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  1. Anti-kindling Effect of Bezafibrate, a Peroxisome Proliferator-activated Receptors Alpha Agonist, in Pentylenetetrazole Induced Kindling Seizure Model.

    Science.gov (United States)

    Saha, Lekha; Bhandari, Swati; Bhatia, Alka; Banerjee, Dibyajyoti; Chakrabarti, Amitava

    2014-12-01

    Studies in the animals suggested that Peroxisome proliferators activated receptors (PPARs) may be involved in seizure control and selective agonists of PPAR α or PPAR γ raise seizure thresholds. The present study was contemplated with the aim of evaluating the anti kindling effects and the mechanism of bezafibrate, a Peroxisome proliferator-activated receptors α (PPAR-α) agonist in pentylenetetrazole (PTZ) induced kindling model of seizures in rats. In a PTZ kindled Wistar rat model, different doses of bezafibrate (100 mg/kg, 200 mg/kg and 300 mg/kg) were administered intraperitoneally 30 minutes before the PTZ injection. The PTZ injection was given on alternate day till the animal became fully kindled or till 10 weeks. The parameters measured were the latency to develop kindling and incidence of kindling, histopathological study of hippocampus, hippocampal lipid peroxidation studies, serum neuron specific enolase, and hippocampal DNA fragmentation study. In this study, bezafibrate significantly reduced the incidence of kindling in PTZ treated rats and exhibited a marked prolongation in the latencies to seizures. In the present study bezafibrate decreased the thiobarbituric acid-reactive substance i.e. Malondialdehyde levels, increased the reduced glutathione levels, catalase and superoxide dismutase activity in the brain. This added to its additional neuroprotective effects. Bezafibrate also reduced the neuronal damage and apoptosis in hippocampal area of the brain. Therefore bezafibrate exerted anticonvulsant properties in PTZ induced kindling model in rats. These findings may provide insights into the understanding of the mechanism of bezafibrate as an anti kindling agent and could offer a useful support to the basic antiepileptic therapy in preventing the development of PTZ induced seizures, suggesting its potential for therapeutic applications in temporal lobe epilepsy.

  2. Antiapoptotic and neuroprotective role of Curcumin in Pentylenetetrazole (PTZ) induced kindling model in rat.

    Science.gov (United States)

    Saha, Lekha; Chakrabarti, Amitava; Kumari, Sweta; Bhatia, Alka; Banerjee, Dibyojyoti

    2016-02-01

    Kindling, a sub threshold chemical or electrical stimulation, increases seizure duration and enhances accompanied behavior until it reaches a sort of equilibrium state. The present study aimed to explore the effect of curcumin on the development of kindling in PTZ kindled rats and its role in apoptosis and neuronal damage. In a PTZ kindled Wistar rat model, different doses of curcumin (100, 200 and 300 mg/kg) were administrated orally one hour before the PTZ injections on alternate day during the whole kindling days. The following parameters were compared between control and experimental groups: the course of kindling, stages of seizures, Histopathological scoring of hippocampus, antioxidant parameters in the hippocampus, DNA fragmentation and caspase-3 expression in hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses. PTZ, 30 mg/kg, induced kindling in rats after 32.0 ± 1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with curcumin in a dose-dependent manner. Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

  3. Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms.

    Science.gov (United States)

    Wang, Shan; Ding, Yao; Ding, Xiao-Yan; Liu, Zhi-Rong; Shen, Chun-Hong; Jin, Bo; Guo, Yi; Wang, Shuang; Ding, Mei-Ping

    2016-02-12

    The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Anticonvulsant and Antioxidant Effects of Pitavastatin Against Pentylenetetrazol-Induced Kindling in Mice.

    Science.gov (United States)

    Faghihi, Nastaran; Mohammadi, Mohammad Taghi

    2017-06-01

    Purpose: The pleiotropic effects of statins (antioxidant and anti-inflammation) have been reported by previous studies. Therefore, we aimed to determine whether pitavastatin has protective effects against pentylenetetrazol (PTZ)-induced kindling in mice and also whether pitavastatin improves the brain antioxidant capacity and attenuates the oxidative injuries in kindled mice. Methods: Twenty-four mice were randomly divided into four groups (each group n=6); control, PTZ-kindling and PTZ-kindled rats treated with pitavastatin (1&4 mg/kg). PTZ kindling seizures were induced by repetitive intraperitoneal injections of PTZ (65 mg/kg) every 48 hours till day twenty-one. Animals received daily oral pitavastatin for twenty-one days. Latency, score and duration of the seizures were recorded. The activities of catalase (CAT) ad superoxide dismutase (SOD), and likewise the contents of malondialdehyde (MDA) and nitrate were assessed in the brains of all rats. Results: There was a progressive reduction in latency of the kindled rats in the next injections of PTZ. Pitavastatin reduced this value (latency) particularly at higher dose. Seizures duration and score also decreased in treatment groups. SOD and CAT activities significantly decreased in PTZ-kindling group by 62% and 64%, respectively, but pitavastatin did not significantly change the SOD and CAT activities. Brain MDA and nitrate significantly increased in PTZ-kindling group by 53% and 30%, respectively. Pitavastatin at higher dose significantly decreased the MDA and nitrate contents of PTZ-kindling rats by 45% and 32%, respectively. Conclusion: Our findings revealed that pitavastatin can improve the behavioral expression of the PTZ-kindling rats and attenuate the seizure-induced oxidative/nitrosative damage.

  5. Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-san; CHEN Jie-fang; CHEN Guan-feng; HU Xing-yue; DING Mei-ping

    2013-01-01

    Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases.However,whether these drugs can inhibit epileptogenesis remains unclear.This study aimed to investigate the effects of thioperamide,a selective and potent histamine H3 receptor antagonist,on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.Methods Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times,and seizure activity of kindling was recorded for 30 minutes.Control rats were ip injected with saline instead of PTZ.Morris water maze was used to evaluate the spatial memory.Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.Results Intracerebroventricular (icv) injections with thioperamide (10 μg,20 μg) 30 minutes before every PTZ injections,significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages.PTZ-kindling seizures led to the impairment of spatial memory in rats,and thioperamide ameliorated the impairment of spatial learning and memory.Compared to non-kindling rats,there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats,which was reversed by thioperamide.Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats.The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

  6. Ameliorative effect of Asparagus racemosus root extract against pentylenetetrazol-induced kindling and associated depression and memory deficit.

    Science.gov (United States)

    Pahwa, Priyanka; Goel, Rajesh Kumar

    2016-04-01

    Asparagus racemosus (A. racemosus) roots are extensively used in traditional medicine for the management of epilepsy. The aim of the present study was to investigate the ameliorative effect of A. racemosus root extract (ARE) against pentylenetetrazol-induced kindling and associated depression and memory deficit. Kindling was successfully induced by repeated administration of a subconvulsant dose of PTZ (35 mg/kg; i.p.) at an interval of 48 ± 2 h in 43 days (21 injections). Pretreatment with valproate (300 mg/kg; i.p.), a major antiepileptic drug as well as ARE significantly suppressed the progression of kindling. Moreover, ARE also ameliorated the kindling-associated depression and memory deficit as indicated by decreased immobility time and increased step-down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complemented with analogous neurochemical changes. In conclusion, the results of the present study showed that ARE treatment has an ameliorative effect against PTZ-induced kindling and associated behavioral comorbidities. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Anti-epileptogenic and antioxidant effect of Lavandula officinalis aerial part extract against pentylenetetrazol-induced kindling in male mice.

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    Rahmati, Batool; Khalili, Mohsen; Roghani, Mehrdad; Ahghari, Parisa

    2013-06-21

    Repeated application of Lavandula officinalis (L. officinalis) has been recommended for a long time in Iranian traditional medicine for some of nervous disorders like epilepsy and dementia. However, there is no available report for the effect of chronic administration of Lavandula extract in development (acquisition) of epilepsy. Therefore, this study was designed to investigate the anti-epileptogenic and antioxidant activity of repeated administration of Lavandula officinalis extract on pentylenetetrazol (PTZ) kindling seizures in mice model. Lavandula officinalis was tested for its ability (i) to suppress the seizure intensity and lethal effects of PTZ in kindled mice (anti-epileptogenic effect), (ii) to attenuate the PTZ-induced oxidative injury in the brain tissue (antioxidant effect) when given as a pretreatment prior to each PTZ injection during kindling development. Valproate (Val), a major antiepileptic drug, was also tested for comparison. Val and Lavandula officinalis extract showed anti-epileptogenic properties as they reduced seizure score of kindled mice and PTZ-induced mortality. In this regard, Lavandula officinalis was more effective than Val. Both Lavandula officinalis and Val suppressed brain nitric oxide (NO) level of kindled mice in comparison with the control and PTZ group. Meanwhile, Lavandula officinalis suppressed NO level more than Val and Lavandula officinalis also decreased brain MDA level relative to PTZ group. This is the first report to demonstrate NO suppressing and anti-epileptogenic effect of chronic administration of Lavandula officinalis extract on acquisition of epilepsy in PTZ kindling mice model. In this regard, Lavandula officinalis extract was more effective than Val, possibly and in part via brain NO suppression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. II. Effects of the NMDA antagonist MK-801.

    LENUS (Irish Health Repository)

    Robinson, G B

    1991-10-18

    The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg\\/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment continued for the first 10 days of kindling. MK-801 depressed the growth of the afterdischarge duration and suppressed development of behavioral seizures. MK-801 did not block kindling-induced potentiation of either the perforant path-dentate granule cell population spike or excitatory postsynaptic potential. Random impulse train stimulation and non-linear systems analytic techniques were used to examine kindling-induced potentiation of presumed GABAergic recurrent inhibitory circuits. Both the magnitude and duration of kindling-induced response inhibition, to the second of each pair of impulses within the train, were reduced in rabbits pretreated with MK-801. These results suggest that MK-801 differentially affects kindling-induced potentiation of excitatory and inhibitory circuits within the rabbit hippocampal dentate gyrus.

  9. Anti-kindling induced by two-stage coordinated reset stimulation with weak onset intensity

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    Magteld eZeitler

    2016-05-01

    Full Text Available Abnormal neuronal synchrony plays an important role in a number of brain diseases. To specifically counteract abnormal neuronal synchrony by desynchronization, Coordinated Reset (CR stimulation, a spatiotemporally patterned stimulation technique, was designed with computational means. In neuronal networks with spike timing–dependent plasticity CR stimulation causes a decrease of synaptic weights and finally anti-kindling, i.e. unlearning of abnormally strong synaptic connectivity and abnormal neuronal synchrony. Long-lasting desynchronizing aftereffects of CR stimulation have been verified in pre-clinical and clinical proof of concept studies. In general, for different neuromodulation approaches, both invasive and non-invasive, it is desirable to enable effective stimulation at reduced stimulation intensities, thereby avoiding side effects. For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity. Numerical simulations show that a two-stage CR stimulation can induce the same degree of anti-kindling as a single-stage CR stimulation with intermediate stimulation intensity. This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects. This might, e.g., be relevant in the context of acoustic CR stimulation in tinnitus patients with hyperacusis or in the case of electrical deep brain CR stimulation with sub-optimally positioned leads or side effects caused by stimulation of the target itself. We discuss how to apply our method in first in man and proof of concept studies.

  10. The anticonvulsant action of AHR-11748 on kindled amygdaloid seizures in rats.

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    Albertson, T E; Walby, W F

    1987-03-01

    The anticonvulsant effectiveness of AHR-11748 (3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) was evaluated in the kindled amygdaloid seizure model in rats. Doses of AHR-11748 that did not cause prestimulation toxicity significantly attenuated elicited afterdischarge durations and the severity of the accompanying behavioral convulsive response in previously kindled rats. AHR-11748 (25-100 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and suprathreshold (400 microA) paradigms. AHR-11748 (50-100.mg/kg) reduced suprathreshold elicited after discharges and seizure severity. Utilizing a suprathreshold kindling paradigm, the maximum anticonvulsant effectiveness for the 100 mg/kg i.p. dose of AHR-11748 was seen at 180 min. AHR-11748 significantly elevated seizure thresholds only at the 100 mg/kg dose. AHR-11748 (25-100 mg/kg) significantly reduced the severity of threshold elicited seizures. When AHR-11748 (50 and 100 mg/kg i.p.) was administered daily during kindling acquisition, the number of daily trials necessary to complete kindling significantly increased. A reduction in both the duration and the severity of the responses induced by the daily stimulations during the acquisition period was seen with AHR-11748 treatment. This study has demonstrated that AHR-11748 significantly modifies both the acquisition of kindling and the fully kindled amygdaloid seizures at doses that do not cause behavioral toxicity.

  11. Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory.

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    Kojima, Nobuhiko; Borlikova, Gilyana; Sakamoto, Toshiro; Yamada, Kazuyuki; Ikeda, Toshio; Itohara, Shigeyoshi; Niki, Hiroaki; Endo, Shogo

    2008-06-18

    Long-lasting neuronal plasticity as well as long-term memory (LTM) requires de novo synthesis of proteins through dynamic regulation of gene expression. cAMP-responsive element (CRE)-mediated gene transcription occurs in an activity-dependent manner and plays a pivotal role in neuronal plasticity and LTM in a variety of species. To study the physiological role of inducible cAMP early repressor (ICER), a CRE-mediated gene transcription repressor, in neuronal plasticity and LTM, we generated two types of ICER mutant mice: ICER-overexpressing (OE) mice and ICER-specific knock-out (KO) mice. Both ICER-OE and ICER-KO mice show no apparent abnormalities in their development and reproduction. A comprehensive battery of behavioral tests revealed no robust changes in locomotor activity, sensory and motor functions, and emotional responses in the mutant mice. However, long-term conditioned fear memory was attenuated in ICER-OE mice and enhanced in ICER-KO mice without concurrent changes in short-term fear memory. Furthermore, ICER-OE mice exhibited retardation of kindling development, whereas ICER-KO mice exhibited acceleration of kindling. These results strongly suggest that ICER negatively regulates the neuronal processes required for long-term fear memory and neuronal plasticity underlying kindling epileptogenesis, possibly through suppression of CRE-mediated gene transcription.

  12. Comparative studies on the effects of clinically used anticonvulsants on the oxidative stress biomarkers in pentylenetetrazole-induced kindling model of epileptogenesis in mice.

    Science.gov (United States)

    Mazhar, Faizan; Malhi, Saima M; Simjee, Shabana U

    2017-01-01

    Oxidative stress plays a key role in the pathogenesis of epilepsy and contributes in underlying epileptogenesis process. Anticonvulsant drugs targeting the oxidative stress domain of epileptogenesis may provide better control of seizure. The present study was carried out to investigate the effect of clinically used anti-epileptic drugs (AEDs) on the course of pentylenetetrazole (PTZ)-induced kindling and oxidative stress markers in mice. Six mechanistically heterogeneous anticonvulsants: phenobarbital, phenytoin, levetiracetam, pregabalin, topiramate, and felbamate were selected and their redox profiles were determined. Diazepam was used as a drug control for comparison. Kindling was induced by repeated injections of a sub-convulsive dose of PTZ (50 mg/kg, s.c.) on alternate days until seizure score 5 was evoked in the control kindled group. Anticonvulsants were administered daily. Following PTZ kindling, oxidative stress biomarkers were assessed in homogenized whole brain samples and estimated for the levels of nitric oxide, peroxide, malondialdehyde, protein carbonyl, reduced glutathione, and activities of nitric oxide synthase and superoxide dismutase. Biochemical analysis revealed a significant increase in the levels of reactive oxygen species with a parallel decrease in endogenous anti-oxidants in PTZ-kindled control animals. Daily treatment with levetiracetam and felbamate significantly decreased the PTZ-induced seizure score as well as the levels of nitric oxide (panticonvulsant effect by the diversified mechanism of action such as levetiracetam, felbamate, and topiramate exhibited superior anti-oxidative stress activity in addition to their anticonvulsant activity.

  13. Involvement of over-expressed BMP4 in pentylenetetrazol kindling-induced cell proliferation in the dentate gyrus of adult rats

    International Nuclear Information System (INIS)

    Yin Jinbo; Ma Yuxin; Yin Qing; Xu Haiwei; An Ning; Liu Shiyong; Fan Xiaotang; Yang Hui

    2007-01-01

    The dentate gyrus (DG) of the hippocampus is one of a few regions in the adult mammalian brain characterized by ongoing neurogenesis. Proliferation of neural precursors in the granule cell layer of the DG has been identified in pentylenetetrazol (PTZ) kindling epilepsy model, however, little is known about the molecular mechanism. We previously reported that the expression pattern of bone morphogenetic proteins-4 (BMP4) mRNA in the hippocampus was developmentally regulated and mainly localized in the DG of the adult. To explore the role of BMP4 in epileptic activity, we detected BMP4 expression in the DG during PTZ kindling process and explore its correlation with cell proliferation combined with bromodeoxyuridine (BrdU) labeling technique. We found that dynamic changes in BMP4 level and BrdU labeled cells dependent on the kindling stage of PTZ induced seizure-prone state. The number of BMP4 mRNA-positive cells and BrdU labeled cells reached the top level 1 day after PTZ kindled, then declined to base level 2 months later. Furthermore, there was a significant correlation between increased BMP4 mRNA expression and increased number of BrdU labeled cells. After effectively blocked expression of BMP4 with antisense oligodeoxynucleotides(ASODN), the BrdU labeled cells in the dentate gyrus subgranular zone(DG-SGZ) and hilus were significantly decreased 16d after First PTZ injection and 1, 3, 7, 14d after kindled respectively. These findings suggest that increased proliferation in the DG of the hippocampus resulted from kindling epilepsy elicited by PTZ maybe be modulated by BMP4 over-expression

  14. Kindle Paperwhite for dummies

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    Nicoll, Leslie H

    2014-01-01

    Get the inside story on the all-new Kindle Paperwhite with help from For Dummies It reads like a book, but it's so much more. The Kindle Paperwhite is the ultimate e-reader, and this updated edition of Kindle Paperwhite For Dummies is your ultimate guide to getting more from this one-of-a-kind device. You'll learn to set up your Paperwhite, adjust the font to your liking, find your favorite books, magazines, and newspapers, and sync your Kindle content across devices before moving on to new Paperwhite features like Kindle FreeTime, Goodreads integration, Vocabulary Builder, In-line Footnotes

  15. A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.

    Directory of Open Access Journals (Sweden)

    Hong-Liu Sun

    Full Text Available Reduction of glutamine synthetase (GS function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl, a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated. It was found that low doses of MSO (5 or 10 µg significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×10(6 TU/2 µl of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis.

  16. The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats

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    Rajabzadeh Aliakbar

    2012-05-01

    Full Text Available Abstract Background Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM, which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. Methods Forty timed-pregnant Wistar rats were divided into four groups: A Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy rats that received repeated intraperitoneal (i.p. pentylenetetrazol, PTZ injections on gestational days (GD 14-19; B Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry. Results Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001 and Kind-/Seiz+ (p = 0.001 groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007 and Kind-/Seiz+ (p = 0.007 group’s newborns on both PD1 and 14. Conclusion Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.

  17. [The role of the opiate mechanisms of the hippocampus and substantia nigra in the behavioral and convulsive disorders in picrotoxin-induced kindling].

    Science.gov (United States)

    Kryzhanovskiĭ, G N; Shandra, A A; Godlevskiĭ, L S; Mazarati, A M; Nguyen, T T

    1991-03-01

    It was shown in the experiments on rats that the repeated picrotoxin administration resulted in the kindling of generalized seizures. Generalized convulsions were followed by the development of either postictal depression or explosiveness. The injection of mu-opiate agonist met-enkephalin into hippocampus of kindled rats resulted in the increase in the severity of seizure reactions which were induced by picrotoxin and also in the increase in the number of animals with postictal explosiveness. The injection of dynorphin-A-1-13 (kappa-opiate agonist) into substantia nigra reticulata induced the locomotor depression which was like one in postictal period and resulted in the decrease of picrotoxin-induced seizures severity. It was concluded that mu-opiate system of hippocampus took part in the formation of generator of pathologically enhanced excitation in the structure during kindling and the development of seizure syndrome, providing also the postictal explosiveness. Kappa-opiate system of substantia nigra plays an important role in the activation of the antiepileptic system, limitation of seizures and the development of postictal depression.

  18. The anticonvulsant action of nafimidone on kindled amygdaloid seizures in rats.

    Science.gov (United States)

    Albertson, T E; Walby, W F

    1988-01-01

    The anticonvulsant effectiveness of nafimidone (1-[2-naphthoylmethyl]imidazole hydrochloride) was evaluated in the kindled amygdaloid seizure model in rats. Nafimidone (3.1-120 mg/kg i.p.) was evaluated at 30 min in previously kindled rats using both threshold (20 microA increments) and supranthreshold (400 microA) paradigms. Nafimidone (25-50 mg/kg) significantly reduced supranthreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity. The maximum anticonvulsant effectiveness for the 25 mg/kg i.p. dose of nafimidone was seen between 15 and 30 min utilizing a suprathreshold kindling paradigm. Nafimidone did not significantly elevate seizure thresholds at the doses tested; however, nafimidone (3.1-50 mg/kg) reduced the severity and afterdischarge duration of threshold elicited seizures in a non-dose response manner. Drug-induced electroencephalographic spikes were seen in both cortex and amygdala in most kindled rats receiving 100-120 mg/kg i.p. within 30 min of dosing before electrical stimulation. The frequency of spike and wave complexes increased in most of these animals leading to drug-induced spontaneous seizures and death in approximately 25% before electrical stimulation. This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy.

  19. Kindle Forensics: Acquisition & Analysis

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    Peter Hannay

    2011-06-01

    Full Text Available The Amazon Kindle eBook reader supports a wide range of capabilities beyond reading books. This functionality includes an inbuilt cellular data connection known as Whispernet. The Kindle provides web browsing, an application framework, eBook delivery and other services over this connection. The historic data left by user interaction with this device may be of forensic interest. Analysis of the Amazon Kindle device has resulted in a method to reliably extract and interpret data from these devices in a forensically complete manner.

  20. Curcumin inhibits amygdaloid kindled seizures in rats.

    Science.gov (United States)

    DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

    2009-06-20

    Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

  1. Curcumin-loaded chitosan-alginate-STPP nanoparticles ameliorate memory deficits and reduce glial activation in pentylenetetrazol-induced kindling model of epilepsy.

    Science.gov (United States)

    Hashemian, Mona; Anissian, Diana; Ghasemi-Kasman, Maryam; Akbari, Atefeh; Khalili-Fomeshi, Mohsen; Ghasemi, Shahram; Ahmadi, Fatemeh; Moghadamnia, Ali Akbar; Ebrahimpour, Anahita

    2017-10-03

    Despite several beneficial effects of curcumin, its medical application has been hampered due to low water solubility. To improve the aqueous solubility of curcumin, it has been loaded on chitosan (CS)-alginate (ALG) - sodium tripolyphosphate (STPP) nanoparticles (NPs). Then, the effect of curcumin NPs on memory improvement and glial activation was investigated in pentylenetetrazol (PTZ)-induced kindling model. Male NMRI mice have received the daily injection of curcumin NPs at dose of 12.5 or 25mg/kg. All interventions were injected intraperitoneally (i.p), 10days before PTZ administration and the injections were continued until 1h before each PTZ injection. Spatial learning and memory was evaluated using Morris water maze test after the 7th PTZ injection. Animals have received 10 injections of PTZ and then, brain tissues were removed for histological evaluation. Nissl staining was used to determine the level of cell death in hippocampus and immunostaining method was performed against NeuN and GFAP/Iba1 for assessment of neuronal density and glial activation respectively. Behavioral results showed that curcumin NPs exhibit anticonvulsant activity and prevent cognitive impairment in fully kindled animals. The level of cell death and glial activation reduced in animals which have received curcumin NPs compared to those received free curcumin. To conclude, these findings suggest that curcumin NPs effectively ameliorate memory impairment and attenuate the level of activated glial cells in a mice model of chronic epilepsy. Copyright © 2017. Published by Elsevier Inc.

  2. Brain redox imaging in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy by using in vivo electron paramagnetic resonance and a nitroxide imaging probe.

    Science.gov (United States)

    Emoto, Miho C; Yamato, Mayumi; Sato-Akaba, Hideo; Yamada, Ken-ichi; Fujii, Hirotada G

    2015-11-03

    Much evidence supports the idea that oxidative stress is involved in the pathogenesis of epilepsy, and therapeutic interventions with antioxidants are expected as adjunct antiepileptic therapy. The aims of this study were to non-invasively obtain spatially resolved redox data from control and pentylenetetrazole (PTZ)-induced kindled mouse brains by electron paramagnetic resonance (EPR) imaging and to visualize the brain regions that are sensitive to oxidative damage. After infusion of the redox-sensitive imaging probe 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), a series of EPR images of PTZ-induced mouse heads were measured. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of redox status in vivo and mapped as a redox map. The obtained redox map showed heterogeneity in the redox status in PTZ-induced mouse brains compared with control. The co-registered image of the redox map and magnetic resonance imaging (MRI) for both control and PTZ-induced mice showed a clear change in the redox status around the hippocampus after PTZ. To examine the role of antioxidants on the brain redox status, the levels of antioxidants were measured in brain tissues of control and PTZ-induced mice. Significantly lower concentrations of glutathione in the hippocampus of PTZ-kindled mice were detected compared with control. From the results of both EPR imaging and the biochemical assay, the hippocampus was found to be susceptible to oxidative damage in the PTZ-induced animal model of epilepsy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice.

    Science.gov (United States)

    Agarwal, Nidhi Bharal; Agarwal, Nitin Kumar; Mediratta, Pramod Kumari; Sharma, Krishna Kishore

    2011-04-01

    Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. Mesolimbic dopaminergic supersensitivity following electrical kindling of the amygdala

    International Nuclear Information System (INIS)

    Csernansky, J.G.; Mellentin, J.; Beauclair, L.; Lombrozo, L.

    1988-01-01

    Limbic seizures developed in rats following daily electrical stimulation of the basolateral nucleus of the amygdala. Animals were designated as kindled after five complete (stage 5) behavioral seizures were observed. A subgroup, designated as superkindled, received three additional weeks of electrical stimulations. Kindled rats were significantly subsensitive to the stereotypy-inducing effects of apomorphine, a direct dopamine agonist, compared to controls. Superkindled rats were supersensitive to the effects of apomorphine. However, both kindled and superkindled rats demonstrated an increase in 3 H-spiperone Bmax values, reflecting dopamine D2-receptor densities, in the nucleus accumbens ipsilateral to the stimulating electrode. The number of interictal spikes recorded from the stimulating amygdaloid electrode during the last week of kindling was correlated with changes in apomorphine sensitivity in individual animals

  5. Synaptic degeneration and remodelling after fast kindling of the olfactory bulb

    DEFF Research Database (Denmark)

    Woldbye, D P; Bolwig, T G; Kragh, J

    1996-01-01

    in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling...

  6. Kindle Fire HDX for dummies

    CERN Document Server

    Muir, Nancy C

    2013-01-01

    Spark your interest in Kindle Fire HDX and start burning through books, movies, music, and more with this bestselling guide! The Kindle Fire HDX is Amazon's premiere tablet. With its new, more powerful Android operating system, this latest version has some exciting bells and whistles along with the features that have made the Fire a tablet fan favorite: access to the amazing Amazon Appstore, online music storage, a large music and video store, a huge e-book library, and easy one-step ordering from Amazon. This full-color, For Dummies guide shows you how to take advantage of all the Kindle Fi

  7. Age-Dependent Effects of Topiramate on the Acquisition and the Retention of Rapid Kindling

    Science.gov (United States)

    Mazarati, Andréy; Shin, Don; Auvin, Stéphane; Sankar, Raman

    2008-01-01

    Summary Purpose To examine antiepileptogenic, disease-modifying, and anticonvulsant effects of topiramate under conditions of rapid kindling at different stages of development. Methods Afterdischarge threshold (ADT) and duration (ADD) were examined in two-, three-, and five-week old Wistar rats before and after administration of topiramate (200 mg/kg). Animals underwent a rapid kindling protocol (sixty 10 second trains, bipolar 20 Hz square wave pulses delivered every five minutes). The progression of behavioral and electrographic seizures, and responses to test stimulations 24 hours after the protocol were compared between topiramate and vehicle treated control rats. In addition, rats that were previously given vehicle only prior to kindling, were then given topiramate to examine the effect on established kindled seizures. Results In two-week old animals, topiramate affected neither the baseline afterdischarge, nor the progression of kindled seizures. In three-week old rats, topiramate did not modify the baseline afterdischarge, but significantly delayed the occurrence of full motor seizures in response to repeated stimulations. Topiramate treatment of five-week old rats increased baseline ADT, shortened ADD, and delayed the progression of kindled seizures. Twenty four hours after the last kindling stimulation, animals of all ages exhibited a decreased ADT, an increase ADD, and developed behavioral seizures in response to threshold stimulation. Vehicle treated kindled rats that were then given topiramate displayed significantly attenuated behavioral seizures induced by the threshold stimulation. Conclusions Topiramate exhibited age-dependent disease-modifying effects under conditions of rapid kindling, but failed to block epileptogenesis. Topiramate also inhibited kindled seizures with equal efficacy across the three ages. PMID:17319916

  8. Levetiracetam attenuates hippocampal expression of synaptic plasticity-related immediate early and late response genes in amygdala-kindled rats

    Directory of Open Access Journals (Sweden)

    Watson William P

    2010-01-01

    Full Text Available Abstract Background The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined. Results Cyclooxygenase-2 (Cox-2, Protocadherin-8 (Pcdh8 and TGF-beta-inducible early response gene-1 (TIEG1 were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-α, RGS2, Egr2/krox-20 and β-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration. Conclusions The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus.

