa; Soares, Danusa D; Tagougui, Semah; Heyman, Elsa; Meeusen, Romain

    2016-12-01

    Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO2), deoxygenated (ΔHHb), and total haemoglobin (ΔHbtot) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO2 during the resting CT was increased by CF, compared with PL. ΔHbO2, ΔHHb, and ΔHbtot increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.

  3. Effects of sleep deprivation on autonomic and endocrine functions throughout the day and on exercise tolerance in the evening.

    PubMed

    Konishi, Masayuki; Takahashi, Masaki; Endo, Naoya; Numao, Shigeharu; Takagi, Shun; Miyashita, Masashi; Midorikawa, Taishi; Suzuki, Katsuhiko; Sakamoto, Shizuo

    2013-01-01

    The aim of this study was to investigate the effects of sleep deprivation on autonomic and endocrine functions during the day and on exercise tolerance in the evening. Ten healthy young males completed two, 2-day control and sleep deprivation trials. For the control trial, participants were allowed normal sleep from 23:00 to 07:00 h. For the sleep deprivation trial, participants did not sleep for 34 h. Autonomic activity was measured from 19:00 h on day 1 to 16:00 h on day 2 by frequency-domain measures of heart rate variability. Endocrine function was examined by measuring adrenocorticotropic hormone and cortisol from venous blood samples collected on day 2 at 09:00, 13:00, and 17:00 h and immediately after an exercise tolerance testing. Autonomic regulation, particularly parasympathetic regulation estimated from the high-frequency component of heart rate variability analysis, was significantly higher in the sleep deprivation trial than in the control trial in the morning and afternoon of day 2. Plasma adrenocorticotropic hormone concentrations were significantly higher at 09:00 and 13:00 h of day 2 under sleep deprivation. Heart rate during exercise was significantly lower following sleep deprivation. Therefore, the effects of sleep deprivation on autonomic regulation depend on the time of the day.

  4. Effectiveness of acute geriatric units on functional decline, living at home, and case fatality among older patients admitted to hospital for acute medical disorders: meta-analysis

    PubMed Central

    Suárez-García, Francisco M; López-Arrieta, Jesús; Rodríguez-Mañas, Leocadio; Rodríguez-Artalejo, Fernando

    2009-01-01

    Objective To assess the effectiveness of acute geriatric units compared with conventional care units in adults aged 65 or more admitted to hospital for acute medical disorders. Design Systematic review and meta-analysis. Data sources Medline, Embase, and the Cochrane Library up to 31 August 2008, and references from published literature. Review methods Randomised trials, non-randomised trials, and case-control studies were included. Exclusions were studies based on administrative databases, those that assessed care for a single disorder, those that evaluated acute and subacute care units, and those in which patients were admitted to the acute geriatric unit after three or more days of being admitted to hospital. Two investigators independently selected the studies and extracted the data. Results 11 studies were included of which five were randomised trials, four non-randomised trials, and two case-control studies. The randomised trials showed that compared with older people admitted to conventional care units those admitted to acute geriatric units had a lower risk of functional decline at discharge (combined odds ratio 0.82, 95% confidence interval 0.68 to 0.99) and were more likely to live at home after discharge (1.30, 1.11 to 1.52), with no differences in case fatality (0.83, 0.60 to 1.14). The global analysis of all studies, including non-randomised trials, showed similar results. Conclusions Care of people aged 65 or more with acute medical disorders in acute geriatric units produces a functional benefit compared with conventional hospital care, and increases the likelihood of living at home after discharge. PMID:19164393

  5. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    PubMed Central

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  6. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-08

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  7. Application of Acute Maximal Exercise to Enhance Mechanisms Underlying Blood Pressure Regulation and Orthostatic Tolerance After Exposure to Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Engelke, K. A.; Doerr, D. F.

    1999-01-01

    Development of orthostatic hypotension and intolerance in astronauts who return to earth following a spaceflight mission represents a significant operational concern to NASA. Reduced plasma volume, vascular resistance, and baroreflex responsiveness following exposure to actual and ground-based analogs of microgravity have been associated with orthostatic instability, suggesting that these mechanisms may contribute alone or in combination to compromise of blood pressure regulation after spaceflight. It therefore seems reasonable that development of procedures designed to reverse or restore the effects of microgravity on regulatory mechanisms of blood volume, vascular resistance and cardiac function should provide some protection against postflight orthostatic intolerance. Several investigations have provided evidence that a single bout of exhaustive dynamic exercise enhances functions of mechanisms responsible for blood pressure stability. Therefore, the purpose of our research project was to conduct a series of experiments using ground-based analogs of reduced gravity (i.e., prolonged restriction to the upright standing posture) in human subjects to investigate the hypothesis that a single bout of dynamic maximal exercise would restore blood volume, vascular resistance and cardiac function and improve blood pressure stability.

  8. Molecular and Functional Characterization of Wheat ARGOS Genes Influencing Plant Growth and Stress Tolerance

    PubMed Central

    Zhao, Yue; Tian, Xuejun; Li, Yuanyuan; Zhang, Liyuan; Guan, Panfeng; Kou, Xiaoxia; Wang, Xiaobo; Xin, Mingming; Hu, Zhaorong; Yao, Yingyin; Ni, Zhongfu; Sun, Qixin; Peng, Huiru

    2017-01-01

    Auxin Regulated Gene involved in Organ Size (ARGOS) is significantly and positively associated with organ size and is involved in abiotic stress responses in plants. However, no studies on wheat ARGOS genes have been reported to date. In the present study, three TaARGOS homoeologous genes were isolated and located on chromosomes 4A, 4B, and 4D of bread wheat, all of which are highly conserved in wheat and its wild relatives. Comparisons of gene expression in different tissues demonstrated that the TaARGOSs were mainly expressed in the stem. Furthermore, the TaARGOS transcripts were significantly induced by drought, salinity, and various phytohormones. Transient expression of the TaARGOS-D protein in wheat protoplasts showed that TaARGOS-D localized to the endoplasmic reticulum. Moreover, overexpression of TaARGOS-D in Arabidopsis resulted in an enhanced germination rate, larger rosette diameter, increased rosette leaf area, and higher silique number than in wild-type (WT) plants. The roles of TaARGOS-D in the control of plant growth were further studied via RNA-seq, and it was found that 105 genes were differentially expressed; most of these genes were involved in ‘developmental processes.’ Interestingly, we also found that overexpression of TaARGOS-D in Arabidopsis improved drought and salinity tolerance and insensitivity to ABA relative to that in WT plants. Taken together, these results demonstrate that the TaARGOSs are involved in seed germination, seedling growth, and abiotic stress tolerance. PMID:28228774

  9. Peripheral B cell tolerance and function in transgenic mice expressing an IgD superantigen.

    PubMed

    Duong, Bao Hoa; Ota, Takayuki; Aït-Azzouzene, Djemel; Aoki-Ota, Miyo; Vela, José Luis; Huber, Christoph; Walsh, Kevin; Gavin, Amanda L; Nemazee, David

    2010-04-15

    Transitional B cells turn over rapidly in vivo and are sensitive to apoptosis upon BCR ligation in vitro. However, little direct evidence addresses their tolerance sensitivity in vivo. A key marker used to distinguish these cells is IgD, which, through alternative RNA splicing of H chain transcripts, begins to be coexpressed with IgM at this stage. IgD is also expressed at high levels on naive follicular (B-2) and at lower levels on marginal zone and B-1 B cells. In this study, mice were generated to ubiquitously express a membrane-bound IgD-superantigen. These mice supported virtually no B-2 development, a greatly reduced marginal zone B cell population, but a relatively normal B-1 compartment. B cell development in the spleen abruptly halted at the transitional B cell population 1 to 2 stage, a block that could not be rescued by either Bcl-2 or BAFF overexpression. The developmentally arrested B cells appeared less mature and turned over more rapidly than nontransgenic T2 cells, exhibiting neither conventional features of anergy nor appreciable receptor editing. Paradoxically, type-2 T-independent responses were more robust in the transgenic mice, although T-dependent responses were reduced and had skewed IgL and IgH isotype usages. Nevertheless, an augmented memory response to secondary challenge was evident. The transgenic mice also had increased serum IgM, but diminished IgG, levels mirrored by the increased numbers of IgM(+) plasma cells. This model should facilitate studies of peripheral B cell tolerance, with the advantages of allowing analysis of polyclonal populations, and of B cells naturally lacking IgD.

  10. Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.

    PubMed

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H; English, Mark; Talcott, Susanne; Jaffe, Iris Z; Christou, Demetra D

    2016-01-01

    Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure.

  11. Acute Effect of Mineralocorticoid Receptor Antagonism on Vascular Function in Healthy Older Adults

    PubMed Central

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H.; English, Mark; Talcott, Susanne; Jaffe, Iris Z.; Christou, Demetra D.

    2015-01-01

    Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 y; mean ± SE, 53–79 y) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4mg) following eplerenone (100 mg/dose, 2 doses, 24 hours between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6 %, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOSSer1177 to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5 %, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77± 4/2 mmHg, P ≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure. PMID:26639352

  12. Effect of coronary artery recanalization on right ventricular function in patients with acute myocardial infarction

    SciTech Connect

    Verani, M.S.; Tortoledo, F.E.; Batty, J.W.; Raizner, A.E.

    1985-05-01

    The effects of coronary artery recanalization by intracoronary administration of streptokinase on left ventricular function during acute myocardial infarction have received increasing attention in recent years. Although myocardial dysfunction is often more pronounced in the right ventricle than in the left ventricle in patients with acute inferior wall myocardial infarction, the effect of coronary artery recanalization on right ventricular dysfunction has not been previously addressed. Accordingly, in this investigation, 54 patients who participated in a prospective, controlled, randomized trial of recanalization during acute myocardial infarction were studied. Among 30 patients with inferior wall infarction, 19 had right ventricular dysfunction on admission; 11 of these 19 had positive uptake of technetium-99m pyrophosphate in the right ventricle, indicative of right ventricular infarction. Patients with successful recanalization exhibited improved right ventricular ejection fraction from admission to day 10. However, control patients and patients who did not undergo recanalization also exhibited improvement. These data indicate that the right ventricular dysfunction commonly associated with inferior wall infarction is often transient, and improvement is the rule, irrespective of early recanalization of the infarct vessel.

  13. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

    PubMed Central

    Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

    2016-01-01

    Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

  14. Pulmonary function of children with acute leukemia in maintenance phase of chemotherapy☆

    PubMed Central

    de Macêdo, Thalita Medeiros Fernandes; Campos, Tania Fernandes; Mendes, Raquel Emanuele de França; França, Danielle Corrêa; Chaves, Gabriela Suéllen da Silva; de Mendonça, Karla Morganna Pereira Pinto

    2014-01-01

    OBJECTIVE: The aim of this study was to assess the pulmonary function of children with acute leukemia. METHODS: Cross-sectional observational analytical study that enrolled 34 children divided into groups A (17 with acute leukemia in the maintenance phase of chemotherapy) and B (17 healthy children). The groups were matched for sex, age and height. Spirometry was measured using a spirometer Microloop Viasys(r) in accordance with American Thoracic Society and European Respiratory Society guidelines. Maximal respiratory pressures were measured with an MVD300 digital manometer (Globalmed(r)). Maximal inspiratory pressures and maximal expiratory pressures were measured from residual volume and total lung capacity, respectively. RESULTS: Group A showed a significant decrease in maximal inspiratory pressures when compared to group B. No significant difference was found between the spirometric values of the two groups, nor was there any difference between maximal inspiratory pressure and maximal expiratory pressure values in group A compared to the lower limit values proposed as reference. CONCLUSION: Children with acute leukemia, myeloid or lymphoid, during the maintenance phase of chemotherapy exhibited unchanged spirometric variables and maximal expiratory pressure; However, there was a decrease in inspiratory muscle strength. PMID:25510995

  15. Perception of acute airway function changes by patients with mild asthma.

    PubMed

    Malakauskas, Kestutis; Ragaisiene, Sandra; Sakalauskas, Raimundas; Sakalauskas, Rainundas

    2009-01-01

    The objective of this study was to compare the perception of dyspnea during acute bronchoconstriction and bronchodilation in patients with mild asthma with normal lung function who never experienced severe asthma exacerbations in the past. We studied 83 mild, stable asthmatic patients aged 18-58 years. All patients underwent the methacholine challenge followed by the bronchodilation test with salbutamol. The perceptual sensitivity of changes in airway function was analyzed by linear regression coefficients, slope alpha(constr), and slope alpha(dilat). Additionally, the perception score was determined at a 20% decrease in FEV(1) (PS(20)) during the methacholine challenge. The finding was that perceptual sensitivity for bronchoconstriction and bronchodilation, expressed as slope alpha(constr) and slope alpha(dilat), was similar in the study subjects (mean +/- SD, 0.09 +/- 0.05 and 0.10 +/- 0.05, respectively). The two subgroups under assessment were named poor perceivers when PS(20) < 1 (n = 19) and good perceivers when PS(20) > or = 1 (n = 64). While assessing them, the values of slope alpha(constr) did not differ from the values of slope alpha(dilat) in either of the subgroups of poor perceivers or good perceivers. However, the poor perceivers sensed changes in airway function significantly less than the good perceivers did, although overlapping values of slope alpha were observed. In conclusion, this study indicates that perceptual sensitivity during acute bronchoconstriction and bronchodilation is comparably the same in mild, stable asthmatic patients. However, some of these asthmatic patients may display a diminished perception of dyspnea, which can lead to the deterioration of their asthma without their noticing the corresponding symptoms. Thus, they may delay treatment for acute asthma.

  16. Pulmonary Artery Dilation and Right Ventricular Function in Acute Kawasaki Disease.

    PubMed

    Numano, Fujito; Shimizu, Chisato; Tremoulet, Adriana H; Dyar, Dan; Burns, Jane C; Printz, Beth F

    2016-03-01

    Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center. Clinical, laboratory, and echocardiographic data from 143 acute KD subjects were analyzed. PA dilation was documented in 23 subjects (16.1 %); these subjects had higher median right ventricle myocardial performance index (RV MPI), higher ratio of early tricuspid inflow velocity to tricuspid annular early diastolic velocity (TV E/e'), and lower median TV e' velocity compared to the non-PA dilation group (0.50 vs 0.38 p < 0.01, 4.2 vs 3.6 p < 0.05, and 13.5 vs 15.2 cm/s p < 0.01, respectively). Almost all subjects with PA dilation had improved PA Z-score, RV MPI, and TV E/e' in the subacute phase (p < 0.01). There were no significant differences in indices of left ventricle function between PA dilation group and non-PA dilation group. In summary, PA dilation was documented in 16 % of acute KD subjects. These subjects were more likely to have echocardiographic indices consistent with isolated RV dysfunction that improved in the subacute phase. The long-term consequence of these findings will require longitudinal studies of this patient population.

  17. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction.

  18. [Evaluation of oral glucose tolerance test in the assessment of reserved function of liver for patients with hepatocellular carcinoma].

    PubMed

    Wen, T; Zheng, G; Meng, X; Chen, L

    1997-06-01

    The aim of this study was to evaluate oral glucose tolerance test(OGTT)in the assessment of reserved function of liver for predicting the tolerability of patients to hepatectomy and hence provided a criteria for selecting the candidates for undergoing hepatectomy, since the majority of hepatocellular carcinoma (HCC) patients were associated with posthepatitis cirrhosis. The preoperative and postoperative OGTT and liver biopsy for pathological investigation were carried out in 62 cases of hepatecomized patients and 49 cases of unresected patients for comparison. The results revealed that the patients whose preoperative OGTT curve was of P type recovered uneventfully after hepatectomy, but those whose curve was of L type of tolerated poorly to hepatectomy and were liable to postoperative hepatic failure and complications. The severity of cirrbosis in those poor risk patients fell to C III or C IV histological degree. 29 patients with intermediate feature of OGTT curve between P type and L type, i.e. I type underwent regional vascular occlusion at hepatic hilus as hepatectomy, and infusion of Danshen extract solution before vascular occlusion to prevent hepatocytes from reperfusion injury. Of them, 20 recovered uneventfully, 8 suffered from complications such as ascites and/or juandice, and 1 died within 1 month after operation. The followup study showed that the survival time of patients with P type OGTT curve was longer than that of I type, and the latter was longer than that of L type. The pattern of OGTT curve could change from preoperative P type to postoperative L type, depending on the severity of vascular interruption of liver and the ischemic injury to hepatocytic mass in operation.

  19. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice

    PubMed Central

    Ringelstetter, Ashley; Khatib, Hasan; Abbott, David H.; Salih, Sana M.

    2015-01-01

    Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2–24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the “infertility index” (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse

  20. The relationship between executive functions and capacity to consent to treatment in acute psychiatric hospitalization.

    PubMed

    Mandarelli, Gabriele; Parmigiani, Giovanna; Tarsitani, Lorenzo; Frati, Paola; Biondi, Massimo; Ferracuti, Stefano

    2012-12-01

    Despite the acknowledged influence of cognition on patients' capacity to consent to treatment, the specific neuropsychological domains involved remain elusive, as does the role of executive functions. We investigated possible associations between executive functions and decisional capacity in a sample of acute psychiatric inpatients. Patients were recruited and evaluated through the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the 24-item Brief Psychiatric Rating Scale (BPRS), the Mini-Mental State Examination (MMSE), and the Wisconsin Card Sorting Test (WCST). Patients with poor executive functioning performed worse in MacCAT understanding, appreciation, and expression of a choice, compared with good performers. These findings point to the importance of cognition in decisional capacity processes. In addition, the strong association found between learning abilities and informed consent decision-making provide empirical evidence indicating possible cognitive enhancement strategies that may improve psychiatric patients' competency.

  1. Dynamic regulation of heart rate during acute hypotension: new insight into baroreflex function

    NASA Technical Reports Server (NTRS)

    Zhang, R.; Behbehani, K.; Crandall, C. G.; Zuckerman, J. H.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

    2001-01-01

    To examine the dynamic properties of baroreflex function, we measured beat-to-beat changes in arterial blood pressure (ABP) and heart rate (HR) during acute hypotension induced by thigh cuff deflation in 10 healthy subjects under supine resting conditions and during progressive lower body negative pressure (LBNP). The quantitative, temporal relationship between ABP and HR was fitted by a second-order autoregressive (AR) model. The frequency response was evaluated by transfer function analysis. Results: HR changes during acute hypotension appear to be controlled by an ABP error signal between baseline and induced hypotension. The quantitative relationship between changes in ABP and HR is characterized by a second-order AR model with a pure time delay of 0.75 s containing low-pass filter properties. During LBNP, the change in HR/change in ABP during induced hypotension significantly decreased, as did the numerator coefficients of the AR model and transfer function gain. Conclusions: 1) Beat-to-beat HR responses to dynamic changes in ABP may be controlled by an error signal rather than directional changes in pressure, suggesting a "set point" mechanism in short-term ABP control. 2) The quantitative relationship between dynamic changes in ABP and HR can be described by a second-order AR model with a pure time delay. 3) The ability of the baroreflex to evoke a HR response to transient changes in pressure was reduced during LBNP, which was due primarily to a reduction of the static gain of the baroreflex.

  2. Acute Cognitively Engaging Exergame-Based Physical Activity Enhances Executive Functions in Adolescents

    PubMed Central

    Heinks, Theda; Eggenberger, Noëmi; Schmidt, Mirko

    2016-01-01

    The study aimed to elucidate the influence of cognitive engagement comprised in an acute bout of exergame-based physical activity on executive functions (inhibition, cognitive flexibility) in adolescents. Therefore, the level of cognitive engagement and the intensity of physical activity were systematically varied across three experimental conditions. Sixty-five healthy male adolescents (13–16 years) were randomly assigned to one of three conditions: (a) physical activity with high levels of cognitive engagement during active video gaming, (b) physical activity with low levels of cognitive engagement during active video gaming, (c) sedentary with low levels of cognitive engagement during passive video watching. Manipulation checks, including subjective and objective operationalizations of cognitive engagement, were applied. Executive functions were assessed before and after each condition using the D-KEFS design fluency test. Results showed that cognitive engagement, operationalized by subjects’ ratings and heart rate variability, differed between conditions. The physical activity condition with a high level of cognitive engagement resulted in significantly better performance in cognitive flexibility compared to conditions with low levels of cognitive engagement. Regarding benefits for executive functions in male adolescents, the results indicate that acute physical activity with high cognitive engagement could be more efficient than physical activity of the same intensity with low cognitive engagement. Even though further evidence is needed, these results extend previous research and suggest a methodological approach for measuring cognitive engagement. PMID:28030542

  3. Disrupted functional connectivity of the default mode network due to acute vestibular deficit.

    PubMed

    Klingner, Carsten M; Volk, Gerd F; Brodoehl, Stefan; Witte, Otto W; Guntinas-Lichius, Orlando

    2014-01-01

    Vestibular neuritis is defined as a sudden unilateral partial failure of the vestibular nerve that impairs the forwarding of vestibular information from the labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural instability with a tendency toward ipsilesional falls. Although vestibular neuritis is a common disease, the central mechanisms to compensate for the loss of precise vestibular information remain poorly understood. It was hypothesized that symptoms following acute vestibular neuritis originate from difficulties in the processing of diverging sensory information between the responsible brain networks. Accordingly an altered resting activity was shown in multiple brain areas of the task-positive network. Because of the known balance between the task-positive and task-negative networks (default mode network; DMN) we hypothesize that also the DMN is involved. Here, we employ functional magnetic resonance imaging (fMRI) in the resting state to investigate changes in the functional connectivity between the DMN and task-positive networks, in a longitudinal design combined with measurements of caloric function. We demonstrate an initially disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that the disturbed connectivity between the default mode network and particular parts of the task-positive network might be related to a sustained utilization of processing capacity by diverging sensory information. The current results provide some insights into mechanisms of central compensation following an acute vestibular deficit and the importance of the DMN in this disease.

  4. Disrupted functional connectivity of the default mode network due to acute vestibular deficit

    PubMed Central

    Klingner, Carsten M.; Volk, Gerd F.; Brodoehl, Stefan; Witte, Otto W.; Guntinas-Lichius, Orlando

    2014-01-01

    Vestibular neuritis is defined as a sudden unilateral partial failure of the vestibular nerve that impairs the forwarding of vestibular information from the labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural instability with a tendency toward ipsilesional falls. Although vestibular neuritis is a common disease, the central mechanisms to compensate for the loss of precise vestibular information remain poorly understood. It was hypothesized that symptoms following acute vestibular neuritis originate from difficulties in the processing of diverging sensory information between the responsible brain networks. Accordingly an altered resting activity was shown in multiple brain areas of the task-positive network. Because of the known balance between the task-positive and task-negative networks (default mode network; DMN) we hypothesize that also the DMN is involved. Here, we employ functional magnetic resonance imaging (fMRI) in the resting state to investigate changes in the functional connectivity between the DMN and task-positive networks, in a longitudinal design combined with measurements of caloric function. We demonstrate an initially disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that the disturbed connectivity between the default mode network and particular parts of the task-positive network might be related to a sustained utilization of processing capacity by diverging sensory information. The current results provide some insights into mechanisms of central compensation following an acute vestibular deficit and the importance of the DMN in this disease. PMID:25379422

  5. Acute exhaustive aerobic exercise training impair cardiomyocyte function and calcium handling in Sprague-Dawley rats

    PubMed Central

    Ljones, Kristine; Ness, Henning Ofstad; Solvang-Garten, Karin; Gaustad, Svein Erik; Andre Høydal, Morten

    2017-01-01

    Introduction Recent data from long-distance endurance participants suggest that cardiac function is impaired after completion. Existing data further indicate that right ventricular function is more affected than left ventricular function. The cellular mechanisms underpinning cardiac deterioration are limited and therefore the aim of this study was to examine cardiomyocyte and molecular responses of the right and left ventricle to an acute bout of exhaustive endurance exercise. Materials and methods Male Sprague-Dawley rats were assigned to sedentary controls or acute exhaustive endurance exercise consisting of a 120 minutes long forced treadmill run. The contractile function and Ca2+ handling properties in isolated cardiomyocytes, protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban including two of its phosphorylated states (serine 16 and threonine 17), and the mitochondrial respiration in permeabilized cardiac muscle fibers were analyzed. Results The exercise group showed a significant reduction in cardiomyocyte fractional shortening (right ventricle 1 Hz and 3 Hz p<0.001; left ventricle 1 Hz p<0.05), intracellular Ca2+ amplitude (right ventricle 1 and 3 Hz p<0.001; left ventricle 1 Hz p<0.01 and 3 Hz p<0.05) and rate of diastolic Ca2+ decay (right ventricle 1 Hz p<0.001 and 3 Hz p<0.01; left ventricle 1 and 3 Hz p<0.01). Cardiomyocyte relaxation during diastole was only significantly prolonged at 3 Hz in the right ventricle (p<0.05) compared to sedentary controls. We found an increase in phosphorylation of phospholamban at serine 16 and threonine 17 in the left (p<0.05), but not the right, ventricle from exhaustively exercised animals. The protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban was not changed. Furthermore, we found a reduction in maximal oxidative phosphorylation and electron transport system capacities of mitochondrial respiration in the right (p<0.01 and p<0.05, respectively), but not the

  6. Function of the HD-Zip I gene Oshox22 in ABA-mediated drought and salt tolerances in rice.

    PubMed

    Zhang, Shuxin; Haider, Imran; Kohlen, Wouter; Jiang, Li; Bouwmeester, Harro; Meijer, Annemarie H; Schluepmann, Henriette; Liu, Chun-Ming; Ouwerkerk, Pieter B F

    2012-12-01

    Oshox22 belongs to the homeodomain-leucine zipper (HD-Zip) family I of transcription factors, most of which have unknown functions. Here we show that the expression of Oshox22 is strongly induced by salt stress, abscisic acid (ABA), and polyethylene glycol treatment (PEG), and weakly by cold stress. Trans-activation assays in yeast and transient expression analyses in rice protoplasts demonstrated that Oshox22 is able to bind the CAAT(G/C)ATTG element and acts as a transcriptional activator that requires both the HD and Zip domains. Rice plants homozygous for a T-DNA insertion in the promoter region of Oshox22 showed reduced Oshox22 expression and ABA content, decreased sensitivity to ABA, and enhanced tolerance to drought and salt stresses at the seedling stage. In contrast, transgenic rice over-expressing Oshox22 showed increased sensitivity to ABA, increased ABA content, and decreased drought and salt tolerances. Based on these results, we conclude that Oshox22 affects ABA biosynthesis and regulates drought and salt responses through ABA-mediated signal transduction pathways.

  7. The rice gene OsZFP6 functions in multiple stress tolerance responses in yeast and Arabidopsis.

    PubMed

    Guan, Qing-jie; Wang, Li-feng; Bu, Qing-yun; Wang, Zhen-yu

    2014-09-01

    The role of zinc finger proteins in organismal stress conditions has been widely reported. However, little is known concerning the function of CCHC-type zinc finger proteins in rice. In this study, OsZFP6, a rice CCHC-type zinc finger protein 6 gene, was cloned from rice using RT-PCR. The OsZFP6 protein contains 305 amino acids and a conserved zinc finger domain and is localised to the nucleus. Southern blot analysis revealed that a single copy was encoded in the rice genome. OsZFP6 expression was increased by abiotic stress, including salt (NaCl), alkali (NaHCO3) and H2O2 treatment. When OsZFP6 was transformed into yeast, the transgenic yeast showed significantly increased resistance to NaHCO3 compared to the control. Moreover, Arabidopsis transgenic plants overexpressing OsZFP6 were more tolerant to both NaHCO3 and H2O2 treatments. Overall, we uncovered a role for OsZFP6 in abiotic stress responses and identified OsZFP6 as a putatively useful gene for developing crops with increased alkali and H2O2 tolerance.

  8. Molecular cloning and functional analysis of the drought tolerance gene MsHSP70 from alfalfa (Medicago sativa L.).

    PubMed

    Li, Zhenyi; Long, Ruicai; Zhang, Tiejun; Wang, Zhen; Zhang, Fan; Yang, Qingchuan; Kang, Junmei; Sun, Yan

    2017-03-01

    Heat shock proteins (HSPs) are a ubiquitously expressed class of protective proteins that play a key role in plant response to stressful conditions. This study aimed to characterize and investigate the function of an HSP gene in alfalfa (Medicago sativa). MsHSP70, which contains a 2028-bp open reading frame, was identified through homology cloning. MsHSP70 shares high sequence identity (94.47%) with HSP70 from Medicago truncatula. Expression analysis of MsHSP70 in alfalfa organs revealed a relatively higher expression level in aerial organs such as flowers, stems and leaves than in roots. MsHSP70 was induced by heat shock, abscisic acid (ABA) and hydrogen peroxide. Transgenic Arabidopsis seedlings overexpressing MsHSP70 were hyposensitive to polyethylene glycol (PEG) and ABA treatments, suggesting that exogenous expression of MsHSP70 enhanced Arabidopsis tolerance to these stresses. Examination of physiological indexes related to drought and ABA stress demonstrated that in comparison with non-transgenic plants, T3 transgenic Arabidopsis plants had an increased proline content, higher superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content. Furthermore, higher relative water content (RWC) was detected in transgenic plants compared with non-transgenic plants under drought stress. These findings clearly indicate that molecular manipulation of MsHSP70 in plants can have substantial effects on stress tolerance.

  9. Efficacy and tolerability of an ectoine mouth and throat spray compared with those of saline lozenges in the treatment of acute pharyngitis and/or laryngitis: a prospective, controlled, observational clinical trial.

    PubMed

    Müller, Dörte; Lindemann, Torben; Shah-Hosseini, Kija; Scherner, Olaf; Knop, Markus; Bilstein, Andreas; Mösges, Ralph

    2016-09-01

    The aim of this observational trial was to evaluate the efficacy and tolerability of a mouth and throat spray containing ectoine in the treatment of acute pharyngitis and/or laryngitis. The outcome was compared with control treatment using saline lozenges. This study was designed as a prospective, controlled, non-randomized, observational multicenter clinical trial and was conducted in Germany. The study population consisted of 95 patients. The decision for treatment with either spray or lozenges was based on the patients' preference for pharyngeal or oral application. Investigators assessed symptoms specific to acute pharyngitis/laryngitis and determined the pharyngitis symptom score. Both patients and investigators evaluated the tolerability and efficacy of the treatment applied. Treatment with the spray showed higher efficacy, 1.95 ± 0.81 versus 1.68 ± 0.67 (investigators) and 1.97 ± 0.88 versus 1.57 ± 0.69 (patients, p < 0.05). Treatment with the spray resulted in significantly greater reduction of cervical lymph node swelling (p < 0.05), ∆ spray = 0.44 ± 0.62, ∆ lozenges = 0.21 ± 0.62. The lozenges showed some advantage in relieving cough, ∆ lozenges = 0.62 ± 0.94 versus ∆ spray = 0.44 ± 0.85. Both patients and investigators rated the tolerability of both medical devices as "good" to "very good". Adverse events of mild to moderate severity were either possibly related or not related to the medical devices used. No serious adverse events occurred. Taken together, while the tolerability was consistent in both treatment groups, the ectoine-based spray showed superior efficacy in treating acute pharyngitis and/or laryngitis.

