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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

    2016-01-01

    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

  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. Tolerance bands for functional data.

    PubMed

    Rathnayake, Lasitha N; Choudhary, Pankaj K

    2016-06-01

    Often the object of inference in biomedical applications is a range that brackets a given fraction of individual observations in a population. A classical estimate of this range for univariate measurements is a "tolerance interval." This article develops its natural extension for functional measurements, a "tolerance band," and proposes a methodology for constructing its pointwise and simultaneous versions that incorporates both sparse and dense functional data. Assuming that the measurements are observed with noise, the methodology uses functional principal component analysis in a mixed model framework to represent the measurements and employs bootstrapping to approximate the tolerance factors needed for the bands. The proposed bands also account for uncertainty in the principal components decomposition. Simulations show that the methodology has, generally, acceptable performance unless the data are quite sparse and unbalanced, in which case the bands may be somewhat liberal. The methodology is illustrated using two real datasets, a sparse dataset involving CD4 cell counts and a dense dataset involving core body temperatures. PMID:26574904

  5. Sleep restriction acutely impairs glucose tolerance in rats.

    PubMed

    Jha, Pawan K; Foppen, Ewout; Kalsbeek, Andries; Challet, Etienne

    2016-06-01

    Chronic sleep curtailment in humans has been related to impairment of glucose metabolism. To better understand the underlying mechanisms, the purpose of the present study was to investigate the effect of acute sleep deprivation on glucose tolerance in rats. A group of rats was challenged by 4-h sleep deprivation in the early rest period, leading to prolonged (16 h) wakefulness. Another group of rats was allowed to sleep during the first 4 h of the light period and sleep deprived in the next 4 h. During treatment, food was withdrawn to avoid a postmeal rise in plasma glucose. An intravenous glucose tolerance test (IVGTT) was performed immediately after the sleep deprivation period. Sleep deprivation at both times of the day similarly impaired glucose tolerance and reduced the early-phase insulin responses to a glucose challenge. Basal concentrations of plasma glucose, insulin, and corticosterone remained unchanged after sleep deprivation. Throughout IVGTTs, plasma corticosterone concentrations were not different between the control and sleep-deprived group. Together, these results demonstrate that independent of time of day and sleep pressure, short sleep deprivation during the resting phase favors glucose intolerance in rats by attenuating the first-phase insulin response to a glucose load. In conclusion, this study highlights the acute adverse effects of only a short sleep restriction on glucose homeostasis. PMID:27354542

  6. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  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. The role of experiential avoidance in acute pain tolerance: a laboratory test.

    PubMed

    Feldner, Matthew T; Hekmat, Hamid; Zvolensky, Michael J; Vowles, Kevin E; Secrist, Zachary; Leen-Feldner, Ellen W

    2006-06-01

    The present investigation examined the role of experiential avoidance in terms of acute pain tolerance and subsequent recovery. Seventy nonclinical participants completed the Acceptance and Action Questionnaire and underwent a well-established cold pressor task. Results indicated that individuals reporting higher levels of experiential avoidance had lower pain endurance and tolerance and recovered more slowly from this particular type of aversive event. Consistent with theoretical prediction, these findings suggest that experiential avoidance may play a role in tolerance of acute pain. PMID:15882839

  9. The relationship between NMDA receptor function and the high ammonia tolerance of anoxia-tolerant goldfish.

    PubMed

    Wilkie, Michael P; Pamenter, Matthew E; Duquette, Stephanie; Dhiyebi, Hadi; Sangha, Navjeet; Skelton, Geoffrey; Smith, Matthew D; Buck, Leslie T

    2011-12-15

    Acute ammonia toxicity in vertebrates is thought to be characterized by a cascade of deleterious events resembling those associated with anoxic/ischemic injury in the central nervous system. A key event is the over-stimulation of neuronal N-methyl-D-aspartate (NMDA) receptors, which leads to excitotoxic cell death. The similarity between the responses to acute ammonia toxicity and anoxia suggests that anoxia-tolerant animals such as the goldfish (Carassius auratus Linnaeus) may also be ammonia tolerant. To test this hypothesis, the responses of goldfish were compared with those of the anoxia-sensitive rainbow trout (Oncorhynchus mykiss Walbaum) during exposure to high external ammonia (HEA). Acute toxicity tests revealed that goldfish are ammonia tolerant, with 96 h median lethal concentration (LC(50)) values of 199 μmol l(-1) and 4132 μmol l(-1) for NH(3) and total ammonia ([T(Amm)]=[NH(3)]+[NH(4)(+)]), respectively. These values were ~5-6 times greater than corresponding NH(3) and T(Amm) LC(50) values measured in rainbow trout. Further, the goldfish readily coped with chronic exposure to NH(4)Cl (3-5 mmol l(-1)) for 5 days, despite 6-fold increases in plasma [T] to ~1300 μmol l(-1) and 3-fold increases in brain [T(Amm)] to 6700 μmol l(-1). Muscle [T(Amm)] increased by almost 8-fold from ~900 μmol kg(-1) wet mass (WM) to greater than 7000 μmol kg(-1) WM by 48 h, and stabilized. Although urea excretion rates (J(Urea)) increased by 2-3-fold during HEA, the increases were insufficient to offset the inhibition of ammonia excretion that occurred, and increases in urea were not observed in the brain or muscle. There was a marked increase in brain glutamine concentration at HEA, from ~3000 μmol kg(-1) WM to 15,000 μmol kg(-1) WM after 48 h, which is consistent with the hypothesis that glutamine production is associated with ammonia detoxification. Injection of the NMDA receptor antagonists MK801 (0.5-8 mg kg(-1)) or ethanol (1-8 mg kg(-1)) increased trout

  10. Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia.

    PubMed Central

    Hayreh, S. S.; Weingeist, T. A.

    1980-01-01

    Ophthalmoscopic, fluorescein angiographic, electrophysiological, and morphological studies on 63 eyes of rhesus monkeys with acute transient experimental occlusion of the central artery of the retina (OCAR) showed that the retina suffered irreparable damage after ischaemia of 105 minutes but recovered well after ischaemia of 97-98 minutes. The tolerance time of the brain to acute transient ischaemia is many times shorter than that of the retina. The metabolism of ischaemic neurones (in the retina and brain) is discussed with a view to explaining this difference, and also the various factors possibly responsible for the retina's longer tolerance to ischaemia, as compared to the brain. PMID:7426553

  11. Abundance of plasma antioxidant proteins confers tolerance to acute hypobaric hypoxia exposure.

    PubMed

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

    2013-09-01

    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 cardiovascular exercise and executive control function.

    PubMed

    Hillman, Charles H; Snook, Erin M; Jerome, Gerald J

    2003-06-01

    Acute cardiovascular exercise effects on cognitive function were examined using an executive control task by comparing neuroelectric and behavioral performance at baseline with post-exercise in 20 undergraduates. A within-subjects design was used to assess the P3 component of an event-related brain potential (ERP) and behavioral performance using a task that varied the amount of executive control required. The baseline session involved participation on the Eriksen flankers task followed by a graded maximal exercise test to measure cardiovascular fitness. The exercise session consisted of a 30-min acute bout of exercise on a treadmill followed by the Eriksen flankers task after heart rate returned to within 10% of pre-exercise levels. Across midline recordings sites, results indicated larger P3 amplitude following acute exercise compared to baseline. Shorter P3 latency was observed during the baseline Eriksen flankers task for the neutral compared to the incompatible condition; an effect not found following the acute bout of exercise. These findings suggest that acute bouts of cardiovascular exercise affect neuroelectric processes underlying executive control through the increased allocation of neuroelectric resources and through changes in cognitive processing and stimulus classification speed. PMID:12798990

  13. 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. PMID:23500188

  14. Intrathecal morphine attenuates acute opioid tolerance secondary to remifentanil infusions during spinal surgery in adolescents

    PubMed Central

    Tripi, Paul A; Kuestner, Matthew E; Poe-Kochert, Connie S; Rubin, Kasia; Son-Hing, Jochen P; Thompson, George H; Tobias, Joseph D

    2015-01-01

    Introduction The unique pharmacokinetic properties of remifentanil with a context-sensitive half-life unaffected by length of infusion contribute to its frequent use during anesthetic management during posterior spinal fusion in children and adolescents. However, its intraoperative administration can lead to increased postoperative analgesic requirements, which is postulated to be the result of acute opioid tolerance with enhancement of spinal N-methyl-D-aspartate receptor function. Although strategies to prevent or reduce tolerance have included the coadministration of longer acting opioids or ketamine, the majority of these studies have demonstrated little to no benefit. The current study retrospectively evaluates the efficacy of intrathecal morphine (ITM) in preventing hyperalgesia following a remifentanil infusion. Methods We retrospectively analyzed 54 patients undergoing posterior spinal fusion with segmental spinal instrumentation, to evaluate the effects of ITM on hyperalgesia from remifentanil. Patients were divided into two groups based on whether they did or did not receive remifentanil during the surgery: no remifentanil (control group) (n=27) and remifentanil (study group) (n=27). Data included demographics, remifentanil dose and duration, Wong–Baker visual analog scale postoperative pain scores, and postoperative intravenous morphine consumption in the first 48 postoperative hours. Results The demographics of the two study groups were similar. There were no differences in the Wong–Baker visual analog scale pain scores in the postanesthesia care unit and on postoperative days 1 and 3. Pain scores were higher in the remifentanil group on postoperative day 2 (2.9 vs 3.8). Postoperative morphine requirements were similar between the two groups (0.029 vs 0.017 mg/kg/48 h for the control group and the study group, respectively). Conclusion In patients receiving preincisional ITM during spinal surgery, intraoperative remifentanil does not increase

  15. Acute effects of exposure to orthochlorobenzylidene malononitrile (CS) and the development of tolerance

    PubMed Central

    Beswick, F. W.; Holland, P.; Kemp, K. H.

    1972-01-01

    Beswick, F. W., Holland, P., and Kemp, K. H. (1972).Brit. J. industr. Med.,29, 298-306. Acute effects of exposure to orthochlorobenzylidene malononitrile (CS) and the development of tolerance. Of the many compounds capable of producing irritation of the eyes and upper respiratory tract two, ω-chloroacetophenone and orthochlorobenzylidene malononitrile (CS), have been used as riot control agents. The latter, CS, has been in use for more than 10 years and is currently still in service. When dispersed as a smoke consisting of 1-micron diameter particles CS will produce lachrymation and pain and discomfort in the upper respiratory tract and chest. Exposed individuals become apprehensive and highly motivated to escape from the smoke. Recovery from these effects occurs within minutes of the affected individual reaching fresh air. The present study reports the effects produced by CS aerosol on 35 healthy male volunteers who were exposed in such a way that the total dose of the agent received by each man was greater than that which he might have received in an actual riot; this was achieved by taking advantage of the fact that adaptation to the effects of CS occurs if exposure is gradual and to low concentrations. In addition to the clinical observations, cardiological, respiratory, and biochemical observations were made. No abnormalities were observed in the electrocardiogram, respiratory function tests or the blood biochemistry and cell constitution. Such changes that were observed could be ascribed to the emotional stress and discomfort of the experiment. PMID:5044601

  16. εPKC confers acute tolerance to cerebral ischemic reperfusion injury

    PubMed Central

    Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

    2008-01-01

    In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

  17. 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

  18. 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.

  19. 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

  20. Effects of Acute Alcohol Tolerance on Perceptions of Danger and Willingness to Drive after Drinking

    PubMed Central

    Amlung, Michael T.; Morris, David H.; McCarthy, Denis M.

    2014-01-01

    Rationale Drinking and driving is associated with elevated rates of motor vehicle accidents and fatalities. Previous research suggests that alcohol impairs judgments about the dangers of risky behaviors; however, how alcohol affects driving-related judgments is less clear. Impairments have also been shown to differ across limbs of the blood alcohol concentration (BAC) curve, which is known as acute tolerance. Objectives Examine whether perceptions about the dangerousness of driving after drinking and willingness to drive differed across ascending and descending limbs of the BAC curve. Test whether reductions in perceived danger were associated with willingness to drive on the descending limb. Methods Fifty-six participants were randomly assigned to receive either a moderate dose of alcohol (peak BAC = 0.10 g%) or placebo. We assessed perceived dangerousness and willingness to drive at matched BACs (~0.067-0.068 g%) on the ascending and descending limbs. Results Both perceived danger and willingness to drive showed acute tolerance in the alcohol group. Participants judged driving to be significantly less dangerous and were more willing to drive on the descending limb compared to the ascending limb. The magnitude of change in perceived danger significantly predicted willingness to drive on the descending limb. Conclusions Decreased impairment associated with acute tolerance may lead individuals to underestimate the dangerousness of driving after drinking and in turn make poor decisions regarding driving. This study further emphasizes the descending limb as a period of increased risk and offers support for enhancing prevention efforts by targeting drivers at declining BAC levels. PMID:24752657

  1. [Intramuscular etofenamate in the treatment of acute lumbago. Effectiveness and tolerance in comparison with intramuscular diclofenac-Na].

    PubMed

    Stratz, T

    1990-04-30

    In a controlled multi-center single-blind study, the relative efficacy and tolerance of i.m. injectable preparations of etofenamat(e) and diclofenac sodium were investigated in 96 patients with acute lumbago. Treatment resulted in obvious improvement in function and reduction in pain, no statistical difference being found between the two drugs. In 43% of the patients treated with etofenamat(e) and 27% of those receiving diclofenac, the final medical report indicated very good therapeutic results. Under etofenamat(e) i.m. therapy, no side effects occurred, and in no case did treatment have to be discontinued. Under diclofenac, two patients experienced adverse reactions, one allergic exanthema, and the other itching and a sensation of heat. A further patient experienced no improvement after the first injection and discontinued treatment. PMID:2142116

  2. Pharmacokinetics and acute tolerance of a double virus inactivated plasma derived factor VIII concentrate.

    PubMed

    Saez, A; Bosh, N; Boadas, N; Arguello, A; Horvat, D; Dinapoli, G; Lisciani, R

    1999-07-01

    To further reduce the risk of possible viral disease transmission, an additional virucidal step was performed in the manufacturing process of a solvent/detergent treated factor VIII concentrate, which consisted of heating the lyophilized preparation at 100 degrees C for 30 min (Emoclot DI; ISI, Italy). Because thermal treatment may modify factor VIII bioavailability, the pharmacokinetic parameters and the acute tolerance of the single viral inactivated concentrate (preparation A) were compared with that of the double viral inactivated one (preparation B). Fifteen patients with severe haemophilia A and positive for HAV Ab were enrolled in a double-blind cross-over study and injected with 32.5 IU kg-1 of preparation A and 27 IU kg-1 of the preparation B. No significant differences between terminal half-life, area under the curve/dose, clearance/kg, volume of distribution at the steady state, in vivo recovery and acute tolerance of the two preparations was observed. The only statistical difference was restricted to Cmax. PMID:10469180

  3. Efficacy and Tolerability of 5- vs 10-Day Cefixime Therapy in Acute Exacerbations of Chronic Bronchitis.

    PubMed

    Lorenz, J; Steinfeld, P; Drath, L; Keienburg, T; Troester, K

    1998-01-01

    The efficacy and tolerability of oral cefixime 400mg once daily for 5 days was compared with standard 10-day therapy in a multicentre, double-blind, randomised, controlled clinical trial of 222 patients with acute exacerbations of chronic bronchitis. Clinical and bacteriological efficacy were assessed after 6, 11 and 30 days. A total of 167 patients were evaluable for efficacy on a per-protocol basis. Clinical efficacy (cure or improvement based on the quality and quantity of expectorated sputum and symptoms of dyspnoea) at day 11 was statistically equivalent (p < 0.01) between the treatment groups, with a successful clinical response achieved in 91% (5-day) and 89% (10-day) of patients. Bacteriological efficacy was also similar with 5- and 10-day treatment. During treatment, more patients reported an adverse event possibly or probably related to the study medication in the 10-day than in the 5-day treatment group (19 vs 14%). However, this difference was not statistically significant. Oral cefixime 400mg once daily is an effective and well tolerated treatment for acute exacerbations of chronic bronchitis. Short-term (5-day) therapy offers clinical efficacy similar to that of standard (10-day) therapy. PMID:18370461

  4. Inflammatory stimuli acutely modulate peripheral taste function.

    PubMed

    Kumarhia, Devaki; He, Lianying; McCluskey, Lynnette Phillips

    2016-06-01

    Inflammation-mediated changes in taste perception can affect health outcomes in patients, but little is known about the underlying mechanisms. In the present work, we hypothesized that proinflammatory cytokines directly modulate Na(+) transport in taste buds. To test this, we measured acute changes in Na(+) flux in polarized fungiform taste buds loaded with a Na(+) indicator dye. IL-1β elicited an amiloride-sensitive increase in Na(+) transport in taste buds. In contrast, TNF-α dramatically and reversibly decreased Na(+) flux in polarized taste buds via amiloride-sensitive and amiloride-insensitive Na(+) transport systems. The speed and partial amiloride sensitivity of these changes in Na(+) flux indicate that IL-1β and TNF-α modulate epithelial Na(+) channel (ENaC) function. A portion of the TNF-mediated decrease in Na(+) flux is also blocked by the TRPV1 antagonist capsazepine, although TNF-α further reduced Na(+) transport independently of both amiloride and capsazepine. We also assessed taste function in vivo in a model of infection and inflammation that elevates these and additional cytokines. In rats administered systemic lipopolysaccharide (LPS), CT responses to Na(+) were significantly elevated between 1 and 2 h after LPS treatment. Low, normally preferred concentrations of NaCl and sodium acetate elicited high response magnitudes. Consistent with this outcome, codelivery of IL-1β and TNF-α enhanced Na(+) flux in polarized taste buds. These results demonstrate that inflammation elicits swift changes in Na(+) taste function, which may limit salt consumption during illness. PMID:27009163

  5. Chronic functional ethanol tolerance in mice influenced by body temperature during acquisition

    SciTech Connect

    Alkana, R.L.; Bejanian, M.; Syapin, P.J.; Finn, D.A.

    1987-07-27

    Previous studies have found that body temperature during intoxication influences brain sensitivity to ethanol with the sensitivity being less at cool than at warm body temperatures. If this effect of temperature reflects alterations in the acute membrane perturbing action of ethanol, as suggested by in vitro studies, then body temperature reduction during tolerance acquisition should reduce the effectiveness of a given ethanol concentration and, in turn, should reduce the development of chronic functional ethanol tolerance. To test this hypothesis, adult drug-naive C57BL/6J mice were injected i.p. once daily for five days with 3.6 g/kg ethanol and were exposed to 34C or 25C for five hours following injection. On day 6, both ethanol acquisition groups and naive mice were injected i.p. with 4.0 g/kg ethanol and exposed to 25C. During acquisition, the group exposed to 34C had significantly higher body temperatures than the mice exposed to 25C, and there were no statistically significant differences in blood ethanol concentrations between treatment conditions. The extent of tolerance on day 6 was significantly greater in the 34C acquisition group than in the 25C acquisition group. 31 references, 1 figure, 2 tables.

  6. A review of the clinical efficacy and tolerability of almotriptan in acute migraine.

    PubMed

    Dodick, David W

    2003-07-01

    Almotriptan is a serotonin (5-hydroxytryptamine, 5HT)(1B/1D)-receptor agonist approved for the acute treatment of migraine. In 3500 acute migraine patients enrolled in short-term trials and 1500 patients in long-term open-label trials, almotriptan 12.5 mg was effective and well-tolerated. Almotriptan maintains a consistency of response across three attacks and patients continue to respond to almotriptan for up to 1 year. Results from two comparative studies and a meta-analysis of 53 randomised, placebo-controlled studies of oral triptans in > 24,000 patients, confirm that almotriptan 12.5 mg demonstrates comparable efficacy with sumatriptan 50 and 100 mg. The incidence of treatment-related adverse events with almotriptan is comparable to that of placebo and significantly lower than that with sumatriptan. Drug-drug interaction studies indicate that almotriptan may be coadministered with other commonly prescribed drugs without dose modification. Almotriptan can be recommended as first-line treatment for acute migraine. PMID:12831340

  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. Tolerance of acute hypoxia while performing operator activity and after a prolonged period under altered gas environment conditions

    NASA Technical Reports Server (NTRS)

    Bloshchinskiy, P.; Golets, L.; Agadzhanyan, N. A.; Sergiyenko, A. V.

    1974-01-01

    Human and animal studies on physiological factors in resistance to acute hypoxia are elaborated. Results show that tolerance of acute hypoxia depends on gas composition and temperature in a sealed cabin, on the length of the stay and motive regime, and on the kind of operator and professional activity. After preliminary adaptation to hypoxia, resistance of the body increases not only to insufficiency of oxygen in inspired air, but also to the effects of other extremum factors of manned space flight.

  9. Acute pain management in opioid-tolerant patients: a growing challenge.

    PubMed

    Huxtable, C A; Roberts, L J; Somogyi, A A; MacIntyre, P E

    2011-09-01

    In Australia and New Zealand, in parallel with other developed countries, the number of patients prescribed opioids on a long-term basis has grown rapidly over the last decade. The burden of chronic pain is more widely recognised and there has been an increase in the use of opioids for both cancer and non-cancer indications. While the prevalence of illicit opioid use has remained relatively stable, the diversion and abuse of prescription opioids has escalated, as has the number of individuals receiving methadone or buprenorphine pharmacotherapy for opioid addiction. As a result, the proportion of opioid-tolerant patients requiring acute pain management has increased, often presenting clinicians with greater challenges than those faced when treating the opioid-naïve. Treatment aims include effective relief of acute pain, prevention of drug withdrawal, assistance with any related social, psychiatric and behavioural issues, and ensuring continuity of long-term care. Pharmacological approaches incorporate the continuation of usual medications (or equivalent), short-term use of sometimes much higher than average doses of additional opioid, and prescription of non-opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to limit duration of additional opioid use. Legislative requirements may restrict which drugs can be prescribed at the time of hospital discharge. At all stages, there should be appropriate and regular consultation and liaison with the patient, other treating teams and specialist services. PMID:21970125

  10. Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine.

    PubMed

    Allais, G; Acuto, G; Cabarrocas, X; Esbri, R; Benedetto, C; Bussone, G

    2006-05-01

    Menstrual migraine (MM) attacks are a challenge for the headache specialist, because they are particularly difficult to treat. Almotriptan is a second-generation triptan successfully used for the acute treatment of migraine. No data on the efficacy and safety of almotriptan in MM treatment have been published previously. The objective was to evaluate the efficacy and tolerability of almotriptan in the symptomatic treatment of MM attacks and to compare these parameters to those obtained with zolmitriptan, another second-generation triptan. Data from a multicentre, multinational, randomised, double-blind, parallel clinical trial, conducted at 118 centres in 9 European countries, to evaluate the efficacy and tolerability of almotriptan 12.5 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine were analysed retrospectively. Of the 1061 patients included, 902 were women and 255 of these treated a MM attack: 136 with almotriptan and 119 with zolmitriptan. No significant difference between the two treatments was found. Two hours after dosing, 67.9% of almotriptan-treated and 68.6% of zolmitriptan-treated patients had obtained pain relief; while 44.9% and 41.2%, respectively, were pain free. Recurrence rates 2-24 h after dosing were 32.8% for almotriptan and 34.7% for zolmitriptan. Adverse events in the 24 h after dosing were reported by 19.8% of those taking almotriptan and 23.1% of those taking zolmitriptan. In conclusion, almotriptan is effective and safe in the treatment of MM attacks. PMID:16688629

  11. 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.

  12. 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.

  13. Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1

    PubMed Central

    Yang, Nai-Bin; Ni, Shun-Lan; Li, Shan-Shan; Zhang, Sai-Nan; Hu, Dan-Ping; Lu, Ming-Qin

    2015-01-01

    High mobility group box 1 (HMGB1) has been widely reported to mediate damage caused by inflammatory responses. The aim of our study is to investigate the role of HMGB1 in endotoxin tolerance (ET) alleviating inflammation of acute liver failure (ALF) rats and its possible signaling mechanism. To mimic ET, male Sprague-Dawley rats were pretreated with low dose of lipopolysaccharide (LPS) (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent ALF induction. ALF was induced by intraperitoneal administration of D-GalN/LPS. ET induced by LPS pretreatment significantly improved the survival rate of ALF rats. Moreover, after ALF induction, ET+ALF rats exhibited lower serum enzyme (ALT, AST and TBiL) levels, lower production of inflammatory cytokines (IL-6, TNF-a and HMGB1) and more minor liver histopathological damage than ALF rats. ET+ALF rats showed enhanced expression levels of HMGB1, decreased levels of STAT1 and p-STAT1, augmented expression of SOCS1 in liver tissues than ALF rats. These results indicated that ET induced by low-dose LPS pretreatment may alleviate inflammation and liver injury in experimental acute liver failure rats mainly through inhibition of hepatic HMGB1 translocation and release. PMID:26464648

  14. Endotoxin tolerance alleviates experimental acute liver failure via inhibition of high mobility group box 1.

    PubMed

    Yang, Nai-Bin; Ni, Shun-Lan; Li, Shan-Shan; Zhang, Sai-Nan; Hu, Dan-Ping; Lu, Ming-Qin

    2015-01-01

    High mobility group box 1 (HMGB1) has been widely reported to mediate damage caused by inflammatory responses. The aim of our study is to investigate the role of HMGB1 in endotoxin tolerance (ET) alleviating inflammation of acute liver failure (ALF) rats and its possible signaling mechanism. To mimic ET, male Sprague-Dawley rats were pretreated with low dose of lipopolysaccharide (LPS) (0.1 mg/kg once a day intraperitoneally for consecutive five days) before subsequent ALF induction. ALF was induced by intraperitoneal administration of D-GalN/LPS. ET induced by LPS pretreatment significantly improved the survival rate of ALF rats. Moreover, after ALF induction, ET+ALF rats exhibited lower serum enzyme (ALT, AST and TBiL) levels, lower production of inflammatory cytokines (IL-6, TNF-a and HMGB1) and more minor liver histopathological damage than ALF rats. ET+ALF rats showed enhanced expression levels of HMGB1, decreased levels of STAT1 and p-STAT1, augmented expression of SOCS1 in liver tissues than ALF rats. These results indicated that ET induced by low-dose LPS pretreatment may alleviate inflammation and liver injury in experimental acute liver failure rats mainly through inhibition of hepatic HMGB1 translocation and release. PMID:26464648

  15. Synaptic action of ethanol on cerebellar auditory granule cells reveals acute tolerance

    SciTech Connect

    Huang, C.M.; Liu, G.; Huang, R.H. )

    1991-03-11

    The cerebellum is very sensitive to acute intoxication by ethanol. The authors have recorded electrophysiological responses of granule cells to auditory stimulation from the posterior cerebellar vermis of cats before and after a relatively low dose of ethanol. Auditory responses of granule cells were severely inhibited by ethanol at a transient, peak ethanol concentration of 15-18 mM in the cerebrospinal fluid (CSF). Thereafter, the clearance of ethanol from CSF followed an exponential time course, with 50% of the CSF ethanol being cleared with every passing hour. Auditory responses of granule cells returned to control levels within 60-90 minutes, despite the presence of a DSF ethanol concentration at 8-10mM, indicating acute tolerance. Moreover, a second, identical dose of ethanol, delivered two hours after the first dose produced an attenuated inhibition in the auditory response of cerebellar granule cells. The inhibition took a longer time to be evident but a shorter time to recover than that followed by the first dose of ethanol.

  16. The choice of the intravenous fluid influences the tolerance of acute normovolemic anemia in anesthetized domestic pigs

    PubMed Central

    2012-01-01

    Introduction The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O2) supply during acute normovolemic anemia has not been investigated so far. Methods Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit). Hbcrit was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O2-consumption (VO2). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hbcrit, secondary endpoints were parameters of central hemodynamics, O2 transport and tissue oxygenation. Results In each animal, normovolemia was maintained throughout the protocol. Hbcrit was met at 3.7 ± 0.6 g/dl (RS), 3.0 ± 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 ± 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 ± 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO2), and O2 extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hbcrit. Conclusions The choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e.g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function. PMID:22546374

  17. Evaluating the therapeutic efficacy, tolerability, and safety of an aqueous extract of Costus speciosus rhizome in acute pharyngitis and acute tonsillitis

    PubMed Central

    Bakhsh, Zainab A.; Al-Khatib, Talal A.; Al-Muhayawi, Saad M.; ElAssouli, Sufian M.; Elfiky, Iman A.; Mourad, Samiha A.

    2015-01-01

    Objectives: To determine the efficacy, tolerability, and safety of an aqueous extract of Costus speciosus (C. speciosus) rhizome in pediatric and adult patients suffering from acute pharyngitis and tonsillitis as an alternative to antibiotics use. Methods: This pilot cohort trial was conducted at King Abdulaziz University in Saudi Arabia between May and December 2014, among 15 patients with acute pharyngitis and tonsillitis who were administered nasal drops of aqueous extract of C. speciosus rhizome at a dose of 15-30 drops every 8 hours for 3 days. The primary outcome measure was the clinical improvement and remission rate within the first 5 days. Results: The administration of C. speciosus resulted in an improvement in acute symptoms in 60% of the patients treated within the first 24 hours, and remission rate of 93% by day 5, without any recorded adverse effects. Conclusion: This study revealed a significant efficacy of the aqueous extract of C. speciosus rhizome in acute pharyngitis and tonsillitis. PMID:26219454

  18. Low tolerance and dependence liabilities of etizolam: molecular, functional, and pharmacological correlates.

    PubMed

    Sanna, Enrico; Busonero, Fabio; Talani, Giuseppe; Mostallino, Maria Cristina; Mura, Maria Luisa; Pisu, Maria Giuseppina; Maciocco, Elisabetta; Serra, Mariangela; Biggio, Giovanni

    2005-09-01

    The effects of prolonged exposure to and subsequent withdrawal of the thienotriazolobenzodiazepine etizolam on gamma-aminobutyric acid (GABA) type A receptor gene expression and function were compared with those of the benzodiazepine lorazepam. Exposure of rat hippocampal neurons in culture to 10 microM etizolam for 5 days reduced the amounts of alpha5 and gamma2S receptor subunit mRNAs, whereas etizolam withdrawal was associated with a persistent reduction in gamma2S mRNA and an increase in alpha2 and alpha3 mRNAs. Neither chronic exposure to nor withdrawal of etizolam affected the acute modulatory effects of etizolam or lorazepam on GABA-evoked Cl- current. Treatment with 10 microM lorazepam for 5 days reduced the amounts of alpha1 and gamma2S subunit mRNAs and increased that of alpha3 mRNA, whereas lorazepam withdrawal was associated with persistence of the changes in alpha3 and gamma2S mRNAs and an increase in alpha2 and alpha4 mRNAs. Parallel changes in the abundance of alpha1 and alpha4 subunit proteins induced by chronic exposure to and withdrawal of lorazepam, but not etizolam, were detected by immunocytofluorescence analysis. Chronic lorazepam treatment resulted in a reversible reduction in the modulatory efficacy of this drug and conferred on flumazenil the ability to potentiate GABA-evoked Cl- current. The anticonvulsant action of etizolam was not altered in mice chronically treated with this drug, whereas lorazepam-treated animals became tolerant to the acute anticonvulsant effect of this benzodiazepine. These data suggest that etizolam is endowed with a reduced liability to induce tolerance and dependence compared with classical benzodiazepines. PMID:16107249

  19. 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…

  20. Dynamic regulation of metabolic efficiency explains tolerance to acute hypoxia in humans.

    PubMed

    Schiffer, Tomas A; Ekblom, Björn; Lundberg, Jon O; Weitzberg, Eddie; Larsen, Filip J

    2014-10-01

    The maximum power principle dictates that open biological systems tend to self-organize to a level of efficiency that allows maximal power production. Applying this principle to cellular energetics and whole-body physiology would suggest that for every metabolic challenge, an optimal efficiency exists that maximizes power production. On exposure to hypoxia, it would be favorable if metabolic efficiency would rapidly adjust so as to better preserve work performance. We tested this idea in humans by measuring metabolic efficiency and exercise tolerance under normoxic (Fio2=20.9%) and hypoxic (Fio2=16%) conditions, where Fio2 is fraction of inhaled oxygen. The results were compared with respirometric analyses of skeletal muscle mitochondria from the same individuals. We found that among healthy trained subjects (n=14) with a wide range of metabolic efficiency (ME), those with a high ME during normoxic exercise were able to better maintain exercise capacity (Wmax) in hypoxia. On hypoxic exposure, these subjects acutely decreased their efficiency from 19.2 to 17.4%, thereby likely shifting it closer to a degree of efficiency where maximal power production is achieved. In addition, mitochondria from these subjects had a lower intrinsic respiration compared to subjects that showed a large drop in Wmax in hypoxia An acute shift in efficiency was also demonstrated in isolated mitochondria exposed to physiological levels of hypoxia as P/O ratio increased from 0.9 to 1.3 with hypoxic exposure. These findings suggest the existence of a physiological adaptive response by which metabolic efficiency is dynamically optimized to maximize power production. PMID:24970395

  1. 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

  2. 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. PMID:26438355

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

    PubMed

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

    2015-02-01

    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 Ca(2+) 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

  4. 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

  5. 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

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

    PubMed

    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 × 10(6) 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

  7. Application of an Alcohol Clamp Paradigm to Examine Inhibitory Control, Subjective Responses and Acute Tolerance in Late Adolescence

    PubMed Central

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

    2015-01-01

    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 80mg% in 20 minutes) and a BAC plateau (80mg% for 80 minutes). Serial assessments included a cued go/no-go task and measures of stimulation, sedation and craving. Relevant individual difference factors (ADHD symptoms and sensation seeking) were examined as moderators. Multi-level 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 pseudo-constant BAC, and potential moderators of these outcomes, in late adolescence. Additional studies with placebo-controlled designs are necessary to confirm these findings. PMID:26053322

  8. 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

  9. Acute rapamycin treatment improved glucose tolerance through inhibition of hepatic gluconeogenesis in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Dai, Weiwei; Panserat, Stéphane; Terrier, Frédéric; Seiliez, Iban; Skiba-Cassy, Sandrine

    2014-11-15

    Our aim was to investigate the potential role of TOR (target of rapamycin) signaling pathway in the regulation of hepatic glucose metabolism in rainbow trout. Fasted fish were first treated with a single intraperitoneal injection of rapamycin or vehicle and then submitted to a second intraperitoneal administration of glucose 4 h later. Our results revealed that intraperitoneal administration of glucose induced hyperglycemia for both vehicle and rapamycin treatments, which peaked at 2 h. Plasma glucose level in vehicle-treated fish was significantly higher than in rapamycin-treated fish at 8 and 17 h, whereas it remained at the basal level in rapamycin-treated fish. Glucose administration significantly enhanced the phosphorylation of Akt and ribosomal protein S6 kinase (S6K1) in vehicle-treated fish, while rapamycin completely abolished the activation of S6K1 in rapamycin-treated fish, without inhibiting the phosphorylation of Akt on Thr-308 or Ser-473. Despite the lack of significant variation in phosphoenolpyruvate carboxykinase mRNA abundance, mRNA abundance for glucokinase (GK), glucose 6-phosphatase (G6Pase) I and II, and fructose 1,6-bisphosphatase (FBPase) was reduced by rapamycin 17 h after glucose administration. The inhibition effect of rapamycin on GK and FBPase was further substantiated at the activity level. The suppression of GK gene expression and activity by rapamycin provided the first in vivo evidence in fish that glucose regulates hepatic GK gene expression and activity through a TORC1-dependent manner. Unlike in mammals, we observed that acute rapamycin treatment improved glucose tolerance through the inhibition of hepatic gluconeogenesis in rainbow trout. PMID:25163922

  10. Central nervous system effects of meclizine and dimenhydrinate: evidence of acute tolerance to antihistamines.

    PubMed

    Manning, C; Scandale, L; Manning, E J; Gengo, F M

    1992-11-01

    Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00 AM, 12:00 PM, and 4:00 PM; meclizine, 50 mg, at 8:00 AM, with placebo at 12:00 PM and 4:00 PM; or placebo at all three times in this randomized, double-blind, three-way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self-assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 +/- 7) and were not different from the greatest measured change after meclizine (5.8 +/- 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self-rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimenhydrinate. PMID:1474173

  11. [Equilibrium function in patients with acute sensorineural hearing loss].

    PubMed

    Pal'chun, V T; Ganichkina, I Ia; Luchikhin, L A; Derevianko, S N

    2002-01-01

    Equilibrium function was investigated with computer-assisted stabilography (CS) in patients with acute neurosensory hypoacusis. This new diagnostic tool was employed in combination with extended vestibulometric and audiologic examinations. Correlations were found between stabilographic and vestibulometric findings. CS is recommended as a method of screening diagnosis in examination of patients with imbalanced equilibrium. PMID:12227024

  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. [Change in pancreatic exocrine function in acute appendicitis].

    PubMed

    Ivanov, Iu A

    1979-10-01

    In order to study changes in the functional state of the pancreas 1572 investigations of the blood and urine amylase, atoxylresistant lipase of the blood serum before operation were performed in different postoperative periods in 131 patients with acute appendicitis. The enzyme activity was established to increase, especially in destructive forms of appendicitis and in elderly patients. PMID:505800

  14. Effect of acute hyperglycemia on potassium (86Rb+) permeability and plasma lipid peroxidation in subjects with normal glucose tolerance.

    PubMed

    Güven, M; Onaran, I; Ulutin, T; Sultuybek, G; Hatemi, H

    2001-04-01

    Hyperglycemia is likely to be one of the important determinants of ion transport as it is known to induce oxidative stress and may thus enhance non-specific permeability of membranes. The aim of the present study was to evaluate the effects of an acute increase in glycemia on 86Rb+ (a marker for K+) influx and lipid peroxidation. We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modification on 86Rb+ influx and plasma lipid peroxidation in 20 subjects with normal glucose tolerance (NGT). After 2-hour glucose loading, the levels of passive 86Rb+ influx and plasma lipid peroxidation were significantly increased, whereas the active influx of 86Rb+ was unchanged. The total and passive influx of 86Rb+ into erythrocytes was significantly correlated with the level of plasma lipid peroxidation. This study demonstrates that acute hyperglycemia induces an increase in the passive influx of 86Rb+ in subjects with NGT, suggesting that acute hyperglycemia may produce an oxidative stress in plasma. These changes may be among the earliest changes occurring in response to hyperglycemia. PMID:11383909

  15. Effect of acute hyperglycemia on potassium (86Rb+) permeability and plasma lipid peroxidation in subjects with normal glucose tolerance.

    PubMed

    Güven, M; Onaran, I; Ulutin, T; Sultuybek, G; Hatemi, H

    2001-01-01

    Hyperglycemia is likely to be one of the important determinants of ion transport as it is known to induce oxidative stress and may thus enhance non-specific permeability of membranes. The aim of the present study was to evaluate the effects of an acute increase in glycemia on 86Rb+ (a marker for K+) influx and lipid peroxidation. We evaluated the 75-g oral glucose tolerance test (OGTT)-induced modification on 86Rb+ influx and plasma lipid peroxidation in 20 subjects with normal glucose tolerance (NGT). After 2-hour glucose loading, the levels of passive 86Rb+ influx and plasma lipid peroxidation were significantly increased, whereas the active influx of 86Rb+ was unchanged. The total and passive influx of 86Rb+ into erythrocytes was significantly correlated with the level of plasma lipid peroxidation. This study demonstrates that acute hyperglycemia induces an increase in the passive influx of 86Rb+ in subjects with NGT, suggesting that acute hyperglycemia may produce an oxidative stress in plasma. These changes may be among the earliest changes occurring in response to hyperglycemia. PMID:11508792

  16. 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

  17. Spontaneous resolution of acute rejection and tolerance induction with IL-2 fusion protein in vascularized composite allotransplantation.

    PubMed

    Jindal, R; Unadkat, J; Zhang, W; Zhang, D; Ng, T W; Wang, Y; Jiang, J; Lakkis, F; Rubin, P; Lee, W P A; Gorantla, V S; Zheng, X X

    2015-05-01

    Vascularized composite allotransplantation (VCA) has emerged as a treatment option for treating nonlife-threatening conditions. Therefore, in order to make VCA a safe reconstruction option, there is a need to minimize immunosuppression, develop tolerance-inducing strategies and elucidate the mechanisms of VCA rejection and tolerance. In this study we explored the effects of hIL-2/Fc (a long-lasting human IL-2 fusion protein), in combination with antilymphocyte serum (ALS) and short-term cyclosporine A (CsA), on graft survival, regulatory T cell (Treg) proliferation and tolerance induction in a rat hind-limb transplant model. We demonstrate that hIL-2/Fc therapy tips the immune balance, increasing Treg proliferation and suppressing effector T cells, and permits VCA tolerance as demonstrated by long-term allograft survival and donor-antigen acceptance. Moreover, we observe two distinct types of acute rejection (AR), progressive and reversible, within hIL-2/Fc plus ALS and CsA treated recipients. Our study shows differential gene expression profiles of FoxP3 versus GzmB, Prf1 or interferon-γ in these two types of AR, with reversible rejection demonstrating higher Treg to Teff gene expression. This correlation of gene expression profile at the first clinical sign of AR with VCA outcomes can provide the basis for further inquiry into the mechanistic aspects of VCA rejection and future drug targets. PMID:25676865

  18. EFFECT OF ZINC EXPOSURE ON SUBSEQUENT ACUTE TOLERANCE TO HEAVY METALS IN RAINBOW TROUT

    EPA Science Inventory

    Fish usually show increased tolerance to metals in solution if proviously given an opportunity to acclimate to near lethal concentrations of the metal (Dixon and Sprngue 1981a; McCarter and Roch 1983; Bradley et al. 1985; Chapman 1985), and tolerence has been correlated with an i...