  9. Unilateral Hypothalamus Inactivation Prevents PTZ Kindling Development through Hippocampal Orexin Receptor 1 Modulation

    Directory of Open Access Journals (Sweden)

    Nasibe Akbari

    2014-02-01

    Full Text Available Introduction: Epilepsy is a neural disorder in which abnormal plastic changes during short and long term periods lead to increased excitability of brain tissue. Kindling is an animal model of epileptogenesis which results in changes of synaptic plasticity due to repetitive electrical or chemical sub-convulsive stimulations of the brain. Lateral hypothalamus, as the main niche of orexin neurons with extensive projections, is involved in sleep and wakefulness and so it affects the excitability of the brain. Therefore, we investigated whether lateral hypothalamic area (LHA inactivation or orexin-A receptor blocking could change convulsive behavior of acute and kindled PTZ treated animals and if glutamate has a role in this regard.  Methods: Kindling was induced by 40 mg/kg PTZ, every 48 hours up to 13 injections to each rat. Three consecutive stages 4 or 5 of convulsive behavior were used to ensure kindling. Lidocaine was injected stereotaxically to inactivate LHA, unilaterally. SB334867 used for orexin receptor 1 (OX1R blocking administered in CSF.  Results: We demonstrated that LHA inactivation prevented PTZ kindling and hence, excitability evolution. Hippocampal glutamate content was decreased due to LHA inactivation, OX1R antagonist infusion, lidocaine injection and kindled groups. In accordance, OX1R antagonist (SB334867 and lidocaine injection decreased PTZ single dose induced convulsive behavior. While orexin-A i.c.v. infusion increased hippocampal glutamate content, it did not change PTZ induced convulsive intensity.  Discussion: It is concluded that LHA inactivation prevented kindling development probably through orexin receptor antagonism. CSF orexin probably acts as an inhibitory step on convulsive intensity through another unknown process.

  10. Developmental Exposure to an Environmental PCB Mixture Delays the Propagation of Kindling in the Amygdala

    Science.gov (United States)

    Developmental PCB exposure impairs hearing and induces brainstem audiogenic seizures in adult offspring. The degree to which this enhanced susceptibility to seizure is manifest in other brain regions has not been examined. Thus, electrical kindling of the amygdala was used to eva...

  11. Anxiolytic and antidepressive effects of electric stimulation of the paleocerebellar cortex in pentylenetetrazol kindled rats

    NARCIS (Netherlands)

    Godlevsky, L.S.; Muratova, T.N.; Kresyun, N.V.; Luijtelaar, E.L.J.M. van; Coenen, A.M.L.

    2014-01-01

    Anxiety and depression are component of interictal behavioral deteriorations that occur as a consequence of kindling, a procedure to induce chronic epilepsy. The aim of this study was to evaluate the possible effects of electrical stimulation (ES) of paleocerebellar cortex on anxiety and

  12. How Kindle Could Change the Textbook Market

    Science.gov (United States)

    Young, Jeffrey R.

    2009-01-01

    Amazon is subsidizing pilot projects at six institutions--Arizona State, Case Western Reserve, Pace, and Princeton Universities, Reed College, and the University of Virginia's business school. It's picking up half the tab for the experiment on each campus, in which some sections of a few courses will be given the new Kindle DX, as the device is…

  13. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat

    OpenAIRE

    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P. Andy; Sun, Tao

    2013-01-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral sei...

  14. Role of myocardial ischemia on exercise-induced ST elevation

    International Nuclear Information System (INIS)

    Saito, Muneyasu; Sumiyoshi, Tetsuya; Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kouhei; Haze, Kazuo; Fukami, Ken-ichi; Hiramori, Katsuhiko

    1986-01-01

    Exercise-induced ST elevation in patients with previous myocardial infarction (MI) has been recognized to be related to left ventricular (LV) asynergy, however it is also recognized that myocardial ischemia can induce ST elevation. In this study, factors which determine the extent of ST elevation, with special reference to myocardial ischemia, was re-evaluated using quantitative analysis of stress myocardial scintigraphy (S-SG). Among 65 patients with previous anterior myocardial infarction and documented single vessel disease of left anterior descending artery (LAD), 19 patients who had exercise-induced ST elevation (ΔST ≥ 2.0 mm) had more abnormal Q waves (p < 0.01), lower LV ejection fraction (EF) (p < 0.01), more severe LV asynergy (p < 0.05) and less incidence of post-MI angina pectoris (AP) (p < 0.01), compared to those with ΔST < 2.0 mm, indicating that ST elevation is primarily related to LV asynergy. Correlation studies among clinical, angiographic and scintigraphic parameters show that ΔST was significantly related to a size of MI represented by Tl score or relative defect Tl activity and number of abnormal Q waves (No.Q), the magnitude of work load expressed by changes in double product (ΔDP) and intervals between the onset and exercise test, as well as myocardial ischemia expressed by the extent of redistribution (%RD) in S-SG. Among 23 patients with post-MI AP, ΔST significantly correlated with %RD (r = 0.47), indicating that myocardial ischemia can be a mechanism of exercise-induced ST elevation in patients with previous MI. Furtheremore, among those with ST elevation, concave-type ST elevation was more related to myocardial ischemia compared to convex-type ST elevation as expressed by the incidence of post-MI AP and/or significant redistribution. (J.P.N.)

  15. Opiate modification of amygdaloid-kindled seizures in rats.

    Science.gov (United States)

    Stone, W S; Eggleton, C E; Berman, R F

    1982-05-01

    Male Long-Evans rats were stereotaxically implanted bilaterally with bipolar electrodes in the central amygdala. Rats were then kindled once daily for 1 sec until 3 consecutive Stage V [25] kindled seizures were elicited. On the following day, animals were injected (IP) with either saline, naloxone (10 mg/kg), naltrexone (10mg/kg) or morphine sulfate (10 mg/kg) and again stimulated at the kindling stimulation parameters. Saline injected animals continued to show long bilateral AD's and behaviors (i.e., forelimb clonus, rearing, falling) typical of Stage V kindled animals. In contrast, rats injected with naloxone or naltrexone showed reduced behavioral seizures. Potentiation of post-ictal spiking by morphine in amygdaloid-kindled rats was also observed supporting previous reports [7,21]. In a second experiment, the reduction of kindled seizure serverity by naloxone was systematically replicated. It is concluded that opiates can significantly modify amygdaloid-kindled seizures, and that brain endorphins may play a role in the development or maintenance of an amygdaloid-kindled seizure focus.

  16. A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

    Directory of Open Access Journals (Sweden)

    Juan Carlos Morales

    2014-07-01

    Full Text Available Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK, the rapid kindling types (RK described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and inmunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA stimulation with 10 trains of biphasic pulses (10s;50Hz per day with 20 minutes-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through EEG recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental

  17. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats.

    Science.gov (United States)

    Saberi, Mehdi; Rezvanizadeh, Alireza; Bakhtiarian, Azam

    2008-08-22

    The antiepileptic activity of hydrophilic extract of Vitex agnus castus fruit (Vitex) was evaluated by the kindling model of epilepsy. Intact male rats (250-300 g) were stereotaxically implanted with a tripolar and two monopolar electrodes in amygdala and dura, respectively. The afterdischarge (AD) threshold was determined in each animal and stimulated daily until fully kindled. The animals were administered different doses (60, 120 or 180 mg/kg) of Vitex or 0.1 ml of hydro alcoholic solvent intra-peritoneally (i.p.) and kindling parameters including AD threshold, seizure stages (SS), afterdischarge duration (ADD), stage 4 latency (S4L) and stage 5 duration (S5D) were recorded 30 min post-injection. The obtained data showed that even low dose (60 mg/kg) of Vitex could significantly increase the AD threshold and decrease the ADD and S5D (PVitex at the dose of 120 mg/kg, induced significant increment in S4L (PVitex can reduce or prevent epileptic activity as demonstrated by reduction of ADD and S5D (length of convulsion) in a dose dependent manner. In conclusion, Vitex at appropriate dose can probably reduce or control epileptic activities.

  18. Dataset of quantitative spectral EEG of different stages of kindling acquisition in rats.

    Science.gov (United States)

    Jalilifar, Mostafa; Yadollahpour, Ali

    2018-02-01

    The data represented here are in relation with the manuscript "Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat" (Jalilifar et al., 2017) [1] which quantitatively classified different main stages of the kindling process based on their electrophysiological characteristics using EEG signal processing. The data in the graphical form reported the contribution of different sub bands of EEG in different stages of kindling- induced epileptogenesis. Only EEG signals related to stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 (generalized seizure stages (GSSs) were transferred into frequency function by Fast Fourier Transform (FFT) and their power spectrum and power of each sub bands including delta (1-4 Hz), Theta (4-8 Hz), alpha (8-12 Hz), beta (12-28 Hz), gamma (28-40 Hz) were calculated with MATLAB 2013b. Accordingly, all results were obtained quantitatively which can contribute to reduce the errors in the behavioral assessments.

  19. Anticonvulsant and Neuroprotective Activities of Phragmanthera austroarabica Extract in Pentylenetetrazole-Kindled Mice

    Directory of Open Access Journals (Sweden)

    Hibah M. Aldawsari

    2017-01-01

    Full Text Available Anticonvulsant and neuroprotective activity of Phragmanthera austroarabica extract were tested in pentylenetetrazole-kindled mice. All the chemical constituents of the plant extract were identified. Additionally, the extract was standardized and proved to contain total phenolic contents equal to 379.92±1.32 mg gallic acid equivalents/g dry plant extract. Induction of kindling was achieved by repeated intraperitoneal administration of pentylenetetrazole (35 mg/kg twice weekly. Male albino mice were given P. austroarabica extract (200, 400, or 800 mg/kg. The two higher doses (400 or 800 mg/kg of the extract significantly caused notable reduction in seizure activity and hippocampal malondialdehyde level compared to pentylenetetrazole control group. The highest dose enhanced cortical GSH level and showed intact DNA in the laddering assay. Upon studying the neuroprotective effect, mice treated with the higher dose of the extract demonstrated an improvement in the percent of surviving neurons in the cortex and hippocampus. We concluded that P. austroarabica extract ameliorated seizure activity and protected cortical and hippocampal neurons against pentylenetetrazole-induced kindling in mice.

  20. Kindling: A Model for the Development of Tardive Dyskinesia?

    Directory of Open Access Journals (Sweden)

    B. Glenthøj

    1988-01-01

    Full Text Available Tardive dyskinesia (TD from long-term neuroleptic treatment may be irreversible; therefore prevention has become a major concern. A controversial issue with regard to the clinical use of neuroleptic drugs is the possible influence on the development of TD of drug holidays. The major characteristics of kindling, theories of TD and the role of multiplicity in the development of TD are described. Some clinical studies point to interruption of neuroleptic therapy being a risk factor for development of irreversible TD. Induction of dyskinesia in non-human primates has been demonstrated after repeated administration of haloperidol. Rodent studies have not been conclusive. Several experimental results link TD with kindling: both conditions involve repeated stimulations, both seem to involve increased receptor responsiveness and in both conditions does depression in GABA transmission in SNR (substantia nigra; pars reticulata play an important role. It is concluded that the kindling hypothesis is relevant to the investigation of TD.

  1. A user experience evaluation of Amazon Kindle mobile application

    Science.gov (United States)

    Hussain, Azham; Mkpojiogu, Emmanuel O. C.; Musa, Ja'afaru; Mortada, Salah

    2017-10-01

    There is a dramatic increase in the development of mobile applications in recent years. This makes the usability evaluation of these mobile applications an important aspect in the advancement and application of technology. In this paper, a laboratory-based usability evaluation was carried out on the Amazon Kindle app using 15 users who performed 5 tasks on the Kindle e-book mobile app. A post-test questionnaire was administered to elicit users' perception on the usability of the application. The results demonstrate that almost all the participants were satisfied with services provided by the Amazon Kindle e-book mobile app. On all the four user experience factors examined, namely, perceived ease-of-use, perceived visibility, perceived enjoyabilty, and perceived efficiency, the evaluation outcome shows that the participants had a good and rich mobile experience with the application.

  2. Anticonvulsive evaluation of THIP in the murine pentylenetetrazole kindling model

    DEFF Research Database (Denmark)

    Simonsen, Charlotte; Boddum, Kim; von Schoubye, Nadia L

    2017-01-01

    . Evaluation of THIP as a potential anticonvulsant has given contradictory results in different animal models and for this reason, we reevaluated the anticonvulsive properties of THIP in the murine pentylenetetrazole (PTZ) kindling model. As loss of δ-GABAA R in the dentate gyrus has been associated...... the observed upregulation of δ-GABAA Rs. Even in the demonstrated presence of functional δ-GABAA Rs, THIP (0.5-4 mg/kg) showed no anticonvulsive effect in the PTZ kindling model using a comprehensive in vivo evaluation of the anticonvulsive properties....

  3. Developmental exposure to an environmental PCB mixture delays the propagation of electrical kindling from the amygdala.

    Science.gov (United States)

    Bandara, Suren B; Sadowski, Renee N; Schantz, Susan L; Gilbert, Mary E

    2017-01-01

    Developmental PCB exposure impairs hearing and induces brainstem audiogenic seizures in adult offspring. The degree to which this enhanced susceptibility to seizure is manifest in other brain regions has not been examined. Thus, electrical kindling of the amygdala was used to evaluate the effect of developmental exposure to an environmentally relevant PCB mixture on seizure susceptibility in the rat. Female Long-Evans rats were dosed orally with 0 or 6mg/kg/day of the PCB mixture dissolved in corn oil vehicle 4 weeks prior to mating and continued through gestation and up until postnatal day (PND) 21. On PND 21, pups were weaned, and two males from each litter were randomly selected for the kindling study. As adults, the male rats were implanted bilaterally with electrodes in the basolateral amygdala. For each animal, afterdischarge (AD) thresholds in the amygdala were determined on the first day of testing followed by once daily stimulation at a standard 200μA stimulus intensity until three stage 5 generalized seizures (GS) ensued. Developmental PCB exposure did not affect the AD threshold or total cumulative AD duration, but PCB exposure did increase the latency to behavioral manifestations of seizure propagation. PCB exposed animals required significantly more stimulations to reach stage 2 seizures compared to control animals, indicating attenuated focal (amygdala) excitability. A delay in kindling progression in the amygdala stands in contrast to our previous finding of increased susceptibility to brainstem-mediated audiogenic seizures in PCB-exposed animals in response to a an intense auditory stimulus. These seemingly divergent results are not unexpected given the distinct source, type, and mechanistic underpinnings of these different seizure models. A delay in epileptogenesis following focal amygdala stimulation may reflect a decrease in neuroplasticity following developmental PCB exposure consistent with reductions in use-dependent synaptic plasticity that

  4. Kindling: The Amazon e-Reader as an Educational Tool

    Science.gov (United States)

    Brezicki, Colin

    2011-01-01

    The revolutionary electronic reading device, Amazon's Kindle, is already obsolete. Such is the breakneck speed of technology that the machine touted to spell the death of printed books is already heading for the scrap heap, replaced by e-readers like the iPad that access the Internet, make phone calls, download movies, and connect users with all…

  5. Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

    Science.gov (United States)

    Fournier, Neil M; Botterill, Justin J; Marks, Wendie N; Guskjolen, Axel J; Kalynchuk, Lisa E

    2013-06-01

    Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.e., rats receive 99-electrical stimulations) to examine the effect of repeated seizures on hippocampal neurogenesis and behavior. We labeled seizure-generated cells with the proliferation marker BrdU after 30-stimulations and continued kindling for an additional 4weeks to allow newborn neurons to mature under conditions of repeated seizures. After kindling was complete, rats were tested in a trace fear conditioning task and sacrificed 2h later to examine if 4-week old newborn cells were recruited into circuits involved in the retrieval of emotional memory. Compared to non-kindled controls, long-term kindled rats showed significant impairments in fear memory reflected in a decrease in conditioned freezing to both tone and contextual cues during testing. Moreover, long-term kindling also prevented the activation of 4-week old newborn cells in response to fear memory retrieval. These results indicate that the presence of seizure activity during cell maturation impedes the ability of new neurons to integrate properly into circuits important in memory formation. Together, our findings suggest that aberrant seizure-induced neurogenesis might contribute to the development of learning impairments in chronic epilepsy and raise the possibility that targeting the reduced activation of adult born neurons could represent a beneficial strategy to reverse cognitive deficits in some epileptic patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

    Science.gov (United States)

    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

    2013-11-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

  7. Influence of elevator acceleration induced loading on injury levels

    NARCIS (Netherlands)

    Funai, K.; Schijndel-de Nooij, M. van; Nunen, E. van

    2008-01-01

    The influence on human body of the acceleration caused by the elevator emergency stop has been studied. Experiments were performed with an automotive dummy in an elevator. The study is furthermore based on numerical simulations in MADYMO with an active human model. Kinematics and contact forces of

  8. Elevated temperature drives kelp microbiome dysbiosis, while elevated carbon dioxide induces water microbiome disruption.

    Directory of Open Access Journals (Sweden)

    Jeremiah J Minich

    Full Text Available Global climate change includes rising temperatures and increased pCO2 concentrations in the ocean, with potential deleterious impacts on marine organisms. In this case study we conducted a four-week climate change incubation experiment, and tested the independent and combined effects of increased temperature and partial pressure of carbon dioxide (pCO2, on the microbiomes of a foundation species, the giant kelp Macrocystis pyrifera, and the surrounding water column. The water and kelp microbiome responded differently to each of the climate stressors. In the water microbiome, each condition caused an increase in a distinct microbial order, whereas the kelp microbiome exhibited a reduction in the dominant kelp-associated order, Alteromondales. The water column microbiomes were most disrupted by elevated pCO2, with a 7.3 fold increase in Rhizobiales. The kelp microbiome was most influenced by elevated temperature and elevated temperature in combination with elevated pCO2. Kelp growth was negatively associated with elevated temperature, and the kelp microbiome showed a 5.3 fold increase Flavobacteriales and a 2.2 fold increase alginate degrading enzymes and sulfated polysaccharides. In contrast, kelp growth was positively associated with the combination of high temperature and high pCO2 'future conditions', with a 12.5 fold increase in Planctomycetales and 4.8 fold increase in Rhodobacteriales. Therefore, the water and kelp microbiomes acted as distinct communities, where the kelp was stabilizing the microbiome under changing pCO2 conditions, but lost control at high temperature. Under future conditions, a new equilibrium between the kelp and the microbiome was potentially reached, where the kelp grew rapidly and the commensal microbes responded to an increase in mucus production.

  9. Endorphin mediation of post-ictal effects of kindled seizures in rats.

    Science.gov (United States)

    Kelsey, J E; Belluzzi, J D

    1982-12-16

    Brief electrical stimulation of the enkephalin-rich globus pallidus at 1-h intervals produced kindled, clonic seizures in rats as rapidly as similar stimulation of the amygdala. Massing the kindling trials at 10-min intervals inhibited the occurrence of subsequent seizures, especially following globus pallidus stimulation. Naloxone (20 mg/kg), an opiate receptor antagonist, reversed this post-ictal inhibition of seizures following massed trials, but had no effect on seizures kindled at 1-h intervals. Thus, endorphin-released during seizures do not appear to mediate the production of kindled seizures, but do appear to mediate the transient posts ictal inhibition of seizures.

  10. Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

    DEFF Research Database (Denmark)

    Egholm, Gro; Pareek, Manan

    2015-01-01

    for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found...

  11. Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

    Directory of Open Access Journals (Sweden)

    Gro Egholm

    2015-01-01

    Full Text Available The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found. Asymptomatic cardiac troponin T elevations during rhabdomyolysis may be due to either cardiac involvement or false positive results stemming from skeletal muscle injury.

  12. Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol ...

    African Journals Online (AJOL)

    In this study, we examined the potential protective effects of administration of vitamin C on acute and chronic sleep deprivation-induced metabolic derangement. In addition, possible processes involved in vitamin C effects on acute and chronic sleep deprivation-induced metabolic derangement were determined. Thirty-five ...

  13. The Psychoanalytic Concept of Jouissance and the Kindling Hypothesis.

    Science.gov (United States)

    Dimitriadis, Yorgos

    2017-01-01

    This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is "kindled" and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the-exclusively-Lacanian concept of the object petit a . Lacan's later conceptualization of language as jouissance (the notion of lalangue ) is then discussed in relation to Freud's early ideas ("Letter 52") on the different kinds of inscriptions that help form the mental apparatus. Finally, the author tries to formulate a hypothesis regarding specific neurophysiological mechanisms, based on clinical situations where jouissance becomes "kindled" and escapes the control of the symbolic processes through the neurophysiological mechanisms of conditioning, "kindling-sensitization" and "excitotoxicity." In these cases, jouissance can have a destructive effect on the body and can affect, among others organs, the brain-a process the author has previously described heuristically as the "psychosomatic diseases of the brain." This would be a special mechanism of automatism that would be triggered under the specific conditions of the fragility of the signifying chain (foreclosure of the Name-of-the-Father or solidification of the signifying chain) in combination with biological factors, including genetic factors. In this process, signifiers are reduced to signals, which in turn may be reduced to stimuli, with a tendency toward self-perpetuation, while affects are reduced to emotions and moods. Thus, conditioning and kindling-sensitization could also be understood in terms of a "semiotic

  14. Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol ...

    African Journals Online (AJOL)

    olayemitoyin

    person can be aroused by sensory or other stimuli. (Hall, 2015), is an ... 2007). This can be acute (a single period of extended ... short-term (acute) Sleep Deprivation, such studies for .... induced memory impairment: the role of oxidative stress.

  15. Exercise induced ST elevation and residual myocardial ischemia in previous myocardial infarction

    International Nuclear Information System (INIS)

    Shimonagata, Tsuyoshi; Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Saito, Muneyasu; Sumiyoshi, Tetsuya

    1987-01-01

    The purpose of this study was to evaluate the clinical significance of stress induced ST elevation on infarcted area in 65 patients with previous myocardial infarction (single vessel disease) who had stress thallium scan. Stress induced ST changes on infarcted area were compared with quantitative assessment of myocardial ischemia (thallium ischemic score; TIS) and extent of myocardial infarction (defect score; DS) derived from circumferential profile analysis. In patients with previous myocardial infarction in less than 3 month from the onset (n = 36), left ventricular ejection fraction (LVEF) and extent of abnormal LV wall motion were not significantly different between patients with stress induced ST elevation ( ≥ 2 mm, n = 26) and those with stress induced ST elevation ( < 2 mm, n = 10), while, in patients with previous myocardial infarction in more than 3 month (n = 29), patients with stress induced ST elevation ( ≥ 2 mm, n = 15) showed left ventricular dyskinesis more frequently than those with ST elevation ( < 2 mm, n = 14). In addition, the former showed significantly higher DS and significantly lower TIS than the latter. In patients with previous myocardial infarction in less than 3 month, patients with ST elevation ( ≥ 2 mm, n = 15) with prominent upright T wave (n = 15) had transient thallium defect in infarcted area in 73 % and they had significantly higher LVEF and TIS than those with ST elevation ( < 2 mm, n = 11). These results indicated that ST elevation in infarcted area reflect different significance according to the recovery of injured myocardium and stress induced ST elevation with prominent upright T wave in infarcted area reflect residual myocardial ischemia in less than 3 month from the onset of myocardial infarction. (author)

  16. Obesity-induced vascular inflammation involves elevated arginase activity.

    Science.gov (United States)

    Yao, Lin; Bhatta, Anil; Xu, Zhimin; Chen, Jijun; Toque, Haroldo A; Chen, Yongjun; Xu, Yimin; Bagi, Zsolt; Lucas, Rudolf; Huo, Yuqing; Caldwell, Ruth B; Caldwell, R William

    2017-11-01

    Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-( S )-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.

  17. Inhibitory Effect of High Dose of the Flavonoid Quercetin on Amygdala Electrical Kindling in Rats

    Directory of Open Access Journals (Sweden)

    Tourandokht Baluchnejadmojarad

    2010-05-01

    Full Text Available A B S T R A C T Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. Therefore, the anti-convulsant effect of a high dose of quercetin was evaluated in amygdala kindling model in male rats. Methods: Rats were divided into sham-operated group, quercetintreated SH, kindled, and quercetin-treated kindled rats. Quercetin was administered i.p. one day before amygdale kindling for 3 weeks (40 mg/kg/day. The parameters seizure stage, AD duration, the latency to the onset of stage 4, and the duration of stage 5 were analyzed. Results: The results showed that quercetin pretreatment causes a lower seizure intensity in treated kindled rats (p<0.05-0.01, a lower after-discharge duration (p<0.05-0.01, and a higher latency to stage IV (p<0.05 as compared to untreated kindled ones. Discussion: To conclude, chronic administration of quercetin inhibits amygdala electrical kindling and more studies are warranted to clarify its underlying mechanisms.

  18. The role of GABAA receptor activity in post-ictal depression period in a rat kindling model of epilepsy

    Directory of Open Access Journals (Sweden)

    Javad Mirnajafi-Zadeh

    2009-02-01

    Full Text Available Introduction: Following the seizure there is an inhibitory period named “post-ictal depressionperiod” which has a depressing effect on the following seizure. In this study, the role of GABAAreceptors on post-ictal depression period was investigated in amygdala kindling model of epilepsy inrat.Materials and Methods: Animals were kindled by electrical stimulation of amygdala. Then, theywere divided into four groups. Different groups of kindled animals were received a second stimulationat 10, 30, 60 and 90 min after the first stimulation and the percentage of suppression of seizureparameters after the second stimulation was calculated. In another four groups, bicucullin, a selectiveGABAA receptor antagonist (100 nM, was intra-cerebroventricularly microinjected 10 min before thesecond stimulation and its effect on the percentage of suppression induced by the first stimulation wasinvestigated. Six animals were used in each group.Results: When the second stimulation was applied at 10 and 30 min after the first stimulation asignificant reduction was observed in the seizure severity and seizure parameters were depressed afterthe second stimulation. Bicucullin microinjection significantly decreased the percentage of depressionin seizure parameters following the second stimulation compared to the animals received the solventalone (P<0.05. This decrease was significant when the second stimulation was applied at 10 and 30min after the first stimulation.Conclusion: Obtained results showed that activity of GABAA receptors by endogenous GABA isone of the mechanisms involved in post-ictal depressing period. However, the blocking of thesereceptors could not completely prevent this period. Thus, other factors have also role in its induction.

  19. Cannabidiol induces intracellular calcium elevation and cytotoxicity in oligodendrocytes.

    Science.gov (United States)

    Mato, Susana; Victoria Sánchez-Gómez, María; Matute, Carlos

    2010-11-01

    Heavy marijuana use has been linked to white matter histological alterations. However, the impact of cannabis constituents on oligodendroglial pathophysiology remains poorly understood. Here, we investigated the in vitro effects of cannabidiol, the main nonpsychoactive marijuana component, on oligodendrocytes. Exposure to cannabidiol induced an intracellular Ca(2+) rise in optic nerve oligodendrocytes that was not primarily mediated by entry from the extracellular space, nor by interactions with ryanodine or IP(3) receptors. Application of the mitochondrial protonophore carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP; 1 μM) completely prevented subsequent cannabidiol-induced Ca(2+) responses. Conversely, the increase in cytosolic Ca(2+) levels elicited by FCCP was reduced after previous exposure to cannabidiol, further suggesting that the mitochondria acts as the source of cannabidiol-evoked Ca(2+) rise in oligodendrocytes. n addition, brief exposure to cannabidiol (100 nM-10 μM) led to a concentration-dependent decrease of oligodendroglial viability that was not prevented by antagonists of CB(1), CB(2), vanilloid, A(2A) or PPARγ receptors, but was instead reduced in the absence of extracellular Ca(2+). The oligodendrotoxic effect of cannabidiol was partially blocked by inhibitors of caspase-3, -8 and -9, PARP-1 and calpains, suggesting the activation of caspase-dependent and -independent death pathways. Cannabidiol also elicited a concentration-dependent alteration of mitochondrial membrane potential, and an increase in reactive oxygen species (ROS) that was reduced in the absence of extracellular Ca(2+). Finally, cannabidiol-induced cytotoxicity was partially prevented by the ROS scavenger trolox. Together, these results suggest that cannabidiol causes intracellular Ca(2+) dysregulation which can lead to oligodendrocytes demise.