  10. DREB1/CBF transcription factors: their structure, function and role in abiotic stress tolerance in plants.

    PubMed

    Akhtar, M; Jaiswal, A; Taj, G; Jaiswal, J P; Qureshi, M I; Singh, N K

    2012-01-01

    Drought, high salinity and low temperature are major abiotic stresses that influence survival, productivity and geographical distribution of many important crops across the globe. Plants respond to these environmental challenges via physiological, cellular and molecular processes, which results in adjusted metabolic and structural alterations. The dehydration-responsiveelement-binding (DREB) protein / C-repeat binding factors (CBFs) belong to APETALA2 (AP2) family transcription factors that bind to DRE/CRT cis-element and regulate the expression of stress-responsive genes. DREB1/CBF genes, therefore, play an important role in increasing stress tolerance in plants and their deployment using transgenic technology seems to be a potential alternative in management of abiotic stresses in crop plants. This review is mainly focussed on the structural characteristics as well as transcriptional regulation of gene expression in response to various abiotic stresses, with particular emphasis on the role of DREB1/CBF regulon in stress-responsive gene expression. The recent progress related to genetic engineering of DREB1/CBF transcription factors in various crops and model plants is also summarized.

  11. Providing Alternative Reinforcers to Facilitate Tolerance to Delayed Reinforcement Following Functional Communication Training

    ERIC Educational Resources Information Center

    Austin, Jillian E.; Tiger, Jeffrey H.

    2015-01-01

    The earliest stages of functional communication training (FCT) involve providing immediate and continuous reinforcement for a communicative response (FCR) that is functionally equivalent to the targeted problem behavior. However, maintaining immediate reinforcement is not practical, and the introduction of delays is associated with increased…

  12. Effects of acute tryptophan depletion on raphé functional connectivity in depression

    PubMed Central

    Weinstein, Jodi J.; Rogers, Baxter P.; Taylor, Warren D.; Boyd, Brian D.; Cowan, Ronald L.; Shelton, K. Maureen; Salomon, Ronald M.

    2015-01-01

    Depression remains a great societal burden and a major treatment challenge. Most antidepressant medications target serotonergic raphé nuclei. Acute tryptophan depletion (ATD) modulates serotonin function. To better understand the raphé's role in mood networks, we studied raphé functional connectivity in depression. Fifteen depressed patients were treated with sertraline for 12 weeks and scanned during ATD and sham conditions. Based on our previous findings in a separate cohort, resting state MRI functional connectivity between raphé and other depression-related regions (ROIs) was analyzed in narrow frequency bands. ATD decreased raphé functional connectivity with the bilateral thalamus within 0.025–0.05 Hz, and also decreased raphé functional connectivity with the right pregenual anterior cingulate cortex within 0.05–0.1 Hz. Using the control broadband filtlter 0.01–0.1 Hz, no significant differences in raphé-ROI functional connectivity were observed. Post-hoc analysis by remission status suggested increased raphé functional connectivity with left pregenual anterior cingulate cortex in remitters (n = 10) and decreased raphé functional connectivity with left thalamus in non-remitters (n = 5), both within 0.025–0.05 Hz. Reducing serotonin function appears to alter coordination of these mood-related networks in specific, low frequency ranges. For examination of effects of reduced serotonin function on mood-related networks, specific low frequency BOLD fMRI signals can identify regions implicated in neural circuitry and may enable clinically-relevant interpretation of functional connectivity measures. The biological significance of these low frequency signals detected in the raphé merits further study. PMID:26411798

  13. Probability of Treatment Following Acute Drop in Lung Function in Children with Cystic Fibrosis is related to baseline pulmonary function

    PubMed Central

    Morgan, Wayne J.; Wagener, Jeffrey S.; Yegin, Ashley; Pasta, David J.; Millar, Stefanie J.; Konstan, Michael W.

    2014-01-01

    Objective To hypothesize whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute drops (sudden decline events) in FEV1. Study design Patients with CF aged 6-17 years enrolled in ESCF were assessed for a sudden decline event, defined as a 10% relative drop in FEV1 % predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1 % predicted age-specific decile using a logistic regression adjusting for age group (6-12y, 13-17y) and presence of Pseudomonas aeruginosa on respiratory culture. Results 10,888 patients had at least one sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (odds ratio [OR], 0.14; 95% confidence interval [CI], 0.11-0.18; P<.001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P<.001) following decline. Conclusions Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute drop in FEV1, which may explain their greater rate of FEV1 decline. PMID:23810128

  14. Predicting the acute behavioral effects in rats inhaling toluene for up to 24 hrs: Inhaled vs, internal dose metrics and tolerance.

    EPA Science Inventory

    The acute toxicity of toluene, a model volatile organic compound (VOC), depends on the concentration (C) and duration (t) of exposure, and guidelines for acute exposures have traditionally used extrelationships to extrapolate protective and/or effective concentrations across dura...

  15. Oral glucose tolerance test for preoperative assessment of liver function in liver resection

    PubMed Central

    Rachapoodivenkata, Raghavendra Rao

    2017-01-01

    Backgrounds/Aims We intended to determine the role of the Oral glucose tolerance test (OGTT), in addition to volumetry, in preoperative assessment of patients undergoing liver resection. Methods This was a prospective study conducted at a tertiary care hospital, between February 2009 and February 2011. OGTT curve (parabolic/linear), linearity index (LI) and Parenchymal Hepatic Resection Rate (PHRR) were correlated with postoperative outcomes in terms of postoperative liver failure (PLF), by 50-50 criteria, morbidity, mortality and hospital stay. Results Of the 33 patients included in the study, 23 (69.7%) patients underwent major liver resections. Hepatocellular carcinoma (30.3%) was the leading indication. The overall postoperative morbidity rate was 72.7%, but major complications occurred in 3 (9.1%) patients only. There was no 90-day mortality. The 50-50 criteria were met by 3 patients undergoing major resection. Significant correlation was noted between the linear OGTT curve and the overall hospital stay (12.1 days vs. 9.6 days in parabolic; p=0.04). Patients with linear OGTT met the 50-50 criteria more often (18%) than those having a parabolic curve (4.5%; p=0.25). Although the OGTT was more often linear with occurrence of morbidity (41.7% vs 11.1%), major morbidity (66.7% vs 30%) and PLF by 50-50 criteria (66.7% vs 30%), it was not statistically significant. The linearity index was marginally lower (0.9 vs 1.2) in the presence of major morbidity and PLF by 50-50 criteria. Conclusions Linear OGTT affects the PLF and major morbidity, therein impacting the hospital stay. OGTT LI and PHRR can help predict postoperative outcome for a given extent of liver resection. PMID:28317039

  16. Xenon protects left ventricular diastolic function during acute ischemia, less than ischemic preconditioning

    PubMed Central

    Baumert, Jan-H.; Roehl, Anna B.; Funcke, Sandra; Hein, Marc

    2016-01-01

    Anesthetics modify regional left ventricular (LV) dysfunction following ischemia/reperfusion but their effects on global function in this setting are less clear. Aim of this study was to test the hypothesis that xenon would limit global LV dysfunction as caused by acute anterior wall ischemia, comparable to ischemic preconditioning. In an open-chest model under thiopental anesthesia, 30 pigs underwent 60-minute left anterior descending coronary artery occlusion, followed by 120 minutes of reperfusion. A xenon group (constant inhalation from previous to ischemia through end of reperfusion) was compared to control and ischemic preconditioning. Load-independent measures of diastolic function (end-diastolic pressure-volume relation, time constant of relaxation) and systolic function (end-systolic pressure-volume relation, preload-recruitable stroke work) were determined. Heart rate, arterial pressure, cardiac output, and arterial elastance were recorded. Data were compared in 26 pigs. Ischemia impaired global diastolic but not systolic function in control, which recovered during reperfusion. Xenon limited and preconditioning abolished diastolic dysfunction during ischemia. Arterial pressure decreased during reperfusion while arterial elastance increased. Tachycardia and antero-septal wall edema during reperfusion were observed in all groups. In spite of ischemia of 40% of LV mass, global systolic function was preserved. Deterioration in global diastolic function was limited by xenon and prevented by preconditioning. PMID:27867480

  17. Functional Group Tolerant Nickel-Catalyzed Cross-Coupling Reaction for Enantioselective Construction of 30 Methyl-Bearing Stereocenters

    PubMed Central

    Wisniewska, Hanna M.; Swift, Elizabeth C.; Jarvo, Elizabeth R.

    2013-01-01

    The first Negishi nickel-catalyzed stereospecific cross-coupling reaction of secondary benzylic esters is reported. A series of traceless directing groups are evaluated for ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially-available 2-(methylthio)acetic acid are most effective. The products are formed in high yield and with excellent stereospecificity. A variety of functional groups are tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation is highlighted in the enantioselective synthesis of a retinoic acid receptor (RAR) agonist and a fatty acid amide hydrolase (FAAH) inhibitor. PMID:23751004

  18. Leydig-cell function in children after direct testicular irradiation for acute lymphoblastic leukemia

    SciTech Connect

    Brauner, R.; Czernichow, P.; Cramer, P.; Schaison, G.; Rappaport, R.

    1983-07-07

    To assess the effect of testicular irradiation on testicular endocrine function, we studied 12 boys with acute lymphoblastic leukemia who had been treated with direct testicular irradiation 10 months to 8 1/2 years earlier. Insufficient Leydig-cell function, manifested by a low response of plasma testosterone to chorionic gonadotropin or an increased basal level of plasma luteinizing hormone (or both), was observed in 10 patients, 7 of whom were pubertal. Two of these patients had a compensated testicular endocrine insufficiency with only high plasma concentrations of luteinizing hormone. Testosterone secretion was severely impaired in three pubertal boys studied more than four years after testicular irradiation. A diminished testicular volume indicating tubular atrophy was found in all pubertal patients, including three who had not received cyclophosphamide or cytarabine. These data indicate that testosterone insufficiency is a frequent complication of testicular irradiation, although some patients continue to have Leydig-cell activity for several years after therapy.

  19. Hematuria and decreased kidney function as initial signs of acute B-cell lymphoblastic leukemia.

    PubMed

    Seo-Mayer, Patricia; Kenney, Barton; McNamara, Joseph; Stein, Jeffrey; Moeckel, Gilbert W

    2010-11-01

    We report the case of a 14-year-old boy who presented with hematuria and decreased kidney function as initial manifestations of acute lymphoblastic leukemia (ALL). Computed tomography of the abdomen showed extensive retroperitoneal lymphadenopathy and bilateral nephromegaly. The patient's kidney biopsy specimen showed a dense monomorphous interstitial infiltrate of small round blue cells with significant nuclear atypia. Immunohistochemical workup showed positive staining for CD20, CD10, and terminal deoxynucleotidyl transferase (TdT), consistent with ALL. The patient underwent induction chemotherapy, attained remission 4 weeks after induction, and presently is stable in the consolidation phase of chemotherapy. This is an unusual case of ALL involving both kidneys with initial presenting signs of hematuria and decreased kidney function.

  20. Acute Effect of Treatment of Mitral Stenosis on Left Atrium Function

    PubMed Central

    Rohani, Atooshe; Kargar, Shahram; Fazlinejad, Afsoon; Ghaderi, Fereshte; Vakili, Vida; Falsoleiman, Homa; Bagheri, Ramin Khamene

    2017-01-01

    Aim: Peak atrial longitudinal strain (PALS) is used to evaluate left atrium (LA) function in patients with mitral stenosis (MS), before and after percutaneous transmitral commissurotomy (PTMC) and mitral valve replacement (MVR). Methods: Patients with severe symptomatic MS, who were referred to our echocardiographic laboratory for a diagnostic examination before cardiac surgery or PTMC from October of 2014 to October of 2015, were included in the study. Result: The peak systolic global LA strain improved post-PTMC (P < 0.001) and post-MVR (P = 0.012). This difference was statistically highly significant. Conclusion: PALS is impaired in patients with severe symptomatic MS and improved acutely after treatment and may be a good indicator of LA function and may predict the right time for intervention on mitral valve. PMID:28074794

  1. Providing alternative reinforcers to facilitate tolerance to delayed reinforcement following functional communication training.

    PubMed

    Austin, Jillian E; Tiger, Jeffrey H

    2015-09-01

    The earliest stages of functional communication training (FCT) involve providing immediate and continuous reinforcement for a communicative response (FCR) that is functionally equivalent to the targeted problem behavior. However, maintaining immediate reinforcement is not practical, and the introduction of delays is associated with increased problem behavior. The present study evaluated the effects of providing alternative reinforcers during delays to reinforcement with a 13-year-old boy with an intellectual disability. Problem behavior was less likely when alternative reinforcers were available during delays.

  2. [Effect of apparatus plasmapheresis on the bowel barrier and motility function in patients with acute necrotizing pancreatitis].

    PubMed

    Dronov, O I; Koval's'ka, I O; Uvarov, V Iu; Horlach, A I; Fedoruk, V I; Burmich, K S; Lykhodeĭ, K O; Shvets', Iu P

    2013-04-01

    Influence of therapeutic plasmapheresis on bowel barrier function and evacuation was investigated in 83 patients with severe acute necrotizing pancreatitis. Except standard therapy patient obtained therapeutic plasmapheresis using "Haemonetics" PCS 2 system. Complex treatment of patients with acute necrotizing pancreatitis and dynamic ileus using plasmapheresis increases contractive and propulsive function of stomach and duodenum and prolongs period of activity of these organs on 32%. Intestinal barrier function associates with restoration of bowel evacuation. Addition of plasmapheresis to standard therapy of necrotizing pancreatitis can be effective prevention of dynamic ileus.

  3. Damage tolerant functionally graded materials for advanced wear and friction applications

    NASA Astrophysics Data System (ADS)

    Prchlik, Lubos

    The research work presented in this dissertation focused on processing effects, microstructure development, characterization and performance evaluation of composite and graded coatings used for friction and wear control. The following issues were addressed. (1) Definition of prerequisites for a successful composite and graded coating formation by means of thermal spraying. (2) Improvement of characterization methods available for homogenous thermally sprayed coating and their extension to composite and graded materials. (3) Development of novel characterization methods specifically for FGMs, with a focus on through thickness property measurement by indentation and in-situ curvature techniques. (4) Design of composite materials with improved properties compared to homogenous coatings. (5) Fabrication and performance assessment of FGM with improved wear and impact damage properties. Materials. The materials studied included several material systems relevant to low friction and contact damage tolerant applications: MO-Mo2C, WC-Co cermets as materials commonly used sliding components of industrial machinery and NiCrAlY/8%-Yttria Partially Stabilized Zirconia composites as a potential solution for abradable sections of gas turbines and aircraft engines. In addition, uniform coatings such as molybdenum and Ni5%Al alloy were evaluated as model system to assess the influence of microstructure variation onto the mechanical property and wear response. Methods. The contact response of the materials was investigated through several techniques. These included methods evaluating the relevant intrinsic coating properties such as elastic modulus, residual stress, fracture toughness, scratch resistance and tests measuring the abrasion and friction-sliding behavior. Dry-sand and wet two-body abrasion testing was performed in addition to traditional ball on disc sliding tests. Among all characterization techniques the spherical indentation deserved most attention and enabled to

  4. On testing of functionally equivalent components of fault-tolerant software

    NASA Technical Reports Server (NTRS)

    Vouk, Mladen A.; Helsabeck, Michael L.; Tai, Kuo-Chung; Mcallister, David F.

    1986-01-01

    Six functionally equivalent programs were tested with specification based random and extremal/special value (ESV) test cases. Statement and branch coverage were used to measure and compare the attained testing effectiveness. It was observed that both measures reached a nearly steady state value after 25 to 75 random test cases. Coverage saturation curves appear to follow an exponential growth model. However, the steady state values for branch coverage of different components, but the same input cases, differed by as much as 22 percent. The effect is the result of the differences in the detailed structure of the components. Improvement in coverage provided by the random test data, after the ESV cases were executed, was only about 1 percent. Results indicate that extensive random testing can be a process of diminishing returns, and that in the FTS context functional ('black box') testing can provide a very uneven execution coverage of the functionally equivalent software, and therefore should be supplemented by structure based testing.

  5. The administration of psilocybin to healthy, hallucinogen-experienced volunteers in a mock-functional magnetic resonance imaging environment: a preliminary investigation of tolerability.

    PubMed

    Carhart-Harris, Robin L; Williams, Tim M; Sessa, Ben; Tyacke, Robin J; Rich, Ann S; Feilding, Amanda; Nutt, David J

    2011-11-01

    This study sought to assess the tolerability of intravenously administered psilocybin in healthy, hallucinogen-experienced volunteers in a mock-magnetic resonance imaging environment as a preliminary stage to a controlled investigation using functional magnetic resonance imaging to explore the effects of psilocybin on cerebral blood flow and activity. The present pilot study demonstrated that up to 2 mg of psilocybin delivered as a slow intravenous injection produces short-lived but typical drug effects that are psychologically and physiologically well tolerated. With appropriate care, this study supports the viability of functional magnetic resonance imaging work with psilocybin.

  6. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-02

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.

  7. Functional Role of Monocytes and Macrophages for the Inflammatory Response in Acute Liver Injury

    PubMed Central

    Zimmermann, Henning W.; Trautwein, Christian; Tacke, Frank

    2012-01-01

    Different etiologies such as drug toxicity, acute viral hepatitis B, or acetaminophen poisoning can cause acute liver injury or even acute liver failure (ALF). Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-1beta, or monocyte-chemoattractant protein-1 (MCP-1, CCL2) as well as activating other non-parenchymal liver cells, e.g., endothelial or hepatic stellate cells. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g., via caspase activation, but also activate protective signaling pathways, e.g., via nuclear factor kappa B (NF-κB). Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+) monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1) are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation, and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF. PMID:23091461

  8. Effect and clinical prediction of worsening renal function in acute decompensated heart failure.

    PubMed

    Breidthardt, Tobias; Socrates, Thenral; Noveanu, Markus; Klima, Theresia; Heinisch, Corinna; Reichlin, Tobias; Potocki, Mihael; Nowak, Albina; Tschung, Christopher; Arenja, Nisha; Bingisser, Roland; Mueller, Christian

    2011-03-01

    We aimed to establish the prevalence and effect of worsening renal function (WRF) on survival among patients with acute decompensated heart failure. Furthermore, we sought to establish a risk score for the prediction of WRF and externally validate the previously established Forman risk score. A total of 657 consecutive patients with acute decompensated heart failure presenting to the emergency department and undergoing serial creatinine measurements were enrolled. The potential of the clinical parameters at admission to predict WRF was assessed as the primary end point. The secondary end point was all-cause mortality at 360 days. Of the 657 patients, 136 (21%) developed WRF, and 220 patients had died during the first year. WRF was more common in the nonsurvivors (30% vs 41%, p = 0.03). Multivariate regression analysis found WRF to independently predict mortality (hazard ratio 1.92, p <0.01). In a single parameter model, previously diagnosed chronic kidney disease was the only independent predictor of WRF and achieved an area under the receiver operating characteristic curve of 0.60. After the inclusion of the blood gas analysis parameters into the model history of chronic kidney disease (hazard ratio 2.13, p = 0.03), outpatient diuretics (hazard ratio 5.75, p <0.01), and bicarbonate (hazard ratio 0.91, p <0.01) were all predictive of WRF. A risk score was developed using these predictors. On receiver operating characteristic curve analysis, the Forman and Basel prediction rules achieved an area under the curve of 0.65 and 0.71, respectively. In conclusion, WRF was common in patients with acute decompensated heart failure and was linked to significantly worse outcomes. However, the clinical parameters failed to adequately predict its occurrence, making a tailored therapy approach impossible.

  9. OsSUV3 dual helicase functions in salinity stress tolerance by maintaining photosynthesis and antioxidant machinery in rice (Oryza sativa L. cv. IR64).

    PubMed

    Tuteja, Narendra; Sahoo, Ranjan Kumar; Garg, Bharti; Tuteja, Renu

    2013-10-01

    To overcome the salinity-induced loss of crop yield, a salinity-tolerant trait is required. The SUV3 helicase is involved in the regulation of RNA surveillance and turnover in mitochondria, but the helicase activity of plant SUV3 and its role in abiotic stress tolerance have not been reported so far. Here we report that the Oryza sativa (rice) SUV3 protein exhibits DNA and RNA helicase, and ATPase activities. Furthermore, we report that SUV3 is induced in rice seedlings in response to high levels of salt. Its expression, driven by a constitutive cauliflower mosaic virus 35S promoter in IR64 transgenic rice plants, confers salinity tolerance. The T1 and T2 sense transgenic lines showed tolerance to high salinity and fully matured without any loss in yields. The T2 transgenic lines also showed tolerance to drought stress. These results suggest that the introduced trait is functional and stable in transgenic rice plants. The rice SUV3 sense transgenic lines showed lesser lipid peroxidation, electrolyte leakage and H2 O2 production, along with higher activities of antioxidant enzymes under salinity stress, as compared with wild type, vector control and antisense transgenic lines. These results suggest the existence of an efficient antioxidant defence system to cope with salinity-induced oxidative damage. Overall, this study reports that plant SUV3 exhibits DNA and RNA helicase and ATPase activities, and provides direct evidence of its function in imparting salinity stress tolerance without yield loss. The possible mechanism could be that OsSUV3 helicase functions in salinity stress tolerance by improving photosynthesis and antioxidant machinery in transgenic rice.

  10. Increasing atmospheric [CO2] from glacial through future levels affects drought tolerance via impacts on leaves, xylem and their integrated function

    PubMed Central

    Medeiros, Juliana S.; Ward, Joy K.

    2013-01-01

    Summary Changes in atmospheric carbon dioxide concentration ([CO2]) affect plant carbon/water trade-offs, with implications for drought tolerance. Leaf-level studies often indicate that drought tolerance may increase with rising [CO2], but integrated leaf and xylem responses are not well understood in this respect. In addition, the influence of low [CO2] of the last glacial period on drought tolerance and xylem properties is not well understood.We investigated the interactive effects of a broad range of [CO2] and plant water potentials on leaf function, xylem structure and function and the integration of leaf and xylem function in Phaseolus vulgaris.Elevated [CO2] decreased vessel implosion strength, reduced conduit specific hydraulic conductance, and compromised leaf specific xylem hydraulic conductance under moderate drought. By contrast, at glacial [CO2], transpiration was maintained under moderate drought via greater conduit specific and leaf specific hydraulic conductance in association with increased vessel implosion strength.Our study involving the integration of leaf and xylem responses suggests that increasing [CO2] does not improve drought tolerance. We show that under glacial conditions changes in leaf and xylem properties could increase drought tolerance, while under future conditions greater productivity may only occur when higher water use can be accommodated. PMID:23668237

  11. Increasing atmospheric [CO2] from glacial to future concentrations affects drought tolerance via impacts on leaves, xylem and their integrated function.

    PubMed

    Medeiros, Juliana S; Ward, Joy K

    2013-08-01

    Changes in atmospheric carbon dioxide concentration ([CO2]) affect plant carbon/water tradeoffs, with implications for drought tolerance. Leaf-level studies often indicate that drought tolerance may increase with rising [CO2], but integrated leaf and xylem responses are not well understood in this respect. In addition, the influence of the low [CO2] of the last glacial period on drought tolerance and xylem properties is not well understood. We investigated the interactive effects of a broad range of [CO2] and plant water potentials on leaf function, xylem structure and function and the integration of leaf and xylem function in Phaseolus vulgaris. Elevated [CO2] decreased vessel implosion strength, reduced conduit-specific hydraulic conductance, and compromised leaf-specific xylem hydraulic conductance under moderate drought. By contrast, at glacial [CO2], transpiration was maintained under moderate drought via greater conduit-specific and leaf-specific hydraulic conductance in association with increased vessel implosion strength. Our study involving the integration of leaf and xylem responses suggests that increasing [CO2] does not improve drought tolerance. We show that, under glacial conditions, changes in leaf and xylem properties could increase drought tolerance, while under future conditions, greater productivity may only occur when higher water use can be accommodated.

  12. Effects of acute exercise on attenuated vagal baroreflex function during bed rest

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.; Doerr, Donald F.; Guell, Antonio; Marini, J.-F.

    1992-01-01

    We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 deg head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally-mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4 percent (p less than 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p less than 0.05) by 10.7 +/- 3.7 percent above pre-bed rest levels and 34.3 +/- 7.9 percent above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise.

  13. Acute kidney function and morphology following topload administration of recombinant hemoglobin solution.

    PubMed

    Martucci, Alexandre Fabricio; Abreu Martucci, Ana Carolina Carvalho Ferreira; Cabrales, Pedro; Nascimento, Paulo do; Intaglietta, Marcos; Tsai, Amy G; Castiglia, Yara Marcondes Machado

    2017-02-01

    There is a 0.138% incidence of adverse reactions related to blood transfusion. Transfusion-related acute lung injury, immunosuppression, fever, pathogen transmission, and hemolytic transfusion reactions are the most common ones. Synthetic oxygen carriers have been developed to deal with blood shortages and for use in the field where stored blood was not available. They were also designed to be pathogen free, including unknown viruses. In this study, we used Male Golden Syrian Hamsters implemented with a dorsal window chamber to determine how infusion of three different, genetically crosslinked recombinant acellular hemoglobin (rHb) solutions with different oxygen affinities and nitric oxide kinetics affect mean arterial pressure (MAP), heart rate (HR), kidney function, and kidney structure. We found that the administration of all three rHb solutions caused mild hypertension and bradycardia 30 minutes after infusion. However, acute changes in glomerular filtration rate (GFR) were not detected, even though histological analysis was performed 72 hours after treatment revealed some structural changes. All the rHb solutions resulted in hypertension 30 minutes after a 10% topload administration. Regardless of their properties, the presence of acellular Hb causes significant alterations to kidney tissue.

  14. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation

    PubMed Central

    Malyszko, Jolanta; Lukaszyk, Ewelina; Glowinska, Irena; Durlik, Magdalena

    2015-01-01

    Renal transplantation ensures distinct advantages for patients with end-stage kidney disease. However, in some cases early complications can lead to allograft dysfunction and consequently graft loss. One of the most common early complications after kidney transplantation is delayed graft function (DGF). Unfortunately there is no effective treatment for DGF, however early diagnosis of DGF and therapeutic intervention (eg modification of immunosuppression) may improve outcome. Therefore, markers of acute kidney injury are required. Creatinine is a poor biomarker for kidney injury due principally to its inability to help diagnose early acute renal failure and complete inability to help differentiate among its various causes. Different urinary and serum proteins have been intensively investigated as possible biomarkers in this setting. There are promising candidate biomarkers with the ability to detect DGF. We focused on emerging biomarkers of DGF with NGAL is being the most studied followed by KIM-1, L-FABP, IL-18, and others. However, large randomized studies are needed to establish the value of new, promising biomarkers, in DGF diagnosis, prognosis and its cost-effectiveness. PMID:26175216

  15. microRNA function is limited to cytokine control in the acute response to virus infection

    PubMed Central

    Aguado, Lauren C.; Schmid, Sonja; Sachs, David; Shim, Jaehee V.; Lim, Jean K.; tenOever, Benjamin R.

    2015-01-01

    SUMMARY With the capacity to fine-tune protein expression via sequence-specific interactions, microRNAs (miRNAs) help regulate cell maintenance and differentiation. While some studies have also implicated miRNAs as regulators of the antiviral response, others have found that the RISC complex that facilitates miRNA-mediated silencing is rendered non-functional during cellular stress, including virus infection. To determine the global role of miRNAs in the cellular response to virus infection, we generated a vector that rapidly eliminates total cellular miRNA populations in terminally differentiated primary cultures. Loss of miRNAs has a negligible impact on both innate sensing of and immediate response to acute viral infection. In contrast, miRNA depletion specifically enhances cytokine expression, providing a post-translational mechanism for immune cell activation during cellular stress. This work highlights the physiological role of miRNAs during the antiviral response and suggests their contribution is limited to chronic infections and the acute activation of the adaptive immune response. PMID:26651947

  16. Acute effects of grayanotoxin in rhododendron honey on kidney functions in rats.

    PubMed

    Silici, S; Doğan, Z; Sahin, H; Atayoğlu, T; Yakan, B

    2016-02-01

    The aim of the study is to evaluate the acute biochemical and histological changes in rat kidneys after treatment with grayanotoxin (GTX) of rhododendron honey (RH). A total of 60 Sprague-Dawley female rats were divided into five groups of 12 rats each, one being a control group (group 1) and group 2 was treated with 0.015 mg/kg/bw of GTX standard preparation via intraperitoneal injection. Groups 3, 4, and 5 were given RH at doses of 0.1, 0.5, and 2.5 g/kg/bw, respectively, via oral gavage. Compared to the control group, significant increases were observed in glucose, blood urea nitrogen (BUN), and creatinine levels of the GTX-injected groups after 1 h. However, in low dose RH group, such an increase was not observed and had a normal appearance histologically. Therefore, low dose (1 g/kg/bw) of RH produces no acute adverse effects on renal functions of rats.

  17. Functional roles of the pepper RING finger protein gene, CaRING1, in abscisic acid signaling and dehydration tolerance.

    PubMed

    Lim, Chae Woo; Hwang, Byung Kook; Lee, Sung Chul

    2015-09-01

    Plants are constantly exposed to a variety of biotic and abiotic stresses, which include pathogens and conditions of high salinity, low temperature, and drought. Abscisic acid (ABA) is a major plant hormone involved in signal transduction pathways that mediate the defense response of plants to abiotic stress. Previously, we isolated Ring finger protein gene (CaRING1) from pepper (Capsicum annuum), which is associated with resistance to bacterial pathogens, accompanied by hypersensitive cell death. Here, we report a new function of the CaRING1 gene product in the ABA-mediated defense responses of plants to dehydration stress. The expression of the CaRING1 gene was induced in pepper leaves treated with ABA or exposed to dehydration or NaCl. Virus-induced gene silencing of CaRING1 in pepper plants exhibited low degree of ABA-induced stomatal closure and high levels of transpirational water loss in dehydrated leaves. These led to be more vulnerable to dehydration stress in CaRING1-silenced pepper than in the control pepper, accompanied by reduction of ABA-regulated gene expression and low accumulation of ABA and H2O2. In contrast, CaRING1-overexpressing transgenic plants showed enhanced sensitivity to ABA during the seedling growth and establishment. These plants were also more tolerant to dehydration stress than the wild-type plants because of high ABA accumulation, enhanced stomatal closure and increased expression of stress-responsive genes. Together, these results suggest that the CaRING1 acts as positive factor for dehydration tolerance in Arabidopsis by modulating ABA biosynthesis and ABA-mediated stomatal closing and gene expression.