  19. 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. PMID:26053322

  20. Autonomic Function following Acute Organophosphorus Poisoning: A Cohort Study

    PubMed Central

    Jayasinghe, Sudheera S.; Pathirana, Kithsiri D.

    2012-01-01

    Autonomic dysfunction after chronic low level exposure to organophosphorus (OP) pesticides has been consistently reported in the literature, but not following a single acute overdose. In order to study autonomic function after an acute OP overdose, sixty-six overdose patients were compared to 70 matched controls. Assessment of autonomic function was done by heart rate response to standing, deep breathing (HR-DB) and Valsalva manoeuvre; blood pressure (BP) response to standing and sustained hand grip; amplitude and latency of sympathetic skin response (SSR); pupil size and post-void urine volume. The patients were assessed one and six weeks after the exposure. The number of patients who showed abnormal autonomic function compared to standard cut-off values did not show statistically significantly difference from that of controls by Chi-Square test. When compared to the controls at one week the only significant differences consistent with autonomic dysfunction were change of diastolic BP 3 min after standing, HR-DB, SSR-Amplitude, SSR-Latency, post-void urine volume and size of the pupil. At 6 weeks significant recovery of autonomic function was observed and only HR-DB was decreased to a minor degree, −5 beats/min [95%CI 2–8]. This study provides good evidence for the lack of long term autonomic dysfunction following acute exposure to OP pesticides. PMID:22655091

  1. 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

    2016-01-01

    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

  2. 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

  3. Executive function and endocrinological responses to acute resistance exercise

    PubMed Central

    Tsai, Chia-Liang; Wang, Chun-Hao; Pan, Chien-Yu; Chen, Fu-Chen; Huang, Tsang-Hai; Chou, Feng-Ying

    2014-01-01

    This study had the following two aims: First, to explore the effects of acute resistance exercise (RE, i.e., using exercise machines to contract and stretch muscles) on behavioral and electrophysiological performance when performing a cognitive task involving executive functioning in young male adults; Second, to investigate the potential biochemical mechanisms of such facilitative effects using two neurotrophic factors [i.e., growth hormone (GH) and insulin-like growth factor-1 (IGF-1)] and the cortisol levels elicited by such an exercise intervention mode with two different exercise intensities. Sixty young male adults were recruited and randomly assigned to a high-intensity (HI) exercise group, moderate-intensity (MI) exercise group, and non-exercise-intervention (NEI) group. Blood samples were taken, and the behavioral and electrophysiological indices were simultaneously measured when individuals performed a Go/No-Go task combined with the Erikson Flanker paradigm at baseline and after either an acute bout of 30 min of moderate- or high-intensity RE or a control period. The results showed that the acute RE could not only benefit the subjects' behavioral (i.e., RTs and accuracy) performance, as found in previous studies, but also increase the P3 amplitude. Although the serum GH and IGF-1 levels were significantly increased via moderate or high intensity RE in both the MI and HI groups, the increased serum levels of neurotrophic factors were significantly decreased about 20 min after exercise. In addition, such changes were not correlated with the changes in cognitive (i.e., behavioral and electrophysiological) performance. In contrast, the serum levels of cortisol in the HI and MI groups were significantly lower after acute RE, and the changes in cortisol levels were significantly associated with the changes in electrophysiological (i.e., P3 amplitude) performance. The findings suggest the beneficial effects of acute RE on executive functioning could be due to

  4. Acute cross-tolerance to opioids in heroin delta-opioid-responding Swiss Webster mice.

    PubMed

    Rady, J J; Fujimoto, J M

    2000-01-01

    It is generally thought that the mu receptor actions of metabolites, 6-monoacetylmorphine (6MAM) and morphine, account for the pharmacological actions of heroin. However, upon intracerebroventricular (i.c.v.) administration in Swiss Webster mice, heroin and 6MAM act on delta receptors while morphine acts on mu receptors. Swiss Webster mice made tolerant to subcutaneous (s.c.) morphine by morphine pellet were not cross-tolerant to s.c. heroin (at 20 min in the tail flick test). Now, opioids were given in combination, s.c. (6.5 h) and i.c.v. (3 h) preceding testing the challenging agonist i.c.v. (at 10 min in the tail flick test). The combination (s.c. + i.c.v.) morphine pretreatment induced tolerance to the mu action of morphine but no cross-tolerance to the delta action of heroin, 6MAM and DPDPE and explained why morphine pelleting did not produce cross-tolerance to s.c. heroin above. Heroin plus heroin produced tolerance to delta agonists but not to mu agonists. Surprisingly, all combinations of morphine with the delta agonists produced tolerance to morphine which now acted through delta receptors (inhibited by i.c.v. naltrindole), an unusual change in receptor selectivity for morphine. PMID:10810246

  5. Cardiogenic shock: A look at acute functional mitral incompetence.

    PubMed

    Steyn, F A; Vosloo, J; Naude, H; Steyn, A J

    2016-08-01

    A 44-year-old man presented with cardiogenic shock secondary to acute functional mitral incompetence as well as septic shock related to pneumonia. The patient deteriorated haemodynamically despite adequate medical therapy. An echocardiogram revealed a massive mitral incompetence and an ejection fraction of 32%. An intra-aortic balloon pump was placed and the patient improved dramatically. On day 6 after admission the echocardiogram was repeated, revealing a mild mitral incompetence and an ejection fraction of 58%. PMID:27499404

  6. 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

  7. Targeting dendritic cell function during systemic autoimmunity to restore tolerance.

    PubMed

    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

  8. BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF ACUTE CHLORPYRIFOS IN RATS: TOLERANCE TO PROLONGED INHIBITION OF CHOLINESTERASE

    EPA Science Inventory

    Chlorpyrifos (CPF), a commercially prevalent organophosphate (OP) pesticide, inhibits blood and brain cholinesterase for up to 10 weeks after acute s.c. injection in rats. his prolonged inhibition suggested that acute CPF may affect muscarinic receptors and behavior as does repea...

  9. 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

  10. 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).

  11. Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

    PubMed

    Coppola, Ludovico; Coppola, Antonino; Grassia, Antonio; Mastrolorenzo, Luigia; Lettieri, Biagio; De Lucia, Domenico; De Nanzio, Annarita; Gombos, Giorgio

    2004-10-01

    To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations. PMID:15613917

  12. Gene mining in halophytes: functional identification of stress tolerance genes in Lepidium crassifolium.

    PubMed

    Rigó, Gábor; Valkai, Ildikó; Faragó, Dóra; Kiss, Edina; Van Houdt, Sara; Van de Steene, Nancy; Hannah, Matthew A; Szabados, László

    2016-09-01

    Extremophile plants are valuable sources of genes conferring tolerance traits, which can be explored to improve stress tolerance of crops. Lepidium crassifolium is a halophytic relative of the model plant Arabidopsis thaliana, and displays tolerance to salt, osmotic and oxidative stresses. We have employed the modified Conditional cDNA Overexpression System to transfer a cDNA library from L. crassifolium to the glycophyte A. thaliana. By screening for salt, osmotic and oxidative stress tolerance through in vitro growth assays and non-destructive chlorophyll fluorescence imaging, 20 Arabidopsis lines were identified with superior performance under restrictive conditions. Several cDNA inserts were cloned and confirmed to be responsible for the enhanced tolerance by analysing independent transgenic lines. Examples include full-length cDNAs encoding proteins with high homologies to GDSL-lipase/esterase or acyl CoA-binding protein or proteins without known function, which could confer tolerance to one or several stress conditions. Our results confirm that random gene transfer from stress tolerant to sensitive plant species is a valuable tool to discover novel genes with potential for biotechnological applications. PMID:27343166

  13. EHD1 functions in endosomal recycling and confers salt tolerance.

    PubMed

    Bar, Maya; Leibman, Meirav; Schuster, Silvia; Pitzhadza, Hilla; Avni, Adi

    2013-01-01

    Endocytosis is a crucial process in all eukaryotic organisms including plants. We have previously shown that two Arabidopsis proteins, AtEHD1 and AtEHD2, are involved in endocytosis in plant systems. Knock-down of EHD1 was shown to have a delayed recycling phenotype in mammalians. There are many works in mammalian systems detailing the importance of the various domains in EHDs but, to date, the domains of plant EHD1 that are required for its activity have not been characterized. In this work we demonstrate that knock-down of EHD1 causes a delayed recycling phenotype and reduces Brefeldin A sensitivity in Arabidopsis seedlings. The EH domain of EHD1 was found to be crucial for the localization of EHD1 to endosomal structures. Mutant EHD1 lacking the EH domain did not localize to endosomal structures and showed a phenotype similar to that of EHD1 knock-down seedlings. Mutants lacking the coiled-coil domain, however, showed a phenotype similar to wild-type or EHD1 overexpression seedlings. Salinity stress is a major problem in current agriculture. Microarray data demonstrated that salinity stress enhances the expression of EHD1, and this was confirmed by semi quantitative RT-PCR. We demonstrate herein that transgenic plants over expressing EHD1 possess enhanced tolerance to salt stress, a property which also requires an intact EH domain. PMID:23342166

  14. Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

    PubMed Central

    Di Lazzaro, Vincenzo; Pellegrino, Giovanni; Di Pino, Giovanni; Ranieri, Federico; Lotti, Fiorenza; Florio, Lucia; Capone, Fioravante

    2016-01-01

    The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. PMID:26858590

  15. Efficacy and tolerability of treatment with azacitidine for 5 days in elderly patients with acute myeloid leukemia

    PubMed Central

    Sadashiv, Santhosh K; Hilton, Christie; Khan, Cyrus; Rossetti, James M; Benjamin, Heather L; Fazal, Salman; Sahovic, Entezam; Shadduck, Richard K; Lister, John

    2014-01-01

    Acute myeloid leukemia (AML) patients aged ≥60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m2/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20–30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m2/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13–724 days). Grade 3–4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1–2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m2/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML. PMID:25132519

  16. Acute effects of guar gum on glucose tolerance and intestinal absorption of nutrients in rats.

    PubMed

    Daumerie, C; Henquin, J C

    1982-03-01

    The mechanism by which non-digestible fibres improve oral glucose tolerance is still unclear. We have studied the effects of guar gum on oral carbohydrate tolerance and intestinal absorption of nutrients in anaesthetized rats. Addition of guar to an intragastric glucose load (1 g/kg) markedly delayed the rise in plasma glucose levels when the concentration of the gum was adequate (10 mg/ml). The insulin response was somewhat less marked, but the differences were not significant. When glucose was introduced directly into the duodenum, the gum only slightly reduced the rise in glucose levels, during the first 15 min. If sucrose (1 g/kg) was infused in the duodenum, acarboseR, an alpha-glucosidase inhibitor, but not guar, slowed the rise in plasma glucose and insulin levels. Intestinal absorption was measured in a tied duodenojejunal loop. Guar decreased active transport of glucose (4 mmol/l) by approximately 20%, but had no significant effect on the passive transport of glucose (100 mmol/l), nor on the absorption of sucrose (40 mmol/l) or leucine (4 mmol/l). At the concentration which improved glucose tolerance (10 mg/ml), but not at lower concentrations, guar gum markedly slowed gastric emptying. These results suggest that guar gum improves tolerance to oral carbohydrates mainly by decreasing the rate of gastric emptying, but inhibition of intestinal absorption may also be involved in the presence of low concentrations of the sugars. PMID:6284563

  17. Analgesic effect and tolerance of Voltaren and Ketogan in acute renal or ureteric colic.

    PubMed

    Sommer, P; Kromann-Andersen, B; Lendorf, A; Lyngdorf, P; Møller, P

    1989-01-01

    Fifty-six patients with renal or ureteric colic were entered into a randomised, prospective, double-blind investigation of the analgesic efficacy and tolerance of Voltaren versus Ketogan, both administered intramuscularly. There were no significant differences regarding pain-relief but side effects were fewer in patients treated with Voltaren. PMID:2645969

  18. Functional expression of a blood tolerant laccase in Pichia pastoris

    PubMed Central

    2013-01-01

    Background Basidiomycete high-redox potential laccases (HRPLs) working in human physiological fluids (pH 7.4, 150 mM NaCl) arise great interest in the engineering of 3D-nanobiodevices for biomedical uses. In two previous reports, we described the directed evolution of a HRPL from basidiomycete PM1 strain CECT 2971: i) to be expressed in an active, soluble and stable form in Saccharomyces cerevisiae, and ii) to be active in human blood. In spite of the fact that S. cerevisiae is suited for the directed evolution of HRPLs, the secretion levels obtained in this host are not high enough for further research and exploitation. Thus, the search for an alternative host to over-express the evolved laccases is mandatory. Results A blood-active laccase (ChU-B mutant) fused to the native/evolved α-factor prepro-leader was cloned under the control of two different promoters (PAOX1 and PGAP) and expressed in Pichia pastoris. The most active construct, which contained the PAOX1 and the evolved prepro-leader, was fermented in a 42-L fed-batch bioreactor yielding production levels of 43 mg/L. The recombinant laccase was purified to homogeneity and thoroughly characterized. As happened in S. cerevisiae, the laccase produced by P. pastoris presented an extra N-terminal extension (ETEAEF) generated by an alternative processing of the α-factor pro-leader at the Golgi compartment. The laccase mutant secreted by P. pastoris showed the same improved properties acquired after several cycles of directed evolution in S. cerevisiae for blood-tolerance: a characteristic pH-activity profile shifted to the neutral-basic range and a greatly increased resistance against inhibition by halides. Slight biochemical differences between both expression systems were found in glycosylation, thermostability and turnover numbers. Conclusions The tandem-yeast system based on S. cerevisiae to perform directed evolution and P. pastoris to over-express the evolved laccases constitutes a promising approach for

  19. 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…

  20. Yeast functional screen to identify genetic determinants capable of conferring abiotic stress tolerance in Jatropha curcas

    PubMed Central

    2010-01-01

    Background Environmentally inflicted stresses such as salinity and drought limit the plant productivity both in natural and agricultural system. Increasing emphasis has been directed to molecular breeding strategies to enhance the intrinsic ability of plant to survive stress conditions. Functional screens in microorganisms with heterologous genes are a rapid, effective and powerful tool to identify stress tolerant genes in plants. Jatropha curcas (Physic nut) has been identified as a potential source of biodiesel plant. In order to improve its productivity under stress conditions to benefit commercial plantations, we initiated prospecting of novel genes expressed during stress in J. curcas that can be utilized to enhance stress tolerance ability of plant. Results To identify genes expressed during salt tolerance, cDNA expression libraries were constructed from salt-stressed roots of J. curcas, regulated under the control of the yeast GAL1 system. Using a replica based screening, twenty thousand yeast transformants were screened to identify transformants expressing heterologous gene sequences from J. curcas with enhanced ability to tolerate stress. From the screen we obtained 32 full length genes from J. curcas [GenBank accession numbers FJ489601-FJ489611, FJ619041-FJ619057 and FJ623457-FJ623460] that can confer abiotic stress tolerance. As a part of this screen, we optimized conditions for salt stress in J. curcas, defined parameters for salt stress in yeast, as well as isolated three salt hypersensitive yeast strains shs-2, shs-6 and shs-8 generated through a process of random mutagenesis, and exhibited growth retardation beyond 750 mM NaCl. Further, we demonstrated complementation of the salt sensitive phenotypes in the shs mutants, and analyzed the expression patterns for selected J. curcas genes obtained from the screen in both leaf and root tissues after salt stress treatments. Conclusions The approach described in this report provides a rapid and universal

  1. 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

  2. Functional heterogeneity of genetically defined subclones in acute myeloid leukemia

    PubMed Central

    Klco, Jeffery M.; Spencer, David H.; Miller, Christopher A.; Griffith, Malachi; Lamprecht, Tamara L.; O’Laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan T.; Fulton, Robert S.; Eades, William C.; Link, Daniel C.; Graubert, Timothy A.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Wilson, Richard K.; Ley, Timothy J.

    2014-01-01

    Summary The relationships between clonal architecture and functional heterogeneity in acute myeloid leukemia (AML) samples are not yet clear. We used targeted sequencing to track AML subclones identified by whole genome sequencing using a variety of experimental approaches. We found that virtually all AML subclones trafficked from the marrow to the peripheral blood, but some were enriched in specific cell populations. Subclones showed variable engraftment potential in immunodeficient mice. Xenografts were predominantly comprised of a single genetically-defined subclone, but there was no predictable relationship between the engrafting subclone and the evolutionary hierarchy of the leukemia. These data demonstrate the importance of integrating genetic and functional data in studies of primary cancer samples, both in xenograft models and in patients. PMID:24613412

  3. 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

  4. Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications

    PubMed Central

    Chou, Timothy Y; Hong, Bennett Y

    2014-01-01

    Eye disease due to herpes simplex virus (HSV) is a leading cause of ocular morbidity and the number one infectious cause of unilateral corneal blindness in the developed parts of the globe. Recurrent keratitis can result in progressive corneal scarring, thinning, and vascularization. Antiviral agents employed against HSV have primarily been nucleoside analogs. Early generation drugs included idoxuridine, iododesoxycytidine, vidarabine, and trifluridine. While effective, they tended to have low bioavailability and measurable local cellular toxicity due to their nonselective mode of action. Acyclovir 0.3% ointment is a more selective agent, and had become a first-line topical drug for acute HSV keratitis in Europe and other places outside of the US. Ganciclovir 0.15% gel is the most recently approved topical treatment for herpes keratitis. Compared to acyclovir 0.3% ointment, ganciclovir 0.15% gel has been shown to be better tolerated and no less effective in several Phase II and III trials. Additionally, topical ganciclovir does not cause adverse systemic side effects and is therapeutic at lower concentrations. Based on safety, efficacy, and tolerability, ganciclovir 0.15% gel should now be considered a front-line topical drug in the treatment of dendritic herpes simplex epithelial keratitis. Topics of future investigation regarding other potential uses for ganciclovir gel may include the prophylaxis of recurrent HSV epithelial keratitis, treatment of other forms of ocular disease caused by herpesviruses and adenovirus, and ganciclovir gel as an adjunct to antitumor therapy. PMID:25187721

  5. 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

  6. 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.

  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. 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. PMID:24366547

  9. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status

    PubMed Central

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  10. Functional Magnetic Resonance Imaging in Acute Kidney Injury: Present Status.

    PubMed

    Zhou, Hai Ying; Chen, Tian Wu; Zhang, Xiao Ming

    2016-01-01

    Acute kidney injury (AKI) is a common complication of hospitalization that is characterized by a sudden loss of renal excretory function and associated with the subsequent development of chronic kidney disease, poor prognosis, and increased mortality. Although the pathophysiology of renal functional impairment in the setting of AKI remains poorly understood, previous studies have identified changes in renal hemodynamics, perfusion, and oxygenation as key factors in the development and progression of AKI. The early assessment of these changes remains a challenge. Many established approaches are not applicable to humans because of their invasiveness. Functional renal magnetic resonance (MR) imaging offers an alternative assessment tool that could be used to evaluate renal morphology and function noninvasively and simultaneously. Thus, the purpose of this review is to illustrate the principle, application, and role of the techniques of functional renal MR imaging, including blood oxygen level-dependent imaging, arterial spin labeling, and diffusion-weighted MR imaging, in the management of AKI. The use of gadolinium in MR imaging may exacerbate renal impairment and cause nephrogenic systemic fibrosis. Therefore, dynamic contrast-enhanced MR imaging will not be discussed in this paper. PMID:26925411

  11. Involvement of protein kinase C and Src tyrosine kinase in acute tolerance to ethanol inhibition of spinal NMDA-induced pressor responses in rats

    PubMed Central

    Hsieh, W-K; Lin, H-H; Lai, C-C

    2009-01-01

    Background and purpose: The present study was carried out to examine the role of protein kinases in the development of acute tolerance to the effects of ethanol on spinal N-methyl-D-aspartate (NMDA) receptor-mediated pressor responses during prolonged ethanol exposure. Experimental approach: Blood pressure responses induced by intrathecal injection of NMDA were recorded. The levels of several phosphorylated residues on NMDA receptor NR1 (GluN1) (NR1) and NMDA receptor NR2B (GluN2B) (NR2B) subunits were determined by immunohistochemistry and Western blot analysis. Key results: Ethanol inhibited spinal NMDA-induced pressor responses at 10 min, but the inhibition was significantly reduced at 40 min following continuous infusion. This effect was dose-dependently blocked by chelerythrine [a protein kinase C (PKC) inhibitor, 1–1000 pmol] or PP2 (a Src family tyrosine kinase inhibitor, 1–100 pmol) administered intrathecally 10 min following ethanol infusion. A significant increase in the immunoreactivity of phosphoserine 896 of NR1 subunits (pNR1-Ser896) and phosphotyrosine 1336 of NR2B subunits (pNR2B-Tyr1336) was found in neurons of intermediolateral cell column during the development of tolerance. Levels of pNR1-Ser896 and pNR2B-Tyr1336 were also significantly increased in lateral horn regions of the spinal cord slices incubated with ethanol for 40 min in vitro. The increases in pNR1-Ser896 and pNR2B-Tyr1336 levels were inhibited by post-treatment with chelerythrine and PP2, respectively, both in the in vivo and in vitro studies. Conclusions and implications: The results suggest that activation of PKC and Src tyrosine kinase during prolonged ethanol exposure leading to increases in the levels of pNR1-Ser896 and pNR2B-Tyr1336 may contribute to acute tolerance to inhibition by ethanol of NMDA receptor function. PMID:19703167

  12. 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.

  13. Acute and chronic wound fluids influence keratinocyte function differently.

    PubMed

    Thamm, Oliver C; Koenen, Paola; Bader, Nicola; Schneider, Alina; Wutzler, Sebastian; Neugebauer, Edmund A M; Spanholtz, Timo A

    2015-04-01

    Wound healing requires a proper functioning of keratinocytes that migrate, proliferate and lead to a competent wound closure. Impaired wound healing might be due to a disturbed keratinocyte function caused by the wound environment. Basically, chronic wound fluid (CWF) differs from acute wound fluid (AWF). The aim of this study was to analyse the effects of AWF and CWF on keratinocyte function. We therefore investigated keratinocyte migration and proliferation under the influence of AWF and CWF using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test and scratch assay. We further measured the gene expression by qRT-PCR regarding growth factors and matrixmetalloproteinases (MMPs) involved in regeneration processes. AWF had a positive impact on keratinocyte proliferation over time, whereas CWF had an anti-proliferative effect. Keratinocyte migration was significantly impaired by CWF in contrast to an undisturbed wound closure under the influence of AWF. MMP-9 expression was strongly upregulated by CWF compared with AWF. Keratinocyte function was significantly impaired by CWF. An excessive induction of MMP-9 by CWF might lead to a permanent degradation of extracellular matrix and thereby prevent wounds from healing. PMID:23517467

  14. Improving the prediction of the functional impact of cancer mutations by baseline tolerance transformation

    PubMed Central

    2012-01-01

    High-throughput prioritization of cancer-causing mutations (drivers) is a key challenge of cancer genome projects, due to the number of somatic variants detected in tumors. One important step in this task is to assess the functional impact of tumor somatic mutations. A number of computational methods have been employed for that purpose, although most were originally developed to distinguish disease-related nonsynonymous single nucleotide variants (nsSNVs) from polymorphisms. Our new method, transformed Functional Impact score for Cancer (transFIC), improves the assessment of the functional impact of tumor nsSNVs by taking into account the baseline tolerance of genes to functional variants. PMID:23181723

  15. 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

  16. 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.

  17. A new merit function for evaluating the flaw tolerance of composite laminates

    NASA Technical Reports Server (NTRS)

    Mikulas, Martin M., Jr.; Sumpter, Rod

    1995-01-01

    Advanced composite materials are providing notable savings in numerous aerospace and non-aerospace applications by virtue of their uniquely high strength-to-density ratio and high stiffness-to-density ratio. However, their full potential for high performance has yet to be achieved because of the low tolerance of the 'brittle' material to impact, holes, flaws, and localized discontinuities due to relatively low toughness. In the present paper a new and simple merit function is proposed for maximizing the strength performance of flawed composite laminate for different design requirement. This new merit function takes into account the flaw tolerance of a composite laminated as well as its stiffness. After development of the new merit function, an example is presented of its application to a practical laminate family.

  18. 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. PMID:22260861

  19. 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. PMID:21910735

  20. The efficacy and tolerability of frovatriptan and dexketoprofen for the treatment of acute migraine attacks.

    PubMed

    Allais, Gianni; Rolando, Sara; De Lorenzo, Cristina; Benedetto, Chiara

    2014-08-01

    Frovatriptan is a triptan characterized by a high affinity for 5-HT1B/1D receptors and a long half-life contributing to a more sustained and prolonged action than other triptans. Dexketoprofen is a nonsteroidal anti-inflammatory drug with a relatively short half-life and rapid onset of action, blocking the action of cyclo-oxygenase, which is involved in prostaglandins' production, thus reducing inflammation and pain. Both drugs have been successfully employed as monotherapies for the treatment of acute migraine attacks. The combination of these two drugs (frovatriptan 2.5 mg plus dexketoprofen 25 or 37.5 mg) has been tested in migraine sufferers, showing a rapid and good initial efficacy, with 2-h pain free rates of 51%, and a high persistence in the 48-h following the onset of pain: recurrence occurred in only 29% of attacks and sustained pain free rates were 43% at 24- and 33% at 48-h. PMID:25056381

  1. Safety, Tolerability, and Efficacy of GSK1322322 in the Treatment of Acute Bacterial Skin and Skin Structure Infections

    PubMed Central

    Corey, Ralph; O'Riordan, William D.; Dumont, Etienne; Jones, Lori S.; Kurtinecz, Milena; Zhu, John Z.

    2014-01-01

    GSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at 600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with a ≥20% decrease in lesion area from the baseline at 48 and 72 h after treatment initiation. GSK1322322 administration was associated with mild-to-moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea, and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%) were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and linezolid was associated with ≥20% decreases from the baseline in the lesion area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores were comparable between the GSK1322322 and linezolid treatments. The clinical success rates within the intent-to-treat population and the per-protocol population that completed this study were 67 and 91%, respectively, in the GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated group. These results will be used to guide dose selection in future studies with GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs. (This study has been registered at ClinicalTrials.gov under registration no. NCT01209078 and at http://www.gsk-clinicalstudyregister.com [PDF113414].) PMID:25136015

  2. Return of lymphatic function after flap transfer for acute lymphedema.

    PubMed Central

    Slavin, S A; Van den Abbeele, A D; Losken, A; Swartz, M A; Jain, R K

    1999-01-01

    OBJECTIVE: The goals of this work were to develop animal models of lymphedema and tissue flap transfer, and to observe physiologic changes in lymphatic function that occur in these models over time, both systemically with lymphoscintigraphy (LS) and locally using fluorescence microlymphangiography (FM). SUMMARY BACKGROUND DATA: Although lymphedema has been managed by a combination of medical and surgical approaches, no effective long-term cure exists. Surgical attempts aimed at reconnecting impaired lymphatic channels or bypassing obstructed areas have failed. METHODS: The tails of rats (A groups) and mice (B groups) were used because of their different features. Lymphedema was created by ligation of the lymphatics at the tail base and quantified by diameter measurements there. In the experimental group, rectus abdominis myocutaneous flap was transferred across the ligation. In addition to the ligation (A1 and B1) and ligation + flap (A2 and B2) groups, three control groups were included: sham flap with ligation (B4), sham flap alone (B5), and normal (A3 and B3) animals. Observations were made at weekly time points for lymphatic function and continuity. RESULTS: Lymphedema was successfully created in the mouse ligation groups (B1 and B4) and sustained for the entire length of observation (up to 14 weeks). Lymphatic continuity was restored in those animals with transferred flaps across the ligation site (A2 and B2), as seen both by LS and FM. Sham flaps did not visibly affect lymphatic function nor did they cause any visible swelling in the tail. CONCLUSIONS: Acute lymphedema developing after ligation of tail lymphatics in mice can be prevented by myocutaneous flap transfer. Restored lymphatic continuity and function were demonstrable using lymphoscintigraphy and fluorescence microlymphangiography. Images Figure 2. Figure 4. Figure 5. PMID:10077056

  3. 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. PMID:19728023

  4. Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer's disease.

    PubMed

    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 predicted

  5. 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. PMID:26342688

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

    PubMed

    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

  7. 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

  8. 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.

  9. 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

  10. The Impact of Acute Phase Domain-Specific Cognitive Function on Post-stroke Functional Recovery

    PubMed Central

    Park, Jihong; Lee, Gangpyo; Lee, Shi-Uk

    2016-01-01

    Objective To assess whether the cognitive function in the acute stage evaluated by domain-specific neuropsychological assessments would be an independent predictor of functional outcome after stroke. Methods Forty patients underwent 4 domain-specific neuropsychological examinations about 3 weeks after the onset of stroke. The tests included the Boston Naming Test (BNT), the construction recall test (CRT), the construction praxis test (CPT), and the verbal fluency test (VFT). The Korean version of Modified Barthel Index (K-MBI) at 3 months and the modified Rankin Scale (mRS) at 6 months were investigated as functional outcome after stroke. Functional improvement was assessed using the change in K-MBI during the first 3 months and subjects were dichotomized into 'good status' and 'poor status' according to mRS at 6 months. The domain-specific cognitive function along with other possible predictors for functional outcome was examined using regression analysis. Results The z-score of CPT (p=0.044) and CRT (p<0.001) were independent predictors for functional improvement measured by the change in K-MBI during the first 3 months after stroke. The z-score of CPT (p=0.049) and CRT (p=0.048) were also independent predictors of functional status at post-stroke 6 months assessed by mRS. Conclusion Impairment in visuospatial construction and memory within one month after stroke can be an independent prognostic factor of functional outcome. Domain-specific neuropsychological assessments could be considered in patients with stroke in the acute phase to predict long-term functional outcome. PMID:27152270

  11. Myocardial structure, function and ischaemic tolerance in a rodent model of obesity with insulin resistance.

    PubMed

    Wensley, I; Salaveria, K; Bulmer, A C; Donner, D G; du Toit, E F

    2013-11-01

    Obesity and its comorbidities (dyslipidaemia, insulin resistance and hypertension) that together constitute the metabolic syndrome are all risk factors for ischaemic heart disease. Although obesity has been reported to be an independent risk factor for congestive heart failure, whether obesity-induced heart failure develops in the absence of increased afterload (induced by hypertension) is not clear. We have previously shown that obesity with insulin resistance decreases myocardial tolerance to ischaemia-reperfusion, but the mechanism for this decreased tolerance remains unclear. We hypothesize that obesity with insulin resistance induces adverse cardiac remodelling and pump dysfunction, as well as adverse changes in myocardial prosurvival reperfusion injury salvage kinase (RISK) pathway signalling to reduce myocardial tolerance to ischaemia-reperfusion. Wistar rats were fed an obesogenic (obese group) or a standard rat chow diet (control group) for 32 weeks. Echocardiography was performed over the 32 weeks before isolated Langendorff-perfused hearts were subjected to 40 min coronary artery ligation followed by reperfusion, and functional recovery (rate-pressure product), infarct size and RISK pathway function were assessed (Western blot analysis). Obesity with insulin resistance increased myocardial lipid accumulation but had no effect on in vivo or ex vivo left ventricular structure/function. Hearts from obese rats had lower reperfusion rate-pressure products (13115 ± 562 beats min(-1) mmHg for obese rats versus 17781 ± 1109 beats min(-1) mmHg for control rats, P < 0.05) and larger infarcts (36.3 ± 5.6% of area at risk in obese rats versus 14.1 ± 2.8% of area at risk in control rats, P < 0.01) compared with control hearts. These changes were associated with reductions in RISK pathway function, with 30-50 and 40-60% reductions in Akt and glycogen synthase kinase 3 beta (GSK-3β) expression and phosphorylation, respectively, in obese rat hearts compared with

  12. 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

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

    PubMed

    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

  14. Splenic CD11c(low)CD45RB(high) dendritic cells derived from endotoxin-tolerant mice attenuate experimental acute liver failure.

    PubMed

    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

  15. Diastolic function in acute myocardial infarction: a radionuclide study

    SciTech Connect

    Bonaduce, D.; Morgano, G.; Petretta, M.; Arrichiello, P.; Conforti, G.; Betocchi, S.; Salvatore, M.; Chiariello, M.

    1988-11-01

    We studied left ventricular diastolic function by equilibrium gated radionuclide angiography in patients as follows: 75 with acute myocardial infarction (AMI), 35 with anterior or anteroseptal necrosis (Group A) and 40 with inferior, inferolateral, or posterior necrosis (Group I). The ejection fraction (EF) was lower in Group A than Group I (41.9 +/- 2.5 vs. 57.1 +/- 2.0%, p less than 0.001), as was peak diastolic filling rate normalized to end diastolic volume (PDFR-EDV/sec) (1.9 +/- 0.1 vs. 2.4 +/- 0.1 EDV/sec, p less than 0.05). PDFR normalized to stroke volume was similar in both groups. An excellent linear correlation was found between EF and PDFR-EDV/sec in the total study population. Isovolumic relaxation period (IRP) was beyond our upper normal value of 94 msec in 64% of patients and it was shorter in Group A than I (95.8 +/- 12.7 vs. 147.0 +/- 13.6 msec, p less than 0.05). The presence of shorter IRP in Group A than in I is probably a result of an earlier mitral valve opening as a consequence of higher left atrial pressure.

  16. Effects of oral montelukast on airway function in acute asthma.

    PubMed

    Cýllý, A; Kara, A; Ozdemir, T; Oğüş, C; Gülkesen, K H

    2003-05-01

    Montelukast, a specific cysteinyl leukotriene receptor antagonist, has been shown to improve pulmonary function within 1 h of ingestion. This study was undertaken to compare the effects on peak expiratory flow rate (PEFR) of oral montelukast added to intravenous steroid, intravenous steroid alone and placebo during the 24 h period following administration. Seventy asthmatic patients (FEV1 40-80% predicted and > or = 15% improvement after inhaled beta agonist) were enrolled in a single blind study to receive oral montelukast (10 mg) plus intravenous prednisolone (1 mg/kg), intravenous prednisolone (1 mg/kg) or placebo in a randomised fashion. The patients received one ofthe above three groups of medication before any other treatments. This was immediately followed by the aerosol treatments of 100 mcg of terbutaline sulphate divided into three doses during 1 h as described in the consensus statement. Thereafter, patients were observed for 24 h to document the effects on PEFR, Borg dyspnoea score and need for rescue medication. The primary end point was percentage change at different time points. Secondary end points were Borg dyspnoea score and use of rescue medication. Compared with placebo, montelukast added to the prednisolone group and the prednisolone alone group had significant percentage change from baseline in PEFR in the entire 24 h period (P<0.05). The difference in PEFR between montelukast plus prednisolone group and prednisolone group favoured the montelukast plus prednisolone group but did not reach statistical significance. Furthermore, montelukast plus prednisolone group required less inhaled short-acting beta agonistthan other two groups. The results of this study indicate that adding montelukast to steroid in acute asthma may have some additive improvement in lung functions. PMID:12735671

  17. 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. PMID:26350412

  18. Development and Validation of the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ)

    PubMed Central

    Zempsky, William T; O’Hara, Emily A; Santanelli, James P; New, Tamara; Smith-Whitley, Kim; Casella, James; Palermo, Tonya M.

    2014-01-01

    Physical function and functional recovery are important aspects of the acute pain experience in children and adolescents in hospitalized settings. Measures of function related to pediatric acute pain do not exist currently, limiting understanding of recovery in youth undergoing acute and procedural pain. To address this gap, we developed and assessed the clinical utility and preliminary validity of the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ). We evaluated psychometric properties of this measure in 159 patients with sickle cell disease, ages 7–21 years who were hospitalized for vasoocclusive episodes at four urban children’s hospitals. The YAPFAQ demonstrated strong internal reliability and test-retest reliability. An exploratory factor analysis (EFA) was conducted to examine the preliminary factor structure, and to help reduce the number of items for the final scale. Evidence for moderate construct validity was demonstrated among validated measures of pain burden, motor function, functional ability and quality of life. The YAPFAQ is a new measure of youth functional ability in the acute pain setting. Further evaluation of this measure in additional pediatric populations is needed to understand applicability across a spectrum of youth experiencing acute pain related to illness, trauma, and medical/surgical procedures. PERSPECTIVE Measures of function in response to acute pain are needed in order to more comprehensively evaluate acute pain interventions in pediatrics; however, no specific measures are available. Our preliminary psychometric evaluation of an acute pain functional ability measure for youth indicates that it may be a promising tool for further refinement in additional pediatric acute pain populations. PMID:25277425

  19. 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

  20. Efficacy of multi-functional liposomes containing daunorubicin and emetine for treatment of acute myeloid leukaemia.

    PubMed

    Myhren, Lene; Nilssen, Ida Mostrøm; Nicolas, Valérie; Døskeland, Stein Ove; Barratt, Gillian; Herfindal, Lars

    2014-09-01

    Despite recent advances in chemotherapy against acute myeloid leukaemia (AML), the disease still has high mortality, particularly for patients who tolerate extensive chemotherapy poorly. Nano-formulations have potential to minimise the adverse effects of chemotherapy. We present here a liposomal formulation encapsulating both the anthracycline daunorubicin (DNR) and emetine (Eme) for enhanced cytotoxic effect against AML cells. Eme could be loaded into the PEGylated liposomes together with DNR by the acid precipitation principle, with a loading efficiency of Eme at about 50% of that of DNR. The liposome surface was modified with folate to enhance drug loading into cells, giving higher cytotoxic activity. Both intracellular drug loading and cytotoxic activity could be further increased by anti-folate treatment of AML cells with methotrexate (MTX). The combination of DNR and Eme also increased drug loading in MTX-treated cells compared to DNR alone. Liposomes with both DNR and Eme were particularly efficient against AMLs with deficient p53. In conclusion, we have produced a multi-functional liposomal anti-leukaemic drug formulation designed to overcome some of the problems in anthracycline chemotherapy: (1) Combination of DNR and Eme to diminish drug resistance. (2) Using PEGylated stealth liposomes to minimise adverse side-effects. (3) Molecules on the liposomal surface target proteins on AML-cells ensure selectivity, which was enhanced by priming the leukaemia cells with MTX. PMID:24747809

  1. Structural and functional analysis of transmembrane segment IV of the salt tolerance protein Sod2.

    PubMed

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

    2013-08-23

    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) ((126)FPQINFLGSLLIAGCITSTDPVLSALI(152)) 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

  2. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury.

    PubMed

    Damtew, B; Marino, J A; Fratianne, R B; Spagnuolo, P J

    1993-02-01

    Leukotrienes, especially leukotriene B4, are important modulators of various neutrophil functions including adherence and chemotaxis. In previous work, we demonstrated that neutrophil adherence to extracellular matrixes was diminished in the acute stages of burn injury. In this study, we demonstrated that neutrophil adhesion to human and bovine endothelium in the baseline state and after stimulation with leukotriene B4 is depressed markedly after burn injury. The defect in stimulated adherence to endothelium was not specific to leukotriene B4 because impaired adhesion was observed with n-formyl-methionyl-leucyl-phenylalanine and ionophore A23187 as well. Moreover, the adherence defect correlated with 95% and 81% decreases in the release of leukotriene B4 and 5-hydroxy-(6E,87,117,147)-eicosatetraenoic acid, respectively, from burn PMN treated with A23187. Burn neutrophils also released proportionately more byproducts of leukotriene B4 omega oxidation, particularly 20-COOH-leukotriene B4, than did control neutrophils. When examined 3 1/2 weeks after injury, abnormalities in neutrophil leukotriene B4 generation and the adherence of burn neutrophils had recovered to near normal values. To determine whether the decreased release of leukotriene B4 from burn neutrophils was due to increased degradation or diminished synthesis of leukotriene B4, we examined the degradation of exogenous tritiated leukotriene B4 as well as the production of leukotriene B4 from tritiated arachidonic acid in neutrophils. Burn neutrophils converted significantly greater quantities of tritiated leukotriene B4 to tritiated 20-COOH-leukotriene B4 and synthesized markedly less tritiated leukotriene B4 from tritiated arachidonic acid than did control neutrophils, suggesting that decreased leukotriene B4 release by burn neutrophils was the result of both enhanced degradation and decreased synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8381849

  3. Functionalized nanoparticles provide early cardioprotection after acute myocardial infarction.

    PubMed

    Chang, Ming-Yao; Yang, Yu-Jen; Chang, Chih-Han; Tang, Alan C L; Liao, Wei-Yin; Cheng, Fong-Yu; Yeh, Chen-Sheng; Lai, James J; Stayton, Patrick S; Hsieh, Patrick C H

    2013-09-10

    Recent developments in nanotechnology have created considerable potential toward diagnosis and cancer therapy. In contrast, the use of nanotechnology in tissue repair or regeneration remains largely unexplored. We hypothesized that intramyocardial injection of insulin-like growth factor (IGF)-1-complexed poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-IGF-1 NPs) increases IGF-1 retention, induces Akt phosphorylation, and provides early cardioprotection after acute myocardial infarction (MI). We synthesized 3 different sizes of PLGA particles (60 nm, 200 nm, and 1 μm) which were complexed with IGF-1 using electrostatic force to preserve the biological function of IGF-1. Afterward, we injected PLGA-IGF-1 NPs in the heart after MI directly. Compared with the other two larger particles, the 60 nm-sized PLGA-IGF-1 NPs carried more IGF-1 and induced more Akt phosphorylation in cultured cardiomyocytes. PLGA-IGF-1 NPs also prolonged Akt activation in cardiomyocytes up to 24h and prevented cardiomyocyte apoptosis induced by doxorubicin in a dose-dependent manner. In vivo, PLGA-IGF-1 NP treatment significantly retained more IGF-1 in the myocardium than the IGF-1 alone treatment at 2, 6, 8, and 24 h. Akt phosphorylation was detected in cardiomyocytes 24h post-MI only in hearts receiving PLGA-IGF-1 NP treatment, but not in hearts receiving injection of PBS, IGF-1 or PLGA NPs. Importantly, a single intramyocardial injection of PLGA-IGF-1 NPs was sufficient to prevent cardiomyocyte apoptosis (P<0.001), reduce infarct size (P<0.05), and improve left ventricle ejection fraction (P<0.01) 21 days after experimental MI in mice. Our results not only demonstrate the potential of nanoparticle-based technology as a new approach to treating MI, but also have significant implications for translation of this technology into clinical therapy for ischemic cardiovascular diseases. PMID:23665256

  4. Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 maintain functional tolerance to ethanol.