  20. Biochar addition induced the same plant responses as elevated CO2 in mine spoil.

    Science.gov (United States)

    Zhang, Yaling; Drigo, Barbara; Bai, Shahla Hosseini; Menke, Carl; Zhang, Manyun; Xu, Zhihong

    2018-01-01

    Nitrogen (N) limitation is one of the major constrain factors for biochar in improving plant growth, the same for elevated atmospheric carbon dioxide (CO 2 ). Hence, we hypothesized that (1) biochar would induce the same plant responses as elevated CO 2 under N-poor conditions; (2) elevated CO 2 would decrease the potential of biochar application in improving plant growth. To test these hypotheses, we assessed the effects of pinewood biochar, produced at three pyrolytic temperatures (650, 750 and 850 °C), on C and N allocation at the whole-plant level of three plant species (Austrostipa ramossissima, Dichelachne micrantha and Isolepis nodosa) grown in the N poor mine spoil under both ambient (400 μL L -1 ) and elevated (700 μL L -1 ) CO 2 concentrations. Our data showed that biochar addition (1) significantly decreased leaf total N and δ 15 N (P < 0.05); (2) decreased leaf total N and δ 15 N more pronouncedly than those of root; and (3) showed more pronounced effects on improving plant biomass under ambient CO 2 than under elevated CO 2 concentration. Hence, it remained a strong possibility that biochar addition induced the same plant physiological responses as elevated CO 2 in the N-deficient mine spoil. As expected, elevated CO 2 decreased the ability of biochar addition in improving plant growth.

  1. IPhone or Kindle: Competition of Electronic Books Sales

    Science.gov (United States)

    Chen, Li

    With the technical development of the reading equipment, e-books have witnessed a gradual and steady increase in sales in recent years. Last year, smart phones announced to be able to perform additional functions as e-book reading devices, making it possible for retailers selling e-books for smart phones (SPR) such as iPhone to differentiate with those selling e-books for specific reading equipment (SER) such as Amazon Kindle. We develop a game theory model to examine the competition between SER and SPR retailers. We derive the equilibrium price and analyze the factors that affect equilibrium outcomes under both scenarios of complete and incomplete information. Our results suggest that reduced cost due to inconvenience of reading e-books over iPhone lowers equilibrium prices, and reduced cost of specific reading equipment leads to more intense price competition. Under information asymmetry, we show that SER retailers will increase the price at equilibrium.

  2. The effect of exogenous GM1 ganglioside on kindled-amygdaloid seizures.

    Science.gov (United States)

    Albertson, T E; Walby, W F

    1987-01-01

    The effects of 12 daily doses of 30 mg/kg GM1 ganglioside i.p. on the acquisition of kindled-amygdaloid seizures in the rat was studied. No modification in the rate of kindling or the expression of the elicited seizures was noted during the acquisition phase. Further studies with additional fully amygdaloid kindled rats failed to show significant modification of suprathreshold or threshold elicited seizures after single 30-60 mg/kg i.p. doses of GM1 ganglioside. Despite previous studies which have shown antibodies to GM1 ganglioside to be convulsive, no anticonvulsant activity was demonstrated in this study with exogenous GM1 ganglioside using a battery of kindled-amygdaloid seizure tests in the rat.

  3. Elevated carbon dioxide reduces emission of herbivore-induced volatiles in Zea mays.

    Science.gov (United States)

    Block, Anna; Vaughan, Martha M; Christensen, Shawn A; Alborn, Hans T; Tumlinson, James H

    2017-09-01

    Terpene volatiles produced by sweet corn (Zea mays) upon infestation with pests such as beet armyworm (Spodoptera exigua) function as part of an indirect defence mechanism by attracting parasitoid wasps; yet little is known about the impact of climate change on this form of plant defence. To investigate how a central component of climate change affects indirect defence, we measured herbivore-induced volatile emissions in plants grown under elevated carbon dioxide (CO 2 ). We found that S. exigua infested or elicitor-treated Z. mays grown at elevated CO 2 had decreased emission of its major sesquiterpene, (E)-β-caryophyllene and two homoterpenes, (3E)-4,8-dimethyl-1,3,7-nonatriene and (3E,7E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene. In contrast, inside the leaves, elicitor-induced (E)-β-caryophyllene hyper-accumulated at elevated CO 2 , while levels of homoterpenes were unaffected. Furthermore, gene expression analysis revealed that the induction of terpene synthase genes following treatment was lower in plants grown at elevated CO 2 . Our data indicate that elevated CO 2 leads both to a repression of volatile synthesis at the transcriptional level and to limitation of volatile release through effects of CO 2 on stomatal conductance. These findings suggest that elevated CO 2 may alter the ability of Z. mays to utilize volatile terpenes to mediate indirect defenses. © 2017 John Wiley & Sons Ltd.

  4. Radio frequency-induced temperature elevations in the human head considering small anatomical structures

    International Nuclear Information System (INIS)

    Schmid, G.; Ueberbacher, R.; Samaras, T.

    2007-01-01

    In order to enable a detailed numerical radio frequency (RF) dosimetry and the computations of RF-induced temperature elevations, high-resolution (0.1 mm) numerical models of the human eye, the inner ear organs and the pineal gland were developed and inserted into a commercially available head model. As radiation sources, generic models of handsets at 400, 900 and 1850 MHz operating in close proximity to the head were considered. The results, obtained by finite-difference time domain-based computations, showed a highly heterogeneous specific absorption rate (SAR) distribution and SAR-peaks inside the inner ear structures; however, the corresponding RF-induced temperature elevations were well below 0.1 deg. C, when considering typical output power values of hand-held devices. In case of frontal exposure, with the radiation sources ∼2.5 cm in front of the closed eye, maximum temperature elevations in the eye in the range of ∼0.2-0.6 deg. C were found for typical device output powers. A reduction in tissue perfusion mainly affected the maximum RF-induced temperature elevation of tissues deep inside the head. Similarly, worst-case considerations regarding pulsed irradiation affected temperature elevations in deep tissue significantly more than in superficial tissues. (authors)

  5. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    International Nuclear Information System (INIS)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An; Wu Lijun

    2008-01-01

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of α-particle irradiation, the fraction of γ-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy α-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H 2 O 2 ), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress

  6. Impact of statin use on exercise-induced cardiac troponin elevations.

    NARCIS (Netherlands)

    Eijsvogels, T.M.H.; Januzzi, J.L., Jr.; Taylor, B.A.; Isaacs, S.K.; D'Hemecourt, P.; Zaleski, A.; Dyer, S.; Troyanos, C.; Weiner, R.B.; Thompson, P.D.; Baggish, A.L.

    2014-01-01

    Marathon running commonly causes a transient elevation of creatine kinase and cardiac troponin I (cTnI). The use of statins before marathon running exacerbates the release of creatine kinase from skeletal muscle, but the effect of statin use on exercise-induced cTnI release is unknown. We therefore

  7. Elevated [CO2] does not ameliorate the negative effects of elevated temperature on drought-induced mortality in Eucalyptus radiata seedlings.

    Science.gov (United States)

    Duan, Honglang; Duursma, Remko A; Huang, Guomin; Smith, Renee A; Choat, Brendan; O'Grady, Anthony P; Tissue, David T

    2014-07-01

    It has been reported that elevated temperature accelerates the time-to-mortality in plants exposed to prolonged drought, while elevated [CO(2)] acts as a mitigating factor because it can reduce stomatal conductance and thereby reduce water loss. We examined the interactive effects of elevated [CO(2)] and temperature on the inter-dependent carbon and hydraulic characteristics associated with drought-induced mortality in Eucalyptus radiata seedlings grown in two [CO(2)] (400 and 640 μL L(-1)) and two temperature (ambient and ambient +4 °C) treatments. Seedlings were exposed to two controlled drying and rewatering cycles, and then water was withheld until plants died. The extent of xylem cavitation was assessed as loss of stem hydraulic conductivity. Elevated temperature triggered more rapid mortality than ambient temperature through hydraulic failure, and was associated with larger water use, increased drought sensitivities of gas exchange traits and earlier occurrence of xylem cavitation. Elevated [CO(2)] had a negligible effect on seedling response to drought, and did not ameliorate the negative effects of elevated temperature on drought. Our findings suggest that elevated temperature and consequent higher vapour pressure deficit, but not elevated [CO(2)], may be the primary contributors to drought-induced seedling mortality under future climates. © 2013 John Wiley & Sons Ltd.

  8. Involvement of Smad3 pathway in atrial fibrosis induced by elevated hydrostatic pressure.

    Science.gov (United States)

    Wei, Wei; Rao, Fang; Liu, Fangzhou; Xue, Yumei; Deng, Chunyu; Wang, Zhaoyu; Zhu, Jiening; Yang, Hui; Li, Xin; Zhang, Mengzhen; Fu, Yongheng; Zhu, Wensi; Shan, Zhixin; Wu, Shulin

    2018-06-01

    Hypertension is a main risk factor for atrial fibrillation, but the direct effects of hydrostatic pressure on the atrial fibrosis are still unknown. The present study investigated whether hydrostatic pressure is responsible for atrial fibrosis, and addressed a potential role of the Smad pathway in this pathology. Biochemical assays were used to study regulation and expression of fibrotic factors in spontaneously hypertensive rats (SHRs) and Wistar rats, and in cardiac fibroblasts (CFs) cultured under standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure. Levels of atrial fibrosis and protein expression of fibrotic factors Col-1A1/-3A1, TGF-β1, and MMP-2 in SHRs' left atrial tissues were higher than those in Wistar rats. Exposure to elevated pressure was associated with the proliferation of CFs. The protein expression of Col-1A1/-3A1, TGF-β1, and MMP-2 in CFs was also up-regulated in a pressure-dependent manner. The proliferation of CFs and increased expressions of fibrotic markers induced by elevated hydrostatic pressure could be reversed by the Smad3 inhibitor naringenin. The activation of Smad3 pathway was also stimulated by elevated hydrostatic pressure. These results demonstrate that CF secretory function and proliferation can be up-regulated by exposure to elevated pressure, and that Smad3 may modulate CF activation induced by high hydrostatic pressure. © 2017 Wiley Periodicals, Inc.

  9. The Psychoanalytic Concept of Jouissance and the Kindling Hypothesis

    Directory of Open Access Journals (Sweden)

    Yorgos Dimitriadis

    2017-09-01

    Full Text Available This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is “kindled” and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the—exclusively—Lacanian concept of the object petit a. Lacan's later conceptualization of language as jouissance (the notion of lalangue is then discussed in relation to Freud's early ideas (“Letter 52” on the different kinds of inscriptions that help form the mental apparatus. Finally, the author tries to formulate a hypothesis regarding specific neurophysiological mechanisms, based on clinical situations where jouissance becomes “kindled” and escapes the control of the symbolic processes through the neurophysiological mechanisms of conditioning, “kindling-sensitization” and “excitotoxicity.” In these cases, jouissance can have a destructive effect on the body and can affect, among others organs, the brain—a process the author has previously described heuristically as the “psychosomatic diseases of the brain.” This would be a special mechanism of automatism that would be triggered under the specific conditions of the fragility of the signifying chain (foreclosure of the Name-of-the-Father or solidification of the signifying chain in combination with biological factors, including genetic factors. In this process, signifiers are reduced to signals, which in turn may be reduced to stimuli, with a tendency toward self-perpetuation, while affects are reduced to emotions and moods. Thus, conditioning and kindling-sensitization could also

  10. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    International Nuclear Information System (INIS)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang; Wu Lijun

    2007-01-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of γ-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process ( G -methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy α-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose α-particle irradiation and nitric oxide generated by irradiation was also very important in this process

  11. Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

    Science.gov (United States)

    Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

    2016-09-01

    Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

  12. Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia.

    Science.gov (United States)

    Huang, Aji; Wu, Hongyu; Iriyama, Takayuki; Zhang, Yujin; Sun, Kaiqi; Song, Anren; Liu, Hong; Peng, Zhangzhe; Tang, Lili; Lee, Minjung; Huang, Yun; Ni, Xin; Kellems, Rodney E; Xia, Yang

    2017-07-01

    Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA hypomethylation. Immunohistochemical studies revealed that elevated placental adenosine-mediated DNA hypomethylation predominantly occurs in spongiotrophoblasts and labyrinthine trophoblasts and that this effect is independent of A2B adenosine receptor activation in both preeclampsia models. Extending our mouse findings to humans, we used cultured human trophoblasts to demonstrate that adenosine functions intracellularly and induces DNA hypomethylation without A2B adenosine receptor activation. Altogether, both mouse and human studies reveal novel mechanisms underlying placental DNA hypomethylation and potential therapeutic approaches for preeclampsia. © 2017 American Heart Association, Inc.

  13. Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

    Science.gov (United States)

    Albertson, T E; Joy, R M; Stark, L G

    1984-03-01

    The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Elevated thyroid stimulating hormone in a neonate: Drug induced or disease?

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2011-01-01

    Full Text Available Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most common abnormality is absent or insufficient thyroid peroxidase enzyme. Maternal intake of antithyroid drug can also lead to elevated thyroid stimulating hormone (TSH in a neonate, albeit the scenario is temporary. We report one such interesting case where a clinically euthyroid neonate borne to a mother on antithyroid drug presents on 12 th day of life with reports of elevated TSH and increased tracer uptake in 99mTc thyroid scan. Disproportionately high TSH in comparison to low maternal antithyroid drug dosage and further elevation of TSH after stopping mother′s antithyroid drugs ruled out maternal antithyroid drug-induced congenital hypothyroidism in the baby. Early institution of therapy in these patients can prevent mental retardation and other features of hypothyroidism.

  15. Monoterpene and herbivore-induced emissions from cabbage plants grown at elevated atmospheric CO 2 concentration

    Science.gov (United States)

    Vuorinen, Terhi; Reddy, G. V. P.; Nerg, Anne-Marja; Holopainen, Jarmo K.

    The warming of the lower atmosphere due to elevating CO 2 concentration may increase volatile organic compound (VOC) emissions from plants. Also, direct effects of elevated CO 2 on plant secondary metabolism are expected to lead to increased VOC emissions due to allocation of excess carbon on secondary metabolites, of which many are volatile. We investigated how growing at doubled ambient CO 2 concentration affects emissions from cabbage plants ( Brassica oleracea subsp. capitata) damaged by either the leaf-chewing larvae of crucifer specialist diamondback moth ( Plutella xylostella L.) or generalist Egyptian cotton leafworm ( Spodoptera littoralis (Boisduval)). The emission from cabbage cv. Lennox grown in both CO 2 concentrations, consisted mainly of monoterpenes (sabinene, limonene, α-thujene, 1,8-cineole, β-pinene, myrcene, α-pinene and γ-terpinene). ( Z)-3-Hexenyl acetate, sesquiterpene ( E, E)- α-farnesene and homoterpene ( E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) were emitted mainly from herbivore-damaged plants. Plants grown at 720 μmol mol -1 of CO 2 had significantly lower total monoterpene emissions per shoot dry weight than plants grown at 360 μmol mol -1 of CO 2, while damage by both herbivores significantly increased the total monoterpene emissions compared to intact plants. ( Z)-3-Hexenyl acetate, ( E, E)- α-farnesene and DMNT emissions per shoot dry weight were not affected by the growth at elevated CO 2. The emission of DMNT was significantly enhanced from plants damaged by the specialist P. xylostella compared to the plants damaged by the generalist S. littoralis. The relative proportions of total monoterpenes and total herbivore-induced compounds of total VOCs did not change due to the growth at elevated CO 2, while insect damage increased significantly the proportion of induced compounds. The results suggest that VOC emissions that are induced by the leaf-chewing herbivores will not be influenced by elevated CO 2 concentration.

  16. Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China)], E-mail: ljw@ipp.ac.cn

    2007-11-01

    Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of {gamma}-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process (<1 h post irradiation), and the generation of micronuclei (MN), a sensitive marker for relative long process of RIBE. Our results showed that in the absence of irradiation, NaCl at elevated concentration such as 8.0, 9.0 and 10.0 g/L did not significantly increase the frequency of {gamma}-H2AX foci-positive cells and the number of foci per positive cell comparing with that NaCl at a normal concentration (6.8 g/L). However, with 0.2 cGy {alpha}-particle irradiation, the induced fraction of {gamma}-H2AX foci-positive cells and the number of induced {gamma}-H2AX foci per positive cell were significantly increased in both irradiated and adjacent non-irradiated regions. Similarly, the induction of MN by 0.2 cGy {alpha}-particle irradiation also increased with the elevated NaCl concentrations. With N{sup G}-methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy {alpha}-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose {alpha}-particle irradiation and nitric oxide generated by irradiation was also very important in this process.

  17. Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

    Directory of Open Access Journals (Sweden)

    Kurt R. Stover

    2017-12-01

    Full Text Available The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2–3 and 18–22 months of age via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.

  18. Radiation-induced bystander effects enhanced by elevated sodium chloride through sensitizing cells to bystander factors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Lingyan; Han Wei; Chen Shaopeng; Zhao Ye; Jiang Erkang; Bao Lingzhi; Pei Bei; Yang Gen; Zhao Guoping; Wang Jun; Xu An [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China); Wu Lijun [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, Anhui (China)], E-mail: ljw@ipp.ac.cn

    2008-09-26

    Radiation-induced bystander effects (RIBE) have been demonstrated to occur widely in various cell lines. However, very little data is available on the genotoxic effects of RIBE combined with other factor(s). We reported previously that with a low dose of {alpha}-particle irradiation, the fraction of {gamma}-H2AX foci-positive cells in non-irradiated bystander cells was significantly increased under elevated NaCl culture conditions. In this study, we further investigated the functional role of NaCl in the enhancement of RIBE using a specially designed co-culture system and micronucleus (MN) test. It was shown that the MN frequency was not increased significantly by elevated NaCl (9.0 g/L) alone or by medium exposure. However, with 1.0 cGy {alpha}-particle irradiation, the induced MN frequency increased significantly in both irradiated and non-irradiated bystander regions. Additional studies showed that elevated NaCl made the non-irradiated bystander cells more vulnerable to bystander factors. Furthermore, it was found that the induced MN frequency in cells both in irradiated and non-irradiated bystander regions was weakened when the hypertonic medium was changed to normotonic medium for 2 h before irradiation. Such observations were quite similar to the co-effect of NaCl and hydrogen peroxide (H{sub 2}O{sub 2}), indicating that elevated NaCl might sensitize non-irradiated cells to bystander factors-induced oxidative stress.

  19. Failure of Elevating Calcium Induces Oxidative Stress Tolerance and Imparts Cisplatin Resistance in Ovarian Cancer Cells

    OpenAIRE

    Ma, Liwei; Wang, Hongjun; Wang, Chunyan; Su, Jing; Xie, Qi; Xu, Lu; Yu, Yang; Liu, Shibing; Li, Songyan; Xu, Ye; Li, Zhixin

    2016-01-01

    Cisplatin is a commonly used chemotherapeutic drug, used for the treatment of malignant ovarian cancer, but acquired resistance limits its application. There is therefore an overwhelming need to understand the mechanism of cisplatin resistance in ovarian cancer, that is, ovarian cancer cells are insensitive to cisplatin treatment. Here, we show that failure of elevating calcium and oxidative stress tolerance play key roles in cisplatin resistance in ovarian cancer cell lines. Cisplatin induce...

  20. Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

    Directory of Open Access Journals (Sweden)

    Lili Ji

    Full Text Available Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

  1. Quercetin Prevents Pyrrolizidine Alkaloid Clivorine-Induced Liver Injury in Mice by Elevating Body Defense Capacity

    Science.gov (United States)

    Ji, Lili; Ma, Yibo; Wang, Zaiyong; Cai, Zhunxiu; Pang, Chun; Wang, Zhengtao

    2014-01-01

    Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin. PMID:24905073

  2. Phenylephrine-induced elevations in arterial blood pressure are attenuated in heat-stressed humans

    Science.gov (United States)

    Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

    2002-01-01

    To test the hypothesis that phenylephrine-induced elevations in blood pressure are attenuated in heat-stressed humans, blood pressure was elevated via steady-state infusion of three doses of phenylephrine HCl in 10 healthy subjects in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature by 0.5 degrees C, muscle sympathetic nerve activity (MSNA), heart rate, and cardiac output and decreased total peripheral vascular resistance (TPR; all P blood pressure (MAP; P > 0.05). At the highest dose of phenylephrine, the increase in MAP and TPR from predrug baselines was significantly attenuated during the heat stress [DeltaMAP 8.4 +/- 1.2 mmHg; DeltaTPR 0.96 +/- 0.85 peripheral resistance units (PRU)] compared with normothermia (DeltaMAP 15.4 +/- 1.4 mmHg, DeltaTPR 7.13 +/- 1.18 PRU; all P blood pressure, as well as the slope of the relationship between heart rate and systolic blood pressure, respectively, was similar between thermal conditions (each P > 0.05). These data suggest that phenylephrine-induced elevations in MAP are attenuated in heat-stressed humans without affecting baroreflex control of MSNA or heart rate.

  3. Calpain: a molecule to induce AIF-mediated necroptosis in RGC-5 following elevated hydrostatic pressure

    Science.gov (United States)

    2014-01-01

    Background RIP3 (Receptor-interacting protein 3) pathway was mainly described as the molecular mechanism of necroptosis (programmed necrosis). But recently, non-RIP3 pathways were found to mediate necroptosis. We deliberate to investigate the effect of calpain, a molecule to induce necroptosis as reported (Cell Death Differ 19:245–256, 2012), in RGC-5 following elevated hydrostatic pressure. Results First, we identified the existence of necroptosis of RGC-5 after insult by using necrostatin-1 (Nec-1, necroptosis inhibitor) detected by flow cytometry. Immunofluorescence staining and western blot were used to detect the expression of calpain. Western blot analysis was carried out to describe the truncated AIF (tAIF) expression with or without pretreatment of ALLN (calpain activity inhibitor). Following elevated hydrostatic pressure, necroptotic cells pretreated with or without ALLN was stained by Annexin V/PI, The activity of calpain was also examined to confirm the inhibition effect of ALLN. The results showed that after cell injury there was an upregulation of calpain expression. Upon adding ALLN, the calpain activity was inhibited, and tAIF production was reduced upon injury along with the decreased number of necroptosis cells. Conclusion Our study found that calpain may induce necroptosis via tAIF-modulation in RGC-5 following elevated hydrostatic pressure. PMID:24884644

  4. Offsetting global warming-induced elevated greenhouse gas emissions from an arable soil by biochar application.

    Science.gov (United States)

    Bamminger, Chris; Poll, Christian; Marhan, Sven

    2018-01-01

    Global warming will likely enhance greenhouse gas (GHG) emissions from soils. Due to its slow decomposability, biochar is widely recognized as effective in long-term soil carbon (C) sequestration and in mitigation of soil GHG emissions. In a long-term soil warming experiment (+2.5 °C, since July 2008) we studied the effect of applying high-temperature Miscanthus biochar (0, 30 t/ha, since August 2013) on GHG emissions and their global warming potential (GWP) during 2 years in a temperate agroecosystem. Crop growth, physical and chemical soil properties, temperature sensitivity of soil respiration (R s ), and metabolic quotient (qCO 2 ) were investigated to yield further information about single effects of soil warming and biochar as well as on their interactions. Soil warming increased total CO 2 emissions by 28% over 2 years. The effect of warming on soil respiration did not level off as has often been observed in less intensively managed ecosystems. However, the temperature sensitivity of soil respiration was not affected by warming. Overall, biochar had no effect on most of the measured parameters, suggesting its high degradation stability and its low influence on microbial C cycling even under elevated soil temperatures. In contrast, biochar × warming interactions led to higher total N 2 O emissions, possibly due to accelerated N-cycling at elevated soil temperature and to biochar-induced changes in soil properties and environmental conditions. Methane uptake was not affected by soil warming or biochar. The incorporation of biochar-C into soil was estimated to offset warming-induced elevated GHG emissions for 25 years. Our results highlight the suitability of biochar for C sequestration in cultivated temperate agricultural soil under a future elevated temperature. However, the increased N 2 O emissions under warming limit the GHG mitigation potential of biochar. © 2017 John Wiley & Sons Ltd.

  5. Limited Investigation of the Effects of Elevator Rate Limiting and Stick Dynamics on Longitudinal Pilot Induced Oscillations (HAVE GRIP)

    National Research Council Canada - National Science Library

    Peters, Patrick

    1996-01-01

    This report presents the results of the HAVE GRIP flight test program. This program performed a limited investigation of the effects of stick dynamics and elevator rate limiting on longitudinal pilot induced oscillations (PIOs...

  6. A sub-threshold dose of pilocarpine increases glutamine synthetase in reactive astrocytes and enhances the progression of amygdaloid-kindling epilepsy in rats.

    Science.gov (United States)

    Sun, Hong-Liu; Deng, Da-Ping; Pan, Xiao-Hong; Wang, Chao-Yun; Zhang, Xiu-Li; Chen, Xiang-Ming; Wang, Chun-Hua; Liu, Yu-Xia; Li, Shu-Cui; Bai, Xian-Yong; Zhu, Wei

    2016-03-02

    The prognosis of patients exposed to a sub-threshold dose of a proconvulsant is difficult to establish. In this study, we investigated the effect of a single sub-threshold dose of the proconvulsant pilocarpine (PILO) on the progression of seizures that were subsequently induced by daily electrical stimulation (kindling) of the amygdaloid formation. Male Sprague–Dawley rats were each implanted with an electrode in the right basolateral amygdala and an indwelling cannula in the right ventricle. The animals were randomized into groups and were administered one of the following treatments: saline, PILO, saline+L-α-aminoadipic acid (L-AAA; one dosage tested), PILO+L-AAA, or PILO+L-methionine sulfoximine (three dosages tested). Amygdaloid stimulation and electroencephalography were performed once daily. We performed immunohistochemistry and western blot for glial fibrillary acidic protein and glutamine synthetase (GS). We also assayed the enzymic activity of GS in discrete brain regions. An intraperitoneal injection of a sub-threshold PILO dose enhanced the progression of amygdaloid-kindling seizures and was accompanied by an increase in reactive-astrocyte and GS (content and activity) in the hippocampus and piriform cortex. L-AAA and L-methionine sulfoximine, inhibitors of astrocytic and GS function, respectively, abolished the effect of PILO on amygdaloid-kindling seizures. We conclude that one sub-threshold dose of a proconvulsant may enhance the progression of subsequent epilepsy and astrocytic GS may play a role in this phenomenon. Thus, a future therapy for epilepsy could be inhibition of astrocytes and/or GS.

  7. Inter- and intraobserver agreement of seizure behavior scoring in the amygdala kindled rat

    NARCIS (Netherlands)

    Groot, L.J.J.; Gosens, N.; Vles, J.S.H.; Hoogland, G.; Aldenkamp, Albert; Rouhl, Rob P W

    2015-01-01

    Introduction: The Racine scale is a 5-point seizure behavior scoring paradigm used in the amygdala kindled rat. Though this scale has been applied widely in experimental epilepsy research, studies of reproducibility are rare. The aim of the current study was, therefore, to assess its interobserver

  8. Kindled seizures selectively reduce a subpopulation of (/sup 3/H)quinuclidinyl benzilate binding sites in rat dentate gyrus

    Energy Technology Data Exchange (ETDEWEB)

    Savage, D.D.; McNamara, J.O.