  18. From immunosuppression to tolerance.

    PubMed

    Adams, David H; Sanchez-Fueyo, Alberto; Samuel, Didier

    2015-04-01

    The past three decades have seen liver transplantation becoming a major therapeutic approach in the management of end-stage liver diseases. This is due to the dramatic improvement in survival after liver transplantation as a consequence of the improvement of surgical and anaesthetic techniques, of post-transplant medico-surgical management and of prevention of disease recurrence and other post-transplant complications. Improved use of post-transplant immunosuppression to prevent acute and chronic rejection is a major factor in these improved results. The liver has been shown to be more tolerogenic than other organs, and matching of donor and recipients is mainly limited to ABO blood group compatibility. However, long-term immunosuppression is required to avoid severe acute and chronic rejection and graft loss. With the current immunosuppression protocols, the risk of acute rejection requiring additional therapy is 10-40% and the risk of chronic rejection is below 5%. However, the development of histological lesions in the graft in long-term survivors suggest atypical forms of graft rejection may develop as a consequence of under-immunosuppression. The backbone of immunosuppression remains calcineurin inhibitors (CNI) mostly in association with steroids in the short-term and mycophenolate mofetil or mTOR inhibitors (everolimus). The occurrence of post-transplant complications related to the immunosuppressive therapy has led to the development of new protocols aimed at protecting renal function and preventing the development of de novo cancer and of dysmetabolic syndrome. However, there is no new class of immunosuppressive drugs in the pipeline able to replace current protocols in the near future. The aim of a full immune tolerance of the graft is rarely achieved since only 20% of selected patients can be weaned successfully off immunosuppression. In the future, immunosuppression will probably be more case oriented aiming to protect the graft from rejection and at

  19. Cardiac function after acute support with direct mechanical ventricular actuation in chronic heart failure.

    PubMed

    McConnell, Patrick I; Anstadt, Mark P; Del Rio, Carlos L; Preston, Thomas J; Ueyama, Yukie; Youngblood, Brad L

    2014-01-01

    Direct mechanical ventricular actuation (DMVA) exerts direct cardiac compression/decompression and does not require blood contact. The safety and effects of DMVA support in chronically dysfunctional beating hearts in vivo have not been established. This study evaluated hemodynamics and load-independent systolic/diastolic cardiac function before/after acute support (2 hours) using DMVA in small hearts with induced chronic failure. Chronic heart failure was created in seven small dogs (15 ± 2 kg) via either serial coronary microembolizations or right-ventricular overdrive pacing. Dogs were instrumented to measure cardiac output, hemodynamic pressures, left ventricular volumes for pressure-volume analysis via preload reduction. Temporary cardiac support using a DMVA device was instituted for 2 hours. Hemodynamic and mechanical assessments, including dobutamine dose-responses, were compared both before and after support. Hemodynamic indices were preserved with support. Both left-ventricular systolic and diastolic function were improved postsupport, as the slopes of the preload-recruitable stroke work (+29 ± 7%, p < 0.05) and the end-diastolic pressure-volume relationship (EDPVR: -28 ± 9%, p < 0.05) improved post-DMVA support. Diastolic/systolic myocardial reserve, as assessed by responsiveness to dobutamine challenges, was preserved after DMVA support. Short-term DMVA support can safely and effectively sustain hemodynamics, whereas triggering favorable effects on cardiac function in the setting of chronic heart failure. In particular, DMVA support preserved load-independent diastolic function and reserve.

  20. Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets.

    PubMed

    Doi, Kent; Rabb, Hamid

    2016-03-01

    Acute kidney injury (AKI) is a common complication in critically ill patients and subsequently worsens outcomes. Although many drugs to prevent and treat AKI have shown benefits in preclinical models, no specific agent has been shown to benefit AKI in humans. Moreover, despite remarkable advances in dialysis techniques that enable management of AKI in hemodynamically unstable patients with shock, dialysis-requiring severe AKI is still associated with an unacceptably high mortality rate. Thus, focusing only on kidney damage and loss of renal function has not been sufficient to improve outcomes of patients with AKI. Recent data from basic and clinical research have begun to elucidate complex organ interactions in AKI between kidney and distant organs, including heart, lung, spleen, brain, liver, and gut. This review serves to update the topic of organ cross talk in AKI and focuses on potential therapeutic targets to improve patient outcomes during AKI-associated multiple organ failure.

  1. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    PubMed

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  2. Biofertilizers function as key player in sustainable agriculture by improving soil fertility, plant tolerance and crop productivity

    PubMed Central

    2014-01-01

    Current soil management strategies are mainly dependent on inorganic chemical-based fertilizers, which caused a serious threat to human health and environment. The exploitation of beneficial microbes as a biofertilizer has become paramount importance in agriculture sector for their potential role in food safety and sustainable crop production. The eco-friendly approaches inspire a wide range of application of plant growth promoting rhizobacteria (PGPRs), endo- and ectomycorrhizal fungi, cyanobacteria and many other useful microscopic organisms led to improved nutrient uptake, plant growth and plant tolerance to abiotic and biotic stress. The present review highlighted biofertilizers mediated crops functional traits such as plant growth and productivity, nutrient profile, plant defense and protection with special emphasis to its function to trigger various growth- and defense-related genes in signaling network of cellular pathways to cause cellular response and thereby crop improvement. The knowledge gained from the literature appraised herein will help us to understand the physiological bases of biofertlizers towards sustainable agriculture in reducing problems associated with the use of chemicals fertilizers. PMID:24885352

  3. Biofertilizers function as key player in sustainable agriculture by improving soil fertility, plant tolerance and crop productivity.

    PubMed

    Bhardwaj, Deepak; Ansari, Mohammad Wahid; Sahoo, Ranjan Kumar; Tuteja, Narendra

    2014-05-08

    Current soil management strategies are mainly dependent on inorganic chemical-based fertilizers, which caused a serious threat to human health and environment. The exploitation of beneficial microbes as a biofertilizer has become paramount importance in agriculture sector for their potential role in food safety and sustainable crop production. The eco-friendly approaches inspire a wide range of application of plant growth promoting rhizobacteria (PGPRs), endo- and ectomycorrhizal fungi, cyanobacteria and many other useful microscopic organisms led to improved nutrient uptake, plant growth and plant tolerance to abiotic and biotic stress. The present review highlighted biofertilizers mediated crops functional traits such as plant growth and productivity, nutrient profile, plant defense and protection with special emphasis to its function to trigger various growth- and defense-related genes in signaling network of cellular pathways to cause cellular response and thereby crop improvement. The knowledge gained from the literature appraised herein will help us to understand the physiological bases of biofertlizers towards sustainable agriculture in reducing problems associated with the use of chemicals fertilizers.

  4. Exercise pressor reflex function following acute hemi-section of the spinal cord in cats

    PubMed Central

    Murphy, Megan N.; Ichiyama, Ronaldo M.; Iwamoto, Gary A.; Mitchell, Jere H.; Smith, Scott A.

    2013-01-01

    Cardiovascular disease is a leading cause of morbidity and mortality in patients post spinal cord injury (SCI). The prescription of exercise as a therapeutic modality for disease prevention in this population is promising. It is logical to suggest that the sooner an exercise program can begin the more benefit the patient will receive from the therapy. However, the time point after injury at which the requisite circulatory responses needed to support exercise are viable remains largely unknown. The skeletal muscle exercise pressor reflex (EPR) significantly contributes to cardiovascular control during exercise in healthy individuals. Experiments in patients with a chronic lateral hemi-section of the spinal cord (Brown-Séquard syndrome) suggest that the EPR, although blunted, is operational when examined months to years post injury. However, whether this critically important reflex remains functional immediately after lateral SCI or, in contrast, experiences a period of reduced capacity due to spinal shock has not been established. This study was designed to assess EPR function after acute lateral transection of the spinal cord. The EPR was selectively activated in seven decerebrate cats via electrically stimulated static contraction of the triceps surae muscles of each hindlimb before and after lateral hemi-section of the T13–L2 region of the spinal cord. Compared to responses prior to injury, increases in mean arterial pressure (MAP) were significantly decreased when contracting the hindlimb either ipsilateral to the lesion (MAP = 17 ± 3 mmHg before and 9 ± 2 mmHg after) or contralateral to the lesion (MAP = 22 ± 5 mmHg before and 12 ± 4 mmHg after). The heart rate (HR) response to stimulation of the EPR was largely unaffected by induction of acute SCI. The findings suggest that the EPR maintains the ability to importantly contribute to cardiovascular regulation during exercise immediately following a Brown-Séquard-like injury. PMID:23403764

  5. Acute effects of intravenous dronedarone on electrocardiograms, hemodynamics and cardiac functions in anesthetized dogs.

    PubMed

    Saengklub, Nakkawee; Limprasutr, Vudhiporn; Sawangkoon, Suwanakiet; Buranakarl, Chollada; Hamlin, Robert L; Kijtawornrat, Anusak

    2016-02-01

    Dronedarone is a class III antiarrhythmic that has been used for management of atrial fibrillation in humans, but limited information was found in dogs. The objective of this study was to determine the acute effects of escalating concentrations of dronedarone on electrocardiograms (ECG), hemodynamics and cardiac mechanics in healthy dogs. A total of 7 beagle dogs were anesthetized with isoflurane and instrumented to obtain lead II ECG, pressures at ascending aorta, right atrium, pulmonary artery and left ventricle, and left ventricular pressure-volume relationship. Five dogs were given vehicle and followed by escalating doses of dronedarone (0.5, 1.0 and 2.5 mg/kg, 15 min for each dose), and two dogs were used as a vehicle-treated control. All parameters were measured at 15 min after the end of each dose. The results showed that all parameters in vehicle-treated dogs were unaltered. Dronedarone at 2.5 mg/kg significantly lengthened PQ interval (P<0.01), reduced cardiac output (P<0.01) and increased systemic vascular resistance (P<0.01). Dronedarone produced negative inotropy assessed by significantly lowered end-systolic pressure-volume relationship, preload recruitable stroke work, contractility index and dP/dtmax. It also impaired diastolic function by significantly increased end-diastolic pressure-volume relationship, tau and dP/dtmin. These results suggested that acute effects of dronedarone produced negative dromotropy, inotropy and lusitropy in anesthetized dogs. Care should be taken when given dronedarone to dogs, especially when the patients have impaired cardiac function.

  6. Carryover Effects of Acute DEHP Exposure on Ovarian Function and Oocyte Developmental Competence in Lactating Cows

    PubMed Central

    Kalo, Dorit; Hadas, Ron; Furman, Ori; Ben-Ari, Julius; Maor, Yehoshua; Patterson, Donald G.; Tomey, Cynthia; Roth, Zvi

    2015-01-01

    We examined acute exposure of Holstein cows to di(2-ethylhexyl) phthalate (DEHP) and its carryover effects on ovarian function and oocyte developmental competence. Synchronized cows were tube-fed with water or 100 mg/kg DEHP per day for 3 days. Blood, urine and milk samples were collected before, during and after DEHP exposure to examine its clearance pattern. Ovarian follicular dynamics was monitored through an entire estrous cycle by ultrasonographic scanning. Follicular fluids were aspirated from the preovulatory follicles on days 0 and 29 of the experiment and analyzed for phthalate metabolites and estradiol concentration. The aspirated follicular fluid was used as maturation medium for in-vitro embryo production. Findings revealed that DEHP impairs the pattern of follicular development, with a prominent effect on dominant follicles. The diameter and growth rate of the first- and second-wave dominant follicles were lower (P < 0.05) in the DEHP-treated group. Estradiol concentration in the follicular fluid was lower in the DEHP-treated group than in controls, and associated with a higher number of follicular pathologies (follicle diameter >25 mm). The pattern of growth and regression of the corpus luteum differed between groups, with a lower volume in the DEHP-treated group (P < 0.05). The follicular fluid aspirated from the DEHP-treated group, but not the controls, contained 23 nM mono(2-ethylhexyl) phthalate. Culturing of cumulus oocyte complexes in the follicular fluid aspirated from DEHP-treated cows reduced the proportion of oocytes progressing to the MII stage, and the proportions of 2- to 4-cell-stage embryos (P < 0.04) and 7-day blastocysts (P < 0.06). The results describe the risk associated with acute exposure to DEHP and its deleterious carryover effects on ovarian function, nuclear maturation and oocyte developmental competence. PMID:26154164

  7. Effect of acute and chronic excesses of dietary nitrogen on blood neutrophil functions in cattle.

    PubMed

    Raboisson, D; Caubet, C; Tasca, C; De Marchi, L; Ferraton, J M; Gannac, S; Millet, A; Enjalbert, F; Schelcher, F; Foucras, G

    2014-12-01

    Excess dietary nitrogen (EDN) is commonly expected in dairy herds, but no data are available regarding its consequences on cattle immunity. In this study neutrophil functions were assessed during EDN in steers. In experiment 1, 4 one-month periods, 4 diets [16% crude protein (CP; DM basis), 20% CP based on soybean meal, 20% CP based on urea, and 24% CP based on urea and soybean meal], and 4 steers were included in a crossover design to determine the effects of a chronic excess. In experiment 2, the repercussions of an acute excess were assessed with 2 periods of 10 d, the same 4 steers, and 2 diets containing 14 and 20% CP. Sampling was done during the fourth week of each period in experiment 1, and on d 0, 1, 2, 3, 7, and 9 of each period in experiment 2. Individual blood biochemistry parameters were measured and neutrophil factors, such as counts, recovery after isolation, surface expression of CD11b and CD62L, phagocytosis, diapedesis, reactive oxygen species (ROS) production, and bacteria killing, were determined. Data were analyzed by general linear models of R, with period, diet or biochemical component, and animal as explanatory variables. The outcome variables were biochemical or immune variables. The variables diet, period, and animal were forced as fixed effects. Data collected over the entire period of experiment 2 were pooled. Several multiples linear regressions or ANOVA were performed and a Bonferroni correction was applied. In experiment 2 (acute EDN), neutrophil counts were negatively associated with nitrogen intake, conversely to CD62L expression. The observed relative neutropenia may be due to neutrophil margination because CD62L-expressing neutrophils are more likely to stick to endothelium. Interestingly, ROS production was changed by EDN: chronic EDN (experiment 1) was negatively associated with opsonized zymozan (OZ)-induced ROS production and acute EDN (experiment 2) with spontaneous ROS production. For chronic EDN, ROS production upon

  8. The copYAZ Operon Functions in Copper Efflux, Biofilm Formation, Genetic Transformation, and Stress Tolerance in Streptococcus mutans

    PubMed Central

    Singh, Kamna; Senadheera, Dilani B.; Lévesque, Céline M.

    2015-01-01

    ABSTRACT In bacteria, copper homeostasis is closely monitored to ensure proper cellular functions while avoiding cell damage. Most Gram-positive bacteria utilize the copYABZ operon for copper homeostasis, where copA and copB encode copper-transporting P-type ATPases, whereas copY and copZ regulate the expression of the cop operon. Streptococcus mutans is a biofilm-forming oral pathogen that harbors a putative copper-transporting copYAZ operon. Here, we characterized the role of copYAZ operon in the physiology of S. mutans and delineated the mechanisms of copper-induced toxicity in this bacterium. We observed that copper induced toxicity in S. mutans cells by generating oxidative stress and disrupting their membrane potential. Deletion of the copYAZ operon in S. mutans strain UA159 resulted in reduced cell viability under copper, acid, and oxidative stress relative to the viability of the wild type under these conditions. Furthermore, the ability of S. mutans to form biofilms and develop genetic competence was impaired under copper stress. Briefly, copper stress significantly reduced cell adherence and total biofilm biomass, concomitantly repressing the transcription of the gtfB, gtfC, gtfD, gbpB, and gbpC genes, whose products have roles in maintaining the structural and/or functional integrity of the S. mutans biofilm. Furthermore, supplementation with copper or loss of copYAZ resulted in significant reductions in transformability and in the transcription of competence-associated genes. Copper transport assays revealed that the ΔcopYAZ strain accrued significantly large amounts of intracellular copper compared with the amount of copper accumulation in the wild-type strain, thereby demonstrating a role for CopYAZ in the copper efflux of S. mutans. The complementation of the CopYAZ system restored copper expulsion, membrane potential, and stress tolerance in the copYAZ-null mutant. Taking these results collectively, we have established the function of the S. mutans

  9. Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia.

    PubMed

    Stringaris, Kate; Sekine, Takuya; Khoder, Ahmad; Alsuliman, Abdullah; Razzaghi, Bonnie; Sargeant, Ruhena; Pavlu, Jiri; Brisley, Gill; de Lavallade, Hugues; Sarvaria, Anushruthi; Marin, David; Mielke, Stephan; Apperley, Jane F; Shpall, Elizabeth J; Barrett, A John; Rezvani, Katayoun

    2014-05-01

    The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-α and IFN-γ production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-α production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-α and IFN-γ production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival.

  10. Acute effects of inspiratory muscle warm-up on pulmonary function in healthy subjects.

    PubMed

    Özdal, Mustafa

    2016-06-15

    The acute effects of inspiratory muscle warm-up on pulmonary functions were examined in 26 healthy male subjects using the pulmonary function test (PFT) in three different trials. The control trial (CON) did not involve inspiratory muscle warm-up, while the placebo (IMWp) and experimental (IMW) trials involved inspiratory muscle warm-up. There were no significant changes between the IMWp and CON trials (p>0.05). All the PFT measurements, including slow vital capacity, inspiratory vital capacity, forced vital capacity, forced expiratory volume in one second, maximal voluntary ventilation, and maximal inspiratory pressure were significantly increased by 3.55%, 12.52%, 5.00%, 2.75%, 2.66%, and 7.03% respectively, in the subjects in the IMW trial than those in the CON trial (p<0.05). These results show that inspiratory muscle warm-up improved the pulmonary functions. The mechanisms responsible for these improvements are probably associated with the concomitant increase in the inspiratory muscle strength, and the cooperation of the upper thorax, neck, and respiratory muscles, and increased level of reactive O2 species in muscle tissue, and potentially improvement of muscle O2 delivery-to-utilization. However, further investigation is required to determine the precise mechanisms responsible from among these candidates.

  11. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    PubMed

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  12. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis

    PubMed Central

    Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  13. Acute effects of volcanic ash from Mount Saint Helens on lung function in children.

    PubMed

    Buist, A S; Johnson, L R; Vollmer, W M; Sexton, G J; Kanarek, P H

    1983-06-01

    To evaluate the acute effects of volcanic ash from Mt. St. Helens on the lung function of children, we studied 101 children 8 to 13 yr of age who were attending a 2-wk summer camp for children with diabetes mellitus in an area where about 1.2 cm of ash had fallen after the June 12, 1980, eruption. The outcome variables used were forced vital capacity, forced expiratory volume in one second, their ratio and mean transit time. Total and respirable dust levels were measured using personal sampling pumps. The children were tested on arrival and twice (early morning [A.M.] and late afternoon [P.M.]) every second or third day during the session. A within-day effect was measured by the P.M./A.M. ratio for the lung function variables; a between-day effect was measured by the change in the P.M. measurements over the 2 wk of camp. We found no strong evidence of either a within-day or a between-day effect on lung function, even in a subgroup of children who had preexisting lung disease or symptoms, despite daytime dust/ash levels that usually exceeded the Environmental Protection Agency's significant harm level for particulate matter.

  14. The effect of an acute bout of exercise on executive function among individuals with schizophrenia.

    PubMed

    Subramaniapillai, Mehala; Tremblay, Luc; Grassmann, Viviane; Remington, Gary; Faulkner, Guy

    2016-12-30

    Cognitive impairment represents a significant source of disability among individuals with schizophrenia. Therefore, the aim of this study was to investigate, at a proof-of-concept level, whether one single bout of exercise can improve executive function among these individuals. In this within-participant, counterbalanced experiment, participants with schizophrenia (n=36) completed two sessions (cycling at moderate-intensity and passively sitting) for 20min, with a one-week washout period between the two sessions. Participants completed the Wisconsin Card Sorting Test (WCST) before and after each session to measure changes in executive function. The inclusion of both sessions completed by each participant in the analyses revealed a significant carryover effect. Consequently, only the WCST scores from the first session completed by each participant was analyzed. There was a significant time by session interaction effect for non-perseverative errors. Post-hoc Tukey's HSD contrasts revealed a significant reduction in non-perseverative errors in the exercise group that was of moderate-to-large effect. Furthermore, there was also a moderate between-group difference at post-testing. Therefore, an acute bout of exercise can improve performance on an executive function task in individuals with schizophrenia. Specifically, the reduction in non-perseverative errors on the WCST may reflect improved attention, inhibition and overall working memory.

  15. Natural variation underlies alterations in NRAT1 expression and function that play a key role in rice aluminum tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum (Al) toxicity is a major constraint for crop production on acid soils which comprise approximately 40% of arable land in the tropics and subtropics. Rice is the most Al tolerant cereal crop, and offers a good model for identifying Al tolerance genes and mechanisms. Here we investigated natu...

  16. The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol.

    PubMed

    Shields, Grant S; Sazma, Matthew A; Yonelinas, Andrew P

    2016-09-01

    Core executive functions such as working memory, inhibition, and cognitive flexibility are integral to daily life. A growing body of research has suggested that acute stress may impair core executive functions. However, there are a number of inconsistencies in the literature, leading to uncertainty about how or even if acute stress influences core executive functions. We addressed this by conducting a meta-analysis of acute stress effects on working memory, inhibition, and cognitive flexibility. We found that stress impaired working memory and cognitive flexibility, whereas it had nuanced effects on inhibition. Many of these effects were moderated by other variables, such as sex. In addition, we compared effects of acute stress on core executive functions to effects of cortisol administration and found some striking differences. Our findings indicate that stress works through mechanisms aside from or in addition to cortisol to produce a state characterized by more reactive processing of salient stimuli but greater control over actions. We conclude by highlighting some important future directions for stress and executive function research.

  17. Characterization of a Functional Role of the Bradyrhizobium japonicum Isocitrate Lyase in Desiccation Tolerance.

    PubMed

    Jeon, Jeong-Min; Lee, Hae-In; Sadowsky, Michael J; Sugawara, Masayuki; Chang, Woo-Suk

    2015-07-22

    Bradyrhizobium japonicum is a nitrogen-fixing symbiont of soybean. In previous studies, transcriptomic profiling of B. japonicum USDA110, grown under various environmental conditions, revealed the highly induced gene aceA, encoding isocitrate lyase (ICL). The ICL catalyzes the conversion of isocitrate to succinate and glyoxylate in the glyoxylate bypass of the TCA cycle. Here, we evaluated the functional role of B. japonicum ICL under desiccation-induced stress conditions. We purified AceA (molecular mass = 65 kDa) from B. japonicum USDA110, using a His-tag and Ni-NTA column approach, and confirmed its ICL enzyme activity. The aceA mutant showed higher sensitivity to desiccation stress (27% relative humidity (RH)), compared to the wild type. ICL activity of the wild type strain increased approximately 2.5-fold upon exposure to 27% RH for 24 h. The aceA mutant also showed an increased susceptibility to salt stress. Gene expression analysis of aceA using qRT-PCR revealed a 148-fold induction by desiccation, while other genes involved in the glyoxylate pathway were not differentially expressed in this condition. Transcriptome analyses revealed that stress-related genes, such as chaperones, were upregulated in the wild-type under desiccating conditions, even though fold induction was not dramatic (ca. 1.5-2.5-fold).

  18. VOLTAGE-GATED POTASSIUM CHANNELS AT THE CROSSROADS OF NEURONAL FUNCTION, ISCHEMIC TOLERANCE, AND NEURODEGENERATION

    PubMed Central

    Shah, Niyathi Hegde; Aizenman, Elias

    2013-01-01

    Voltage-gated potassium (Kv) channels are widely expressed in the central and peripheral nervous system, and are crucial mediators of neuronal excitability. Importantly, these channels also actively participate in cellular and molecular signaling pathways that regulate the life and death of neurons. Injury-mediated increased K+ efflux through Kv2.1 channels promotes neuronal apoptosis, contributing to widespread neuronal loss in neurodegenerative disorders such as Alzheimer’s disease and stroke. In contrast, some forms of neuronal activity can dramatically alter Kv2.1 channel phosphorylation levels and influence their localization. These changes are normally accompanied by modifications in channel voltage-dependence, which may be neuroprotective within the context of ischemic injury. Kv1 and Kv7 channel dysfunction leads to neuronal hyperexcitability that critically contributes to the pathophysiology of human clinical disorders such as episodic ataxia and epilepsy. This review summarizes the neurotoxic, neuroprotective, and neuroregulatory roles of Kv channels, and highlights the consequences of Kv channel dysfunction on neuronal physiology. The studies described in this review thus underscore the importance of normal Kv channel function in neurons, and emphasize the therapeutic potential of targeting Kv channels in the treatment of a wide range of neurological diseases. PMID:24323720

  19. Molecular cloning and functional characterization of a novel apple MdCIPK6L gene reveals its involvement in multiple abiotic stress tolerance in transgenic plants.

    PubMed

    Wang, Rong-Kai; Li, Ling-Li; Cao, Zhong-Hui; Zhao, Qiang; Li, Ming; Zhang, Ling-Yun; Hao, Yu-Jin

    2012-05-01

    CBL-interacting protein kinases (CIPKs) are involved in many aspects of plant responses to abiotic stresses. However, their functions are poorly understood in fruit trees. In this study, a salt-induced MdCIPK6L gene was isolated from apple. Its expression was positively induced by abiotic stresses, stress-related hormones and exogenous Ca(2+). MdCIPK6L was not homologous to AtSOS2, however, its ectopic expression functionally complemented Arabidopsis sos2 mutant. Furthermore, yeast two-hybrid assay showed that MdCIPK6L protein interacted with AtSOS3, indicating that it functions in salt tolerance partially like AtSOS2 through SOS pathway. As a result, the overexpression of both MdCIPK6L and MdCIPK6LT175D remarkably enhanced the tolerance to salt, osmotic/drought and chilling stresses, but did not affect root growth, in transgenic Arabidopsis and apple. Also, T-to-D mutation to MdCIPK6L at Thr175 did not affect its function. These differences between MdCIPK6L and other CIPKs, especially CIPK6s, indicate that MdCIPK6L encodes a novel CIPK in apple. Finally, MdCIPK6L overexpression also conferred tolerance to salt, drought and chilling stresses in transgenic tomatoes. Therefore, MdCIPK6L functions in stress tolerance crossing the species barriers, and is supposed to be a potential candidate gene to improve stress tolerance by genetic manipulation in apple and other crops.

  20. Relative contribution of resting haemodynamic profile and lung function to exercise tolerance in male patients with chronic heart failure

    PubMed Central

    Faggiano, P; D'Aloia, A; Gualeni, A; Giordano, A

    2001-01-01

    OBJECTIVE—To clarify the relative contribution of resting haemodynamic profile and pulmonary function to exercise capacity in patients with heart failure.
SETTING—Cardiology department and cardiac rehabilitation unit in a tertiary centre.
DESIGN—161 male patients (mean (SD) age 59 (9) years) with heart failure (New York Heart Association class II-IV, left ventricular ejection fraction 23 (7)%) underwent spirometry, alveolar capillary diffusing capacity (DLCO), and mouth inspiratory and expiratory pressures (MIP, MEP, respectively, in 100 patients). Right heart catheterisation and a symptom limited cardiopulmonary exercise test were performed in 137 patients within 3-4 days.
RESULTS—Mean peak exercise oxygen consumption (V̇O2) was 13 (3.9) ml/kg/min. Among resting haemodynamic variables only cardiac index showed a significant correlation with peak V̇O2. There were no differences in haemodynamic variables between patients with peak V̇O2 ⩽ or > 14 ml/kg/min. There was a moderate correlation (p < 0.05) between several pulmonary function variables and peak V̇O2. Forced vital capacity (3.5 (0.9) v 3.2 (0.8) l, p < 0.05) and DLCO (21.6 (6.9) v 17.7 (5.5) ml/mm Hg/min, p < 0.05) were higher in patients with peak V̇O2 > 14 ml/kg/min than in those with peak V̇O2 ⩽ 14 ml/kg/min. Using a stepwise regression analysis, the respiratory and haemodynamic variables which correlated significantly with peak V̇O2 were DLCO, MEP, and cardiac index, with an overall R value of 0.63.
CONCLUSIONS—The data confirm previous studies showing a poor correlation between resting indices of cardiac function and exercise capacity in heart failure. However, several pulmonary function variables were related to peak exercise V̇O2. In particular, lung diffusing capacity and respiratory muscle function seem to affect exercise tolerance during heart failure.


Keywords: heart failure; exercise; pulmonary function; alveolar-capillary diffusing

  1. Spectral analysis of time functions of plasma glucose and immunoreactive insulin during intravenous glucose tolerance testing on atherosclerosis and noninsulin-dependent diabetes mellitus

    NASA Astrophysics Data System (ADS)

    Malinov, Igor A.; Denisova, Tatyana P.; Malinova, Lidia I.; Brook, Sergey B.

    2000-04-01

    The time functions of plasma glucose and insulin obtained during intravenous glucose tolerance test were approximated by sections of Fourier series. The convincing quantitative and quality distinctions of amplitudes both phases of the first and second harmonics of decomposition of the indicated time functions are obtained. These distinctions were used as a basis of diagnostic algorithm of metabolic violations appropriate for atherosclerosis and non-insulin dependent diabetes mellitus in clinically obvious and preclinical stages.

  2. Acute aerobic exercise increases cortical activity during working memory: a functional MRI study in female college students.

    PubMed

    Li, Lin; Men, Wei-Wei; Chang, Yu-Kai; Fan, Ming-Xia; Ji, Liu; Wei, Gao-Xia

    2014-01-01

    There is increasing evidence that acute aerobic exercise is associated with improved cognitive function. However, neural correlates of its cognitive plasticity remain largely unknown. The present study examined the effect of a session of acute aerobic exercise on working memory task-evoked brain activity as well as task performance. A within-subjects design with a counterbalanced order was employed. Fifteen young female participants (M = 19.56, SD = 0.81) were scanned using functional magnetic resonance imaging while performing a working memory task, the N-back task, both following an acute exercise session with 20 minutes of moderate intensity and a control rest session. Although an acute session of exercise did not improve behavioral performance, we observed that it had a significant impact on brain activity during the 2-back condition of the N-back task. Specifically, acute exercise induced increased brain activation in the right middle prefrontal gyrus, the right lingual gyrus, and the left fusiform gyrus as well as deactivations in the anterior cingulate cortexes, the left inferior frontal gyrus, and the right paracentral lobule. Despite the lack of an effect on behavioral measures, significant changes after acute exercise with activation of the prefrontal and occipital cortexes and deactivation of the anterior cingulate cortexes and left frontal hemisphere reflect the improvement of executive control processes, indicating that acute exercise could benefit working memory at a macro-neural level. In addition to its effects on reversing recent obesity and disease trends, our results provide substantial evidence highlighting the importance of promoting physical activity across the lifespan to prevent or reverse cognitive and neural decline.