    PubMed

    Szabò, G; Hoffman, P L

    1995-12-01

    Neurotrophins and growth factors not only affect neuronal development, but also maintain neuronal survival and influence neuronal function in the adult brain, and affect various cognitive processes related to learning and memory. Functional tolerance to ethanol represents an adaptive change in the central nervous system that has been hypothesized to have mechanisms in common with those underlying learning or memory. In the present work, the effects of neurotrophins on ethanol tolerance were compared to the effect of the neuropeptide, arginine vasopressin, which maintains (reduces the rate of dissipation of) both ethanol tolerance and memory. Functional tolerance to ethanol was induced in C57BL/6J mice by feeding them an ethanol-containing liquid diet, and the effect of neurotrophins on the rate of dissipation of tolerance to the hypnotic effect of ethanol was assessed. Human recombinant brain-derived neutrophic factor, neurotrophin-3 and neurotrophin-4/5, injected intracerebroventricularly once daily following ethanol withdrawal, maintained ethanol tolerance, while tolerance dissipated in ethanol-fed mice injected with vehicle (artificial cerebrospinal fluid) or with basic fibroblast growth factor. The results demonstrate that some neurotrophins can modulate neuroadaptation to ethanol, supporting the hypothesis that these factors can influence the function of postmitotic neurons in the adult brain. PMID:8666023

  5. 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

  6. A common gene signature across multiple studies relate biomarkers and functional regulation in tolerance to renal allograft

    PubMed Central

    Baron, Daniel; Ramstein, Gérard; Chesneau, Mélanie; Echasseriau, Yann; Pallier, Annaick; Paul, Chloé; Degauque, Nicolas; Hernandez-Fuentes, Maria P; Sanchez-Fueyo, Alberto; Newell, Kenneth A; Giral, Magali; Soulillou, Jean-Paul; Houlgatte, Rémi; Brouard, Sophie

    2015-01-01

    Patients tolerant to a kidney graft display a specific blood cell transcriptional pattern but results from five different studies were inconsistent, raising the question of relevance for future clinical application. To resolve this, we sought to identify a common gene signature, specific functional and cellular components, and discriminating biomarkers for tolerance following kidney transplantation. A meta-analysis of studies identified a robust gene signature involving proliferation of B and CD4 T cells, and inhibition of CD14 monocyte related functions among 96 tolerant samples. This signature was further supported through a cross-validation approach, yielding 92.5% accuracy independent of the study of origin. Experimental validation, performed on new tolerant samples and using a selection of the top-20 biomarkers, returned 91.7% of good classification. Beyond the confirmation of B-cell involvement, our data also indicated participation of other cell subsets in tolerance. Thus, the use of the top 20 biomarkers, mostly centered on B cells, may provide a common and standardized tool towards personalized medicine for the monitoring of tolerant or low-risk patients among kidney allotransplant recipients. These data point to a global preservation of genes favoring the maintenance of a homeostatic and ‘healthy' environment in tolerant patients and may contribute to a better understanding of tolerance maintenance mechanisms. PMID:25629549

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

    PubMed

    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

  9. 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...

  10. 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

  11. Copper tolerant ecotypes of Heliscus lugdunensis differ in their ecological function and growth.

    PubMed

    Quainoo, Scott; Seena, Sahadevan; Graça, Manuel A S

    2016-02-15

    Metal tolerance in aquatic hyphomycetes varies with the level of pollution at the fungal isolation site. While the focus of previous research has been on the effects of metal exposure on interspecies diversity, intraspecies variation of aquatic hyphomycetes remains largely unexplored. In this study we investigate the effects of Cu on ecological function (litter decomposition) and growth of five strains of Heliscus lugdunensis, isolated from contaminated and un-contaminated streams, in order to examine whether strains are expressed as ecotypes with distinct growth and functional signatures in response to metal stress. When exposed to Cu, strains of H. lugdunensis differed significantly in their litter decomposition and reproductive activity (sporulation) as well as mycelial growth, corresponding to the Cu concentrations at their isolation site. Strains isolated from sites with high Cu concentrations induced the highest litter decomposition or invested most in growth. This study broadens our understanding of Cu pollution in streams, which may lead to evolved adaptations of Cu tolerant ecotypes of H. lugdunensis differing in their ecological function, behaviour and morphology when exposed to metals. PMID:26657362

  12. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  13. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction.

    PubMed

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2013-10-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell-selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

  14. 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.

  15. Change in Psychosocial Functioning and Depressive Symptoms during Acute-Phase Cognitive Therapy for Depression

    PubMed Central

    Dunn, Todd W.; Vittengl, Jeffrey R.; Clark, Lee Anna; Carmody, Thomas; Thase, Michael E.; Jarrett, Robin B.

    2013-01-01

    Background Major Depressive Disorder (MDD) is highly prevalent, is recurrent, and impairs people’s work, relationships, and leisure. Acute-phase treatments improve psychosocial impairment associated with MDD, but how these improvements occur is unclear. In this study, we tested the hypotheses that reductions in depressive symptoms exceed, precede, and predict improvements in psychosocial functioning. Method Patients with recurrent MDD (N = 523; 68% women, 81% Caucasian; M = 42 years old) received acute-phase Cognitive Therapy (CT; Beck, Rush, Shaw & Emery, 1979). We measured functioning and symptom severity with the Social Adjustment Scale—Self-Report (Weissman & Bothwell, 1976), Range of Impaired Functioning Tool (Leon et al., 1999), Beck Depression Inventory (Beck, Ward, Mendelson, Mock, & Erbaugh, 1961), Hamilton Rating Scale for Depression (Hamilton, 1960) and Inventory for Depressive Symptomatology—Self-Report (Rush et al., 1996). We tested cross-lagged correlations between functioning and symptoms measured at baseline and the beginning, middle and end of acute phase CT. Results Pre- to post- treatment improvement in psychosocial functioning and depressive symptoms was large and inter-correlated. Depressive symptoms improved more and sooner than did psychosocial functioning. But among four assessments across the course of treatment, improvements in functioning more strongly predicted later improvement in symptoms than vice versa. Conclusions Improvements in psychosocial functioning and depressive symptoms correlate substantially during acute-phase CT, and improvements in functioning may play a role in subsequent symptom reduction during acute-phase CT. PMID:21781377

  16. 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.

  17. 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

  18. 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. PMID:20739429

  19. Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

    PubMed Central

    Ruberti, Maristela; Fernandes, Luis Gustavo Romani; Simioni, Patricia Ucelli; Gabriel, Dirce Lima; Yamada, Áureo Tatsumi; Tamashiro, Wirla Maria da Silva Cunha

    2012-01-01

    In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs) from small intestine of transgenic (TGN) DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+ and CD4+ T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103+ cells in CD4+ T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β+ T-cell subset in IELs of TGN. The frequency of Foxp3+ cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+ subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa. PMID:22400033

  20. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    PubMed

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function. PMID:26612091

  1. Acute response and chronic stimulus for cardiac structural and functional adaptation in a professional boxer.

    PubMed

    Oxborough, David; George, Keith; Utomi, Victor; Lord, Rachel; Morton, James; Jones, Nigel; Somauroo, John

    2014-06-01

    The individual response to acute and chronic changes in cardiac structure and function to intense exercise training is not fully understood and therefore evidence in this setting may help to improve the timing and interpretation of pre-participation cardiac screening. The following case report highlights an acute increase in right ventricular (RV) size and a reduction in left ventricular (LV) basal radial function with concomitant increase at the mid-level in response to a week's increase in training volume in a professional boxer. These adaptations settle by the second week; however, chronic physiological adaptation occurs over a 12-week period. Electrocardiographic findings demonstrate an acute lateral T-wave inversion at 1 week, which revert to baseline for the duration of training. It appears that a change in training intensity and volume generates an acute response within the RV that acts as a stimulus for chronic adaptation in this professional boxer. PMID:25988031

  2. 11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

    PubMed

    Alongi, Filippo; Liardo, Rocco L E; Iftode, Cristina; Lopci, Egesta; Villa, Elisa; Comito, Tiziana; Tozzi, Angelo; Navarria, Pierina; Ascolese, Anna M; Mancosu, Pietro; Tomatis, Stefano; Bellorofonte, Carlo; Arturo, Chiti; Scorsetti, Marta

    2014-10-01

    The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer

  3. Extracellular functional noncoding nucleic acid bioaptamers and angiotropin RNP ribokines in vascularization and self-tolerance.

    PubMed

    Wissler, Josef H; Wissler, Joerg E; Logemann, Enno

    2008-08-01

    Endogenous extracellular and circulating functional small noncoding nucleic acids (ncNAs; <200 nucleotides) and complexes with proteins (ribonucleoproteins; RNPs) make up varying biolibraries of molecular imprints of cellular histories. They are nascently formed upon cellular activation by extrinsic (environmental) factors, including mitogens, cell-mediated immune memory reactions (Landsteiner-Chase-Lawrence transfer factors), and metabolic (hypoxia) and (physical) shear stress forces. Those factors are conventional models for epigenetic (non-Mendelian) vascular remodeling variations directed rather to proteinaceous gene expression and regulation than genomic DNA sequence changes. Structurally defined ncNAs are described as small hairpin nc-shRNA bioaptamers in interaction with proteins forming functional (Cu,Ca,Na,K)-metalloregulated complexes (CuRNP; angiotropins). As nonmitogenic angiomorphogen cytokines (ribokines), they may reprogram confluent quiescent (contact-inhibited) endothelial cell types to migratory, phagokinetically active phenotypes in the morphogenesis of tolerated neovascular patterns. Their functions in organized and mess-chaotic vascular patterns were investigated with regard to master gene, information, epigenetic, vascular, and tumor factors. Some ncNAs feature three-dimensional codes (3D episcripts) for distinct protein conformer phases. They are suggested as being specific recognition types, the estimated repertoires of which are superior in diversity and specificity to conventional immune (glyco-)proteins. For episcription of phenotype variations, they may address and integrate information flow on molecular shapes to protein-mediated nucleic acid processing and [post-]translational modification mechanisms in ncNA-, redox, and metalloregulated conformation phase pathway-locked loops (CPLL). Several vascular and cancer epigenetic regulator proteins are shown to be entangled by sharing helix-nucleating structural (proteomic) domains for

  4. Pretransplant thymic function predicts acute rejection in antithymocyte globulin-treated renal transplant recipients.

    PubMed

    Bamoulid, Jamal; Courivaud, Cécile; Crepin, Thomas; Carron, Clémence; Gaiffe, Emilie; Roubiou, Caroline; Laheurte, Caroline; Moulin, Bruno; Frimat, Luc; Rieu, Philippe; Mousson, Christiane; Durrbach, Antoine; Heng, Anne-Elisabeth; Rebibou, Jean-Michel; Saas, Philippe; Ducloux, Didier

    2016-05-01

    Lack of clear identification of patients at high risk of acute rejection hampers the ability to individualize immunosuppressive therapy. Here we studied whether thymic function may predict acute rejection in antithymocyte globulin (ATG)-treated renal transplant recipients in 482 patients prospectively studied during the first year post-transplant of which 86 patients experienced acute rejection. Only CD45RA(+)CD31(+)CD4(+) T cell (recent thymic emigrant [RTE]) frequency (RTE%) was marginally associated with acute rejection in the whole population. This T-cell subset accounts for 26% of CD4(+) T cells. Pretransplant RTE% was significantly associated with acute rejection in ATG-treated patients (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08) for each increased percent in RTE/CD4(+) T cells), but not in anti-CD25 monoclonal (αCD25 mAb)-treated patients. Acute rejection was significantly more frequent in ATG-treated patients with high pretransplant RTE% (31.2% vs. 16.4%) or absolute number of RTE/mm(3) (31.7 vs. 16.1). This difference was not found in αCD25 monclonal antibody-treated patients. Highest values of both RTE% (>31%, hazard ratio, 2.50; 95% confidence interval, 1.09-5.74) and RTE/mm(3) (>200/mm(3), hazard ratio, 3.71; 95% confidence interval, 1.59-8.70) were predictive of acute rejection in ATG-treated patients but not in patients having received αCD25 monoclonal antibody). Results were confirmed in a retrospective cohort using T-cell receptor excision circle levels as a marker of thymic function. Thus, pretransplant thymic function predicts acute rejection in ATG-treated patients. PMID:27083287

  5. 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. PMID:26901150

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

    PubMed Central

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

    2015-01-01

    SUMMARY Autoreactive B cells play critical roles in a large diversity of autoimmune diseases, but the molecular pathways controlling these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed miRNA library and identified the microRNA 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 upon B cell receptor engagement via suppressing the expression of Gadd45a, Pten and Bcl2l11, which encodes the pro-apoptotic factor Bim. Furthermore, increased expression of miR-148a, which occurs frequently in lupus patients and lupus-prone mice, facilitated the development of lethal autoimmune disease in a lupus mouse model. These studies demonstrate that miR-148a functions as an important regulator of B cell tolerance and autoimmunity. PMID:26901150

  7. 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. PMID:19816097

  8. The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance.

    PubMed

    Wu, Jian-Xin; Li, Jian; Liu, Zhe; Yin, Jian; Chang, Zhen-Yi; Rong, Chan; Wu, Jia-Li; Bi, Fang-Cheng; Yao, Nan

    2015-03-01

    Ceramidases hydrolyze ceramide into sphingosine and fatty acids. In mammals, ceramidases function as key regulators of sphingolipid homeostasis, but little is known about their roles in plants. Here we characterize the Arabidopsis ceramidase AtACER, a homolog of human alkaline ceramidases. The acer-1 T-DNA insertion mutant has pleiotropic phenotypes, including reduction of leaf size, dwarfing and an irregular wax layer, compared with wild-type plants. Quantitative sphingolipid profiling showed that acer-1 mutants and the artificial microRNA-mediated silenced line amiR-ACER-1 have high ceramide levels and decreased long chain bases. AtACER localizes predominantly to the endoplasmic reticulum, and partially to the Golgi complex. Furthermore, we found that acer-1 mutants and AtACER RNAi lines showed increased sensitivity to salt stress, and lines overexpressing AtACER showed increased tolerance to salt stress. Reduction of AtACER also increased plant susceptibility to Pseudomonas syringae. Our data highlight the key biological functions of ceramidases in biotic and abiotic stresses in plants. PMID:25619405

  9. Aluminum-activated citrate and malate transporters encoded by distinct Al tolerance genes function independently in Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum (Al) -activated malate and citrate exudation from roots plays an important role in conferring Al tolerance to many plant species. Here, we report on the identification and characterization of AtMATE, the gene encoding an Al-activated root citrate efflux transporter that functions in Arabid...

  10. 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…

  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. 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

  13. Effects of oxytocin-related peptides on acute morphine tolerance: opposite actions by oxytocin and its receptor antagonists.

    PubMed

    Kovács, G L; Sarnyai, Z; Izbéki, F; Szabó, G; Telegdy, G; Barth, T; Jost, K; Brtnik, F

    1987-05-01

    The hormonally and behaviorally active nonapeptide oxytocin (OXT), its behaviorally active N-terminal octapeptide desglycinamide9-OXT and Z-prolyl-D-leucine, a synthetic analog of the C-terminal prolyl7-leucine8 sequence, inhibited the development both of a moderate and of a strong tolerance to morphine. N-alpha-Acetyl-(2-0-methyltyrosine)-OXT and (penicillamine1-2-0-methyltyrosine)- lysine8-vasopressin, both OXT receptor antagonists, facilitated the development of a moderate morphine tolerance. The i.c.v. injection of either antagonist prevented the effects of i.c.v. and s.c. OXT treatment on the development of tolerance. The effect of desglycinamide9-OXT, but not that of Z-prolyl-D-leucine was also prevented by N-alpha-acetyl-(2-0-methyltyrosine)-OXT. It is concluded that OXT and desglycinamide9-OXT, but not Z-prolyl-D-leucine, attenuate morphine tolerance by affecting putative oxytocinergic binding sites in the mouse brain. The fact that i.c.v. injection of the receptor antagonist also blocked the effect of s.c. OXT treatment argues in favor of the possibility that a minor proportion of s.c. OXT (or behaviorally active fragments thereof) may reach central nervous system target sites. PMID:3033220

  14. Depression in acute and chronic aphasia: symptoms, pathoanatomical-clinical correlations and functional implications.

    PubMed Central

    Herrmann, M; Bartels, C; Wallesch, C W

    1993-01-01

    Depressive alterations were investigated in 21 acute and 21 chronic aphasic patients with single left sided strokes. The assessment of depression was based on a psychometrically evaluated German version of the Cornell Scale for Depression (CDS) and the Research Diagnostic Criteria (RDC). No significant difference was found concerning depression sum-scores between the two aphasic groups. The acute group, however, exhibited significantly higher ratings in items related to physical signs of depression and disturbances of cyclic functions. Patients corresponding to the RDC-syndrome of major depression were only found in the acute group. Neither age, sex nor degree of hemiparesis discriminated the patients on the severity of depressive symptoms. In the acute patient group, nonfluency of aphasia was the only parameter that could be identified which had an effect on the mood symptom scores. A CT scan analysis in the acute patient group showed an association between the severity of depression and anterior lesions. A significant correlation was found between CDS sum-scores and the proximity of the anterior border of the lesion to the frontal pole of the hemisphere whereas the volume of lesions seemed to have no effect on depressive alterations in acute aphasic patients. Superimposition of the lesions of the aphasic patients with major depressive disorders showed a common subcortical lesion area involving putaminal and external pallidal structures. Images PMID:8509782

  15. 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)…

  16. Utility of EEG measures of brain function in patients with acute stroke.

    PubMed

    Wu, Jennifer; Srinivasan, Ramesh; Burke Quinlan, Erin; Solodkin, Ana; Small, Steven L; Cramer, Steven C

    2016-06-01

    EEG has been used to study acute stroke for decades; however, because of several limitations EEG-based measures rarely inform clinical decision-making in this setting. Recent advances in EEG hardware, recording electrodes, and EEG software could overcome these limitations. The present study examined how well dense-array (256 electrodes) EEG, acquired with a saline-lead net and analyzed with whole brain partial least squares (PLS) modeling, captured extent of acute stroke behavioral deficits and varied in relation to acute brain injury. In 24 patients admitted for acute ischemic stroke, 3 min of resting-state EEG was acquired at bedside, including in the ER and ICU. Traditional quantitative EEG measures (power in a specific lead, in any frequency band) showed a modest association with behavioral deficits [NIH Stroke Scale (NIHSS) score] in bivariate models. However, PLS models of delta or beta power across whole brain correlated strongly with NIHSS score (R(2) = 0.85-0.90) and remained robust when further analyzed with cross-validation models (R(2) = 0.72-0.73). Larger infarct volume was associated with higher delta power, bilaterally; the contralesional findings were not attributable to mass effect, indicating that EEG captures significant information about acute stroke effects not available from MRI. We conclude that 1) dense-array EEG data are feasible as a bedside measure of brain function in patients with acute stroke; 2) high-dimension EEG data are strongly correlated with acute stroke behavioral deficits and are superior to traditional single-lead metrics in this regard; and 3) EEG captures significant information about acute stroke injury not available from structural brain imaging. PMID:26936984

  17. 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.

  18. 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. PMID:25054178

  19. The Functions of Serine 687 Phosphorylation of Human DNA Polymerase η in UV Damage Tolerance.

    PubMed

    Dai, Xiaoxia; You, Changjun; Wang, Yinsheng

    2016-06-01

    DNA polymerase η (polη) is a Y-family translesion synthesis polymerase that plays a key role in the cellular tolerance toward UV irradiation-induced DNA damage. Here, we identified, for the first time, the phosphorylation of serine 687 (Ser(687)), which is located in the highly conserved nuclear localization signal (NLS) region of human polη and is mediated by cyclin-dependent kinase 2 (CDK2). We also showed that this phosphorylation is stimulated in human cells upon UV light exposure and results in diminished interaction of polη with proliferating cell nuclear antigen (PCNA). Furthermore, we demonstrated that the phosphorylation of Ser(687) in polη confers cellular protection from UV irradiation and increases the efficiency in replication across a site-specifically incorporated cyclobutane pyrimidine dimer in human cells. Based on these results, we proposed a mechanistic model where Ser(687) phosphorylation functions in the reverse polymerase switching step of translesion synthesis: The phosphorylation brings negative charges to the NLS of polη, which facilitates its departure from PCNA, thereby resetting the replication fork for highly accurate and processive DNA replication. Thus, our study, together with previous findings, supported that the posttranslational modifications of NLS of polη played a dual role in polymerase switching, where Lys(682) deubiquitination promotes the recruitment of polη to PCNA immediately prior to lesion bypass and Ser(687) phosphorylation stimulates its departure from the replication fork immediately after lesion bypass. PMID:26988343

  20. Genome-Wide Functional Profiling Reveals Genes Required for Tolerance to Benzene Metabolites in Yeast

    PubMed Central

    North, Matthew; Tandon, Vickram J.; Thomas, Reuben; Loguinov, Alex; Gerlovina, Inna; Hubbard, Alan E.; Zhang, Luoping; Smith, Martyn T.; Vulpe, Chris D.

    2011-01-01

    Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease. PMID:21912624

  1. Time representation of mitochondrial morphology and function after acute spinal cord injury

    PubMed Central

    Jia, Zhi-qiang; Li, Gang; Zhang, Zhen-yu; Li, Hao-tian; Wang, Ji-quan; Fan, Zhong-kai; Lv, Gang

    2016-01-01

    Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na+-K+-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged. PMID:26981103

  2. Functional genomics of chlorine-induced acute lung injury in mice.

    PubMed

    Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

    2010-07-01

    Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury. PMID:20601635

  3. 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. PMID:25343829

  4. 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...

  5. 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...

  6. The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

    PubMed Central

    Obad, Ante; Palada, Ivan; Valic, Zoran; Ivančev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Željko

    2007-01-01

    Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting

  7. 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...

  8. Stepwise discriminant function analysis for rapid identification of acute promyelocytic leukemia from acute myeloid leukemia with multiparameter flow cytometry.

    PubMed

    Chen, Zhanguo; Li, Yan; Tong, Yongqing; Gao, Qingping; Mao, Xiaolu; Zhang, Wenjing; Xia, Zunen; Fu, Chaohong

    2016-03-01

    Diagnosis of acute promyelocytic leukemia (APL) has been accelerated by multiparameter flow cytometry (MFC). However, diagnostic interpretation of MFC readouts for APL depends on individual experience and knowledge, which inevitably increases the risk of arbitrariness. We appraised the feasibility of using stepwise discriminant function analysis (SDFA) based on MFC to optimize the minimal variables needed to distinguish APL from other acute myeloid leukemia (AML) without complicated data interpretation. Samples from 327 patients with APL (n = 51) and non-APL AML (n = 276) were randomly allocated into training (243 AML) and test sets (84 AML) for SDFA. The discriminant functions from SDFA were examined by correct classification, and the final variables were validated by differential expression. Finally, additional 20 samples from patients with atypical APL and AML confusable with APL were also identified by SDFA method and morphological analysis. The weighed discriminant function reveals seven differentially expressed variables (CD2/CD9/CD11b/CD13/CD34/HLA-DR/CD117), which predict a molecular result for APL characterization with an accuracy that approaches 99 % (99.6 and 98.8 % for AML samples in training and test sets, respectively). Furthermore, the SDFA outperformed either single variable analysis or the more limited 3-component analysis (CD34/CD117/HLA-DR) via separate SDFA, and was also superior to morphological analysis in terms of diagnostic efficacy. The established SDFA based on MFC with seven variables can precisely and rapidly differentiate APL and non-APL AML, which may contribute to the urgent initiation of all-trans-retinoic acid-based APL therapy. PMID:26759321

  9. Effects of acute physical exercise on executive functions: a comparison between aerobic and strength exercise.

    PubMed

    Alves, Christiano Rodrigues; Gualano, Bruno; Takao, Pollyana Pereira; Avakian, Paula; Fernandes, Rafael Mistura; Morine, Diego; Takito, Monica Yuri

    2012-08-01

    The aim of this study was to compare the effects of acute aerobic and strength exercises on selected executive functions. A counterbalanced, crossover, randomized trial was performed. Forty-two healthy women were randomly submitted to three different conditions: (1) aerobic exercise, (2) strength exercise, and (3) control condition. Before and after each condition, executive functions were measured by the Stroop Test and the Trail Making Test. Following the aerobic and strength sessions, the time to complete the Stroop "non-color word" and "color word" condition was lower when compared with that of the control session. The performance in the Trail Making Test was unchanged. In conclusion, both acute aerobic and strength exercises improve the executive functions. Nevertheless, this positive effect seems to be task and executive function dependent. PMID:22889693

  10. 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. PMID:23829369

  11. Acute Modulations in Permeability Barrier Function Regulate Epidermal Cornification

    PubMed Central

    Demerjian, Marianne; Hachem, Jean-Pierre; Tschachler, Erwin; Denecker, Geertrui; Declercq, Wim; Vandenabeele, Peter; Mauro, Theodora; Hupe, Melanie; Crumrine, Debra; Roelandt, Truus; Houben, Evi; Elias, Peter M.; Feingold, Kenneth R.

    2008-01-01

    Stratum corneum comprises corneocytes, derived from outer stratum granulosum during terminal differentiation, embedded in a lipid-enriched extracellular matrix, secreted from epidermal lamellar bodies. Permeability barrier insults stimulate rapid secretion of preformed lamellar bodies from the outer stratum granulosum, regulated through modulations in ionic gradients and serine protease (SP)/protease-activated receptor type 2 (PAR2) signaling. Because corneocytes are also required for barrier function, we hypothesized that corneocyte formation could also be regulated by barrier function. Barrier abrogation by two unrelated methods initiated a wave of cornification, assessed as TdT-mediated dUTP nick end-labeling-positive cells in stratum granulosum and newly cornified cells by electron microscopy. Because cornification was blocked by occlusion, corneocytes formed specifically in response to barrier, rather than injury or cell replacement, requirements. SP inhibitors and hyperacidification (which decreases SP activity) blocked cornification after barrier disruption. Similarly, cornification was delayed in PAR2−/− mice. Although classical markers of apoptosis [poly(ADP-ribose)polymerase and caspase (Casp)-3] remained unchanged, barrier disruption activated Casp-14. Moreover, the pan-Casp inhibitor Z-VAD-FMK delayed cornification, and corneocytes were structurally aberrant in Casp14−/− mice. Thus, permeability barrier requirements coordinately drive both the generation of the stratum corneum lipid-enriched extracellular matrix and the transformation of granular cells into corneocytes, in an SP- and Casp-14-dependent manner, signaled by PAR2. PMID:18156206

  12. Functional neuroimaging of acute oculomotor deficits in concussed athletes.

    PubMed

    Johnson, Brian; Zhang, Kai; Hallett, Mark; Slobounov, Semyon

    2015-09-01

    In the pursuit to better understand the neural underpinnings of oculomotor deficits following concussion we performed a battery of oculomotor tests while performing simultaneous functional magnetic resonance imaging (fMRI). Based on the increasing evidence that concussion can disrupt multiple brain functional networks, including the oculomotor control networks, a series of classic saccadic and smooth pursuit tasks were implemented. Nine concussed athletes were tested within seven days of injury along with nine age and sex matched healthy normal volunteers. Both behavioral and fMRI data revealed differential results between the concussed and normal volunteer groups. Concussed subjects displayed longer latency time in the saccadic tasks, worse position errors, and fewer numbers of self-paced saccades compared to normal volunteer subjects. Furthermore, the concussed group showed recruitment of additional brain regions and larger activation sites as evidenced by fMRI. As a potential diagnostic and management tool for concussion, oculomotor testing shows promise, and here we try to understand the reasons for this disrupted performance with the aide of advanced neuroimaging tools. PMID:25179246

  13. 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. PMID:27102012

  14. 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

  15. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice

    PubMed Central

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-01-01

    AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels

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

    PubMed Central

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

    2015-01-01

    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 points Few studies have investigated the effects of the intensity of exercise on executive function in older women Executive function improved after 20-min of aerobic exercise regardless of exercise intensity in older women Findings from the study were not confounded by prescribed medications; all participants who were older women were not taking any medications PMID:26336345

  17. 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. PMID:21457274

  18. Functional Imaging of Cognitive Control During Acute Alcohol Intoxication

    PubMed Central

    Anderson, Beth M; Stevens, Michael C; Meda, Shashwath; Jordan, Kathryn; Calhoun, Vince D; Pearlson, Godfrey D

    2010-01-01

    The anterior cingulate and a collection of other prefrontal and parietal brain regions are implicated in error processing and cognitive control. The effects of different doses of alcohol on activity within these brain regions during an fMRI task where errors are frequently committed have not been fully explored. This study examined the impact of a placebo [Breath Alcohol Concentration (BrAC) = 0.00%], moderate (BrAC = 0.05%) and high (BrAC = 0.10%) doses of alcohol on brain hemodynamic activity during a functional MRI (fMRI) Go/No-Go task in thirty-eight healthy volunteers. Alcohol increased reaction time and false alarm errors in a dose-dependent manner. FMRI analyses showed alcohol decreased activity in anterior cingulate, lateral prefrontal cortex, insula and parietal lobe regions during false alarm responses to No-Go stimuli. These findings indicate that brain regions implicated in error processing are affected by alcohol and might provide a neural basis for alcohol's effects on behavioral performance. PMID:20958334

  19. Efficacy of a whole-body vibration intervention to effect exercise tolerance and functional performance of the lower limbs of people with chronic obstructive pulmonary disease

    PubMed Central

    2012-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterised by dyspnoea, excessive sputum production, chronic cough, bronchitis and emphysema. Functionally, exercise tolerance is poor for people with COPD and is linked to difficulty in performing daily tasks. More specifically, exercise difficulties are due partly to dyspnoea and lower limb skeletal muscle dysfunction. The benefit of exercise that does not exacerbate the disease while improving exercise tolerance is salient. Whole-body vibration (WBV) is a mode of physical activity known to improve muscular function of the lower limbs, yet efficacy has not been investigated for a WBV intervention conducted in a home-based setting for people with COPD. Methods/design This clinically registered trial is a non-randomised placebo cross-over intervention based in the home of each participant (ACTRN12612000508875). Participants diagnosed with COPD will complete a six-week WBV intervention and then after a two-week washout period, will complete a six-week placebo training intervention. Participants will complete sessions twice a week. The duration of the trial is 14 weeks. Community-dwelling older adults with COPD will provide informed voluntary consent to participate. Outcome measures will include immediate, acute, and long-term responses to exercise. Discussion Quantifying responses to WBV among people with COPD will allow discussion of efficacy of WBV as a mode of physical activity. The skill required by the participant to perform physical activity with WBV is not demanding and may enhance habitual sustainability. The results of this trial could be used to support further research in both clinical and community settings. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR12612000508875) PMID:23181339

  20. Effects of Acute Exposures to Carbon Dioxide Upon Cognitive Functions

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

    Large quantities of carbon dioxide (CO2) originate from human metabolism and typically, within spacecraft, remain about 10-fold higher in concentration 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 International Space Station (ISS) that associates CO2 levels with reports of headaches by crewmembers. Additionally, there is concern that CO2 may contribute to vision impairment and intracranial pressure that has been observed in some crewmembers. Consequently, flight rules have been employed to control the level of CO2 below 4 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. However, the flight rule imposed limit, which places additional demands upon resources and current technology, still exceeds the lower bound of the threshold range for reportable headaches (2 - 5 mm Hg). Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached. The causes of the headaches may elicit other subtle adverse effects that occur at CO2 levels well below that for headaches. The concern that CO2 may have effects at levels below the threshold for headaches appears to be substantiated in unexpected findings 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. If findings of the earlier study are confirmed in crew-like subjects, our findings would provide additional evidence that CO2 may need to be

  1. 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...

  2. Phytochrome A and B Function Antagonistically to Regulate Cold Tolerance via Abscisic Acid-Dependent Jasmonate Signaling1[OPEN

    PubMed Central

    Guo, Zhixin; Li, Huizi; Wang, Mengmeng; Zhou, Jie; Xia, Xiaojian; Shi, Kai; Yu, Jingquan

    2016-01-01

    Light signaling and phytohormones both influence plant growth, development, and stress responses; however, cross talk between these two signaling pathways in response to cold remains underexplored. Here, we report that far-red light (FR) and red light (R) perceived by phytochrome A (phyA) and phyB positively and negatively regulated cold tolerance, respectively, in tomato (Solanum lycopersicum), which were associated with the regulation of levels of phytohormones such as abscisic acid (ABA) and jasmonic acid (JA) and transcript levels of ABA- and JA-related genes and the C-REPEAT BINDING FACTOR (CBF) stress signaling pathway genes. A reduction in the R/FR ratio did not alter cold tolerance, ABA and JA accumulation, and transcript levels of ABA- and JA-related genes and the CBF pathway genes in phyA mutant plants; however, those were significantly increased in wild-type and phyB plants with the reduction in the R/FR ratio. Even though low R/FR treatments did not confer cold tolerance in ABA-deficient (notabilis [not]) and JA-deficient (prosystemin-mediated responses2 [spr2]) mutants, it up-regulated ABA accumulation and signaling in the spr2 mutant, with no effect on JA levels and signaling in the not mutant. Foliar application of ABA and JA further confirmed that JA functioned downstream of ABA to activate the CBF pathway in light quality-mediated cold tolerance. It is concluded that phyA and phyB function antagonistically to regulate cold tolerance that essentially involves FR light-induced activation of phyA to induce ABA signaling and, subsequently, JA signaling, leading to an activation of the CBF pathway and a cold response in tomato plants. PMID:26527654

  3. 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.

  4. Acute effects of a winter air pollution episode on pulmonary function and respiratory symptoms of children

    SciTech Connect

    Hoek, G.; Brunekreef, B. )

    1993-09-01

    The acute respiratory effects of a wintertime air pollution episode were studied in a general population sample of 112 children who were 7-12 y of age and who lived in a nonurban community. Spirometry was performed on 6 d, with a fixed interval of 3 wk between successive tests. During an air pollution episode, an additional pulmonary function test was made. Acute respiratory symptoms of the children were noted in a diary. Ambient concentrations of sulfur dioxide, black smoke, particulate matter with an aerodynamic diameter less than 10 microns, and nitrogen dioxide were considered as exposure variables. The association of air pollution with pulmonary function and prevalence of acute respiratory symptoms was assessed by individual linear regression analysis and time series analysis, respectively. In February 1991, an air pollution episode occurred during which daily average sulfur dioxide concentrations were slightly above 100 micrograms/m3, and particulate matter (with an aerodynamic diameter of less than 10 microns) concentrations reached 174 micrograms/m3. During the episode, forced vital capacity, forced expiratory volume in 1 s, and maximal mid-expiratory flow were lower than on baseline tests. Significant negative associations were found between the concentration of sulfur dioxide, black smoke, and particulate matter with an aerodynamic diameter of less than 10 microns. No association between prevalence of acute respiratory symptoms and the concentration of these compounds was found.

  5. Functional Characterization of Core Genes From Patients With Acute Hepatitis C

    PubMed Central

    Tang, Xi; Wagoner, Jessica; Negash, Amina; Austin, Michael; McLauchlan, John; Hahn, Young S.; Rosen, Hugo R.; Polyak, Stephen J.

    2009-01-01

    The HCV core protein is implicated in diverse aspects of HCV-induced pathogenesis. There is a paucity of information on core in acute hepatitis C infection. We analyzed core gene sequences and protein functions from 13 patients acutely infected with HCV genotype 1. While core isolates differed slightly between patients, core quasispecies were relatively homogeneous within a patient. In 2 of 4 patients studied temporally, core quasispecies did not change over time. Comparison with more than 2700 published core isolates indicated that amino acid changes from a prototype reference strain found in acute core isolates were present in chronically infected persons at low frequency (6.4%, range 0-32%). Core isolates associated with lipid droplets (LDs) to similar degrees in Huh7 cells. Core diffusion in cells was not affected by non-conservative changes F130L and G161S in the lipid targeting domain of core. Core isolates inhibited ISRE- and NF-κB-dependent transcription, and TNF-α- induced nuclear translocation of NF-κB and were also secreted from Huh7 cells. The data suggest that upon transmission, core quasispecies undergo genetic homogenization associated with amino acid changes that are rarely found in chronic infection, and that despite genetic variation, acute core isolates retain similar functions in vitro. PMID:20170366

  6. 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

  7. A systematic review on the treatment of acute ankle sprain: brace versus other functional treatment types.

    PubMed

    Kemler, Ellen; van de Port, Ingrid; Backx, Frank; van Dijk, C Niek

    2011-03-01

    Ankle injuries, especially ankle sprains, are a common problem in sports and medical care. Ankle sprains result in pain and absenteeism from work and/or sports participation, and can lead to physical restrictions such as ankle instability. Nowadays, treatment of ankle injury basically consists of taping the ankle. The purpose of this review is to evaluate the effectiveness of ankle braces as a treatment for acute ankle sprains compared with other types of functional treatments such as ankle tape and elastic bandages. A computerized literature search was conducted using PubMed, EMBASE, CINAHL and the Cochrane Clinical Trial Register. This review includes randomized controlled trials in English, German and Dutch, published between 1990 and April 2009 that compared ankle braces as a treatment for lateral ankle sprains with other functional treatments. The inclusion criteria for this systematic review were (i) individuals (sports participants as well as non-sports participants) with an acute injury of the ankle (acute ankle sprains); (ii) use of an ankle brace as primary treatment for acute ankle sprains; (iii) control interventions including any other type of functional treatment (e.g. Tubigrip™, elastic wrap or ankle tape); and (iv) one of the following reported outcome measures: re-injuries, symptoms (pain, swelling, instability), functional outcomes and/or time to resumption of sports, daily activities and/or work. Eight studies met all inclusion criteria. Differences in outcome measures, intervention types and patient characteristics precluded pooling of the results, so best evidence syntheses were conducted. A few individual studies reported positive outcomes after treatment with an ankle brace compared with other functional methods, but our best evidence syntheses only demonstrated a better treatment result in terms of functional outcome. Other studies have suggested that ankle brace treatment is a more cost-effective method, so the use of braces after acute

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

    DOE PAGESBeta

    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.

  9. Physiological and iTRAQ-Based Proteomic Analyses Reveal the Function of Spermidine on Improving Drought Tolerance in White Clover.