    1982-09-01

    Amygdala-kindled seizures reduced significantly the total number of (/sup 3/H)quinuclidinyl benzilate binding sites in both dentate and hippocampal gyri compared to electrode implanted unstimulated controls. Both high and low affinity carbachol displaceable binding site populations were significantly reduced in hippocampal gyrus. By contrast, a selective decline of low affinity sites was found in dentate gyrus membranes. The selectivity of the decline in dentate but not hippocampus gyrus underscores the specificity of this molecular response to amygdala-kindled seizures. We suggest that these receptor alterations underlie adaptive mechanisms which antagonize kindled epileptogenesis.

  9. Kindled seizures selectively reduce a subpopulation of [3H]quinuclidinyl benzilate binding sites in rat dentate gyrus

    International Nuclear Information System (INIS)

    Savage, D.D.; McNamara, J.O.

    1982-01-01

    Amygdala-kindled seizures reduced significantly the total number of [ 3 H]quinuclidinyl benzilate binding sites in both dentate and hippocampal gyri compared to electrode implanted unstimulated controls. Both high and low affinity carbachol displaceable binding site populations were significantly reduced in hippocampal gyrus. By contrast, a selective decline of low affinity sites was found in dentate gyrus membranes. The selectivity of the decline in dentate but not hippocampus gyrus underscores the specificity of this molecular response to amygdala-kindled seizures. We suggest that these receptor alterations underlie adaptive mechanisms which antagonize kindled epileptogenesis

  10. Trauma-induced secondary cardiac injury is associated with hyperacute elevations in inflammatory cytokines.

    Science.gov (United States)

    De'Ath, Henry D; Manson, Joanna; Davenport, Ross; Glasgow, Simon; Renfrew, Ian; Davies, L Ceri; Uppal, Rakesh; Brohi, Karim

    2013-05-01

    Clinical evidence supports the existence of a trauma-induced secondary cardiac injury. Experimental research suggests inflammation as a possible mechanism. The study aimed to determine if there was an early association between inflammation and secondary cardiac injury in trauma patients. A cohort study of critically injured patients between January 2008 and January 2010 was undertaken. Levels of the cardiac biomarkers troponin I and heart-specific fatty acid-binding protein and the cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, and IL-8 were measured on admission to hospital, and again at 24 and 72 h. Participants were reviewed for adverse cardiac events (ACEs) and in-hospital mortality. Of 135 patients recruited, 18 (13%) had an ACE. Patients with ACEs had higher admission plasma levels of TNF-α (5.4 vs. 3.8 pg/mL; P = 0.03), IL-6 (140 vs. 58.9 pg/mL, P = 0.009), and IL-8 (19.3 vs. 9.1 pg/mL, P = 0.03) compared with those without events. Hour 24 cytokines were not associated with events, but IL-8 (14.5 vs. 5.8 pg/mL; P = 0.01) and IL-1β (0.55 vs. 0.19 pg/mL; P = 0.04) were higher in patients with ACEs at 72 hours. Admission IL-6 was independently associated with heart-specific fatty acid-binding protein increase (P < 0.05). Patients who presented with an elevated troponin I combined with either an elevated TNF-α (relative risk [RR], 11.0; 95% confidence interval [CI], 1.8-66.9; P = 0.015), elevated IL-6 (RR, 17.3; 95% CI, 2.9-101.4; P = 0.001), or elevated IL-8 (RR, 15.0; 95% CI, 3.1-72.9; P = 0.008) were at the highest risk of in-hospital death when compared with individuals with normal biomarker and cytokine values. There is an association between hyperacute elevations in inflammatory cytokines with cardiac injury and ACEs in critically injured patients. Biomarker evidence of cardiac injury and inflammation on admission is associated with a higher risk of in-hospital death.

  11. Cofilin phosphorylation is elevated after F-actin disassembly induced by Rac1 depletion.

    Science.gov (United States)

    Liu, Linna; Li, Jing; Zhang, Liwang; Zhang, Feng; Zhang, Rong; Chen, Xiang; Brakebusch, Cord; Wang, Zhipeng; Liu, Xinyou

    2015-01-01

    Cytoskeletal reorganization is essential to keratinocyte function. Rac1 regulates cytoskeletal reorganization through signaling pathways such as the cofilin cascade. Cofilin severs actin filaments after activation by dephosphorylation. Rac1 was knocked out in mouse keratinocytes and it was found that actin filaments disassembled. In the epidermis of mice in which Rac1 was knocked out only in keratinocytes, cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1). These effects were independent of the signaling pathways for p21-activated kinase/LIM kinase (Pak/LIMK), protein kinase C, or protein kinase D or generation of reactive oxygen species. Similarly, when actin polymerization was specifically inhibited or Rac1 was knocked down, cofilin phosphorylation was enhanced and SSH1 was repressed. Repression of SSH1 partially blocked actin depolymerization induced by Rac1 depletion. Therefore, aberrant cofilin phosphorylation that induces actin polymerization might be a consequence of actin disassembly induced by the absence of Rac1. © 2015 International Union of Biochemistry and Molecular Biology.

  12. Hippocampal low-frequency stimulation inhibits afterdischarge and increases GABA (A) receptor expression in amygdala-kindled pharmacoresistant epileptic rats.

    Science.gov (United States)

    Wu, Guofeng; Wang, Likun; Hong, Zhen; Ren, Siying; Zhou, Feng

    2017-08-01

    The purpose of the present study was to observe the effects of hippocampal low-frequency stimulation (Hip-LFS) on amygdala afterdischarge and GABA (A) receptor expression in pharmacoresistant epileptic (PRE) rats. A total of 110 healthy adult male Wistar rats were used to generate a model of epilepsy by chronic stimulation of the amygdala. Sixteen PRE rats were selected from 70 amygdala-kindled rats by testing their response to Phenytoin and Phenobarbital, and they were randomly assigned to a pharmacoresistant stimulation group (PRS group, 8 rats) or a pharmacoresistant control group (PRC group, 8 rats). A stimulation electrode was implanted into the hippocampus of all of the rats. Hip-LFS was administered twice per day in the PRS group for two weeks. Simultaneously, amygdala stimulus-induced seizures and afterdischarge were recorded. After the hippocampal stimulation was terminated, the brain tissues were obtained to determine the GABA (A) receptors by a method of immumohistochemistry and a real-time polymerase chain reaction. The stages and duration of the amygdala stimulus-induced epileptic seizures were decreased in the PRS group. The afterdischarge threshold was increased and the duration as well as the afterdischarge frequency was decreased. Simultaneously, the GABA (A) expression was significantly increased in the PRS group. Hip-LFS may inhibit amygdala stimulus-induced epileptic seizures and up-regulate GABA (A) receptor expression in PRE rats. The antiepileptic effects of hippocampal stimulation may be partly achieved by increasing the GABA (A) receptor.

  13. The difference in endolymphatic hydrostatic pressure elevation induced by isoproterenol between the ampulla and the cochlea.

    Science.gov (United States)

    Inamoto, Ryuhei; Miyashita, Takenori; Matsubara, Ai; Hoshikawa, Hiroshi; Mori, Nozomu

    2017-06-01

    The purpose of the study was to investigate the difference in the responses of endolymphatic hydrostatic pressure to isoproterenol, β-adrenergic receptor agonist, between pars superior and pars inferior. The hydrostatic pressure of endolymph and perilymph and endolymphatic potential in the ampulla and the cochlea during the intravenous administration of isoproterenol were recorded using a servo-null system in guinea pigs. The hydrostatic pressure of endolymph and perilymph in the ampulla and cochlea was similar in magnitude. Isoproterenol significantly increased hydrostatic pressure of ampullar and cochlear endolymph and perilymph with no change in the ampullar endolymphatic potential and endocochlear potential, respectively. The isoproterenol-induced maximum change of endolymphatic hydrostatic pressure in ampulla was significantly (phydrostatic pressure in the ampulla disappeared like that in the cochlea. Isoproterenol elevates endolymphatic hydrostatic pressure in different manner between the vestibule and the cochlea. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Temporal pattern of AP-1 DNA-binding activity in the rat hippocampus following a kindled seizure

    Energy Technology Data Exchange (ETDEWEB)

    Shomori, T. [Department of Neurology, Okayama University Medical School, 2-5-1, Shikata-cho Okayama (Japan); Hayabara, T. [Clinical Research Institute, National Sanatorium Minamiokayama Hospital, 4066 Hayashima-cho (Japan); Ishihara, T. [Department of Neuropsychiatry, Okayama University Medical School, 2-5-1 Shikata-cho Okayama (Japan); Okada, S. [Department of Neurology, Okayama University Medical School, 2-5-1, Shikata-cho Okayama (Japan); Akiyama, K. [Department of Neuropsychiatry, Okayama University Medical School, 2-5-1 Shikata-cho Okayama (Japan); Sato, K. [Clinical Research Institute, National Sanatorium Minamiokayama Hospital, 4066 Hayashima-cho (Japan); Kashihara, K. [Department of Neurology, Okayama University Medical School, 2-5-1, Shikata-cho Okayama (Japan)

    1997-07-28

    DNA binding by transcripton factor AP-1 was enhanced remarkably following kindling stimulation in rat amygdala. Maximum increase occurred 2 h after stimulation with return to baseline within 24 h. Supershift and western analyses revealed that 38,000 mol. wt Fos-related antigen and JunD were the main components of the evoked AP-1 complexes at the time their induction reached maximum. AP-1 induction 2 h after the last kindling stimulation was more prominent in samples from previously kindled rats than in those from non-kindled rats. This study sought to establish the role of AP-1 in plastic changes of the hippocampus associated with kindling. Male Sprague-Dawley rats were kindled from the left amygdala until they exhibited Racine [15] class 5 generalized seizures. Nuclear proteins were extracted from dorsal hippocampi obtained from 0 to 24 h after final stimulations. From these, we evaluated the temporal pattern of DNA binding by AP-1 using a gel mobility-shift assay with a {sup 32}P-labelled AP-1 probe. Supershift and western analyses were added to investigate components of the seizure-evoked AP-1 complexes. Our results suggest that the basal level of AP-1 complexes is not associated with the seizure susceptibility in kindling. However, development of kindling appears to facilitate stimulus-evoked AP-1 induction, probably via plastic changes in the central nervous system. AP-1 may mediate such changes by regulating expression of certain genes. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  15. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  16. Micro-mechanisms of Surface Defects Induced on Aluminum Alloys during Plastic Deformation at Elevated Temperatures

    Science.gov (United States)

    Gali, Olufisayo A.

    Near-surface deformed layers developed on aluminum alloys significantly influence the corrosion and tribological behavior as well as reduce the surface quality of the rolled aluminum. The evolution of the near-surface microstructures induced on magnesium containing aluminum alloys during thermomechanical processing has been investigated with the aim generating an understanding of the influence of individual forming parameters on its evolution and examine the microstructure of the roll coating induced on the mating steel roll through material transfer during rolling. The micro-mechanisms related to the various features of near-surface microstructure developed during tribological conditions of the simulated hot rolling process were identified. Thermomechanical processing experiments were performed with the aid of hot rolling (operating temperature: 550 to 460 °C, 4, 10 and 20 rolling pass schedules) and hot forming (operating temperature: 350 to 545 °C, strain rate: 4 x 10-2 s-1) tribo-simulators. The surface, near-surface features and material transfer induced during the elevated temperature plastic deformation were examined and characterized employing optical interferometry, SEM/EDS, FIB and TEM. Near-surface features characterized on the rolled aluminum alloys included; cracks, fractured intermetallic particles, aluminum nano-particles, oxide decorated grain boundaries, rolled-in oxides, shingles and blisters. These features were related to various individual rolling parameters which included, the work roll roughness, which induced the formation of shingles, rolling marks and were responsible for the redistribution of surface oxide and the enhancements of the depth of the near-surface damage. The enhanced stresses and strains experienced during rolling were related to the formation and propagation of cracks, the nanocrystalline structure of the near-surface layers and aluminum nano-particles. The mechanism of the evolution of the near-surface microstructure were

  17. Postictal in situ MRS brain lactate in the rat kindling model.

    Science.gov (United States)

    Maton, B M; Najm, I M; Wang, Y; Lüders, H O; Ng, T C

    1999-12-10

    To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: 3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. In the epilepsy.

  18. Behavioral and electrographic effects of opioids on kindled seizures in rats.

    Science.gov (United States)

    Caldecott-Hazard, S; Shavit, Y; Ackermann, R F; Engel, J; Frederickson, R C; Liebeskind, J C

    1982-11-18

    Our laboratory previously suggested that opioid peptides are released by an amygdaloid kindled seizure and may affect the elicitation of a subsequent seizure. The present study examined the effects of morphine, naloxone, enkephalin analogues, and conditions of morphine tolerance and withdrawal on the severity and duration of a series of amygdaloid kindled seizures. The results suggest two distinct opiate/opioid actions on seizures. The first is an anticonvulsant effect on the behavioral manifestations of seizures. This effect is seen following a high dose (50 mg/kg) of morphine or a low dose (6 mg/kg) of enkephalin analogue (LY146104), and is reversed by naloxone. The second is a naloxone-reversible prolonging effect of the high dose of morphine on the electrographic components of the seizures. Receptor affinities of these various opiate/opioid drugs suggest that these two actions are mediated by different receptors which appear not to include high affinity mu receptors.

  19. Dynamic study on cerebral perfusion of the pentylenetetrazol kindling cats by SPECT

    International Nuclear Information System (INIS)

    Hou Min; Liu Xingdang; Wang Kaiyan

    2004-01-01

    Objective: To learn the change of cerebral perfusion in the pentylenetetrazol kindling cats during the development of epilepsy. Methods: firstly, we performed 12 basic 99m Tc- ethyl cysteinate dimmer (ECD) SPECT as auto-control before the cats were made into epileptic models. Then, according to seizure level of epileptic model, SPECT was performed when the cats began to seizure in the form of facial tic(level 1), nodding spasm (level 2), limb tonic seizures (level 3) and generalized tonic-clonic seizures(level 4). At the same time, we detected the EEG at each level of seizure in order to contrast with SPECT findings. Results:There is no abnormal SPECT finding of cats before using PTZ. The SPECT at each level of kindling: hyperperfusion in forehead and basal ganglia at level 1; more evident hyperperfusion in forehead at level 2; the hyperperfusion in forehead being weakened and another hyperperfusion appearing in deep parietal lobe at level 3; the hyperperfusion in forehead disappearing and the hyperfusion in deep parietal lobe becoming more obvious and a hypoperfusion beside it appearing at level 4. As the time going on, the hyperperfusion disappeared completely and the hypoperfusion became more and more clear. The SPECT findings are coincided with EEG findings. Conclusion: 1. During the kindling of cats, a regional hyperperfusion appeared in the cats' brain: at the stage of focal seizure, the cerebral perfusion increased in forehead and ganglia; at the stage of generalized seizure, the hyperperfusion region gradually moved from forehead to deep parietal lobe. 2. Once the model animal was completely kindled, there would be a fixed hypoperfusion region instead, which may be the epileptic focus. (authors)

  20. Mycobacterium tuberculosis has diminished capacity to counteract redox stress induced by elevated levels of endogenous superoxide.

    Science.gov (United States)

    Tyagi, Priyanka; Dharmaraja, Allimuthu T; Bhaskar, Ashima; Chakrapani, Harinath; Singh, Amit

    2015-07-01

    Mycobacterium tuberculosis (Mtb) has evolved protective and detoxification mechanisms to maintain cytoplasmic redox balance in response to exogenous oxidative stress encountered inside host phagocytes. In contrast, little is known about the dynamic response of this pathogen to endogenous oxidative stress generated within Mtb. Using a noninvasive and specific biosensor of cytoplasmic redox state of Mtb, we for first time discovered a surprisingly high sensitivity of this pathogen to perturbation in redox homeostasis induced by elevated endogenous reactive oxygen species (ROS). We synthesized a series of hydroquinone-based small molecule ROS generators and found that ATD-3169 permeated mycobacteria to reliably enhance endogenous ROS including superoxide radicals. When Mtb strains including multidrug-resistant (MDR) and extensively drug-resistant (XDR) patient isolates were exposed to this compound, a dose-dependent, long-lasting, and irreversible oxidative shift in intramycobacterial redox potential was detected. Dynamic redox potential measurements revealed that Mtb had diminished capacity to restore cytoplasmic redox balance in comparison with Mycobacterium smegmatis (Msm), a fast growing nonpathogenic mycobacterial species. Accordingly, Mtb strains were extremely susceptible to inhibition by ATD-3169 but not Msm, suggesting a functional linkage between dynamic redox changes and survival. Microarray analysis showed major realignment of pathways involved in redox homeostasis, central metabolism, DNA repair, and cell wall lipid biosynthesis in response to ATD-3169, all consistent with enhanced endogenous ROS contributing to lethality induced by this compound. This work provides empirical evidence that the cytoplasmic redox poise of Mtb is uniquely sensitive to manipulation in steady-state endogenous ROS levels, thus revealing the importance of targeting intramycobacterial redox metabolism for controlling TB infection. Copyright © 2015 The Authors. Published by

  1. Angiotensin II-induced arterial thickening, fibrosis and stiffening involves elevated arginase function.

    Directory of Open Access Journals (Sweden)

    Anil Bhatta

    Full Text Available Arterial stiffness (AS is an independent risk factor for cardiovascular morbidity/mortality. Smooth muscle cell (SMC proliferation and increased collagen synthesis are key features in development of AS. Arginase (ARG, an enzyme implicated in many cardiovascular diseases, can compete with nitric oxide (NO synthase for their common substrate, L-arginine. Increased arginase can also provide ornithine for synthesis of polyamines via ornithine decarboxylase (ODC and proline/collagen via ornithine aminotransferase (OAT, leading to vascular cell proliferation and collagen formation, respectively. We hypothesized that elevated arginase activity is involved in Ang II-induced arterial thickening, fibrosis, and stiffness and that limiting its activity can prevent these changes.We tested this by studies in mice lacking one copy of the ARG1 gene that were treated with angiotensin II (Ang II, 4 weeks. Studies were also performed in rat aortic Ang II-treated SMC. In WT mice treated with Ang II, we observed aortic stiffening (pulse wave velocity and aortic and coronary fibrosis and thickening that were associated with increases in ARG1 and ODC expression/activity, proliferating cell nuclear antigen, hydroxyproline levels, and collagen 1 protein expression. ARG1 deletion prevented each of these alterations. Furthermore, exposure of SMC to Ang II (1 μM, 48 hrs increased ARG1 expression, ARG activity, ODC mRNA and activity, cell proliferation, collagen 1 protein expression and hydroxyproline content. Treatment with ABH prevented these changes.Arginase 1 is crucially involved in Ang II-induced SMC proliferation and arterial fibrosis and stiffness and represents a promising therapeutic target.

  2. Resistance of human erythrocytes containing elevated levels of vitamin E to radiation-induced hemolysis

    International Nuclear Information System (INIS)

    Brown, M.A.

    1983-01-01

    Human erythrocytes were isolated from the blood of healthy donors and then incubated in the presence of suspensions of alpha-tocopherol for 30 min at 37 degrees C. Unabsorbed tocopherol was removed by centrifugation using several washes of isotonic phosphate-buffered saline. Washed erythrocytes were resuspended to 0.05%. Hct and exposed to hemolyzing doses of 60 Co gamma radiation, and hemolysis was monitored continuously by light scattering at 700 nm in a recording spectrophotometer. The extent of hemolysis with time was sigmoid and data analysis was carried out on the time taken for 50% hemolysis to occur (t50%). The vitamin E content of erythrocytes was significantly elevated by the incubation procedure and resulted in the cells exhibiting a significantly increased resistance to hemolysis as reflected by the extended t50% values. Oral supplementation of 500 IU of vitamin E per day to eight normal human subjects for a period of 16 days also resulted in their washed erythrocytes exhibiting a significant increase in resistance to radiation-induced hemolysis. When comparing vitamin E incubated cells with control cells, both the dose-reducing factor (DRF) and the time for 50% hemolysis quotient (Qt50%) were observed to increase with increasing radiation dose

  3. GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction.

    Directory of Open Access Journals (Sweden)

    Raquel Montero

    Full Text Available We previously described increased levels of growth and differentiation factor 15 (GDF-15 in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21. To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction.We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA.Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM relative to healthy (350, 21 and myopathic (350, 32 controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4% and 92.3% (81.5%-97.9%, respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated.Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF

  4. Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

    2014-08-01

    Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

  5. Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers

    Directory of Open Access Journals (Sweden)

    Erick O. Hernández-Ochoa

    2017-01-01

    Full Text Available A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC—the sequential link between action potentials (AP, intracellular Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.. Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay; most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.

  6. Selected durability studies of geopolymer concrete with respect to carbonation, elevated temperature, and microbial induced corrosion

    Science.gov (United States)

    Badar, Mohammad Sufian

    This thesis reports a comprehensive study related to the experimental evaluation of carbonation in reinforced geopolymer concrete, the evaluation of geopolymer concretes at elevated temperature, and the resistance of geopolymer concrete to microbial induced corrosion (MIC). Carbonation: Reinforced concretes, made of geopolymer, prepared from two class F fly ashes and one class C fly ash, were subjected to accelerated carbonation treatment for a period of 450 days. Electrochemical, microstructure and pore structure examinations were performed to evaluate the effect of corrosion caused due to carbonation. GPC specimens prepared from class F fly ash exhibited lower corrosion rates by a factor of 21, and higher pH values (pH>12) when compared with concrete specimens prepared from class C Fly ash (GPCMN). Microstructure and pore characterization of GPC prepared using class F fly ash revealed lower porosity by a factor of 2.5 as compared with thier counterparts made using GPC-MN. The superior performace of GPC prepared with the class F fly ash could be attributed to the dense pore structure and formation of the protective layer of calcium and sodium alumino silicate hydrates (C/N-A-S-H) geopolymeric gels around the steel reinforcement. Elevated Temperature: Geopolymers are an emerging class of cementitious binders which possess a potential for high temperature resistance that could possibly be utilized in applications such as nozzles, aspirators and refractory linings. This study reports on the results of an investigation into the performance of a fly ash based geopolymer binder in high temperature environments. Geopolymer concrete (GPC) was prepared using eleven types of fly ashes obtained from four countries. High content alumina and silica sand was used in the mix for preparing GPC. GPC was subjected to thermal shock tests following ASTM C 1100-88. The GPC samples prepared with tabular alumina were kept at 1093° C and immediately quenched in water. GPC specimens

  7. The participation of elevated levels of cyclic GMP in the recovery from radiation-induced mitotic delay

    International Nuclear Information System (INIS)

    Daniel, J.W.; Oleinick, N.L.

    1984-01-01

    The levels of cyclic AMP and cyclic GMP have been measured in Physarum plasmodia before and after treatment with gamma-radiation, 2 mM caffeine, or combinations of the two agents compared to the length of the radiation-induced mitotic delay. Caffeine alone produces a rapid transient elevation of cyclic AMP and a slower delayed elevation of cyclic GMP. Irradiation elicits an immediate transient increase in cyclic AMP and a later cyclic GMP increase which accompanies or precedes the delayed mitosis. A composite pattern is produced by combinations of radiation and caffeine, a distinctive feature of which is an elevated level of cyclic GMP near the time of the radiation-delayed and caffeine-promoted mitosis. With pretreatment by caffeine, the least radiation-induced mitotic delay occurs when plasmodia are irradiated during the caffeine-elicited increase in cyclic GMP. The plasmodium becomes refractory to the reduction of mitotic delay by caffeine at approximately the time it becomes refractory to the further elevation of cyclic GMP by caffeine. The data support a role for cyclic AMP in the onset of and for cyclic GMP in the recovery from mitotic delay induced by ionizing radiation. (author)

  8. Effect of low frequency electrical stimulation on seizure-induced short- and long-term impairments in learning and memory in rats.

    Science.gov (United States)

    Esmaeilpour, Khadijeh; Sheibani, Vahid; Shabani, Mohammad; Mirnajafi-Zadeh, Javad

    2017-01-01

    Kindled seizures can impair learning and memory. In the present study the effect of low-frequency electrical stimulation (LFS) on kindled seizure-induced impairment in spatial learning and memory was investigated and followed up to one month. Animals were kindled by electrical stimulation of hippocampal CA1 area in a semi-rapid manner (12 stimulations per day). One group of animals received four trials of LFS at 30s, 6h, 24h, and 30h following the last kindling stimulation. Each LFS trial was consisted of 4 packages at 5min intervals. Each package contained 200 monophasic square wave pulses of 0.1ms duration at 1Hz. The Open field, Morris water maze, and novel object recognition tests were done 48h, 1week, 2weeks, and one month after the last kindling stimulation respectively. Kindled animals showed a significant impairment in learning and memory compared to control rats. LFS decreased the kindling-induced learning and memory impairments at 24h and one week following its application, but not at 2week or 1month after kindling. In the group of animals that received the same 4 trials of LFS again one week following the last kindling stimulation, the improving effect of LFS was observed even after one month. Obtained results showed that application of LFS in fully kindled animals has a long-term improving effect on spatial learning and memory. This effect can remain for a long duration (one month in this study) by increasing the number of applied LFS. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

    Science.gov (United States)

    Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

    2017-05-01

    Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

  10. Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis.

    Science.gov (United States)

    Park, Jeongho; Goergen, Craig J; HogenEsch, Harm; Kim, Chang H

    2016-03-01

    Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10(+) regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell-mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell-derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. Full characterization of multiphase, multimorphological kinetics in flow-induced crystallization of IPP at elevated pressure

    NARCIS (Netherlands)

    Troisi, E.M.; Caelers, H.J.M.; Peters, G.W.M.

    2017-01-01

    Understanding the complex crystallization behavior of isotactic polypropylene (iPP) in conditions comparable to those found in polymer processing, where the polymer melt experiences a combination of high shear rates and elevated pressures, is key for modeling and therefore predicting the final

  12. MK-801 induced amnesia for the elevated plus-maze in mice

    Czech Academy of Sciences Publication Activity Database

    Hliňák, Zdeněk; Krejčí, I.

    2002-01-01

    Roč. 131, 1-2 (2002), s. 221-225 ISSN 0166-4328 R&D Projects: GA ČR GA309/00/1644 Institutional research plan: CEZ:AV0Z5011922 Keywords : amnesia * elevated plus-maze * MK-801 Subject RIV: FH - Neurology Impact factor: 2.791, year: 2002

  13. A threshold for low-protein-diet-induced elevations in parathyroid hormone

    DEFF Research Database (Denmark)

    Kerstetter, J E; Svastisalee, C M; Caseria, D M

    2000-01-01

    We reported previously that lowering dietary protein intake in young healthy women to 0.7 g/kg depressed intestinal calcium absorption and was accompanied by elevations in parathyroid hormone (PTH). Moderate amounts of dietary protein (1.0 g/kg) did not appear to perturb calcium homeostasis....

  14. Self-reported health-related quality of life in kindergarten children : psychometric properties of the Kiddy-KINDL

    NARCIS (Netherlands)

    Villalonga-Olives, E.; Kiese-Himmel, C.; Witte, C.; Almansa, J.; Dusilova, I.; Hacker, K.; von Steinbuechel, N.

    Objectives: To assess the psychometric properties of the German self-reported version of the Kiddy-KINDL that measures Health Related Quality of Life (HRQoL) in 3 to 5 year old kindergarten children. Study design: The population of the study comprised baseline data of a longitudinal study whose main

  15. Social evaluation-induced amylase elevation and economic decision-making in the dictator game in humans.

    Science.gov (United States)

    Takahashi, Taiki; Ikeda, Koki; Hasegawa, Toshikazu

    2007-10-01

    Little is known regarding the relationship between social evaluation-induced neuroendocrine responses and generosity in game-theoretic situations. Previous studies demonstrated that reputation formation plays a pivotal role in prosocial behavior. This study aimed to examine the relationships between a social evaluation-induced salivary alpha-amylase (sAA) response and generosity in the dictator game. The relationship is potentially important in neuroeconomics of altruism and game theory. We assessed sAA and allocated money in the dictator game in male students with and without social evaluation. RESULTS Social evaluation-responders allocated significantly more money than controls; while there was no significant correlation between social evaluation-induced sAA elevation and the allocated money. Social evaluation significantly increases generosity in the dictator game, and individual differences in trait characteristics such as altruism and reward sensitivity may be important determinants of generosity in the dictator game task.

  16. Elevating your elevator talk

    Science.gov (United States)

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

  17. Drought-induced weakening of growth-temperature associations in high-elevation Iberian pines

    Czech Academy of Sciences Publication Activity Database

    Diego Galvan, J.; Büntgen, Ulf; Ginzler, Ch.; Grudd, H.; Gutierrez, E.; Labuhn, I.; Julio Camarero, J.