  3. Crossed cerebellar diaschisis in acute ischemic stroke: Impact on morphologic and functional outcome.

    PubMed

    Kunz, Wolfgang G; Sommer, Wieland H; Höhne, Christopher; Fabritius, Matthias P; Schuler, Felix; Dorn, Franziska; Othman, Ahmed E; Meinel, Felix G; von Baumgarten, Louisa; Reiser, Maximilian F; Ertl-Wagner, Birgit; Thierfelder, Kolja M

    2017-01-01

    Crossed cerebellar diaschisis (CCD) is the phenomenon of hypoperfusion and hypometabolism of the contralateral cerebellar hemisphere caused by dysfunction of the related supratentorial region. Our aim was to analyze its influence on morphologic and functional outcome in acute ischemic stroke. Subjects with stroke caused by a large vessel occlusion of the anterior circulation were selected from an initial cohort of 1644 consecutive patients who underwent multiparametric CT including whole-brain CT perfusion. Two experienced readers evaluated the posterior fossa in terms of CCD absence (CCD-) or presence (CCD+). A total of 156 patients formed the study cohort with 102 patients (65.4%) categorized as CCD- and 54 (34.6%) as CCD+. In linear and logistic regression analyses, no significant association between CCD and final infarction volume (β = -0.440, p = 0.972), discharge mRS ≤ 2 (OR = 1.897, p = 0.320), or 90-day mRS ≤ 2 (OR = 0.531, p = 0.492) was detected. CCD+ patients had larger supratentorial cerebral blood flow deficits (median: 164 ml vs. 115 ml; p = 0.001) compared to CCD-patients. Regarding complications, CCD was associated with a higher rate of parenchymal hematomas (OR = 4.793, p = 0.035). In conclusion, CCD is frequently encountered in acute ischemic stroke caused by large vessel occlusion of the anterior circulation. CCD was associated with the occurrence of parenchymal hematoma in the ipsilateral cerebral infarction but did not prove to significantly influence patient outcome.

  4. Acute right ventricular pressure overload compromises left ventricular function by altering septal strain and rotation.

    PubMed

    Chua, Jason; Zhou, Wei; Ho, Jonathan K; Patel, Nikhil A; Mackensen, G Burkhard; Mahajan, Aman

    2013-07-15

    While right ventricular (RV) dysfunction has long been known to affect the performance of left ventricle (LV), the mechanisms remain poorly defined. Recently, speckle-tracking echocardiography has demonstrated that preservation of strain and rotational dynamics is crucial to both LV systolic and diastolic function. We hypothesized that alteration in septal strain and rotational dynamics of the LV occurs during acute RV pressure overload (RVPO) and leads to decreased cardiac performance. Seven anesthetized pigs underwent median sternotomy and placement of intraventricular pressure-volume conductance catheters. Two-dimensional echocardiographic images and LV pressure-volume loops were acquired for offline analysis at baseline and after banding of the pulmonary artery to achieve RVPO (>50 mmHg) induced RV dysfunction. RVPO resulted in a significant decrease (P < 0.05) in LV end-systolic elastance (50%), systolic change in pressure over change in time (19%), end-diastolic volume (22%), and cardiac output (37%) that correlated with decrease in LV global circumferential strain (58%), LV apical rotation (28%), peak untwisting (reverse rotation) rate (27%), and prolonged time to peak rotation (17%), while basal rotation was not significantly altered. RVPO reduced septal radial and circumferential strain, while no other segment of the LV midpapillary wall was affected. RVPO decreased septal radial strain on LV side by 27% and induced a negative radial strain from 28 ± 5 to -16 ± 2% on the RV side of the septum. The septal circumferential strain on both LV and RV side decreased by 46 and 50%, respectively, following RVPO (P < 0.05). Our results suggest that acute RVPO impairs LV performance by primarily altering septal strain and apical rotation.

  5. Expression and functional characterization of CD33 transcript variants in human acute myeloid leukemia

    PubMed Central

    Laszlo, George S.; Harrington, Kimberly H.; Gudgeon, Chelsea J.; Beddoe, Mary E.; Fitzgibbon, Matthew P.; Ries, Rhonda E.; Lamba, Jatinder K.; McIntosh, Martin W.; Meshinchi, Soheil; Walter, Roland B.

    2016-01-01

    With the demonstration of improved survival of some acute myeloid leukemia (AML) patients with the CD33 antibody-drug conjugate, gemtuzumab ozogamicin (GO), CD33 has been validated as a target for antigen-specific immunotherapy. Since previous studies identified a CD33 splice variant missing exon 2 (CD33∆E2) and, consequently, the immune-dominant membrane-distal V-set domain, we investigated the expression and functional characteristics of CD33 transcript variants in AML. In primary AML specimens, we not only found full-length CD33 (CD33FL) and CD33∆E2 but also corresponding variants containing an alternate exon 7 predicted to encode a CD33 protein lacking most of the intracellular domain (CD33E7a and, not previously described, CD33∆E2,E7a) in almost all cases. In acute leukemia cell sublines engineered to express individual CD33 splice variants, all splice variants had endocytic properties. CD33FL and CD33E7a mediated similar degrees of GO cytotoxicity, whereas CD33∆E2 and CD33∆E2,E7a could not serve as target for GO. Co-expression of CD33∆E2 did not interfere with CD33FL endocytosis and did not impact CD33FL-mediated GO cytotoxicity. Together, our findings document a greater-than-previously thought complexity of CD33 expression in human AML. They identify CD33 variants that lack exon 2 and are not recognized by current CD33-directed therapeutics as potential target for future unconjugated or conjugated antibodies. PMID:27248327

  6. Effect of the Interaction between Recanalization and Collateral Circulation on Functional Outcome in Acute Ischaemic Stroke

    PubMed Central

    Mangiafico, Salvatore; Saia, Valentina; Nencini, Patrizia; Romani, Ilaria; Palumbo, Vanessa; Pracucci, Giovanni; Consoli, Arturo; Rosi, Andrea; Renieri, Leonardo; Nappini, Sergio; Limbucci, Nicola; Inzitari, Domenico; Gensini, Gian Franco

    2014-01-01

    Summary Identification of patients with acute ischaemic stroke who could most benefit from arterial recanalization after endovascular treatment remains an unsettled issue. Although several classifications of collateral circulation have been proposed, the clinical role of collaterals is still debated. We evaluated the effect of the collateral circulation in relation to recanalization as a predictor of clinical outcome. Data were prospectively collected from 102 patients consecutively treated for proximal middle cerebral or internal carotid artery occlusion. The collateral circulation was evaluated with a novel semiquantitative-qualitative score, the Careggi collateral score (CCS), in six grades. Both CCS and recanalization grades (TICI) were analysed in relation to clinical outcome. A statistical analysis was performed to evaluate the effect of interaction between recanalization and collateral circulation on clinical outcome. Out of the 102 patients, 37 (36.3%) had poor collaterals, and 65 (63.7%) had good collaterals. Patients with good collaterals had lower basal National Institute of Health Stroke Scale (NIHSS), more distal occlusion, smaller lesions at 24h CT scan and better functional outcome. After multivariate analysis, the interaction between recanalization and collateral grades was significantly stronger as a predictor of good outcome (OR 6.87, 95% CI 2.11 – 22.31) or death (OR 4.66, 95%CI 1.48 – 14.73) compared to the effect of the single variables. Collaterals showed an effect of interaction with the recanalization grade in determining a favourable clinical outcome. Assessment of the collateral circulation might help predict clinical results after recanalization in patients undergoing endovascular treatment for acute ischaemic stroke. PMID:25496680

  7. Contractile function and sarcolemmal permeability after acute low-load resistance exercise with blood flow restriction.

    PubMed

    Wernbom, Mathias; Paulsen, Gøran; Nilsen, Tormod S; Hisdal, Jonny; Raastad, Truls

    2012-06-01

    Conflicting findings have been reported regarding muscle damage with low-intensity resistance exercise with blood flow restriction (BFR) by pressure cuffs. This study investigated muscle function and muscle fibre morphology after a single bout of low-intensity resistance exercise with and without BFR. Twelve physically active subjects performed unilateral knee extensions at 30% of their one repetition maximum (1RM), with partial BFR on one leg and the other leg without occlusion. With the BFR leg, five sets were performed to concentric torque failure, and the free-flow leg repeated the exact same number of repetitions and sets. Biopsies were obtained from vastus lateralis before and 1, 24 and 48 h after exercise. Maximum isometric torque (MVC) and resting tension were measured before and after exercise and at 4, 24, 48, 72, 96 and 168 h post-exercise. The results demonstrated significant decrements in MVC (lasting ≥48 h) and delayed onset muscle soreness in both legs, and increased resting tension for the occluded leg both acutely and at 24 h post-exercise. The percentage of muscle fibres showing elevated intracellular staining of the plasma protein tetranectin, a marker for sarcolemmal permeability, was significantly increased from 9% before exercise to 27-38% at 1, 24 and 48 h post-exercise for the BFR leg. The changes in the free-flow leg were significant only at 24 h (19%). We conclude that an acute bout of low-load resistance exercise with BFR resulted in changes suggesting muscle damage, which may have implications both for safety aspects and for the training stimulus with BFR exercise.

  8. [Acute effect of ambient air pollution on small airway lung functions among school children in Shanghai].

    PubMed

    Zhang, L J; Guo, C Y; Xu, H H; Xu, D; Shen, X B; Du, X Y; Zhang, M H; Tan, J G; Zhang, J H; Dong, C Y; Qian, H L; Shi, Y W; Pan, M Z; Zhou, X D

    2017-02-10

    Objective: To study the acute effects of compound ambient air pollution on small airway lung functions among school children in Shanghai. Method: A longitudinal survey on lung functions was conducted among 233 school-children from three schools (A, B and C, located in innerring, mid-ring and outer-ring areas). Lung function test was performed once a week for 3 times respectively, among children in school A and B in Dec. 2013 and in school C in Dec. 2014. The fourth lung function test was tested in Jun. 2014 and May 2015 in the respective schools. Results: from the lung function would include items as: forced mid-expiratory flow at 25% of forced vital capacity (MEF(25%)), mid-expiratory flow at 50% of forced vital capacity (MEF(50%)), mid-expiratory flow at 75% of forced vital capacity (MEF(75%)) and mid-expiratory flow between 25% and 75% of the forced vital capacity (FEF(25%-75%)). Data regarding the daily air quality real-time of PM(2.5), PM(10), SO(2) and NO(2) in Dec. 2013, Dec. 2014, Jun. 2014 and May. 2015 from the three environmental monitoring spots and meteorological data from the Shanghai Meteorological Service system which were physically close to the three schools, were collected simultaneously. Linear mixed effect model was used to examine the levels of correlation between lung function indicators and ambient air pollutants. Results When confounding factors on meteorology and individuals were controlled, the lag effects and accumulated lag effects were found to have existed between the internal quarter rang (IQR) concentration of PM(2.5) and PM(10) in lag2 day and lag02 days, IQR concentration of SO(2) in lag02 day and IQR concentration of NO(2) lag0 day, when small airway lung functions like MEF(25%), MEF(50%), MEF(75%) and FEF(25%-75%)(P<0.05) were inspected. Results from the two air pollutants model analysis showed that SO(2) and NO(2) presenting interactive effects with PM(2.5), PM(10) and lag effects more significant than the individual SO(2) and

  9. Functional analysis of thioredoxin from the desert lichen-forming fungus, Endocarpon pusillum Hedwig, reveals its role in stress tolerance

    PubMed Central

    Li, Hui; Wei, Jiang-Chun

    2016-01-01

    Endocarpon pusillum is a lichen-forming fungus with an outstanding stress resistance property closely related to its antioxidant system. In this study, thioredoxin (Trx), one of the main components of antioxidant defense systems in E. pusillum (EpTrx), was characterized and analyzed both in transgenic yeasts and in vitro. Our analyses identified that the heterologous expression of EpTrx in the yeast Pichia pastoris significantly enhanced its resistance to osmotic and oxidative stresses. Assays in vitro showed EpTrx acted as a disulfide reductase as well as a molecular chaperone by assembling into various polymeric structures. Upon exposure to heat-shock stress, EpTrx exhibited weaker disulfide reductase activity but stronger chaperone activity, which coincided with the switching of the protein complexes from low molecular weight forms to high molecular weight complexes. Specifically, we found that Cys31 near but not at the active site was crucial in promoting the structural and functional transitions, most likely by accelerating the formation of intermolecular disulfide bond. Transgenic Saccharomyces cerevisiae harboring the native EpTrx exhibited stronger tolerance to oxidative, osmotic and high temperature stresses than the corresponding yeast strain containing the mutant EpTrx (C31S). Our results provide the first molecular evidence on how Trx influences stress response in lichen-forming fungi. PMID:27251605

  10. Functional capacities of blood neurtrophils are influenced by both acute and chronic dexamethasone stress models in beef steers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study investigated the effects of acute and chronic stress models on the functional capacity of blood neutrophils in beef steers. Steers (N=32; 209 +/- 8 kg) were blocked by BW and assigned to 1 of 3 treatments: 1) Control (CON), no dexamethasone (DEX); 2) Chronic stress (CHR), 0.5 mg/kg BW DEX...

  11. Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function

    EPA Science Inventory

    Toluene is a volatile organic compound (VOC) and a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several modes of action in the CNS have been proposed. Therefore, we sought to identify potential pathways ...

  12. Acute Effects of Classroom Exercise Breaks on Executive Function and Math Performance: A Dose-Response Study

    ERIC Educational Resources Information Center

    Howie, Erin K.; Schatz, Jeffrey; Pate, Russell R.

    2015-01-01

    Purpose: The purpose of this study was to determine the acute dose-response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min, 10-min, or 20-min classroom exercise breaks to 10 min of sedentary classroom activity. Method: This study used a within-subjects…

  13. Mild sensory stimulation re-establishes cortical function during the acute phase of ischemia

    PubMed Central

    Lay, Christopher C.; Davis, Melissa F.; Chen-Bee, Cynthia H.; Frostig, Ron D.

    2011-01-01

    When delivered within 1 and in most cases 2 hours of permanent middle cerebral artery occlusion (pMCAO), mild sensory stimulation (intermittent single whisker stimulation) was shown to be completely neuroprotective according to assessment with multiple techniques 24 hours after pMCAO in a rodent model of ischemic stroke (Lay et al., 2010). The acute effect of stimulation treatment on the ischemic cortex however, had yet to be reported. Here we characterize cortical function and perfusion during the 120 minute whisker stimulation period in four experimental groups with treatment initiated 0, 1, 2 hours (protected groups) or 3 hours post-pMCAO (unprotected group) using multiple techniques. According to functional imaging, a gradual return of evoked whisker functional representation to baseline levels was initiated with treatment onset and completed within the treatment period. Evoked neuronal activity and reperfusion to the ischemic area also showed a gradual recovery in protected animals. Surprisingly, a similar recovery profile was observed in response to treatment in all protected animals, irrespective of treatment onset time. Non-stimulated pMCAO control group data demonstrate that reperfusion is not spontaneous. This makes the complete protection observed in the majority of animals stimulated at 2 hours post-pMCAO even more surprising as these animals recovered despite having been in this severely ischemic state for two full hours. In summary, when delivered within a 2 hour window post- pMCAO, whisker stimulation treatment initiated reperfusion and a gradual recovery of cortical function that was completed or nearly completed within the treatment period. PMID:21832179

  14. Acute damage threshold for infrared neural stimulation of the cochlea: functional and histological evaluation.

    PubMed

    Goyal, Vinay; Rajguru, Suhrud; Matic, Agnella I; Stock, Stuart R; Richter, Claus-Peter

    2012-11-01

    This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0-127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea.

  15. Ultraviolet-B-induced DNA damage and ultraviolet-B tolerance mechanisms in species with different functional groups coexisting in subalpine moorlands.

    PubMed

    Wang, Qing-Wei; Kamiyama, Chiho; Hidema, Jun; Hikosaka, Kouki

    2016-08-01

    High doses of ultraviolet-B (UV-B; 280-315 nm) radiation can have detrimental effects on plants, and especially damage their DNA. Plants have DNA repair and protection mechanisms to prevent UV-B damage. However, it remains unclear how DNA damage and tolerance mechanisms vary among field species. We studied DNA damage and tolerance mechanisms in 26 species with different functional groups coexisting in two moorlands at two elevations. We collected current-year leaves in July and August, and determined accumulation of cyclobutane pyrimidine dimer (CPD) as UV-B damage and photorepair activity (PRA) and concentrations of UV-absorbing compounds (UACs) and carotenoids (CARs) as UV-B tolerance mechanisms. DNA damage was greater in dicot than in monocot species, and higher in herbaceous than in woody species. Evergreen species accumulated more CPDs than deciduous species. PRA was higher in Poaceae than in species of other families. UACs were significantly higher in woody than in herbaceous species. The CPD level was not explained by the mechanisms across species, but was significantly related to PRA and UACs when we ignored species with low CPD, PRA and UACs, implying the presence of another effective tolerance mechanism. UACs were correlated negatively with PRA and positively with CARs. Our results revealed that UV-induced DNA damage significantly varies among native species, and this variation is related to functional groups. DNA repair, rather than UV-B protection, dominates in UV-B tolerance in the field. Our findings also suggest that UV-B tolerance mechanisms vary among species under evolutionary trade-off and synergism.

  16. Fluid shifts and muscle function in humans during acute simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Tipton, C. M.; Gollnick, P. D.; Mubarak, S. J.; Tucker, B. J.; Akeson, W. H.

    1983-01-01

    The acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surface reflex time were studied in eight supine human subjects who were placed in a 5 degrees head-down tilt position for 8 hr. Results show a cephalic fluid shift from the legs as indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. The interstitial fluid pressure in the tibialis anterior muscle and subcutaneous tissue of the lower leg was found to fall significantly, while other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. The total water content of the soleus muscle was unchanged during the head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged, while the triceps surae reflex time associated with plantar flexion movement slowed slightly. These results demonstrate a dehydration effect of head-down tilt on muscle and subcutaneous tissue of the lower leg that may affect muscle function.

  17. Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception

    PubMed Central

    Reimann, Henning Matthias; Hentschel, Jan; Marek, Jaroslav; Huelnhagen, Till; Todiras, Mihail; Kox, Stefanie; Waiczies, Sonia; Hodge, Russ; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

    2016-01-01

    Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus. PMID:26821826

  18. Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.

    PubMed

    Daly, Eileen; Ecker, Christine; Hallahan, Brian; Deeley, Quinton; Craig, Michael; Murphy, Clodagh; Johnston, Patrick; Spain, Debbie; Gillan, Nicola; Gudbrandsen, Maria; Brammer, Michael; Giampietro, Vincent; Lamar, Melissa; Page, Lisa; Toal, Fiona; Schmitz, Nicole; Cleare, Anthony; Robertson, Dene; Rubia, Katya; Murphy, Declan G M

    2014-09-01

    It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target.

  19. Acute improvement of endothelial functions after oral ingestion of isohumulones, bitter components of beer.

    PubMed

    Tomita, Junko; Mochizuki, Seiichi; Fujimoto, Sohachi; Kashihara, Naoki; Akasaka, Takashi; Tanimoto, Mitsune; Yoshida, Kiyoshi

    2017-03-18

    Isohumulones, principal components of the bitter taste of beers, have antioxidant capacity. We studied i) the effects of oral ingestion of isomerized hop extract (IHE) on the endothelial functions in smokers as well as non-smokers and ii) the effects of IHE on cultured endothelial cells in high oxidative stress state. Twelve cigarette smokers and eleven non-smokers ingested IHE and placebo in a randomized crossover design. Flow-mediated vasodilatation (FMD) was measured using ultrasonography. We also studied the effects of isohumulones on i) the cell viability under hypoxia and ii) the levels of angiotensin II (AT-II)-induced reactive oxygen species (ROS) in the cultured human aortic endothelial cells (HAECs). At baseline, the FMDs of the smokers were significantly lower than those of the non-smokers. The FMDs increased significantly after 30 min and 120 min of IHE ingestion in both the smokers and the non-smokers. IHE protected the HAECs from hypoxia-induced cell death as assessed by cell viability. IHE also reduced the AT-II-induced intracellular ROS level. Oral ingestion of IHE appears to exert acute beneficial effects on the endothelial functions in both the smokers and non-smokers, and the in vitro experiments using HAECs suggested that the effect be through reducing intracellular oxidative stress.

  20. Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception

    NASA Astrophysics Data System (ADS)

    Reimann, Henning Matthias; Hentschel, Jan; Marek, Jaroslav; Huelnhagen, Till; Todiras, Mihail; Kox, Stefanie; Waiczies, Sonia; Hodge, Russ; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

    2016-01-01

    Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus.

  1. Acute, whole-body microwave exposure and testicular function of rats

    SciTech Connect

    Lebovitz, R.M.; Johnson, L.

    1987-01-01

    Male Sprague-Dawley rats were exposed for 8 h to continuous-wave microwave radiation (MWR, 1.3 Ghz) at a mean specific absorbed dose rate of 9 mW/g. MWR exposure and sham-irradiation took place in unidirectionally energized cylindrical waveguide sections, within which the animals were essentially unrestrained. The MWR treatment in this setting was determined to yield an elevation of deep rectal temperature to 4.5 degrees C. The animals were taken for analysis at 6.5, 13, 26, and 52 days following treatment, which corresponded to .5, 1, 2, and 4 cycles of the seminiferous epithelium. Net mass of testes, epididymides, and seminal vesicles; daily sperm production (DSP) per testis and per gram of testis; and the number of epididymal sperm were determined. The levels of circulating follicle-stimulating hormone (FSH) and leutinizing hormone (LH) were derived via radioimmunoassay of plasma samples taken at the time of sacrifice. Despite the evident acute thermogenesis of the MWR at 9 mW/g, no substantial decrement in testicular function was found. We conclude that, in the unrestrained rat, whole body irradiation at 9 mW/g, while sufficient to induce evident hyperthermia, is not a sufficient condition for disruption of any of these key measures of testicular function.

  2. Altered mitochondrial function after acute alteration of the endogenous insulin/glucagon ratio

    SciTech Connect

    Rohweder-Dunn, G.; Aprille, J.R.

    1986-05-01

    Mannoheptulose (MH) affects pancreatic Islet cells to cause a drop in serum insulin and a rise in glucagon. This effect peaks 1 hr after injection and results in a 3-fold increase in serum glucose. Here they examined whether metabolic functions of liver mitochondria (mito) are altered by this change in hormone status. Rats fed ad lib on 12 hr light/dark cycles were given MH (2g/kg) or vehicle i.p. during the first 2 hrs of the light cycle. Liver mito were isolated 1 hr later. Acid-extracts were assayed for ATP+ADP+AMP (nmol/mg prot). Citrulline synthesis and pyruvate carboxylation rates (nmol/min/mg prot) were assayed by following H(/sup 14/C)O/sub 3//sup -/ fixation in appropriate media. State 3 and 2,4-DNP-uncoupled respiratory rates (1/2 nmol O/sub 2//min/mg prot) were assayed polarographically with succinate. The effects of MH on mito are comparable to reported effects of glucagon injection. MH evokes acute reciprocal changes in insulin and glucagon that are highly reproducible. Thus, MH offers an interesting model for studying the effect of endogenous hormones on mito functions.

  3. Moving and academic learning are not antagonists: acute effects on executive function and enjoyment.

    PubMed

    Vazou, Spyridoula; Smiley-Oyen, Ann

    2014-10-01

    Classroom-based physical activity is a new approach aiming to improve both physical activity levels and academic achievement. This study investigated the acute effect of a 10-min bout of aerobic physical activity integrated with math practice, compared with a seated math practice, on executive function and enjoyment among normal-weight (n = 24) and overweight children (n = 11). Thirty-five typically developing prepubescent children (10.55 ± 0.74 years) completed a session of physical activity integrated with math practice and a seated math practice session in counterbalanced order. Results showed that following integrated physical activity, the response time in the Standard Flanker improved more than after seated practice. Among the overweight children, physical activity benefitted performance in the Standard Flanker by preventing the decline associated with seated practice. Children enjoyed the physical activity practice more than the seated practice. These findings suggest that integrating physical activity with academic instruction may be a realistic strategy for promoting physical activity because it may facilitate, not antagonize, executive function.

  4. Interferon-α acutely impairs whole-brain functional connectivity network architecture - A preliminary study.

    PubMed

    Dipasquale, Ottavia; Cooper, Ella A; Tibble, Jeremy; Voon, Valerie; Baglio, Francesca; Baselli, Giuseppe; Cercignani, Mara; Harrison, Neil A

    2016-11-01

    Interferon-alpha (IFN-α) is a key mediator of antiviral immune responses used to treat Hepatitis C infection. Though clinically effective, IFN-α rapidly impairs mood, motivation and cognition, effects that can appear indistinguishable from major depression and provide powerful empirical support for the inflammation theory of depression. Though inflammation has been shown to modulate activity within discrete brain regions, how it affects distributed information processing and the architecture of whole brain functional connectivity networks have not previously been investigated. Here we use a graph theoretic analysis of resting state functional magnetic resonance imaging (rfMRI) to investigate acute effects of systemic interferon-alpha (IFN-α) on whole brain functional connectivity architecture and its relationship to IFN-α-induced mood change. Twenty-two patients with Hepatitis-C infection, initiating IFN-α-based therapy were scanned at baseline and 4h after their first IFN-α dose. The whole brain network was parcellated into 110 cortical and sub-cortical nodes based on the Oxford-Harvard Atlas and effects assessed on higher-level graph metrics, including node degree, betweenness centrality, global and local efficiency. IFN-α was associated with a significant reduction in global network connectivity (node degree) (p=0.033) and efficiency (p=0.013), indicating a global reduction of information transfer among the nodes forming the whole brain network. Effects were similar for highly connected (hub) and non-hub nodes, with no effect on betweenness centrality (p>0.1). At a local level, we identified regions with reduced efficiency of information exchange and a sub-network with decreased functional connectivity after IFN-α. Changes in local and particularly global functional connectivity correlated with associated changes in mood measured on the Profile of Mood States (POMS) questionnaire. IFN-α rapidly induced a profound shift in whole brain network structure

  5. The acute anorexic effect of liraglutide, a GLP-1 receptor agonist, does not require functional leptin receptor, serotonin, and hypothalamic POMC and CART activities in mice.

    PubMed

    Nonogaki, Katsunori; Kaji, Takao

    2016-10-01

    The acute anorexic effect of liraglutide, a GLP-1 receptor agonist, did not require functional leptin receptor, serotonin, and hypothalamic proopiomelanocortin and cocaine amphetamine regulated transcript activities in mice, although decrease in functional hypothalamic orexin activity might be involved in the acute anorexic effect of liraglutide.

  6. Effects of chronic and acute protein administration on renal function in patients with chronic renal insufficiency.

    PubMed

    Bilo, H J; Schaap, G H; Blaak, E; Gans, R O; Oe, P L; Donker, A J

    1989-01-01

    In 6 volunteers with normal renal function, we investigated the effects of various kinds of protein (soy, lactoprotein and beef) and various amounts of an intravenously administered amino acid solution on glomerular filtration (GFR) and effective renal plasma flow (ERPF). As for the protein-induced changes in renal function, rises in GFR and ERPF were lowest with soy protein, and highest with beef (baseline GFR, 110 +/- 5; soy, 122 +/- 5; beef, 131 +/- 5 ml/min/1.73 m2; mean +/- SEM). High doses of intravenous amino acids induced a rise in GFR comparable to that after beef (132 +/- 5 ml/min/1.73 m2). In a combined test a liquid mixed meal together with intravenously administered amino acids induced a comparable increase of the GFR (baseline 114 +/- 5 versus 129 +/- 5 ml/min/1.73 m2). When investigating 9 patients with chronic renal insufficiency after 4 weeks of low protein intake (LP) and after 4 weeks of high protein intake (HP), GFR and ERPF rose significantly under baseline conditions (GFR-LP41 +/- 9 versus GFR-HP 45 +/- 9 ml/min/1.73 m2, p less than 0.02; ERPF-LP 169 +/- 39 versus ERPF-HP 180 +/- 40 ml/min/1.73 m2, p less than 0.02; paired Wilcoxon). At the end of both dietary periods a comparable rise in renal function could be induced through acute stimulation (GFR-LP 20 +/- 5, GFR-HP 16 +/- 4; ERPF-LP 23 +/- 7, ERPF-HP 22 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Acute effects of self-myofascial release using a foam roller on arterial function.

    PubMed

    Okamoto, Takanobu; Masuhara, Mitsuhiko; Ikuta, Komei

    2014-01-01

    Flexibility is associated with arterial distensibility. Many individuals involved in sport, exercise, and/or fitness perform self-myofascial release (SMR) using a foam roller, which restores muscles, tendons, ligaments, fascia, and/or soft-tissue extensibility. However, the effect of SMR on arterial stiffness and vascular endothelial function using a foam roller is unknown. This study investigates the acute effect of SMR using a foam roller on arterial stiffness and vascular endothelial function. Ten healthy young adults performed SMR and control (CON) trials on separate days in a randomized controlled crossover fashion. Brachial-ankle pulse wave velocity (baPWV), blood pressure, heart rate, and plasma nitric oxide (NO) concentration were measured before and 30 minutes after both SMR and CON trials. The participants performed SMR of the adductor, hamstrings, quadriceps, iliotibial band, and trapezius. Pressure was self-adjusted during myofascial release by applying body weight to the roller and using the hands and feet to offset weight as required. The roller was placed under the target tissue area, and the body was moved back and forth across the roller. In the CON trial, SMR was not performed. The baPWV significantly decreased (from 1,202 ± 105 to 1,074 ± 110 cm·s-1) and the plasma NO concentration significantly increased (from 20.4 ± 6.9 to 34.4 ± 17.2 μmol·L-1) after SMR using a foam roller (both p < 0.05), but neither significantly differed after CON trials. These results indicate that SMR using a foam roller reduces arterial stiffness and improves vascular endothelial function.

  8. Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction.

    PubMed

    Zhu, Guiyue; Yao, Yucai; Pan, Lingyun; Zhu, Wei; Yan, Suhua

    2015-12-17

    BACKGROUND This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. MATERIAL AND METHODS AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. RESULTS Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group. CONCLUSIONS Decrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats.