    PubMed

    Li, Zhou; Zhang, Yan; Xu, Yi; Zhang, Xinquan; Peng, Yan; Ma, Xiao; Huang, Linkai; Yan, Yanhong

    2016-05-01

    Endogenous spermidine interacting with phytohormones may be involved in the regulation of differentially expressed proteins (DEPs) associated with drought tolerance in white clover. Plants treated with or without spermidine (50 μM) were subjected to 20% PEG 6000 nutrient solution to induce drought stress (50% leaf-relative water content). The results showed that increased endogenous spermidine induced by exogenous spermidine altered endogenous phytohormones in association with improved drought tolerance, as demonstrated by the delay in water-deficit development, improved photosynthesis and water use efficiency, and lower oxidative damage. As compared to untreated plants, Spd-treated plants maintained a higher abundance of DEPs under drought stress involved in (1) protein biosynthesis (ribosomal and chaperone proteins); (2) amino acids synthesis; (3) the carbon and energy metabolism; (4) antioxidant and stress defense (ascorbate peroxidase, glutathione peroxidase, and dehydrins); and (5) GA and ABA signaling pathways (gibberellin receptor GID1, ABA-responsive protein 17, and ABA stress ripening protein). Thus, the findings of proteome could explain the Spd-induced physiological effects associated with drought tolerance. The analysis of functional protein-protein networks further proved that the alteration of endogenous spermidine and phytohormones induced the interaction among ribosome, photosynthesis, carbon metabolism, and amino acid biosynthesis. These differences could contribute to improved drought tolerance. PMID:27030016

  10. Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs

    PubMed Central

    Sahu, Nisebita; Stephan, Jean-Philippe; Cruz, Darlene Dela; Merchant, Mark; Haley, Benjamin; Bourgon, Richard; Classon, Marie; Settleman, Jeff

    2016-01-01

    Acquired resistance to cancer drug therapies almost always occurs in advanced-stage patients even following a significant response to treatment. In addition to mutational mechanisms, various non-mutational resistance mechanisms have now been recognized. We previously described a chromatin-mediated subpopulation of reversibly drug-tolerant persisters that is dynamically maintained within a wide variety of tumour cell populations. Here we explore a potential role for microRNAs in such transient drug tolerance. Functional screening of 879 human microRNAs reveals miR-371-3p as a potent suppressor of drug tolerance. We identify PRDX6 (peroxiredoxin 6) as a key target of miR-371-3p in establishing drug tolerance by regulating PLA2/PKCα activity and reactive oxygen species. PRDX6 expression is associated with poor prognosis in cancers of multiple tissue origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest that co-targeting of peroxiredoxin 6 or modulating miR-371-3p expression together with targeted cancer therapies may delay or prevent acquired drug resistance. PMID:27484502

  11. Effects of acute and chronic hypohydration on kidney health and function.

    PubMed

    Feehally, John; Khosravi, Maryam

    2015-09-01

    The kidneys play a critical role in the homeostasis of body fluid tonicity and effective circulating volume. Renal homeostatic mechanisms are frequently challenged in acutely ill people. Fluid depletion causing hypovolemia may result in renal hypoperfusion that, if left untreated, may lead to acute kidney failure. Some populations, notably older people and neonates, are less tolerant of extremes in fluid loading and deprivation, similar to those with established chronic kidney disease. Risk of kidney injury during fluid depletion is increased by medications including diuretics, nonsteroidal antiinflammatory drugs, and renin-angiotensin system blockers. There is no consistent evidence indicating that lower-than-average fluid intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Increasing consumption of sugar-containing beverages is, however, a major concern for kidney health as a precursor of obesity and diabetes. There is no evidence that high dietary protein intake can cause chronic kidney disease, nor accelerate progression of established kidney disease. Idiosyncratic, adverse renal responses have been described with creatine supplements. There are only a few clinical conditions for which high fluid intake should be considered. These include recurrent kidney stones or urinary tract infections and, possibly, polycystic kidney disease. PMID:26290296

  12. Effect of acute doses of controlled-release carbamazepine on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function.

    PubMed

    van der Meyden, C H; Bartel, P R; Sommers, D K; Blom, M; Becker, P; Erasmus, S; Griesel, D

    1992-01-01

    The neurotoxic effect of acute doses of carbamazepine controlled-release (CBZ-CR) divitabs (800, 1,200, and 1,600 mg) was assessed on clinical, psychomotor, electrophysiological, and cognitive parameters of brain function in 10 healthy volunteers in a double-blind, randomised, placebo-controlled, phase I study. Significant changes compared to placebo were demonstrated for the clinical scales, ataxia (AT), convergence of the near-point (CNP), peak saccadic velocity (PSV), critical flicker fusion (CFF), spectral analysis of the EEG, and brainstem auditory evoked potential (BAEP) tests. Digit repetition, digit symbol substitution, Sternberg memory scanning time, Sternberg choice reaction time, saccadic latency, and saccadic accuracy showed important negative findings. Significant clinical tolerance to side effects developed within 20 to 33 h after CBZ-CR dosage during a period in which the mean CBZ blood levels remained virtually unchanged. CBZ-CR, 800, 1,200, and 1,600 mg yielded low, medium, and high therapeutic blood levels, respectively, for +10 to +33 h after dosage without the development of severe clinical side effects. PMID:1547763

  13. Effect of acute exercise on some haematological parameters and neutrophil functions in active and inactive subjects.

    PubMed

    Benoni, G; Bellavite, P; Adami, A; Chirumbolo, S; Lippi, G; Brocco, G; Cuzzolin, L

    1995-01-01

    In this work we studied the possible effects of acute exercise on some haematological parameters and on some functions of neutrophils in seven active and six inactive subjects. Physical exercise (10 min on a cycle ergometer at a heart rate of 150 beats.min-1) induced a significant increase in total leucocyte, lymphocyte and neutrophil concentrations in active subjects; serum iron and ferritin concentrations were lower in active compared to inactive subjects. Cellular adhesion, bactericidal activity and superoxide anion production did not change after exercise, while we also observed some differences between active and inactive subjects before exercise. In particular, the neutrophils from active subjects showed a significantly higher percentage of adhesion, higher bactericidal activity and lower superoxide anion production. In conclusion, the training induced changes in some neutrophil functions, while acute exercise influenced, overall, leucocyte concentrations. PMID:7768243

  14. [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. PMID:21641686

  15. Admission glucose and left ventricular systolic function in non-diabetic patients with acute myocardial infarction.

    PubMed

    Gierach, Joanna; Gierach, Marcin; Świątkiewicz, Iwona; Woźnicki, Marek; Grześk, Grzegorz; Sukiennik, Adam; Koziñski, Marek; Kubica, Jacek

    2016-03-01

    Carbohydrate metabolism disorder in patients hospitalized due to acute ST-segment elevation myocardial infarction (STEMI) is associated with poor outcome. The association is even stronger in non-diabetic patients compared to the diabetics. Poor outcome of patients with elevated parameters of carbohydrate metabolism may be associated with negative impact of these disorders on left ventricular (LV) function. The aim of the study was to determine the impact of admission glycemia on LV systolic function in acute phase and 6 months after myocardial infarction in STEMI patients treated with primary angioplasty, without carbohydrate disorders. The study group consisted of 52 patients (9 female, 43 male) aged 35-74 years, admitted to the Department of Cardiology and Internal Medicine, Collegium Medicum in Bydgoszcz, due to the first STEMI treated with primary coronary angioplasty with stent implantation, without diabetes in anamnesis and carbohydrate metabolism disorders diagnosed during hospitalization. Echocardiography was performed in all patients in acute phase and 6 months after MI. Plasma glucose were measured at hospital admission. In the subgroup with glycemia ≥7.1 mmol/l, in comparison to patients with glycemia <7.1 mmol/l, significantly lower ejection fraction (EF) was observed in acute phase of MI (44.4 ± 5.4 vs. 47.8 ± 6.3 %, p = 0.04) and trend to lower EF 6 months after MI [47.2 ± 6.5 vs. 50.3 ± 6.3 %, p = 0.08 (ns)]. Higher admission glycemia in patients with STEMI and without carbohydrate metabolism disturbances, may be a marker of poorer prognosis resulting from lower LV ejection fraction in the acute phase and in the long-term follow-up. PMID:25539622

  16. Investigation of intestine function during acute viral hepatitis using combined sugar oral loads.

    PubMed Central

    Parrilli, G; Cuomo, R; Nardone, G; Maio, G; Izzo, C M; Budillon, G

    1987-01-01

    One fifth of all cases of A virus hepatitis (AVH) have symptoms of gastroenteritis at the onset. This study investigated the mediated intestinal absorption of D-xylose (D-xyl) and 3-o-methyl-D-glucose (3-omG) and the non-mediated permeation of lactulose (Lacl, mol wt 342) and L-rhamnose (L-rh, mol wt 164) during acute and remission phases of AVH. Ten patients with AVH were given an oral load containing these sugars (5 g D-xyl: 2.5 g 3-omG, 1 g L-rh, 5 g lacl in 250 ml water) once during the acute phase and again during remission. The same load was given once to a group of 22 healthy controls. The mean concentration of D-xyl in urine and the ratio of D-xyl to 3-omG in plasma and urine were normal in both the AVH phases, ruling out intestinal malabsorption even in the acute phase. This study showed a significant increase in non-mediated permeation to Lacl, but not to L-rh, during the acute phase. These data indicate that the barrier function of the intestine is compromised in AVH infection while the absorptive function is not. An abnormally low concentration of D-xyl and 3-omG in plasma at one hour was found in all patients during the acute phase. This finding cannot be explained by alterations in intestinal absorption, but could be accounted for by increased space distribution of the sugars because of increased diffusion into tissue cells and/or expansion of the extracellular space by fluid retention. PMID:3428669

  17. Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function.

    PubMed

    Curtsinger, Julie M; Lins, Debra C; Mescher, Matthew F

    2003-05-01

    Activation of naive CD8 T cells to undergo clonal expansion and develop effector function requires three signals: (a) Ag, (b) costimulation, and (c) IL-12 or adjuvant. The requirement for the third signal to stimulate Ag-dependent proliferation is variable, making the greatest contribution when Ag levels are low. At high Ag levels, extensive proliferation can occur in vitro or in vivo in the absence of a third signal. However, despite having undergone the same number of divisions, cells that expand in the absence of a third signal fail to develop cytolytic effector function. Thus, proliferation and development of cytolytic function can be fully uncoupled. Furthermore, these cells are rendered functionally tolerant in vivo, in that subsequent restimulation with a potent stimulus results in limited clonal expansion, impaired IFN-gamma production, and no cytolytic function. Thus, the presence or absence of the third signal appears to be a critical variable in determining whether stimulation by Ag results in tolerance versus development of effector function and establishment of a responsive memory population. PMID:12732656

  18. 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. PMID:24832967

  19. 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...

  20. Abnormal hepatic function and splenomegaly on the newly diagnosed acute leukemia patients.

    PubMed

    Sharma Poudel, B; Karki, L

    2007-01-01

    To evaluate the liver function, splenomegaly and related factors in the newly diagnosed acute leukemia patients. One hundred of fifty eight acute leukemia patients admitted in our hospital from March 2003 to April 2006 were studied. The related factors such as peripheral WBC count, bone marrow blasts, peripheral blasts, sex, age, AML, ALL affecting the liver function and splenomegaly were evaluated. Sixty two (39.24%) patients presented with splenomegaly. Twelve (7.59%) patients presented with hepatomegaly. Serum ALT was elevated in 54 (34.17%) patients. Similarly, serum AST, GGT, ALP, and Direct bilirubin were elevated in 26 (16.45%), 32 (20.25%), 20 (12.65%), and 22 (13.92%) patients, respectively. Low serum albumin was found in 40 (25.31%) patients. PT was prolonged in 62 (39.24%) patients. Statistical study shows that there is a relation between high WBC counts and elevated serum ALT (P<0.05) and high WBC counts and splenomegaly (P<0.05). Acute leukemia patients with leukocytosis are more prone to develop abnormal liver function and splenomegaly. PMID:18340367

  1. 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 Central

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

    2013-01-01

    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 parenting-specific persistence behavior. PMID:23906942

  2. 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…

  3. The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

    PubMed Central

    Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

    2015-01-01

    Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

  4. Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial.

    PubMed

    Craddock, Charles; Jilani, Nadira; Siddique, Shamyla; Yap, Christina; Khan, Josephine; Nagra, Sandeep; Ward, Janice; Ferguson, Paul; Hazlewood, Peter; Buka, Richard; Vyas, Paresh; Goodyear, Oliver; Tholouli, Eleni; Crawley, Charles; Russell, Nigel; Byrne, Jenny; Malladi, Ram; Snowden, John; Dennis, Mike

    2016-02-01

    Disease relapse is the major causes of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute myeloid leukemia (AML). As well as demonstrating significant clinical activity in AML, azacitidine (AZA) upregulates putative tumor antigens, inducing a CD8(+) T cell response with the potential to augment a graft-versus-leukemia effect. We, therefore, studied the feasibility and clinical sequelae of the administration of AZA during the first year after transplantation in 51 patients with AML undergoing allogeneic SCT. Fourteen patients did not commence AZA either because of transplantation complications or withdrawal of consent. Thirty-seven patients commenced AZA at a median of 54 days (range, 40 to 194 days) after transplantation, which was well tolerated in the majority of patients. Thirty-one patients completed 3 or more cycles of AZA. Sixteen patients relapsed at a median time of 8 months after transplantation. No patient developed extensive chronic graft-versus-host disease. The induction of a post-transplantation CD8(+) T cell response to 1 or more tumor-specific peptides was studied in 28 patients. Induction of a CD8(+) T cell response was associated with a reduced risk of disease relapse (hazard ratio [HR], .30; 95% confidence interval [CI], .10 to .85; P = .02) and improved relapse-free survival (HR, .29; 95% CI, .10 to .83; P = .02) taking into account death as a competing risk. In conclusion, AZA is well tolerated after transplantation and appears to have the capacity to reduce the relapse risk in patients who demonstrate a CD8(+) T cell response to tumor antigens. These observations require confirmation in a prospective clinical trial. PMID:26363443

  5. Tolerability and Clinical Activity of Post-Transplantation Azacitidine in Patients Allografted for Acute Myeloid Leukemia Treated on the RICAZA Trial

    PubMed Central

    Craddock, Charles; Jilani, Nadira; Siddique, Shamyla; Yap, Christina; Khan, Josephine; Nagra, Sandeep; Ward, Janice; Ferguson, Paul; Hazlewood, Peter; Buka, Richard; Vyas, Paresh; Goodyear, Oliver; Tholouli, Eleni; Crawley, Charles; Russell, Nigel; Byrne, Jenny; Malladi, Ram; Snowden, John; Dennis, Mike

    2016-01-01

    Disease relapse is the major causes of treatment failure after allogeneic stem cell transplantation (SCT) in patients with acute myeloid leukemia (AML). As well as demonstrating significant clinical activity in AML, azacitidine (AZA) upregulates putative tumor antigens, inducing a CD8+ T cell response with the potential to augment a graft-versus-leukemia effect. We, therefore, studied the feasibility and clinical sequelae of the administration of AZA during the first year after transplantation in 51 patients with AML undergoing allogeneic SCT. Fourteen patients did not commence AZA either because of transplantation complications or withdrawal of consent. Thirty-seven patients commenced AZA at a median of 54 days (range, 40 to 194 days) after transplantation, which was well tolerated in the majority of patients. Thirty-one patients completed 3 or more cycles of AZA. Sixteen patients relapsed at a median time of 8 months after transplantation. No patient developed extensive chronic graft-versus-host disease. The induction of a post-transplantation CD8+ T cell response to 1 or more tumor-specific peptides was studied in 28 patients. Induction of a CD8+ T cell response was associated with a reduced risk of disease relapse (hazard ratio [HR], .30; 95% confidence interval [CI], .10 to .85; P = .02) and improved relapse-free survival (HR, .29; 95% CI, .10 to .83; P = .02) taking into account death as a competing risk. In conclusion, AZA is well tolerated after transplantation and appears to have the capacity to reduce the relapse risk in patients who demonstrate a CD8+ T cell response to tumor antigens. These observations require confirmation in a prospective clinical trial. PMID:26363443

  6. 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

  7. Effect of acute exercise and cardiovascular fitness on cognitive function: an event-related cortical desynchronization study.

    PubMed

    Chang, Yu-Kai; Chu, Chien-Heng; Wang, Chun-Chih; Song, Tai-Fen; Wei, Gao-Xia

    2015-03-01

    This study aimed to clarify the effects of acute exercise and cardiovascular fitness on cognitive function using the Stroop test and event-related desynchronization (ERD) in an aged population. Old adults (63.10 ± 2.89 years) were first assigned to either a high-fitness or a low-fitness group, and they were then subjected to an acute exercise treatment and a reading control treatment in a counterbalanced order. Alpha ERD was recorded during the Stroop test, which was administered after both treatments. Acute exercise improved cognitive performance regardless of the level of cognition, and old adults with higher fitness levels received greater benefits from acute exercise. Additionally, acute exercise, rather than overall fitness, elicited greater lower and upper alpha ERDs relative to the control condition. These findings indirectly suggest that the beneficial effects of acute exercise on cognitive performance may result from exercise-induced attentional control observed during frontal neural excitation. PMID:25308605

  8. 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

  9. Executive Function Late Effects in Survivors of Pediatric Brain Tumors and Acute Lymphoblastic Leukemia

    PubMed Central

    Winter, Amanda L.; Conklin, Heather M.; Tyc, Vida L.; Stancel, Heather; Hinds, Pamela S.; Hudson, Melissa M.; Kahalley, Lisa S.

    2014-01-01

    BACKGROUND Survivors of pediatric brain tumors (BT) and acute lymphoblastic leukemia (ALL) are at risk for neurocognitive late effects related to executive function. PROCEDURE Survivors of BT (48) and ALL (50) completed neurocognitive assessment. Executive function was compared to estimated IQ and population norms by diagnostic group. RESULTS Both BT and ALL demonstrated relative executive function weaknesses. As a group, BT survivors demonstrated weaker executive functioning than expected for age. Those BT survivors with deficits exhibited a profile suggestive of global executive dysfunction, while affected ALL survivors tended to demonstrate specific rapid naming deficits. CONCLUSION Findings suggest that pediatric BT and ALL survivors may exhibit different profiles of executive function late effects, which may necessitate distinct intervention plans. PMID:25126830

  10. Function of Ikaros as a tumor suppressor in B cell acute lymphoblastic leukemia

    PubMed Central

    Kastner, Philippe; Dupuis, Arnaud; Gaub, Marie-Pierre; Herbrecht, Raoul; Lutz, Patrick; Chan, Susan

    2013-01-01

    The Ikaros transcription factor is crucial for many aspects of hematopoiesis. Loss of function mutations in IKZF1, the gene encoding Ikaros, have been implicated in adult and pediatric B cell acute lymphoblastic leukemia (B-ALL). These mutations result in haploinsufficiency of the Ikaros gene in approximately half of the cases. The remaining cases contain more severe or compound mutations that lead to the generation of dominant-negative proteins or complete loss of function. All IKZF1 mutations are associated with a poor prognosis. Here we review the current genetic, clinical and mechanistic evidence for the role of Ikaros as a tumor suppressor in B-ALL. PMID:23358883

  11. 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.

  12. 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…

  13. Cement dust exposure and acute lung function: A cross shift study

    PubMed Central

    2010-01-01

    Background Few studies have been carried out on acute effects of cement dust exposure. This study is conducted to investigate the associations between current "total" dust exposure and acute respiratory symptoms and respiratory function among cement factory workers. Methods A combined cross-sectional and cross-shift study was conducted in Dire Dawa cement factory in Ethiopia. 40 exposed production workers from the crusher and packing sections and 20 controls from the guards were included. Personal "total" dust was measured in the workers' breathing zone and peak expiratory flow (PEF) was measured for all selected workers before and after the shift. When the day shift ended, the acute respiratory symptoms experienced were scored and recorded on a five-point Likert scale using a modified respiratory symptom score questionnaire. Results The highest geometric mean dust exposure was found in the crusher section (38.6 mg/m3) followed by the packing section (18.5 mg/m3) and the guards (0.4 mg/m3). The highest prevalence of respiratory symptoms for the high exposed workers was stuffy nose (85%) followed by shortness of breath (47%) and "sneezing" (45%). PEF decreased significantly across the shift in the high exposed group. Multiple linear regression showed a significant negative association between the percentage cross-shift change in PEF and total dust exposure. The number of years of work in high-exposure sections and current smoking were also associated with cross-shift decrease in PEF. Conclusions Total cement dust exposure was related to acute respiratory symptoms and acute ventilatory effects. Implementing measures to control dust and providing adequate personal respiratory protective equipment for the production workers are highly recommended. PMID:20398255

  14. 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.

  15. The acute extracellular flux (XF) assay to assess compound effects on mitochondrial function.

    PubMed

    Wang, Ruolan; Novick, Steven J; Mangum, James B; Queen, Kennedy; Ferrick, David A; Rogers, George W; Stimmel, Julie B

    2015-03-01

    Numerous investigations have linked mitochondrial dysfunction to adverse health outcomes and drug-induced toxicity. The pharmaceutical industry is challenged with identifying mitochondrial liabilities earlier in drug development and thereby reducing late-stage attrition. Consequently, there is a demand for reliable, higher-throughput screening methods for assessing the impact of drug candidates on mitochondrial function. The extracellular flux (XF) assay described here is a plate-based method in which galactose-conditioned HepG2 cells were acutely exposed to test compounds, then real-time changes in the oxygen consumption rate and extracellular acidification rate were simultaneously measured using a Seahorse Bioscience XF-96 analyzer. The acute XF assay was validated using marketed drugs known to modulate mitochondrial function, and data analysis was automated using a spline curve fitting model developed at GlaxoSmithKline. We demonstrate that the acute XF assay is a robust, sensitive screening platform for evaluating drug-induced effects on mitochondrial activity in whole cells. PMID:25381255

  16. Sexual dimorphism in lung function responses to acute influenza A infection

    PubMed Central

    Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Jessica E.; Dousha, Lovisa F.; Zosky, Graeme R.; Sly, Peter D.

    2011-01-01

    Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background  Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and females. Objectives  To determine whether sexual dimorphism exists in the physiological/inflammatory responses of weanling and adult BALB/c mice to influenza. Methods  Weanling and adult mice of both sexes were inoculated with influenza A or appropriate control solution. Respiratory mechanics, responsiveness to methacholine (MCh), viral titre and bronchoalveolar lavage (BAL) cellular inflammation/cytokines were measured 4 (acute) and 21 (resolution) days post‐inoculation. Results  Acute infection impaired lung function and induced hyperresponsiveness and cellular inflammation in both sexes at both ages. Males and females responded differently with female mice developing greater abnormalities in tissue damping and elastance and greater MCh responsiveness at both ages. BAL inflammation, cytokines and lung viral titres were similar between the sexes. At resolution, all parameters had returned to baseline levels in adults and weanling males; however, female weanlings had persisting hyperresponsiveness. Conclusions  We identified significant differences in the physiological responses of male and female mice to infection with influenza A, which occurred in the absence of variation in viral titre and cellular inflammation. PMID:21668688

  17. 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

  18. Slow channel inhibitor effects on brain function: tolerance to severe hypoxia in the rat.

    PubMed Central

    Cartheuser, C. F.

    1988-01-01

    1. The protective effects of ten slow channel inhibitor drugs against severe progressive hypoxia were investigated in rats breathing spontaneously during light anaesthesia. Respiration, heart rate, electrocorticogram (ECoG) and/or electroencephalogram (EEG) were recorded. 2. Tolerance times were monitored from hypoxia onset until cessation of respiration, ECoG, EEG synchronization, and 'background-EEG'. Drugs were administered i.v. 5 min before the onset of hypoxia. 3. Verapamil, gallopamil, and nimodipine resulted in a significant increase of tolerance times; fendiline and bepridil showed a small increase (not significant); bencyclan and prenylamine were ineffective; cinnarizine and diltiazem slightly reduced tolerance times as did flunarizine at low doses. 4. At protective doses, verapamil, gallopamil, and nimodipine significantly raised the respiration rate but had little or no cardiac depressor effects. Bencyclan showed ventilatory drive but cardiocirculatory depression. A clear-cut ventilatory drive did not occur with the other ineffective slow channel inhibitors. 5. It is suggested that the protective actions observed were not due to slow channel inhibition per se, nor to spasmolytic potency or increased cerebral blood flow. Ventilatory drive associated with other cardiopulmonary actions which secondarily raise the brain oxygen supply are likely to be responsible for this effect. PMID:3264735

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

    PubMed

    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

  20. Are species shade and drought tolerance reflected in leaf-level structural and functional differentiation in Northern Hemisphere temperate woody flora?

    PubMed

    Hallik, Lea; Niinemets, Ulo; Wright, Ian J

    2009-01-01

    Leaf-level determinants of species environmental stress tolerance are still poorly understood. Here, we explored dependencies of species shade (T(shade)) and drought (T(drought)) tolerance scores on key leaf structural and functional traits in 339 Northern Hemisphere temperate woody species. In general, T(shade) was positively associated with leaf life-span (L(L)), and negatively with leaf dry mass (M(A)), nitrogen content (N(A)), and photosynthetic capacity (A(A)) per area, while opposite relationships were observed with drought tolerance. Different trait combinations responsible for T(shade) and T(drought) were observed among the key plant functional types: deciduous and evergreen broadleaves and evergreen conifers. According to principal component analysis, resource-conserving species with low N content and photosynthetic capacity, and high L(L) and M(A), had higher T(drought), consistent with the general stress tolerance strategy, whereas variation in T(shade) did not concur with the postulated stress tolerance strategy. As drought and shade often interact in natural communities, reverse effects of foliar traits on these key environmental stress tolerances demonstrate that species niche differentiation is inherently constrained in temperate woody species. Different combinations of traits among key plant functional types further explain the contrasting bivariate correlations often observed in studies seeking functional explanation of variation in species environmental tolerances. PMID:19674334

  1. 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. PMID:24771143

  2. 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

  3. 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

  4. Maximum tolerated volume in drinking tests with water and a nutritional beverage for the diagnosis of functional dyspepsia

    PubMed Central

    Montaño-Loza, Aldo; Schmulson, Max; Zepeda-Gómez, Sergio; Remes-Troche, Jose Maria; Valdovinos-Diaz, Miguel Angel

    2005-01-01

    AIM: Recently, drinking load tests with water or nutritional beverages have been proposed as diagnostic tools for functional dyspepsia (FD), therefore we sought to reproduce if these tests can discriminate between FD patients and controls in a Mexican population. METHODS: Twenty FD-Rome II patients were matched by age and gender with 20 healthy controls. All underwent both drinking tests at a 15 mL/min rate, randomly, 7 d apart. Every 5 min within each test, four symptoms were evaluated (satiety, bloating, nausea and pain) by Likert scales. Maximum tolerated volume (MTV) was defined as the ingested volume when a score of 5 was reached for any symptom or when the test had to be stopped because the patients could not tolerate more volume. Sensitivity and specificity were analyzed. RESULTS: FD patients had higher symptom scores for both tests compared to controls (water: t = 4.1, P = 0.001<0.01; Nutren®: t = 5.2, P = 0.001<0.01). The MTV for water and Nutren® were significantly lower in FD (water: 1014±288 vs 1749±275 mL; t = 7.9, P = 0.001<0.01; Nutren®: 652±168 vs 1278±286 mL; t = 6.7, P = 0.001<0.01). With the volume tolerated by the controls, the percentile 10 was determined as the lower limit for tolerance. Sensitivity and specificity were 0.90, 0.95 for water and 0.95, 0.95 for Nutren® tests. CONCLUSION: A drinking test with water or a nutritional beverage can discriminate between FD patients and healthy subjects in Mexico, with high sensitivity and specificity. These tests could be used as objective, noninvasive, and safe diagnostic approaches for FD patients. PMID:15918201

  5. Disparities between black and white patients in functional improvement after hospitalization for an acute illness.

    PubMed

    Sands, Laura P; Landefeld, C Seth; Ayers, Sandra Moody; Yaffe, Kristine; Palmer, Robert; Fortinsky, Richard; Counsell, Steven R; Covinsky, Kenneth E

    2005-10-01

    The aim of this study was to determine whether older black and white patients experience different rates of improvement in functioning after being acutely hospitalized. Of the 2,364 community-living patients in this prospective cohort study, 25% self-reported their race/ethnicity to be black. The outcomes were improvement in basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) from admission to discharge and 90 days postdischarge. Multivariable models that included statistical adjustment for age, illness severity, in-hospital social service referral, dementia, admission level of functioning, and change in functioning from 2 weeks before admission were computed to determine whether black and white patients experienced significantly different rates of recovery at discharge and 90 days after discharge in ADL and IADL functioning. Black patients were as likely as white patients to improve in ADL functioning by discharge (odds ratio (OR)=0.97, 95% confidence interval (CI)=0.76-1.24) or by 90 days after discharge (OR=0.95, 95% CI=0.73-1.24) but significantly less likely to improve IADL functioning by discharge (OR=0.72, 95% CI=0.56-0.93) or by 90 days after discharge (OR=0.68, 95% CI=0.51-0.90). The findings suggest that differential rates of recovery in functioning after an acute hospitalization may contribute to racial/ethnic disparities in IADL functioning, which has implications for the setting of future interventions oriented toward reducing these disparities. PMID:16181184

  6. Reduced functional connectivity in the thalamo-insular subnetwork in patients with acute anorexia nervosa.

    PubMed

    Ehrlich, Stefan; Lord, Anton R; Geisler, Daniel; Borchardt, Viola; Boehm, Ilka; Seidel, Maria; Ritschel, Franziska; Schulze, Anne; King, Joseph A; Weidner, Kerstin; Roessner, Veit; Walter, Martin

    2015-05-01

    The neural underpinnings of anorexia nervosa (AN) are poorly understood. Results from existing functional brain imaging studies using disorder-relevant food- or body-stimuli have been heterogeneous and may be biased due to varying compliance or strategies of the participants. In this study, resting state functional connectivity imaging was used. To explore the distributed nature and complexity of brain function we characterized network patterns in patients with acute AN. Thirty-five unmedicated female acute AN patients and 35 closely matched healthy female participants underwent resting state functional magnetic resonance imaging. We used a network-based statistic (NBS) approach [Zalesky et al., 2010a] to identify differences between groups by isolating a network of interconnected nodes with a deviant connectivity pattern. Group comparison revealed a subnetwork of connections with decreased connectivity including the amygdala, thalamus, fusiform gyrus, putamen and the posterior insula as the central hub in the patient group. Results were not driven by changes in intranodal or global connectivity. No network could be identified where AN patients had increased coupling. Given the known involvement of the identified thalamo-insular subnetwork in interoception, decreased connectivity in AN patients in these nodes might reflect changes in the propagation of sensations that alert the organism to urgent homeostatic imbalances and pain-processes that are known to be severely disturbed in AN and might explain the striking discrepancy between patient's actual and perceived internal body state. PMID:25611053

  7. 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

  8. Local Sampling of the Wigner Function at Telecom Wavelength with Loss-Tolerant Detection of Photon Statistics.

    PubMed

    Harder, G; Silberhorn, Ch; Rehacek, J; Hradil, Z; Motka, L; Stoklasa, B; Sánchez-Soto, L L

    2016-04-01

    We report the experimental point-by-point sampling of the Wigner function for nonclassical states created in an ultrafast pulsed type-II parametric down-conversion source. We use a loss-tolerant time-multiplexed detector based on a fiber-optical setup and a pair of photon-number-resolving avalanche photodiodes. By capitalizing on an expedient data-pattern tomography, we assess the properties of the light states with outstanding accuracy. The method allows us to reliably infer the squeezing of genuine two-mode states without any phase reference. PMID:27081977

  9. Local Sampling of the Wigner Function at Telecom Wavelength with Loss-Tolerant Detection of Photon Statistics

    NASA Astrophysics Data System (ADS)

    Harder, G.; Silberhorn, Ch.; Rehacek, J.; Hradil, Z.; Motka, L.; Stoklasa, B.; Sánchez-Soto, L. L.

    2016-04-01

    We report the experimental point-by-point sampling of the Wigner function for nonclassical states created in an ultrafast pulsed type-II parametric down-conversion source. We use a loss-tolerant time-multiplexed detector based on a fiber-optical setup and a pair of photon-number-resolving avalanche photodiodes. By capitalizing on an expedient data-pattern tomography, we assess the properties of the light states with outstanding accuracy. The method allows us to reliably infer the squeezing of genuine two-mode states without any phase reference.

  10. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance.

    PubMed

    Ring, Margareta; Eriksson, Maria J; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R; Caidahl, Kenneth

    2015-09-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima-media thickness in the radial and carotid arteries, echogenicity of the carotid intima-media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  11. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance

    PubMed Central

    Eriksson, Maria J.; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R.; Caidahl, Kenneth

    2015-01-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima–media thickness in the radial and carotid arteries, echogenicity of the carotid intima–media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  12. 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

  13. 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

    2016-01-01

    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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. Dose Ranging, Expanded Acute Toxicity and Safety Pharmacology Studies for Intravenously Administered Functionalized Graphene Nanoparticle Formulations

    PubMed Central

    Kanakia, Shruti; Toussaint, Jimmy; Chowdhury, Sayan Mullick; Tembulkar, Tanuf; Lee, Stephen; Jiang, Ya-Ping; Lin, Richard Z.; Shroyer, Kenneth R.; Moore, William; Sitharaman, Balaji

    2014-01-01

    Graphene nanoparticles dispersions show immense potential as multifunctional agents for in vivo biomedical applications. Herein, we follow regulatory guidelines for pharmaceuticals that recommend safety pharmacology assessment at least 10 – 100 times higher than the projected therapeutic dose, and present comprehensive single dose response, expanded acute toxicology, toxicokinetics, and respiratory/cardiovascular safety pharmacology results for intravenously administered dextran-coated graphene oxide nanoplatelet (GNP-Dex) formulations to rats at doses between 1–500 mg/kg. Our results indicate that the maximum tolerable dose (MTD) of GNP-Dex is between 50 mg/kg ≤ MTD < 125 mg/kg, blood half-life < 30 minutes, and majority of nanoparticles excreted within 24 hours through feces. Histopathology changes were noted at ≥ 250 mg/kg in the heart, liver, lung, spleen, and kidney; we found no changes in the brain and no GNP-Dex related effects in the cardiovascular parameters or hematological factors (blood, lipid, and metabolic panels) at doses < 125 mg/kg. The results open avenues for pivotal preclinical single and repeat dose safety studies following good laboratory practices (GLP) as required by regulatory agencies for investigational new drug (IND) application. PMID:24854092

  19. 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. PMID:26681305

  20. 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. PMID:26441146

  1. A bi-functional xyloglucan galactosyltransferase is an indispensable salt stress tolerance determinant in Arabidopsis.

    PubMed

    Li, Wenbo; Guan, Qingmei; Wang, Zhen-Yu; Wang, Yingdian; Zhu, Jianhua

    2013-07-01

    Salinity is an abiotic stress that substantially limits crop production worldwide. To identify salt stress tolerance determinants, we screened for Arabidopsis mutants that are hypersensitive to salt stress and designated these mutants as short root in salt medium (rsa). One of these mutants, rsa3-1, is hypersensitive to NaCl and LiCl but not to CsCl or to general osmotic stress. Reactive oxygen species (ROS) over-accumulate in rsa3-1 plants under salt stress. Gene expression profiling with Affymetrix microarray analysis revealed that RSA3 controls expression of many genes including genes encoding proteins for ROS detoxification under salt stress. Map-based cloning showed that RSA3 encodes a xyloglucan galactosyltransferase, which is allelic to a gene previously named MUR3/KAM1. The RSA3/MUR3/KAM1-encoded xylogluscan galactosyltransferase regulates actin microfilament organization (and thereby contributes to endomembrane distribution) and is also involved in cell wall biosynthesis. In rsa3-1, actin cannot assemble and form bundles as it does in the wild-type but instead aggregates in the cytoplasm. Furthermore, addition of phalloidin, which prevents actin depolymerization, can rescue salt hypersensitivity of rsa3-1. Together, these results suggest that RSA3/MUR3/KAM1 along with other cell wall-associated proteins plays a critical role in salt stress tolerance by maintaining the proper organization of actin microfilaments in order to minimize damage caused by excessive ROS. PMID:23571490

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

    PubMed Central

    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. PMID:25763502

  3. Functional mapping of the neuronal substrates for drug tolerance in Drosophila.

    PubMed

    Ghezzi, Alfredo; Al-Hasan, Yazan M; Krishnan, Harish R; Wang, Yan; Atkinson, Nigel S

    2013-05-01

    Physical dependence on alcohol and anesthetics stems from neuroadaptive changes that act to counter the effects of sedation in the brain. In Drosophila, exposure to either alcohol or solvent anesthetics have been shown to induce changes in expression of the BK-type Ca(2+)-activated K(+) channel gene slo. An increase in slo expression produces an adaptive modulation of neural activity that generates resistance to sedation and promotes drug tolerance and dependence. Increased BK channel activity counteracts the sedative effects of these drugs by reducing the neuronal refractory period and enhancing the capacity of neurons for repetitive firing. However, the brain regions or neuronal populations capable of producing inducible resistance or tolerance remain unknown. Here we map the neuronal substrates relevant for the slo-dependent modulation of drug sensitivity. Using spatially-controlled induction of slo expression we identify the mushroom bodies, the ellipsoid body and a subset of the circadian clock neurons as pivotal regions for the control of recovery from sedation. PMID:23371357

  4. Cross Acclimation between Heat and Hypoxia: Heat Acclimation Improves Cellular Tolerance and Exercise Performance in Acute Normobaric Hypoxia

    PubMed Central

    Lee, Ben J.; Miller, Amanda; James, Rob S.; Thake, Charles D.

    2016-01-01

    Background: The potential for cross acclimation between environmental stressors is not well understood. Thus, the aim of this investigation was to determine the effect of fixed-workload heat or hypoxic acclimation on cellular, physiological, and performance responses during post acclimation hypoxic exercise in humans. Method: Twenty-one males (age 22 ± 5 years; stature 1.76 ± 0.07 m; mass 71.8 ± 7.9 kg; V˙O2 peak 51 ± 7 mL.kg−1.min−1) completed a cycling hypoxic stress test (HST) and self-paced 16.1 km time trial (TT) before (HST1, TT1), and after (HST2, TT2) a series of 10 daily 60 min training sessions (50% N V˙O2 peak) in control (CON, n = 7; 18°C, 35% RH), hypoxic (HYP, n = 7; fraction of inspired oxygen = 0.14, 18°C, 35% RH), or hot (HOT, n = 7; 40°C, 25% RH) conditions. Results: TT performance in hypoxia was improved following both acclimation treatments, HYP (−3:16 ± 3:10 min:s; p = 0.0006) and HOT (−2:02 ± 1:02 min:s; p = 0.005), but unchanged after CON (+0:31 ± 1:42 min:s). Resting monocyte heat shock protein 72 (mHSP72) increased prior to HST2 in HOT (62 ± 46%) and HYP (58 ± 52%), but was unchanged after CON (9 ± 46%), leading to an attenuated mHSP72 response to hypoxic exercise in HOT and HYP HST2 compared to HST1 (p < 0.01). Changes in extracellular hypoxia-inducible factor 1-α followed a similar pattern to those of mHSP72. Physiological strain index (PSI) was attenuated in HOT (HST1 = 4.12 ± 0.58, HST2 = 3.60 ± 0.42; p = 0.007) as a result of a reduced HR (HST1 = 140 ± 14 b.min−1; HST2 131 ± 9 b.min−1 p = 0.0006) and Trectal (HST1 = 37.55 ± 0.18°C; HST2 37.45 ± 0.14°C; p = 0.018) during exercise. Whereas PSI did not change in HYP (HST1 = 4.82 ± 0.64, HST2 4.83 ± 0.63). Conclusion: Heat acclimation improved cellular and systemic physiological tolerance to steady state exercise in moderate hypoxia. Additionally we show, for the first time, that heat acclimation improved cycling time trial performance to a magnitude

  5. 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

  6. Daily acute intermittent hypoxia elicits functional recovery of diaphragm and inspiratory intercostal muscle activity after acute cervical spinal injury

    PubMed Central

    Navarrete-Opazo, A.; Vinit, S; Dougherty, B.J.; Mitchell, G.S.