    2015-01-01

    Roč. 124, JAN (2015), s. 95-106 ISSN 0921-8181 Institutional support: RVO:67179843 Keywords : tree-ring chronologies * regional curve standardization * pinus-uncinata * european alps * spatial variability * summer temperatures * divergence problem * spanish pyrenees * fagus-sylvatica * large-scale * Climate change * Drought * Growth response * High-elevation forest * Pyrenees * Summer temperature Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 3.548, year: 2015

  18. Drought-induced weakening of growth-temperature associations in high-elevation Iberian pines

    Science.gov (United States)

    Diego Galván, J.; Büntgen, Ulf; Ginzler, Christian; Grudd, Håkan; Gutiérrez, Emilia; Labuhn, Inga; Julio Camarero, J.

    2015-01-01

    The growth/climate relationship of theoretically temperature-controlled high-elevation forests has been demonstrated to weaken over recent decades. This is likely due to new tree growth limiting factors, such as an increasing drought risk for ecosystem functioning and productivity across the Mediterranean Basin. In addition, declining tree growth sensitivity to spring temperature may emerge in response to increasing drought stress. Here, we evaluate these ideas by assessing the growth/climate sensitivity of 1500 tree-ring width (TRW) and 102 maximum density (MXD) measurement series from 711 and 74 Pinus uncinata trees, respectively, sampled at 28 high-elevation forest sites across the Pyrenees and two relict populations of the Iberian System. Different dendroclimatological standardization and split period approaches were used to assess the high- to low-frequency behavior of 20th century tree growth in response to temperature means, precipitation totals and drought indices. Long-term variations in TRW track summer temperatures until about 1970 but diverge afterwards, whereas MXD captures the recent temperature increase in the low-frequency domain fairly well. On the other hand summer drought has increasingly driven TRW along the 20th century. Our results suggest fading temperature sensitivity of Iberian high-elevation P. uncinata forest growth, and reveal the importance of summer drought that is becoming the emergent limiting factor of tree ring width formation in many parts of the Mediterranean Basin.

  19. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

    International Nuclear Information System (INIS)

    Fang, Zhong-Ze; Zhang, Dunfang; Cao, Yun-Feng; Xie, Cen; Lu, Dan; Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao; Chen, Qianming; Chen, Yu; Wang, Haina; Gonzalez, Frank J.

    2016-01-01

    Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4 + naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4 + naive T cells.

  20. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Zhong-Ze [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Department of Toxicology, School of Public Health, Tianjin Medical University, Tianjin (China); Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Zhang, Dunfang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Cao, Yun-Feng [Joint Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences and First Affiliated Hospital of Liaoning Medical University, Dalian (China); Xie, Cen [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Lu, Dan [Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, Tianjin (China); Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Chen, Qianming; Chen, Yu [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu (China); Wang, Haina [School of Pharmaceutical Sciences, Shandong University, Jinan (China); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

    2016-01-15

    Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4{sup +} naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4{sup +} naive T cells.

  1. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    Science.gov (United States)

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

  2. The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation.

    Science.gov (United States)

    Li, Xin; Lao, Yuanzhi; Zhang, Hong; Wang, Xiaoyu; Tan, Hongsheng; Lin, Zhixiu; Xu, Hongxi

    2015-04-11

    In a cytotoxicity screen in serum-free medium, Guttiferone F showed strong growth inhibitory effect against prostate cancer cells. Prostate cancer cells LNCaP and PC3 were treated with Guttiferone F in serum depleted medium. Sub-G1 phase distributions were estimated with flow cytometry. Mitochondrial disruption was observed under confocal microscope using Mitotracker Red staining. Gene and protein expression changes were detected by real-time PCR and Western blotting. Ca(2+) elevation was examined by Fluo-4 staining under fluorescence microscope. PC3 xenografts in mice were examined by immunohistochemical analysis. Guttiferone F had strong growth inhibitory effect against prostate cancer cell lines under serum starvation. It induced a significant increase in sub-G1 fraction and DNA fragmentation. In serum-free medium, Guttiferone F triggered mitochondria dependent apoptosis by regulating Bcl-2 family proteins. In addition, Guttiferone F attenuated the androgen receptor expression and phosphorylation of ERK1/2, while activating the phosphorylation of JNK and Ca(2+) flux. Combination of caloric restriction with Guttiferone F in vivo could increase the antitumor effect without causing toxicity. Guttiferone F induced prostate cancer cell apoptosis under serum starvation via Ca(2+) elevation and JNK activation. Combined with caloric restriction, Guttiferone F exerted significant growth inhibition of PC3 cells xenograft in vivo. Guttiferone F is therefore a potential anti-cancer compound.

  3. Cofilin phosphorylation is elevated after F-actin disassembly induced by Rac1 depletion

    DEFF Research Database (Denmark)

    Liu, Linna; Li, Jing; Zhang, Liwang

    2015-01-01

    Cytoskeletal reorganization is essential to keratinocyte function. Rac1 regulates cytoskeletal reorganization through signaling pathways such as the cofilin cascade. Cofilin severs actin filaments after activation by dephosphorylation. Rac1 was knocked out in mouse keratinocytes and it was found...... that actin filaments disassembled. In the epidermis of mice in which Rac1 was knocked out only in keratinocytes, cofilin phosphorylation was aberrantly elevated, corresponding to repression of the phosphatase slingshot1 (SSH1). These effects were independent of the signaling pathways for p21-activated kinase....../LIM kinase (Pak/LIMK), protein kinase C, or protein kinase D or generation of reactive oxygen species. Similarly, when actin polymerization was specifically inhibited or Rac1 was knocked down, cofilin phosphorylation was enhanced and SSH1 was repressed. Repression of SSH1 partially blocked actin...

  4. Rigor mortis development at elevated temperatures induces pale exudative turkey meat characteristics.

    Science.gov (United States)

    McKee, S R; Sams, A R

    1998-01-01

    Development of rigor mortis at elevated post-mortem temperatures may contribute to turkey meat characteristics that are similar to those found in pale, soft, exudative pork. To evaluate this effect, 36 Nicholas tom turkeys were processed at 19 wk of age and placed in water at 40, 20, and 0 C immediately after evisceration. Pectoralis muscle samples were taken at 15 min, 30 min, 1 h, 2 h, and 4 h post-mortem and analyzed for R-value (an indirect measure of adenosine triphosphate), glycogen, pH, color, and sarcomere length. At 4 h, the remaining intact Pectoralis muscle was harvested, and aged on ice 23 h, and analyzed for drip loss, cook loss, shear values, and sarcomere length. By 15 min post-mortem, the 40 C treatment had higher R-values, which persisted through 4 h. By 1 h, the 40 C treatment pH and glycogen levels were lower than the 0 C treatment; however, they did not differ from those of the 20 C treatment. Increased L* values indicated that color became more pale by 2 h post-mortem in the 40 C treatment when compared to the 20 and 0 C treatments. Drip loss, cook loss, and shear value were increased whereas sarcomere lengths were decreased as a result of the 40 C treatment. These findings suggested that elevated post-mortem temperatures during processing resulted in acceleration of rigor mortis and biochemical changes in the muscle that produced pale, exudative meat characteristics in turkey.

  5. Oviduct Binding and Elevated Environmental pH Induce Protein Tyrosine Phosphorylation in Stallion Spermatozoa

    NARCIS (Netherlands)

    Leemans, B.; Gadella, B.M.; Sostaric, E.; Nelis, H.; Stout, T.A.E.; Hoogewijs, M.; van Soom, A.

    2014-01-01

    Sperm-oviduct binding is an essential step in the capacitation process preparing the sperm for fertilization in several mammalian species. In many species, capacitation can be induced in vitro by exposing spermatozoa to bicarbonate, Ca2+, and albumin; however, these conditions are insufficient in

  6. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli

    NARCIS (Netherlands)

    Oei, N.Y.L.; Both, S.; van Heemst, D.; van der Grond, J.

    2014-01-01

    Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in

  7. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli

    OpenAIRE

    Oei, Nicole Y. L.; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

    2014-01-01

    Summary Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain’s ‘‘reward system’’, and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PETstudies indicate that the stress hormone cortisol may be crucial in the interaction between st...

  8. Elevated CO2 induces changes in the ecohydrological functions of forests - from mechanisms to models

    Science.gov (United States)

    Pötzelsberger, Elisabeth; Warren, Jeffrey M.; Wullschleger, Stan D.; Thornton, Peter E.; Norby, Richard J.; Hasenauer, Hubert

    2010-05-01

    Forests are known to considerably influence ecosystem water balance as a result of the many dynamic interactions between the plant physiology, morphology, phenology and other biophysical properties and environmental conditions. A changing climate will exert a new environmental setting for the forests and the biological feedbacks will be considerable. With the mechanistic ecosystem model Biome-BGC the dense net of cause-response relationships among carbon, nitrogen, water and energy cycles at a free-air CO2 enrichment (FACE) site in a North American deciduous broadleaved forest can be represented. At the Oak Ridge National Laboratory (ORNL) closed canopy sweetgum plantation elevated CO2 caused a decrease in stomatal conductance, and concurrent changes in daily transpiration were observed. This is in agreement with data from other FACE experiments. At the ORNL FACE site average transpiration reduction in a growing season was 10-16%, with 7-16% during mid summer, depending on the year. After parameterization of the model for this ecosystem the observed transpiration patterns could be well represented. Most importantly, the complete water budget at the site could be described and increased outflow could be observed (~15%). This yields crucial information for broader scale future water budget simulations. Changes in the water balance of deciduous forests will affect a wide range of ecosystem functions, from decomposition, over carbon and nutrient cycling to plant-plant competition and species composition.

  9. Risk of Microgravity-Induced Visual Impairment and Elevated Intracranial Pressure (VIIP)

    Science.gov (United States)

    Otto, Christian

    2011-01-01

    Eight cases identified, represent 23.5% of the 34 crewmembers flown on the ISS, with inflight visual changes and pre-to-postflight refractive changes. In some cases, the changes were transient while in others they are persistent with varying degrees of visual impairment. (1) Decreased intraocular pressure (IOP) postflight was observed in 3 cases. (2) Fundoscopic exams revealed postflight findings of choroidal folds in 4 cases, optic disc edema in 5 cases and presence of cotton wool spots in 3 cases. (3) Optical coherence tomography (OCT) confirmed findings of choroidal folds and disc edema and documented retinal nerve fiber layer thickening (4 cases). (4) Findings from MRI examinations showed posterior globe flattening (5 cases) and optic nerve sheath distension (6 cases). (5) Opening cerebrospinal fluid (CSF) pressure was elevated in 4 cases postflight reflecting raised intracranial pressure. While the etiology remains unknown, hypotheses speculate that venous insufficiency or hypertension in the brain caused by cephalad fluid shifts during spaceflight are possible mechanisms for ocular changes in astronauts.

  10. Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

    Directory of Open Access Journals (Sweden)

    Hagman R

    2006-03-01

    Full Text Available Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite, progesterone and oestradiol (E2-17β levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

  11. Artesunate prevents rats from the clozapine-induced hepatic steatosis and elevation in plasma triglycerides

    Directory of Open Access Journals (Sweden)

    Li Y

    2017-09-01

    Full Text Available Yanmei Li,1,2 Ruibing Su,3 Shuqin Xu,2 Qingjun Huang,1 Haiyun Xu1,2 1The Mental Health Center, Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 3Department of Forensics and Pathology, Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China Abstract: Clozapine is an atypical antipsychotic with therapeutic efficacy in treatment-resistant schizophrenia patients and low incidence of extrapyramidal side effects. However, the use of clozapine has been limited by its adverse effects on metabolism. Artesunate is a semisynthetic derivative of artemisinin and was shown to decrease the plasma cholesterol and triglyceride in rabbits and rats in recent studies. The aim of this study was to examine possible effects of artesunate on the clozapine-induced metabolic alterations in rats given saline, clozapine, artesunate, or clozapine plus artesunate for 6 weeks. The clozapine group showed significantly high plasma levels of triglyceride, hepatic steatosis, and fibrosis along with high levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase compared to the saline group. But the treatment had no effect on weight gain and caused no hyperglycemia, hyperinsulinemia, and behavioral changes in the rats. More significantly, these clozapine-induced changes were not seen in rats coadministered with clozapine plus artesunate. These results added evidence supporting psychiatrists to try add-on treatment of artesunate in schizophrenia patients to ameliorate clozapine-induced adverse metabolic effects. Keywords: artesunate, clozapine, dyslipidemia, hepatic steatosis, schizophrenia 

  12. Low-frequency electrical stimulation enhances the effectiveness of phenobarbital on GABAergic currents in hippocampal slices of kindled rats.

    Science.gov (United States)

    Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi-Chameh, Homeira; Ghafouri, Samireh; Sheibani, Vahid; Mirnajafi-Zadeh, Javad

    2016-08-25

    Low frequency stimulation (LFS) has been proposed as a new approach in the treatment of epilepsy. The anticonvulsant mechanism of LFS may be through its effect on GABAA receptors, which are the main target of phenobarbital anticonvulsant action. We supposed that co-application of LFS and phenobarbital may increase the efficacy of phenobarbital. Therefore, the interaction of LFS and phenobarbital on GABAergic inhibitory post-synaptic currents (IPSCs) in kindled and control rats was investigated. Animals were kindled by electrical stimulation of basolateral amygdala in a semi rapid manner (12 stimulations/day). The effect of phenobarbital, LFS and phenobarbital+LFS was investigated on GABAA-mediated evoked and miniature IPSCs in the hippocampal brain slices in control and fully kindled animals. Phenobarbital and LFS had positive interaction on GABAergic currents. In vitro co-application of an ineffective pattern of LFS (100 pulses at afterdischarge threshold intensity) and a sub-threshold dose of phenobarbital (100μM) which had no significant effect on GABAergic currents alone, increased the amplitude and area under curve of GABAergic currents in CA1 pyramidal neurons of hippocampal slices significantly. Interestingly, the sub-threshold dose of phenobarbital potentiated the GABAergic currents when applied on the hippocampal slices of kindled animals which received LFS in vivo. Post-synaptic mechanisms may be involved in observed interactions. Obtained results implied a positive interaction between LFS and phenobarbital through GABAA currents. It may be suggested that a combined therapy of phenobarbital and LFS may be a useful manner for reinforcing the anticonvulsant action of phenobarbital. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Comparison of benzodiazepine receptor and regional cerebral blood flow imagings of epileptiform foci in hippocampal kindled rabbits

    International Nuclear Information System (INIS)

    Kurokawa, Kenzo

    1993-01-01

    To compare the benzodiazepine (Bz) receptor imaging and regional cerebral blood flow (rCBF) imaging in the detection of epileptic foci, the distribution pattern of the Bz receptor and rCBF in hippocampal kindled rabbits was examined by a double tracer autoradiography using ethyl 7-[ 125 I]-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1, 5-a][1,4] benzodiazepine-3-carboxylate ( 125 I-Ro 16-0154) and 99m Tc-hexamethyl-propyleneamine oxime ( 99m Tc-HMPAO). In visual and quantitative analyses, 125 I-Ro 16-0154 accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled CA1 region mimicking a primary epileptic focus. 125 I-Ro 16-0154 accumulation was moderately decreased in the ipsilateral temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99m Tc-HMPAO accumulation was found to be decreased in the ipsilateral CA1, frontal, temporal and dentate gyri. However, the decrease was much more slight and less extensive than that in 125 I-Ro 16-0154 accumulation. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy. (author)

  14. Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors.

    Science.gov (United States)

    Wang, Z; Liu, Q; Zhang, R; Liu, S; Xia, Z; Hu, Y

    2009-11-10

    The purpose of this work is to study the effect of catalpol, an iridoid from Rehmannia glutinosa on neurodegenerative changes induced by beta-amyloid peptide Abeta(25-35) or Abeta(25-35)+ibotenic acid and the underlying mechanism. Results showed that catalpol significantly improved the memory deficits in the neurodegenerative mouse model produced by injection of Abeta(25-35)+ibotenic acid to the nucleus magnocellularis basalis, yet it is neither a cholinesterase inhibitor nor a muscarinic (M) receptor agonist. Instead, the choline acetyl transferase (ChAT) activity and the M receptor density in brain were significantly decreased in the model mice and catalpol could significantly elevate their levels. Furthermore, the brain-derived neurotrophic factor (BDNF) content in brain was significantly decreased in the model mice and catalpol elevated it to normal level (83%+/-3% and 102%+/-2% of normal respectively). There is a significant positive correlation between BDNF content and memory. Primary culture of forebrain neurons revealed that aggregated Abeta(25-35) induced significant decrease of ChAT positive neuron number, neurite outgrowth length, and M receptor density, while catalpol added to the culture medium 2 h prior to Abeta addition showed significant dose dependent protective effect. Notably, 24 h and 48 h after the addition of Abeta to the cultured cells, the BDNF mRNA level in the neurons decreased to 76%+/-7% and 66%+/-3% of control without catalpol treatment, but became 128%+/-17% and 131%+/-23% of control with catalpol treatment. When the action of BDNF was inhibited by k252a in the cultured neurons, the protective effect of catalpol was completely (neurite outgrowth length) or partially (ChAT positive neuron number and the M receptor density) abolished. Taken together, catalpol improves memory and protects the forebrain neurons from neurodegeneration through increasing BDNF expression. Whether catalpol could reverse the neurodegenerative changes already

  15. The Impact of Central and Peripheral Cyclooxygenase Enzyme Inhibition on Exercise-Induced Elevations in Core Body Temperature.

    Science.gov (United States)

    Veltmeijer, Matthijs T W; Veeneman, Dineke; Bongers, Coen C C W; Netea, Mihai G; van der Meer, Jos W; Eijsvogels, Thijs M H; Hopman, Maria T E

    2017-05-01

    Exercise increases core body temperature (T C ) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 (IL-6) may also contribute to the rise in T C by increasing the hypothalamic temperature set point. This study investigated whether the exercise-induced increase in T C is partly caused by an altered hypothalamic temperature set point. Fifteen healthy, active men age 36 ± 14 y were recruited. Subjects performed submaximal treadmill exercise in 3 randomized test conditions: (1) 400 mg ibuprofen and 1000 mg acetaminophen (IBU/APAP), (2) 1000 mg acetaminophen (APAP), and (3) a control condition (CTRL). Acetaminophen and ibuprofen were used to block the effect of IL-6 at a central and peripheral level, respectively. T C , skin temperature, and heart rate were measured continuously during the submaximal exercise tests. Baseline values of T C , skin temperature, and heart rate did not differ across conditions. Serum IL-6 concentrations increased in all 3 conditions. A significantly lower peak T C was observed in IBU/APAP (38.8°C ± 0.4°C) vs CTRL (39.2°C ± 0.5°C, P = .02) but not in APAP (38.9°C ± 0.4°C) vs CTRL. Similarly, a lower ΔT C was observed in IBU/APAP (1.7°C ± 0.3°C) vs CTRL (2.0°C ± 0.5°C, P exercise compared with a CTRL. This observation suggests that a prostaglandin-E2-induced elevated hypothalamic temperature set point may contribute to the exercise-induced rise in T C .

  16. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

    International Nuclear Information System (INIS)

    Dearth, Robert K; Kuiatse, Isere; Wang, Yu-Fen; Liao, Lan; Hilsenbeck, Susan G; Brown, Powel H; Xu, Jianming; Lee, Adrian V

    2011-01-01

    Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm 3 . For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Using the first transgenic animal model to

  17. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

    Science.gov (United States)

    Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

    2014-01-01

    Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, pcortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but they may ultimately be more vulnerable to increased reward

  18. Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice

    Directory of Open Access Journals (Sweden)

    Zhen Zhang

    2016-01-01

    Full Text Available The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1 of hippocampus and mediodorsal thalamus (MDT in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine’s rank standard was employed to classify the stage of behavioral responses (stage 1~5. The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1 High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2 In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

  19. Cytokinin-induced cell death is associated with elevated expression of alternative oxidase in tobacco BY-2 cells.

    Science.gov (United States)

    Mlejnek, Petr

    2013-10-01

    N(6)-benzyladenine (BA) and N(6)-benzyladenosine ([9R]BA) induce massive production of reactive oxygen species (ROS) that is eventually followed by a loss of cell viability in tobacco BY-2 cells (Mlejnek et al. Plant Cell Environ 26:1723-1735, 2003, Plant Sci 168:389-395, 2005). Results presented in this work suggest that the main sources of ROS are likely mitochondria and that the maintenance of the mitochondrial transmembrane potential is crucial for ROS production in cytokinin-treaded BY-2 cells. Therefore, the possible involvement of alternative oxidase (AOX) in cell death process induced by BA and [9R]BA was studied. About three- to fourfold increase in mRNA levels of AOX1 was observed a few hours after the BA and [9R]BA addition into the growth medium. The elevated expression of AOX1 mRNA could be prevented by adding adenine and adenosine which simultaneously reduced the cytotoxic effects of BA and [9R]BA, respectively. N(6)-benzyladenine 7-β-D-glucoside ([7G]BA) which is a common non-toxic metabolite of BA and [9R]BA did not affect the AOX1 mRNA expression. Although AOX1 seemed to be involved in protection of BY-2 cells against the abiotic stress induced by BA and [9R]BA, the results do not support the idea that it protects cells from death exclusively by scavenging of reactive oxygen species. Indeed, N-propyl gallate, an inhibitor of AOX, decreased cell survival despite it concomitantly decreased the ROS production. This finding is in contrast to the effect of salicylhydroxamic acid, another well-known inhibitor of AOX, which also increased the number of dying cells while it increased the ROS production.

  20. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

    Science.gov (United States)

    Kechagias, S; Ernersson, A; Dahlqvist, O; Lundberg, P; Lindström, T; Nystrom, F H

    2008-05-01

    To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Prospective interventional study with parallel control group. University Hospital of Linköping, Sweden. 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

  1. Elevated androgen levels induce hyperinsulinemia through increase in Ins1 transcription in pancreatic beta cells in female rats.

    Science.gov (United States)

    Mishra, Jay S; More, Amar S; Kumar, Sathish

    2018-01-22

    Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test. DHT females had no change in islet number, size and beta cell proliferation/apoptosis but exhibited significant mitochondrial dysfunction (higher ADP/ATP ratio, decreased mtDNA copy number, increased reactive oxygen production and downregulation of mitochondrial biogenesis) and enhanced glucose-stimulated insulin secretion. Ins expression was increased in DHT islets. In vitro incubation of control islets with DHT dose-dependently stimulated Ins transcription. Analysis of Ins1 gene revealed a putative androgen responsive element in the promoter. Chromatin-immunoprecipitation assays showed that androgen receptors bind to this element in response to DHT stimulation. Furthermore, reporter assays showed that the promoter element is highly responsive to androgens. Insulin stimulated glucose uptake in skeletal muscle was decreased with associated decrease in IRβ expression in DHT females. Our studies identified a novel androgen-mediated mechanism for the control of Ins expression via transcriptional regulation providing a molecular mechanism linking elevated androgens and hyperinsulemia. Decreased IRβ expression in the skeletal muscles may contribute, in part, to glucose intolerance in this model. © The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of

  2. Improvement in hippocampal kindling analysis through computational processing data Aprimorando a análise do modelo de kindling hipocampal com o auxílio de processamento computacional

    Directory of Open Access Journals (Sweden)

    Joacir Graciolli Cordeiro

    2009-09-01

    Full Text Available The kindling phenomenon is classically investigated in epileptology research. The present study aims to provide further information about hippocampal kindling through computational processing data. Adult Wistar rats were implanted with dorsal hippocampal and frontal neocortical electrodes to perform the experiment. The processing data was obtained using the Spike2 and Matlab softwares. An inverse relationship between the number of "wet dog shakes" and the Racine's motor stages development was found. Moreover it was observed a significant increase in the afterdischarge (AD duration and its frequency content. The highest frequencies were, however, only reached at the beginning of behavioral seizures. During the primary AD, fast transients (ripples were registered in both hippocampi superimposed to slower waves. This experiment highlights the usefulness of computational processing applied to animal models of temporal lobe epilepsy and supports a relevant role of the high frequency discharges in temporal epileptogenesis.O fenômeno de kindling é classicamente utilizado no campo da epileptologia experimental. Este trabalho objetiva aprofundar a análise do modelo kindling hipocampal através de processamento computacional. Ratos wistar adultos receberam eletrodos hipocampais dorsais e neocorticais frontais para a realização do experimento. O processamento dos dados encontrados foi realizado pelos softwares Matlab e Spike2. Encontrou-se uma relação inversa entre wet dog shakes e o desenvolvimento dos estágios motores de Racine. A duração e o conteúdo de freqüência das pós-descargas hipocampais aumentaram durante o processo, sendo observadas descargas de alta freqüência (ripples em ambos os hipocampos durante as pós-descargas primárias, superimpostas a ondas lentas. As mais altas freqüências, entretanto, foram apenas atingidas com o início das crises epilépticas. A utilização de sistemas computacionais para a confecção e an

  3. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.

    Science.gov (United States)

    Clark, Erica S; Flannery, Brenna M; Gardner, Elizabeth M; Pestka, James J

    2015-10-19

    Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  4. High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses

    Directory of Open Access Journals (Sweden)

    Erica S. Clark

    2015-10-01

    Full Text Available Deoxynivalenol (DON, a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos and adult (3 mos mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg and dietary (1, 2.5, 10 ppm DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

  5. Measurement equivalence of the KINDL questionnaire across child self-reports and parent proxy-reports: a comparison between item response theory and ordinal logistic regression.

    Science.gov (United States)

    Jafari, Peyman; Sharafi, Zahra; Bagheri, Zahra; Shalileh, Sara

    2014-06-01

    Measurement equivalence is a necessary assumption for meaningful comparison of pediatric quality of life rated by children and parents. In this study, differential item functioning (DIF) analysis is used to examine whether children and their parents respond consistently to the items in the KINDer Lebensqualitätsfragebogen (KINDL; in German, Children Quality of Life Questionnaire). Two DIF detection methods, graded response model (GRM) and ordinal logistic regression (OLR), were applied for comparability. The KINDL was completed by 1,086 school children and 1,061 of their parents. While the GRM revealed that 12 out of the 24 items were flagged with DIF, the OLR identified 14 out of the 24 items with DIF. Seven items with DIF and five items without DIF were common across the two methods, yielding a total agreement rate of 50 %. This study revealed that parent proxy-reports cannot be used as a substitute for a child's ratings in the KINDL.

  6. Assessing health-related quality of life in adolescents: some psychometric properties of the first Norwegian version of KINDL.

    Science.gov (United States)

    Helseth, Sølvi; Lund, Thorleif

    2005-06-01

    The study presented in this paper is part of a larger Norwegian investigation among adolescents, where the overall aim is to develop methods to promote their quality of life (QoL), to discover risk factors or threats to adolescents' well-being, and finally to prevent the negative effects of such factors. An adequate generic health-related quality of life (HR-QoL) measure is therefore needed. However, only a limited number of well validated instruments that measure HR-QoL in adolescents exist, and to date only a few has been translated into Norwegian. The purpose of this study was therefore to examine some psychometric properties of the first Norwegian version of a simple, generic, German HR-QoL questionnaire for adolescents, KINDL. The instrument consists of 24-items, distributed in six subscales, which correspond to six domains of adolescents' HR-QoL. Based on a sample of 239 healthy adolescents, the internal consistency reliability is satisfactory for both the total scale and the subscales of 'Self-esteem and Family', fairly good for the 'Emotional' subscale, but lower for the subscales 'Physical', 'Friends' and 'School'. Factor analyses, which concerns construct validity, yielded interpretable solutions. The factor solutions at item level were interpreted to be in line with the original subscales, while factor analysis at subscale level indicated that a common QoL core is involved. To conclude, the Norwegian version of KINDL appears, in general, to be a psychometrically acceptable method of measuring HR-QoL in healthy adolescents. However, the alpha-values of some of the subscales are not optimal, and these scales should be used with caution in research and profession. Still KINDL-N is considered suitable for screening purposes in the public health area and especially within school-health care.

  7. Acute, food-induced moderate elevation of plasma uric acid protects against hyperoxia-induced oxidative stress and increase in arterial stiffness in healthy humans.