  9. Lipoic Acid Use and Functional Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke and Diabetes

    PubMed Central

    Choi, Kang-Ho; Kim, Joon-Tae; Kim, Hyung-Seok; Kim, Ja-Hae; Nam, Tai-Seung; Choi, Seong-Min; Lee, Seung-Han; Kim, Byeong-Chae; Kim, Myeong-Kyu; Cho, Ki-Hyun

    2016-01-01

    Background Alpha-lipoic acid (aLA) is a strong antioxidant commonly used for treating diabetic polyneuropathy. Previously, we demonstrated the neurorestorative effects of aLA after cerebral ischemia in rats. However, its effects on patients with stroke remain unknown. We investigated whether patients treated with aLA have better functional outcomes after acute ischemic stroke (AIS) and reperfusion therapy than patients not receiving aLA. Methods In this retrospective study of 172 prospectively registered patients with diabetes and AIS treated with tissue plasminogen activator (tPA), we investigated the relationship between aLA use and functional outcome both after 3 months and after 1 year. The functional outcomes included occurrence of hemorrhagic transformation (HT), early neurological deterioration (END), and early clinical improvement (ECI). Favorable outcomes were defined as modified Rankin Scale (mRS) scores of 0–2. Results Of the 172 patients with AIS and diabetes, 47 (27.3%) used aLA. In the entire cohort, favorable outcomes occurred at significantly higher rates both at 3 months and at 1 year in those treated with aLA. The risks for END and HT were lower and the occurrence of ECI was higher in patients treated with aLA. In multivariable analysis, aLA use was associated with favorable outcomes both at 3 months and at 1 year. Age, HT, and increased National Institutes of Health Stroke Scale scores were negative predictors of a favorable outcome. Conclusions The use of aLA in patients with AIS and diabetes who are treated with tPA is associated with favorable outcomes. These results indicate that aLA could be a useful intervention for the treatment of AIS after reperfusion therapy. PMID:27677185

  10. The Effect of Exercise Training on Diastolic and Systolic Function After Acute Myocardial Infarction

    PubMed Central

    Fontes-Carvalho, Ricardo; Azevedo, Ana Isabel; Sampaio, Francisco; Teixeira, Madalena; Bettencourt, Nuno; Campos, Lilibeth; Gonçalves, Francisco Rocha; Ribeiro, Vasco Gama; Azevedo, Ana; Leite-Moreira, Adelino

    2015-01-01

    Abstract After acute myocardial infarction (AMI), diastolic dysfunction is frequent and an important determinant of adverse outcome. However, few interventions have proven to be effective in improving diastolic function. We aimed to determine the effect of exercise training on diastolic and systolic function after AMI. One month after AMI, 188 patients were prospectively randomized (1:1) to an 8-week supervised program of endurance and resistance exercise training (n = 86; 55.9 ± 10.8 years) versus standard of care (n = 89; 55.4 ± 10.3 years). All patients were submitted to detailed echocardiography and cardiopulmonary exercise test, at baseline and immediately after the study. Diastolic function was evaluated by the determination of tissue-Doppler derived early diastolic velocities (E′ velocity at the septal and lateral sides of mitral annulus) and by the E/E′ (ratio between the E wave velocity from mitral inflow and the E’ velocity) as recommended in the consensus document for diastolic function assessment. At the end of the study, there was no significant change in E′ septal velocity or E/E′ septal ratio in the exercise group. We observed a small, although nonsignificant, improvement in E′ lateral (mean change 0.1 ± 2.0 cm/s; P = 0.40) and E/E′ lateral ratio (mean change of −0.3 ± 2.5; P = 0.24), while patients in the control group had a nonsignificant reduction in E′ lateral (mean change −0.4 ± 1.9 cm/s; P = 0.09) and an increase in E/E′ lateral ratio (mean change + 0.3 ± 3.3; P = 0.34). No relevant changes occurred in other diastolic parameters. The exercise-training program also did not improve systolic function (either tissue Doppler systolic velocities or ejection fraction). Exercise capacity improved only in the exercise-training group, with an increase of 1.6 mL/kg/min in pVO2 (P = 0.001) and of 1.9 mL/kg/min in VO2 at anaerobic threshold (P < 0.001). After AMI

  11. Low zone tolerance to contact allergens in mice: a functional role for CD8+ T helper type 2 cells

    PubMed Central

    1996-01-01

    Normal skin is permeable to low molecular hydrophobic substances, including allergenic chemicals. Whereas such foreign matter appears to enter the skin naturally, it rarely induces contact hypersensitivity. This suggests that immunological tolerance would be the normal state of affairs. In search of a suitable model, we painted picryl chloride or oxazolone once or repeatedly on normal skin of BALB/c or C57B1/6 mice and found subsensitizing doses to be tolerogenic. The most effective doses in inducing tolerance were doses between those at the point of inflection from no responses to threshold sensitivity. But even doses three orders of magnitude lower than these suppressed subsequent sensitization if applied repeatedly. C57B1/6 mice (low responders) were consistently easier to make tolerant than BALB/c mice (high responders). The tolerant state established by a single painting was found to be fully developed at 48 h after initiation and long-lasting (>14 d). It could be adoptively transferred by intravenous injection of total spleen cells (SC), lymph node cells (LNC), or purified T cells and shown to be hapten specific. Pretreatment with cyclophosphamide (Cy) prevented tolerization. The T cells capable of transferring suppressive activity were found to be generated irrespective of the dose applied. On day 2 after painting, tolerance could be transferred with LNC from both tolerant and sensitized animals. On day 5, however, only cells from tolerant donors transferred tolerance. But by action of Cy, suppression was shown to be part of every sensitization, although masked. Production of hapten-specific antibodies was suppressed as well. Through depletion by monoclonal antibody in vitro the T suppressor cells were shown to belong to the murine CD8+ subset (Lyt2+). Upon restimulation in vitro by haptenized and irradiated normal SC, LNC from tolerant donors produced predominantly interleukin (IL)-4, IL-5, and IL-10. In contrast, LNC from sensitized donors produced

  12. Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis

    PubMed Central

    Bleau, Christian; Filliol, Aveline; Samson, Michel

    2016-01-01

    ABSTRACT Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million

  13. Acute aortocaval fistula: role of low perfusion pressure and subendocardial remodeling on left ventricular function

    PubMed Central

    Mazzo, Flávia R R; de Carvalho Frimm, Clovis; Moretti, Ana Iochabel S; Guido, Maria C; Koike, Marcia K

    2013-01-01

    The experimental model of aortocaval fistula is a useful model of cardiac hypertrophy in response to volume overload. In the present study it has been used to investigate the pathologic subendocardial remodeling associated with the development of heart failure during the early phases (day 1, 3, and 7) following volume overload. Compared with sham treated rats, aortocaval fistula rats showed lower systemic blood pressure and higher left ventricular end-diastolic pressure This resulted in lower coronary driving pressure and left ventricular systolic and diastolic dysfunction. Signs of myocyte necrosis, leukocyte cell infiltration, fibroplasia and collagen deposition appeared sequentially in the subendocardium where remodeling was more prominent than in the non-subendocardium. Accordingly, increased levels of TNF-alpha, IL-1 beta, and IL-6, and enhanced MMP-2 activity were all found in the subendocardium of rats with coronary driving pressure ≤60 mmHg. The coronary driving pressure was inversely correlated with MMP-2 activity in subendocardium in all time-points studied, and blood flow in this region showed positive correlation with systolic and diastolic function at day 7. Thus the predominant subendocardial remodeling that occurs in response to low myocardial perfusion pressure during the acute phases of aortocaval fistula contributes to early left ventricular dysfunction. PMID:23593971

  14. The Impact of Acute Loss of Weight on Eustachian Tube Function

    PubMed Central

    Pascoto, Gabriela; Abreu, Cassiana; Silva, Maria Laura; Weber, Raimar; Pignatari, Shirley Shizue; Stamm, Aldo

    2014-01-01

    Introduction The eustachian tube is one of the key structures responsible for the functional balance of the middle ear. Some clinical conditions associated with tubal malfunction can cause extremely unpleasant symptoms. These symptoms could be triggered by acute loss of weight, for example, after bariatric surgery. Objective To evaluate the frequency and intensity of auditory tube dysfunction symptoms in obese patients after bariatric surgery. Methods Nineteen patients with accepted formal indications for bariatric surgery underwent a hearing evaluation (otoscopy, tonal and vocal audiometry, and impedanceometry) and a hearing questionnaire before, at the time of, 3 months after surgery (first postoperative evaluation), and 6 months (second postoperative evaluation) after surgery. Patients with a history of ear disease or ear surgery were excluded. Results None of the patients reported tubal dysfunction symptoms before surgery. Postsurgical results showed that 5 (26.3%) patients presented symptoms related to dysfunction of the eustachian tube at the first postoperative evaluation. After the 6-month follow-up, 9 (47.3%) patients reported symptoms of tubal dysfunction. Conclusion This study suggests that bariatric surgery can cause symptoms of eustachian tube dysfunction, probably due to rapid weight loss and the consequent loss of peritubal fat. PMID:25992125

  15. Acute effect of brisk walking with graduated compression stockings on vascular endothelial function and oxidative stress.

    PubMed

    Okamoto, Takanobu; Sakamaki-Sunaga, Mikako; Min, Seokki; Miura, Takashi; Iwasaki, Tetsuji

    2013-11-01

    The purpose of this study was to investigate the acute effect of brisk walking with and without graduated compression stockings (GCSs) on vascular endothelial function and oxidative stress. Ten young healthy subjects walked briskly for 30 min with (GCS trial) and without (CON trial) GCSs in a randomized crossover trial. Brachial artery flow-mediated dilation (FMD) was measured as the per cent rise in the peak diameter from the baseline value at prior occlusion at each FMD measurement using B-mode ultrasonography before and 30 min after walking in the two trials. Derivatives of reactive oxygen metabolites (d-ROM), as an index of products of reactive oxygen species, and biological anti-oxidant potential (BAP), as an index of anti-oxidant potential, were also measured using a free radical elective evaluator before and 30 min after walking in both trials. FMD significantly decreased after brisk walking in both trials (P<0·05). However, FMD after brisk walking in the GCS trial was significantly higher than that in the CON trial (P<0·05). The d-ROM did not change before and after both trials, whereas the BAP significantly increased after walking in the GCS trial (P<0·05). These findings demonstrate that brisk walking while wearing GCSs suppresses the decrease in FMD and increases BAP.

  16. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

    PubMed Central

    Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.

    2014-01-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473

  17. Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute Lymphoblastic Leukemia

    PubMed Central

    Ge, Zheng; Gu, Yan; Han, Qi; Zhao, Gang; Li, Min; Li, Jianyong; Chen, Baoan; Sun, Tianyu; Dovat, Sinisa; Gale, Robert Peter; Song, Chunhua

    2016-01-01

    Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression in other types of ALL are not reported. We studied DNM2 mRNA level in adults with B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals in both forms of ALL. High DNM2 expression is associated with some clinical and laboratory features, inferior outcomes and with leukaemia cell proliferation. We also found Ikaros directly binds the DNM2 promoter and suppresses DNM2 expression. Consequently IKZF1 deletion is associated with high DNM2 expression. Conversely, casein kinase-2 (CK2)-inhibitor increases Ikaros function thereby inhibiting DNM2 expression. Inhibiting DNM2 suppresses proliferation of leukemia cells and synergizes with CK2 inhibition. Our data indicate high DNM2 expression is associated with Ikaros dysregulation and may be important in the development of B-ALL. PMID:27885263

  18. Functionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia

    PubMed Central

    Bhola, Patrick D.; Mar, Brenton G.; Lindsley, R. Coleman; Ryan, Jeremy A.; Hogdal, Leah J.; Vo, Thanh Trang; DeAngelo, Daniel J.; Galinsky, Ilene; Ebert, Benjamin L.

    2016-01-01

    Upfront resistance to chemotherapy and relapse following remission are critical problems in leukemia that are generally attributed to subpopulations of chemoresistant tumor cells. There are, however, limited means for prospectively identifying these subpopulations, which hinders an understanding of therapeutic resistance. BH3 profiling is a functional single-cell analysis using synthetic BCL-2 BH3 domain–like peptides that measures mitochondrial apoptotic sensitivity or “priming.” Here, we observed that the extent of apoptotic priming is heterogeneous within multiple cancer cell lines and is not the result of experimental noise. Apoptotic priming was also heterogeneous in treatment-naive primary human acute myeloid leukemia (AML) myeloblasts, and this heterogeneity decreased in chemotherapy-treated AML patients. The priming of the most apoptosis-resistant tumor cells, rather than the median priming of the population, best predicted patient response to induction chemotherapy. For several patients, these poorly primed subpopulations of AML tumor cells were enriched for antiapoptotic proteins. Developing techniques to identify and understand these apoptosis-insensitive subpopulations of tumor cells may yield insights into clinical chemoresistance and potentially improve therapeutic outcomes in AML. PMID:27599292

  19. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions.

    PubMed

    Cavalcanti-Galdino, M K; Silva, J A da; Mendes, L C; Santos, N A da; Simas, M L B

    2014-04-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions.

  20. Impairment in functional status and survival in patients with acute myeloid leukaemia.

    PubMed

    Wedding, Ulrich; Röhrig, Bernd; Klippstein, Almuth; Fricke, Hans-Joerg; Sayer, Herbert G; Höffken, Klaus

    2006-10-01

    Acute myeloid leukaemia (AML) is mainly affecting elderly patients. Elderly patients are increasingly affected by impairment of functional status (FS). FS is of prognostic relevance for survival in different tumours. Data for patients with AML are rare. Within a prospective trial we recruited patients with newly diagnosed AML and measured FS by two different methods: Karnofsky performance status (KPS) and instrumental activities of daily living (IADL). Sixty-three patients aged 19-85 years (median 61.1) were included. Twenty-three had prior myelodisplastic syndrome (MDS), 7 favourable, 17 unfavourable karyotype. Fifty received induction chemotherapy, 13 palliative chemotherapy. Median survival was 15.2 months (95% CI, 10.8-22.3) in all patients. Age, cytogenetic risk group, and impaired KPS and IADL significantly influenced median survival in univariate analysis. Impairment of IADL was the single most predictive variable. In multivariate analysis, impairment of IADL Score (HR:4.3, 95% CI 1.7-10.5, P = 0.001) and of KPS (HR:4.8, 95% CI 1.9-12.3, P = 0.001), and unfavourable cytogenetic risk group (HR:6.0, 95% CI 2.5-14.3, P < 0.001) significantly predicted median survival. In patients with AML, FS and not age is a major predictor of survival. The influence of FS is independent from cytogenetic risk group. IADL measurement adds information to KPS. The results have to be confirmed in a large sample of patients.

  1. Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs.

    PubMed

    Lafuente, Hector; Alvarez, Francisco J; Pazos, M Ruth; Alvarez, Antonia; Rey-Santano, M Carmen; Mielgo, Victoria; Murgia-Esteve, Xabier; Hilario, Enrique; Martinez-Orgado, José

    2011-09-01

    Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100β protein and brain tissue percentage of TNFα(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 ± 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 ± 1.4 points). HI induced histological changes, and NSE and S100β concentration and TNFα(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.

  2. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

    PubMed

    Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

    2015-02-01

    We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

  3. C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia

    PubMed Central

    Ding, Ye; Wang, Ze-chuan; Zheng, Yi; Hu, Zheng; Li, Yang; Luo, Dong-feng; Wang, Shao-yuan

    2016-01-01

    Recent reports have described a new post-transcriptional regulation that RNA transcripts can crosstalk with each other by competing for their common microRNAs. These RNA transcripts termed competing endogenous RNAs (ceRNAs) regulate the distribution of miRNAs on their targets. One corollary from ceRNA interaction is that chromosomal translocation in acute promyelocytic leukemia (APL) would perturb ceRNA regulation due to altered expression of 3′UTRs. In our study, we demonstrate that expression of PML/RARα, the APL-associated fusion oncogene is repressed by c-Myc mRNA transcript independent of protein-coding function but dependent upon microRNA. Attenuation of c-Myc transcript results in PML/RARα-degraded cellular phenotypes in APL cells, but these Myc reduction-associated cell phenotypes are sufficient to abrogate in a microRNA dependent manner. We also show that let-7 microRNA family members promote differentiation of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are affected by expression levels of both c-Myc and PML/RARα through altering miRNA targets. These results indicate that c-Myc mRNA represses PML/RARα expression via altering the distribution of let-7 miRNAs on their targets. Our findings reveal a previously unrecognized role of c-Myc as a potential ceRNA for PML/RARα in APL. PMID:27486764

  4. Impaired mitochondrial function is abrogated by dexrazoxane in doxorubicin-treated childhood acute lymphoblastic leukemia survivors

    PubMed Central

    Lipshultz, Steven E.; Anderson, Lynn M.; Miller, Tracie L.; Gerschenson, Mariana; Stevenson, Kristen E.; Neuberg, Donna S.; Franco, Vivian I.; LiButti, Daniel E.; Silverman, Lewis B.; Vrooman, Lynda M.; Sallan, Stephen E.

    2015-01-01

    BACKGROUND Impaired cardiac function in doxorubicin-treated childhood cancer survivors is partly mediated by disruption of mitochondrial energy production. Doxorubicin intercalates into mitochondrial DNA (mtDNA) disrupting genes encoding for polypeptides that make ATP. METHODS This cross-sectional study examined mtDNA copy numbers/cell and oxidative phosphorylation (OXPHOS) in peripheral blood mononuclear cells (PBMCs) in 64 childhood survivors of high-risk acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute Childhood ALL protocols who had received doxorubicin alone (42%) or with dexrazoxane (58%), a cardioprotectant. Mitochondrial DNA copies per cell and OXPHOS enzyme activities of nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I, CI) and cytochrome c oxidase (Complex IV, CIV) were measured by quantitative real time-polymerase chain reaction (qRT-PCR) immunoassay and thin layer chromatography, respectively. RESULTS At a median follow-up of 7.8 years after treatment, the median number of mtDNA copies per cell for patients treated with doxorubicin alone was significantly higher than for those who also received dexrazoxane (medians, 1106.3 and 310.5; P=0.001). No significant differences were detected between groups for CI or CIV activities. CONCLUSIONS Doxorubicin-treated survivors had increased PBMC mtDNA copies/cell and concomitant use of dexrazoxane was associated with lower mtDNA copies/cell. Due to a possible compensatory increase in mtDNA copies/cell to maintain mitochondrial function in the setting of mitochondrial dysfunction, overall OXPHOS activity was not different between groups. The long-term sustainability of this compensatory response in these survivors at risk for cardiac dysfunction over their lifespan is concerning. PMID:26762648

  5. Acute effects of rotavirus and malnutrition on intestinal barrier function in neonatal piglets

    PubMed Central

    Jacobi, Sheila K; Moeser, Adam J; Blikslager, Anthony T; Rhoads, J Marc; Corl, Benjamin A; Harrell, Robert J; Odle, Jack

    2013-01-01

    AIM: To investigate the effect of protein-energy malnutrition on intestinal barrier function during rotavirus enteritis in a piglet model. METHODS: Newborn piglets were allotted at day 4 of age to the following treatments: (1) full-strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of adjustment to the feeding rates, pigs were infected with rotavirus and acute effects on growth and diarrhea were monitored for 3 d and jejunal samples were collected for Ussing-chamber analyses. RESULTS: Piglets that were malnourished or infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three days post-infection, marked diarrhea and weight loss were accompanied by sharp reductions in villus height (59%) and lactase activity (91%) and increased crypt depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio was reduced (67%) with viral infection. There was a trend for reduction in transepithelial electrical resistance with rotavirus infection and malnutrition (P = 0.1). 3H-mannitol flux was significantly increased (50%; P < 0.001) in rotavirus-infected piglets compared to non-infected piglets, but there was no effect of nutritional status. Furthermore, rotavirus infection reduced localization of the tight junction protein, occludin, in the cell membrane and increased localization in the cytosol. CONCLUSION: Overall, malnutrition had no additive effects to rotavirus infection on intestinal barrier function at day 3 post-infection in a neonatal piglet model. PMID:23964143

  6. Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

    PubMed Central

    Concel, Vincent J.; Bein, Kiflai; Liu, Pengyuan; Berndt, Annerose; Martin, Timothy M.; Ganguly, Koustav; Jang, An Soo; Brant, Kelly A.; Dopico, Richard A.; Upadhyay, Swapna; Cario, Clinton; Di, Y. P. Peter; Vuga, Louis J.; Kostem, Emrah; Eskin, Eleazar; You, Ming; Kaminski, Naftali; Prows, Daniel R.; Knoell, Daren L.; Fabisiak, James P.

    2013-01-01

    In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Candidates were selected that contained a promoter SNP that could alter a putative transcription factor binding site and had variable expression by transcriptomic analyses. The latter two criteria also required that ≥10% of mice carried the minor allele and that this allele could account for ≥10% of the phenotypic difference noted between the strains at the phenotypic extremes. This integrative, functional approach revealed 14 candidate genes that included Atp1a1, Alox5, Galnt11, Hrh1, Mbd4, Phactr2, Plxnd1, Ptprt, Reln, and Zfand4, which had significant SNP associations, and Itga9, Man1a2, Mapk14, and Vwf, which had suggestive SNP associations. Of the genes with significant SNP associations, Atp1a1, Alox5, Plxnd1, Ptprt, and Zfand4 could be associated with ALI in several ways. Using a competitive electrophoretic mobility shift analysis, Atp1a1 promoter (rs215053185) oligonucleotide containing the minor G allele formed a major distinct faster-migrating complex. In addition, a gene with a suggestive SNP association, Itga9, is linked to transforming growth factor β1 signaling, which previously has been associated with the susceptibility to ALI in mice. PMID:23590305

  7. Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction

    SciTech Connect

    McGhie, A.I.; Corbett, J.R.; Akers, M.S.; Kulkarni, P.; Sills, M.N.; Kremers, M.; Buja, L.M.; Durant-Reville, M.; Parkey, R.W.; Willerson, J.T. )

    1991-02-01

    The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.

  8. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  9. Influence of Parasite Load on Renal Function in Mice Acutely Infected with Trypanosoma cruzi

    PubMed Central

    Parreira, Ricardo Cambraia; Miguel, Renata Botelho; de Paula Rogerio, Alexandre; Oliveira, Carlo Jose Freire; Chica, Javier Emilio Lazo

    2013-01-01

    Background Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Despite the vast number of studies evaluating the pathophysiological mechanisms of the disease, the influence of parasite burden on kidney lesions remains unclear. Thus, the main goal of this work was to evaluate the effect of T. cruzi infection on renal function and determine whether there was a correlation between parasite load and renal injury using an acute experimental model of the disease. Methodology/Principal Findings Low, medium and high parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000 (medium) or 30,000 (high) numbers of “Y” strain trypomastigotes. We found that mice infected with T. cruzi trypomastigotes show increased renal injury. The infection resulted in reduced urinary excretion and creatinine clearance. We also observed a marked elevation in the ratio of urine volume to kidney and body weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti-inflammatory cytokines and the number of leukocytes in the blood and/or renal tissues of infected mice. Additionally, we observed the presence of the parasite in the cortical/medullary and peri-renal region, an increase of inflammatory infiltrate and of vascular permeability of the kidney. Overall, most renal changes occurred mainly in animals infected with high parasitic loads. Conclusions/Significance These data demonstrate that T. cruzi impairs kidney function, and this impairment is more evident in mice infected with high parasitic loads. Moreover, these data suggest that, in addition to the extensively studied cardiovascular effects, renal injury should be regarded as an important indicator for better understanding the pan-infectivity of the parasite and consequently for understanding the disease in experimental models. PMID:23951243

  10. Acute ozone-induced lung injury in rats: Structural-functional relationships of developing alveolar edema

    SciTech Connect

    Paterson, J.F.; Hammond, M.D.; Montgomery, M.R.; Sharp, J.T.; Farrier, S.E.; Balis, J.U. )

    1992-11-01

    As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH[sub 2]O/kg) from a control value of 0.84 [plus minus] 0.02 (SEM) to 0.72 [plus minus] 0.04 and 0.57 [plus minus] 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO[sub 2] to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H[sub 2]O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions.

  11. Clinical and functional outcomes of acute lower extremity compartment syndrome at a Major Trauma Hospital

    PubMed Central

    Lollo, Loreto; Grabinsky, Andreas

    2016-01-01

    Background: Acute lower extremity compartment syndrome (CS) is a condition that untreated causes irreversible nerve and muscle ischemia. Treatment by decompression fasciotomy without delay prevents permanent disability. The use of intracompartmental pressure (iCP) measurement in uncertain situations aids in diagnosis of severe leg pain. As an infrequent complication of lower extremity trauma, consequences of CS include chronic pain, nerve injury, and contractures. The purpose of this study was to observe the clinical and functional outcomes for patients with lower extremity CS after fasciotomy. Methods: Retrospective chart analysis for patients with a discharge diagnosis of CS was performed. Physical demographics, employment status, activity at time of injury, injury severity score, fracture types, pain scores, hours to fasciotomy, iCP, serum creatine kinase levels, wound treatment regimen, length of hospital stay, and discharge facility were collected. Lower extremity neurologic examination, pain scores, orthopedic complications, and employment status at 30 days and 12 months after discharge were noted. Results: One hundred twenty-four patients were enrolled in this study. One hundred and eight patients were assessed at 12 months. Eighty-one percent were male. Motorized vehicles caused 51% of injuries in males. Forty-one percent of injuries were tibia fractures. Acute kidney injury occurred in 2.4%. Mean peak serum creatine kinase levels were 58,600 units/ml. Gauze dressing was used in 78.9% of nonfracture patients and negative pressure wound vacuum therapy in 78.2% of fracture patients. About 21.6% of patients with CS had prior surgery. Nearly 12.9% of patients required leg amputation. Around 81.8% of amputees were male. Sixty-seven percent of amputees had associated vascular injuries. Foot numbness occurred in 20.5% of patients and drop foot palsy in 18.2%. Osteomyelitis developed in 10.2% of patients and fracture nonunion in 6.8%. About 14.7% of patients

  12. Effects of Acute Exposure to Moderate Altitude on Vascular Function, Metabolism and Systemic Inflammation

    PubMed Central

    Stöwhas, Anne-Christin; Latshang, Tsogyal D.; Lo Cascio, Christian M.; Lautwein, Sina; Stadelmann, Katrin; Tesler, Noemi; Ayers, Lisa; Berneis, Kaspar; Gerber, Philipp A.; Huber, Reto; Achermann, Peter; Bloch, Konrad E.; Kohler, Malcolm

    2013-01-01

    Background Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. Objectives To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. Methods In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Results Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Conclusions Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. Trial Registration ClinicalTrials.gov NCT01130948 PMID:23936377

  13. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

    PubMed

    Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

    2016-12-01

    Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD.

  14. Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes

    PubMed Central

    Hassan, Sarah F.; Wearne, Travis A.; Cornish, Jennifer L.

    2016-01-01

    Key points Methamphetamine (METH) abuse is escalating worldwide, with the most common cause of death resulting from cardiovascular failure and hyperthermia; however, the underlying physiological mechanisms are poorly understood.Systemic administration of METH in anaesthetised rats reduced the effectiveness of some protective cardiorespiratory reflexes, increased central respiratory activity independently of metabolic function, and increased heart rate, metabolism and respiration in a pattern indicating that non‐shivering thermogenesis contributes to the well‐described hyperthermia.In animals that showed METH‐induced behavioural sensitisation following chronic METH treatment, no changes were evident in baseline cardiovascular, respiratory and metabolic measures and the METH‐evoked effects in these parameters were similar to those seen in saline‐treated or drug naïve animals.Physiological effects evoked by METH were retained but were neither facilitated nor depressed following chronic treatment with METH.These data highlight and identify potential mechanisms for targeted intervention in patients vulnerable to METH overdose. Abstract Methamphetamine (METH) is known to promote cardiovascular failure or life‐threatening hyperthermia; however, there is still limited understanding of the mechanisms responsible for evoking the physiological changes. In this study, we systematically determined the effects on both autonomic and respiratory outflows, as well as reflex function, following acute and repeated administration of METH, which enhances behavioural responses. Arterial pressure, heart rate, phrenic nerve discharge amplitude and frequency, lumbar and splanchnic sympathetic nerve discharge, interscapular brown adipose tissue and core temperatures, and expired CO2 were measured in urethane‐anaesthetised male Sprague‐Dawley rats. Novel findings include potent increases in central inspiratory drive and frequency that are not dependent on METH

  15. Change in blood coagulation indices as a function of the incubation period of plasma in a constant magnetic field. [considering heparin tolerance and recalcification

    NASA Technical Reports Server (NTRS)

    Yepishina, S. G.

    1974-01-01

    The influence of a constant magnetic field (CMF) with a strength of 250 and 2500 oersteds on the recalcification reaction and the tolerance of plasma to heparin was studied as a function of the exposure time of the plasma to the CMF. The maximum and reliable change in the activation of the coagulatory system of the blood was observed after a 20-hour incubation of the plasma in a CMF. As the exposure time increased, the recalcification reaction changed insigificantly; the difference between the mean arithmetic of the experiment and control values was not statistically reliable. The tolerance of the plasma to heparin as a function of the exposure time to the CMF of the plasma was considerably modified, an was statistically reliable.

  16. Genome-Wide Expression Analysis Reveals Diverse Effects of Acute Nicotine Exposure on Neuronal Function-Related Genes and Pathways

    PubMed Central

    Wang, Ju; Cui, Wenyan; Wei, Jinxue; Sun, Dongxiao; Gutala, Ramana; Gu, Jun; Li, Ming D.

    2011-01-01

    Previous human and animal studies demonstrate that acute nicotine exposure has complicated influences on the function of the nervous system, which may lead to long-lasting effects on the behavior and physiology of the subject. To determine the genes and pathways that might account for long-term changes after acute nicotine exposure, a pathway-focused oligoarray specifically designed for drug addiction research was used to assess acute nicotine effect on gene expression in the neuron-like SH-SY5Y cells. Our results showed that 295 genes involved in various biological functions were differentially regulated by 1 h of nicotine treatment. Among these genes, the expression changes of 221 were blocked by mecamylamine, indicating that the majority of nicotine-modulated genes were altered through the nicotinic acetylcholine receptors (nAChRs)-mediated signaling process. We further identified 14 biochemical pathways enriched among the nicotine-modulated genes, among which were those involved in neural development/synaptic plasticity, neuronal survival/death, immune response, or cellular metabolism. In the genes significantly regulated by nicotine but blocked by mecamylamine, 13 enriched pathways were detected. Nine of these pathways were shared with those enriched in the genes regulated by nicotine, including neuronal function-related pathways such as glucocorticoid receptor signaling, p38 MAPK signaling, PI3K/AKT signaling, and PTEN signaling, implying that nAChRs play important roles in the regulation of these biological processes. Together, our results not only provide insights into the mechanism underlying the acute response of neuronal cells to nicotine but also provide clues to how acute nicotine exposure exerts long-term effects on the nervous system. PMID:21556275

  17. Acute and chronic methyl mercury poisoning impairs rat adrenal and testicular function

    SciTech Connect

    Burton, G.V.; Meikle, A.W.

    1980-05-01

    Animals poisoned with methyl mercury (CH/sub 3/Hg) exhibit stress intolerance and decreased sexual activity, which suggest both adrenal and testicular dysfunction. Adrenal and testicular function was studied in male rats after treatment with CH/sub 3/Hg. In animals treated chronically, the adrenal glands were markedly hyperplastic with enlargement of the zona fasciculata. The mean basal serum levels of corticosterone were similar in experimental (17.8 ..mu..g/dl) and control (16.8 ..mu..g/dl) groups. However, with ether stress, experimental animals had a subnormal response, and the mean serum levels of corticosterone increased to only 23.9 ..mu../dl compared to 40.6 ..mu..g/dl in the controls. Exogenous ACTH stimulation produced a mean level of 19.0 ..mu..g/dl in the CH/sub 3/Hg-treated animals and 49.7 ..mu..g/dl in the controls. In vitro studies demonstrated a defect in the conversion of cholesterol to pregnenolone. A profound impairment in swimming was partially reversed with glucocorticoid therapy. In animals treated with CH/sub 3/Hg, serum testosterone was lower than normal in the basal state. Human chorionic gonadotropin stimulation increased the mean serum concentration of testosterone to 23.4 ng/ml in controls, but it was only 4.50 ng/ml in experimental animals. The data indicate that CH/sub 3/Hg poisoning impairs adrenal and testicular steroid hormone secretion, which accounts in part for the diminished stress tolerance and decreased sexual activity observed in CH/sub 3/Hg-intoxicated animals.