    2015-01-01

    A major cause of mortality after spinal cord injury is respiratory failure. In normal rats, acute intermittent hypoxia (AIH) induces respiratory motor plasticity, expressed as diaphragm (Dia) and second external intercostal (T2 EIC) long-term facilitation (LTF). Dia (not T2 EIC) LTF is enhanced by systemic adenosine 2A (A2a) receptor inhibition in normal rats. We investigated the respective contributions of Dia and T2 EIC to daily AIH-induced functional recovery of breathing capacity with/without A2a receptor antagonist (KW6002, i.p.) following C2 hemisection (C2HS). Rats received daily AIH (dAIH: 10, 5-min episodes, 10.5% O2; 5-min normoxic intervals; 7 successive days beginning 7 days post-C2HS) or daily normoxia (dNx) with/without KW6002, followed by weekly (reminder) presentations for 8 weeks. Ventilation and EMGs from bilateral diaphragm and T2 EIC muscles were measured with room air breathing (21% O2) and maximum chemoreceptor stimulation (MCS: 7% CO2, 10.5% O2). dAIH increased tidal volume (Vt) in C2HS rats breathing room air (dAIH + vehicle: 0.47 ± 0.02, dNx + vehicle: 0.40 ± 0.01ml/100 g; p<0.05) and MCS (dAIH + vehicle: 0.83 ± 0.01, dNx + vehicle: 0.73 ± 0.01ml/100g; p<0.001); KW6002 had no significant effect. dAIH enhanced contralateral (uninjured) diaphragm EMG activity, an effect attenuated by KW6002, during room air breathing and MCS (p<0.05). Although dAIH enhanced contralateral T2 EIC EMG activity during room air breathing, KW6002 had no effect. dAIH had no statistically significant effects on diaphragm or T2 EIC EMG activity ipsilateral to injury. Thus, two weeks post-C2HS: 1) dAIH enhances breathing capacity by effects on contralateral diaphragm and T2 EIC activity; and 2) dAIH-induced recovery is A2a dependent in diaphragm, but not T2 EIC. Daily AIH may be a useful in promoting functional recovery of breathing capacity after cervical spinal injury, but A2a receptor antagonists (eg. caffeine) may undermine its effectiveness shortly after

  7. Acute Rhabdomyolysis Associated with Coadministration of Levofloxacin and Simvastatin in a Patient with Normal Renal Function

    PubMed Central

    Paparoupa, Maria; Pietrzak, Sebastian; Gillissen, Adrian

    2014-01-01

    We report a rare case of severe acute rhabdomyolysis in association with coadministration of levofloxacin and simvastatin in a patient with normal renal function. A 70-year-old Caucasian male was treated due to community acquired pneumonia with levofloxacin in a dosage of 500 mg once and then twice a day. On the 8th day of hospitalization the patient presented with acute severe rhabdomyolysis requiring an intensive care support. After discontinuation of levofloxacin and concomitant medication with simvastatin 80 mg/day, clinical and laboratory effects were totally reversible. Up to now, levofloxacin has been reported to induce rhabdomyolysis mainly in patients with impaired renal function, as the medication has a predominant renal elimination. In our case renal function remained normal during the severe clinical course. According to a recent case report rhabdomyolysis was observed due to interaction of simvastatin and ciprofloxacin. To our best knowledge this is the first case of interaction between simvastatin and levofloxacin to be reported. This case emphasizes the need of close monitoring of creatine kinase in patients under more than one potentially myotoxic medication especially when patients develop muscle weakness. PMID:25140181

  8. 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.

  9. 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

  10. 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…

  11. A tolerant lactic acid bacteria, Lactobacillus paracasei, and its immunoregulatory function.

    PubMed

    Kou, Xiaohong; Chen, Qiong; Ju, Xiaoying; Liu, Huiping; Chen, Wenrong; Xue, Zhaohui

    2014-11-01

    The aim of the present investigation was to isolate a probiotic strain from 23 samples of yurts cheese and 21 samples of kumiss (collected from scattered households in Xinjiang and Inner Mongolia), and from eN-Lac Capsules, a health-promoting product. The isolates were subjected to biochemical characterization analysis and were tested for tolerance to low pH, sodium salt, bile salt, pepsin, and trypsin. 16S DNA sequence analysis was conducted to identify the strain. The possible dose-dependent role of strain LP2 in immunomodulation was investigated using the ICR mouse model (from the Institute of Cancer Research). Daily, we conducted clinical observations, a carbon clearance test, a spleen lymphocyte proliferation test, and measurements of body mass and lymphoid organ index. Natural killer cell activity and delayed-type hypersensitivity reaction were determined. The results showed that 3 selected strains (LP2, LP4, and LP9) had high tolerance to low pH, sodium chloride, and bile salt and were not significantly different from Lactobacillus paracasei in terms of morphology, colony, and biochemistry characterizations. A further tolerance test showed that LP2 had the highest survival rate (90%) under the conditions of pH 3.0, 0.3% bile salt, 10 mg/mL pepsin, and 10 mg/mL trypsin for 24 h. The sequence heterogeneities within the 16S rDNA genes molecularly elucidated that the LP2 belongs to the L. paracasei family, on the basis of a homology of 99.6%. A significant enhanced footpad swelling reaction and natural killer cell activity in the middle-dose (10(8) cfu/mL) and the high-dose (10(9) cfu/mL) groups were observed but without obvious dose dependence (P < 0.05). Lymphocyte proliferation was also increased significantly in a dose-dependent manner (P < 0.01) compared with that of the control group, indicating a positive immunoregulatory effect. PMID:25319770

  12. The role of glutathione in mercury tolerance resembles its function under cadmium stress in Arabidopsis.

    PubMed

    Sobrino-Plata, Juan; Carrasco-Gil, Sandra; Abadía, Javier; Escobar, Carolina; Álvarez-Fernández, Ana; Hernández, Luis E

    2014-02-01

    Recent research efforts have highlighted the importance of glutathione (GSH) as a key antioxidant metabolite for metal tolerance in plants. Little is known about the mechanisms involved in stress due to mercury (Hg), one of the most hazardous metals to the environment and human health. To understand the implication of GSH metabolism for Hg tolerance, we used two γ-glutamylcysteine synthetase (γECS) Arabidopsis thaliana allele mutants (rax1-1 and cad2-1) and a phytochelatin synthase (PCS) mutant (cad1-3). The leaves of these mutants and of wild type (Col-0) were infiltrated with a solution containing Cd or Hg (0, 3 and 30 μM) and incubated for 24 and 48 h. The formation of phytochelatins (PCs) in the leaf extracts was followed by two different HPLC-based methods and occurred in Col-0, cad2-1 and rax1-1 plants exposed to Cd, whereas in the Hg treatments, PCs accumulated mainly in Col-0 and rax1-1, where Hg-PC complexes were also detected. ASA and GSH/GSSG levels increased under moderate metal stress conditions, accompanied by increased GSH reductase (GR) activity and expression. However, higher metal doses led to a decrease in the analysed parameters, and stronger toxic effects appeared with 30 μM Hg. The GSH concentration was significantly higher in rax1-1 (70% of Col-0) than in cad2-1 (40% of Col-0). The leaves of rax1-1 were less sensitive than cad2-1, in accordance with the greater expression of γECS in rax1-1. Our results underline the existence of a minimal GSH concentration threshold needed to minimise the toxic effects exerted by Hg. PMID:24452078

  13. Docosahexaenoic acid pretreatment confers protection and functional improvements after acute spinal cord injury in adult rats.

    PubMed

    Figueroa, Johnny D; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I; Walker, Robert L; Miranda, Jorge D; Leon, Marino De

    2012-02-10

    Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  14. Docosahexaenoic Acid Pretreatment Confers Protection and Functional Improvements after Acute Spinal Cord Injury in Adult Rats

    PubMed Central

    Figueroa, Johnny D.; Cordero, Kathia; Baldeosingh, Keisha; Torrado, Aranza I.; Walker, Robert L.; Miranda, Jorge D.

    2012-01-01

    Abstract Currently, few interventions have been shown to successfully limit the progression of secondary damage events associated with the acute phase of spinal cord injury (SCI). Docosahexaenoic acid (DHA, C22:6 n-3) is neuroprotective when administered following SCI, but its potential as a pretreatment modality has not been addressed. This study used a novel DHA pretreatment experimental paradigm that targets acute cellular and molecular events during the first week after SCI in rats. We found that DHA pretreatment reduced functional deficits during the acute phase of injury, as shown by significant improvements in Basso-Beattie-Bresnahan (BBB) locomotor scores, and the detection of transcranial magnetic motor evoked potentials (tcMMEPs) compared to vehicle-pretreated animals. We demonstrated that, at 7 days post-injury, DHA pretreatment significantly increased the percentage of white matter sparing, and resulted in axonal preservation, compared to the vehicle injections. We found a significant increase in the survival of NG2+, APC+, and NeuN+ cells in the ventrolateral funiculus (VLF), dorsal corticospinal tract (dCST), and ventral horns, respectively. Interestingly, these DHA protective effects were observed despite the lack of inhibition of inflammatory markers for monocytes/macrophages and astrocytes, ED1/OX42 and GFAP, respectively. DHA pretreatment induced levels of Akt and cyclic AMP responsive element binding protein (CREB) mRNA and protein. This study shows for the first time that DHA pretreatment ameliorates functional deficits, and increases tissue sparing and precursor cell survival. Further, our data suggest that DHA-mediated activation of pro-survival/anti-apoptotic pathways may be independent of its anti-inflammatory effects. PMID:21970623

  15. The function of the left anterior temporal pole: evidence from acute stroke and infarct volume

    PubMed Central

    Tsapkini, Kyrana; Frangakis, Constantine E.

    2011-01-01

    The role of the anterior temporal lobes in cognition and language has been much debated in the literature over the last few years. Most prevailing theories argue for an important role of the anterior temporal lobe as a semantic hub or a place for the representation of unique entities such as proper names of peoples and places. Lately, a few studies have investigated the role of the most anterior part of the left anterior temporal lobe, the left temporal pole in particular, and argued that the left anterior temporal pole is the area responsible for mapping meaning on to sound through evidence from tasks such as object naming. However, another recent study indicates that bilateral anterior temporal damage is required to cause a clinically significant semantic impairment. In the present study, we tested these hypotheses by evaluating patients with acute stroke before reorganization of structure–function relationships. We compared a group of 20 patients with acute stroke with anterior temporal pole damage to a group of 28 without anterior temporal pole damage matched for infarct volume. We calculated the average percent error in auditory comprehension and naming tasks as a function of infarct volume using a non-parametric regression method. We found that infarct volume was the only predictive variable in the production of semantic errors in both auditory comprehension and object naming tasks. This finding favours the hypothesis that left unilateral anterior temporal pole lesions, even acutely, are unlikely to cause significant deficits in mapping meaning to sound by themselves, although they contribute to networks underlying both naming and comprehension of objects. Therefore, the anterior temporal lobe may be a semantic hub for object meaning, but its role must be represented bilaterally and perhaps redundantly. PMID:21685458

  16. Kidney-specific Overexpression of Sirt1 Protects against Acute Kidney Injury by Retaining Peroxisome Function

    PubMed Central

    Hasegawa, Kazuhiro; Wakino, Shu; Yoshioka, Kyoko; Tatematsu, Satoru; Hara, Yoshikazu; Minakuchi, Hitoshi; Sueyasu, Keiko; Washida, Naoki; Tokuyama, Hirobumi; Tzukerman, Maty; Skorecki, Karl; Hayashi, Koichi; Itoh, Hiroshi

    2010-01-01

    Sirt1, a NAD-dependent protein deacetylase, is reported to regulate intracellular metabolism and attenuate reactive oxidative species (ROS)-induced apoptosis leading to longevity and acute stress resistance. We created transgenic (TG) mice with kidney-specific overexpression of Sirt1 using the promoter sodium-phosphate cotransporter IIa (Npt2) driven specifically in proximal tubules and investigated the kidney-specific role of Sirt1 in the protection against acute kidney injury (AKI). We also elucidated the role of number or function of peroxisome and mitochondria in mediating the mechanisms for renal protective effects of Sirt1 in AKI. Cisplatin-induced AKI decreased the number and function of peroxisomes as well as mitochondria and led to increased local levels of ROS production and renal tubular apoptotic cells. TG mice treated with cisplatin mitigated AKI, local ROS, and renal tubular apoptotic tubular cells. Consistent with these results, TG mice treated with cisplatin also exhibited recovery of peroxisome number and function, as well as rescued mitochondrial function; however, mitochondrial number was not recovered. Immunoelectron microscopic findings consistently demonstrated that the decrease in peroxisome number by cisplatin in wild type mice was restored in transgenic mice. In HK-2 cells, a cultured proximal tubule cell line, overexpression of Sirt1 rescued the cisplatin-induced cell apoptosis through the restoration of peroxisome number, although the mitochondria number was not restored. These results indicate that Sirt1 overexpression in proximal tubules rescues cisplatin-induced AKI by maintaining peroxisomes number and function, concomitant up-regulation of catalase, and elimination of renal ROS levels. Renal Sirt1 can be a potential therapeutic target for the treatment of AKI. PMID:20139070

  17. 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

  18. Comparison of efficacy and tolerance of intravenously and orally administered ciprofloxacin in cystic fibrosis patients with acute exacerbations of lung infection.

    PubMed

    Strandvik, B; Hjelte, L; Lindblad, A; Ljungberg, B; Malmborg, A S; Nilsson-Ehle, I

    1989-01-01

    Twenty patients (17-27 yr) with cystic fibrosis were given ciprofloxacin at 30 pulmonary infectious exacerbations. All patients were chronically colonized with Pseudomonas aeruginosa. Twenty-five courses were completed, 13 orally (15 mg/kg b.i.d.) and 12 intravenously (4-6 mg/kg b.i.d.). Clinical efficacy was excellent or good in 85-90% of the courses and growth of P. aeruginosa was markedly reduced in 33-46%. Body weight and clinical score improved significantly. White blood cell count decreased and pulmonary function was improved. Reversible adverse effects, mainly rash and urticaria, appeared at seven occasions, five severe enough to cause interruption of treatment. Clinical efficacy and tolerance were better with oral than intravenous administration at the dosages used in this study. Excellent bioavailability provides additional basis for oral treatment with ciprofloxacin in cystic fibrosis patients. PMID:2756354

  19. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome

    PubMed Central

    Iltumur, Kenan; Olmez, Gonul; Arıturk, Zuhal; Taskesen, Tuncay; Toprak, Nizamettin

    2005-01-01

    Introduction It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event. Method Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (<5 min, 5–10 min and >10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group. Results The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P < 0.0001). On the other hand, there were no significant differences between T4, free T4 and TSH levels between the three groups (P > 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively). Conclusion TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick

  20. Acute heart inflammation: ultrastructural and functional aspects of macrophages elicited by Trypanosoma cruzi infection

    PubMed Central

    Melo, Rossana C N

    2009-01-01

    Abstract The heart is the main target organ of the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. During the acute disease, tissue damage in the heart is related to the intense myocardium parasitism. To control parasite multiplication, cells of the monocytic lineage are highly mobilized. In response to inflammatory and immune stimulation, an intense migration and extravasation of monocytes occurs from the bloodstream into heart. Monocyte differentiation leads to the formation of tissue phagocytosing macrophages, which are strongly activated and direct host defence. Newly elicited monocyte-derived macrophages both undergo profound physiological changes and display morphological heterogeneity that greatly differs from originally non-inflammatory macrophages, and underlie their functional activities as potent inflammatory cells. Thus, activated macrophages play a critical role in the outcome of parasite infection. This review covers functional and ultrastructural aspects of heart inflammatory macrophages triggered by the acute Chagas' disease, including recent discoveries on morphologically distinct, inflammation-related organelles, termed lipid bodies, which are actively formed in vivo within macrophages in response to T. cruzi infection. These findings are defining a broader role for lipid bodies as key markers of macrophage activation during innate immune responses to infectious diseases and attractive targets for novel anti-inflammatory therapies. Modulation of macrophage activation may be central in providing therapeutic benefits for Chagas' disease control. PMID:18624767

  1. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  2. Functional cluster analysis of CT perfusion maps: a new tool for diagnosis of acute stroke?

    PubMed

    Baumgartner, Christian; Gautsch, Kurt; Böhm, Christian; Felber, Stephan

    2005-09-01

    CT perfusion imaging constitutes an important contribution to the early diagnosis of acute stroke. Cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) maps are used to estimate the severity of cerebral damage after acute ischemia. We introduce functional cluster analysis as a new tool to evaluate CT perfusion in order to identify normal brain, ischemic tissue and large vessels. CBF, CBV and TTP maps represent the basis for cluster analysis applying a partitioning (k-means) and density-based (density-based spatial clustering of applications with noise, DBSCAN) paradigm. In patients with transient ischemic attack and stroke, cluster analysis identified brain areas with distinct hemodynamic properties (gray and white matter) and segmented territorial ischemia. CBF, CBV and TTP values of each detected cluster were displayed. Our preliminary results indicate that functional cluster analysis of CT perfusion maps may become a helpful tool for the interpretation of perfusion maps and provide a rapid means for the segmentation of ischemic tissue. PMID:15827821

  3. Effect of acute exercise on executive function in children with attention deficit hyperactivity disorder.

    PubMed

    Chang, Yu-Kai; Liu, Suyen; Yu, Hui-Hsiang; Lee, Yuan-Hung

    2012-03-01

    This study was conducted to determine the effect of acute aerobic exercise on executive function in children with attention deficit hyperactivity disorder (ADHD). Forty children with ADHD were randomly assigned into exercise or control groups. Participants in the exercise group performed a moderate intensity aerobic exercise for 30 min, whereas the control group watched a running/exercise-related video. Neuropsychological tasks, the Stroop Test and the Wisconsin Card Sorting Test (WCST), were assessed before and after each treatment. The results indicated that acute exercise facilitated performance in the Stroop Test, particularly in the Stroop Color-Word condition. Additionally, children in the exercise group demonstrated improvement in specific WCST performances in Non-perseverative Errors and Categories Completed, whereas no influences were found in those performances in the control group. Tentative explanations for the exercise effect postulate that exercise allocates attention resources, influences the dorsolateral prefrontal cortex, and is implicated in exercise-induced dopamine release. These findings are promising and additional investigations to explore the efficacy of exercise on executive function in children with ADHD are encouraged. PMID:22306962

  4. BET Bromodomain Inhibition Suppresses the Function of Hematopoietic Transcription Factors in Acute Myeloid Leukemia.

    PubMed

    Roe, Jae-Seok; Mercan, Fatih; Rivera, Keith; Pappin, Darryl J; Vakoc, Christopher R

    2015-06-18

    The bromodomain and extraterminal (BET) protein BRD4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that BRD4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) PU.1, FLI1, ERG, C/EBPα, C/EBPβ, and MYB at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate BRD4 recruitment to their occupied sites to promote transcriptional activation. Chemical inhibition of BET bromodomains was found to suppress the functional output of each hematopoietic TF, thereby interfering with essential lineage-specific transcriptional circuits in this disease. These findings reveal a chromatin-based signaling cascade comprised of hematopoietic TFs, p300/CBP, and BRD4 that supports leukemia maintenance and is suppressed by BET bromodomain inhibition. PMID:25982114

  5. 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.

  6. 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. PMID:27126336

  7. Changes in cochlear function during acute endolymphatic hydrops development in guinea pigs.

    PubMed

    Brown, Daniel J; Chihara, Yasuhiro; Curthoys, Ian S; Wang, Yuan; Bos, Marieke

    2013-02-01

    Previous studies have injected artificial endolymph into scala media in anaesthetized guinea pigs as an acute model of endolymphatic hydrops. Here, we have injected artificial endolymph into scala media in guinea pigs at rates of 40-80 nl/min, whilst monitoring Compound Action Potential (CAP) thresholds, the Summating Potential (SP)/CAP ratio, Cochlear Microphonic (CM) distortion, low-frequency modulated Distortion Product Otoacoustic Emissions (DPOAEs), and the Endocochlear Potential (EP). We found that abrupt recovery of CAP thresholds, SP/CAP ratio, and CM and DPOAE asymmetric distortion could occur several times during a single injection of less than 3 μl, suggesting that endolymph pressure could periodically decrease while the injection was ongoing. Larger volumes are thought to produce a rupture of the membranous labyrinth, however, our results suggest that multiple injections, each larger than 3 μl and within 40 min of each other, cause multiple pressure-related changes, which are difficult to be explained on the basis of a simple labyrinth rupture. We have also examined the morphological changes of the temporal bones ex vivo using X-ray micro-tomography. Both the functional changes and the micro-CT images suggest ruptures of the membranous labyrinth may not always be responsible for abrupt changes in inner ear function. Our results provide a new insight into the changes in cochlear function occurring during acute hydrops development, which compares well to the clinical findings observed in Ménière's Disease. We suggest that hydrops development may be a continual process, yet cause discontinuous functional changes due to mechanisms other than a simple rupture of the membranous labyrinth. PMID:23270618

  8. ICE1 of Poncirus trifoliata functions in cold tolerance by modulating polyamine levels through interacting with arginine decarboxylase

    PubMed Central

    Huang, Xiao-San; Zhang, Qinghua; Zhu, Dexin; Fu, Xingzheng; Wang, Min; Zhang, Qian; Moriguchi, Takaya; Liu, Ji-Hong

    2015-01-01

    ICE1 (Inducer of CBF Expression 1) encodes a MYC-like basic helix–loop–helix transcription factor that acts as a central regulator of cold response. In this study, we elucidated the function and underlying mechanisms of PtrICE1 from trifoliate orange [Poncirus trifoliata (L.) Raf.]. PtrICE1 was upregulated by cold, dehydration, and salt, with the greatest induction under cold conditions. PtrICE1 was localized in the nucleus and could bind to a MYC-recognizing sequence. Ectopic expression of PtrICE1 in tobacco and lemon conferred enhanced tolerance to cold stresses at either chilling or freezing temperatures. Yeast two-hybrid screening revealed that 21 proteins belonged to the PtrICE1 interactome, in which PtADC (arginine decarboxylase) was confirmed as a bona fide protein interacting with PtrICE1. Transcript levels of ADC genes in the transgenic lines were slightly elevated under normal growth condition but substantially increased under cold conditions, consistent with changes in free polyamine levels. By contrast, accumulation of the reactive oxygen species, H2O2 and O2 –, was appreciably alleviated in the transgenic lines under cold stress. Higher activities of antioxidant enzymes, such as superoxide dismutase and catalase, were detected in the transgenic lines under cold conditions. Taken together, these results demonstrated that PtrICE1 plays a positive role in cold tolerance, which may be due to modulation of polyamine levels through interacting with the ADC gene. PMID:25873670

  9. ICE1 of Poncirus trifoliata functions in cold tolerance by modulating polyamine levels through interacting with arginine decarboxylase.

    PubMed

    Huang, Xiao-San; Zhang, Qinghua; Zhu, Dexin; Fu, Xingzheng; Wang, Min; Zhang, Qian; Moriguchi, Takaya; Liu, Ji-Hong

    2015-06-01

    ICE1 (Inducer of CBF Expression 1) encodes a MYC-like basic helix-loop-helix transcription factor that acts as a central regulator of cold response. In this study, we elucidated the function and underlying mechanisms of PtrICE1 from trifoliate orange [Poncirus trifoliata (L.) Raf.]. PtrICE1 was upregulated by cold, dehydration, and salt, with the greatest induction under cold conditions. PtrICE1 was localized in the nucleus and could bind to a MYC-recognizing sequence. Ectopic expression of PtrICE1 in tobacco and lemon conferred enhanced tolerance to cold stresses at either chilling or freezing temperatures. Yeast two-hybrid screening revealed that 21 proteins belonged to the PtrICE1 interactome, in which PtADC (arginine decarboxylase) was confirmed as a bona fide protein interacting with PtrICE1. Transcript levels of ADC genes in the transgenic lines were slightly elevated under normal growth condition but substantially increased under cold conditions, consistent with changes in free polyamine levels. By contrast, accumulation of the reactive oxygen species, H2O2 and O2 (-), was appreciably alleviated in the transgenic lines under cold stress. Higher activities of antioxidant enzymes, such as superoxide dismutase and catalase, were detected in the transgenic lines under cold conditions. Taken together, these results demonstrated that PtrICE1 plays a positive role in cold tolerance, which may be due to modulation of polyamine levels through interacting with the ADC gene. PMID:25873670

  10. Function and expression of a novel rat salt-tolerant protein: evidence of a role in cellular sodium metabolism.

    PubMed

    Tsuji, E; Tsuji, Y; Sasaguri, M; Arakawa, K

    1998-09-01

    Higher dietary salt intake in humans is associated with higher BP, but the BP response to NaCl, so-called salt sensitivity, is heterogeneous among individuals. It has been postulated that modifications in cellular cation metabolism may be related to salt sensitivity in mammalian hypertension. The authors have isolated a novel rat complementary DNA, called salt-tolerant protein (STP), that can functionally complement Saccharomyces cervisiae HAL1, which improves salt tolerance by modulating the cation transport system. On high-salt (8% NaCl) diets, both Dahl salt-sensitive and salt-resistant rats displayed an elevated BP and increased STP mRNA expression. Immunohistochemistry using an anti-rat STP antibody demonstrated the presence of STP immunoreactivity in the proximal tubules. In cells that transiently expressed STP, the intracellular [Na+]/[K+] ratio was higher than that in control cells. STP contains predicted coiled-coil and Src homology 3 domains, and shows a partially high degree of nucleotide identity to human thyroid-hormone receptor interacting protein. These results suggest that STP may play an important role in salt sensitivity through cellular sodium metabolism by mediating signal transduction and a hormone-dependent transcription mechanism. PMID:9727364

  11. Molecular and Functional Characterization of a Wheat B2 Protein Imparting Adverse Temperature Tolerance and Influencing Plant Growth.

    PubMed

    Singh, Akanksha; Khurana, Paramjit

    2016-01-01

    Genomic attempts were undertaken to elucidate the plant developmental responses to heat stress, and to characterize the roles of B2 protein in mediating those responses. A wheat expressed sequence tag for B2 protein was identified which was cloned and characterized to assess its functional relevance causing plant growth and development during stress adaptation. Here, we show that wheat B2 protein is highly expressed in root and shoot tissues as well as in developing seed tissues under high temperature stress conditions. Morphological studies of transgenic Arabidopsis overexpressing gene encoding wheat B2 protein and Δb2 mutant plants were studied at major developmental stages. The stunted growth phenotype of mutant plants, together with hypocotyl and root elongation analysis of transgenic plants showed that B2 protein exhibits a crucial role in plant growth and development. Additional physiological analyses highlights the role of B2 protein in increased tolerance to heat and cold stresses by maintaining high chlorophyll content, strong activity of photosystem II and less membrane damage of overexpression transgenics as compared with the wild-type. Furthermore, the constitutive overexpression of TaB2 in Arabidopsis resulted in ABA hypersensitivity. Taken together, these studies suggest a novel perspectives of B2 protein in plant development and in mediating the thermal stress tolerance. PMID:27242843

  12. Molecular and Functional Characterization of a Wheat B2 Protein Imparting Adverse Temperature Tolerance and Influencing Plant Growth

    PubMed Central

    Singh, Akanksha; Khurana, Paramjit

    2016-01-01

    Genomic attempts were undertaken to elucidate the plant developmental responses to heat stress, and to characterize the roles of B2 protein in mediating those responses. A wheat expressed sequence tag for B2 protein was identified which was cloned and characterized to assess its functional relevance causing plant growth and development during stress adaptation. Here, we show that wheat B2 protein is highly expressed in root and shoot tissues as well as in developing seed tissues under high temperature stress conditions. Morphological studies of transgenic Arabidopsis overexpressing gene encoding wheat B2 protein and Δb2 mutant plants were studied at major developmental stages. The stunted growth phenotype of mutant plants, together with hypocotyl and root elongation analysis of transgenic plants showed that B2 protein exhibits a crucial role in plant growth and development. Additional physiological analyses highlights the role of B2 protein in increased tolerance to heat and cold stresses by maintaining high chlorophyll content, strong activity of photosystem II and less membrane damage of overexpression transgenics as compared with the wild-type. Furthermore, the constitutive overexpression of TaB2 in Arabidopsis resulted in ABA hypersensitivity. Taken together, these studies suggest a novel perspectives of B2 protein in plant development and in mediating the thermal stress tolerance. PMID:27242843

  13. Effect of upper airway obstruction in acute stroke on functional outcome at 6 months

    PubMed Central

    Turkington, P; Allgar, V; Bamford, J; Wanklyn, P; Elliott, M

    2004-01-01

    Background: The aim of this study was to determine whether upper airway obstruction occurring within the first 24 hours of stroke onset has an effect on outcome following stroke at 6 months. Traditional definitions used for obstructive sleep apnoea (OSA) are arbitrary and may not apply in the acute stroke setting, so a further aim of the study was to redefine respiratory events and to assess their impact on outcome. Methods: 120 patients with acute stroke underwent a sleep study within 24 hours of onset to determine the severity of upper airway obstruction (respiratory disturbance index, RDI-total study). Stroke severity (Scandinavian Stroke Scale, SSS) and disability (Barthel score) were also recorded. Each patient was subsequently followed up at 6 months to determine morbidity and mortality. Results: Death was independently associated with SSS (OR (95% CI) 0.92 (0.88 to 0.95), p<0.00001) and RDI-total study (OR (95% CI) 1.07 (1.03 to 1.12), p<0.01). The Barthel index was independently predicted by SSS (p = 0.0001; r = 0.259; 95% CI 0.191 to 0.327) and minimum oxygen saturation during the night (p = 0.037; r = 0.16; 95% CI 0.006 to 0.184). The mean length of the respiratory event most significantly associated with death at 6 months was 15 seconds (sensitivity 0.625, specificity 0.525) using ROC curve analysis. Conclusion: The severity of upper airway obstruction appears to be associated with a worse functional outcome following stroke, increasing the likelihood of death and dependency. Longer respiratory events appear to have a greater effect. These data suggest that long term outcome might be improved by reducing upper airway obstruction in acute stroke. PMID:15115859

  14. Map based cloning of cereal abiotic stress tolerance genes at the Australian Centre for Plant Functional Genomics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Map-based cloning is one of the approaches we are using to isolate cereal genes conferring tolerance to abiotic stresses. Targets include barley 4HL and wheat 7BL boron tolerance genes, a 1HL barley gene that influences shoot sodium accumulation, a 2HL barley frost tolerance gene, and a rye 7RS alum...

  15. 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…

  16. 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.

  17. Disruption of auditory function by acute administration of a room odorizer containing butyl nitrite in rats

    SciTech Connect

    Fechter, L.D.; Richard, C.L.; Mungekar, M.; Gomez, J.; Strathern, D.

    1989-01-01

    Butyl nitrite is the predominant and presumed active ingredient in a variety of commercial preparations sold as ''room odorizers.'' These compounds have significant abuse potential, giving the user the sensation of a ''rush'', which may be related to their intense cardiovascular effects. The pharmacological properties of butyl nitrites are similar to those of amyl nitrite which is also abused for its psychological effects, but whose availability is limited by prescription for treatment of angina. A significant body of literature suggests that the inner ear is vulnerable to acute hypoxic exposure. Since butyl nitrite induces high levels of methemoglobin and also reduces blood pressure due to peripheral vasodilation, we hypothesized that this compound might produce auditory dysfunction. We studied the effect of acute exposure to a butyl nitrite ''room odorizer'' on 10- and 40-kHz auditory function in rats. A loss in auditory sensitivity was found at both frequencies on the day following administration of the compound. Auditory dysfunction tended to subside over the next several days at 40 kHz, although a significant loss of sensitivity for tones of 10 kHz was observed over a 6-day period after administration of the agent. Methemoglobin levels measured in rats of the same age were elevated significantly 30 and 60 min after butyl nitrite to levels of 30-45%. Methemoglobin levels were found to be normal 18 hr after administration when the first audiometric tests were conducted. The data suggest that auditory function in the middle of the rats' auditory range, 10 kHz, was disrupted for a longer period than was high-frequency (40 kHz) auditory function.

  18. Pyridoxamine reduces postinjury fibrosis and improves functional recovery after acute kidney injury.

    PubMed

    Skrypnyk, Nataliya I; Voziyan, Paul; Yang, Haichun; de Caestecker, Christian R; Theberge, Marie-Claude; Drouin, Mathieu; Hudson, Billy; Harris, Raymond C; de Caestecker, Mark P

    2016-08-01

    Acute kidney injury (AKI) is a common and independent risk factor for death and chronic kidney disease (CKD). Despite promising preclinical data, there is no evidence that antioxidants reduce the severity of injury, increase recovery, or prevent CKD in patients with AKI. Pyridoxamine (PM) is a structural analog of vitamin B6 that interferes with oxidative macromolecular damage via a number of different mechanisms and is in a phase 3 clinical efficacy trial to delay CKD progression in patients with diabetic kidney disease. Because oxidative stress is implicated as one of the main drivers of renal injury after AKI, the ability of PM to interfere with multiple aspects of oxidative damage may be favorable for AKI treatment. In these studies we therefore evaluated PM treatment in a mouse model of AKI. Pretreatment with PM caused a dose-dependent reduction in acute tubular injury, long-term postinjury fibrosis, as well as improved functional recovery after ischemia-reperfusion AKI (IR-AKI). This was associated with a dose-dependent reduction in the oxidative stress marker isofuran-to-F2-isoprostane ratio, indicating that PM reduces renal oxidative damage post-AKI. PM also reduced postinjury fibrosis when administered 24 h after the initiating injury, but this was not associated with improvement in functional recovery after IR-AKI. This is the first report showing that treatment with PM reduces short- and long-term injury, fibrosis, and renal functional recovery after IR-AKI. These preclinical findings suggest that PM, which has a favorable clinical safety profile, holds therapeutic promise for AKI and, most importantly, for prevention of adverse long-term outcomes after AKI. PMID:27194713

  19. Conduction failure following spinal cord injury: functional and anatomical changes from acute to chronic stages

    PubMed Central

    James, Nicholas D.; Bartus, Katalin; Grist, John; Bennett, David L. H.; McMahon, Stephen B.; Bradbury, Elizabeth J.

    2012-01-01

    In the majority of spinal cord injuries (SCIs) some axonal projections remain intact. We examined the functional status of these surviving axons, since they represent a prime therapeutic target. Using a novel electrophysiological preparation, adapted from techniques used to study primary demyelination, we quantified conduction failure across a SCI and studied conduction changes over time in adult rats with a moderate severity spinal contusion (150 kilodyne, Infinite Horizon impactor). By recording antidromically activated single units from teased dorsal root filaments we demonstrate complete conduction block in ascending dorsal column axons acutely (1-7 days) post-injury, followed by a period of restored conduction over the sub-acute phase (2-4 weeks), with no further improvements in conduction at chronic stages (3-6 months). By cooling the lesion site additional conducting fibres could be recruited, thus revealing a population of axons that are viable but unable to conduct under normal physiological conditions. Importantly, this phenomenon is still apparent at the most chronic (6 month) time point. The time course of conduction changes corresponded with changes in behavioural function, and ultrastructural analysis of dorsal column axons revealed extensive demyelination during the period of conduction block, followed by progressive remyelination. A proportion of dorsal column axons remained chronically demyelinated, suggesting that these are the axons recruited with the cooling paradigm. Thus, using a clinically relevant SCI model we have identified a population of axons present at chronic injury stages which are intact but fail to conduct and are therefore a prime target for therapeutic strategies to restore function. PMID:22171053

  20. Identification of functional cooperative mutations of SETD2 in human acute leukemia

    PubMed Central

    Zhu, Xiaofan; He, Fuhong; Zeng, Huimin; Ling, Shaoping; Chen, Aili; Wang, Yaqin; Yan, Xiaomei; Wei, Wei; Pang, Yakun; Cheng, Hui; Hua, Chunlan; Zhang, Yue; Yang, Xuejing; Lu, Xin; Cao, Lihua; Hao, Lingtong; Dong, Lili; Zou, Wei; Wu, Jun; Li, Xia; Zheng, Si; Yan, Jin; Zhou, Jing; Zhang, Lixia; Mi, Shuangli; Wang, Xiaojuan; Zhang, Li; Zou, Yao; Chen, Yumei; Geng, Zhe; Wang, Jianmin; Zhou, Jianfeng; Liu, Xin; Wang, Jianxiang; Yuan, Weiping; Huang, Gang; Cheng, Tao; Wang, Qian-fei

    2015-01-01

    Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy1,2, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene-rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene3 and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase)4. Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development. PMID:24509477

  1. 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

  2. Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system

    PubMed Central

    Sabino, KR; Petroianu, A; Alberti, LR

    2011-01-01

    Rationale:Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. Objective: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods and Results: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) – control, and Group 2 (n = 8) – animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with ⁸⁸mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. Discussion: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice. PMID:22514578

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

    PubMed

    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

  4. Acute Zonal Occult Outer Retinopathy in Japanese Patients: Clinical Features, Visual Function, and Factors Affecting Visual Function

    PubMed Central

    Saito, Saho; Saito, Wataru; Saito, Michiyuki; Hashimoto, Yuki; Mori, Shohei; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2015-01-01

    Purpose To evaluate the clinical features and investigate their relationship with visual function in Japanese patients with acute zonal occult outer retinopathy (AZOOR). Methods Fifty-two eyes of 38 Japanese AZOOR patients (31 female and 7 male patients; mean age at first visit, 35.0 years; median follow-up duration, 31 months) were retrospectively collected: 31 untreated eyes with good visual acuity and 21 systemic corticosteroid-treated eyes with progressive visual acuity loss. Variables affecting the logMAR values of best-corrected visual acuity (BCVA) and the mean deviation (MD) on Humphrey perimetry at initial and final visits were examined using multiple stepwise linear regression analysis. Results In untreated eyes, the mean MD at the final visit was significantly higher than that at the initial visit (P = 0.00002). In corticosteroid-treated eyes, the logMAR BCVA and MD at the final visit were significantly better than the initial values (P = 0.007 and P = 0.02, respectively). The final logMAR BCVA was 0.0 or less in 85% of patients. Variables affecting initial visual function were moderate anterior vitreous cells, myopia severity, and a-wave amplitudes on electroretinography; factors affecting final visual function were the initial MD values, female sex, moderate anterior vitreous cells, and retinal atrophy. Conclusions Our data indicated that visual functions in enrolled patients significantly improved spontaneously or after systemic corticosteroids therapy, suggesting that Japanese patients with AZOOR have good visual outcomes during the follow-up period of this study. Furthermore, initial visual field defects, gender, anterior vitreous cells, and retinal atrophy affected final visual functions in these patients. PMID:25919689

  5. Emodin enhances alveolar epithelial barrier function in rats with experimental acute pancreatitis

    PubMed Central

    Xia, Xian-Ming; Wang, Fang-Yu; Wang, Zhen-Kai; Wan, Hai-Jun; Xu, Wen-An; Lu, Heng

    2010-01-01

    claudin-4, claudin-5 and occluding was increased, and the pulmonary dye extravasation was reduced in lung tissue samples from rats with acute pancreatitis after treatment with emodin. CONCLUSION: Emodin attenuates pulmonary edema and inflammation, enhances alveolar epithelial barrier function, and promotes expression of claudin-4, claudin-5 and occludin in lung tissue samples from rats with acute pancreatitis. PMID:20572302

  6. Acute Physical Exercise Affects Cognitive Functioning in Children With Cerebral Palsy.

    PubMed

    Maltais, Désirée B; Gane, Claire; Dufour, Sophie-Krystale; Wyss, Dominik; Bouyer, Laurent J; McFadyen, Bradford J; Zabjek, Karl; Andrysek, Jan; Voisen, Julien I

    2016-05-01

    Little is known about the effects of acute exercise on the cognitive functioning of children with cerebral palsy (CP). Selected cognitive functions were thus measured using a pediatric version of the Stroop test before and after maximal, locomotor based aerobic exercise in 16 independently ambulatory children (8 children with CP), 6-15 years old. Intense exercise had: 1) a significant, large, positive effect on reaction time (RT) for the CP group (preexercise: 892 ± 56.5 ms vs. postexercise: 798 ± 45.6 ms, p < .002, d = 1.87) with a trend for a similar but smaller response for the typically developing (TD) group (preexercise: 855 ± 56.5 ms vs. postexercise: 822 ± 45.6 ms, p < .08, d = 0.59), and 2) a significant, medium, negative effect on the interference effect for the CP group (preexercise: 4.5 ± 2.5%RT vs. postexercise: 13 ± 2.9%RT, p < .04, d = 0.77) with no significant effect for the TD group (preexercise: 7.2 ± 2.5%RT vs. postexercise: 6.9 ± 2.9%RT, p > .4, d = 0.03). Response accuracy was high in both groups pre- and postexercise (>96%). In conclusion, intense exercise impacts cognitive functioning in children with CP, both by increasing processing speed and decreasing executive function. PMID:26502458

  7. 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

  8. A novel adaptive switching function on fault tolerable sliding mode control for uncertain stochastic systems.

    PubMed

    Zahiripour, Seyed Ali; Jalali, Ali Akbar

    2014-09-01

    A novel switching function based on an optimization strategy for the sliding mode control (SMC) method has been provided for uncertain stochastic systems subject to actuator degradation such that the closed-loop system is globally asymptotically stable with probability one. In the previous researches the focus on sliding surface has been on proportional or proportional-integral function of states. In this research, from a degree of freedom that depends on designer choice is used to meet certain objectives. In the design of the switching function, there is a parameter which the designer can regulate for specified objectives. A sliding-mode controller is synthesized to ensure the reachability of the specified switching surface, despite actuator degradation and uncertainties. Finally, the simulation results demonstrate the effectiveness of the proposed method. PMID:24954808

  9. 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.