    Science.gov (United States)

    Vukovic, Jonatan; Modun, Darko; Budimir, Danijela; Sutlovic, Davorka; Salamunic, Ilza; Zaja, Ivan; Boban, Mladen

    2009-11-01

    We examined the effects of acute, food-induced moderate increase of plasma uric acid (UA) on arterial stiffness and markers of oxidative damage in plasma in healthy males exposed to 100% normobaric oxygen. Acute elevation of plasma UA was induced by consumption of red wine, combination of ethanol and glycerol, or fructose. By using these beverages we were able to separate the effects of UA, wine polyphenols and ethanol. Water was used as a control beverage. Ten males randomly consumed test beverages in a cross-over design over the period of 4 weeks, one beverage per week. They breathed 100% O(2) between 60(th) and 90(th)min of the 4-h study protocol. Pulse wave augmentation index (AIx) at brachial and radial arteries, plasma antioxidant capacity (AOC), thiobarbituric acid-reactive substances (TBARS), lipid hydroperoxides (LOOH) assessed by xylenol orange method, UA and blood ethanol concentrations were determined before and 60, 90, 120, 150 and 240 min after beverage consumption. Consumption of the beverages did not affect the AIx, TBARS or LOOH values during 60 min before exposure to hyperoxia, while AOC and plasma UA increased except in the water group. Significant increase of AIx, plasma TBARS and LOOH, which occurred during 30 min of hyperoxia in the water group, was largely prevented in the groups that consumed red wine, glycerol+ethanol or fructose. In contrast to chronic hyperuricemia, generally considered as a risk factor for cardiovascular diseases and metabolic syndrome, acute increase of UA acts protectively against hyperoxia-induced oxidative stress and related increase of arterial stiffness in large peripheral arteries.

  8. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been...... screening model for AEDs. To this end, we compared the in vitro and in vivo pharmacological profile of several selected AEDs (phenobarbital, phenytoin, tiagabine, fosphenytoin, valproate, and carbamazepine) along with citalopram using the PTZ-kindled model and brain slices from naïve, saline...

  9. Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

    DEFF Research Database (Denmark)

    Hansen, Suzanne L; Nielsen, Ane H; Knudsen, Katrine E

    2009-01-01

    The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure...... activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does...

  10. Inhibition of neutral sphingomyelinase decreases elevated levels of inducible nitric oxide synthase and apoptotic cell death in ocular hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Aslan, Mutay, E-mail: mutayaslan@akdeniz.edu.tr [Department of Medical Biochemistry, Akdeniz University Faculty of Medicine, Antalya (Turkey); Basaranlar, Goksun [Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya (Turkey); Unal, Mustafa [Department of Ophthalmology, Akdeniz University Faculty of Medicine, Antalya (Turkey); Ciftcioglu, Akif [Department of Pathology, Akdeniz University Faculty of Medicine, Antalya (Turkey); Derin, Narin [Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya (Turkey); Mutus, Bulent [Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario (Canada)

    2014-11-01

    Endoplasmic reticulum (ER) stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS2) have been implicated in the pathogenesis of neuronal retinal cell death in ocular hypertension. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression, hence this study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on retinal NOS2 levels, ER stress, apoptosis and visual evoked potentials (VEPs) in a rat model of elevated intraocular pressure (EIOP). NOS2 expression and retinal protein nitration were significantly greater in EIOP and significantly decreased with N-SMase inhibition. A significant increase was observed in retinal ER stress markers pPERK, CHOP and GRP78 in EIOP, which were not significantly altered by N-SMase inhibition. Retinal TUNEL staining showed increased apoptosis in all EIOP groups; however N-SMase inhibition significantly decreased the percent of apoptotic cells in EIOP. Caspase-3, -8 and -9 activities were significantly increased in EIOP and returned to baseline levels following N-SMase inhibition. Latencies of all VEP components were significantly prolonged in EIOP and shortened following N-SMase inhibition. Data confirm the role of nitrative injury in EIOP and highlight the protective effect of N-SMase inhibition in EIOP via down-regulation of NOS2 levels and nitrative stress. - Highlights: • Inhibition of N-SMase decreases NOS2 levels in ocular hypertension. • Inhibition of N-SMase decreases protein nitration in ocular hypertension. • Inhibition of N-SMase decreases caspase activation in ocular hypertension. • Inhibition of N-SMase decreases apoptosis in ocular hypertension.

  11. A Case Study of Mobile Technology-enabled English Language Learning: the Amazon Kindle e-Reader Initiative in Palestine

    Directory of Open Access Journals (Sweden)

    Khitam Yousuf Shraim

    2014-06-01

    Full Text Available The proliferation of increasingly interactive e-reader devices such as the Amazon Kindle represents an opportunity to explore their evolving pedagogical value. This study aims to investigate how use of the Kindle can enhance individuals’ English language learning—more specifically their attitudes, reading comprehension, vocabulary development and pronunciation performance—in the context of informal and lifelong learning in Palestine, and to explore the further potential of scaling up the use of e-readers at a national level. At the piloting stage of this initiative, the study operated at two levels (micro and meso of the M3 evaluation framework. Mixed methods were used: qualitative data were obtained through a case study of the practices and perceptions of two teachers in two classrooms in the Qalqilia center and quantitative data were collected through a survey of 114 learners. The study shows that the Kindle’s technological affordances are effective in creating a flexible, authentic and interactive environment for English language learning, provided that teachers change their teaching methods to take full advantage of the features of mobile technologies to create innovative learning approaches aligned with the needs of the e-generation. It was also found that despite some concerns with the usability issue, attitudes towards learning English changed positively and learners’ vocabulary and pronunciation improved.

  12. Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP

    DEFF Research Database (Denmark)

    Sørensen, Andreas T; Nikitidou, Litsa; Ledri, Marco

    2009-01-01

    (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY...... is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected...... injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP...

  13. Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M. [West Virginia University School of Medicine, Morgantown (United States)

    2016-06-15

    Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date.

  14. iPhone, Android, or Kindle: The Emma S. Clark Memorial Library Has an App for That and So Can You

    Science.gov (United States)

    Johnson, Bob; Gutmann, Ted

    2013-01-01

    If you are like the millions of people buying the latest smartphone, iPhone 5, or Samsung Galaxy S III, your local library should have something to offer you. The Emma S. Clark Memorial Library, for one, has an app for that! Dubbed "Emma Mobile," the library's application works with iOS (Apple), Android (Google), and Amazon Kindle Fire…

  15. Diet-induced obesity elevates colonic TNF-α in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer.

    Science.gov (United States)

    Liu, Zhenhua; Brooks, Ryan S; Ciappio, Eric D; Kim, Susan J; Crott, Jimmy W; Bennett, Grace; Greenberg, Andrew S; Mason, Joel B

    2012-10-01

    Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3β was elevated in the colonic mucosa of obese mice (P<.02). Moreover, β-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P<.05), as was the expression of a downstream target gene, c-myc (P<.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

    Science.gov (United States)

    Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

    2015-10-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.

  17. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

    Science.gov (United States)

    Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

    2015-01-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633

  18. Cycling-induced degradation of LiCoO2 thin-film cathodes at elevated temperature

    International Nuclear Information System (INIS)

    Van Sluytman, J.S.; West, W.C.; Whitacre, J.F.; Alamgir, F.M.; Greenbaum, S.G.

    2006-01-01

    The cycle life of LiCoO 2 -based all solid-state thin-film cells has been studied at room temperature, and at elevated temperatures of 50, 100, and 150 deg. C. X-ray diffraction, as well as Raman analysis, has been used to complement the electrochemical data in examining structural and chemical changes. XRD and Raman spectroscopy data indicate that elevated temperature soaks of the thin-film batteries in the quiescent state causes no discernable changes in the LiCoO 2 cathode layer. However, when the thin-film batteries are cycled at elevated temperatures, decreases in average grain size of the LiCoO 2 film occur with dramatic concomitant charge and discharge capacity loss

  19. Cycling-induced degradation of LiCoO{sub 2} thin-film cathodes at elevated temperature

    Energy Technology Data Exchange (ETDEWEB)

    Van Sluytman, J.S.; Alamgir, F.M.; Greenbaum, S.G. [Department of Physics and Astronomy, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10021 (United States); West, W.C.; Whitacre, J.F. [Electrochemical Technologies Group, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States)

    2006-04-01

    The cycle life of LiCoO{sub 2}-based all solid-state thin-film cells has been studied at room temperature, and at elevated temperatures of 50, 100, and 150{sup o}C. X-ray diffraction, as well as Raman analysis, has been used to complement the electrochemical data in examining structural and chemical changes. XRD and Raman spectroscopy data indicate that elevated temperature soaks of the thin-film batteries in the quiescent state causes no discernible changes in the LiCoO{sub 2} cathode layer. However, when the thin-film batteries are cycled at elevated temperatures, decreases in average grain size of the LiCoO{sub 2} film occur with dramatic concomitant charge and discharge capacity loss. (author)

  20. Elevated CO2 and warming induce substantial and persistent declines in forage quality irrespective of warming in mixed grass prairie

    Science.gov (United States)

    Increasing atmospheric [CO2] and temperature are expected to affect the productivity, species composition, biogeochemistry, and therefore the quantity and quality of forage available to herbivores in rangeland ecosystems. Both elevated CO2 (eCO2) and warming affect plant tissue chemistry through mul...

  1. Modificação do metodo "kindling" para obtenção de status epilepticus experimental em ratos

    Directory of Open Access Journals (Sweden)

    Carlos J. Reis de Campos

    1980-03-01

    Full Text Available Foi utilizada em nova espécie animal (ratos, uma modificação do método "kindling", introduzida por Taber e col. (1977 para obtenção de status epilepticus experimental. Para isso foram implantados mediante cirurgia estereotáxica, eletrodos duplos, torcidos no hipocampo dorsal de 12 ratos machos albinos. Esses animais foram submetidos, após uma semana de pós-operatório, a 1 segundo de estimulação elétrica de baixa intensidade em forma intermitente, um estímulo por minuto durante 2 horas, desenvolvendo-se em prazo de 30 minutos um estado de epilepsia eletrográfica e comportamental duradoura. Vários padrões de descargas epilépticas eletrográficas foram observados bem como manifestações convulsivas tônico-clônicas. Os animais que foram submetidos a novas sessões de estimulação após 7 e 14 dias mostraram aumento de atividade epiléptica demonstrando uma modificação plástica do hipocampo do rato submetido a estimulação elétrica a qual perdura no tempo. O método permite a obtenção de "kindling" em tempo bem mais curto (horas, comparativamente às técnicas anteriormente descritas (dias, tornando-se um promissor modelo de epilepsia para testes de drogas anticonvulsivantes e para o estudo dos mecanismos fisiopatológicos e bioquímicos envolvidos na descarga epiléptica.

  2. Occurrence and exposure to polycyclic aromatic hydrocarbons in kindling-free-charcoal grilled meat products in Taiwan.

    Science.gov (United States)

    Kao, Tsai Hua; Chen, Shaun; Huang, Chun Wei; Chen, Chia Ju; Chen, Bing Huei

    2014-09-01

    This study aimed to determine the contents of 16 PAHs in kindling-free-charcoal grilled meat and seafood products by GC-MS coupled with a QuEChERS method, and estimate the potential risk associated with consumption of those products in Taiwan. Results showed that the total PAHs contents ranged from 6.3±0.9 to 238.8±8.3 ng/g in poultry meat, 0.1±0.0-547.5±12.2 ng/g in red meat, and 6.6±1.4-249.7±6.4 ng/g in seafood products. Among various PAHs, the highly carcinogenic benzo[a]pyrene was detected in chicken breast grilled at 84°C (30 min), chicken heart at 100°C (26 min), chicken drumstick at 74°C (20 min), duck drumstick at 85°C (40 min), and lamb steak at 88°C (12 min), with its level amounting to 1.3±0.0, 2.4±0.1, 4.0±1.3, 3.1±0.0, and 5.8±0.5 ng/g, respectively. The generation of PAHs was associated with grilling time, temperature and fat content. Risk assessment of dietary exposure to PAHs revealed toxicity equivalent to range from ND - 6.174±0.505 μg/g and margin of exposure was >10,000, which agreed with the EFSA's definition of low public health concern. The lifelong average daily PAHs intake was higher for adults than for elderly people in Taiwan, however, consumption of kindling-free-charcoal grilled meat should not be a public health concern based on cancer risk potency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Brain levels of N-acylethanolamine phospholipids in mice during pentylenetetrazol-induced seizure

    DEFF Research Database (Denmark)

    Moesgaard, B.; Hansen, H.H.; Petersen, G.

    2003-01-01

    occur in response to seizure activity. Therefore, we investigated the effect of pentylenetetrazol (PTZ)-induced seizures in PTZ-kindled mice on the level of NAPE in the brain. Male NMRI mice were kindled with PTZ injections 3 times/wk, thereby developing clonic seizures in response to PTZ. Mice were...... killed within 30 min after the clonic seizure on the test day (12th injection) and the brains were collected. Eight species of NAPE were analyzed as the glycerophospho-N-acylethanolamines by high-performance liquid chromatography-coupled electrospray ionization mass spectrometry. No effect of the PTZ...... accumulate during seizure....

  4. Lactic Acid is Elevated in Idiopathic Pulmonary Fibrosis and Induces Myofibroblast Differentiation Via pH-Dependent Activation of Transforming Growth Factor-β

    Energy Technology Data Exchange (ETDEWEB)

    Kottman, R. M.; Kulkarni, Ajit A.; Smolnycki, Katie A.; Lyda, Elizabeth; Dahanayake, Thinesh; Salibi, Rami; Honnons, Sylvie; Jones, Carolyn; Isern, Nancy G.; Hu, Jian Z.; Nathan, Steven D.; Grant, Geraldine; Phipps, Richard P.; Sime, Patricia J.

    2012-10-15

    Rationale: Idiopathic pulmonary fibrosis (IPF) is a complex disease for which the pathogenesis is poorly understood. In this study, we identified lactic acid as a metabolite that is elevated in the lung tissue of patients with IPF. Objectives: This study examines the effect of lactic acid on myofibroblast differentiation and pulmonary fibrosis. Methods:We used metabolomic analysis to examine cellular metabolism in lung tissuefrom patients with IPFanddeterminedthe effects of lactic acid and lactate dehydrogenase-5 (LDH5) overexpression on myofibroblast differentiation and transforming growth factor (TGF)-b activation in vitro. Measurements and Main Results: Lactic acid concentrations from healthy and IPF lung tissue were determined by nuclear magnetic resonance spectroscopy; a-smooth muscle actin, calponin, and LDH5 expression were assessed by Western blot of cell culture lysates. Lactic acid and LDH5 were significantly elevated in IPF lung tissue compared with controls. Physiologic concentrations of lactic acid induced myofibroblast differentiation via activation of TGF-b. TGF-b induced expression of LDH5 via hypoxia-inducible factor 1a (HIF1a). Importantly, overexpression of both HIF1a and LDH5 in human lung fibroblasts induced myofibroblast differentiation and synergized with low dose TGF-b to induce differentiation. Furthermore, inhibition of both HIF1a and LDH5 inhibited TGF-b–induced myofibroblast differentiation. Conclusions: We have identified the metabolite lactic acid as an important mediator of myofibroblast differentiation via a pHdependent activation of TGF-b. We propose that the metabolic milieu of the lung, and potentially other tissues, is an important driving force behind myofibroblast differentiation and potentially the initiation and progression of fibrotic disorders.

  5. Elevated temperature inhibits recruitment of transferrin-positive vesicles and induces iron-deficiency genes expression in Aiptasia pulchella host-harbored Symbiodinium.

    Science.gov (United States)

    Song, Po-Ching; Wu, Tsung-Meng; Hong, Ming-Chang; Chen, Ming-Chyuan

    2015-10-01

    Coral bleaching is the consequence of disruption of the mutualistic Cnidaria-dinoflagellate association. Elevated seawater temperatures have been proposed as the most likely cause of coral bleaching whose severity is enhanced by a limitation in the bioavailability of iron. Iron is required by numerous organisms including the zooxanthellae residing inside the symbiosome of cnidarian cells. However, the knowledge of how symbiotic zooxanthellae obtain iron from the host cells and how elevated water temperature affects the association is very limited. Since cellular iron acquisition is known to be mediated through transferrin receptor-mediated endocytosis, a vesicular trafficking pathway specifically regulated by Rab4 and Rab5, we set out to examine the roles of these key proteins in the iron acquisition by the symbiotic Symbiodinium. Thus, we hypothesized that the iron recruitments into symbiotic zooxanthellae-housed symbiosomes may be dependent on rab4/rab5-mediated fusion with vesicles containing iron-bound transferrins and will be retarded under elevated temperature. In this study, we cloned a novel monolobal transferrin (ApTF) gene from the tropical sea anemone Aiptasia pulchella and confirmed that the association of ApTF with A. pulchella Rab4 (ApRab4) or A. pulchella Rab5 (ApRab5) vesicles is inhibited by elevated temperature through immunofluorescence analysis. We confirmed the iron-deficient phenomenon by demonstrating the induced overexpression of iron-deficiency-responsive genes, flavodoxin and high-affinity iron permease 1, and reduced intracellular iron concentration in zooxanthellae under desferrioxamine B (iron chelator) and high temperature treatment. In conclusion, our data are consistent with algal iron deficiency being a contributing factor for the thermal stress-induced bleaching of symbiotic cnidarians. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. A nested modeling study of elevation-dependent climate change signals in California induced by increased atmospheric CO2

    International Nuclear Information System (INIS)

    Kim, Jinwon

    2001-01-01

    Dynamically downscaled climate change signals due to increased atmospheric CO2 are investigated for three California basins. The downscaled signals show strong elevation dependence, mainly due to elevated freezing levels in the increased CO2 climate. Below 2.5 km, rainfall increases by over 150% while snowfall decreases by 20-40% in the winter. Above 2.5 km, rainfall and snowfall both increase in the winter, as the freezing levels appear mostly below this level. Winter snowmelt increases in all elevations due to warmer temperatures in the increased CO2 climate. Reduced snowfall and enhanced snowmelt during the winter decreases snowmelt-driven spring runoff below the 2.5 km level, where the peak snowmelt occurs one month earlier in the increased CO2 climate. Above 2.5km, increased winter snowfall maintains snowmelt-driven runoff through most of the warm season. The altered hydrologic characteristics in the increased CO2 climate affect the diurnal temperature variation mainly via snow-albedo-soil moisture feedback

  7. Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Jerry W. Marlin

    2009-03-01

    Full Text Available p21-Activated kinase 2 (PAK-2 seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis.

  8. A benzoxazine derivative induces vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 by elevating NADPH oxidase activity and reactive oxygen species levels.

    Science.gov (United States)

    Zhao, Jing; He, Qiuxia; Cheng, Yizhe; Zhao, Baoxiang; Zhang, Yun; Zhang, Shangli; Miao, Junying

    2009-09-01

    Previously, we found that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO) promoted apoptosis of human umbilical vascular endothelial cells (HUVECs) deprived of growth factors. In this study, we aimed to investigate the effect of DBO and its mechanism of action on angiogenesis and apoptosis of HUVECs in the presence of fibroblast growth factor-2 (FGF-2), which promotes angiogenesis and inhibits apoptosis in vivo and in vitro. DBO significantly inhibited capillary-like tube formation by promoting apoptosis of HUVECs in the presence of FGF-2 in vitro. Furthermore, DBO elevated the levels of reactive oxygen species (ROS) and nitric oxide (NO) and increased the activity of NADPH oxidase and inducible nitric oxide synthase (iNOS) in promoting apoptosis under this condition. Moreover, when NADPH oxidase was inhibited by its specific inhibitor, dibenziodolium chloride (DPI), DBO could not elevate ROS and NO levels in HUVECs. The data suggest that DBO is a new modulator of apoptosis in vitro, and it might function by increasing the activity of NADPH oxidase and iNOS, subsequently elevating the levels of ROS and NO in HUVECs. The findings of this study provide a new small molecule for investigating the FGF-2/NADPH oxidase/iNOS signaling pathway in apoptosis.

  9. Data Elevator

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-29

    Data Elevator: Efficient Asynchronous Data Movement in Hierarchical Storage Systems Multi-layer storage subsystems, including SSD-based burst buffers and disk-based parallel file systems (PFS), are becoming part of HPC systems. However, software for this storage hierarchy is still in its infancy. Applications may have to explicitly move data among the storage layers. We propose Data Elevator for transparently and efficiently moving data between a burst buffer and a PFS. Users specify the final destination for their data, typically on PFS, Data Elevator intercepts the I/O calls, stages data on burst buffer, and then asynchronously transfers the data to their final destination in the background. This system allows extensive optimizations, such as overlapping read and write operations, choosing I/O modes, and aligning buffer boundaries. In tests with large-scale scientific applications, Data Elevator is as much as 4.2X faster than Cray DataWarp, the start-of-art software for burst buffer, and 4X faster than directly writing to PFS. The Data Elevator library uses HDF5's Virtual Object Layer (VOL) for intercepting parallel I/O calls that write data to PFS. The intercepted calls are redirected to the Data Elevator, which provides a handle to write the file in a faster and intermediate burst buffer system. Once the application finishes writing the data to the burst buffer, the Data Elevator job uses HDF5 to move the data to final destination in an asynchronous manner. Hence, using the Data Elevator library is currently useful for applications that call HDF5 for writing data files. Also, the Data Elevator depends on the HDF5 VOL functionality.

  10. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver[S

    Science.gov (United States)

    Satapati, Santhosh; Sunny, Nishanth E.; Kucejova, Blanka; Fu, Xiaorong; He, Tian Teng; Méndez-Lucas, Andrés; Shelton, John M.; Perales, Jose C.; Browning, Jeffrey D.; Burgess, Shawn C.

    2012-01-01

    The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo 2H/13C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis. PMID:22493093

  11. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver.

    Science.gov (United States)

    Satapati, Santhosh; Sunny, Nishanth E; Kucejova, Blanka; Fu, Xiaorong; He, Tian Teng; Méndez-Lucas, Andrés; Shelton, John M; Perales, Jose C; Browning, Jeffrey D; Burgess, Shawn C

    2012-06-01

    The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo (2)H/(13)C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis.

  12. Antioxidant activity and protective effect of bee bread (honey and pollen) in aluminum-induced anemia, elevation of inflammatory makers and hepato-renal toxicity.

    Science.gov (United States)

    Bakour, Meryem; Al-Waili, Noori S; El Menyiy, Nawal; Imtara, Hamada; Figuira, Anna Cristina; Al-Waili, Thia; Lyoussi, Badiaa

    2017-12-01

    Aluminum toxicity might be related to oxidative stress, and the antioxidant activity and protective effect of bee bread, which contains pollen, honey and bees' enzymes, on aluminum induced blood and hepato-renal toxicity was investigated in rats. Chemical analysis and antioxidant capacity of bee bread were conducted. The animal experiment in rats included; group 1: received distilled water (10 ml/kg b.wt), group 2: received aluminum chloride (662.2 mg/kg b.wt), group 3: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (500 mg/kg b.wt), and group 4: received aluminum chloride (662.2 mg/kg b.wt) and ethanolic extract of the bee bread (750 mg/kg b.wt). Doses were given once daily via a gavage. C-reactive protein, transaminases, urea, creatinine, creatinine clearance, sodium and potassium and urine sodium and potassium were determined on day 28 of the experiment. Bee bread contained protein, fat, fiber, ash, carbohydrate, phenol and flavonoids and it exhibited antioxidant activity. Aluminum caused a significant elevation of blood urea, transaminase, C-reactive protein and monocyte count and significantly decreased hemoglobin. These changes were significantly ameliorated by the use of bee bread. Bee bread has an antioxidant property, and exhibited a protective effect on aluminum induced blood and hepato-renal toxicity and elevation of inflammatory markers C-reactive protein, leukocyte and monocyte counts.

  13. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant

    Science.gov (United States)

    Waisertreiger, Irina S.-R.; Menezes, Miriam R.; Randazzo, James; Pavlov, Youri I.

    2010-01-01

    Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA) hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP) deoxynucleoside triphosphate) and thus regulates nucleotide pools and protects cells from DNA damage. We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA. A human polymorphic allele of the ITPA, 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP. The polymorphism has been associated with adverse reaction to purine base-analog drugs. The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant. The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs. PMID:20936128

  14. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant

    Directory of Open Access Journals (Sweden)

    Irina S.-R. Waisertreiger

    2010-01-01

    Full Text Available Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP deoxynucleoside triphosphate and thus regulates nucleotide pools and protects cells from DNA damage. We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA. A human polymorphic allele of the ITPA, 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP. The polymorphism has been associated with adverse reaction to purine base-analog drugs. The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant. The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs.

  15. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses.

    Directory of Open Access Journals (Sweden)

    Tamer A Sharafeldin

    Full Text Available Newly emergent turkey arthritis reoviruses (TARV were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O'Neil strain. Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi. Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1-2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV.

  16. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Loginovskiy, V.I.; Medinger, N.V.; Rasskazov, V.A.; Solonitsyn, V.A.

    1983-01-01

    An elevator is proposed which includes a body, spring loaded cams and a shut-off ring. To increase the reliability of the elevator by eliminating the possibility of spontaneous shifting of the shut-off ring, the latter is equipped with handles hinged to it and is made with evolvent grooves. The cams are equipped with rollers installed in the evolvent grooves of the shut off ring, where the body is made with grooves for the handles.

  17. Significant and sustaining elevation of blood oxygen induced by Chinese cupping therapy as assessed by near-infrared spectroscopy.

    Science.gov (United States)

    Li, Ting; Li, Yaoxian; Lin, Yu; Li, Kai

    2017-01-01

    Cupping therapy has been used in traditional Chinese medicine for thousands of years to relieve muscle pain/tendency/fatigue and to cure or reduce symbols of other diseases. However, its therapeutic effect is sparsely interpreted in the language of modern physiology. To objectively evaluate its therapeutic effect, we focused on dry cupping treatment and utilized near-infrared spectroscopy (NIRS) to assess the concentration change in oxy-hemoglobin ([HbO 2 ]), deoxy-hemoglobin ([Hb]), and blood volume in the course of cupping therapy over 13 volunteers on the infraspinatus muscle, where is usually applied for shoulder pains. Both a prominent drop in [Hb] and a significant elevation in [HbO 2 ] in the tissue surrounding the cupping site were observed during both cupping and post-treatment, manifesting the enhancement of oxygen uptake. This resulting promotion indicates potential positive therapeutic effect of cupping therapy in hemodynamics for facilitating muscular functions.

  18. Elevated systemic glutamic acid level in the non-obese diabetic mouse is Idd linked and induces beta cell apoptosis.

    Science.gov (United States)

    Banday, Viqar Showkat; Lejon, Kristina

    2017-02-01

    Although type 1 diabetes (T1D) is a T-cell-mediated disease in the effector stage, the mechanism behind the initial beta cell assault is less understood. Metabolomic differences, including elevated levels of glutamic acid, have been observed in patients with T1D before disease onset, as well as in pre-diabetic non-obese diabetic (NOD) mice. Increased levels of glutamic acid damage both neurons and beta cells, implying that this could contribute to the initial events of T1D pathogenesis. We investigated the underlying genetic factors and consequences of the increased levels of glutamic acid in NOD mice. Serum glutamic acid levels from a (NOD×B6)F 2 cohort (n = 182) were measured. By genome-wide and Idd region targeted microsatellite mapping, genetic association was detected for six regions including Idd2, Idd4 and Idd22. In silico analysis of potential enzymes and transporters located in and around the mapped regions that are involved in glutamic acid metabolism consisted of alanine aminotransferase, glutamic-oxaloacetic transaminase, aldehyde dehydrogenase 18 family, alutamyl-prolyl-tRNA synthetase, glutamic acid transporters GLAST and EAAC1. Increased EAAC1 protein expression was observed in lysates from livers of NOD mice compared with B6 mice. Functional consequence of the elevated glutamic acid level in NOD mice was tested by culturing NOD. Rag2 -/- Langerhans' islets with glutamic acid. Induction of apoptosis of the islets was detected upon glutamic acid challenge using TUNEL assay. Our results support the notion that a dysregulated metabolome could contribute to the initiation of T1D. We suggest that targeting of the increased glutamic acid in pre-diabetic patients could be used as a potential therapy. © 2016 John Wiley & Sons Ltd.

  19. The Impact of Central and Peripheral Cyclooxygenase Enzyme Inhibition on Exercise-Induced Elevations in Core Body Temperature.

    NARCIS (Netherlands)

    Veltmeijer, M.T.W.; Veeneman, D.; Bongers, C.C.W.G.; Netea, M.G.; Meer, J.W.M. van der; Eijsvogels, T.M.H.; Hopman, M.T.E.