  18. Polyamine oxidase 5 loss-of-function mutations in Arabidopsis thaliana trigger metabolic and transcriptional reprogramming and promote salt stress tolerance.

    PubMed

    Zarza, Xavier; Atanasov, Kostadin E; Marco, Francisco; Arbona, Vicent; Carrasco, Pedro; Kopka, Joachim; Fotopoulos, Vasileios; Munnik, Teun; Gómez-Cadenas, Aurelio; Tiburcio, Antonio F; Alcázar, Rubén

    2017-04-01

    The family of polyamine oxidases (PAO) in Arabidopsis (AtPAO1-5) mediates polyamine (PA) back-conversion, which reverses the PA biosynthetic pathway from spermine and its structural isomer thermospermine (tSpm) into spermidine and then putrescine. Here, we have studied the involvement of PA back-conversion in Arabidopsis salinity tolerance. AtPAO5 is the Arabidopsis PAO gene member most transcriptionally induced by salt stress. Two independent loss-of-function mutants (atpao5-2 and atpao5-3) were found to exhibit constitutively higher tSpm levels, with associated increased salt tolerance. Using global transcriptional and metabolomic analyses, the underlying mechanisms were studied. Stimulation of abscisic acid and jasmonate (JA) biosynthesis and accumulation of important compatible solutes, such as sugars, polyols and proline, as well as TCA cycle intermediates were observed in atpao5 mutants under salt stress. Expression analyses indicate that tSpm modulates the transcript levels of several target genes, including many involved in the biosynthesis and signalling of JA, some of which are already known to promote salinity tolerance. Transcriptional modulation by tSpm is isomer-dependent, thus demonstrating the specificity of this response. Overall, we conclude that tSpm triggers metabolic and transcriptional reprogramming that promotes salt stress tolerance in Arabidopsis.

  19. Clinical aspects of left ventricular diastolic function assessed by Doppler echocardiography following acute myocardial infarction.

    PubMed

    Poulsen, S H

    2001-11-01

    abnormal myocardial relaxation which can be reversed to normal by restoring normal myocardial blood flow. The diastolic abnormality is present within seconds and a characteristic impaired relaxation filling pattern are identified by mitral and pulmonary venous flow analysis. Diastolic dysfunction has been recognized during the early as well during the post-MI phase with or without LV systolic dysfunction. In the acute phase both an abnormal relaxation pattern and restrictive LV filling pattern are present which has been related to in-hospital heart failure. The identification of a pseudonormal or restrictive LV filling pattern are associated with later readmission to hospital with heart failure and cardiac death. Abnormal relaxation filling is the most pronounced filling pattern after one year which might be related to the remodeling process including compensatory hypertrophy, scarring of the infarct zone leading to a non-uniform relaxation of the LV. Remodeling of the LV following a MI is subject to several factors which might involve diastolic function. This is supported by the presence of an impaired relaxation and restrictive filling pattern are associated with progressive LV dilatation following Ml. Furthermore, the LV remodeling process following the very early phase includes the scarring process with collagen deposition in the infarcted and non-infarcted myocardium. The extent and quality of the repair process involving collagen deposition are believed to influence the remodeling process. Increased collagen deposition in the subacute phase of Ml indicated by elevated values of the collagen marker PIIINP is found to be related to LV dilation, depressed systolic function and restrictive LV filling. Development of a restrictive filling in patients with increased collagen deposition might be due to increasing LV volume but also to increased myocardial stiffness. Regarding prognosis diastolic dysfunction seems to be an important marker of outcome as abnormal diastolic

  20. Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study.

    PubMed

    Byun, Kyeongho; Hyodo, Kazuki; Suwabe, Kazuya; Ochi, Genta; Sakairi, Yosuke; Kato, Morimasa; Dan, Ippeita; Soya, Hideaki

    2014-09-01

    Despite the practical implication of mild exercise, little is known about its influence on executive function and its neural substrates. To address these issues, the present study examined the effect of an acute bout of mild exercise on executive function and attempted to identify potential neural substrates using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-five young individuals performed a color-word matching Stroop task (CWST) and a two-dimensional scale to measure changes of psychological mood states both before and after a 10-minute exercise session on a cycle ergometer at light intensity (30% v(·)o2peak) and, for the control session, without exercise. Cortical hemodynamic changes in the prefrontal area were monitored with fNIRS during the CWST in both sessions. The acute bout of mild exercise led to improved Stroop performance, which was positively correlated with increased arousal levels. It also evoked cortical activations regarding Stroop interference on the left dorsolateral prefrontal cortex and frontopolar area. These activations significantly corresponded with both improved cognitive performance and increased arousal levels. Concurrently, this study provides empirical evidence that an acute bout of mild exercise improves executive function mediated by the exercise-induced arousal system, which intensifies cortical activation in task-related prefrontal sub-regions.

  1. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    SciTech Connect

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  2. Effects of acute exercise on liver function and blood redox status in heavy drinkers

    PubMed Central

    GEORGAKOULI, KALLIOPI; MANTHOU, EIRINI; FATOUROS, IOANNIS G.; DELI, CHARIKLIA K.; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.; KOURETAS, DEMETRIOS; KOUTEDAKIS, YIANNIS; THEODORAKIS, YANNIS; JAMURTAS, ATHANASIOS Z.

    2015-01-01

    Excessive alcohol consumption can induce oxidative stress, resulting in the development of several diseases. Exercise has been reported to prevent and/or improve a number of health issues through several mechanisms, including an improvement in redox status. It has also been previously suggested that exercise can help individuals with alcohol use disorders reduce their alcohol intake; however, research in this field is limited. The aim of the present study was to investigage the effects of acute exercise of moderate intensity on the liver function and blood redox status in heavy drinkers. For this purpose, a total of 17 heavy drinkers [age, 31.6±3.2 years; body mass index (BMI), 27.4±0.8 kg/m2; experimental group (EG)] and 17 controls [age, 33.5±1.3 years; BMI, 26.1±1.4 kg/m2; control group (CG), who did not exceed moderate alcohol consumption], underwent one trial of acute exercise of moderate intensity (50–60% of the heart rate reserve) for 30 min on a cycle ergometer, following an overnight fast, and abstaining from smoking and alcohol consumption. Blood samples were obtained before and immediately after exercise for later determination of the indices of liver function and blood redox status. The subjects in the EG had significantly higher (p<0.05) baseline γ-glutamyl transferase (γ-GT) levels compared to the subjects in the CG. Exercise thus resulted in significantly higher γ-GT levels (p<0.005) only in the EG. No significant differences in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) baseline levels were observed between the 2 groups. Following exercise, the AST levels increased significantly (p<0.001) in both groups, whereas the ALT levels increased significantly (p<0.01) only in the EG. The baseline glutathione (GSH) levels were significantly lower (p<0.05) and remained low following exercise in the EG. In addition, we observed a trend for higher (p=0.07) baseline levels of thiobarbituric acid-reactive substances (TBARS), which

  3. Acute Acrolein Exposure Induces Impairment of Vocal Fold Epithelial Barrier Function

    PubMed Central

    Zheng, Wei; Sivasankar, M. Preeti

    2016-01-01

    Acrolein is a ubiquitous pollutant abundant in cigarette smoke, mobile exhaust, and industrial waste. There is limited literature on the effects of acrolein on vocal fold tissue, although there are clinical reports of voice changes after pollutant exposures. Vocal folds are responsible for voice production. The overall objective of this study was to investigate the effects of acrolein exposure on viable, excised vocal fold epithelial tissue and to characterize the mechanism underlying acrolein toxicity. Vocal fold epithelia were studied because they form the outermost layer of the vocal folds and are a primary recipient of inhaled pollutants. Porcine vocal fold epithelia were exposed to 0, 50, 100, 500, 900 or 1300 μM of acrolein for 3 hours; the metabolic activity, epithelial resistance, epithelial permeability, tight junction protein (occludin and claudin 3) expression, cell membrane integrity and lipid peroxidation were investigated. The data demonstrated that acrolein exposure at 500 μM significantly reduced vocal fold epithelial metabolic activity by 27.2% (p≤0.001). Incubation with 100 μM acrolein caused a marked increase in epithelial permeability by 130.5% (p<0.05) and a reduction in transepithelial electrical resistance (TEER) by 180.0% (p<0.001). While the expression of tight junctional protein did not change in acrolein-treated samples, the cell membrane integrity was significantly damaged with a 45.6% increase of lipid peroxidation as compared to controls (p<0.05). Taken together, these data provide evidence that acute acrolein exposure impairs vocal fold epithelial barrier integrity. Lipid peroxidation-induced cell membrane damage may play an important role in reducing the barrier function of the epithelium. PMID:27643990

  4. Outcomes of renal function in elderly patients with acute kidney injury

    PubMed Central

    Li, Qinglin; Zhao, Meng; Du, Jing; Wang, Xiaodan

    2017-01-01

    Objectives The aim of this study was to explore the prognostic impact of clinical factors on the short-term outcomes of renal function (RF) in very elderly patients with acute kidney injury (AKI). Patients and methods We carried out a retrospective cohort study of only very elderly patients who developed AKI at the geriatric department of a tertiary medical center during the period 2007–2015. All patients with AKI were followed up for 90 days after AKI diagnosis or until death. Survivors were divided into recovery and nonrecovery groups according to their RF 90 days post-AKI. RF recovery was defined as an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2. Results In total, 668 patients (39.0%) developed AKI, and 652 patients were included in the final analysis. The median age of this population was 87 years, with 95.6% being male. The 90-day mortality rate was 33.6%. Of the 433 survivors, 316 (73.0%) recovered to their baseline eGFR. Body mass index (BMI), baseline eGFR, low mean aortic pressure (MAP), low prealbumin level, hypoalbuminemia, oliguria, blood urea nitrogen (BUN) level, and more severe AKI stage were independent risk factors associated with nonrenal recovery or death. AKI etiology, evaluated by peak serum creatinine (SCr) level and the requirement for dialysis, was not associated with nonrenal recovery. Conclusion Risk factors for the poor outcomes of RF in very elderly patients with AKI were BMI, baseline eGFR, low MAP, low prealbumin level, hypoalbuminemia, oliguria, BUN level, and more severe AKI stage. Identifying risk factors may help to improve patient outcomes. PMID:28176909

  5. Expression and functional roles of the chemokine receptor CXCR7 in acute myeloid leukemia cells

    PubMed Central

    Kim, Ha-Yon; Lee, So-Yeon; Kim, Deog-Young; Moon, Ji-Young; Choi, Yoon-Seok; Song, Ik-Chan; Lee, Hyo-Jin; Yun, Hwan-Jung; Kim, Samyong

    2015-01-01

    Background The C-X-C chemokine receptor 7 (CXCR7) has been shown to be a decoy receptor for CXCR4 in certain cell types. We investigated the expression status and functional roles of CXCR7 in acute myeloid leukemia (AML) cells in vitro. Methods CXCR7 mRNA was knocked down in AML cells by using small interfering RNA (siRNA) technology, and subsequent biological alterations in the cells were evaluated in vitro. Results All AML cell lines examined in this study (U937, K562, KG1a, HL-60, and MO7e) and primary CD34+ cells obtained from patients with AML expressed CXCR7 mRNA at various levels. Western blotting showed that all AML cells produced CXCR7. Furthermore, all AML cells expressed CXCR7 in both the cytoplasm and on the cell surface at various levels. Stromal cell-derived factor-1 (SDF-1; C-X-C motif ligand 12 (CXCL12)) induced internalization of cell surface CXCR7. However, neither hypoxia nor the examined hematopoietic growth factors (interleukin-1β (IL-1β), IL-3, IL-6, granulocyte-colony-stimulating factor, granulocyte, macrophage-colony-stimulating factor, and stem cell factor) and proinflammatory cytokines (interferon-γ, transforming growth factor-β, and tumor necrosis factor-α) were found to alter cell surface CXCR7 expression. The transfection of AML cells with CXCR4 siRNA, but not CXCR7 siRNA, significantly impaired the CXCL12-induced transmigration of the cells. The transfection of AML cells with CXCR7 siRNA did not affect the survival or proliferation of these cells. Knockdown of CXCR7, but not CXCR4, induced the upregulation of CXCL12 mRNA expression and CXCL12 production in AML cells. Conclusion CXCR7 is involved in the regulation of autocrine CXCL12 in AML cells. PMID:26770949

  6. The effects of cardiorespiratory fitness and acute aerobic exercise on executive functioning and EEG entropy in adolescents

    PubMed Central

    Hogan, Michael J.; O’Hora, Denis; Kiefer, Markus; Kubesch, Sabine; Kilmartin, Liam; Collins, Peter; Dimitrova, Julia

    2015-01-01

    The current study examined the effects of cardiorespiratory fitness, identified with a continuous graded cycle ergometry, and aerobic exercise on cognitive functioning and entropy of the electroencephalogram (EEG) in 30 adolescents between the ages of 13 and 14 years. Higher and lower fit participants performed an executive function task after a bout of acute exercise and after rest while watching a film. EEG entropy, using the sample entropy measure, was repeatedly measured during the 1500 ms post-stimulus interval to evaluate changes in entropy over time. Analysis of the behavioral data for lower and higher fit groups revealed an interaction between fitness levels and acute physical exercise. Notably, lower fit, but not higher fit, participants had higher error rates (ER) for No Go relative to Go trials in the rest condition, whereas in the acute exercise condition there were no differences in ER between groups; higher fit participants also had significantly faster reaction times in the exercise condition in comparison with the rest condition. Analysis of EEG data revealed that higher fit participants demonstrated lower entropy post-stimulus than lower fit participants in the left frontal hemisphere, possibly indicating increased efficiency of early stage stimulus processing and more efficient allocation of cognitive resources to the task demands. The results suggest that EEG entropy is sensitive to stimulus processing demands and varies as a function of physical fitness levels, but not acute exercise. Physical fitness, in turn, may enhance cognition in adolescence by facilitating higher functionality of the attentional system in the context of lower levels of frontal EEG entropy. PMID:26539093

  7. Regulation of µ-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance

    PubMed Central

    Williams, John T.; Ingram, Susan L.; Henderson, Graeme; Chavkin, Charles; von Zastrow, Mark; Schulz, Stefan; Koch, Thomas; Evans, Christopher J.

    2013-01-01

    Morphine and related µ-opioid receptor (MOR) agonists remain among the most effective drugs known for acute relief of severe pain. A major problem in treating painful conditions is that tolerance limits the long-term utility of opioid agonists. Considerable effort has been expended on developing an understanding of the molecular and cellular processes that underlie acute MOR signaling, short-term receptor regulation, and the progression of events that lead to tolerance for different MOR agonists. Although great progress has been made in the past decade, many points of contention and controversy cloud the realization of this progress. This review attempts to clarify some confusion by clearly defining terms, such as desensitization and tolerance, and addressing optimal pharmacological analyses for discerning relative importance of these cellular mechanisms. Cellular and molecular mechanisms regulating MOR function by phosphorylation relative to receptor desensitization and endocytosis are comprehensively reviewed, with an emphasis on agonist-biased regulation and areas where knowledge is lacking or controversial. The implications of these mechanisms for understanding the substantial contribution of MOR signaling to opioid tolerance are then considered in detail. While some functional MOR regulatory mechanisms contributing to tolerance are clearly understood, there are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids. Further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance. PMID:23321159

  8. Transgenic Mice with Increased Astrocyte Expression of IL-6 Show Altered Effects of Acute Ethanol on Synaptic Function

    PubMed Central

    Hernandez, Ruben V.; Puro, Alana C.; Manos, Jessica C.; Huitron-Resendiz, Salvador; Reyes, Kenneth C.; Liu, Kevin; Vo, Khanh; Roberts, Amanda J.; Gruol, Donna L.

    2015-01-01

    A growing body of evidence has revealed that resident cells of the central nervous system (CNS), and particularly the glial cells, comprise a neuroimmune system that serves a number of functions in the normal CNS and during adverse conditions. Cells of the neuroimmune system regulate CNS functions through the production of signaling factors, referred to as neuroimmune factors. Recent studies show that ethanol can activate cells of the neuroimmune system, resulting in the elevated production of neuroimmune factors, including the cytokine interleukin-6 (IL-6). Here we analyzed the consequences of this CNS action of ethanol using transgenic mice that express elevated levels of IL-6 through increased astrocyte expression (IL-6-tg) to model the increased IL-6 expression that occurs with ethanol use. Results show that increased IL-6 expression induces neuroadaptive changes that alter the effects of ethanol. In hippocampal slices from non-transgenic (non-tg) littermate control mice, synaptically evoked dendritic field excitatory postsynaptic potential (fEPSP) and somatic population spike (PS) at the Schaffer collateral to CA1 pyramidal neuron synapse were reduced by acute ethanol (20 or 60 mM). In contrast, acute ethanol enhanced the fEPSP and PS in hippocampal slices from IL-6 tg mice. Long-term synaptic plasticity of the fEPSP (i.e., LTP) showed the expected dose-dependent reduction by acute ethanol in non-tg hippocampal slices, whereas LTP in the IL-6 tg hippocampal slices was resistant to this depressive effect of acute ethanol. Consistent with altered effects of acute ethanol on synaptic function in the IL-6 tg mice, EEG recordings showed a higher level of CNS activity in the IL-6 tg mice than in the non-tg mice during the period of withdrawal from an acute high dose of ethanol. These results suggest a potential role for neuroadaptive effects of ethanol-induced astrocyte production of IL-6 as a mediator or modulator of the actions of ethanol on the CNS, including

  9. Transgenic mice with increased astrocyte expression of IL-6 show altered effects of acute ethanol on synaptic function.

    PubMed

    Hernandez, Ruben V; Puro, Alana C; Manos, Jessica C; Huitron-Resendiz, Salvador; Reyes, Kenneth C; Liu, Kevin; Vo, Khanh; Roberts, Amanda J; Gruol, Donna L

    2016-04-01

    A growing body of evidence has revealed that resident cells of the central nervous system (CNS), and particularly the glial cells, comprise a neuroimmune system that serves a number of functions in the normal CNS and during adverse conditions. Cells of the neuroimmune system regulate CNS functions through the production of signaling factors, referred to as neuroimmune factors. Recent studies show that ethanol can activate cells of the neuroimmune system, resulting in the elevated production of neuroimmune factors, including the cytokine interleukin-6 (IL-6). Here we analyzed the consequences of this CNS action of ethanol using transgenic mice that express elevated levels of IL-6 through increased astrocyte expression (IL-6-tg) to model the increased IL-6 expression that occurs with ethanol use. Results show that increased IL-6 expression induces neuroadaptive changes that alter the effects of ethanol. In hippocampal slices from non-transgenic (non-tg) littermate control mice, synaptically evoked dendritic field excitatory postsynaptic potential (fEPSP) and somatic population spike (PS) at the Schaffer collateral to CA1 pyramidal neuron synapse were reduced by acute ethanol (20 or 60 mM). In contrast, acute ethanol enhanced the fEPSP and PS in hippocampal slices from IL-6 tg mice. Long-term synaptic plasticity of the fEPSP (i.e., LTP) showed the expected dose-dependent reduction by acute ethanol in non-tg hippocampal slices, whereas LTP in the IL-6 tg hippocampal slices was resistant to this depressive effect of acute ethanol. Consistent with altered effects of acute ethanol on synaptic function in the IL-6 tg mice, EEG recordings showed a higher level of CNS activity in the IL-6 tg mice than in the non-tg mice during the period of withdrawal from an acute high dose of ethanol. These results suggest a potential role for neuroadaptive effects of ethanol-induced astrocyte production of IL-6 as a mediator or modulator of the actions of ethanol on the CNS, including

  10. Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

    PubMed Central

    Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

    2015-01-01

    Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

  11. ACUTE AND REPEATED INHALATION OF TOLUENE BY RATS PERFORMING A SIGNAL DETECTION TASK LEADS TO BEHAVIORAL TOLERANCE ON SOME PERFORMANCE MEASURES.

    EPA Science Inventory

    Previous work showed that trichloroethylene (TCE) impairs accuracy and latency in a signal detection task (SDT) in rats, and that these effects abate during repeated exposures if rats inhale TCE during SDT testing. The present experiment compared the effects of acute and repeated...

  12. Extrapolating the Acute Behavioral Effects of Toluene from 1-Hour to 24-Hour Exposures in Rats: Roles of Dose Metric, and Metabolic and Behavioral Tolerance.

    EPA Science Inventory

    Recent research on the acute effects of volatile organic compounds (VQCs) suggests that extrapolation from short (~ 1 h) to long durations (up to 4 h) may be improved by using estimates of brain toluene concentration (Br[Tol]) instead of cumulative inhaled dose (C x t) as a metri...

  13. Behavior Therapy for Tics in Children: Acute and Long-Term Effects on Psychiatric and Psychosocial Functioning

    PubMed Central

    Woods, Douglas W.; Piacentini, John C.; Scahill, Lawrence; Peterson, Alan L.; Wilhelm, Sabine; Chang, Susanna; Deckersbach, Thilo; McGuire, Joseph; Specht, Matt; Conelea, Christine A.; Rozenman, Michelle; Dzuria, James; Liu, Haibei; Levi-Pearl, Sue; Walkup, John T.

    2014-01-01

    Children (n = 126) ages 9 to 17 years with chronic tic or Tourette disorder were randomly assigned to receive either behavior therapy or a control treatment over 10 weeks. This study examined acute effects of behavior therapy on secondary psychiatric symptoms and psychosocial functioning and long-term effects on these measures for behavior therapy responders only. Baseline and end point assessments conducted by a masked independent evaluator assessed several secondary psychiatric symptoms and measures of psychosocial functioning. Responders to behavior therapy at the end of the acute phase were reassessed at 3-month and 6-month follow-up. Children in the behavior therapy and control conditions did not differentially improve on secondary psychiatric or psychosocial outcome measures at the end of the acute phase. At 6-month posttreatment, positive response to behavior therapy was associated with decreased anxiety, disruptive behavior, and family strain and improved social functioning. Behavior therapy is a tic-specific treatment for children with tic disorders. PMID:21555779

  14. The effects of very early mirror therapy on functional improvement of the upper extremity in acute stroke patients.

    PubMed

    Yeldan, Ipek; Huseyınsınoglu, Burcu Ersoz; Akıncı, Buket; Tarakcı, Ela; Baybas, Sevim; Ozdıncler, Arzu Razak

    2015-11-01

    [Purpose] The aim of the study was to evaluate the effects of a very early mirror therapy program on functional improvement of the upper extremity in acute stroke patients. [Subjects] Eight stroke patients who were treated in an acute neurology unit were included in the study. [Methods] The patients were assigned alternatively to either the mirror therapy group receiving mirror therapy and neurodevelopmental treatment or the neurodevelopmental treatment only group. The primary outcome measures were the upper extremity motor subscale of the Fugl-Meyer Assessment, Motricity Index upper extremity score, and the Stroke Upper Limb Capacity Scale. Somatosensory assessment with the Ayres Southern California Sensory Integration Test, and the Barthel Index were used as secondary outcome measures. [Results] No statistically significant improvements were found for any measures in either group after the treatment. In terms of minimally clinically important differences, there were improvements in Fugl-Meyer Assessment and Barthel Index in both mirror therapy and neurodevelopmental treatment groups. [Conclusion] The results of this pilot study revealed that very early mirror therapy has no additional effect on functional improvement of upper extremity function in acute stroke patients. Multicenter trials are needed to determine the results of early application of mirror therapy in stroke rehabilitation.

  15. The effects of very early mirror therapy on functional improvement of the upper extremity in acute stroke patients

    PubMed Central

    Yeldan, Ipek; Huseyınsınoglu, Burcu Ersoz; Akıncı, Buket; Tarakcı, Ela; Baybas, Sevim; Ozdıncler, Arzu Razak

    2015-01-01

    [Purpose] The aim of the study was to evaluate the effects of a very early mirror therapy program on functional improvement of the upper extremity in acute stroke patients. [Subjects] Eight stroke patients who were treated in an acute neurology unit were included in the study. [Methods] The patients were assigned alternatively to either the mirror therapy group receiving mirror therapy and neurodevelopmental treatment or the neurodevelopmental treatment only group. The primary outcome measures were the upper extremity motor subscale of the Fugl-Meyer Assessment, Motricity Index upper extremity score, and the Stroke Upper Limb Capacity Scale. Somatosensory assessment with the Ayres Southern California Sensory Integration Test, and the Barthel Index were used as secondary outcome measures. [Results] No statistically significant improvements were found for any measures in either group after the treatment. In terms of minimally clinically important differences, there were improvements in Fugl-Meyer Assessment and Barthel Index in both mirror therapy and neurodevelopmental treatment groups. [Conclusion] The results of this pilot study revealed that very early mirror therapy has no additional effect on functional improvement of upper extremity function in acute stroke patients. Multicenter trials are needed to determine the results of early application of mirror therapy in stroke rehabilitation. PMID:26696729

  16. Ontogeny of salinity tolerance and hyper-osmoregulation by embryos of the intertidal crabs Hemigrapsus edwardsii and Hemigrapsus crenulatus (Decapoda, Grapsidae): survival of acute hyposaline exposure.

    PubMed

    Taylor, H H; Seneviratna, Deepani

    2005-04-01

    The adults of Hemigrapsus edwardsii and Hemigrapsus crenulatus are euryhaline crabs and strong hyper-osmoregulators. Their embryos are carried externally attached to the abdominal pleopods of female crabs, where they are exposed to temporal and spatial changes in salinity associated with their intertidal and estuarine habitats. Although embryos lack the branchial and excretory organs responsible for adult osmoregulation, post-gastrula embryos were highly tolerant of exposure to hypo-osmotic sea water. Detached eggs (embryos+envelopes), of both species, at all developmental stages between gastrulation and hatching, exhibited 80-100% survival for periods up to 96 h in sea water (osmolality, 1050 mmol kg(-1)) and in dilutions to 50%, 10%, and 1%. Cleavage stages were less tolerant of dilution; H. edwardsii, <50% survived 24 h in 10% sea water; H. crenulatus <50% survived 6 h in 10% sea water. Post-gastrulation stages strongly hyper-osmoregulated but cleavage stages were hyper-osmoconformers (maintaining internal osmolality approximately 150 mmol kg(-1) above external). Osmoregulatory capacity was reduced just prior hatching, particularly in H. crenulatus, although salinity tolerance remained high. Gastrulation therefore marks a critical stage in the ontogeny of osmoregulation and salinity tolerance. Total Na+/K(+)-ATPase activity increased greatly during embryogenesis of H. crenulatus (undetectable in blastulae; gastrulae 0.31+/-0.05 pmol P(i) embryo(-1) min(-1); pre-hatching 16.4+/-1.0 pmol P(i) embryo(-1) min(-1)). Na+/K(+)-ATPase activity increased in embryos exposed to dilute sea water for 24 h implicating regulation of this transporter in a short-term acclimation response.

  17. Lipoxygenase products in the urine correlate with renal function and body temperature but not with acute transplant rejection.

    PubMed

    Reinhold, Stephan W; Scherl, Thomas; Stölcker, Benjamin; Bergler, Tobias; Hoffmann, Ute; Weingart, Christian; Banas, Miriam C; Kollins, Dmitrij; Kammerl, Martin C; Krüger, Bernd; Kaess, Bernhard; Krämer, Bernhard K; Banas, Bernhard

    2013-02-01

    Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.

  18. Acute exercise has a general facilitative effect on cognitive function: A combined ERP temporal dynamics and BDNF study.

    PubMed

    Chang, Yu-Kai; Alderman, Brandon L; Chu, Chien-Heng; Wang, Chun-Chih; Song, Tai-Fen; Chen, Feng-Tzu

    2017-02-01

    This study examined whether acute moderate intensity exercise results in a general or selective improvement in cognitive function. In addition, multiple stimulus-locked ERP components and serum BDNF levels were assessed to investigate potential neurobiological mechanisms underlying acute exercise effects on select aspects of cognitive performance. Thirty young adults were recruited and participated in exercise and reading control sessions in a counterbalanced order. Following treatments, the Stroop task was administrated, and N1, N2, P3, and N450 components of the ERP waveform were recorded and analyzed. Additionally, blood samples were withdrawn immediately following exercise or rest conditions prior to administration of the Stroop task. Acute exercise facilitated response times for both Stroop congruent and incongruent task conditions, with a similar magnitude of improvement. Larger P3 and reduced N450 amplitudes as well as decreased N450 latency were observed following exercise, but no effects on N1 and N2 components were found. This dose of exercise also did not influence serum BDNF levels. These findings suggest that moderate intensity acute exercise results in a generalized rather than selective improvement in cognition. The facilitation may be related to an increase in attentional or neural resource allocation and conflict detection processes reflected by longer latency endogenous components (P3, N450), but is not influenced by earlier sensory and monitoring processes revealed by earlier ERP components or by serum levels of BDNF.

  19. Differential effects of grape juice on gastric emptying and renal function from cisplatin-induced acute adverse toxicity.

    PubMed

    Ko, J-L; Tsai, C-H; Liu, T-C; Lin, M-Y; Lin, H-L; Ou, C-C

    2016-08-01

    Grape skin and seeds contain large amounts of phytochemicals such as polyphenols, resveratrol, and proanthocyanidins, which possess antioxidant activities. Cisplatin is widely used in the treatment of cancer. High doses of cisplatin have also been known to produce acute adverse effects. The aim of this study was to investigate the protective effects of antioxidant properties of whole grape juice (with skin and seeds) on cisplatin-induced acute gastrointestinal tract disorders and nephrotoxicity in Wistar rats. Gastric emptying is significantly increased in whole grape juice-pretreated rats when compared to cisplatin treatment alone. The expression of ghrelin mRNA of stomach is increased in rats with whole grape juice. However, pretreatment with whole grape juice did not reduce renal function markers in acute renal toxicity. No significant changes were recorded in the oxidative stress/antioxidant status parameters of any study group. In contrast, pretreatment with whole grape juice slightly improved tubular cell vacuolization, tubular dilatation, and cast formation in renal tubules. These results show that consumption of whole grape juice induces somewhat beneficial effects in preventing cisplatin-mediated dyspepsia but does not offer protection against cisplatin-induced acute renal toxicity.

  20. Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial

    PubMed Central

    Kumar, Amaravadi Sampath; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

    2016-01-01

    Introduction Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. Aim To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. Materials and Methods A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni’s ‘t’-test. Exercise tolerance was analysed by Paired ‘T’-test. Results Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1st, 2nd and 3rd postoperative day when compared with preoperative day. On 4th and 5th postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group

  1. Effect of initial temperature changes on myocardial enzyme levels and cardiac function in acute myocardial infarction.