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

    PubMed Central

    SAENGKLUB, Nakkawee; LIMPRASUTR, Vudhiporn; SAWANGKOON, Suwanakiet; BURANAKARL, Chollada; HAMLIN, Robert L.; KIJTAWORNRAT, Anusak

    2015-01-01

    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. PMID:26346474

  11. 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

    2016-03-01

    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. PMID:26346474

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

    PubMed

    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

  13. 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

  14. Acute exercise stimulates macrophage function: possible role of NF-kappaB pathways.

    PubMed

    Silveira, Elza M S; Rodrigues, Mariana F; Krause, Maurício S; Vianna, Damiana R; Almeida, Bibiana S; Rossato, Juliane S; Oliveira, Lino P; Curi, Rui; de Bittencourt, Paulo I Homem

    2007-01-01

    Moderate physical activity when performed on a regular basis presents a number of benefits to the whole organism, especially regarding immune system function, such as augmenting resistance to infections and to cancer growth. Although glutamine production by active muscle cells as well as neuroendocrine alterations mediated by the chronic adaptation to exercise may play a role, the entire mechanism by which exercise makes the immune system aware of challenges remains mostly uncovered. This is particularly true for the effects of an acute exercise session on immune function. In this work, circulating monocytes/macrophages from sedentary rats submitted to an acute (1 h) swimming session were tested for the ability of phagocytosing zymosan particles, phorbol myristate acetate (PMA)-induced hydrogen peroxide production, nitric oxide (NO) release (assessed by nitrate and nitrite production) and the expression of NO synthases (NOS-1, NOS-2 and NOS-3). The results showed that an exercise bout induced a 2.4-fold rise in macrophage phagocytic capacity (p = 0.0041), a 9.6-fold elevation in PMA-induced hydrogen peroxide release into the incubation media (1-h, p = 0.0022) and a 95.5%-augmentation in nitrite basal production (1-h incubation; p = 0.0220), which was associated with a marked expression of NOS-2 (the inducible NOS isoform; p = 0.0319), but not in other NOS gene products. Although NOS-2 expression is nuclear factor-kappaB (NF-kappaB)-dependent, no systemic oxidative stress was found, as inferred from the data of plasma TBARS and glutathione disulphide (GSSG) to glutathione (GSH) ratio in circulating blood erythrocytes which remained constant after the acute exercise. Also, no stressful situation seemed to be faced by monocytes/macrophages, since the expression of the 70-kDa heat shock protein (HSP70) remained unchanged. We conclude that NF-kappaB-dependent induction of NOS-2 and macrophage activation must be related to local factor(s) produced in the surroundings of

  15. β-Cell Function, Incretin Effect, and Incretin Hormones in Obese Youth Along the Span of Glucose Tolerance From Normal to Prediabetes to Type 2 Diabetes

    PubMed Central

    Michaliszyn, Sara F.; Mari, Andrea; Lee, SoJung; Bacha, Fida; Tfayli, Hala; Farchoukh, Lama; Ferrannini, Ele

    2014-01-01

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia. PMID:24947360

  16. 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. PMID:24488563

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

    PubMed Central

    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

    2014-01-01

    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. PMID:24488563

  18. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.

    PubMed

    Jin, Yuepeng; Bai, Yongyu; 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

  19. Acute effects of ambient ozone on pulmonary function of children in The Netherlands

    SciTech Connect

    Hoek, G.; Fischer, P.; Brunekreef, B.; Lebret, E.; Hofschreuder, P.; Mennen, M.G. )

    1993-01-01

    In the spring and summer of 1989 an epidemiologic study was conducted to evaluate the acute effects of photochemical air pollution episodes on pulmonary function of children living in three nonindustrial towns in the Netherlands. Spirometry was performed repeatedly in the schools of the children, mostly during the morning hours. Data from 533 children having more than four valid pulmonary function tests were included in the analyses. The association between previous-day ambient ozone concentration and pulmonary function was evaluated, using individual linear regression analysis and subsequent evaluation of the distribution of individual regression coefficients. One hour maximum ambient ozone concentrations frequently exceeded 160 micrograms/m3 but were all lower than the Dutch Air Quality Guideline of 240 micrograms/m3 for all three populations. Significant negative associations of previous-day ambient ozone with FVC, FEV1, peak expiratory flow (PEF), and maximal midexpiratory flow (MMEF) were observed. There were indications of systematic differences in responses among the children. Children with chronic respiratory symptoms did not have a stronger response than children without these symptoms.

  20. Natural killer cell function and lymphoid subpopulations in acute non-lymphoblastic leukaemia in complete remission.

    PubMed Central

    Pizzolo, G.; Trentin, L.; Vinante, F.; Agostini, C.; Zambello, R.; Masciarelli, M.; Feruglio, C.; Dazzi, F.; Todeschini, G.; Chilosi, M.

    1988-01-01

    A long term follow-up study has been undertaken in 33 patients with acute non-lymphoblastic leukaemia (ANLL) in order to establish whether a correlation exists between the clinical course and the immunologic pattern of lymphoid subpopulations. Peripheral blood lymphoid cells have been investigated longitudinally (each 1 to 4 months) during complete remission (CR), by morphologic, phenotypic and functional analyses. Particular attention has been paid to the evaluation of the natural killer (NK) cell compartment, by the detection of cells expressing an NK-related phenotype and by NK in vitro assay. Among the patients so far evaluable, 20 relapsed (R) and 10 are long survivors in CR 'off therapy' (LS). The most relevant finding was represented by statistically higher values of NK activity observed in LS vs. R patients (P less than 0.01). The removal of adherent cells before the NK assay, performed to investigate the possible inhibitory effect on NK function played by the macrophage component, abolished this difference, due to a selective increase of NK function in the R group. The longitudinal study revealed that NK activity tended to decrease in individual patients who subsequently relapsed. These data suggest a possible role of NK cells in the relapse control of ANLL, although it cannot be excluded that the low level of NK activity observed in the R group is the result of impending relapse rather than its cause. PMID:3179190

  1. 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

  2. Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

    PubMed Central

    Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2014-01-01

    Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues. PMID:24876909

  3. 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. PMID:26903486

  4. Effects of acute physical exercise on hepatocyte volume and function in rat.

    PubMed

    Latour, M G; Brault, A; Huet, P M; Lavoie, J M

    1999-05-01

    The goal of the present experiment was to measure the volume of the different compartments in liver of exercised rats and to get some insights into the appropriate working of the hepatic function following exercise. Hence, livers from male rats were isolated and perfused after treadmill exercise or rest. This procedure was performed on rats that were overnight semifasted (50% food restriction) or well fed. To evaluate the hepatocyte cell volume, the multiple-indicator dilution curve technique was used after 40 min of perfusion. Radioactive tracers for red blood cells, sucrose, and water were used to measure liver vascular space, liver interstitial space, and water cellular space, respectively. The hepatocyte function was assessed by taurocholate and propanolol clearance. Oxygen consumption, intrahepatic resistance, bile secretion, and lactate dehydrogenase release estimated liver viability. Liver viability and hepatocyte function were not changed following exercise either in the fed or in the semifasted animals. As expected, liver glycogen levels were significantly (P < 0.01) reduced in the food-restricted rats. Consequently, liver glycogen levels following exercise were decreased significantly (P < 0.01) only in the fed rats. Despite this, exercise decreased the hepatocyte water space in both food-restricted and fed groups ( approximately 15%; P < 0.01) without altering the sinusoidal and interstitial space. The present data show that acute exercise decreased the hepatocyte volume and that this volume change is not entirely linked to a decrease in hepatic glycogen level. PMID:10233015

  5. 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. PMID:6859654

  6. Differential CD95 expression and function in T and B lineage acute lymphoblastic leukemia cells.

    PubMed

    Karawajew, L; Wuchter, C; Ruppert, V; Drexler, H; Gruss, H J; Dörken, B; Ludwig, W D

    1997-08-01

    CD95 (Fas/APO-1) is a cell surface receptor able to trigger apoptosis in a variety of cell types. The expression and function of the CD95 antigen on leukemic blasts from 42 patients with B lineage and 53 patients with T lineage acute lymphoblastic leukemia (ALL) were investigated using immunofluorescence staining and apoptosis assays. The CD95 surface antigen was expressed in most ALL cases, with the T lineage ALL usually showing a higher intensity of surface CD95 expression as compared with the B lineage ALL cells (relative fluorescence intensity, RFI: 4.8 +/- 0.47 vs 2.2 +/- 0.23, respectively, P < 0.01). Functional studies disclosed that upon oligomerization by anti-CD95 monoclonal antibodies the CD95 protein was either not able to initiate apoptosis of leukemic cells (75% of cases) or induced low rates of apoptosis (20% of cases). Only in 5% of cases did the apoptosis rate exceed the 20% level of the CD95-specific apoptosis. Most of the CD95-sensitive cases were found among T lineage ALLs (38% of T lineage vs 10% of B lineage ALLs). Overall, the extent of CD95-induced apoptosis did not correlate with the expression level of CD95. Similarly, no significant correlation between expression level and functionality of CD95 in human leukemia cell lines of B and T cell origin could be observed. Bcl-2 protein has been associated with prolonged cell survival and has been shown to block partially CD95-mediated apoptosis, but for ALL cells no correlation between bcl-2 expression and spontaneous or CD95-mediated apoptosis could be found. The results obtained in this study indicate that, despite constitutive expression of CD95, the ALL cells are mainly resistant to CD95-triggering. More detailed investigations of the molecular mechanisms involved in the intracellular apoptotic signal transduction, such as interactions of the bcl-2 and the other members of the bcl-2 family, and functionality of the interleukin-1beta converting enzyme (ICE) like-proteases, may give new

  7. Salt tolerance function of the novel C2H2-type zinc finger protein TaZNF in wheat.

    PubMed

    Ma, Xiaoli; Liang, Wenji; Gu, Peihan; Huang, Zhanjing

    2016-09-01

    The expression profile chip of the wheat salt-tolerant mutant RH8706-49 was investigated under salt stress in our laboratory. Results revealed a novel gene induced by salt stress with unknown functions. The gene was named as TaZNF (Triticum aestivum predicted Dof zinc finger protein) because it contains the zf-Dof superfamily and was deposited in GenBank (accession no. KF307327). Further analysis showed that TaZNF significantly improved the salt-tolerance of transgenic Arabidopsis. Various physiological indices of the transgenic plant were improved compared with those of the control after salt stress. Non-invasive micro-test (NMT) detection showed that the root tip of transgenic Arabidopsis significantly expressed Na(+) excretion. TaZNF is mainly localized in the nucleus and exhibited transcriptional activity. Hence, this protein was considered a transcription factor. The TaZNF upstream promoter was then cloned and was found to contain three salts, one jasmonic acid methyl ester (MeJA), and several ABA-responsive elements. The GUS staining and quantitative results of different tissues in the full-length promoter in the transgenic plants showed that the promoter was not tissue specific. The promoter activity in the root, leaf, and flower was enhanced after induction by salt stress. Moreover, GUS staining and quantitative measurement of GUS activity showed that the promoter sequence contained the positive regulatory element of salt and MeJA after their respective elements were mutated in the full-length promoter. RNA-Seq result showed that 2727 genes were differentially expressed; most of these genes were involved in the metabolic pathway and biosynthesis of secondary metabolite pathway. PMID:27156137

  8. PtrABF of Poncirus trifoliata functions in dehydration tolerance by reducing stomatal density and maintaining reactive oxygen species homeostasis

    PubMed Central

    Zhang, Qinghua; Wang, Min; Hu, Jianbing; Wang, Wei; Fu, Xingzheng; Liu, Ji-Hong

    2015-01-01

    Abscisic acid-responsive element (ABRE)-binding factors (ABFs) play important roles in abiotic stress responses; however, the underlying mechanisms are poorly understood. In this study, it is reported that overexpression of Poncirus trifoliata PtrABF significantly enhanced dehydration tolerance. The transgenic lines displayed smaller stomatal apertures, reduced stomatal density/index, and lower expression levels of genes associated with stomatal development. PtrABF was found to interact with PtrICE1, a homologue of ICE1 (Inducer of CBF Expression 1) that has been shown to be critical for stomatal development. Microarray analysis revealed that a total of 70 genes were differentially expressed in the transgenic line, 42 induced and 28 repressed. At least two units of ABREs and coupling elements were present in the promoters of most of the induced genes, among which peroxidase and arginine decarboxylase were verified as bona fide targets of PtrABF. Transgenic plants exhibited higher antioxidant enzyme activities and free polyamine levels, but lower levels of reactive oxygen species (ROS) and malondialdehyde. Polyamines were revealed to be associated with ROS scavenging in the transgenic plants due to a modulation of antioxidant enzymes triggered by signalling mediated by H2O2 derived from polyamine oxidase (PAO)-mediated catabolism. Taken together, the results indicate that PtrABF functions positively in dehydration tolerance by limiting water loss through its influence on stomatal movement or formation and maintaining ROS homeostasis via modulation of antioxidant enzymes and polyamines through transcriptional regulation of relevant target genes. PMID:26116025

  9. PtrABF of Poncirus trifoliata functions in dehydration tolerance by reducing stomatal density and maintaining reactive oxygen species homeostasis.

    PubMed

    Zhang, Qinghua; Wang, Min; Hu, Jianbing; Wang, Wei; Fu, Xingzheng; Liu, Ji-Hong

    2015-09-01

    Abscisic acid-responsive element (ABRE)-binding factors (ABFs) play important roles in abiotic stress responses; however, the underlying mechanisms are poorly understood. In this study, it is reported that overexpression of Poncirus trifoliata PtrABF significantly enhanced dehydration tolerance. The transgenic lines displayed smaller stomatal apertures, reduced stomatal density/index, and lower expression levels of genes associated with stomatal development. PtrABF was found to interact with PtrICE1, a homologue of ICE1 (Inducer of CBF Expression 1) that has been shown to be critical for stomatal development. Microarray analysis revealed that a total of 70 genes were differentially expressed in the transgenic line, 42 induced and 28 repressed. At least two units of ABREs and coupling elements were present in the promoters of most of the induced genes, among which peroxidase and arginine decarboxylase were verified as bona fide targets of PtrABF. Transgenic plants exhibited higher antioxidant enzyme activities and free polyamine levels, but lower levels of reactive oxygen species (ROS) and malondialdehyde. Polyamines were revealed to be associated with ROS scavenging in the transgenic plants due to a modulation of antioxidant enzymes triggered by signalling mediated by H2O2 derived from polyamine oxidase (PAO)-mediated catabolism. Taken together, the results indicate that PtrABF functions positively in dehydration tolerance by limiting water loss through its influence on stomatal movement or formation and maintaining ROS homeostasis via modulation of antioxidant enzymes and polyamines through transcriptional regulation of relevant target genes. PMID:26116025

  10. The functions of a cucumber phospholipase D alpha gene (CsPLDα) in growth and tolerance to hyperosmotic stress.

    PubMed

    Li, Shuzhen; Huang, Meili; Di, Qinghua; Ji, Tuo; Wang, Xiufeng; Wei, Min; Shi, Qinghua; Li, Yan; Gong, Biao; Yang, Fengjuan

    2015-12-01

    Plant phospholipase D (PLD), which can hydrolyze membrane phospholipids to produce phosphatidic acid (PA), a secondary signaling molecule, has been proposed to function in diverse plant stress responses. In this research, a qRT-PCR analysis indicated that the expression of a cucumber phospholipase D alpha gene (CsPLDα) was induced by salt and drought stresses in the roots and leaves. To further study the roles of CsPLDα in regulating plant tolerance to salt, polyethylene glycol (PEG) and abscisic acid (ABA) stresses, transgenic tobacco plants constitutively overexpressing CsPLDα were produced. A qRT-PCR analysis showed that the CsPLDα transcript levels were high in transgenic tobacco lines, whereas no expression was found in wild type (WT) tobacco, indicating that CsPLDα was successfully transferred into the tobacco genome and overexpressed. Under normal conditions for 30 d, seeds of transgenic lines germinated neatly, and the seedlings were robust and bigger than WT plants. When treated with different concentrations of NaCl, PEG and ABA, germination rates and seedling sizes of the transgenic lines were significantly greater than WT. In addition, the germination times for transgenic lines were also remarkably shorter. Further studies indicated that transgenic lines had longer primary roots and more biomass accumulation than WT plants. The water loss in transgenic lines was also much lower than in WT. These findings suggest that the CsPLDα overexpression positively regulates plant tolerance to hyperosmotic stresses, and that CsPLDα is involved in the ABA regulation of stomatal closure and the alleviation of ABA inhibition on seed germination and seedling growth. PMID:26476791

  11. Genomic and functional characterization of a methoprene-tolerant gene in the kissing-bug Rhodnius prolixus.

    PubMed

    Villalobos-Sambucaro, María José; Riccillo, Fernando Luis; Calderón-Fernández, Gustavo Mario; Sterkel, Marcos; Diambra, Luis Anibal; Ronderos, Jorge Rafael

    2015-05-15

    Metamorphosis, which depends upon a fine balance between two groups of lipid-soluble hormones such as juvenile hormones (JHs) and ecdysteroids, is an important feature in insect evolution. While it is clear that the onset of metamorphosis depends on the decrease of JH levels, the way in which these hormones exert their activities is not fully understood in Triatominae species. The discovery of a Drosophila melanogaster mutant resistant to the treatment with the JH analog methoprene, led finally to the description of the methoprene-tolerant gene in Tribolium castaneum (TcMet) as a putative JH receptor. Here we present the genomic and functional characterization of an ortholog of the methoprene-tolerant gene in the hemimetabolous insect Rhodnius prolixus (RpMet). The analysis of the R. prolixus gene showed that the exonic structure is different from that described for holometabolous species, although all the critical protein motifs are well conserved. Expression analysis showed the presence of RpMet mRNA in all the tested tissues: ovary, testis, rectum, Malpighian tubules and salivary glands. When juvenile individuals were treated with RpMet specific double strand RNA (dsRNA), we observed abnormal molting events that resulted in individuals with morphological alterations (adultoids). Similarly, treatment of newly emerged fed females with dsRNA resulted in an abnormal development of the ovaries, with eggs revealing anomalies in size and accumulation of yolk, as well as a decrease in the amount of heme-binding protein. Altogether, our results validate that RpMet is involved in the transduction of JH signaling, controlling metamorphosis and reproduction in R. prolixus. PMID:25963043

  12. 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. PMID:26249046

  13. Decline in executive control during acute bouts of exercise as a function of exercise intensity and fitness level.

    PubMed

    Labelle, Véronique; Bosquet, Laurent; Mekary, Saïd; Bherer, Louis

    2013-02-01

    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 for key methodological confounds. Thirty-seven participants (M(age)=23. 8 years; SD=2.6) completed a computerized modified-Stroop task (involving denomination, inhibition and switching conditions) while pedalling at 40%, 60% and 80% of their peak power output (PPO). Results showed that in the switching condition of the task, error rates increased as a function of exercise intensity (from 60% to 80% of PPO) in all participants and that lower fit individuals showed increased reaction time variability. This suggests that acute bouts of cardiovascular exercise can momentarily alter executive control and increase performance instability in lower fit individuals. PMID:23146780

  14. Functional significance of predischarge exercise thallium-201 findings following intravenous streptokinase therapy during acute myocardial infarction

    SciTech Connect

    Touchstone, D.A.; Beller, G.A.; Nygaard, T.W.; Watson, D.D.; Tedesco, C.; Kaul, S.

    1988-12-01

    The purpose of this study was to determine which predischarge exercise thallium-201 imaging pattern(s) best correlate with myocardial salvage following intravenous streptokinase therapy (IVSK). Myocardial salvage was defined as improvement in regional left ventricular function determined by two-dimensional echocardiography between the time of admission and time of discharge in 21 prospectively studied patients receiving IVSK within 4 hours of chest pain. All patients had coronary angiography 2 hours following IVSK. Whereas 16 of the 21 patients (76%) had patent infarct-related vessels, only seven (33%) showed significant improvement in regional function at hospital discharge. Eleven patients demonstrated persistent defects (PD), and five each showed delayed and reverse redistribution. Patients with both delayed and reverse redistribution demonstrated significant improvement in regional left ventricular function score, while those with PD did not (+3.9 +/- 3.3 versus -0.5 +/- 2.9, p = 0.004). All other clinical, exercise, electrocardiographic, scintigraphic, and angiographic variables were similar between all patients, with the exception of the interval between chest pain and the institution of IVSK, which was longer in patients with reverse compared to delayed redistribution (3.5 +/- 0.4 versus 2.2 +/- 0.4 hours, p = 0.001). It is concluded that both delayed and reverse redistribution seen on predischarge exercise thallium-201 imaging are associated with myocardial salvage, defined as serial improvement in regional systolic function. Despite a high infarct vessel patency rate in patients with acute myocardial infarction receiving IVSK within 4 hours of onset of symptoms, only one third demonstrated improvement in regional function that was associated with either delayed or reverse redistribution seen on predischarge exercise thallium-201 imaging.

  15. Semi-Crystalline Polar Polyethylene: Ester-Functionalized Linear Polyolefins Enabled by a Functional-Group-Tolerant, Cationic Nickel Catalyst.

    PubMed

    Long, Brian K; Eagan, James M; Mulzer, Michael; Coates, Geoffrey W

    2016-06-13

    A dibenzobarrelene-bridged, α-diimine Ni(II) catalyst (rac-3) was synthesized and shown to have exceptional behavior for the polymerization of ethylene. The catalyst afforded high molecular weight polyethylenes with narrow dispersities and degrees of branching much lower than those made by related α-diimine nickel catalysts. Catalyst rac-3 demonstrated living behavior at room temperature, produced linear polyethylene (Tm =135 °C) at -20 °C, and, most importantly, was able to copolymerize ethylene with the biorenewable polar monomer methyl 10-undecenoate to yield highly linear ester-functionalized polyethylene. PMID:27135297

  16. Pulmonary function and exercise tolerance are related to disease severity in pre-dialytic patients with chronic kidney disease: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Chronic kidney disease (CKD) involves a progressive, irreversible loss of kidney function. While early-stage CKD patients may show changes in pulmonary function and lowered exercise tolerance, the role of the estimated glomerular filtration rate (eGFR) in these patterns remains unknown. The aim of this study was to investigated pulmonary function and exercise tolerance in pre-dialytic CKD patients. Methods A cross-sectional study was carried out with 38 adult volunteers divided into a control group (CG), consisting of 9 healthy adults, and 29 pre-dialytic CKD patients in stages 3 (G3), 4 (G4), and 5 (G5). All participants underwent spirometric and manovacuometric tests, a cardiopulmonary exercise test (CPET), a 6-minute walk test (6MWT), and laboratory tests. Results The significant differences was observed in maximal exercise tolerance, measured as peak oxygen consumption percentage (VO2peak) (mL/kg/min) (CG = 28.9 ± 7.8, G3 = 23.3 ± 5.6, G4 = 21.4 ± 5.2, G5 = 20.2 ± 6.9; p = 0.03), and submaximal exercise tolerance, measured by 6MWT (m) (CG = 627.6 ± 37.8, G3 = 577.4 ± 66.1, G4 = 542.7 ± 57.3, G5 = 531.5 ± 84.2, p = 0.01). The eGFR was associated with pulmonary function-forced expiratory volume in the first second percentage (FEV1) (%) (r = 0.34, p = 0.02) and maximum inspiratory pressure (PImax) (r = 0.41, p = 0.02) - and exercise tolerance - VO2peak (mL/kg/min) (r = 0.43, p = 0.01) and 6MWT distance (m) (r = 0.55, p < 0.01). Conclusion Pre-dialytic CKD patients showed lower maximal and submaximal exercise tolerances than healthy individuals. PMID:24007403

  17. Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease.

    PubMed

    Shechter, Michael; Shalmon, Guy; Scheinowitz, Mickey; Koren-Morag, Nira; Feinberg, Micha S; Harats, Dror; Sela, Ben Ami; Sharabi, Yehonatan; Chouraqui, Pierre

    2011-05-01

    Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation. PMID:21349479

  18. 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

  19. Versatile functionalization of gene vectors via different types of zwitterionic betaine species for serum-tolerant transfection.

    PubMed

    Xiu, Ke-Mao; Zhao, Na-Na; Yang, Wan-Tai; Xu, Fu-Jian

    2013-07-01

    For ideal polymeric gene vectors, their serum stability is of crucial importance. Polycation vectors usually suffer from colloidal aggregation, which makes them easily cleared from the bloodstream. Recently, we reported a comb-shaped vector (DPD) consisting of a dextran backbone and disulfide-linked cationic poly((2-dimethyl amino)ethyl methacrylate) side chains for efficient gene delivery. In this work, versatile functionalization of DPD (as a model gene vector) was proposed via the introduction of different types of zwitterionic carboxybetaine and sulfobetaine species for improving biophysical properties. The incorporation of zwitterionic betaine did not destroy the DNA condensation capability of vectors. All the zwitterionic betaine-functionalized DPD vectors exhibited lower cytotoxicities than the pristine DPD. The DPD-b-polycarboxybetaine block copolymer (DPDbPC) exhibited better gene delivery abilities than the corresponding DPD-r-polycarboxybetaine random copolymer (DPDrPC). Moreover, in the serum case with a high concentration (30%) of fetal bovine serum, the DPD-b-polysulfobetaine block copolymer (DPDbPS) produced much higher gene transfection efficiencies than DPDbPC. Cellular internalization results indicated that the incorporation of zwitterionic betaine could benefit serum stabilities of vectors and enhance cellular uptake. The present study demonstrated that proper incorporation of zwitterionic betaine into gene carriers was an effective method to produce serum-tolerant transfection vectors. PMID:23571001

  20. 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

    2014-01-01

    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

  1. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  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. PMID:24911975

  3. Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation

    PubMed Central

    Mould, Arne W.; Morgan, Marc A. J.; Nelson, Andrew C.; Bikoff, Elizabeth K.; Robertson, Elizabeth J.

    2015-01-01

    The neonatal intestine is a very complex and dynamic organ that must rapidly adapt and remodel in response to a barrage of environmental stimuli during the first few postnatal weeks. Recent studies demonstrate that the zinc finger transcriptional repressor Blimp1/Prdm1 plays an essential role governing postnatal reprogramming of intestinal enterocytes during this period. Functional loss results in global changes in gene expression patterns, particularly in genes associated with metabolic function. Here we engineered a knock-in allele expressing an eGFP-tagged fusion protein under control of the endogenous regulatory elements and performed genome wide ChIP-seq analysis to identify direct Blimp1 targets and further elucidate the function of Blimp1 in intestinal development. Comparison with published human and mouse datasets revealed a highly conserved core set of genes including interferon-inducible promoters. Here we show that the interferon-inducible transcriptional activator Irf1 is constitutively expressed throughout fetal and postnatal intestinal epithelium development. ChIP-seq demonstrates closely overlapping Blimp1 and Irf1 peaks at key components of the MHC class I pathway in fetal enterocytes. The onset of MHC class I expression coincides with down-regulated Blimp1 expression during the suckling to weaning transition. Collectively, these experiments strongly suggest that in addition to regulating the enterocyte metabolic switch, Blimp1 functions as a gatekeeper in opposition to Irf1 to prevent premature activation of the MHC class I pathway in villus epithelium to maintain tolerance in the neonatal intestine. PMID:26158850

  4. Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation.

    PubMed

    Mould, Arne W; Morgan, Marc A J; Nelson, Andrew C; Bikoff, Elizabeth K; Robertson, Elizabeth J

    2015-07-01

    The neonatal intestine is a very complex and dynamic organ that must rapidly adapt and remodel in response to a barrage of environmental stimuli during the first few postnatal weeks. Recent studies demonstrate that the zinc finger transcriptional repressor Blimp1/Prdm1 plays an essential role governing postnatal reprogramming of intestinal enterocytes during this period. Functional loss results in global changes in gene expression patterns, particularly in genes associated with metabolic function. Here we engineered a knock-in allele expressing an eGFP-tagged fusion protein under control of the endogenous regulatory elements and performed genome wide ChIP-seq analysis to identify direct Blimp1 targets and further elucidate the function of Blimp1 in intestinal development. Comparison with published human and mouse datasets revealed a highly conserved core set of genes including interferon-inducible promoters. Here we show that the interferon-inducible transcriptional activator Irf1 is constitutively expressed throughout fetal and postnatal intestinal epithelium development. ChIP-seq demonstrates closely overlapping Blimp1 and Irf1 peaks at key components of the MHC class I pathway in fetal enterocytes. The onset of MHC class I expression coincides with down-regulated Blimp1 expression during the suckling to weaning transition. Collectively, these experiments strongly suggest that in addition to regulating the enterocyte metabolic switch, Blimp1 functions as a gatekeeper in opposition to Irf1 to prevent premature activation of the MHC class I pathway in villus epithelium to maintain tolerance in the neonatal intestine. PMID:26158850

  5. AAV8-mediated Gene Therapy Prevents Induced Biochemical Attacks of Acute Intermittent Porphyria and Improves Neuromotor Function

    PubMed Central

    Yasuda, Makiko; Bishop, David F; Fowkes, Mary; Cheng, Seng H; Gan, Lin; Desnick, Robert J

    2009-01-01

    Acute intermittent porphyria (AIP), an autosomal dominant hepatic porphyria due to half-normal hydroxymethylbilane synthase (HMB-synthase) activity, is manifested by life-threatening acute neurological attacks that are precipitated by factors that induce heme biosynthesis. The acute attacks are currently treated with intravenous hemin, but a more continuous therapy is needed, particularly for patients experiencing frequent attacks. Thus, a recombinant AAV8-based serotype vector expressing murine HMB-synthase driven by liver-specific regulatory elements was generated and its effectiveness to prevent the biochemical induction of an acute attack was evaluated in an AIP mouse model. Intraperitoneal administration of the adeno-associated viral (AAV) vector resulted in a rapid and dose-dependent increase of HMB-synthase activity that was restricted to the liver. Stable expression of hepatic HMB-synthase was achieved and wild-type or greater levels were sustained for 36 weeks. When heme synthesis was periodically induced by a series of phenobarbital injections, the treated mice did not accumulate urinary δ-aminolevulinic acid (ALA) or porphobilinogen (PBG), indicating that the expressed enzyme was functional in vivo and prevented induction of the acute attack. Further, rotarod performance and footprint analyses improved significantly. Thus, liver-directed gene therapy provided successful long-term correction of the hepatic metabolic abnormalities and improved neuromotor function in the murine model of human AIP. PMID:19861948

  6. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction

    PubMed Central

    Richards, A; Nicholls, M; Yandle, T; Ikram, H; Espiner, E; Turner, J; Buttimore, R; Lainchbury, J; Elliott, J; Frampton, C; Crozier, I; Smyth, D

    1999-01-01

    Objective—To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction.
Design—Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1-4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3-5 months after infarction. Clinical events were recorded over a mean period of 14 months.
Results—Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = −0.60, n = 220, p < 0.001; and r = −0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3-5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death.
Conclusions—Plasma BNP measured within 1-4 days of acute myocardial infarction is a powerful

  7. 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…

  8. 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 ...

  9. Effects of chronic and acute stimulants on brain functional connectivity hubs.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Goldstein, Rita Z

    2015-12-01

    The spatial distribution and strength of information processing 'hubs' are essential features of the brain׳s network topology, and may thus be particularly susceptible to neuropsychiatric disease. Despite growing evidence that drug addiction alters functioning and connectivity of discrete brain regions, little is known about whether chronic drug use is associated with abnormalities in this network-level organization, and if such abnormalities could be targeted for intervention. We used functional connectivity density (FCD) mapping to evaluate how chronic and acute stimulants affect brain hubs (i.e., regions with many short-range or long-range functional connections). Nineteen individuals with cocaine use disorders (CUD) and 15 healthy controls completed resting-state fMRI scans following a randomly assigned dose of methylphenidate (MPH; 20mg) or placebo. Short-range and long-range FCD maps were computed for each participant and medication condition. CUD participants had increased short-range and long-range FCD in the ventromedial prefrontal cortex, posterior cingulate/precuneus, and putamen/amygdala, which in areas of the default mode network correlated with years of use. Across participants, MPH decreased short-range FCD in the thalamus/putamen, and decreased long-range FCD in the supplementary motor area and postcentral gyrus. Increased density of short-range and long-range functional connections to default mode hubs in CUD suggests an overrepresentation of these resource-expensive hubs. While the effects of MPH on FCD were only partly overlapping with those of CUD, MPH-induced reduction in the density of short-range connections to the putamen/thalamus, a network of core relevance to habit formation and addiction, suggests that some FCD abnormalities could be targeted for intervention. PMID:25721787

  10. 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.

  11. 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

  12. 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. PMID:25356611

  13. 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.

  14. Acute moderate exercise does not attenuate cardiometabolic function associated with a bout of prolonged sitting.

    PubMed

    Younger, Amanda M; Pettitt, Robert W; Sexton, Patrick J; Maass, William J; Pettitt, Cherie D

    2016-01-01

    Epidemiological studies suggest that prolonged sitting increases all-cause mortality; yet, physiological causes underpinning prolonged sitting remain elusive. We evaluated cardiometabolic function during prolonged sitting (5 h) in 10 adults with and without 30 min of moderate exercise leading up to the sitting. Mean arterial blood pressure (MAP), heart rate (HR) and posterior tibial artery blood velocity were measured at baseline and every hour subsequently. Blood glucose was measured at baseline, 3 and 5 h, with consumption of a caloric beverage at 1 h. Seated MAP and HR values were ~17 mmHg (P < 0.001) and ~4 bpm (P < 0.05) higher for the moderate exercise versus sitting conditions. A ~ 4 cm·s(-1) (16%) (P < 0.05) decline in posterior tibial artery blood velocity from prolonged sitting was observed, with no benefit conferred from moderate exercise. Postprandial glucose metabolism was not different between conditions (P > 0.05). We conclude prolonged sitting may be related to decreased posterior tibial artery blood velocity. Moreover, an acute bout of moderate exercise does not seem to attenuate cardiometabolic function during prolonged sitting in healthy, young adults. PMID:26186044

  15. 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.

  16. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  17. 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.

  18. 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

  19. Tolerance to ethanol hypothermia in HOT and COLD mice.

    PubMed

    Crabbe, J C

    1994-02-01

    COLD and HOT mice have been selected to be sensitive or resistant, respectively, to the acute hypothermic effect of ethanol. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. By administering several doses of ethanol and recording multiple postdrug temperatures, in the current study we equated the selected lines for area under the curve describing initial hypothermic response over time, a measure reflecting both maximal hypothermia achieved and the duration of total hypothermic response. The dose-response function for COLD mice was much steeper than that for HOT mice, and HOT mice recovered to baseline body temperatures more slowly. Doses were administered daily for 5 days. Both lines developed tolerance to ethanol hypothermia. The magnitude of tolerance developed was greater in COLD than in HOT mice. At higher doses, HOT mice showed a progressively enhanced hypothermic response over days (i.e., sensitization). PMID:8198225

  20. Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans123

    PubMed Central

    Marcovina, Santica; Nelson, James E; Yeh, Matthew M; Kowdley, Kris V; Callahan, Holly S; Song, Xiaoling; Di, Chongzhi; Utzschneider, Kristina M

    2014-01-01

    Background: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n−7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts. Objective: The objective was to investigate whether the intake of trans-16:1n−7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance. Design: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n−7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography–derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity. Results: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n−7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n−7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with β-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for β-cell function. Conclusion: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat. This trial was registered at clinicaltrials.gov as NCT01289639. PMID:24740208

  1. Aluminum-activated citrate and malate transporters from the MATE and ALMT families function independently to confer Arabidopsis aluminum tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum (Al) activated root malate and citrate exudation plays an important role in Al tolerance in many plant species. Here, we report on the identification and characterization of AtMATE, a homolog of the recently discovered sorghum and barley Al tolerance genes, here shown to encode an Al-activ...

  2. Aluminum-activated citrate and malate transporters from the MATE and ALMT families function independently to confer Arabidopsis aluminum tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum (Al) activated root malate and citrate exudation play an important role in Al tolerance in many plant species. AtALMT1, an Al-activated malate transporter, is a major contributor to Arabidopsis Al tolerance. Here, we demonstrate that a second, unrelated gene, AtMATE, encodes an Arabidopsi...

  3. 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...

  4. Pulmonary function abnormalities in adult patients with acute exacerbation of bronchiectasis: A retrospective risk factor analysis.

    PubMed

    Ma, Yanliang; Niu, Yuqian; Tian, Guizhen; Wei, Jingan; Gao, Zhancheng

    2015-08-01

    Lung function impairments, especially airflow obstruction, are important features during acute exacerbation in patients with bronchiectasis. Recognition of the risk factors associated with airflow obstruction is important in the management of these exacerbations. The medical records of adult patients admitted to the Peking University People's Hospital, Beijing, China, from 2004 to 2011 with a diagnosis of bronchiectasis were reviewed retrospectively. Univariate and multivariate analyses were used to evaluate the risk factors associated with airflow obstruction. Airflow obstruction was found in 55.6% of 156 patients hospitalized with acute exacerbation of bronchiectasis, and the risk factors associated with airflow obstruction included young age (≤14 years old) at diagnosis (odds ratio (OR) = 3.454, 95% confidence interval (CI) 1.709-6.982, p = 0.001) as well as the presence of chronic obstructive pulmonary disease (COPD; OR = 14.677, 95% CI 5.696-37.819, p = 0.001), asthma (OR = 3.063, 95% CI 1.403-6.690, p = 0.005), and wheezing on auscultation (OR = 3.279, 95% CI 1.495-7.194, p = 0.003). The C-reactive protein (13.9 mg/dl vs. 6.89 mg/dl, p = 0.005), partial pressure of arterial oxygen (66.7 ± 8.57 mmHg vs. 89.56 ± 12.80 mmHg, p < 0.001), and partial pressure of arterial carbon dioxide (40.52 ± 2.77 mmHg vs. 42.87 ± 5.39 mmHg, p = 0.02) profiles were different between patients with or without airflow obstruction. In addition, patients colonized with potential pathogenic microorganisms had a decreased diffusing capacity (56.0% vs. 64.7%, p = 0.04). Abnormal pulmonary function was common in hospitalized patients with bronchiectasis exacerbations. Airflow obstruction was correlated with the patient's age at diagnosis, as well as the presence of combined COPD and asthma, and wheezing on auscultation, which also resulted in more severe systemic inflammation and hypoxemia. PMID:25882894

  5. Effects of acute radon progeny exposure on rat alveolar macrophage number and function

    SciTech Connect

    Johnson, N.F.; Newton, G.J.; Guilmette, R.A.

    1992-12-31

    Alveolar macrophages play a key role in removal and translocation of inhaled particles and have been shown to influence proliferation of Alveolar Type II cells and fibroblasts. The effect of radon progeny on alveolar macrophage number and function is not documented. Functional impairment of alveolar macrophages may be an ancillary event in the induction of pulmonary lesions and may also indicate dose to the peripheral lung. In our study, rats were exposed to 1000 working level months (WLM) of radon progeny over a 3- to 5-h period, with a vector aerosol of environmental tobacco smoke. Groups of animals were sacrificed, and the lungs were lavaged immediately after exposure and on days 2, 18, 16, 21 and 29 after exposure. The numbers and viabilities of the lavaged macrophages were determined. Cytological preparations were made to determine the number of binucleated/multinucleated macrophages and macrophages containing micronuclei. The DNA content was measured flow-cytometrically using Hoechst 33342, and phagocytosis was assayed by determining the uptake of fluorescent microspheres. The numbers and viabilities of macrophages recovered from exposed animals were similar to the values measured for control animals. There was no evidence of an inflammatory reaction during any period after radon progeny exposure. Nuclear atypia, evidenced by increases in the number of binucleated cells and cells with micronuclei, occurred in animals 8 days after exposure, and this response peaked at 21 days after exposure. The phagocytic capability of the alveolar macrophages was not significantly affected at any time point after exposure. These results show that there was little functional impairment of alveolar macrophages in rats after acute radon-progeny exposure; however, there was long-standing interference with cell division, resulting in binucleated and micronucleated macrophages.

  6. 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. PMID:23575360

  7. Metrics of High-Density Lipoprotein Function and Hospital Mortality in Acute Heart Failure Patients

    PubMed Central

    Potočnjak, Ines; Degoricija, Vesna; Trbušić, Matias; Terešak, Sanda Dokoza; Radulović, Bojana; Pregartner, Gudrun; Berghold, Andrea; Tiran, Beate; Marsche, Gunther; Frank, Saša

    2016-01-01

    Objective The functionality of high-density lipoprotein (HDL) is impaired in chronic ischaemic heart failure (HF). However, the relationship between HDL functionality and outcomes in acute HF (AHF) has not been studied. The present study investigates whether the metrics of HDL functionality, including HDL cholesterol efflux capacity and HDL-associated paraoxonase (PON)-1 arylesterase (AE) activity are associated with hospital mortality in AHF patients. Methods and Results The study was performed as a prospective, single-centre, observational research on 152 patients, defined and categorised according to the ESC and ACCF/AHA Guidelines for HF by time of onset, final clinical presentation and ejection fraction. The mean age of the included patients (52% female) was 75.2 years (SD 10.3) and hospital mortality was 14.5%. HDL cholesterol efflux capacity was examined by measuring the capacity of apoB depleted serum to remove tritium-labelled cholesterol from cultured macrophages. The AE activity of the HDL fraction was examined by a photometric assay. In a univariable regression analysis, low cholesterol efflux, but not AE activity, was significantly associated with hospital mortality [odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64–0.96, p = 0.019]. In multivariable analysis progressively adjusting for important clinical and laboratory parameters the association obtained for cholesterol efflux capacity and hospital mortality by univariable analysis, despite a stable OR, did not stay significant (p = 0.179). Conclusion Our results suggest that HDL cholesterol efflux capacity (but not AE activity) contributes to, but is not an independent risk factor for, hospital mortality in AHF patients. Larger studies are needed to draw firm conclusions. PMID:27304214

  8. Phenotypic, genotypic, and functional characterization of normal and acute myeloid leukemia-derived marrow endothelial cells.