    2017-01-01

    PURPOSE: Exercise increases core body temperature (TC) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 (IL-6) may also contribute to the rise in TC by increasing the hypothalamic temperature set point. This study investigated

  20. Elevating Endogenous GABA Levels with GAT-1 Blockade Modulates Evoked but Not Induced Responses in Human Visual Cortex

    Science.gov (United States)

    Muthukumaraswamy, Suresh D; Myers, Jim F M; Wilson, Sue J; Nutt, David J; Hamandi, Khalid; Lingford-Hughes, Anne; Singh, Krish D

    2013-01-01

    The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations. PMID:23361120

  1. Estrogen receptor-a in the medial amygdala prevents stress-induced elevations in blood pressure in females

    Science.gov (United States)

    Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in femal...

  2. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  3. Dietary elevated sucrose modulation of diesel-induced genotoxicity in the colon and liver of Big Blue rats

    DEFF Research Database (Denmark)

    Risom, L.; Moller, P.; Hansen, Max

    2003-01-01

    Earlier studies have indicated that sucrose possesses either co-carcinogenic or tumor-promoter effects in colon carcinogenesis induced by genotoxic carcinogens. In this study we investigated the role of sucrose on diesel exhaust particle (DEP)-induced genotoxicity in the colonic mucosa and liver......-breaks and DNA adducts in liver. DEP and sucrose treatment did not have any effect on mutation frequency in colon and liver. Oxidative DNA damage detected as 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites was unaltered in colon and liver....... The mRNA expression levels of the DNA repair enzymes N-methylpurine DNA glycosylase (MPG), 8-oxoguanine DNA glycosylase (OGG1) and ERCC1 (part of the nucleotide excision repair complex) measured by reverse transcription-polymerase chain reaction were increased in liver by DEP feeding. In colon...

  4. Progesterone regulates corticosterone elevation and alterations in spatial memory and exploratory behavior induced by stress in Wistar rats

    OpenAIRE

    Diaz-Burke, Yolanda; Universidad de Guadalajara; Valencia-Alfonso, Carlos Eduardo; Netherlands Institute for Neuroscience; González-Sandoval, Claudia Elena; Universidad de Guadalajara; Huerta, Miguel; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima; Trujillo, Xóchitl; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima; Diaz, Lourdes; Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco; García-Estrada, Joaquín; Centro de Investigación Biomédica de Occidente, IMSS-Jalisco; Luquín, Sonia; Universidad de Guadalajara

    2010-01-01

    The hippocampus is sensitive to high levels of glucocorticoids. During stress response, it suffers biochemical and cellular changes that affect functions such as spatial memory and exploratory behavior. In this study, we analyzed the influence of the neurosteroid progesterone (PROG), on stress-induced changes in urinary corticosterone (CORT) levels, spatial memory and exploratory behavior. Castrated adult male rats were implanted with PROG or vehicle (VEHI), and then exposed to chronic stres...

  5. Surgery-induced hippocampal angiotensin II elevation causes blood-brain barrier disruption via MMP/TIMP in aged rats

    Directory of Open Access Journals (Sweden)

    Zhengqian eLi

    2016-04-01

    Full Text Available Reversible BBB disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD. Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2 and -9 (MMP-9, as well as three of their endogenous tissue inhibitors (TIMP-1, -2, -3, and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II and Ang II receptor type 1 (AT1 after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1, as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor.

  6. AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation.

    Science.gov (United States)

    Han, Xiaojuan; Tai, Haoran; Wang, Xiaobo; Wang, Zhe; Zhou, Jiao; Wei, Xiawei; Ding, Yi; Gong, Hui; Mo, Chunfen; Zhang, Jie; Qin, Jianqiong; Ma, Yuanji; Huang, Ning; Xiang, Rong; Xiao, Hengyi

    2016-06-01

    AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress-induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide-induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP-RFP-LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD(+) levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD(+) synthesis. In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence by improving autophagic flux and NAD(+) homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD(+) homeostasis, and it is also valuable in the development of innovative strategies to combat aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  7. True or false? Memory is differentially affected by stress-induced cortisol elevations and sympathetic activity at consolidation and retrieval.

    Science.gov (United States)

    Smeets, Tom; Otgaar, Henry; Candel, Ingrid; Wolf, Oliver T

    2008-11-01

    Adrenal stress hormones released in response to acute stress may yield memory-enhancing effects when released post-learning and impairing effects at memory retrieval, especially for emotional memory material. However, so far these differential effects of stress hormones on the various memory phases for neutral and emotional memory material have not been demonstrated within one experiment. This study investigated whether, in line with their effects on true memory, stress and stress-induced adrenal stress hormones affect the encoding, consolidation, and retrieval of emotional and neutral false memories. Participants (N=90) were exposed to a stressor before encoding, during consolidation, before retrieval, or were not stressed and then were subjected to neutral and emotional versions of the Deese-Roediger-McDermott word list learning paradigm. Twenty-four hours later, recall of presented words (true recall) and non-presented critical lure words (false recall) was assessed. Results show that stress exposure resulted in superior true memory performance in the consolidation stress group and reduced true memory performance in the retrieval stress group compared to the other groups, predominantly for emotional words. These memory-enhancing and memory-impairing effects were strongly related to stress-induced cortisol and sympathetic activity measured via salivary alpha-amylase levels. Neutral and emotional false recall, on the other hand, was neither affected by stress exposure, nor related to cortisol and sympathetic activity following stress. These results demonstrate the importance of stress-induced hormone-related activity in enhancing memory consolidation and in impairing memory retrieval, in particular for emotional memory material.

  8. BDE-47 induces oxidative stress, activates MAPK signaling pathway, and elevates de novo lipogenesis in the copepod Paracyclopina nana.

    Science.gov (United States)

    Lee, Min-Chul; Puthumana, Jayesh; Lee, Seung-Hwi; Kang, Hye-Min; Park, Jun Chul; Jeong, Chang-Bum; Han, Jeonghoon; Hwang, Dae-Sik; Seo, Jung Soo; Park, Heum Gi; Om, Ae-Son; Lee, Jae-Seong

    2016-12-01

    Brominated flame retardant, 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47), has received grave concerns as a persistent organic pollutant, which is toxic to marine organisms, and a suspected link to endocrine abnormalities. Despite the wide distribution in the marine ecosystem, very little is known about the toxic impairments on marine organisms, particularly on invertebrates. Thus, we examined the adverse effects of BDE-47 on life history trait (development), oxidative markers, fatty acid composition, and lipid accumulation in response to BDE-47-induced stress in the marine copepod Paracyclopina nana. Also, activation level of mitogen-activated protein kinase (MAPK) signaling pathways along with the gene expression profile of de novo lipogenesis (DNL) pathways were addressed. As a result, BDE-47 induced oxidative stress (e.g. reactive oxygen species, ROS) mediated activation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) signaling cascades in MAPK pathways. Activated MAPK pathways, in turn, induced signal molecules that bind to the transcription factors (TFs) responsible for lipogenesis to EcR, SREBP, ChREBP promoters. Also, the stress stimulated the conversion of saturated fatty acids (SFAs) to polyunsaturated fatty acids (PUFAs), a preparedness of the organism to adapt the observed stress, which could be correlated with the elongase and desaturase gene (e.g. ELO3, Δ5-DES, Δ9-DES) expressions, and then extended to the delayed early post-embryonic development and increased accumulation of lipid droplets in P. nana. This study will provide a better understanding of how BDE-47 effects on marine invertebrates particularly on the copepods, an important link in the marine food chain. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study.

    Science.gov (United States)

    Ouyang, Jessica; Pace, Edward; Lepczyk, Laura; Kaufman, Michael; Zhang, Jessica; Perrine, Shane A; Zhang, Jinsheng

    2017-07-07

    Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

  10. Ion-Exchange-Induced Selective Etching for the Synthesis of Amino-Functionalized Hollow Mesoporous Silica for Elevated-High-Temperature Fuel Cells.

    Science.gov (United States)

    Zhang, Jin; Liu, Jian; Lu, Shanfu; Zhu, Haijin; Aili, David; De Marco, Roland; Xiang, Yan; Forsyth, Maria; Li, Qingfeng; Jiang, San Ping

    2017-09-20

    As differentiated from conventional synthetic processes, amino-functionalized hollow mesoporous silica (NH 2 -HMS) has been synthesized using a new and facile strategy of ion-exchange-induced selective etching of amino-functionalized mesoporous silica (NH 2 -meso-silica) by an alkaline solution. Nuclear magnetic resonance (NMR) spectroscopy and in situ time-resolved small-angle X-ray scattering (SAXS) reveal that ion-exchange-induced selective etching arises from the gradient distribution of OH - in the NH 2 -meso-silica nanospheres. Moreover, the ion-exchange-induced selective etching mechanism is verified through a successful synthesis of hollow mesoporous silica. After infiltration with phosphotungstic acid (PWA), PWA-NH 2 -HMS nanoparticles are dispersed in the poly(ether sulfone)-polyvinylpyrrolidone (PES-PVP) matrix, forming a hybrid PWA-NH 2 -HMS/PES-PVP nanocomposite membrane. The resultant nanocomposite membrane with an optimum loading of 10 wt % of PWA-NH 2 -HMS showed an enhanced proton conductivity of 0.175 S cm -1 and peak power density of 420 mW cm -2 at 180 °C under anhydrous conditions. Excellent durability of the hybrid composite membrane fuel cell has been demonstrated at 200 °C. The results of this study demonstrated the potential of the facile synthetic strategy in the fabrication of NH 2 -HMS with controlled mesoporous structure for application in nanocomposite membranes as a technology platform for elevated-temperature proton exchange membrane fuel cells.

  11. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China); Yang, Z. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Department of Pathology, Xi' an, China, Department of Pathology, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Yuan, Z.Y. [Xi' an Jiaotong University, Medical College, First Affiliated Hospital, Cardiovascular Department, Xi' an, China, Cardiovascular Department, First Affiliated Hospital, Medical College, Xi' an Jiaotong University, Xi' an (China); Ministry of Education, Key Laboratory of Environment and Genes Related to Diseases, Xi' an, China, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi' an (China)

    2014-03-03

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13{sup BN} rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

  12. Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance.

    Science.gov (United States)

    Zhou, Xin; Ma, Xiaofei; Wang, Zhenhua; Sun, Chao; Wang, Yupei; He, Yang; Zhang, Hong

    2015-12-15

    Radiation-induced hyperproliferation of intestinal crypts is well documented, but its potential tumorigenic effects remain elusive. Here we aim to determine the genomic surveillance process during crypt hyperproliferation, and its consequential outcome after ionizing radiation. Crypt regeneration in the intestine was induced by a single dose of 12Gy abdominal irradiation. γ-H2AX, 53BP1 and DNA-PKcs were used as DNA repair surrogates to investigate the inherent ability of intestinal crypt cells to recognize and repair double-strand breaks. Ki67 staining and the 5-bromo-2'-deoxyuridine incorporation assay were used to study patterns of cell proliferation in regenerating crypts. Staining for ATM, p53, Chk1 and Chk2 was performed to study checkpoint activation and release. Apoptosis was evaluated through H&E staining and terminal deoxynucleotidyl transferase (dUTP) nick-end labeling. The ATM-p53 pathway was immediately activated after irradiation. A second wave of DSBs in crypt cells was observed in regenerating crypts, accompanied with significantly increased chromosomal bridges. The p53-related genomic surveillance pathway was not active during the regeneration phase despite DSBs and chromosomal bridges in the cells of regenerating crypts. Non-homologous end joining (NHEJ) DSBs repair was involved in the DSBs repair process, as indicated by p-DNA-PKcs staining. Intestinal crypt cells retained hyperproliferation with inactive p53-related genomic surveillance system. NHEJ was involved in the resultant genomic instability during hyperproliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The modifying effect of ibuprofen on total body irradiation-induced elevation of oxidative reactions in male hamsters

    International Nuclear Information System (INIS)

    Dokmeci, D.; Akpolat, M.; Aydogdu, N.; Uzal, C.; Turan, N.F.

    2004-01-01

    Radiation therapy plays an important role in curative and palliative treatments of malignant diseases. Because of the lipid component in the membrane, lipid peroxidation has been reported to be particularly susceptible to radiation damage. However, lipid peroxidation is reversed by cellular defense mechanisms, and the use of various antioxidants involved in these mechanisms have recently been suggested to be beneficial. It is known that ibuprofen has antioxidative and/or free radical scavenging activities. Our purpose is to examine the antioxidant capacity of ibuprofen in hamsters undergoing total body irradiation (TBI). Ibuprofen was given by gavage at dose of 10 mg/kg for 15 consecutive days. After this period, animals were exposed to TBI 60 Co gamma irradiation with a single dose of 8 Gy. After 24 h radiation exposure, the hamsters were killed and samples were taken from blood. Plasma thiobarbituric acid reactive substances (TBARS) increased significantly after radiation exposure, and ibuprofen diminished the amounts of TBARS. Significant protection of the radiation-induced changes in the activities of superoxide dismutase (SOD) and catalase was also recorded in the blood of ibuprofen-treated and -irradiated hamsters. These results suggest that ibuprofen with its antioxidant capacity could play a modulatory role against cellular damage effected by free radicals induced by TBI. (author)

  14. Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

    International Nuclear Information System (INIS)

    Wang, Y.; Mu, J.J.; Liu, F.Q.; Ren, K.Y.; Xiao, H.Y.; Yang, Z.; Yuan, Z.Y.

    2014-01-01

    Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13 BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure

  15. Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation.

    Science.gov (United States)

    Fatemi, Ahmad; Kazemi, Ahmad; Kashiri, Meysam; Safa, Majid

    2015-01-01

    Recognition of the molecular mechanisms of cAMP action against DNA damage-induced apoptosis can be useful to improve the efficacy of DNA damaging therapeutic agents. Considering the critical role of bcl-2-associated death promoter (BAD) and p53 proteins in DNA damage -induced apoptosis, the aim of this study was to assess the effect of cAMP-elevating agents on these proteins in doxorubicin-treated pre-B acute lymphoblastic leukemia (pre-B ALL) NALM-6 cells.The pre-B ALL cell line NALM-6 was cultured and treated with doxorubicin in combination with or without cAMP-elevating agents forskolin and 3-isobutyl-1-methylxanthine (IBMX). Cell viability was measured by trypan blue staining and MTT assay. For evaluation of apoptosis, annexin-V staining by flow cytometry and caspase-3 activity assay were used. Protein expression of p53, BAD and phoshorylated BAD was detected by western blotting analysis.cAMP-increasing agents diminished the doxorubicin-mediated cytotoxicity in NALM-6 cells as indicated by the viability assays. Annexin-V apoptosis assay showed that the cAMP-elevating agents decreased doxorubicin-induced apoptosis. Moreover, doxorubicin-induced caspase-3 activity was attenuated in the presence of cAMP-increasing agents. Western blot results revealed the reduced expression of p53 protein in cells treated with combination of cAMP-elevating agents and doxorubicin in contrast to cells treated with doxorubicin alone. Expression of total BAD protein was not affected by doxorubicin and cAMP-elevating agents. However, phosphorylation of BAD protein was induced in the presence of cAMP-elevating agents. Our study suggests that elevated cAMP levels inhibit doxorubicin-induced apoptosis in pre-B ALL cells through induction of BAD phosphorylation and abrogation of p53 accumulation.

  16. Elevation of susceptibility to ozone-induced acute tracheobronchial injury in transgenic mice deficient in Clara cell secretory protein

    International Nuclear Information System (INIS)

    Plopper, C.G.; Mango, G.W.; Hatch, G.E.; Wong, V.J.; Toskala, E.; Reynolds, S.D.; Tarkington, B.K.; Stripp, B.R.

    2006-01-01

    Increases in Clara cell abundance or cellular expression of Clara cell secretory protein (CCSP) may cause increased tolerance of the lung to acute oxidant injury by repeated exposure to ozone (O 3 ). This study defines how disruption of the gene for CCSP synthesis affects the susceptibility of tracheobronchial epithelium to acute oxidant injury. Mice homozygous for a null allele of the CCSP gene (CCSP-/-) and wild type (CCSP+/+) littermates were exposed to ozone (0.2 ppm, 8 h; 1 ppm, 8 h) or filtered air. Injury was evaluated by light and scanning electron microscopy, and the abundance of necrotic, ciliated, and nonciliated cells was estimated by morphometry. Proximal and midlevel intrapulmonary airways and terminal bronchioles were evaluated. There was no difference in airway epithelial composition between CCSP+/+ and CCSP-/- mice exposed to filtered air, and exposure to 0.2 ppm ozone caused little injury to the epithelium of both CCSP+/+ and CCSP-/- mice. After exposure to 1.0 ppm ozone, CCSP-/- mice suffered from a greater degree of epithelial injury throughout the airways compared to CCSP+/+ mice. CCSP-/- mice had both ciliated and nonciliated cell injury. Furthermore, lack of CCSP was associated with a shift in airway injury to include proximal airway generations. Therefore, we conclude that CCSP modulates the susceptibility of the epithelium to oxidant-induced injury. Whether this is due to the presence of CCSP on the acellular lining layer surface and/or its intracellular distribution in the secretory cell population needs to be defined

  17. Elevator wheel

    Energy Technology Data Exchange (ETDEWEB)

    Zhornik, V.I.; Cherkov, Ye.M.; Simonov, A.A.

    1982-01-01

    An elevator wheel is suggested for unloading a sunken product from a bath of a heavy-average separator including discs of a bucket with inner walls, and covering sheets hinged to the buckets. In order to improve the degree of dehydration of the removed product, the inner wall of each bucket is made of sheets installed in steps with gaps of one in relation to the other.

  18. An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer.

    Science.gov (United States)

    Morse, Michael A; Hobeika, Amy C; Osada, Takuya; Berglund, Peter; Hubby, Bolyn; Negri, Sarah; Niedzwiecki, Donna; Devi, Gayathri R; Burnett, Bruce K; Clay, Timothy M; Smith, Jonathan; Lyerly, H Kim

    2010-09-01

    Therapeutic anticancer vaccines are designed to boost patients' immune responses to tumors. One approach is to use a viral vector to deliver antigen to in situ DCs, which then activate tumor-specific T cell and antibody responses. However, vector-specific neutralizing antibodies and suppressive cell populations such as Tregs remain great challenges to the efficacy of this approach. We report here that an alphavirus vector, packaged in virus-like replicon particles (VRP) and capable of efficiently infecting DCs, could be repeatedly administered to patients with metastatic cancer expressing the tumor antigen carcinoembryonic antigen (CEA) and that it overcame high titers of neutralizing antibodies and elevated Treg levels to induce clinically relevant CEA-specific T cell and antibody responses. The CEA-specific antibodies mediated antibody-dependent cellular cytotoxicity against tumor cells from human colorectal cancer metastases. In addition, patients with CEA-specific T cell responses exhibited longer overall survival. These data suggest that VRP-based vectors can overcome the presence of neutralizing antibodies to break tolerance to self antigen and may be clinically useful for immunotherapy in the setting of tumor-induced immunosuppression.

  19. Pre-weaning growth performance of kits of a local Algerian rabbit population: influence of dam coat color, parity and kindling season

    Directory of Open Access Journals (Sweden)

    O. Abdelli-Larbi

    2014-09-01

    Full Text Available This study evaluated the effect of dam coat colours, doe’s parity order, year and kindling season on litter size and growth of suckling kits of a local Algerian rabbit population. Rabbits were reared in the rabbitry of Tizi Ouzou (Algeria in wire mesh cages placed in a building with natural lighting and ventilation and absence of temperature regulation. Weights and size of 572 litters (3795 kits at birth, 7, 14, 21 and 28 d were analysed. The mother’s coat colours (2 levels only: albino or coloured coat, the doe’s parity (1, 2, 3, 4-5, 6-8, ≥9 kindlings, the kindling year (4 consecutive years and the kindling season (3 seasons: Feb-May, June-Sept and Oct-Jan, were used as main fixed factors in a factorial analysis. The population was characterised by an average individual weight of 54 g at birth and 404 g at 30 d, growth rate of 10.24 g/d between birth and 24 d and of 19.02 g/d between 24 and 30 d. The coloured females were more prolific than the albino ones: 5.59 vs. 5.09 weaned/litter (P=0.016; but kits born from albino does had a larger individual weight at weaning: 391 vs. 362 g (P=0.006. The doe’s parity order had no significant influence on the litter weight, individual weight or litter size at kindling. However, it influenced litter weight and litter size from 7 d of age up to 28 d in favour of 2nd and 3rd parity (P<0.02. Litter size was not significantly affected by year of kindling at any considered age. On the contrary, year of birth greatly influenced litter and individual weights. For example, the difference in individual weights at 28 d between the best and the worst year represented 19% of the average weight at this age. The birth season influenced mainly (P<0.001 litter size from birth until weaning in favour of the spring season: 5.92 weaned/litter vs. 5.05 or 5.04 for the 2 other seasons. From day 7 until weaning, the litter weight was larger for the Feb-May season (P<0.02 and represented +0.87 grams

  20. Intracerebral beta-endorphin, met-enkephalin and morphine: kindling of seizures and handling-induced potentiation of epileptiform effects.

    Science.gov (United States)

    Cain, D P; Corcoran, M E

    1984-06-18

    The effects of repeated infusion of small, initially subconvulsive amounts of beta-endorphin, met-enkephalin or morphine sulfate into the amygdala and hippocampus were investigated. beta-endorphin and met-enkephalin evoked epileptiform spiking when infused into the posterior amygdala or ventral hippocampus. Morphine evoked epileptiform spiking when infused into the anterior amygdala. Naloxone blocked or terminated the spiking. Repetition of the infusions led to the gradual development of bilateral generalized convulsions by beta-endorphin and met-enkephalin and to the development of tolerance to morphine. An unexpected observation was that handling, immobilization or conspecific threat potentiated the epileptiform effects of beta-endorphin and morphine in many cases. These results suggest that endogenous opiate mechanisms might play a role in convulsive seizures and that stressful stimuli can exacerbate opiate seizures.

  1. Neuro-overprotection? A functional evaluation of clomethiazole-induced neuroprotection following hypoxic-ischemic injury.

    Science.gov (United States)

    Gilby, K L; Kelly, M E; McIntyre, D C; Robertson, H A

    2005-01-01

    Hypoxic-ischemic (H-I) injury produces extensive damage to the hippocampus of young rats. We have recently shown that administration of 125 mg kg-1 clomethiazole (CMZ), a GABA(A)-agonist, provides complete histological protection against H-I injury if administered 3 h post-H-I (Brain Res 1035 (2005) 194). However, whether that histological protection translates into lasting functional preservation is unclear. To determine whether hippocampal-based circuits remain functionally intact in CMZ-protected H-I rats, we administered 125 mg kg-1 (high dose [CMZ-HD]) or 65 mg kg-1 (low dose [CMZ-LD]) CMZ, 3 h post-H-I, and examined numerous kindling parameters in the dorsal hippocampus 60 days following H-I. Kindling parameters included afterdischarge (AD) thresholds (ADTs), AD durations and kindling rates. Additional groups assessed included vehicle-injected H-I (VIH), hypoxic, ligated and naive rats. VIH, CMZ-HD, CMZ-LD and hypoxic rats all exhibited significantly faster kindling rates than naive rats. Thus, a previous traumatic event, even hypoxia alone, facilitated subsequent seizure propagation. Still, a significantly slower kindling rate was evident in CMZ-HD rats than in hypoxic, VIH or CMZ-LD rats. Moreover, while longer pre-kindling AD durations were observed in the damaged hippocampus of VIH compared with naive rats, this was not true for either CMZ-treated groups, hypoxic or ligated rats. Collectively, these findings suggest CMZ can suppress the epileptogenic effects of H-I. Surprisingly, however, both groups of CMZ-treated rats exhibited a four to nine times greater ADT than any other group and this effect was most profound in the CMZ-protected hippocampus. Thus, CMZ administration protected local neurons against terminal insult and left network excitability relatively normal with respect to seizure offset mechanisms but also caused profound elevation of local ADTs, which suggests a local hypoexcitability/increased inhibition. Finally, this study demonstrates

  2. Caloric restriction protects against electrical kindling of the amygdala by inhibiting the mTOR signaling pathway

    Directory of Open Access Journals (Sweden)

    Bryan Victor Phillips-Farfan

    2015-03-01

    Full Text Available Caloric restriction (CR has been shown to possess antiepileptic properties; however its mechanism of action is poorly understood. CR might inhibit the activity of the mammalian or mechanistic target of rapamycin (mTOR signaling cascade, which seems to participate crucially in the generation of epilepsy. Thus, we investigated the effect of CR on the mTOR pathway and whether CR modified epilepsy generation due to electrical amygdala kindling. The former was studied by analyzing the phosphorylation of adenosine monophosphate-activated protein kinase, protein kinase B and the ribosomal protein S6. The mTOR cascade is regulated by energy and by insulin levels, both of which may be changed by CR; thus we investigated if CR altered the levels of energy substrates in the blood or the level of insulin in plasma. Finally, we studied if CR modified the expression of genes that encode proteins participating in the mTOR pathway. CR increased the after-discharge threshold and tended to reduce the after-discharge duration, indicating an anti-convulsive action. CR diminished the phosphorylation of protein kinase B and ribosomal protein S6, suggesting an inhibition of the mTOR cascade. However, CR did not change glucose, β-hydroxybutyrate or insulin levels; thus the effects of CR were independent from them. Interestingly, CR also did not modify the expression of any investigated gene. The results suggest that the anti-epileptic effect of CR may be partly due to inhibition of the mTOR pathway.

  3. Elevated CO2 induces a global metabolic change in basil (Ocimum basilicum L.) and peppermint (Mentha piperita L.) and improves their biological activity.

    Science.gov (United States)

    Al Jaouni, Soad; Saleh, Ahmed M; Wadaan, Mohammed A M; Hozzein, Wael N; Selim, Samy; AbdElgawad, Hamada

    Many studies have discussed the influence of elevated carbon dioxide (eCO 2 ) on modeling and crop plants. However, much less effort has been dedicated to herbal plants. In this study, a robust monitoring for the levels of 94 primary and secondary metabolites and minerals in two medicinal herbs, basil (Ocimum basilicum L.) and peppermint (Mentha piperita L.), grwon under both ambient (aCO 2 , 360 ppm) and eCO 2 (620 ppm) was performed. We also assessed how the changes in herbal tissue chemistry affected their biological activity. Elevated CO 2 significantly increased herbal biomass, improved the rates of photosynthesis and dark respiration, and altered the tissue chemistry. Principal Component Analysis of the full data set revealed that eCO 2 induced a global change in the metabolomes of the two plants. Moreover, Hierarchical Clustering Analyses showed quantitative differences in the metabolic profiles of the two plants and in their responsiveness to eCO 2 . Out of 94 metabolites, 38 and 31 significantly increased in basil and peppermint, respectively, as affected by eCO 2 . Regardless of the plant species, the levels of non-structural carbohydrates, fumarate, glutamine, glutathione, ascorbate, phylloquinone (vitamin K1), anthocyanins and a majority of flavonoids and minerals were significantly improved by eCO 2 . However, some metabolites tended to show species specificity. Interestingly, eCO 2 caused enhancement in antioxidant, antiprotozoal, anti-bacterial and anticancer (against urinary bladder carcinoma; T24P) activities in both plants, which was consequent with improvement in the levels of antioxidant metabolites such as glutathione, ascorbate and flavonoids. Therefore, this study suggests that the metabolic changes triggered by eCO 2 in the target herbal plants improved their biological activities. Copyright © 2018 Elsevier GmbH. All rights reserved.

  4. Measuring adolescents' HRQoL via self reports and parent proxy reports: an evaluation of the psychometric properties of both versions of the KINDL-R instrument.