    PubMed

    Qian, Yuanyu; Liu, Jie; Ma, Jinling; Meng, Qingyi; Peng, Chaoying

    2014-07-01

    In the present study, the effect of initial body temperature changes on myocardial enzyme levels and cardiac function in acute myocardial infarction (AMI) patients was investigated. A total of 315 AMI patients were enrolled and the mean temperature was calculated based on their body temperature within 24 h of admission to hospital. The patients were divided into four groups according to their normal body temperature: Group A, <36.5°C; group B, ≥36.5°C and <37.0°C; group C, ≥37.0°C and <37.5°C and group D, ≥37.5°C. The levels of percutaneous coronary intervention, myocardial enzymes and troponin T (TNT), as well as cardiac ultrasound images, were analyzed. Statistically significant differences in the quantity of creatine kinase at 12 and 24 h following admission were identified between group A and groups C and D (P<0.01). A significant difference in TNT at 12 h following admission was observed between groups A and D (P<0.05), however, this difference was not observed with groups B and C. The difference in TNT between the groups at 24 h following admission was not statistically significant (P>0.05). Significant differences in lactate dehydrogenase at 12 and 24 h following admission were observed between groups A and D (P<0.05), however, differences were not observed with groups B and C (P>0.05). Significant differences in glutamic-oxaloacetic transaminase at 12 and 24 h following admission were observed between groups A and D (P<0.05), however, differences were not observed in groups B and C (P>0.05). However, no significant differences were identified in cardiac function index between all the groups. Therefore, the results of the present study indicated that AMI patients with low initial body temperatures exhibited decreased levels of myocardial enzymes and TNT. Thus, the observation of an initially low body temperature may be used as a protective factor for AMI and may improve the existing clinical program.

  2. ICE1 of Pyrus ussuriensis functions in cold tolerance by enhancing PuDREBa transcriptional levels through interacting with PuHHP1

    NASA Astrophysics Data System (ADS)

    Huang, Xiaosan; Li, Kongqing; Jin, Cong; Zhang, Shaoling

    2015-12-01

    ICE1 transcription factor plays an important role in plant cold stress via regulating the expression of stress-responsive genes. In this study, a PuICE1 gene isolated from Pyrus ussuriensis was characterized for its function in cold tolerance. The expression levels of the PuICE1 were induced by cold, dehydration and salt, with the greatest induction under cold conditions. PuICE1 was localized in the nucleus and could bind specifically to the MYC element in the PuDREBa promoter. The PuICE1 fused to the GAL4 DNA-binding domain to have transcriptional activation activity. Ectopic expression of the PuICE1 in tomato conferred enhanced tolerance to cold stress at cold temperatures, less electrolyte leakage, less MDA content, higher chlorophyll content, higher survival rate, higher proline content, higher activities of enzymes. In additon, steady-state mRNA levels of six stress-responsive genes coding for either functional or regulatory genes were induced to higher levels in the transgenic lines by cold stress. Yeast two-hybrid, transient assay, split luciferase complementation and BiFC assays all revealed that PuHHP1 protein can physically interact with PuICE1. Taken together, these results demonstrated that PuICE1 plays a positive role in cold tolerance, which may be due to enhancement of PuDREBa transcriptional levels through interacting with the PuHHP1.

  3. FcWRKY70, a WRKY protein of Fortunella crassifolia, functions in drought tolerance and modulates putrescine synthesis by regulating arginine decarboxylase gene.

    PubMed

    Gong, Xiaoqing; Zhang, Jingyan; Hu, Jianbing; Wang, Wei; Wu, Hao; Zhang, Qinghua; Liu, Ji-Hong

    2015-11-01

    WRKY comprises a large family of transcription factors in plants, but most WRKY members are still poorly understood. In this study, we report functional characterization of a Group III WRKY gene (FcWRKY70) from Fortunella crassifolia. FcWRKY70 was greatly induced by drought and abscisic acid, but slightly or negligibly by salt and cold. Overexpression of FcWRKY70 in tobacco (Nicotiana nudicaulis) and lemon (Citrus lemon) conferred enhanced tolerance to dehydration and drought stresses. Transgenic tobacco and lemon exhibited higher expression levels of ADC (arginine decarboxylase), and accumulated larger amount of putrescine in comparison with wild type (WT). Treatment with D-arginine, an inhibitor of ADC, caused transgenic tobacco plants more sensitive to dehydration. Knock-down of FcWRKY70 in kumquat down-regulated ADC abundance and decreased putrescine level, accompanied by compromised dehydration tolerance. The promoter region of FcADC contained two W-box elements, which were shown to be interacted with FcWRKY70. Taken together, our data demonstrated that FcWRKY70 functions in drought tolerance by, at least partly, promoting production of putrescine via regulating ADC expression.

  4. ICE1 of Pyrus ussuriensis functions in cold tolerance by enhancing PuDREBa transcriptional levels through interacting with PuHHP1

    PubMed Central

    Huang, Xiaosan; Li, Kongqing; Jin, Cong; Zhang, Shaoling

    2015-01-01

    ICE1 transcription factor plays an important role in plant cold stress via regulating the expression of stress-responsive genes. In this study, a PuICE1 gene isolated from Pyrus ussuriensis was characterized for its function in cold tolerance. The expression levels of the PuICE1 were induced by cold, dehydration and salt, with the greatest induction under cold conditions. PuICE1 was localized in the nucleus and could bind specifically to the MYC element in the PuDREBa promoter. The PuICE1 fused to the GAL4 DNA-binding domain to have transcriptional activation activity. Ectopic expression of the PuICE1 in tomato conferred enhanced tolerance to cold stress at cold temperatures, less electrolyte leakage, less MDA content, higher chlorophyll content, higher survival rate, higher proline content, higher activities of enzymes. In additon, steady-state mRNA levels of six stress-responsive genes coding for either functional or regulatory genes were induced to higher levels in the transgenic lines by cold stress. Yeast two-hybrid, transient assay, split luciferase complementation and BiFC assays all revealed that PuHHP1 protein can physically interact with PuICE1. Taken together, these results demonstrated that PuICE1 plays a positive role in cold tolerance, which may be due to enhancement of PuDREBa transcriptional levels through interacting with the PuHHP1. PMID:26626798

  5. Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation

    PubMed Central

    Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

    2017-01-01

    Aims To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). Methods 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Results Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Conclusions Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals. PMID:28199386

  6. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy).

    PubMed

    Storey, Robert F; Becker, Richard C; Harrington, Robert A; Husted, Steen; James, Stefan K; Cools, Frank; Steg, Philippe Gabriel; Khurmi, Nardev S; Emanuelsson, Hakan; Lim, Soo Teik; Cannon, Christopher P; Katus, Hugo A; Wallentin, Lars

    2011-12-01

    The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor reduced the risk for cardiovascular events in patients with acute coronary syndromes compared to clopidogrel but was associated with increased incidence of dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy. Patients with advanced lung disease, congestive heart failure, or coronary artery bypass graft surgery after the index event were excluded. Pulse oximetry (blood oxygen saturation), spirometry (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity before and 20 minutes after inhalation of a β(2) agonist), lung volumes (total lung capacity, functional residual capacity, residual volume), and diffusion capacity were performed after patients received study medication for 30 to 40 days. Tests were then repeated <10 days before and approximately 30 days after the discontinuation of study medication. After a mean treatment duration of 31 days, there were no differences between the groups for any of the pulmonary function parameters. At the end of treatment (mean 211 days) and after the discontinuation of study medication (mean 32 days after the last dose), there was also no evidence of a change in pulmonary function in either group. For example, forced expiratory volume in 1 second values before β(2) agonist inhalation in the ticagrelor and clopidogrel groups were 2.81 ± 0.73 and 2.70 ± 0.84 L, respectively, at the first visit and did not change significantly at subsequent visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in this cohort of patients with acute coronary syndromes compared to clopidogrel.

  7. Sustained impairment of respiratory function and swim performance following acute oil exposure in a coastal marine fish.

    PubMed

    Johansen, J L; Esbaugh, A J

    2017-04-06

    Acute exposure to crude oil polycyclic aromatic hydrocarbons (PAH) can severely impair cardiorespiratory function and swim performance of larval fish; however, the effects of acute oil exposure on later life stages and the capacity for subsequent recovery is less clear. Red drum (Sciaenops ocellatus) is an economically important apex predator native to the Gulf of Mexico, which was directly exposed to the 2010 Deep Water Horizon (DWH) oil spill. Here we examine impact and recovery of young adult red drum from exposure to concentrations of 0, 4.1, and 12.1μgL(-1) ΣPAH50 naturally weathered oil-water accommodated fractions (geometric mean), which are well within the range of concentrations measured during the DWH incident. We focused on aerobic scope (ASc), burst- and critical swimming speeds (Uburst and Ucrit), cost of transport (COT), as well as the capacity to repay oxygen debt following exhaustive exercise (EPOC), which are critical parameters for success of all life stages of fishes. A 24h acute exposure to 4.1μgL(-1) ΣPAH caused a significant 9.7 and 12.6% reduction of Uburst and Ucrit respectively, but no change in ASc, COT or EPOC, highlighting a decoupled effect on the respiratory and swimming systems. A higher exposure concentration, 12.1μgL(-1) ΣPAH, caused an 8.6 and 8.4% impairment of Uburst and Ucrit, as well as an 18.4% reduction in ASc. These impairments persisted six weeks post-exposure, suggesting that recorded impacts are entrenched. Large predatory fishes are critically dependent on the cardiorespiratory and swimming systems for ecological fitness, and long-term impairment of performance due to acute oil exposure suggests that even acute exposure events may have long lasting impacts on the ecological fitness of affected populations.

  8. Acute and chronic ethanol exposure differentially regulate CB1 receptor function at glutamatergic synapses in the rat basolateral amygdala.

    PubMed

    Robinson, Stacey L; Alexander, Nancy J; Bluett, Rebecca J; Patel, Sachin; McCool, Brian A

    2016-09-01

    The endogenous cannabinoid (eCB) system has been suggested to play a key role in ethanol preference and intake, the acute effects of ethanol, and in the development of withdrawal symptoms following ethanol dependence. Ethanol-dependent alterations in glutamatergic signaling within the lateral/basolateral nucleus of the amygdala (BLA) are critical for the development and expression of withdrawal-induced anxiety. Notably, the eCB system significantly regulates both glutamatergic and GABAergic synaptic activity within the BLA. Chronic ethanol exposure significantly alters eCB system expression within regions critical to the expression of emotionality and anxiety-related behavior, including the BLA. Here, we investigated specific interactions between the BLA eCB system and its functional regulation of synaptic activity during acute and chronic ethanol exposure. In tissue from ethanol naïve-rats, a prolonged acute ethanol exposure caused a dose dependent inhibition of glutamatergic synaptic activity via a presynaptic mechanism that was occluded by CB1 antagonist/inverse agonists SR141716a and AM251. Importantly, this acute ethanol inhibition was attenuated following 10 day chronic intermittent ethanol vapor exposure (CIE). CIE exposure also significantly down-regulated CB1-mediated presynaptic inhibition at glutamatergic afferent terminals but spared CB1-inhibition of GABAergic synapses arising from local inhibitory-interneurons. CIE also significantly elevated BLA N-arachidonoylethanolamine (AEA or anandamide) levels and decreased CB1 receptor protein levels. Collectively, these data suggest a dynamic regulation of the BLA eCB system by acute and chronic ethanol.

  9. Acute effects of static stretching on peak torque and the hamstrings-to-quadriceps conventional and functional ratios.

    PubMed

    Costa, P B; Ryan, E D; Herda, T J; Walter, A A; Defreitas, J M; Stout, J R; Cramer, J T

    2013-02-01

    Recent evidence has shown acute static stretching may decrease hamstring-to-quadriceps (H:Q) ratios. However, the effects of static stretching on the functional H:Q ratio, which uses eccentric hamstrings muscle actions, have not been investigated. This study examined the acute effects of hamstrings and quadriceps static stretching on leg extensor and flexor concentric peak torque (PT), leg flexor eccentric PT, and the conventional and functional H:Q ratios. Twenty-two women (mean ± SD age=20.6 ± 1.9 years; body mass=64.6 ± 9.1 kg; height=164.5 ± 6.4 cm) performed three maximal voluntary unilateral isokinetic leg extension, flexion, and eccentric hamstring muscle actions at the angular velocities of 60 and 180°/s before and after a bout of hamstrings, quadriceps, and combined hamstrings and quadriceps static stretching, and a control condition. Two-way repeated measures ANOVAs (time × condition) were used to analyze the leg extension, flexion, and eccentric PT as well as the conventional and functional H:Q ratios. Results indicated that when collapsed across velocity, hamstrings-only stretching decreased the conventional ratios (P<0.05). Quadriceps-only and hamstrings and quadriceps stretching decreased the functional ratios (P<0.05). These findings suggested that stretching may adversely affect the conventional and functional H:Q ratios.

  10. Pillar III--optimisation of anaemia tolerance.

    PubMed

    Meier, Jens; Gombotz, Hans

    2013-03-01

    In the case of acute bleeding, the use of the anaemia tolerance of a patient enables the physician to either avoid blood transfusions or delay them after bleeding has ceased. This concept is the cornerstone of the third pillar of modern patient blood management programmes. Its efficacy depends on the degree of utilisation of anaemia tolerance, which is not constant but depends on the compensatory capacity of the individual patient in a given situation. Fortunately, the specifications of anaemia tolerance can be influenced by the anaesthesiologist. This article presents the concept of anaemia tolerance and highlights the options for how anaemia tolerance can be optimised in the pre-, intra-, and postoperative periods.

  11. Circuit Resistance Training Attenuates Acute Exertion-Induced Reductions in Arterial Function but Not Inflammation in Obese Women

    PubMed Central

    Franklin, Nina C.; Robinson, Austin T.; Bian, Jing-Tan; Ali, Mohamed M.; Norkeviciute, Edita; McGinty, Patrick

    2015-01-01

    Abstract Background: Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response. Methods: Eighteen obese [body mass index (BMI) 30.0–40.0 kg·m−2] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed. Results: Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics. Conclusions: This study shows that CRT alleviates acute exertion-induced reductions in endothelial function among obese sedentary women in the absence of changes in inflammation. PMID:25844686

  12. The effect of acute exercise on endothelial function following a high-fat meal.

    PubMed

    Padilla, Jaume; Harris, Ryan A; Fly, Alyce D; Rink, Lawrence D; Wallace, Janet P

    2006-10-01

    The transient impairment of endothelial function following a high-fat meal is well established. Brachial artery flow-mediated dilation (FMD) decreases between 2 and 6 h post ingestion. Whether this impairment can be reduced with acute aerobic exercise has not been investigated. The purpose of this study was to investigate if a single sustained aerobic exercise session can counteract the postprandial attenuation in brachial artery FMD associated with the ingestion of a high-fat meal. Eight apparently healthy adults (five men, three women), age 25.5 +/- 0.8 years, performed three treatment conditions in a counter-balanced design: (1) low-fat meal alone (LFM), (2) high-fat meal alone (HFM), and (3) one session of aerobic exercise presented 2 h after ingesting a high-fat meal (HFM-EX). The examination of brachial artery FMD was performed at baseline and 4 h following the ingestion of the meal for each treatment condition. A 3 x 2 (treatment x time) repeated measures ANOVA exhibited a significant interaction (P = 0.019). Preprandial FMDs were similar (P = 0.863) among all three treatment conditions. The FMDs following the LFM (7.18 +/- 1.31%) and HFM-EX (8.72 +/- 0.94%) were significantly higher (P = 0.001) than the FMD following the HFM (4.29 +/- 1.64%). FMD was significantly elevated above preprandial values following the HFM-EX (5.61 +/- 1.54 to 8.72 +/- 0.94%, P = 0.005) but was unchanged following the LFM (6.17 +/- 0.94 to 7.18 +/- 1.31%, P = 0.317) and the HFM (5.73 +/- 1.23 to 4.29 +/- 1.64%, P = 0.160). These findings suggest that a single aerobic exercise session cannot only counteract the postprandial endothelial dysfunction induced by the ingestion of a high-fat meal, but also increase brachial artery FMD in apparently healthy adults.

  13. Comparisons of the tolerability and sensitivity of quetiapine-XR in the acute treatment of schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and generalized anxiety disorder

    PubMed Central

    Wang, Zuowei; Kemp, David E.; Chan, Philip K.; Fang, Yiru; Ganocy, Stephen J.; Calabrese, Joseph R.; Gao, Keming

    2012-01-01

    Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD. PMID:20875219

  14. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-03-13

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

    SciTech Connect

    Moss, H.A.; Nannis, E.D.; Poplack, D.G.

    1981-07-01

    The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia.

  16. Functional validation of Phragmites communis glutathione reductase (PhaGR) as an essential enzyme in salt tolerance.

    PubMed

    Zhang, Xia; Quan, Geng; Wang, Jing; Han, Huiling; Chen, ShiHua; Guo, ShanLi; Yin, HaiBo

    2015-04-01

    Reed plants (Phragmites communis (Linn.) Trin) are hydrophilic perennial grasses growing in fresh and brackish waters. These plants readily adapt to arid and high salinity conditions; however, their resistance mechanism against abiotic stresses, especially high salinity, is largely unknown. In the present study, we cloned a glutathione reductase gene from P. communis and investigated its role in conferring salt tolerance in reed plants. The expression of PhaGR at the transcriptional level was affected by multiple abiotic stresses including NaCl, Cd(2+), heat, cold, PEG 6000, and abscisic acid (ABA). Furthermore, NaCl and Cd(2+) could increase its expressions at the translational level. NaCl and Cd(2+) also increased the biosynthesis of soluble protein and reduced glutathione (GSH). Reed seedlings that were challenged with NaCl showed higher levels of GR activities, which corroborated our gene expression data. The increase in GR possibly increased the salt tolerance of reed plants through GSH production. Thus, PhaGR is a potential target gene in improving the salt tolerance of crops through genetic manipulation.

  17. Universal Stress Protein Exhibits a Redox-Dependent Chaperone Function in Arabidopsis and Enhances Plant Tolerance to Heat Shock and Oxidative Stress

    PubMed Central

    Jung, Young Jun; Melencion, Sarah Mae Boyles; Lee, Eun Seon; Park, Joung Hun; Alinapon, Cresilda Vergara; Oh, Hun Taek; Yun, Dae-Jin; Chi, Yong Hun; Lee, Sang Yeol

    2015-01-01

    Although a wide range of physiological information on Universal Stress Proteins (USPs) is available from many organisms, their biochemical, and molecular functions remain unidentified. The biochemical function of AtUSP (At3g53990) from Arabidopsis thaliana was therefore investigated. Plants over-expressing AtUSP showed a strong resistance to heat shock and oxidative stress, compared with wild-type and Atusp knock-out plants, confirming the crucial role of AtUSP in stress tolerance. AtUSP was present in a variety of structures including monomers, dimers, trimers, and oligomeric complexes, and switched in response to external stresses from low molecular weight (LMW) species to high molecular weight (HMW) complexes. AtUSP exhibited a strong chaperone function under stress conditions in particular, and this activity was significantly increased by heat treatment. Chaperone activity of AtUSP was critically regulated by the redox status of cells and accompanied by structural changes to the protein. Over-expression of AtUSP conferred a strong tolerance to heat shock and oxidative stress upon Arabidopsis, primarily via its chaperone function. PMID:26734042

  18. Neurocognitive function and state cognitive stress appraisal predict cortisol reactivity to an acute psychosocial stressor in adolescents.

    PubMed

    Slattery, Marcia J; Grieve, Adam J; Ames, Michelle E; Armstrong, Jeffrey M; Essex, Marilyn J

    2013-08-01

    Stress and associated alterations in hypothalamic-pituitary-adrenal (HPA) function have deleterious influence on the development of multiple mental and physical health problems. Prior research has aimed to identify individuals most at risk for the development of these stress-related maladies by examining factors that may contribute to inter-individual differences in HPA responses to acute stress. The objectives of this study were to investigate, in adolescents, (1) whether differences in neurocognitive abilities influenced cortisol reactivity to an acute stressor, (2) whether internalizing psychiatric disorders influenced this relationship, and (3) whether acute cognitive stress-appraisal mechanisms mediated an association between neurocognitive function and cortisol reactivity. Subjects were 70 adolescents from a community sample who underwent standardized neurocognitive assessments of IQ, achievement, and declarative memory measures at mean age 14 and whose physiological and behavioral responses to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) were assessed at mean age 18. Results showed that, among all adolescents, lower nonverbal memory performance predicted lower cortisol reactivity. In addition, internalizing disorders interacted with verbal memory such that the association with cortisol reactivity was strongest for adolescents with internalizing disorders. Finally, lower secondary cognitive appraisal of coping in anticipation of the TSST independently predicted lower cortisol reactivity but did not mediate the neurocognitive-cortisol relationship. Findings suggest that declarative memory may contribute to inter-individual differences in acute cortisol reactivity in adolescents, internalizing disorders may influence this relationship, and cognitive stress appraisal also predicts cortisol reactivity. Developmental, research, and clinical implications are discussed.

  19. The effect of music on brain wave functioning during an acute psychotic episode: a pilot study.

    PubMed

    Morgan, Kylie Anne; Harris, Anthony W; Luscombe, Georgina; Tran, Yvonne; Herkes, Geoff; Bartrop, Roger W

    2010-07-30

    This pilot study compared the differences in the quantified electroencephalogram (qEEG) between two conditions; eyes closed resting and eyes closed listening to music of 15 subjects currently experiencing an acute psychotic episode. The results showed a significant decrease in delta, alpha and beta waves when listening to music compared to resting condition.

  20. PtrBAM1, a β-amylase-coding gene of Poncirus trifoliata, is a CBF regulon member with function in cold tolerance by modulating soluble sugar levels.

    PubMed

    Peng, Ting; Zhu, Xiaofang; Duan, Nian; Liu, Ji-Hong

    2014-12-01

    β-Amylase (BAM) catalyses starch breakdown to generate maltose, which can be incorporated into sugar metabolism. However, the role of BAM genes in cold tolerance is less characterized. In this study, we report the isolation and functional characterization of a chloroplast-localizing BAM-encoding gene PtrBAM1 from Poncirus trifoliata. PtrBAM1 was induced by cold, dehydration and salt, but repressed by maltose. Overexpression of PtrBAM1 in tobacco (Nicotiana nudicaulis) increased BAM activity, promoted starch degradation and enhanced the contents of maltose and soluble sugars, whereas opposite changes were observed when PtrBAM1 homolog in lemon (Citrus lemon) was knocked down. The tobacco overexpressing lines exhibited enhanced tolerance to cold at chilling or freezing temperatures. Under cold stress, higher BAM activity and greater accumulation of maltose and soluble sugars were observed in the overexpressing lines when compared with the wild-type or empty vector transformants. Bioinformatics analysis demonstrated that PtrBAM1 promoter contained a CBF-recognizing element. Yeast one-hybrid assay demonstrated that PtrCBF could interact with the promoter fragment containing the element. Taken together, these results demonstrate that PtrBAM1 is a member of CBF regulon and plays an important role in cold tolerance by modulating the levels of soluble sugars acting as osmolytes or antioxidants.

  1. The effects of acute hypobaric hypoxia on arterial stiffness and endothelial function and its relationship to changes in pulmonary artery pressure and left ventricular diastolic function.

    PubMed

    Boos, C J; Hodkinson, P; Mellor, A; Green, N P; Woods, D R

    2012-06-01

    This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800 m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e'), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO₂ (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3 mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e' filling velocity or E/e'. There was a significant inverse correlation between SpO₂ and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO₂ and change (Δ) in RI (baseline vs. 150 min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.

  2. The impact of recurrent acute chest syndrome on the lung function of young adults with sickle cell disease.

    PubMed

    Knight-Madden, Jennifer M; Forrester, Terrence S; Lewis, Norma A; Greenough, Anne

    2010-12-01

    The aim of this study was to assess the impact of recurrent acute chest syndrome (ACS) episodes on the lung function of young adults with sickle cell disease (SCD). Our prospective study included 80 SCD adults [26 with recurrent acute chest syndrome (ACS)] and 80 ethnically matched controls aged between 18 and 28 years. Lung function (spirometry and lung volumes) was measured and the results were expressed as the percentage predicted for height. Bronchial hyperresponsiveness (BHR) was assessed by the response to either a bronchodilator or an exercise challenge. The adults with recurrent ACS (two or more ACS episodes) had lower median forced vital capacity (74 vs. 83%, p = 0.03), forced expiratory volume in 1 s (79 vs. 90%, p < 0.03), and total lung capacity (69 vs. 81%, p = 0.04) than SCD adults who had one or no ACS episodes. The greater the number of ACS episodes, the greater the reduction in lung function (p = 0.001). The adults with SCD had lower median forced vital capacity (81 vs. 106%), forced expiratory volume in 1 s (85 vs. 107%), and total lung capacity (80 vs. 87%) than the controls (p < 0.001). Similar numbers in each group had BHR (p = 0.2). The prevalence of restrictive ventilatory defect in the patients with SCD was almost double that of the controls (p = 0.004). Young adults with SCD have worse lung function than ethnically matched controls, particularly if they have suffered recurrent ACS episodes.

  3. Differentiated functions of Ras1 and Ras2 proteins in regulating the germination, growth, conidiation, multi-stress tolerance and virulence of Beauveria bassiana.

    PubMed

    Xie, Xue-Qin; Guan, Yi; Ying, Sheng-Hua; Feng, Ming-Guang

    2013-02-01

    Ras1 and Ras2 are two distinct Ras GTPases in Beauveria bassiana, an entomopathogenic fungus whose biocontrol potential against insect pests depends largely on virulence and multi-stress tolerance. The functions of both proteins were characterized for the first time by constructing dominant-active (GTP-bound) Ras1(G19V) and dominant-negative (GDP-bound) Ras1(D126A) and integrating them and normal Ras1 into wild type and ΔRas2 for a series of phenotypic and transcriptional analyses. The resultant mutants showed gradient changes of multiple phenotypes but little difference in conidial thermotolerance. Expression of Ras1(D126A) caused vigorous hyphal growth, severely defective conidiation, and increased tolerances to oxidation, cell wall disturbance, fungicide and UV-A/UV-B irradiations, but affected slightly germination, osmosensitivity and virulence. These phenotypes were antagonistically altered by mRas1(G19V) expressed in either wild type or ΔRas2, which was severely defective in conidial germination and hyphal growth and displayed intermediate changes in other mentioned phenotypes between paired mutants expressing Ras1(G19V) or Ras1(D126A) in wild type and ΔRas2. Their growth, UV tolerance or virulence was significantly correlated with cellular response to oxidation or cell wall disturbance. Transcriptional changes of 35 downstream effector genes involved in conidiation and multi-stress responses also related to most of the phenotypic changes among the mutants. Our findings highlight that Ras1 and Ras2 regulate differentially or antagonistically the germination, growth, conidiation, multi-stress tolerance and virulence of B. bassiana, thereby exerting profound effects on the fungal biocontrol potential.

  4. Extent of copper tolerance and consequences for functional stability of the ammonia-oxidizing community in long-term copper-contaminated soils.

    PubMed

    Mertens, Jelle; Wakelin, Steven A; Broos, Kris; McLaughlin, Mike J; Smolders, Erik

    2010-01-01

    Adaptation of soil microbial communities to elevated copper (Cu) concentrations has been well documented. However, effects of long-term Cu exposure on adaptation responses associated with functional stability and structural composition within the nitrifying community are still unknown. Soils were sampled in three field sites (Denmark, Thailand, and Australia) where Cu gradients had been established from 3 to 80 years prior to sampling. In each field site, the potential nitrification rate (PNR) decreased by over 50% with increasing soil Cu, irrespective of a 20 to >200-fold increase in Cu tolerance (at the highest soil Cu) among the nitrifying communities. This increased tolerance was associated with decreasing numbers (15-120-fold) of ammonia-oxidizing bacteria (AOB), except in the oldest contaminated field site, decreasing numbers of ammonia-oxidizing archaea (AOA; 10-130-fold) and differences in the operational taxonomic unit (OTU) composition of the AOB and, to a lesser extent, AOA communities. The sensitivity of nitrifying communities, previously under long-term Cu exposure, to additional stresses was assessed. Nitrification in soils from the three field sites was measured following acidification, pesticide addition, freeze-thaw cycles, and dry-rewetting cycles. Functional stability of the nitrification process was assessed immediately after stress application (resistance) and after an additional three weeks of incubation (resilience). No indications were found that long-term Cu exposure affected the sensitivity to the selected stressors, suggesting that resistance and resilience were unaffected. It was concluded that the nitrifying community changed structurally in all long-term Cu-exposed field sites and that these changes were associated with increased Cu tolerance but not with a loss of functional stability.

  5. The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects

    PubMed Central

    Almeida, Germana P. L.; Trombetta, Ivani C.; Cepeda, Felipe X.; Hatanaka, Elaine; Curi, Rui; Mostarda, Cristiano; Irigoyen, Maria C.; Barreto-Filho, José A. S.; Krieger, Eduardo M.; Consolim-Colombo, Fernanda M.

    2017-01-01

    Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX–reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2

  6. Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure.

    PubMed

    Leduc, Martin; Hou, Xin; Hamel, David; Sanchez, Melanie; Quiniou, Christiane; Honoré, Jean-Claude; Roy, Olivier; Madaan, Ankush; Lubell, William; Varma, Daya R; Mancini, Joseph; Duhamel, François; Peri, Krishna G; Pichette, Vincent; Heveker, Nikolaus; Chemtob, Sylvain

    2013-01-01

    Acute renal failure (ARF) is a serious medical complication characterized by an abrupt and sustained decline in renal function. Despite significant advances in supportive care, there is currently no effective treatment to restore renal function. PGE(2) is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP(4) receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP(4) receptor, THG213.29, was tested for its efficacy to improve renal function (glomerular filtration rate, renal plasma flow, and urine output) and histological changes in a model of ARF induced by either cisplatin or renal artery occlusion in Sprague-Dawley rats. THG213.29 modulated PGE(2)-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP(4)-mediated relaxation of piglet saphenous vein rings, partially inhibited EP(4)-mediated cAMP production, but did not affect Gα(i) activation or β-arrestin recruitment. In vivo, THG213.29 significantly improved renal function and histological changes in cisplatin- and renal artery occlusion-induced ARF models. THG213.29 increased mRNA expression of heme-oxygenase 1, Bcl2, and FGF-2 in renal cortex; correspondingly, in EP(4)-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP(4)-dependent overexpression of inflammatory IL-6 and of apoptotic death domain-associated protein and BCL2-associated agonist of cell death. Our results demonstrate that THG213.29 represents a novel class of diuretic agent with noncompetitive allosteric modulator effects on EP(4) receptor, resulting in improved renal function and integrity following acute renal failure.

  7. NF-κB in T-cell Acute Lymphoblastic Leukemia: Oncogenic Functions in Leukemic and in Microenvironmental Cells

    PubMed Central

    dos Santos, Nuno R.; Ghezzo, Marinella N.; da Silva, Ricardo C.; Fernandes, Mónica T.