    PubMed

    Pizzo, Russell J; Azadniv, Mitra; Guo, Naxin; Acklin, Joshua; Lacagnina, Kimberly; Coppage, Myra; Liesveld, Jane L

    2016-05-01

    In addition to participation in homing, egress, and transmigration of hematopoietic cells, marrow endothelium also contributes to cell proliferation and survival. Endothelial cells from multiple vascular beds are able to prevent spontaneous or therapy-induced apoptosis in acute myelogenous leukemia (AML) blasts. Marrow-derived endothelial cells from leukemia patients have not been well-characterized, and in this work, endothelial cells were purified from marrow aspirates from normal subjects or from newly diagnosed AML patients to compare these cells phenotypically and functionally. By reverse transcription polymerase chain reaction, these cells express CD31, Tie-2, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS), supporting endothelial origin. They take up acetyl low-density lipoprotein and are able to form tubular structures. Culture of AML cells with endothelial cells from both normal and AML subjects supported adhesion, transmigration, and leukemia colony-forming unit outgrowth. RNA-sequencing analysis revealed 130 genes significantly up- or downregulated in AML-derived endothelial cells as compared with those derived from normal marrow. The genes differentially expressed (p < 0.001) were included in biological function categories involving cancer, cell development, cell growth and proliferation, cell signaling, inflammatory response, and cell death and survival. Further pathway analysis revealed upregulation of c-Fos and genes involved in chemotaxis such as CXCL16. AML-derived endothelial cells are similar in phenotype and function to their normal marrow-derived counterparts, but genomic analysis suggests a differential signature with altered expression of genes, which could play a role in leukemogenesis or leukemia cell maintenance in the marrow microenvironment. PMID:26851308

  9. Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction

    PubMed Central

    Zhu, Guiyue; Yao, Yucai; Pan, Lingyun; Zhu, Wei; Yan, Suhua

    2015-01-01

    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/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. PMID:26675565

  10. 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.

  11. The Relationship between Dyslipidemia and Acute Axonal Function in Type 2 Diabetes Mellitus In Vivo

    PubMed Central

    Kwai, Natalie C. G.; Nigole, William; Poynten, Ann M.; Brown, Christopher; Krishnan, Arun V.

    2016-01-01

    lipoprotein concentration when adjusted for renal function, a separate risk factor for neuropathy development. Our findings indicate that acutely, serum lipids do not exert an acute effect on axonal function in type 2 diabetic patients: TEd(10–20ms)(1.2(-1.4,3.8);P = 0.4) and superexcitability (2.4(-0.05, 4.8);P = 0.06). Conclusions These findings suggest that serum triglyceride levels are not related to axonal function in type 2 diabetic patients. Additional pathogenic mechanisms may play a more substantial role in axonal dysfunction prior to DPN development. PMID:27078166

  12. Role of the durum wheat dehydrin in the function of proteases conferring salinity tolerance in Arabidopsis thaliana transgenic lines.

    PubMed

    Saibi, Walid; Zouari, Nabil; Masmoudi, Khaled; Brini, Faiçal

    2016-04-01

    Dehydrins are claimed to stabilize macromolecules against freezing damage, dehydration, ionic or osmotic stresses, thermal stress and re-folding yield. However, their precise function remains unknown. In this context, we report the behavior of protease activities in dehydrin transgenic Arabidopsis lines against the wild type plant under salt stress (100mM NaCl). Indeed, proteases play key roles in plants, maintaining strict protein quality control and degrading specific sets of proteins in response to diverse environmental and developmental stimuli. We proved that durum wheat DHN-5 modulates the activity of some proteases, summarized on the promotion of the Cysteinyl protease and the decrease of the Aspartyl protease activity. This fact is also upgraded in salt stress conditions. We conclude that the dehydrin transgenic context encodes salinity tolerance in transgenic lines through the modulation of the interaction not only at transcriptional level but also at protein level and also with the impact of salt stress as an endogenous and exogenous effector on some biocatalysts like proteases. PMID:26751399

  13. 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

  14. Functional analysis of thioredoxin from the desert lichen-forming fungus, Endocarpon pusillum Hedwig, reveals its role in stress tolerance.

    PubMed

    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

  15. Tolerability and patient compliance.

    PubMed

    Roose, S P

    1999-01-01

    Currently available antidepressants interact with several types of receptors, which may explain both wanted and unwanted effects of these drugs. These effects are different and distinctive, and knowledge about them may help clinicians understand differences between compounds in terms of their tolerability profiles. Given roughly comparable efficacy, tolerability profile is the critical determinant in selecting an antidepressant medication for a particular patient. In addition, tolerability is inseparably linked to patient compliance, both in acute and long-term treatment, and ultimately to overall success of treatment. Refinement in pharmacologic profiles of all newly introduced antidepressants resulted in overall advantages in tolerability in comparison with older tricyclic compounds. However, differences in receptor interactions between antidepressants are directly reflected in tolerability (adverse event) profiles. Among new antidepressants, mirtazapine and the selective serotonin reuptake inhibitors share favorable overall tolerability and safety, especially with respect to low premature termination rates because of adverse events, cardiac safety, and safety in overdose. However, the different pharmacologic profile of mirtazapine is reflected in its different tolerability profile. Because of interactions with the histamine (H1) receptor, mirtazapine may be related to transient initial somnolence and weight gain in some patients. Its serotonin-2 (5-HT2)-blocking properties may account for lack of sexual dysfunction, insomnia, nervousness, and agitation. Mirtazapine's 5-HT3-blocking properties are unique among all currently available antidepressants and may account for lack of gastrointestinal adverse events. PMID:10446736

  16. Altered regional homogeneity in patients with unilateral acute open-globe injury: a resting-state functional MRI study

    PubMed Central

    Huang, Xin; Li, Hai-Jun; Ye, Lei; Zhang, Ying; Wei, Rong; Zhong, Yu-Lin; Peng, De-Chang; Shao, Yi

    2016-01-01

    Objective To investigate the underlying regional homogeneity (ReHo) brain activity changes in patients with unilateral acute open-globe injury (OGI) and their relationship with their clinical features. Patients and methods In total, 18 patients with acute OGI (16 males and two females) and 18 healthy controls (HCs; 16 males and two females) closely matched in age, sex, and education status participated in the study. Each subject underwent a resting-state functional magnetic resonance imaging scan. The ReHo method was used to assess local features of spontaneous brain activity. Receiver–operating characteristic curve was used to distinguish OGIs from HCs. The nonparametric statistical analysis was used to explore the relationship between the observed mean ReHo values of the different brain areas and the behavioral performance. Results Compared with HCs, acute OGI patients had significantly increased ReHo values in the right cerebellum posterior lobe/lingual gyrus, left superior temporal gyrus/inferior frontal gyrus, left inferior frontal gyrus, left posterior cingulate cortex/precuneus, and left precentral operculum. However, there was no relationship between the observed mean ReHo values of the different brain areas and the behavioral performance. Conclusion Acute OGI may cause dysfunction in many brain regions, which may reflect the underlying pathologic mechanisms of acute vision loss in OGI patients. PMID:27536111

  17. 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. PMID:27139425

  18. 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

  19. 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

  20. Unilateral microinjection of acrolein into thoracic spinal cord produces acute and chronic injury and functional deficits.

    PubMed

    Gianaris, Alexander; Liu, Nai-Kui; Wang, Xiao-Fei; Oakes, Eddie; Brenia, John; Gianaris, Thomas; Ruan, Yiwen; Deng, Ling-Xiao; Goetz, Maria; Vega-Alvarez, Sasha; Lu, Qing-Bo; Shi, Riyi; Xu, Xiao-Ming

    2016-06-21

    Although lipid peroxidation has long been associated with spinal cord injury (SCI), the specific role of lipid peroxidation-derived byproducts such as acrolein in mediating damage remains to be fully understood. Acrolein, an α-β unsaturated aldehyde, is highly reactive with proteins, DNA, and phospholipids and is considered as a second toxic messenger that disseminates and augments initial free radical events. Previously, we showed that acrolein increased following traumatic SCI and injection of acrolein induced tissue damage. Here, we demonstrate that microinjection of acrolein into the thoracic spinal cord of adult rats resulted in dose-dependent tissue damage and functional deficits. At 24h (acute) after the microinjection, tissue damage, motoneuron loss, and spinal cord swelling were observed on sections stained with Cresyl Violet. Luxol fast blue staining further showed that acrolein injection resulted in dose-dependent demyelination. At 8weeks (chronic) after the microinjection, cord shrinkage, astrocyte activation, and macrophage infiltration were observed along with tissue damage, neuron loss, and demyelination. These pathological changes resulted in behavioral impairments as measured by both the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and grid walking analysis. Electron microscopy further demonstrated that acrolein induced axonal degeneration, demyelination, and macrophage infiltration. These results, combined with our previous reports, strongly suggest that acrolein may play a critical causal role in the pathogenesis of SCI and that targeting acrolein could be an attractive strategy for repair after SCI. PMID:27058147

  1. Bone marrow mesenchymal stem cells improve myocardial function in a swine model of acute myocardial infarction.

    PubMed

    Zhao, Jing-Jie; Liu, Xiao-Cheng; Kong, Feng; Qi, Tong-Gang; Cheng, Guang-Hui; Wang, Jue; Sun, Chao; Luan, Yun

    2014-09-01

    The aim of the current study was to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute myocardial infarction (AMI). AMI was induced in mini‑swine by ligating the left anterior descending coronary artery, and BMSCs (1x107) were injected via a sterile microinjection into the ischemic area. Six months postoperatively, electrocardiograph‑gated single photon emission computed tomography revealed that the myocardial filling defect was reduced and the left ventricular ejection fraction was improved in the BMSC group compared with the control group (P<0.05). Histopathological examination indicated that, in the BMSC treatment group, the percentage of survived myocardial tissue and the vessel density were increased, and the percentage of apoptosis was decreased compared with controls (P<0.05). Reverse transcription‑polymerase chain reaction results indicated that the expression levels of multiple inflammatory factors were significantly upregulated in the BMSC group compared with levels in the control group (P<0.05). In conclusion, the present study demonstrated that BMSC injection significantly improved cardiac function and reduced infarct size in six months, indicating that this method may be valuable for future study in clinical trials. PMID:25060678

  2. Initial emergency department systolic blood pressure predicts left ventricular systolic function in acute decompensated heart failure.

    PubMed

    Styron, Joseph F; Jois-Bilowich, Preeti; Starling, Randall; Hobbs, Robert E; Kontos, Michael C; Pang, Peter S; Peacock, W Frank

    2009-01-01

    Ejection fraction (EF) is often unknown in patients who present with acute decompensated heart failure (ADHF). The objective of this study was to determine whether a patient's systolic blood pressure is associated with their left ventricular EF. This study was a retrospective chart review of all patients admitted to an emergency department (ED) observation unit from January 2002 to December 2004. A low EF was defined as <40%. Among 475 patients, the median age was 72 years, 53% were men, 40% were white, 59% were black, and 59% had a low EF. Patients with low EFs were more likely male ( P<.0001), with prior congestive heart disease ( P<.0001), longer QRS duration ( P<.0001), left bundle branch block ( P<.0001), and higher B-type natriuretic peptide ( P<.0001). The low EF group was less likely to have diabetes ( P<.0001). Adjusted odds ratios for an EF >or=40% were significant at all systolic blood pressure readings >120 mm Hg. Having an ED systolic BP >120 mm Hg is associated with significantly higher rates of preserved left ventricular systolic function in patients with ADHF. PMID:19187401

  3. A functional receptor for B-cell activating factor is expressed on human acute lymphoblastic leukemias

    PubMed Central

    Parameswaran, Reshmi; Muschen, Markus; Kim, Yong-mi; Groffen, John; Heisterkamp, Nora

    2010-01-01

    B-lineage acute lymphoblastic leukemia (ALL) arises by transformation of a progenitor (pre-B) cell. Cure rates in adults remain low and treatment is complicated by support provided by the microenvironment to the leukemic cells, indicating an urgent need to better understand the factors that promote their survival. B cell activating factor (BAFF) and its receptor BAFF-R are important for survival and growth of mature normal and malignant B-cells but are not expressed on pre-B cells. Unexpectedly, all cells in the primary Philadelphia-chromosome positive and negative ALL samples tested were positive for high BAFF-R cell surface expression. The BAFF-R was fully competent to bind BAFF and stimulation of the receptor activated both the classical and the non-canonical NFκB pathways. Recombinant BAFF supported survival of the ALL cells in the absence of stroma, and it significantly attenuated the rate of apoptosis caused by exposure to nilotinib, a drug used therapeutically to treat Philadelphia-chromosome positive ALLs. Surprisingly, BAFF mRNA and protein were also expressed in the same cells but BAFF was not shed into the medium. Our report is the first showing universal expression of the BAFF-R by pre-B ALL cells and opens the possibility of blocking its function as an adjuvant therapeutic strategy. PMID:20460528

  4. Dysregulated Hypothalamic–Pituitary–Adrenal Axis Function Contributes to Altered Endocrine and Neurobehavioral Responses to Acute Stress

    PubMed Central

    Kinlein, Scott A.; Wilson, Christopher D.; Karatsoreos, Ilia N.

    2015-01-01

    Organisms react to environmental challenges by activating a coordinated set of brain–body responses known as the stress response. These physiological and behavioral countermeasures are, in large part, regulated by the neuroendocrine hypothalamic–pituitary–adrenal (HPA) axis. Normal functioning of the HPA axis ensures that an organism responds appropriately to altered environmental demands, representing an essential system to promote survival. Over the past several decades, increasing evidence supports the hypothesis that disruption of the HPA axis can lead to dysregulated stress response phenotypes, exacting a physiological cost on the organism commonly referred to as allostatic load. Furthermore, it has been recognized that high allostatic load can contribute to increased vulnerability of the organism to further challenges. This observation leads to the notion that disrupted HPA function and resulting inappropriate responses to stressors may underlie many neuropsychiatric disorders, including depression and anxiety. In the present set of studies, we investigate the role of both the normally functioning and disrupted HPA axis in the endocrine, neural, and behavioral responses to acute stress. Using a model of non-invasive chronic corticosterone treatment in mice, we show that dysregulating the normal function of the HPA leads to a mismatch between the hormonal and neural response to acute stress, resulting in abnormal behavioral coping strategies. We believe this model can be leveraged to tease apart the mechanisms by which altered HPA function contributes to neurobehavioral dysregulation in response to acute stress. PMID:25821436

  5. Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation

    PubMed Central

    2014-01-01

    Background We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR+CD14++CD16+cells) and inducible PMLC (iPMLC, HLA-DR+CD14++CD16- cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. Methods iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. Results rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. Conclusions These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation. PMID:24684897

  6. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers.

    PubMed

    Kjell, Jacob; Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew; Olson, Lars

    2015-11-01

    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

  7. 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

  8. The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function.

    PubMed

    Barnes, Matthew J; Mündel, Toby; Stannard, Stephen R

    2012-02-01

    Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg(-1) body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60 h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60 h. Significantly greater (p < 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60 h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36 h (p = 0.003) and 60 h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p < 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol's effect on the magnitude of EIMD-related decrements in voluntary force generation. PMID:22185621

  9. Alterations in bovine platelet function and acute phase proteins induced by Pasteurella haemolytica A1.

    PubMed Central

    Cheryk, L A; Hooper-McGrevy, K E; Gentry, P A

    1998-01-01

    Platelet function was assessed by aggregometry in 10 Holstein calves before and after exposure to Pasteurella haemolytica (biotype A, serotype 1) by intrabronchial challenge. At 24 h after exposure the platelets had become more reactive to stimulation with known platelet agonists such as adenosine diphosphate (ADP) and platelet-activating factor (PAF) and the platelet aggregates that formed were more resistant to disaggregation. The activation of platelets was an early response in the challenged calves as platelet function had returned to pretreatment levels 72 h after exposure to the bacteria while the acute phase reactant proteins, haptoglobin and fibrinogen, were approaching their peak values and alpha 2-macroglobulin levels had also risen significantly (P < 0.05) at this time. The plasma levels of these proteins were still elevated and albumin levels were depressed 6 d post-treatment. At post-mortem all calves exhibited pneumonic tissue damage. When P. haemolytica leukotoxin was added directly to bovine platelet suspensions both spontaneous aggregation and an increase in the aggregation response to ADP and PAF stimulation were observed. The morphological appearance of the platelet aggregates exhibited the typical pattern for bovine platelets with 2 distinct zones of cells being visible within each aggregate. One zone contained platelets in which the cytoplasmic granules were still evident and the other zone contained irregularly shaped platelets devoid of granular content. In the latter zone, discrete gaps, or pores, were evident in the plasma membrane of numerous platelets. This pore formation is characteristic of leukotoxin action and is not observed in ADP or PAF induced aggregates. Images Figure 2. PMID:9442932

  10. 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

  11. Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion

    PubMed Central

    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.

    2014-01-01

    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. PMID:25070512

  12. Interaction between worsening renal function and persistent congestion in acute decompensated heart failure.

    PubMed

    Wattad, Malak; Darawsha, Wisam; Solomonica, Amir; Hijazi, Maher; Kaplan, Marielle; Makhoul, Badira F; Abassi, Zaid A; Azzam, Zaher S; Aronson, Doron

    2015-04-01

    Worsening renal function (WRF) and congestion are inextricably related pathophysiologically, suggesting that WRF occurring in conjunction with persistent congestion would be associated with worse clinical outcome. We studied the interdependence between WRF and persistent congestion in 762 patients with acute decompensated heart failure (HF). WRF was defined as ≥0.3 mg/dl increase in serum creatinine above baseline at any time during hospitalization and persistent congestion as ≥1 sign of congestion at discharge. The primary end point was all-cause mortality with mean follow-up of 15 ± 9 months. Readmission for HF was a secondary end point. Persistent congestion was more common in patients with WRF than in patients with stable renal function (51.0% vs 26.6%, p <0.0001). Both persistent congestion and persistent WRF were significantly associated with mortality (both p <0.0001). There was a strong interaction (p = 0.003) between persistent WRF and congestion, such that the increased risk for mortality occurred predominantly with both WRF and persistent congestion. The adjusted hazard ratio for mortality in patients with persistent congestion as compared with those without was 4.16 (95% confidence interval [CI] 2.20 to 7.86) in patients with WRF and 1.50 (95% CI 1.16 to 1.93) in patients without WRF. In conclusion, persisted congestion is frequently associated with WRF. We have identified a substantial interaction between persistent congestion and WRF such that congestion portends increased mortality particularly when associated with WRF. PMID:25700802

  13. 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.

  14. Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women.

    PubMed

    Ward, Natalie C; Hodgson, Jonathan M; Woodman, Richard J; Zimmermann, Diane; Poquet, Laure; Leveques, Antoine; Actis-Goretta, Lucas; Puddey, Ian B; Croft, Kevin D

    2016-05-18

    Coffee is a rich source of polyphenols, primarily chlorogenic acids (CGA). Certain polyphenols and polyphenol-rich foods and beverages have been shown to improve endothelial function and lower blood pressure (BP). The aim of the present study was to investigate the acute effect of two doses of CGA (5-CGA) on endothelial function and BP. In a cross-over study, 16 healthy men and women received: (i) 0 mg purified 5-CGA (control group); (ii) 450 mg purified 5-CGA; (iii) 900 mg purified 5-CGA; and (iv) 200 mg purified (-)-epicatechin (positive control) in random order one week apart. Peak and continuous mean (60 to 240 s post ischaemia) flow-mediated dilation (FMD) was measured at baseline, 1 h and 4 h. BP was measured at baseline and every 30 min to 4 h. Plasma CGA and epicatechin levels were significantly increased at both 1 h and 4 h post their respective treatments. Peak FMD was not significantly altered by either dose of 5-CGA or the epicatechin, relative to control (p > 0.05). Relative to control, effects on continuous mean FMD response following 450 mg 5-CGA and 900 mg of 5-CGA (0.47 ± 0.16%, p = 0.016 and 0.65 ± 0.16%, p < 0.001, respectively) at 1 h and (0.18 ± 0.17%, p = 0.99 and 0.44 ± 0.16%, p < 0.05, respectively) at 4 h. There was no significant effect of any of the treatments on BP. In conclusion, the present study has found no significant effect of 5-CGA, at 450 and 900 mg, on peak FMD response. However, there were significant improvements in mean post-ischaemic FMD response, particularly at the 1 h time point in this group of healthy individuals. PMID:27109860

  15. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia.

    PubMed

    Yoda, Akinori; Yoda, Yuka; Chiaretti, Sabina; Bar-Natan, Michal; Mani, Kartik; Rodig, Scott J; West, Nathan; Xiao, Yun; Brown, Jennifer R; Mitsiades, Constantine; Sattler, Martin; Kutok, Jeffrey L; DeAngelo, Daniel J; Wadleigh, Martha; Piciocchi, Alfonso; Dal Cin, Paola; Bradner, James E; Griffin, James D; Anderson, Kenneth C; Stone, Richard M; Ritz, Jerome; Foà, Robin; Aster, Jon C; Frank, David A; Weinstock, David M

    2010-01-01

    The prognosis for adults with precursor B-cell acute lymphoblastic leukemia (B-ALL) remains poor, in part from a lack of therapeutic targets. We identified the type I cytokine receptor subunit CRLF2 in a functional screen for B-ALL-derived mRNA transcripts that can substitute for IL3 signaling. We demonstrate that CRLF2 is overexpressed in approximately 15% of adult and high-risk pediatric B-ALL that lack MLL, TCF3, TEL, and BCR/ABL rearrangements, but not in B-ALL with these rearrangements or other lymphoid malignancies. CRLF2 overexpression can result from translocation with the IGH locus or intrachromosomal deletion and is associated with poor outcome. CRLF2 overexpressing B-ALLs share a transcriptional signature that significantly overlaps with a BCR/ABL signature, and is enriched for genes involved in cytokine receptor and JAK-STAT signaling. In a subset of cases, CRLF2 harbors a Phe232Cys gain-of-function mutation that promotes constitutive dimerization and cytokine independent growth. A mutually exclusive subset harbors activating mutations in JAK2. In fact, all 22 B-ALLs with mutant JAK2 that we analyzed overexpress CRLF2, distinguishing CRLF2 as the key scaffold for mutant JAK2 signaling in B-ALL. Expression of WT CRLF2 with mutant JAK2 also promotes cytokine independent growth that, unlike CRLF2 Phe232Cys or ligand-induced signaling by WT CRLF2, is accompanied by JAK2 phosphorylation. Finally, cells dependent on CRLF2 signaling are sensitive to small molecule inhibitors of either JAKs or protein kinase C family kinases. Together, these findings implicate CRLF2 as an important factor in B-ALL with diagnostic, prognostic, and therapeutic implications. PMID:20018760

  16. Acute Effects of Hemodiafiltration Versus Conventional Hemodialysis on Endothelial Function and Inflammation

    PubMed Central

    Jia, Ping; Jin, Wei; Teng, Jie; Zhang, Hao; Zou, Jianzhou; Liu, Zhonghua; Shen, Bo; Cao, Xuesen; Ding, Xiaoqiang

    2016-01-01

    Abstract Endothelial dysfunction and chronic inflammatory process are prevalent in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). The aim of this study was to evaluate the acute and short-term effects of online hemodiafiltration (OL-HDF) versus conventional HD on endothelial function and inflammation. A prospective, randomized, crossover trial. Twenty stable ESRD patients undergoing chronic HD treatments were randomly assigned with a 1:1 ratio to conventional HD and to OL-HDF both for 2 weeks (either HD followed by OL-HDF or OL-HDF followed by HD). Markers of endothelial dysfunction such as flow-mediated dilatation (FMD) of the brachial artery, soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin (sTM) were measured at baseline, after the first dialysis session and after 2 weeks. Meanwhile, serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels were measured as well. Both a single OL-HDF session and 2-week OL-HDF significantly improved brachial FMD% (18.7 ± 6.9% at baseline; 21.5 ± 5.4% after the first dialysis; 21.5 ± 5.7% after 2 weeks; P < 0.05 vs baseline), decreased the levels of sEPCR (from 394.4 [297.9–457.0] ng/ml at baseline to 234.7 [174.1–345.5] ng/ml after the first dialysis, and to 191.5 [138.2–255.0] ng/ml after 2 weeks; P < 0.01 vs baseline) and sTM. In contrast, HD did not change FMD%, even increased the levels of sEPCR and sTM. A reduction in IL-6 level was observed in OL-HDF patients after 2-week dialysis, while IL-6 did not change in HD patients. There was no significant difference in change of hs-CRP level between the OL-HDF and HD treatments. OL-HDF has both acute and short-term beneficial effects on endothelial dysfunction compared to conventional HD. PMID:27100440

  17. Acute Effects of Hemodiafiltration Versus Conventional Hemodialysis on Endothelial Function and Inflammation: A Randomized Crossover Study.

    PubMed

    Jia, Ping; Jin, Wei; Teng, Jie; Zhang, Hao; Zou, Jianzhou; Liu, Zhonghua; Shen, Bo; Cao, Xuesen; Ding, Xiaoqiang

    2016-04-01

    Endothelial dysfunction and chronic inflammatory process are prevalent in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). The aim of this study was to evaluate the acute and short-term effects of online hemodiafiltration (OL-HDF) versus conventional HD on endothelial function and inflammation.A prospective, randomized, crossover trial.Twenty stable ESRD patients undergoing chronic HD treatments were randomly assigned with a 1:1 ratio to conventional HD and to OL-HDF both for 2 weeks (either HD followed by OL-HDF or OL-HDF followed by HD). Markers of endothelial dysfunction such as flow-mediated dilatation (FMD) of the brachial artery, soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin (sTM) were measured at baseline, after the first dialysis session and after 2 weeks. Meanwhile, serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels were measured as well.Both a single OL-HDF session and 2-week OL-HDF significantly improved brachial FMD% (18.7 ± 6.9% at baseline; 21.5 ± 5.4% after the first dialysis; 21.5 ± 5.7% after 2 weeks; P < 0.05 vs baseline), decreased the levels of sEPCR (from 394.4 [297.9-457.0] ng/ml at baseline to 234.7 [174.1-345.5] ng/ml after the first dialysis, and to 191.5 [138.2-255.0] ng/ml after 2 weeks; P < 0.01 vs baseline) and sTM. In contrast, HD did not change FMD%, even increased the levels of sEPCR and sTM. A reduction in IL-6 level was observed in OL-HDF patients after 2-week dialysis, while IL-6 did not change in HD patients. There was no significant difference in change of hs-CRP level between the OL-HDF and HD treatments.OL-HDF has both acute and short-term beneficial effects on endothelial dysfunction compared to conventional HD. PMID:27100440

  18. Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol.

    PubMed

    Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

    2016-03-01

    Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

  19. 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.

  20. Functional Environmental Screening of a Metagenomic Library Identifies stlA; A Unique Salt Tolerance Locus from the Human Gut Microbiome

    PubMed Central

    Culligan, Eamonn P.; Sleator, Roy D.; Marchesi, Julian R.; Hill, Colin

    2013-01-01

    Functional environmental screening of metagenomic libraries is a powerful means to identify and assign function to novel genes and their encoded proteins without any prior sequence knowledge. In the current study we describe the identification and subsequent analysis of a salt-tolerant clone from a human gut metagenomic library. Following transposon mutagenesis we identified an unknown gene (stlA, for “salt tolerance locus A”) with no current known homologues in the databases. Subsequent cloning and expression in Escherichia coli MKH13 revealed that stlA confers a salt tolerance phenotype in its surrogate host. Furthermore, a detailed in silico analysis was also conducted to gain additional information on the properties of the encoded StlA protein. The stlA gene is rare when searched against human metagenome datasets such as MetaHit and the Human Microbiome Project and represents a novel and unique salt tolerance determinant which appears to be found exclusively in the human gut environment. PMID:24349412

  1. 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. PMID:24799137

  2. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period

    PubMed Central

    Wylie, Glenn R.; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R.

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject’s reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  3. Cognitive Improvement after Mild Traumatic Brain Injury Measured with Functional Neuroimaging during the Acute Period.

    PubMed

    Wylie, Glenn R; Freeman, Kalev; Thomas, Alex; Shpaner, Marina; OKeefe, Michael; Watts, Richard; Naylor, Magdalena R

    2015-01-01

    Functional neuroimaging studies in mild traumatic brain injury (mTBI) have been largely limited to patients with persistent post-concussive symptoms, utilizing images obtained months to years after the actual head trauma. We sought to distinguish acute and delayed effects of mild traumatic brain injury on working memory functional brain activation patterns < 72 hours after mild traumatic brain injury (mTBI) and again one-week later. We hypothesized that clinical and fMRI measures of working memory would be abnormal in symptomatic mTBI patients assessed < 72 hours after injury, with most patients showing clinical recovery (i.e., improvement in these measures) within 1 week after the initial assessment. We also hypothesized that increased memory workload at 1 week following injury would expose different cortical activation patterns in mTBI patients with persistent post-concussive symptoms, compared to those with full clinical recovery. We performed a prospective, cohort study of working memory in emergency department patients with isolated head injury and clinical diagnosis of concussion, compared to control subjects (both uninjured volunteers and emergency department patients with extremity injuries and no head trauma). The primary outcome of cognitive recovery was defined as resolution of reported cognitive impairment and quantified by scoring the subject's reported cognitive post-concussive symptoms at 1 week. Secondary outcomes included additional post-concussive symptoms and neurocognitive testing results. We enrolled 46 subjects: 27 with mild TBI and 19 controls. The time of initial neuroimaging was 48 (+22 S.D.) hours after injury (time 1). At follow up (8.7, + 1.2 S.D., days after injury, time 2), 18 of mTBI subjects (64%) reported moderate to complete cognitive recovery, 8 of whom fully recovered between initial and follow-up imaging. fMRI changes from time 1 to time 2 showed an increase in posterior cingulate activation in the mTBI subjects compared to

  4. Structural and functional analysis of the yeast N-acetyltransferase Mpr1 involved in oxidative stress tolerance via proline metabolism.

    PubMed

    Nasuno, Ryo; Hirano, Yoshinori; Itoh, Takafumi; Hakoshima, Toshio; Hibi, Takao; Takagi, Hiroshi

    2013-07-16

    Mpr1 (sigma1278b gene for proline-analog resistance 1), which was originally isolated as N-acetyltransferase detoxifying the proline analog L-azetidine-2-carboxylate, protects yeast cells from various oxidative stresses. Mpr1 mediates the L-proline and L-arginine metabolism by acetylating L-Δ(1)-pyrroline-5-carboxylate, leading to the L-arginine-dependent production of nitric oxide, which confers oxidative stress tolerance. Mpr1 belongs to the Gcn5-related N-acetyltransferase (GNAT) superfamily, but exhibits poor sequence homology with the GNAT enzymes and unique substrate specificity. Here, we present the X-ray crystal structure of Mpr1 and its complex with the substrate cis-4-hydroxy-L-proline at 1.9 and 2.3 Å resolution, respectively. Mpr1 is folded into α/β-structure with eight-stranded mixed β-sheets and six α-helices. The substrate binds to Asn135 and the backbone amide of Asn172 and Leu173, and the predicted acetyl-CoA-binding site is located near the backbone amide of Phe138 and the side chain of Asn178. Alanine substitution of Asn178, which can interact with the sulfur of acetyl-CoA, caused a large reduction in the apparent kcat value. The replacement of Asn135 led to a remarkable increase in the apparent Km value. These results indicate that Asn178 and Asn135 play an important role in catalysis and substrate recognition, respectively. Such a catalytic mechanism has not been reported in the GNAT proteins. Importantly, the amino acid substitutions in these residues increased the L-Δ(1)-pyrroline-5-carboxylate level in yeast cells exposed to heat stress, indicating that these residues are also crucial for its physiological functions. These studies provide some benefits of Mpr1 applications, such as the breeding of industrial yeasts and the development of antifungal drugs. PMID:23818613

  5. 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

  6. 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

  7. Effects of early enteral nutrition on immune function of severe acute pancreatitis patients

    PubMed Central

    Sun, Jia-Kui; Mu, Xin-Wei; Li, Wei-Qin; Tong, Zhi-Hui; Li, Jing; Zheng, Shu-Yun

    2013-01-01

    AIM: To investigate the effects of early enteral nutrition (EEN) on the immune function and clinical outcome of patients with severe acute pancreatitis (SAP). METHODS: Patients were randomly allocated to receive EEN or delayed enteral nutrition (DEN). Enteral nutrition was started within 48 h after admission in EEN group, whereas from the 8th day in DEN group. All the immunologic parameters and C-reactive protein (CRP) levels were collected on days 1, 3, 7 and 14 after admission. The clinical outcome variables were also recorded. RESULTS: Sixty SAP patients were enrolled to this study. The CD4+ T-lymphocyte percentage, CD4+/CD8+ ratio, and the CRP levels in EEN group became significantly lower than in DEN group from the 7th day after admission. In contrast, the immunoglobulin G (IgG) levels and human leukocyte antigen-DR expression in EEN group became significantly higher than in DEN group from the 7th day after admission. No difference of CD8+ T-lymphocyte percentage, IgM and IgA levels was found between the two groups. The incidences of multiple organ dysfunction syndrome, systemic inflammatory response syndrome, and pancreatic infection as well as the duration of intensive care unit stay were significantly lower in EEN group than in DEN group. However, there was no difference of hospital mortality between the two groups. CONCLUSION: EEN moderates the excessive immune response during the early stage of SAP without leading to subsequent immunosuppression. EEN can improve the clinical outcome, but not decrease the hospital mortality of SAP patients. PMID:23431120

  8. Bim polymorphisms: influence on function and response to treatment in children with acute lymphoblastic leukemia

    PubMed Central

    Gagné, Vincent; Rousseau, Julie; Labuda, Malgorzata; Sharif-Askari, Bahram; Brukner, Ivan; Laverdière, Caroline; Ceppi, Francesco; Sallan, Stephen E.; Silverman, Lewis B.; Neuberg, Donna; Kutok, Jeffery L.; Sinnett, Daniel; Krajinovic, Maja

    2014-01-01

    Purpose Corticosteroids (CS) induce apoptosis in the malignant lymphoid cells and are critical component of combination therapy for acute lymphoblastic leukemia (ALL). Several genome-wide microarray studies demonstrated major implication of proapoptotic Bim in mediating CS-related resistance in leukemia cells. Experimental design We investigated Bim gene polymorphisms and their association with childhood ALL outcome, and the mechanism underlying the observed finding. Results Lower overall survival (OS) was associated with Bim C29201T located in BH3 domain (p=0.01). An association remained significant in multivariate model (p=0.007), was more apparent in high risk (HR) patients (p=0.004) and patients treated with dexamethasone (p=0.009), and was subsequently confirmed in the replication patient cohort (p=0.03). RNA analysis revealed that C29201T affects generation of gamma isoforms (gamma1) that lack pro-apoptotic BH3 domain. The phenotypic effect was minor suggesting the influence of additional factors that may act in conjunction with Bim genotype. Combined analysis with Mcl gene polymorphism (G -486T) revealed profound reduction in OS in individuals with both risk genotypes (p<0.0005 in discovery and p=0.002 in replication cohort) and particularly in HR patients (p≤0.008). Conclusions Increased expression of pro-survival Mcl1 and presence of Bim isoforms lacking pro-apoptotic function might explain marked reduction of OS in a disease and dose dependent manner in ALL patients carrying Bim and Mcl1 risk genotypes. PMID:23908358

  9. Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure.

    PubMed

    Davranche, Karen; Casini, Laurence; Arnal, Pierrick J; Rupp, Thomas; Perrey, Stéphane; Verges, Samuel

    2016-10-01

    The present study aimed to assess specific cognitive processes (cognitive control and time perception) and hemodynamic correlates using functional near-infrared spectroscopy (fNIRS) during acute and prolonged high-altitude exposure. Eleven male subjects were transported via helicopter and dropped at 14 272 ft (4 350 meters) of altitude where they stayed for 4 days. Cognitive tasks, involving a conflict task and temporal bisection task, were performed at sea level the week before ascending to high altitude, the day of arrival (D0), the second (D2) and fourth (D4) day at high altitude. Cortical hemodynamic changes in the prefrontal cortex (PFC) area were monitored with fNIRS at rest and during the conflict task. Results showed that high altitude impacts information processing in terms of speed and accuracy. In the early hours of exposure (D0), participants displayed slower reaction times (RT) and decision errors were twice as high. While error rate for simple spontaneous responses remained twice that at sea level, the slow-down of RT was not detectable after 2 days at high-altitude. The larger fNIRS responses from D0 to D2 suggest that higher prefrontal activity partially counteracted cognitive performance decrements. Cognitive control, assessed through the build-up of a top-down response suppression mechanism, the early automatic response activation and the post-error adjustment were not impacted by hypoxia. However, during prolonged hypoxic exposure the temporal judgments were underestimated suggesting a slowdown of the internal clock. A decrease in cortical arousal level induced by hypoxia could consistently explain both the slowdown of the internal clock and the persistence of a higher number of errors after several days of exposure. PMID:27262217

  10. 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

  11. Relationship between T-wave normalization on exercise ECG and myocardial functional recovery in patients with acute myocardial infarction

    PubMed Central

    Kim, Kyung Jin; Shim, Wan Joo; Jung, Seong Won; Pak, Hui Nam; Lee, Soo Jin; Song, Woo Hyuk; Kim, Young Hoon; Seo, Hong Seog; Oh, Dong Joo; Ro, Young Moo

    2002-01-01

    Background Several studies suggested that T-wave normalization (TWN) in exercise ECG indicates the presence of viable myocardium. But the clinical implication of this phenomenon in patients with acute myocardial infarction who received proper revascularization therapy was not determined. Precisely the aim of this study was to investigate the relationship between TWN in exercise ECG and myocardial functional recovery after acute myocardial infarction. Methods We studied 30 acute myocardial infarction patients with negative T waves in infarct related electrocardiographic leads and who had received successful revascularization therapy. Exercise ECG was performed 10–14days after infarct onset using Naughton protocol. Patients were divided into 2 groups according to presence (group I; n=14) or not (group II; n=16) of TWN in exercise ECG. Exercise parameters and coronary angiographic findings were compared between groups. Baseline and follow-up (mean 11 months) regional and global left ventricular function was analyzed by echocardiography. Results Exercise parameters were similar between groups. There was no difference in baseline ejection fraction and wall motion score between group I and II (EF; 56±12% vs 52±11%, p=ns. WMS; 21±3 vs 23±4, p=ns) and it was improved at the tenth month by similar magnitude (group I/group II, EF % change=12±12% vs 7±6%, p=ns, WMS % change=6±6% vs 7±5%, p=ns). The finding of no relation between TWN and functional recovery was observed also when the patients were analysed according to infarct location and presence or absence of Q-waves. Conclusion As the exercise-induced TWN in patients with acute myocardial infarction was not related with better functional recovery of dysfunctional regional wall motion and ejection fraction, TWN does not appear to be an indicator of myocardial viability. PMID:12164089

  12. Blockade of tolerance to morphine analgesia by cocaine.

    PubMed

    Misra, A L; Pontani, R B; Vadlamani, N L

    1989-07-01

    Tolerance to morphine analgesia was induced in male Sprague-Dawley rats by s.c. implantation of a morphine base pellet (75 mg) on the first and second day and determining the magnitude of tolerance 72 h after the first implant by s.c. injection of a test dose of morphine (5 mg/kg). Implantation of a cocaine hydrochloride pellet (25 mg), concurrently with morphine pellets or of a cocaine hydrochloride (50 mg) pellet after the development of tolerance, blocked both the development and expression of morphine analgesic tolerance. In morphine-pelleted animals pretreatment for 3 days with desipramine or zimelidine or phenoxybenzamine but not haloperidol produced no significant morphine tolerance. Pretreatment with a combination of desipramine and zimelidine, however, was as effective as cocaine in blocking morphine tolerance. Alpha-Methyl-p-tyrosine methyl ester counteracted the effect of cocaine in blocking morphine tolerance and potentiated the tolerance development. Blockade of morphine tolerance by cocaine was reinforced and facilitated by pretreatment with fenfluramine or p-chlorophenylalanine ethyl ester and to a lesser extent by clonidine and haloperidol. Acute administration of fenfluramine or zimelidine or a combination of desipramine and zimelidine or alpha-methyl-p-tyrosine methyl ester or p-chlorophenylalanine ethyl ester did not significantly affect morphine analgesia. The study suggests an important role of the concomitant depletion of both central noradrenaline and serotonin in the blockade of morphine tolerance by cocaine and stresses the importance of the counter-balancing functional relationship between these two neurotransmitters in the central nervous system. PMID:2780065

  13. 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.

  14. 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

  15. 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. PMID:26696729

  16. 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

  17. Function of wheat Ta-UnP gene in enhancing salt tolerance in transgenic Arabidopsis and rice.

    PubMed

    Liang, Wenji; Cui, Weina; Ma, Xiaoli; Wang, Gang; Huang, Zhanjing

    2014-07-18

    Based on microarray analysis results of the salt tolerant wheat mutant, we identified and cloned an unknown salt-induced gene Ta-UnP (Triticum aestivum unknown protein). Quantitative PCR results revealed that Ta-UnP expression was induced not only by salt but also by polyethylene glycol, abscisic acid, and other environmental stress factors. Under salt stress, transgenic Arabidopsis plants that overexpressed Ta-UnP showed superior physiological properties (content of proline, soluble sugar, MDA, and chlorophyll) compared with the control. Subcellular localization demonstrated that Ta-UnP was mainly localized on the cell membrane. The expressions of nine salt tolerance-related genes of Arabidopsis in Ta-UnP-overexpressed Arabidopsis were analyzed via qPCR, and the results revealed that the expressions of SOS2, SOS3, RD29B, and P5CS were significantly up-regulated, whereas the other five genes only slightly changed. The results of the salt tolerance analysis indicated that Ta-UnP can enhance the salt tolerance of transgenic rice plants, and RNAi transgenic rice plants became highly susceptible to salt stress. The results from this study indicate that this novel Ta-UnP may be useful in improving of plant tolerance to salt stress. PMID:24953696

  18. 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. PMID:26429932

  19. An Evidence Based Review of Acute and Long-Term Effects of Cannabis Use on Executive Cognitive Functions

    PubMed Central

    Crean, Rebecca D.; Crane, Natania A.; Mason, Barbara J.

    2011-01-01

    Cannabis use has been shown to impair cognitive functions on a number of levels—from basic motor coordination to more complex executive function tasks, such as the ability to plan, organize, solve problems, make decisions, remember, and control emotions and behavior. These deficits differ in severity depending on the quantity, recency, age of onset and duration of marijuana use. Understanding how cannabis use impairs executive function is important. Individuals with cannabis-related impairment in executive functions have been found to have trouble learning and applying the skills required for successful recovery, putting them at increased risk for relapse to cannabis use. Here we review the research on the acute, residual, and long-term effects of cannabis use on executive functions, and discuss the implications for treatment. PMID:21321675

  20. Acute paraquat exposure determines dose-dependent oxidative injury of multiple organs and metabolic dysfunction in rats: impact on exercise tolerance.

    PubMed

    Novaes, Rômulo D; Gonçalves, Reggiani V; Cupertino, Marli C; Santos, Eliziária C; Bigonha, Solange M; Fernandes, Geraldo J M; Maldonado, Izabel R S C; Natali, Antônio J

    2016-04-01

    This study investigated the pathological morphofunctional adaptations related to the imbalance of exercise tolerance triggered by paraquat (PQ) exposure in rats. The rats were randomized into four groups with eight animals each: (a) SAL (control): 0.5 ml of 0.9% NaCl solution; (b) PQ10: PQ 10 mg/kg; (c) PQ20: PQ 20 mg/kg; and (d) PQ30: PQ 30 mg/kg. Each group received a single injection of PQ. After 72 hours, the animals were subjected to an incremental aerobic running test until fatigue in order to determine exercise tolerance, blood glucose and lactate levels. After the next 24 h, lung, liver and skeletal muscle were collected for biometric, biochemical and morphological analyses. The animals exposed to PQ exhibited a significant anticipation of anaerobic metabolism during the incremental aerobic running test, a reduction in exercise tolerance and blood glucose levels as well as increased blood lactate levels during exercise compared to control animals. PQ exposure increased serum transaminase levels and reduced the glycogen contents in liver tissue and skeletal muscles. In the lung, the liver and the skeletal muscle, PQ exposure also increased the contents of malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase and catalase, as well as a structural remodelling compared to the control group. All these changes were dose-dependent. Reduced exercise tolerance after PQ exposure was potentially influenced by pathological remodelling of multiple organs, in which glycogen depletion in the liver and skeletal muscle and the imbalance of glucose metabolism coexist with the induction of lipid, protein and DNA oxidation, a destructive process not counteracted by the upregulation of endogenous antioxidant enzymes. PMID:27277193

  1. 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. PMID:26707595

  2. 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

  3. Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

    PubMed Central

    Fried, Nathan T.; Moffat, Cynthia; Seifert, Erin L.

    2014-01-01

    Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders. PMID:25252946

  4. Antibodies against acute phase proteins and their functions in the pathogenesis of disease: a collective profile of 25 different antibodies.

    PubMed

    Lakota, Katja; Zigon, Polona; Mrak-Poljsak, Katjusa; Rozman, Blaz; Shoenfeld, Yehuda; Sodin-Semrl, Snezna

    2011-10-01

    The acute phase response is a defense system in which the innate immune response is activated following injury or infection. Positive and negative acute phase proteins (APPs) are crucial for protecting the host organism, as well as returning it to homeostatic levels, the first with elevated concentrations and the latter with decreased concentrations during the acute phase. Reports about the presence of antibodies against APPs are known, however their individual, as well as potentially collective, pathological or physiological roles are still emerging. Some of these autoantibodies are specifically connected with diseases (such as pancreatic secretory trypsin inhibitor and C3, C4 nephritic factors), while others have been reported as natural antibodies. The persistent presence (even if only minor) of autoantibodies in healthy blood donors indicates an overlapping category of autoantibodies, which could become pathogenic, depending on the autoantibody characteristics such as avidity, epitope specificity, changes in the microenvironment leading to different oxidative status and others. This review uses the novel approach of studying the overall autoantibody population against APPs, their functions and connections to diseases. The primary function of autoantibodies against APPs (anti-APPs) is thought to promote their clearance, however autoantibodies against negative APPs have also been found and applying the same role to those is doubtful. There is also the theory of consumption in the stage of inflammation, which could be relevant to anti-APPs. Reports about protective roles of autoantibodies are also emerging, showing lowered levels of antibodies in diseases, which could be interesting for therapeutic intervention. PMID:21718807

  5. 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

  6. GADD45a Promoter Regulation by a Functional Genetic Variant Associated with Acute Lung Injury

    PubMed Central

    Mitra, Sumegha; Wade, Michael S.; Sun, Xiaoguang; Moldobaeva, Nurgul; Flores, Carlos; Ma, Shwu-Fan; Zhang, Wei

    2014-01-01

    Rationale Growth arrest DNA damage inducible alpha (GADD45a) is a stress-induced gene we have shown to participate in the pathophysiology of ventilator-induced lung injury (VILI) via regulation of mechanical stress-induced Akt ubiquitination and phosphorylation. The regulation of GADD45a expression by mechanical stress and its relationship with acute lung injury (ALI) susceptibility and severity, however, remains unknown. Objectives We examined mechanical stress-dependent regulatory elements (MSRE) in the GADD45a promoter and the contribution of promoter polymorphisms in GADD45a expression and ALI susceptibility. Methods and Results Initial studies in GADD45a knockout and heterozygous mice confirmed the relationship of GADD45a gene dose to VILI severity. Human lung endothelial cells (EC) transfected with a luciferase vector containing the full length GADD45a promoter sequence (−771 to +223) demonstrated a >4 fold increase in GADD45a expression in response to 18% cyclic stretch (CS, 4 h) compared to static controls while specific promoter regions harboring CS-dependent MSRE were identified using vectors containing serial deletion constructs of the GADD45a promoter. In silico analyses of GADD45a promoter region (−371 to −133) revealed a potential binding site for specificity protein 1 (SP1), a finding supported by confirmed SP1 binding with the GADD45a promoter and by the significant attenuation of CS-dependent GADD45a promoter activity in response to SP1 silencing. Separately, case-control association studies revealed a significant association of a GADD45a promoter SNP at −589 (rs581000, G>C) with reduced ALI susceptibility. Subsequently, we found allelic variation of this SNP is associated with both differential GADD45a expression in mechanically stressed EC (18% CS, 4 h) and differential binding site of interferon regulatory factor 7 (IRF7) at this site. Conclusion These results strongly support a functional role for GADD45a in ALI/VILI and identify a

  7. Impaired cardiovascular structure and function in adult survivors of severe acute malnutrition.

    PubMed

    Tennant, Ingrid A; Barnett, Alan T; Thompson, Debbie S; Kips, Jan; Boyne, Michael S; Chung, Edward E; Chung, Andrene P; Osmond, Clive; Hanson, Mark A; Gluckman, Peter D; Segers, Patrick; Cruickshank, J Kennedy; Forrester, Terrence E

    2014-09-01

    Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index-matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; P<0.001), stroke volume 0.44 (0.17; P=0.009), cardiac output 0.5 (0.16; P=0.001), and pulse wave velocity 0.32 (0.15; P=0.03) compared with controls but higher diastolic blood pressures (by 4.3; 1.2-7.3 mm Hg; P=0.007). Systemic vascular resistance was higher in marasmus and kwashiorkor survivors (30.2 [1.2] and 30.8 [1.1], respectively) than controls 25.3 (0.8), overall difference 5.5 (95% confidence interval, 2.8-8.4 mm Hg min/L; P<0.0001). No evidence of large vessel or cardiac remodeling was found, except closer relationships between these indices in former marasmic survivors. Other parameters did not differ between SAM survivor groups. We conclude that adult SAM survivors had smaller outflow tracts and cardiac output when compared with controls, yet markedly elevated peripheral resistance. Malnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity. PMID:24980666

  8. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2016-07-26

    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

  9. Acute toxic effects of the herbicide formulation and the active ingredient used in cycloxydim-tolerant maize cultivation on embryos and larvae of the African clawed frog, Xenopus laevis.

    PubMed

    Wagner, Norman; Lötters, Stefan; Veith, Michael; Viertel, Bruno

    2015-04-01

    Most genetically engineered herbicide-tolerant crops are still awaiting approval in Europe. There is, however, a recent trend for the cultivation of cycloxydim-tolerant maize hybrids for use in maize production. We studied the acute toxic effects of the complementary herbicide Focus(®) Ultra and its active ingredient cycloxydim on embryos and early-stage larvae of the African clawed frog (Xenopus laevis). The results indicate that the herbicide formulation is significantly more toxic than the active ingredient alone. Therefore, it is suggested that the added substances either solely or in a synergistic action with the active ingredient are responsible for adverse effects. The formulation was found to be moderately toxic to embryos but highly toxic to early larvae. Based on calculated teratogenic indices, both cycloxydim and Focus(®) Ultra seem to be non-teratogenic and also the minimum Focus(®) Ultra concentration to inhibit growth in embryos and larvae was close to the LC50 values. The data suggest that tests with the rainbow trout are not in all cases appropriate to assess the risk in aquatically developing anurans. This is demonstrated by 96-h LC50 values, which are for rainbow trout more than 50- to 20-fold higher than for early X. laevis larvae. However, based on worst-case predicted environmental concentrations for surface waters, there is apparently a large safety margin in field use of Focus(®) Ultra if buffer strips between the farm land and the amphibian habitats are regarded. PMID:25634323

  10. 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

  11. Supplementation of the diet with the functional fiber PolyGlycoplex® is well tolerated by healthy subjects in a clinical trial

    PubMed Central

    Carabin, Ioana G; Lyon, Michael R; Wood, Simon; Pelletier, Xavier; Donazzolo, Yves; Burdock, George A

    2009-01-01

    Background The relationship of dietary fiber to overall health is of great importance, as beneficial effects have been demonstrated with the use of fiber from diverse sources, some traditional, other novel. PolyGlycopleX® (PGX®) is a unique proprietary product composed of three water-soluble polysaccharides, that when processed using novel technology give rise to a final product – a soluble, highly viscous functional fiber. Methods Because of its potential use in food and dietary supplements, a randomized, double-blind, placebo controlled clinical study was conducted to evaluate the tolerance to PGX ingestion for 21 days, to a maximum dose level of 10 g per day, in healthy male and female volunteers. The main objective of the study was to evaluate the overall gastrointestinal (GI) tolerance, while secondary objectives were to evaluate possible changes in hematological, biochemical, urinary and fecal parameters. Results Results show that PGX is well tolerated as part of a regular diet with only mild to moderate adverse effects, similar to those seen with a moderate intake of dietary fiber in general, and fruits and vegetables. Because PGX is a highly viscous, functional fiber, it also demonstrates several physiological responses including, but not limited to maintaining healthy total and LDL cholesterol and uric acid levels. PMID:19196472

  12. ICE1 of Pyrus ussuriensis functions in cold tolerance by enhancing PuDREBa transcriptional levels through interacting with PuHHP1.

    PubMed

    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

  13. 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

  14. Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation.

    PubMed

    Yu, Junli; Venstrom, Jeffrey M; Liu, Xiao-Rong; Pring, James; Hasan, Reenat S; O'Reilly, Richard J; Hsu, Katharine C

    2009-04-16

    Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient ("missing self"). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell-depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-gamma and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell-derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome. PMID:19179302

  15. 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. PMID:25808564

  16. 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.

  17. Adverse effects of AMP-activated protein kinase alpha2-subunit deletion and high-fat diet on heart function and ischemic tolerance in aged female mice.

    PubMed

    Slámová, K; Papoušek, F; Janovská, P; Kopecký, J; Kolář, F

    2016-03-14

    AMP-activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK alpha2-subunit deletion affects heart function and ischemic tolerance of adult and aged mice. AMPK alpha2(-/-) (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK alpha2-subunit protein level, but no difference in AMPK alpha1-subunit was detected between the strains. Both alpha1- and alpha2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK alpha2-subunit deletion and high-fat feeding on heart function and myocardial ischemic tolerance in aged female mice are not additive. PMID:26596312

  18. Assessing structural and functional responses of murine hearts to acute and sustained β-adrenergic stimulation in vivo

    PubMed Central

    Puhl, Sarah-Lena; Weeks, Kate L.; Ranieri, Antonella; Avkiran, Metin

    2016-01-01

    Introduction Given the importance of β-adrenoceptor signalling in regulating cardiac structure and function, robust protocols are required to assess potential alterations in such regulation in murine models in vivo. Methods Echocardiography was performed in naïve and stressed (isoprenaline; 30 μg/g/day s.c. for up to 14 days) mice, in the absence or presence of acute β-adrenergic stimulation (dobutamine 0.75 μg/g, i.p.). Controls received saline infusion and/or injection. Hearts were additionally analysed gravimetrically, histologically and biochemically. Results In naïve mice, acute β-adrenoceptor stimulation with dobutamine increased heart rate, left ventricular (LV) fractional shortening (LVFS), ejection fraction (LVEF) and wall thickness and decreased LV diameter (p < 0.05). In stressed mice, dobutamine failed to induce further inotropic and chronotropic responses. Furthermore, following dobutamine injection, these mice exhibited lower LVEF and LVFS at identical heart rates, relative to corresponding controls. Sustained isoprenaline infusion induced LV hypertrophy (increased heart weight, heart weight/body weight ratio, heart weight/tibia length ratio and LV wall thickness (p < 0.05)) by 3 days, with little further change at 14 days. In contrast, increases in LVEF and LVFS were seen only at 14 days (p < 0.05). Discussion We describe protocols for and illustrative data from the assessment of murine cardiac responses to acute and sustained β-adrenergic stimulation in vivo, which would be of value in determining the impact of genetic or pharmacological interventions on such responses. Additionally, our data indicate that acute dobutamine stimulation unmasks early signs of LV dysfunction in the remodelled heart, even at a stage when basal function is enhanced. PMID:26836145

  19. ASSESSMENT OF FUNCTIONAL, MORPHOLOGICAL AND ENZYMATIC TEST FOR ACUTE NEPHROTOXICITY INDUCED BY MERCURIC CHLORIDE

    EPA Science Inventory

    The relative merits of a comprehensive series of contemporary methods for detection of acute nephrotoxicity were evaluated. Male Sprague-Dawley rats were given 0, 0.25, 0.5, 1.0, or 30.0 mg mercuric chloride (HgCl2)/kg body weight by ip injection. Indices of nephrotoxicity were e...

  20. Acute restraint stress enhances hippocampal endocannabinoid function via glucocorticoid receptor activation.

    PubMed

    Wang, Meina; Hill, Matthew N; Zhang, Longhua; Gorzalka, Boris B; Hillard, Cecilia J; Alger, Bradley E

    2012-01-01

    Exposure to behavioural stress normally triggers a complex, multilevel response of the hypothalamic-pituitary-adrenal (HPA) axis that helps maintain homeostatic balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic stress, few studies have directly addressed its response to acute stress. Here we show that acute restraint stress enhances eCB-dependent modulation of GABA release measured by whole-cell voltage clamp of inhibitory postsynaptic currents (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro. Both Ca(2+)-dependent, eCB-mediated depolarization-induced suppression of inhibition (DSI), and muscarinic cholinergic receptor (mAChR)-mediated eCB mobilization are enhanced following acute stress exposure. DSI enhancement is dependent on the activation of glucocorticoid receptors (GRs) and is mimicked by both in vivo and in vitro corticosterone treatment. This effect does not appear to involve cyclooxygenase-2 (COX-2), an enzyme that can degrade eCBs; however, treatment of hippocampal slices with the L-type calcium (Ca(2+)) channel inhibitor, nifedipine, reverses while an agonist of these channels mimics the effect of in vivo stress. Finally, we find that acute stress produces a delayed (by 30 min) increase in the hippocampal content of 2-arachidonoylglycerol, the eCB responsible for DSI. These results support the hypothesis that the ECS is a biochemical effector of glucocorticoids in the brain, linking stress with changes in synaptic strength. PMID:21890595

  1. MODULATION OF PHAGOCYTE FUNCTION BY OVOTRANSFERRIN, A CHICKEN ACUTE PHASE PROTEIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovotransferrin (OTF) is an acute phase protein in chickens the serum levels of which is elevated in response to inflammation and infections. To understand whether OTF may influence inflammation through its immunomodulatory effects, we studied its in vitro effects on chicken macrophage-like HD11 cell...

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

    PubMed

    Lents, C A; White, F J; Ciccioli, N H; Floyd-White, L N; Rubio, I; Keisler, D H; Spicer, L J; Wettemann, R P

    2013-09-01

    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 restricted to 0.4 × maintenance requirements (0.4M; d 0). Heifers received PGF2α (25 mg, intramuscularly) on d -10, 0, and 10 to synchronize ovulation. After 30 d, 1.2M and 0.4M heifers were realimented to 1.2 M for 100 d. Blood samples were collected every other day from d 0 to 14 then 3 times weekly thereafter. Heifers in Exp. 2 were managed as in Exp. 1 except that animals were fitted with an indwelling jugular catheter and blood samples were collected at 10-min intervals for 8 h on d 9, 10, and 11. Concentrations of progesterone in plasma were used to quantify ovarian luteal function. All 1.2M heifers ovulated, whereas only 30% of 0.4M heifers ovulated in Exp. 1. Concentrations of NEFA were greater and concentrations of thyroxine and IGF-I were less (P < 0.05) in plasma of 0.4M heifers compared with 1.2M heifers. The size of dominant follicles in Exp. 1 was reduced (P < 0.05) in 0.4M compared with 1.2M heifers. Concentrations of IGF-I were increased and anovulatory heifers resumed ovarian cycles an average of 35 d after realimentation. Concentrations of insulin were greater (P < 0.05) in plasma of 1.2M compared with 0.4M heifers in Exp. 2. The frequency of LH pulses was reduced (P < 0.05) in 0.4M heifers on d 9, and FSH in plasma on d 11 was not influenced by treatment. Reduced concentrations of IGF-I in plasma of nutrient-restricted heifers were associated with the reduced size of dominant follicles and indicated a local effect of growth factors on follicles. The decreased LH pulse frequency of 0.4M heifers before luteolysis indicates that restriction of nutrients decreased LH support of follicle growth. A preovulatory increase in estradiol in plasma and an

  3. Response topography in behavioral tolerance to cocaine with rats.

    PubMed

    Weaver, Matthew T; Dallery, Jesse; Branch, Marc N

    2010-10-01

    Research conducted with rats has shown tolerance to the behavioral effects of psychomotor stimulants to be contingent on chronic drug administration occurring before the experimental session. Recent experiments with pigeons, however, resulted in tolerance when drug administration followed the experimental session. We hypothesized that the apparent species differences in tolerance may be a function of different operantly conditioned response topographies used in these experiments. Specifically, we propose that operantly reinforced consummatory responses, like pecking with pigeons, are less likely to reveal contingent tolerance. This experiment involved rats in a manner that paralleled earlier experiments with pigeons. Rats were subjected to daily sessions that required 20 licking responses to obtain 2.5-s access to water. Acute effects of cocaine were determined by administering precession doses ranging from 1.0 to 30.0 mg/kg, with dosing occurring every fifth day. Rats were then divided into two groups. One group received 17.0 mg/kg cocaine before the session and the other received 17.0 mg/kg cocaine after the session. After 30 daily sessions, the effects of the cocaine-dose range were reassessed. Tolerance to the rate-decreasing effects of cocaine was evident in both the groups, regardless of the temporal relationship between drug administration and the experimental session. The results support the hypothesis that operantly reinforced consummatory responses are less likely to show contingent tolerance. PMID:20823771

  4. Restoration of renal function by a novel prostaglandin EP4 receptor-derived peptide in models of acute renal failure

    PubMed Central

    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

    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. PGE2 is a lipid hormone mediator abundantly produced in the kidney, where it acts locally to regulate renal function; several studies suggest that modulating EP4 receptor activity could improve renal function following kidney injury. An optimized peptidomimetic ligand of EP4 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 PGE2-binding dissociation kinetics, indicative of an allosteric binding mode. Consistently, THG213.29 antagonized EP4-mediated relaxation of piglet saphenous vein rings, partially inhibited EP4-mediated cAMP production, but did not affect Gαi 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 EP4-transfected HEK293 cells, THG213.29 augmented FGF-2 and abrogated EP4-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 EP4 receptor, resulting in improved renal function and integrity following acute renal failure. PMID:23152113

  5. The cytosolic O-acetylserine(thiol)lyase gene is regulated by heavy metals and can function in cadmium tolerance.

    PubMed

    Dominguez-Solís, J R; Gutierrez-Alcalá, G; Vega, J M; Romero, L C; Gotor, C

    2001-03-23

    Regulation of the expression of the cytosolic O-acetylserine(thiol)lyase gene (Atcys-3A) from Arabidopsis thaliana under heavy metal stress conditions has been investigated. Northern blot analysis of Atcys-3A expression shows a 7-fold induction after 18 h of cadmium treatment. Addition of 50 microm CdCl(2) to the irrigation medium of mature Arabidopsis plants induces a rapid accumulation of the mRNA throughout the leaf lamina, the root and stem cortex, and stem vascular tissues when compared with untreated plants, as observed by in situ hybridization. High pressure liquid chromatography analysis of GSH content shows a transient increase after 18 h of metal treatment. Our results are compatible with a high cysteine biosynthesis rate under heavy metal stress required for the synthesis of GSH and phytochelatins, which are involved in the plant detoxification mechanism. Arabidopsis-transformed plants overexpressing the Atcys-3A gene by up to 9-fold show increased tolerance to cadmium when grown in medium containing 250 microm CdCl(2), suggesting that increased cysteine availability is responsible for cadmium tolerance. In agreement with these results, exogenous addition of cystine can, to some extent, also favor the growth of wild-type plants in cadmium-containing medium. Cadmium accumulates to higher levels in leaves of tolerant transformed lines than in wild-type plants. PMID:11121418

  6. Functional Replacement of Ferredoxin by a Cyanobacterial Flavodoxin in Tobacco Confers Broad-Range Stress Tolerance[W

    PubMed Central

    Tognetti, Vanesa B.; Palatnik, Javier F.; Fillat, María F.; Melzer, Michael; Hajirezaei, Mohammad-Reza; Valle, Estela M.; Carrillo, Néstor

    2006-01-01

    Chloroplast ferredoxin (Fd) plays a pivotal role in plant cell metabolism by delivering reducing equivalents to various essential oxidoreductive pathways. Fd levels decrease under adverse environmental conditions in many microorganisms, including cyanobacteria, which share a common ancestor with chloroplasts. Conversely, stress situations induce the synthesis of flavodoxin (Fld), an electron carrier flavoprotein not found in plants, which can efficiently replace Fd in most electron transfer processes. We report here that chloroplast Fd also declined in plants exposed to oxidants or stress conditions. A purified cyanobacterial Fld was able to mediate plant Fd-dependent reactions in vitro, including NADP+ and thioredoxin reduction. Tobacco (Nicotiana tabacum) plants expressing Fld in chloroplasts displayed increased tolerance to multiple sources of stress, including redox-cycling herbicides, extreme temperatures, high irradiation, water deficit, and UV radiation. Oxidant buildup and oxidative inactivation of thioredoxin-dependent plastidic enzymes were decreased in stressed plants expressing plastid-targeted Fld, suggesting that development of the tolerant phenotype relied on productive interaction of this flavoprotein with Fd-dependent oxidoreductive pathways of the host, most remarkably, thioredoxin reduction. The use of Fld provides new tools to investigate the requirements of photosynthesis in planta and to increase plant stress tolerance based on the introduction of a cyanobacterial product that is free from endogenous regulation in higher plants. PMID:16829589

  7. 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

  8. [Acute coronary syndrome with impaired left ventricular function in a carbon monoxide poisoning].

    PubMed

    Capilla, E; Pons, F; Poyet, R; Kerebel, S; Jego, C; Louge, P; Cellarier, G-R

    2016-02-01

    Carbon monoxide poisoning is the leading cause of death by poisoning in France. Neuropsychological symptoms are most common. We report on a patient with acute coronary syndrome and transient left ventricular dysfunction in carbon monoxide poisoning. Patient improved under hyperbaric oxygen therapy. Coronary angiography shows no significant lesion leading to myocardial stunning diagnose. Patients exposed to carbon monoxide must have systematic cardiac evaluation with electrocardiogram and dosage of biomarkers. PMID:25261170

  9. Carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute spinal cord injury in rats.

    PubMed

    Liu, Da; Huang, Ying; Li, Bin; Jia, Changqing; Liang, Feng; Fu, Qin

    2015-02-01

    Acute spinal cord injury (SCI) leads to permanent functional deficits via mechanical injury and secondary mechanisms, but the therapeutic strategy for SCI is limited. Carvedilol has been shown to possess multiple biological and pharmacological properties. The of the present study was to investigate the possible protective effect of carvedilol in SCI rats. An acute SCI rat model was established and neurological function was tested. After carvedilol (10 mg/kg, oral gavage) treatment for 21 days, the status of osteoporosis, neuron damage, astrocyte activation, inflammation, oxidative stress and apoptosis were evaluated in rats. Carvedilol significantly improved locomotor activity that was decreased by SCI. In addition, carvedilol promoted bone growth by regulating the expression of nuclear factor-κB ligand (receptor activator of nuclear factor-κB ligand; RANKL) and osteoprotegerin (OPG), inactivating osteoclasts and thereby increasing bone mineral density in tibias. In addition, carvedilol reduced SCI-induced neural damage, increased neuron number and reduced astrocyte activation in the spinal cord. Furthermore, the production and mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 were significantly reduced, reduced glutathione content and superoxide dismutase activity were markedly increased and malondialdehyde content was markedly decreased in the spinal cords of carvedilol-treated rats. These results indicate that carvedilol exhibits anti-inflammatory and anti-oxidative effects in SCI rats. In addition, the expression of Fas and Fas ligand was reduced by carvedilol treatment, which, in turn, reduced cleaved caspase 3 expression and finally decreased the number of apoptotic cells in the spinal cord. In conclusion, carvedilol promotes neurological function, reduces bone loss and attenuates cell damage after acute SCI in rats. PMID:25424914

  10. 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.

  11. 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. PMID:25821957

  12. 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. PMID:16309937

  13. Copolymer-1 Promotes Neurogenesis and Improves Functional Recovery after Acute Ischemic Stroke in Rats

    PubMed Central

    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. PMID:25821957

  14. Accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection

    PubMed Central

    Wijewardana, Viskam; Bouwer, Anthea L; Brown, Kevin N; Liu, Xiangdong; Barratt-Boyes, Simon M

    2014-01-01

    Myeloid dendritic cells (mDC) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the mDC response, particularly early in acute infection, is ill-defined. We studied acute pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques to address this question. The mDC in blood and bone marrow were depleted within 12 days of intravenous infection with SIVmac251, associated with a marked proliferative response. In lymph nodes, mDC were apoptotic, activated and proliferating, despite normal mDC numbers, reflecting a regenerative response that compensated for mDC loss. Blood mDC had increased expression of MHC class II, CCR7 and CD40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of mDC in blood but resulted in accumulation of immature mDC in lymph nodes. Following SIV infection, lymph node mDC had an increased capacity to secrete tumour necrosis factor-α upon engagement with a Toll-like receptor 7/8 ligand that mimics exposure to viral RNA, and this was inversely correlated with MHC class II and CCR7 expression. Lymph node mDC had an increased ability to capture and cleave soluble antigen, confirming their functionally immature state. These data indicate that acute SIV infection results in increased mDC turnover, leading to accumulation in lymph nodes of immature mDC with an increased responsiveness to virus stimulation. PMID:24684292

  15. Functional and morphologic characteristics of the leukemic cells of a patient with acute monocytic leukemia: correlation with clinical features.

    PubMed

    Schiffer, C A; Sanel, F T; Stechmiller, B K; Wiernik, P H

    1975-07-01

    The clinical course of a patient with acute monocytic leukemia and prominent infiltration of the skin and testes is described. In vitro studies demonstrated that the circulating monocyte precursors were capable of adherence to nylon fibers, and phagocytosis of bacteria and latex particles. In vivo, migration of leukemic cells to skin windows was observed. Extreme nuclear folding, marked surface activity, and morphologic features suggesting nuclear and cytoplasmic maturation were seen by light and electron microscopy. The presence of morphologically and functionally more differentiated monocytic cells may account for the marked tiuuse invasion in this patient and, possibly, in other patients with monocytic leukemia. PMID:1055611

  16. Left Ventricular Function during Acute High-Altitude Exposure in a Large Group of Healthy Young Chinese Men

    PubMed Central

    Rao, Mingyue; Li, Jiabei; Qin, Jun; Zhang, Jihang; Gao, Xubin; Yu, Shiyong; Yu, Jie; Chen, Guozhu; Xu, Baida; Li, Huijie; Rao, Rongsheng; Huang, Lan; Jin, Jun

    2015-01-01

    Objective The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males. Methods A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points. Results Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude. Conclusion Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function. PMID:25629435

  17. Tolerance of the Human Kidney to Isolated Controlled Ischemia

    PubMed Central

    Weinberg, Joel M.; Ercole, Barbara; Torkko, Kathleen C.; Hilton, William; Bennett, Michael; Devarajan, Prasad; Venkatachalam, Manjeri A.

    2013-01-01

    Tolerance of the human kidney to ischemia is controversial. Here, we prospectively studied the renal response to clamp ischemia and reperfusion in humans, including changes in putative biomarkers of AKI. We performed renal biopsies before, during, and after surgically induced renal clamp ischemia in 40 patients undergoing partial nephrectomy. Ischemia duration was >30 minutes in 82.5% of patients. There was a mild, transient increase in serum creatinine, but serum cystatin C remained stable. Renal functional changes did not correlate with ischemia duration. Renal structural changes were much less severe than observed in animal models that used similar durations of ischemia. Other biomarkers were only mildly elevated and did not correlate with renal function or ischemia duration. In summary, these data suggest that human kidneys can safely tolerate 30–60 minutes of controlled clamp ischemia with only mild structural changes and no acute functional loss. PMID:23411786

  18. Characterization of expressed sequence tags (ESTs) of pigeonpea (Cajanus cajan L.) and functional validation of selected genes for abiotic stress tolerance in Arabidopsis thaliana.

    PubMed

    Priyanka, B; Sekhar, K; Sunita, T; Reddy, V D; Rao, Khareedu Venkateswara

    2010-03-01

    Pigeonpea, a major grain legume crop with remarkable drought tolerance traits, has been used for the isolation of stress-responsive genes. Herein, we report generation of ESTs, transcript profiles of selected genes and validation of candidate genes obtained from the subtracted cDNA libraries of pigeonpea plants subjected to PEG/water-deficit stress conditions. Cluster analysis of 124 selected ESTs yielded 75 high-quality ESTs. Homology searches disclosed that 55 ESTs share significant similarity with the known/putative proteins or ESTs available in the databases. These ESTs were characterized and genes relevant to the specific physiological processes were identified. Of the 75 ESTs obtained from the cDNA libraries of drought-stressed plants, 20 ESTs proved to be unique to the pigeonpea. These sequences are envisaged to serve as a potential source of stress-inducible genes of the drought stress-response transcriptome, and hence may be used for deciphering the mechanism of drought tolerance of the pigeonpea. Expression profiles of selected genes revealed increased levels of m-RNA transcripts in pigeonpea plants subjected to different abiotic stresses. Transgenic Arabidopsis lines, expressing Cajanus cajan hybrid-proline-rich protein (CcHyPRP), C. cajan cyclophilin (CcCYP) and C. cajan cold and drought regulatory (CcCDR) genes, exhibited marked tolerance, increased plant biomass and enhanced photosynthetic rates under PEG/NaCl/cold/heat stress conditions. This study represents the first report dealing with the isolation of drought-specific ESTs, transcriptome analysis and functional validation of drought-responsive genes of the pigeonpea. These genes, as such, hold promise for engineering crop plants bestowed with tolerance to major abiotic stresses. PMID:20131066

  19. Acute malocclusion.

    PubMed

    Dupont, John S

    2006-01-01

    Acute malocclusion can result from disturbances in the maxillary/mandibular tooth relationship. These alterations in the occlusal position can result from high fillings, sinus problems, abscesses, periodontal disease, and moving or erupting teeth. Conditions seen less frequently include acute malocclusions secondary to an event (such as trauma) that make a stable dental relationship an unstable one. Patients can demonstrate any of a number of clinical conditions that interfere with their comfort and ability to function. This article provides information on some of the less familiar causes of acute malocclusion. PMID:16689064

  20. 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. PMID:20821416

  1. Prognostic value of left ventricular diastolic function and association with heart rate variability after a first acute myocardial infarction

    PubMed Central

    Poulsen, S; Jensen, S; Moller, J; Egstrup, K

    2001-01-01

    OBJECTIVE—To study the prognostic value of left ventricular (LV) diastolic function and its relation with autonomic balance expressed by heart rate variability (HRV) in patients after a first acute myocardial infarction.
DESIGN—The study population consisted of 64 consecutive patients with first acute myocardial infarction and 31 control subjects. Long and short term HRV indices were evaluated by 24 hour Holter monitoring, and LV systolic and diastolic function were assessed by two dimensional and Doppler echocardiography before discharge. Patients were divided into two groups: those with restrictive LV filling characteristics (deceleration time ⩽ 140 ms) and those with non-restrictive LV filling characteristics (deceleration time > 140 ms).
RESULTS—Both long and short term HRV indices were significantly reduced in patients with restrictive LV filling compared with the non-restrictive group and control subjects. Mitral deceleration time and isovolumetric relaxation time correlated weakly but significantly with all indices of HRV whereas ejection fraction correlated weakly with the long term HRV indices. The mean follow up time was 14.9 (8.7) months. Multivariate analysis showed that mitral deceleration time (χ2 = 6.4, p < 0.001) and ejection fraction ⩽ 40% (χ2 = 4.4, p < 0.05) were independent predictors of cardiac death and readmission to hospital with congestive heart failure.
CONCLUSIONS—A restrictive LV filling pattern was found to be the strongest predictor of adverse outcome independent of HRV and ejection fraction during follow up after a first acute myocardial infarction. Patients with restrictive LV filling characteristics had more reduced HRV than those with non-restrictive diastolic filling.


Keywords: diastole; infarction; autonomic balance PMID:11559672

  2. Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes.

    PubMed

    Haller, M J; Atkinson, M A; Wasserfall, C H; Brusko, T M; Mathews, C E; Hulme, M; Cintron, M; Shuster, J; McGrail, K; Posgai, A; Schatz, D

    2016-03-01

    Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4(+) : CD8(+) T cell ratio or the ratio of naive : memory (CD45RA(+)/CD45RO(+)) CD4(+) T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide. PMID:26462724

  3. Echocardiographic parameters of right ventricular function predict mortality in acute respiratory distress syndrome: a pilot study.

    PubMed

    Shah, Trushil G; Wadia, Subeer K; Kovach, Julie; Fogg, Louis; Tandon, Rajive

    2016-06-01

    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

  4. 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

  5. Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure

    PubMed Central

    Lowery-Gionta, Emily G; Marcinkiewcz, Catherine A; Kash, Thomas L

    2015-01-01

    Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased anxiety-like behavior at both 24 h and 7 days post-ethanol exposure. At 24 h post-ethanol exposure, we observed increased excitability and decreased spontaneous inhibitory transmission (inhibitory postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we observed increased spontaneous and miniature excitatory transmission (excitatory postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are more sensitive to the inhibitory effects of acute ethanol following CIE. On the basis of these findings, we hypothesize that net excitation of DR neurons following chronic ethanol exposure contributes to enhanced anxiety during ethanol withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol exposure may mediate acute ethanol's ability to relieve anxiety during ethanol withdrawal. PMID:25120075

  6. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury.

    PubMed

    Kása, Anita; Csortos, Csilla; Verin, Alexander D

    2015-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  7. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury

    PubMed Central

    Kása, Anita; Csortos, Csilla; Verin, Alexander D

    2014-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  8. Primary sensory and motor cortex function in response to acute muscle pain: A systematic review and meta-analysis.

    PubMed

    Burns, E; Chipchase, L S; Schabrun, S M

    2016-09-01

    Acute muscle pain has both motor and sensory consequences, yet the effect of muscle pain on the primary sensory (S1) and motor (M1) cortices has yet to be systematically evaluated. Here we aimed to determine the strength of the evidence for (1) altered activation of S1/M1 during and after pain, (2) the temporal profile of any change in activation and (3) the relationship between S1/M1 activity and the symptoms of pain. In September 2015, five electronic databases were systematically searched for neuroimaging and electrophysiological studies investigating the effect of acute experimental muscle pain on S1/M1 in healthy volunteers. Demographic data, methodological characteristics and primary outcomes for each study were extracted for critical appraisal. Meta-analyses were performed where appropriate. Twenty-five studies satisfied the inclusion criteria. There was consistent evidence from fMRI for increased S1 activation in the contralateral hemisphere during pain, but insufficient evidence to determine the effect at M1. Meta-analyses of TMS and EEG data revealed moderate to strong evidence of reduced S1 and corticomotor excitability during and following the resolution of muscle pain. A comprehensive understanding of the temporal profile of altered activity in S1/M1, and the relationship to symptoms of pain, is hampered by differences in methodological design, pain modality and pain severity between studies. Overall, the findings of this review indicate reduced S1 and corticomotor activity during and after resolution of acute muscle pain, mechanisms that could plausibly underpin altered sensorimotor function in pain. WHAT DOES THIS REVIEW ADD?: We provide the first systematic evaluation of the primary sensory (S1) and motor (M1) cortex response to acute experimental muscle pain in healthy volunteers. We present evidence from a range of methodologies to provide a comprehensive understanding of the effect of pain on S1/M1. Through meta-analyses we evaluate the strength

  9. The matrix proteins of neurovirulent subacute sclerosing panencephalitis virus and its acute measles virus progenitor are functionally different.

    PubMed Central

    Hirano, A; Wang, A H; Gombart, A F; Wong, T C

    1992-01-01

    Persistence of measles virus in the brains of patients with subacute sclerosing panencephalitis (SSPE) is accompanied by changes in the viral matrix (M) protein. To understand the significance of these changes, cell culture and cell-free assays were developed to compare the functions of the M proteins of an SSPE virus Biken strain and its acute measles virus progenitor Nagahata strain. The Nagahata viral M protein is associated with the intracellular viral nucleocapsids and the plasma membrane, whereas the Biken viral M protein is localized mainly in the cytosol. The lack of M protein in the Biken viral nucleocapsids is due to a failure of the Biken M protein to bind to the viral nucleocapsids. The Biken M protein also fails to bind to the Nagahata viral nucleocapsids. Conversely, the Nagahata M protein can bind to the Biken viral nucleocapsids, although this association is not as stable at physiological salt concentration. These results offer concrete evidence that the M protein of an SSPE virus is functionally different from that of its progenitor acute measles virus. Images PMID:1528889

  10. 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

  11. 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. PMID:12820995

  12. DNA damage tolerance.

    PubMed

    Branzei, Dana; Psakhye, Ivan

    2016-06-01

    Accurate chromosomal DNA replication is fundamental for optimal cellular function and genome integrity. Replication perturbations activate DNA damage tolerance pathways, which are crucial to complete genome duplication as well as to prevent formation of deleterious double strand breaks. Cells use two general strategies to tolerate lesions: recombination to a homologous template, and trans-lesion synthesis with specialized polymerases. While key players of these processes have been outlined, much less is known on their choreography and regulation. Recent advances have uncovered principles by which DNA damage tolerance is regulated locally and temporally - in relation to replication timing and cell cycle stage -, and are beginning to elucidate the DNA dynamics that mediate lesion tolerance and influence chromosome structure during replication. PMID:27060551

  13. 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. PMID:25787721

  14. MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis.

    PubMed

    Mirlekar, Bhalchandra; Patil, Sachin; Bopanna, Ramanamurthy; Chattopadhyay, Samit

    2015-08-21

    Treg cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by Treg cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of Treg phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic Treg cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing Treg cells in SMAR1(-/-) mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic Treg cells that controls acute colitis. This data highlights a critical role of SMAR1 in main