    2010-01-01

    Two main NF-κB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-κB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-κB genes have not been reported in T-ALL, NF-κB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-κB pathways in acute T-cell leukemia, only inhibition of canonical NF-κB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-κB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-κB inhibition as a means to treat T-ALL. PMID:24281204

  8. Functional outcomes and recanalization rates of stent retrievers in acute ischaemic stroke: A systematic review and meta-analysis

    PubMed Central

    Mizzi, Adrian; Pullicino, Richard; Thornton, John; Downer, Jonathan

    2015-01-01

    Background and purpose Intra-arterial therapy for acute ischaemic stroke has evolved rapidly in the last few years. Stent retrievers have now replaced ‘first-generation’ devices, which have been the principle devices tested in stroke trials. Our aims were to determine the rates of successful recanalization and functional independence in acute stroke patients treated with stent retrievers. We also sought to assess the safety outcomes of stent retrievers by assessing the rates of mortality and intra-cranial haemorrhage. Materials and methods We conducted a systematic review and meta-analysis of studies which utilized stent retrievers as sole treatment or as part of a multi-modal approach in acute ischaemic stroke. Results We identified 20 eligible studies: 17 on Solitaire (ev3/Covidien, Irvine, California, USA) (n = 762) and three on Trevo (Stryker, Kalamazoo, Michigan, USA) (n = 210). The mean age of participants was 66.8 (range 62.1–73.0) years and the M:F ratio was 1.1:1. The average stroke severity score (National Institutes of Health Stroke Scale (NIHSS)) at presentation was 17.2. The weighted mean symptom onset to arterial puncture and procedural duration were 265.4 minutes and 54.8 minutes, respectively. Successful recanalization was achieved in 84.5% of patients with a weighted mean of 2.0 stent retriever passes. Independent functional outcome was achieved in 51.2% and the mortality rate was 16.8%. Conclusion Stent retrievers have the potential to achieve a high rate of recanalization and functional independence whilst being relatively safe. They should be assessed in well-designed randomized controlled trials to determine their efficacy and assess whether they compare favourably with ‘standard treatment’ in stroke. PMID:26156097

  9. Inflammation-associated repression of vasodilator-stimulated phosphoprotein (VASP) reduces alveolar-capillary barrier function during acute lung injury

    PubMed Central

    Henes, Janek; Schmit, Marthe A.; Morote-Garcia, Julio C.; Mirakaj, Valbona; Köhler, David; Glover, Louise; Eldh, Therese; Walter, Ulrich; Karhausen, Jörn; Colgan, Sean P.; Rosenberger, Peter

    2009-01-01

    Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function, increased pulmonary vascular permeability, and infiltration of leukocytes into the alveolar space. Pulmonary function might be compromised, its most severe form being the acute respiratory distress syndrome. A protein central to physiological barrier properties is vasodilator-stimulated phosphoprotein (VASP). Given the fact that VASP expression is reduced during periods of cellular hypoxia, we investigated the role of VASP during ALI. Initial studies revealed reduced VASP expressional levels through cytokines in vitro. Studies in the putative human VASP promoter identified NF-κB as a key regulator of VASP transcription. This VASP repression results in increased paracellular permeability and migration of neutrophils in vitro. In a model of LPS-induced ALI, VASP−/− mice demonstrated increased pulmonary damage compared with wild-type animals. These findings were confirmed in a second model of ventilator-induced lung injury. Studies employing bone marrow chimeric animals identified tissue-specific repression of VASP as the underlying cause of decreased barrier properties of the alveolar-capillary barrier during ALI. Taken together these studies identify tissue-specific VASP as a central protein in the control of the alveolar-capillary barrier properties during ALI.—Henes, J., Schmit, M. A., Morote-Garcia, J. C., Mirakaj, V., Köhler, D., Glover, L., Eldh, T., Walter, U., Karhausen, J., Colgan, S. P., Rosenberger, P. Inflammation-associated repression of vasodilator-stimulated phosphoprotein (VASP) reduces alveolar-capillary barrier function during acute lung injury. PMID:19690214

  10. A cross-over study of the acute effects of espresso coffee on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus.

    PubMed

    Krebs, Jeremy D; Parry-Strong, Amber; Weatherall, Mark; Carroll, Richard W; Downie, Michelle

    2012-09-01

    The objective was to determine the effect of a single dose of espresso caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus. Eighteen participants who were habitual coffee drinkers, were studied using a random-order cross-over design. After a fasting blood sample participants consumed either a double-shot black espresso coffee, decaffeinated coffee, or hot water. The main outcomes were area under the curve (AUC) glucose and insulin, and insulin sensitivity (Matsuda index) during a 75 g oral glucose tolerance test (OGTT) performed one hour later. Other outcomes were change in glucose and insulin and also the insulinogenic index (IGI) and disposition index (DI). AUC glucose was marginally different between beverages (P=.06) being greater following caffeinated coffee than water, mean difference 104 mmol/L/180 min (95% CI 0.1 to 198.1, P=.031), or decaffeinated coffee, mean difference 92.1 mmol/L/180 min (95% CI -1.9 to 186.1, P=.055). There was no difference in AUC insulin (P=.87) or insulin sensitivity (P=.47), nor in change in glucose or insulin over the hour following beverage consumption. There was a marginal difference in IGI between beverages (P=.097) with coffee having a lower incremental increase in insulin/glucose than water (P=.037) though no difference between coffee and decaffeinated coffee (P=.54) and no difference in DI (P=.23). Black espresso coffee in people with type 2 diabetes mellitus results in a marginally greater excursion of glucose during a following OGTT compared with water or decaffeinated coffee. This effect does not appear to be mediated by changes in insulin sensitivity.

  11. Obestatin and Ghrelin May Have a Complementary Function During Acute and Chronic Period in Mice.

    PubMed

    Udum, Duygu; Belenli, Deniz; Ilhan, Tuncay; Gunes, Nazmiye; Sonat, Fusun; Yalcin, Murat

    2016-01-01

    Obestatin is described as an anorexigenic peptide, and has adverse effects of ghrelin. It has no inhibitory effects on acute/chronic food intake, and it has been reported by several researchers. The role of obestatin in metabolism is still not clear. In the present study, the purpose is to determine the effects of chronically administrated obestatin. For this purpose, (1 µmol/kg; i.p.) or ghrelin (1 µmol/kg; i.p.) and food restriction (24h fast:24h fed) on plasma obestatin, ghrelin, leptin, insulin, cholecystokinin (CCK) and glucose levels, and body weight gain were investigated for 14 days in mice. Additionally, mice were treated with acute ip (100 nmol/kg) injections of obestatin or ghrelin to investigate the food consumptions, plasma obestatin and ghrelin levels to determine unknown acute effects of obestatin. Plasma ghrelin levels increased significantly in obestatin administered mice when compared with the control group for chronic treatment. This increase is consistent with immunohistochemical findings which claim that the number of ghrelin and obestatin immunopositive cells in fundus tissue of stomach are considerably high in obestatin treated animals. Plasma obestatin and ghrelin levels has shown an increase endogenously in food restricted mice, but plasma leptin and insulin levels have been found to be lower compared to the control group. Acute administration of obestatin caused a decrease in plasma obestatin level at 60 min after injection and had no effect on the reduction of food intake in each treatment time. These results imply that obestatin may not itself be involved in the metabolism regulation; however, obestatin accompanied by ghrelin may play a role in the long-term regulation of metabolism.

  12. Blood Aggravates Histological and Functional Damage after Acute Subdural Hematoma in Rats.

    PubMed

    Jussen, Daniel; Krenzlin, Harald; Papaioannou, Chrysostomos; Ens, Swetlana; Kempski, Oliver; Alessandri, Beat

    2017-02-15

    Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and paraffin oil in a rat model of ASDH. In a histological study, we investigated the effects on acute ICP, cerebral perfusion pressure (CPP), cerebral blood flow (CBF), tissue oxygen changes, and brain damage at 2, 24, and 96 h post-infusion. Inflammatory reaction was analyzed by immuno-staining for microglia (ionized calcium binding adaptor molecule 1 [Iba1]) and activated astrocytes (glial fibrillary acidic protein [GFAP]). Besides acute ICP and CBF changes, we investigated the development of behavior (neuroscore and beamwalk test) for up to 4 days after injury in a behavioral study. Despite comparably increased ICP, there was a more pronounced lesion growth in the blood infusion group during the first 96 h. Further, there was an increased peri-lesional immunoreactive area of Iba1 and GFAP 96 h post-infusion, primarily in the blood infusion group, whereas hippocampal damage was comparable in both infusion groups. In the behavioral evaluation, paraffin-infused animals showed a better recovery, compared with the blood infusion group. In conclusion, comparable acute time-course of ICP, CPP, and CBF clearly indicates that the differences in lesion size, inflammatory reaction, and behavioral deficits after blood- and paraffin oil-induced ASDH are partially due to blood constituents. Therefore, current data suggest that subdural hematomas should be completely removed as quickly as possible; decompression alone may not be sufficient to prevent secondary brain damage.

  13. Effect of the acute crowding stress on the rat brown adipose tissue metabolic function.

    PubMed

    Djordjevic, Jelena; Cvijic, Gordana; Petrovic, Natasa; Davidovic, Vukosava

    2005-12-01

    Our previous results have shown that metabolic and thermal stressors influence interscapular brown adipose tissue (IBAT) metabolic activity by increasing oxygen consumption and, consequently, altering the toxic reactive oxygen species (ROS) production and the antioxidative system activity. Since there is not enough evidence about the effect of psychosocial stressors on these processes, we studied the effect of acute crowding stress on the IBAT and hypothalamic monoamine oxidase (MAO) activity as well as IBAT antioxidative enzymes, manganese (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT), as the relevant indicators of IBAT metabolic alternations under the stress exposure and the returning of animals to control conditions. The results indicated that acute crowding stress did not change the hypothalamic and IBAT MAO activities, the generation of ROS and, consequently, the IBAT CuZnSOD and CAT activities. However, all three antioxidative enzymes were affected only after the recovery period. It seems that peripheral overheating of rats during acute crowding changes the stress nature, by becoming more thermal than psychosocial and by suppression the hypothalamic efferent pathways involved in the IBAT thermogenesis regulation. However, it seems that returning of the animals to the control conditions after the stress termination causes the reactivation of IBAT thermogenesis with tendency to normalise the body temperature.

  14. Evaluation of brain function in acute carbon monoxide poisoning with multimodality evoked potentials

    SciTech Connect

    He, Fengsheng; Liu, Xibao; Yang, Shi; Zhang, Shoulin ); Xu, Guanghua; Fang, Guangchai; Pan, Xiaowen )

    1993-02-01

    The median nerve somatosensory evoked potentials (SEP), pattern reversal visual evoked potentials (VEP), and brain stem auditory evoked potentials (BAEP) were studied in 109 healthy adults and in 88 patients with acute carbon monoxide (CO) poisoning. The upper limits for normal values of peak and interpeak latencies of multimodalities of evoked potentials in the reference group were established by a stepwise multiple regression analysis. SEP changes selectively affecting N32 and N60 were found in 78.8% of patients. There was prolonged PI00 latency of VEP in 58.2% of the cases examined. The prevalence of BAEP abnormalities in comatose patients (36%) was significantly higher than that (8.6%) in conscious patients. BAEP abnormalities were most frequently seen in comatose patients who had diminished brain stem reflexes (77.8%). It has been found that a consistent abnormality involving N2O and subsequent peaks in SEP, a remarkable prolongation of PI00 latency in VEP, or a prolongation of Ill-V interpeak latency in BAEP as well as the reoccurrence of evoked potential abnormalities after initial recovery all indicate unfavorable outcomes in patients with acute CO poisoning. The multimodality evoked potentials have proved to be sensitive indicators in the evaluation of brain dysfunction and in the prediction of prognosis of acute CO poisoning and the development of delayed encephalopathy. 16 refs., 4 figs., 6 tabs.

  15. Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats.

    PubMed

    Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio

    2015-01-01

    Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke.

  16. Healing of the Acutely Injured Anterior Cruciate Ligament: Functional Treatment with the ACL-Jack, a Dynamic Posterior Drawer Brace

    PubMed Central

    Reischl, Nikolaus; Rönn, Karolin; Magnusson, Robert A.; Gautier, Emanuel; Jakob, Roland P.

    2016-01-01

    Background. The injured anterior cruciate ligament (ACL) has a limited healing capacity leading to persisting instability. Hypothesis/Purpose. To study if the application of a brace, producing a dynamic posterior drawer force, after acute ACL injury reduces initial instability. Study Design. Cohort study. Methods. Patients treated with the ACL-Jack brace were compared to controls treated with primary ACL reconstruction und controls treated nonsurgically with functional rehabilitation. Measurements included anterior laxity (Rolimeter), clinical scores (Lysholm, Tegner, and IKDC), and MRI evaluation. Patients were followed up to 24 months. Results. Patients treated with the ACL-Jack brace showed a significant improvement of anterior knee laxity comparable to patients treated with ACL reconstruction, whereas laxity persisted after nonsurgical functional rehabilitation. The failure risk (secondary reconstruction necessary) of the ACL-Jack group was however 21% (18 of 86) within 24 months. Clinical scores were similar in all treatment groups. Conclusion. Treatment of acute ACL tears with the ACL-Jack brace leads to improved anterior knee laxity compared to nonsurgical treatment with functional rehabilitation. PMID:28053787

  17. Healing of the Acutely Injured Anterior Cruciate Ligament: Functional Treatment with the ACL-Jack, a Dynamic Posterior Drawer Brace.

    PubMed

    Jacobi, Matthias; Reischl, Nikolaus; Rönn, Karolin; Magnusson, Robert A; Gautier, Emanuel; Jakob, Roland P

    2016-01-01

    Background. The injured anterior cruciate ligament (ACL) has a limited healing capacity leading to persisting instability. Hypothesis/Purpose. To study if the application of a brace, producing a dynamic posterior drawer force, after acute ACL injury reduces initial instability. Study Design. Cohort study. Methods. Patients treated with the ACL-Jack brace were compared to controls treated with primary ACL reconstruction und controls treated nonsurgically with functional rehabilitation. Measurements included anterior laxity (Rolimeter), clinical scores (Lysholm, Tegner, and IKDC), and MRI evaluation. Patients were followed up to 24 months. Results. Patients treated with the ACL-Jack brace showed a significant improvement of anterior knee laxity comparable to patients treated with ACL reconstruction, whereas laxity persisted after nonsurgical functional rehabilitation. The failure risk (secondary reconstruction necessary) of the ACL-Jack group was however 21% (18 of 86) within 24 months. Clinical scores were similar in all treatment groups. Conclusion. Treatment of acute ACL tears with the ACL-Jack brace leads to improved anterior knee laxity compared to nonsurgical treatment with functional rehabilitation.

  18. [Efficacy and tolerability of cisapride in a new formula of 10 mg effervescent capsules for the treatment of functional dyspepsia].

    PubMed

    Grossi, L; Di Felice, F; Marzio, L

    1993-06-01

    The efficacy and tolerability of Cisapride effervescent granules and a metoclopramide-dimethicone combination were compared double-blind in two comparable groups of 15 patients each with dyspepsia. All patients received three sachets daily of either drug for 6 consecutive weeks. As for efficacy, Cisapride effervescent granules was found to reduce 85% (11/13) of symptoms to a statistically significant extent, as against 42% (5/12) in the reference group. Statistical analysis showed Cisapride effervescent granules to be more effective than the reference drug for 6 out of 11 evaluable symptoms. Mean global improvement was 86% for Cisapride effervescent granules vs 41% for the reference combination. Final judgment by the physician was more favorable for Cisapride effervescent granules than for the reference drug (p < 0.0001). Treatment withdrawal was never necessary and no significant changes of laboratory values were observed. No statistically significant difference between the two treatments as to tolerability was observed. In conclusion, Cisapride effervescent granules was found to have a better risk/benefit ratio than the reference combination.

  19. Lysosomal membrane stability, phagocytosis and tolerance to emersion in the mussel Perna viridis (Bivalvia: Mytilidae) following exposure to acute, sublethal, copper.

    PubMed

    Nicholson, S

    2003-08-01

    The mytilid mussel Perna viridis is distributed throughout the Indo-Pacific region and is potentially a suitable candidate for biological effects (biomarker) monitoring in the subtropics. A suite of cytological and physiological responses to acute (48-72 h) copper exposures of 50-200 microgl(-1) were assessed in order to determine the suitability of P. viridis for marine pollution monitoring. Copper elicited significant destabilisation of the haemocyte lysosomal membranes and also impaired phagocytosis. Survival during emersion following exposure to copper was not related to the experimental copper exposures suggesting that higher metal concentrations may be required to interfere with anaerobic enzymes responsible for suppression of metabolism. Based on this preliminary study, cytological biomarkers evaluated in the haemocytes extracted from P. viridis should prove an effective non-destructive means of assessing metal pollution throughout the mussels subtropical range.

  20. Effects of virtual reality training with modified constraint-induced movement therapy on upper extremity function in acute stage stroke: a preliminary study

    PubMed Central

    Ji, Eun-Kyu; Lee, Sang-Heon

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effects of virtual reality training combined with modified constraint-induced movement therapy on upper extremity motor function recovery in acute stage stroke patients. [Subjects and Methods] Four acute stage stroke patients participated in the study. A multiple baseline single subject experimental design was utilized. Modified constraint-induced movement therapy was used according to the EXplaining PLastICITy after stroke protocol during baseline sessions. Virtual reality training with modified constraint-induced movement therapy was applied during treatment sessions. The Manual Function Test and the Box and Block Test were used to measure upper extremity function before every session. [Results] The subjects’ upper extremity function improved during the intervention period. [Conclusion] Virtual reality training combined with modified constraint-induced movement is effective for upper extremity function recovery in acute stroke patients. PMID:27942143

  1. Effects of virtual reality training with modified constraint-induced movement therapy on upper extremity function in acute stage stroke: a preliminary study.

    PubMed

    Ji, Eun-Kyu; Lee, Sang-Heon

    2016-11-01

    [Purpose] The purpose of this study was to investigate the effects of virtual reality training combined with modified constraint-induced movement therapy on upper extremity motor function recovery in acute stage stroke patients. [Subjects and Methods] Four acute stage stroke patients participated in the study. A multiple baseline single subject experimental design was utilized. Modified constraint-induced movement therapy was used according to the EXplaining PLastICITy after stroke protocol during baseline sessions. Virtual reality training with modified constraint-induced movement therapy was applied during treatment sessions. The Manual Function Test and the Box and Block Test were used to measure upper extremity function before every session. [Results] The subjects' upper extremity function improved during the intervention period. [Conclusion] Virtual reality training combined with modified constraint-induced movement is effective for upper extremity function recovery in acute stroke patients.

  2. Diastolic function in healthy humans: non-invasive assessment and the impact of acute and chronic exercise.

    PubMed

    George, Keith P; Naylor, Louise H; Whyte, Greg P; Shave, Rob E; Oxborough, David; Green, Daniel J

    2010-01-01

    Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultra-endurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.

  3. The potassium transporter OsHAK21 functions in the maintenance of ion homeostasis and tolerance to salt stress in rice.

    PubMed

    Shen, Yue; Shen, Like; Shen, Zhenxing; Jing, Wen; Ge, Hongliang; Zhao, Jiangzhe; Zhang, Wenhua

    2015-12-01

    The intracellular potassium (K(+) ) homeostasis, which is crucial for plant survival in saline environments, is modulated by K(+) channels and transporters. Some members of the high-affinity K(+) transporter (HAK) family are believed to function in the regulation of plant salt tolerance, but the physiological mechanisms remain unclear. Here, we report a significant inducement of OsHAK21 expression by high-salinity treatment and provide genetic evidence of the involvement of OsHAK21 in rice salt tolerance. Disruption of OsHAK21 rendered plants sensitive to salt stress. Compared with the wild type, oshak21 accumulated less K(+) and considerably more Na(+) in both shoots and roots, and had a significantly lower K(+) net uptake rate but higher Na(+) uptake rate. Our analyses of subcellular localizations and expression patterns showed that OsHAK21 was localized in the plasma membrane and expressed in xylem parenchyma and individual endodermal cells (putative passage cells). Further functional characterizations of OsHAK21 in K(+) uptake-deficient yeast and Arabidopsis revealed that OsHAK21 possesses K(+) transporter activity. These results demonstrate that OsHAK21 may mediate K(+) absorption by the plasma membrane and play crucial roles in the maintenance of the Na(+) /K(+) homeostasis in rice under salt stress.

  4. Impact of nutritional status on long-term functional outcomes of post-acute stroke patients in Taiwan.

    PubMed

    Shen, Hsiu-Chu; Chen, Hsueh-Fen; Peng, Li-Ning; Lin, Ming-Hsien; Chen, Liang-Kung; Liang, Chih-Kuang; Lo, Yuk-Keung; Hwang, Shinn-Jang

    2011-01-01

    Nutritional status is important in stroke care, but little is known regarding to the prognostic role of nutritional status on long-term functional outcomes among stroke survivors. The main purpose of this study was to evaluate to the prognostic role of nutritional status on long-term functional outcomes among stroke survivors. Data of acute stroke registry in Kaohsiung Veterans General Hospital were retrieved for analysis. Overall, 483 patients (mean age = 70.7 ± 10.3 years) with first-ever stroke were found. Among them, 95 patients (19.7%) were malnourished at admission, 310 (mean age = 70.4 ± 10.1 years, 63.5% males) survived for 6 months, and 244 (78.7%) had good functional outcomes. Subjects with poor functional outcomes were older (74.7 ± 8.9 vs. 69.0 ± 10.1 years, p < 0.001), more likely to be malnourished (56.2% vs. 26.6%, p < 0.001), to develop pneumonia upon admission (23.3% vs. 12.7%, p = 0.027), had a longer hospital stay (23.5 ± 13.9 vs. 12.5 ± 8.2 days, p < 0.001), had a higher National Institutes of Health Stroke Scale (NIHSS) score (12.9 ± 9.3 vs. 4.9 ± 4.3, p < 0.001), poorer stroke recovery (NIHSS improvement: 6.9% vs. 27.4%, p = 0.005), and poorer functional improvement (Barthel index = BI improvement in the first month: 31.4% vs. 138%, p < 0.001). Older age (odds ratio = OR) = 1.07, 95% confidence interval (CI = 1.03-1.11, p<0.001), baseline NIHSS score (OR = 1.23, 95%CI = 1.15-1.31, p < 0.001) and malnutrition at acute stroke (OR = 2.57, 95%CI: 1.29-5.13, p<0.001) were all independent risk factors for poorer functional outcomes. In conclusion, as a potentially modifiable factor, more attentions should be paid to malnutrition to promote quality of stroke care since the acute stage.

  5. Echocardiographic parameters of right ventricular function predict mortality in acute respiratory distress syndrome: a pilot study

    PubMed Central

    Wadia, Subeer K.; Kovach, Julie; Fogg, Louis; Tandon, Rajive

    2016-01-01

    Abstract Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilot study measuring tricuspid annular plane systolic excursion (TAPSE), Tei index, RV-fractional area change (RV-FAC), pulmonary artery systolic pressure (PASP), and septal shift, reevaluated by an independent blinded cardiologist (JK). Thirty-eight patients were included. Patients were divided on the basis of 30-day survival. Thirty-day mortality was 47%. Survivors were younger than nonsurvivors. Survivors had a higher pH, PaO2∶FiO2 ratio, and TAPSE. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were lower in survivors. TAPSE has the strongest association with increased 30-day mortality from date of TTE. Accordingly, TAPSE has a strong positive correlation with PaO2∶FiO2 ratios, and Tei index has a strong negative correlation with PaO2∶FiO2 ratios. Septal shift was associated with lower PaO2∶FiO2 ratios. Decrease in TAPSE, increase in Tei index, and septal shift were seen in the severe ARDS group. In multivariate logistic regression models, TAPSE maintained a significant association with mortality independent of age, pH, PaO2∶FiO2 ratios, positive end expiratory pressure, PCO2, serum bicarbonate, plateau pressures, driving pressures, APACHE II, SAPS II, and SOFA scores. In conclusion, TAPSE and other TTE parameters should be used as novel predictive indicators for RV dysfunction in ARDS. These parameters can be used as surrogate noninvasive RV hemodynamic measurements to be manipulated to improve mortality in patients with ARDS and contributory RV dysfunction. PMID:27252840

  6. Acute silver toxicity in aquatic animals is a function of sodium uptake rate.

    PubMed

    Bianchini, Adalto; Grosell, Martin; Gregory, Sean M; Wood, Chris M

    2002-04-15

    On the basis of these facts about freshwater fish and invertebrates: (i) the Na+ turnover is a physiological process associated with the gill membranes; (ii) the key mechanism of acute silver toxicity consists of reduction in Na+ uptake by blockade of gill Na+,K+-ATPase; (iii) the mass-specific surface area of the gills depends on animal body mass; and (iv) the gill surface is also the major site of Na+ loss by diffusion, we hypothesized that whole body Na+ uptake rate (i.e., turnover rate) and secondarily body mass would be good predictors of acute silver toxicity. Results obtained from toxicological (LC50 of AgNO3) and physiological (22Na uptake rate) tests performed on juvenile fish (rainbow trout, Oncorhynchus mykiss), early juvenile and adult crayfish (Cambarusdiogenes diogenes), and neonate and adult daphnids (Daphnia magna) in moderately hard water of constant quality support the above hypothesis. Therefore, sensitivity to AgNO3, in terms of either total measured silver or free Ag+, was reliably predicted from the whole body Na+ uptake rate in animals with body mass ranging over 6 orders of magnitude (from micrograms to grams). A positive log-log correlation between acute AgNO3 toxicity and body mass of the same species was also observed. Furthermore, the whole body Na+ uptake rate was inversely related to body mass in unexposed animals. The combination of these last two results explains why the small animals in this study were more sensitive to Ag+ than the larger ones. Taken together, these results clearly point out the possibility of incorporating the Na+ uptake rate into the current version of the Biotic Ligand Model to improve the predictive capacity of this model. In the absence of information on Na+ uptake rate, then body mass may serve as a surrogate.

  7. Major ozonated autohemotherapy promotes the recovery of upper limb motor function in patients with acute cerebral infarction★

    PubMed Central

    Wu, Xiaona; Li, Zhensheng; Liu, Xiaoyan; Peng, Haiyan; Huang, Yongjun; Luo, Gaoquan; Peng, Kairun

    2013-01-01

    Major ozonated autohemotherapy is classically used in treating ischemic disorder of the lower limbs. In the present study, we performed major ozonated autohemotherapy treatment in patients with acute cerebral infarction, and assessed outcomes according to the U.S. National Institutes of Health Stroke Score, Modified Rankin Scale, and transcranial magnetic stimulation motor-evoked potential. Compared with the control group, the clinical total effective rate and the cortical potential rise rate of the upper limbs were significantly higher, the central motor conduction time of upper limb was significantly shorter, and the upper limb motor-evoked potential amplitude was significantly increased, in the ozone group. In the ozone group, the National Institutes of Health Stroke Score was positively correlated with the central motor conduction time and the motor-evoked potential amplitude of the upper limb. Central motor conduction time and motor-evoked potential amplitude of the upper limb may be effective indicators of motor-evoked potentials to assess upper limb motor function in cerebral infarct patients. Furthermore, major ozonated autohemotherapy may promote motor function recovery of the upper limb in patients with acute cerebral infarction. PMID:25206688

  8. Renal impairment and worsening of renal function in acute heart failure: can new therapies help? The potential role of serelaxin.

    PubMed

    Schmieder, Roland E; Mitrovic, Veselin; Hengstenberg, Christian

    2015-08-01

    Renal dysfunction is a frequent finding in patients with acute heart failure (AHF) and an important prognostic factor for adverse outcomes. Worsening of renal function occurs in 30-50% of patients hospitalised for AHF, and is associated with increased mortality, prolonged hospital stay and increased risk of readmission. Likely mechanisms involved in the decrease in renal function include impaired haemodynamics and activation of neurohormonal factors, such as the renin-angiotensin-aldosterone system, the sympathetic nervous system and the arginine-vasopressin system. Additionally, many drugs currently used to treat AHF have a detrimental effect on renal function. Therefore, pharmacotherapy for AHF should carefully take into account any potential complications related to renal function. Serelaxin, currently in clinical development for the treatment of AHF is a recombinant form of human relaxin-2, identical in structure to the naturally occurring human relaxin-2 peptide hormone that mediates cardiac and renal adaptations during pregnancy. Data from both pre-clinical and clinical studies indicate a potentially beneficial effect of serelaxin on kidney function. In this review, we discuss the mechanisms and impact of impairment of renal function in AHF, and the potential benefits of new therapies, such as serelaxin, in this context.

  9. Vasoactive intestinal peptide (VIP)-mediated expression and function of steroidogenic acute regulatory protein (StAR) in granulosa cells.

    PubMed

    Kowalewski, Mariusz P; Dyson, Matthew T; Boos, Alois; Stocco, Douglas M

    2010-10-26

    VIP is a peptide hormone capable of activating the cAMP/PKA pathway and modifying gonadal steroidogenic capacity. Less is known about the molecular mechanisms of VIP-mediated steroidogenesis and its role in regulating the steroidogenic acute regulatory protein (STAR). We examined the impact of VIP on STAR expression and function in immortalized (KK1) and primary mouse granulosa cells, where VIP strongly upregulated STAR expression and steroidogenesis. Inhibitors of the PKA and PKC pathways suggested that both are activated by VIP. VIP did not efficiently phosphorylate STAR (P-STAR); however, VIP together with cAMP-analogs that activate Type II PKA increased P-STAR and further increased steroidogenesis. Our results suggest that VIP-induced STAR expression and function in granulosa cells result from the preferential activation of Type I PKA. Furthermore, the PKA and PKC pathways appear to converge at regulating VIP-mediated Star transcription and translation.

  10. Renal progenitors derived from human iPSCs engraft and restore function in a mouse model of acute kidney injury

    PubMed Central

    Imberti, Barbara; Tomasoni, Susanna; Ciampi, Osele; Pezzotta, Anna; Derosas, Manuela; Xinaris, Christodoulos; Rizzo, Paola; Papadimou, Evangelia; Novelli, Rubina; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina

    2015-01-01

    Acute kidney injury (AKI) is one of the most relevant health issues, leading to millions of deaths. The magnitude of the phenomenon remarks the urgent need for innovative and effective therapeutic approaches. Cell-based therapy with renal progenitor cells (RPCs) has been proposed as a possible strategy. Studies have shown the feasibility of directing embryonic stem cells or induced Pluripotent Stem Cells (iPSCs) towards nephrogenic intermediate mesoderm and metanephric mesenchyme (MM). However, the functional activity of iPSC-derived RPCs has not been tested in animal models of kidney disease. Here, through an efficient inductive protocol, we directed human iPSCs towards RPCs that robustly engrafted into damaged tubuli and restored renal function and structure in cisplatin-mice with AKI. These results demonstrate that iPSCs are a valuable source of engraftable cells with regenerative activity for kidney disease and create the basis for future applications in stem cell-based therapy. PMID:25744951

  11. Genomic and functional analysis of the host response to acute simian varicella infection in the lung

    PubMed Central

    Arnold, Nicole; Girke, Thomas; Sureshchandra, Suhas; Nguyen, Christina; Rais, Maham; Messaoudi, Ilhem

    2016-01-01

    Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host. PMID:27677639

  12. Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

    PubMed Central

    Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

    2014-01-01

    Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

  13. Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

    PubMed

    Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

    2016-07-21

    Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

  14. Acute effects of beer on endothelial function and haemodynamics: a single-blind, cross-over study in healthy volunteers