    Science.gov (United States)

    Erhart, Michael; Ellert, Ute; Kurth, Bärbel-Maria; Ravens-Sieberer, Ulrike

    2009-08-26

    Several instruments are available to assess children's health-related quality of life (HRQoL) based on self reports as well as proxy reports from parents. Previous studies have found only low-to-moderate agreement between self and proxy reports, but few studies have explicitly compared the psychometric qualities of both. This study compares the reliability, factorial validity and convergent and known group validity of the self-report and parent-report versions of the HRQoL KINDL-R questionnaire for children and adolescents. Within the nationally representative cross-sectional German Health Interview and Examination Survey for Children and Adolescents (KiGGS), 6,813 children and adolescents aged 11 to 17 years completed the KINDL-R generic HRQoL instrument while their parents answered the KINDL proxy version (both in paper-and-pencil versions). Cronbach's alpha and confirmatory factor-analysis models (linear structural equation model) were obtained. Convergent and discriminant validity were assessed by calculating the Pearson's correlation coefficient for the Strengths and Difficulties Questionnaire. Known-groups differences were examined (ANOVA) for obese children and children with a lower familial socio-economic status. The parent reports achieved slightly higher Cronbach's alpha values for the total score (0.86 vs. 0.83) and most sub-scores. Confirmatory factor analysis revealed an acceptable fit of the six-dimensional measurement model of the KINDL for the parent (RMSEA=0.07) and child reports (RMSEA=0.06). Factorial invariance across the two versions did not hold with regards to the pattern of loadings, the item errors and the covariation between latent concepts. However the magnitude of the differences was rather small. The parent report version achieved slightly higher convergent validity (r=0.44-0.63 vs. r=0.33-0.59) in the Strengths and Difficulties Questionnaire. No clear differences were observed for known-groups validity. Our study showed that parent

  5. Measuring adolescents' HRQoL via self reports and parent proxy reports: an evaluation of the psychometric properties of both versions of the KINDL-R instrument

    Directory of Open Access Journals (Sweden)

    Ravens-Sieberer Ulrike

    2009-08-01

    Full Text Available Abstract Background Several instruments are available to assess children's health-related quality of life (HRQoL based on self reports as well as proxy reports from parents. Previous studies have found only low-to-moderate agreement between self and proxy reports, but few studies have explicitly compared the psychometric qualities of both. This study compares the reliability, factorial validity and convergent and known group validity of the self-report and parent-report versions of the HRQoL KINDL-R questionnaire for children and adolescents. Methods Within the nationally representative cross-sectional German Health Interview and Examination Survey for Children and Adolescents (KiGGS, 6,813 children and adolescents aged 11 to 17 years completed the KINDL-R generic HRQoL instrument while their parents answered the KINDL proxy version (both in paper-and-pencil versions. Cronbach's alpha and confirmatory factor-analysis models (linear structural equation model were obtained. Convergent and discriminant validity were assessed by calculating the Pearson's correlation coefficient for the Strengths and Difficulties Questionnaire. Known-groups differences were examined (ANOVA for obese children and children with a lower familial socio-economic status. Results The parent reports achieved slightly higher Cronbach's alpha values for the total score (0.86 vs. 0.83 and most sub-scores. Confirmatory factor analysis revealed an acceptable fit of the six-dimensional measurement model of the KINDL for the parent (RMSEA = 0.07 and child reports (RMSEA = 0.06. Factorial invariance across the two versions did not hold with regards to the pattern of loadings, the item errors and the covariation between latent concepts. However the magnitude of the differences was rather small. The parent report version achieved slightly higher convergent validity (r = 0.44 – 0.63 vs. r = 0.33 – 0.59 in the Strengths and Difficulties Questionnaire. No clear differences were

  6. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Gusev, A.S.; Peshkov, L.P.; Rozin, M.M.; Shestov, A.G.

    1983-01-01

    An elevator is proposed which includes a body, a flap, a lock with a catch and a spring-loaded shut-off clamp in the form of upper and lower horizontal levers which are connected by a handle and an axle and one end of which is made in the form of an eccentric cam. The size of the eccentricity of the cam of the levers is increased toward the handle of the clamp in order to increase the operational reliability and to extend the service life.

  7. An elevator

    Energy Technology Data Exchange (ETDEWEB)

    Rastorguyev, M.A.; Maloyarovslavtesv, D.A.; Prokopov, O.I.; Tukayev, Sh.V.; Zanilov, I.F.

    1983-01-01

    An elevator is proposed which includes a body with a turning collar locking device and a rod with longitudinal grooves, which are flexibly linked with jaws positioned in grooves in the body. To increase safety through ensuring automatic locking of the jaws in the closed position, the locking device is made in the form of head on wedges, spring loaded relative to the collar and made with cams and positioned with the capability of interacting with the grooves of the rod and through the cams with the collar.

  8. Bucket elevator

    OpenAIRE

    Chromek, Jiří

    2013-01-01

    Cílem této bakalářské práce je návrh svislého korečkového elevátoru, který má sloužit k dopravě obilovin s dopravní výškou 19 m a dopravovaným množstvím 100 t/hod. Práce se skládá z popisu korečkového elevátoru a jeho hlavních částí, zmiňující se v úvodní rešerši. Tato práce je zaměřena na funkční a kapacitní výpočet, určení pohonu a napínacího zařízení. Další výpočet je kontrolní, skládající se z pevnostní kontroly hnacího hřídele, výpočtu pera, životnosti ložisek a výpočtu napínacího zaříze...

  9. Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Anna Ljungdahl

    Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

  10. Validation of diffuse correlation spectroscopy sensitivity to nicotinamide-induced blood flow elevation in the murine hindlimb using the fluorescent microsphere technique

    Science.gov (United States)

    Proctor, Ashley R.; Ramirez, Gabriel A.; Han, Songfeng; Liu, Ziping; Bubel, Tracy M.; Choe, Regine

    2018-03-01

    Nicotinamide has been shown to affect blood flow in both tumor and normal tissues, including skeletal muscle. Intraperitoneal injection of nicotinamide was used as a simple intervention to test the sensitivity of noninvasive diffuse correlation spectroscopy (DCS) to changes in blood flow in the murine left quadriceps femoris skeletal muscle. DCS was then compared with the gold-standard fluorescent microsphere (FM) technique for validation. The nicotinamide dose-response experiment showed that relative blood flow measured by DCS increased following treatment with 500- and 1000-mg / kg nicotinamide. The DCS and FM technique comparison showed that blood flow index measured by DCS was correlated with FM counts quantified by image analysis. The results of this study show that DCS is sensitive to nicotinamide-induced blood flow elevation in the murine left quadriceps femoris. Additionally, the results of the comparison were consistent with similar studies in higher-order animal models, suggesting that mouse models can be effectively employed to investigate the utility of DCS for various blood flow measurement applications.

  11. Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

    Directory of Open Access Journals (Sweden)

    Tina Khorshid Ahmad

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

  12. Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

    Science.gov (United States)

    Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

    2017-06-12

    Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise

  13. Metabolomics analysis reveals elevation of 3-indoxyl sulfate in plasma and brain during chemically-induced acute kidney injury in mice: Investigation of nicotinic acid receptor agonists

    International Nuclear Information System (INIS)

    Zgoda-Pols, Joanna R.; Chowdhury, Swapan; Wirth, Mark; Milburn, Michael V.; Alexander, Danny C.; Alton, Kevin B.

    2011-01-01

    An investigative renal toxicity study using metabolomics was conducted with a potent nicotinic acid receptor (NAR) agonist, SCH 900424. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques were used to identify small molecule biomarkers of acute kidney injury (AKI) that could aid in a better mechanistic understanding of SCH 900424-induced AKI in mice. The metabolomics study revealed 3-indoxyl sulfate (3IS) as a more sensitive marker of SCH 900424-induced renal toxicity than creatinine or urea. An LC-MS assay for quantitative determination of 3IS in mouse matrices was also developed. Following treatment with SCH 900424, 3IS levels were markedly increased in murine plasma and brain, thereby potentially contributing to renal- and central nervous system (CNS)-related rapid onset of toxicities. Furthermore, significant decrease in urinary excretion of 3IS in those animals due to compromised renal function may be associated with the elevation of 3IS in plasma and brain. These data suggest that 3IS has a potential to be a marker of renal and CNS toxicities during chemically-induced AKI in mice. In addition, based on the metabolomic analysis other statistically significant plasma markers including p-cresol-sulfate and tryptophan catabolites (kynurenate, kynurenine, 3-indole-lactate) might be of toxicological importance but have not been studied in detail. This comprehensive approach that includes untargeted metabolomic and targeted bioanalytical sample analyses could be used to investigate toxicity of other compounds that pose preclinical or clinical development challenges in a pharmaceutical discovery and development. - Research highlights: → Nicotinic acid receptor agonist, SCH 900424, caused acute kidney injury in mice. → MS-based metabolomics was conducted to identify potential small molecule markers of renal toxicity. → 3-indoxyl-sulfate was found to be as a more sensitive marker of renal toxicity than

  14. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

    Directory of Open Access Journals (Sweden)

    Radhakrishnan Sridhar

    2010-05-01

    Full Text Available Abstract Background Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene, a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. Methods We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. Results Resveratrol (100-150 μM exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G0/G1-S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. Conclusions For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and

  15. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways

    International Nuclear Information System (INIS)

    Vanamala, Jairam; Reddivari, Lavanya; Radhakrishnan, Sridhar; Tarver, Chris

    2010-01-01

    Obesity is a global phenomenon and is associated with various types of cancer, including colon cancer. There is a growing interest for safe and effective bioactive compounds that suppress the risk for obesity-promoted colon cancer. Resveratrol (trans-3, 4', 5,-trihydroxystilbene), a stilbenoid found in the skin of red grapes and peanuts suppresses many types of cancers by regulating cell proliferation and apoptosis through a variety of mechanisms, however, resveratrol effects on obesity-promoted colon cancer are not clearly established. We investigated the anti-proliferative effects of resveratrol on HT-29 and SW480 human colon cancer cells in the presence and absence of insulin like growth factor-1 (IGF-1; elevated during obesity) and elucidated the mechanisms of action using IGF-1R siRNA in HT-29 cells which represents advanced colon carcinogenesis. Resveratrol (100-150 μM) exhibited anti-proliferative properties in HT-29 cells even after IGF-1 exposure by arresting G 0 /G 1 -S phase cell cycle progression through p27 stimulation and cyclin D1 suppression. Treatment with resveratrol suppressed IGF-1R protein levels and concurrently attenuated the downstream Akt/Wnt signaling pathways that play a critical role in cell proliferation. Targeted suppression of IGF-1R using IGF-1R siRNA also affected these signaling pathways in a similar manner. Resveratrol treatment induced apoptosis by activating tumor suppressor p53 protein, whereas IGF-1R siRNA treatment did not affect apoptosis. Our data suggests that resveratrol not only suppresses cell proliferation by inhibiting IGF-1R and its downstream signaling pathways similar to that of IGF-1R siRNA but also enhances apoptosis via activation of the p53 pathway. For the first time, we report that resveratrol suppresses colon cancer cell proliferation and elevates apoptosis even in the presence of IGF-1 via suppression of IGF-1R/Akt/Wnt signaling pathways and activation of p53, suggesting its potential role as a

  16. Iodinated chlorin p6 copper complex induces anti-proliferative effect in oral cancer cells through elevation of intracellular reactive oxygen species.

    Science.gov (United States)

    Sarbadhikary, Paromita; Dube, Alok

    2017-11-01

    We investigated the anticancer chemotoxicity of previously reported iodinated chlorin p 6 copper complex (ICp 6 -Cu), a novel chlorophyll derivative in which copper is attached to the side chain carboxylate groups via coordination. Human oral carcinoma cells NT8e, 4451 and the non-cancerous keratinocyte HaCaT cells were treated with ICp 6 -Cu for 48 h in dark and cell viability, proliferation and morphological alterations were examined. ICp 6 -Cu showed pronounced cytotoxicity in cancer cells with IC 50 ∼40 μM, whereas, the viability of HaCaT cells was not affected. Cell proliferation assay revealed that ICp 6 -Cu at IC 50 concentration led to complete inhibition of cell proliferation in both the cell lines. Cell morphology studied by confocal microscopy showed absence of cell death via necrosis or apoptosis. Instead, the treated cells displayed distinct features of non-apoptotic death such as highly vacuolated cytoplasm, lysosomal membrane permeabilization and damage to cytoskeleton F-actin filaments. In addition, ICp 6 -Cu treatment led to time dependent increase in the intracellular level of reactive oxygen species (ROS) and the cytotoxicity of ICp 6 -Cu was significantly inhibited by pre-treatment of cells with antioxidants (glutathione and trolox). These findings revealed that ICp 6 -Cu is a potent chemotoxic agent which can induce cytotoxic effect in cancer cells through elevation of intracellular ROS. It is suggested that ICp 6 -Cu may provide tumor selective chemotoxicity by exploiting difference of redox environment in normal and cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

    Science.gov (United States)

    Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

    2011-11-01

    Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

  18. Lentivirus-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth and Induces Apoptosis through MAPK Pathways in Human Retinoblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Ying Chang

    Full Text Available To explore expression and function of astrocyte elevated gene-1 (AEG-1 in human retinoblastoma (RB.The expression of AEG-1 in histological sections of human RBs and in RB cell lines was examined using immunohistochemical staining and RT-PCR and Western blotting respectively. We knocked down AEG-1 gene levels by AEG-1-siRNA lentivirus transfection of human RB cell lines SO-RB50 and Y79, and using an MTT assay, we assessed the role of AEG-1 on RB cell proliferation. The biological significance of lentivirus transfection induced AEG-1 down-regulation was examined by assessing the apoptosis rate in the transfected RB cells by Annexin V-APC staining and flow cytometry. We additionally measured the expression of Bcl-2, Bax, cleaved-caspase-3 and caspase-3, and the phosphorylation and non-phosphorylation alternation of MAPKs.AEG-1 expression was detected to be strongly positive in the histological slides of 35 out of 54 (65% patients with RB. AEG-1 expression increased significantly (P<0.05 with tumor stage. In the RB cell lines SO-RB50, Y79 and WERI-RB1 as compared with retinal pigment epithelium cells, expression of AEG-1 mRNA and AEG-1 protein was significantly higher. In AEG-1-siRNA lentivirus transfected cell cultures as compared with negative control lentivirus transfected cell cultures, levels of AEG-1 mRNA and of AEG-1 protein (P<0.05 and cell growth rates (P<0.01 were significantly lower, and apoptosis rate (P<0.001, Bax/Bcl-2 ratio and cleaved-caspase-3 protein level were significantly increased. The P-ERK/ERK ratio was significantly decreased in the AEG-1-siRNA lentivirus transfected cell lines.Expression of AEG-1 was associated with RB, in histological slides of patients and in cell culture experiments. Lentivirus transfection induced knockdown of AEG-1 had a tumor suppressive effect, potentially by tumor cell apoptosis induction through inhibition of ERK.

  19. Formaldehyde-Induced Aggravation of Pruritus and Dermatitis Is Associated with the Elevated Expression of Th1 Cytokines in a Rat Model of Atopic Dermatitis

    Science.gov (United States)

    Back, Seung Keun; Lee, Hyunkyoung; Lee, JaeHee; Kim, Hye young; Kim, Hee Jin; Na, Heung Sik

    2016-01-01

    Atopic dermatitis is a complex disease of heterogeneous pathogenesis, in particular, genetic predisposition, environmental triggers, and their interactions. Indoor air pollution, increasing with urbanization, plays a role as environmental risk factor in the development of AD. However, we still lack a detailed picture of the role of air pollution in the development of the disease. Here, we examined the effect of formaldehyde (FA) exposure on the manifestation of atopic dermatitis and the underlying molecular mechanism in naive rats and in a rat model of atopic dermatitis (AD) produced by neonatal capsaicin treatment. The AD and naive rats were exposed to 0.8 ppm FA, 1.2 ppm FA, or fresh air (Air) for 6 weeks (2 hours/day and 5 days/week). So, six groups, namely the 1.2 FA-AD, 0.8 FA-AD, Air-AD, 1.2 FA-naive, 0.8 FA-naive and Air-naive groups, were established. Pruritus and dermatitis, two major symptoms of atopic dermatitis, were evaluated every week for 6 weeks. After that, samples of the blood, the skin and the thymus were collected from the 1.2 FA-AD, the Air-AD, the 1.2 FA-naive and the Air-naive groups. Serum IgE levels were quantified with ELISA, and mRNA expression levels of inflammatory cytokines from extracts of the skin and the thymus were calculated with qRT-PCR. The dermatitis and pruritus significantly worsened in 1.2 FA-AD group, but not in 0.8 FA-AD, compared to the Air-AD animals, whereas FA didn't induce any symptoms in naive rats. Consistently, the levels of serum IgE were significantly higher in 1.2 FA-AD than in air-AD, however, there was no significant difference following FA exposure in naive animals. In the skin, mRNA expression levels of Th1 cytokines such as TNF-α and IL-1β were significantly higher in the 1.2 FA-AD rats compared to the air-AD rats, whereas mRNA expression levels of Th2 cytokines (IL-4, IL-5, IL-13), IL-17A and TSLP were significantly higher in 1.2 FA-naive group than in the Air-naive group. These results suggested that 1

  20. Formaldehyde-Induced Aggravation of Pruritus and Dermatitis Is Associated with the Elevated Expression of Th1 Cytokines in a Rat Model of Atopic Dermatitis.

    Directory of Open Access Journals (Sweden)

    Rafael Taeho Han

    Full Text Available Atopic dermatitis is a complex disease of heterogeneous pathogenesis, in particular, genetic predisposition, environmental triggers, and their interactions. Indoor air pollution, increasing with urbanization, plays a role as environmental risk factor in the development of AD. However, we still lack a detailed picture of the role of air pollution in the development of the disease. Here, we examined the effect of formaldehyde (FA exposure on the manifestation of atopic dermatitis and the underlying molecular mechanism in naive rats and in a rat model of atopic dermatitis (AD produced by neonatal capsaicin treatment. The AD and naive rats were exposed to 0.8 ppm FA, 1.2 ppm FA, or fresh air (Air for 6 weeks (2 hours/day and 5 days/week. So, six groups, namely the 1.2 FA-AD, 0.8 FA-AD, Air-AD, 1.2 FA-naive, 0.8 FA-naive and Air-naive groups, were established. Pruritus and dermatitis, two major symptoms of atopic dermatitis, were evaluated every week for 6 weeks. After that, samples of the blood, the skin and the thymus were collected from the 1.2 FA-AD, the Air-AD, the 1.2 FA-naive and the Air-naive groups. Serum IgE levels were quantified with ELISA, and mRNA expression levels of inflammatory cytokines from extracts of the skin and the thymus were calculated with qRT-PCR. The dermatitis and pruritus significantly worsened in 1.2 FA-AD group, but not in 0.8 FA-AD, compared to the Air-AD animals, whereas FA didn't induce any symptoms in naive rats. Consistently, the levels of serum IgE were significantly higher in 1.2 FA-AD than in air-AD, however, there was no significant difference following FA exposure in naive animals. In the skin, mRNA expression levels of Th1 cytokines such as TNF-α and IL-1β were significantly higher in the 1.2 FA-AD rats compared to the air-AD rats, whereas mRNA expression levels of Th2 cytokines (IL-4, IL-5, IL-13, IL-17A and TSLP were significantly higher in 1.2 FA-naive group than in the Air-naive group. These results

  1. Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway.

    Science.gov (United States)

    Li, Yi; Chen, Yan-Ming; Sun, Ming-Ming; Guo, Xiao-Dan; Wang, Ya-Chen; Zhang, Zhong-Zhi

    2016-04-20

    Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs). High intraocular pressure (HIOP), the main risk factor, causes the optic nerve damage. However, the precise mechanism of HIOP-induced RGC death is not yet completely understood. This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures, explore whether laminin is associated with apoptosis under pressure, whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival. RGC-5 cells were exposed to 0, 20, 40, and 60 mmHg in a pressurized incubator for 6, 12, and 24 h, respectively. The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blotting of cleaved caspase-3 protein. Location and expression of laminin were detected by immunofluorescence. The expression of β1-integrin, phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB, or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis. Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells. Pressure with 40 mmHg for 24 h induced a maximum apoptosis. Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h. After pretreating with laminin, RGC-5 cells survived from elevated pressure. Furthermore, β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group. The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure. Laminin can protect RGC-5 cells against high pressure via β1-integrin/FAK/AKT signaling pathway. These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure, and laminin or activating β1-integrin

  2. Effects of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 on amygdaloid kindled seizures and the anticonvulsant efficacy of diazepam.

    Science.gov (United States)

    Albertson, T E; Walby, W F

    1986-11-01

    The anticonvulsant effectiveness of the benzodiazepine antagonists RO 15-1788, CGS-8216 and PK-11195 were evaluated against threshold and suprathreshold (400 microA) stimulation in fully amygdaloid-kindled rats. Pretreatment with either RO 15-1788 (3, 10 and 30 mg/kg), CGS-8216 (3, 10 and 30 mg/kg) or PK-11195 (10 and 60 mg/kg) failed in this study to modify consistently either the afterdischarge thresholds or elicited suprathreshold seizures or duration of afterdischarge. Using a double injection paradigm, the effectiveness of these three benzodiazepine antagonists to reverse the anti-convulsant and behavioral effects of diazepam were studied. When diazepam (3 mg/kg) was injected 15 min before or after a second injection of the vehicle control DMSO (0.25 ml/kg), a significant reduction in the duration of afterdischarge and seizure rank, elicited by a suprathreshold stimulation in amygdaloid-kindled rats, occurred. When either CGS 8216 (10 mg/kg) or RO 15-1788 (10 mg/kg) were given 15 min before diazepam (3 mg/kg) prior to stimulation, the anticonvulsant properties of diazepam were blocked. When RO 15-1788 (10 mg/kg) was given 15 min after diazepam, antagonism of the anticonvulsant effects on diazepam was shown. However, when either CGS-8216 (10 mg/kg) or PK-11195 (10 and 60 mg/kg) were given 15 min after diazepam (3 mg/kg), the anticonvulsant properties of diazepam were not blocked. The anticonvulsant effects of diazepam were reversed when CGS-8216 (10 mg/kg) was given 5 min after diazepam (3 mg/kg) or when a larger dose (30 mg/kg) was given at the same 15 min interval.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Elevated Medium-Chain Acylcarnitines Are Associated With Gestational Diabetes Mellitus and Early Progression to Type 2 Diabetes and Induce Pancreatic β-Cell Dysfunction.

    Science.gov (United States)

    Batchuluun, Battsetseg; Al Rijjal, Dana; Prentice, Kacey J; Eversley, Judith A; Burdett, Elena; Mohan, Haneesha; Bhattacharjee, Alpana; Gunderson, Erica P; Liu, Ying; Wheeler, Michael B

    2018-05-01

    Specific circulating metabolites have emerged as important risk factors for the development of diabetes. The acylcarnitines (acylCs) are a family of metabolites known to be elevated in type 2 diabetes (T2D) and linked to peripheral insulin resistance. However, the effect of acylCs on pancreatic β-cell function is not well understood. Here, we profiled circulating acylCs in two diabetes cohorts: 1 ) women with gestational diabetes mellitus (GDM) and 2 ) women with recent GDM who later developed impaired glucose tolerance (IGT), new-onset T2D, or returned to normoglycemia within a 2-year follow-up period. We observed a specific elevation in serum medium-chain (M)-acylCs, particularly hexanoyl- and octanoylcarnitine, among women with GDM and individuals with T2D without alteration in long-chain acylCs. Mice treated with M-acylCs exhibited glucose intolerance, attributed to impaired insulin secretion. Murine and human islets exposed to elevated levels of M-acylCs developed defects in glucose-stimulated insulin secretion and this was directly linked to reduced mitochondrial respiratory capacity and subsequent ability to couple glucose metabolism to insulin secretion. In conclusion, our study reveals that an elevation in circulating M-acylCs is associated with GDM and early stages of T2D onset and that this elevation directly impairs β-cell function. © 2018 by the American Diabetes Association.

  4. Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

    Science.gov (United States)

    Mizoguchi, Yoshito; Kato, Takahiro A; Seki, Yoshihiro; Ohgidani, Masahiro; Sagata, Noriaki; Horikawa, Hideki; Yamauchi, Yusuke; Sato-Kasai, Mina; Hayakawa, Kohei; Inoue, Ryuji; Kanba, Shigenobu; Monji, Akira

    2014-06-27

    Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and inflammation in mice

    DEFF Research Database (Denmark)

    Alvheim, Anita R.; Torstensen, Bente E.; Lin, Yu Hong

    2013-01-01

    , arachidonic acid (AA), decreased EPA and DHA, elevated the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and increased TAG accumulation in the salmon liver. In mice, the SO salmon diet increased LA and AA and decreased EPA and DHA in the liver and erythrocyte phospholipids, and elevated......Dietary intake of linoleic acid (LA) has increased dramatically during the twentieth century and is associated with a greater prevalence of obesity. Vegetable oils are recognised as suitable alternatives to fish oil (FO) in feed for Atlantic salmon (Salmo salar L.) but introduce high amounts of LA......-inflammatory properties of EPA and DHA in mice....

  6. National Elevation Dataset (NED)

    Data.gov (United States)

    Kansas Data Access and Support Center — The U.S. Geological Survey has developed a National Elevation Database (NED). The NED is a seamless mosaic of best-available elevation data. The 7.5-minute elevation...

  7. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  8. Exercise-induced serum enzyme elevations confounding the evaluation of investigational drug toxicity. Report of two cases in a vaccine trial.

    Science.gov (United States)

    Johnson, Casey; Monath, Thomas P; Kanesa-Thasan, Niranjan; Mathis, Danell; Miller, Chuck; Shapiro, Seth; Nichols, Richard; McCarthy, Karen; Deary, Alison; Bedford, Philip

    2005-01-01

    Two subjects developed marked elevations in creatine kinase and other serum enzymes associated with mild myalgia during a randomized, double-blind, controlled Phase 1 clinical trial of an investigational live, attenuated vaccine against West Nile virus (ChimeriVax-WN02). One subject had received ChimeriVax-WN02 while the other subject was enrolled in an active control group and received licensed yellow fever 17D vaccine (YF-VAX). Subsequently, the clinical trial was interrupted, and an investigation was begun to evaluate the enzyme abnormalities. As daily serum samples were collected for determination of quantitative viremia, it was possible to define the enzyme elevations with precision and to relate these elevations to physical activity of the subjects, symptoms, and virological and serological measurements. Evaluation of both subjects clearly showed that skeletal muscle injury, and not cardiac or hepatic dysfunction, was responsible for the biochemical abnormalities. This investigation also implicated strenuous exercise as the cause of the apparent muscle injury rather than the study vaccines. As a result of this experience, subjects engaged in future early-stage trials of these live, attenuated viral vaccines will be advised not to engage in contact sports or new or enhanced exercise regimens for which they are not trained or conditioned. The inclusion of placebo control arm (in lieu of or addition to an active vaccine control) will also be useful in differentiating causally related serum enzyme elevations.

  9. A custom-made mouthpiece incorporating tongue depressors and elevators to reduce radiation-induced tongue mucositis during carbon-ion radiation therapy for head and neck cancer.

    Science.gov (United States)

    Ikawa, Hiroaki; Koto, Masashi; Ebner, Daniel K; Takagi, Ryo; Hayashi, Kazuhiko; Tsuji, Hiroshi; Kamada, Tadashi

    We introduce a custom-made mouthpiece for carbon-ion radiation therapy for head and neck malignancy. The mouthpiece incorporates either a tongue depressor or elevator depending on tumor location. The risk of tongue mucositis may be reduced without compromising therapeutic efficacy through mouthpiece shaping. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Gudmundsson, Mikkel; Birk, Jesper Bratz

    2010-01-01

    to the contra-lateral leg (CON) the day before the experiment day. On the experimental days, plasma FFA was ensured normal or remained elevated by consuming breakfast rich (low FFA) or poor (high FFA) in carbohydrate, 2 hours before performing 20 min of two-legged knee extensor exercise. Vastus lateralis...

  11. Bidirectional impact of atrazine-induced elevations in progesterone (P4) on the LH surge in the ovariectomized, estradiol (E2)-primed rat

    Science.gov (United States)

    Multiple daily exposures to the herbicide atrazine (ATZ) have been reported to suppress the luteinizing hormone surge (LHS) in female rats. Exposure has also been found to elevate P4 concentrations, and an increase in P4 is known to have a different directional effect on LH depe...

  12. Elevated CO2 induces substantial and persistent declines in forage digestibility and protein content irrespective of warming in mixed-grass prairie

    Science.gov (United States)

    Increasing atmospheric [CO2] and temperature are expected to affect the productivity, species composition, biogeochemistry, and therefore the quantity and quality of forage available to herbivores in rangeland ecosystems. Both elevated CO2 (eCO2) and warming affect plant tissue chemistry through mul...

  13. LIMITED ELEVATIONS IN ANTITUBERCULOSIS DRUG-INDUCED SERUM ALANINE AMINOTRANSFERASE (ALT) LEVELS IN A COHORT OF NIGERIANS ON TREATMENT FOR PULMONARY TUBERCULOSIS AND HIV INFECTION IN YENAGOA

    NARCIS (Netherlands)

    Ikuabe, Peter Ogie; Ebuenyi, Ikenna Desmond; Harry, Tubonye Clement

    2015-01-01

    BACKGROUND: This study, undertaken in a major tertiary hospital in the Niger Delta region of Nigeria was designed to examine the incidence of elevation in serum alanine aminotransference (ALT) in our patients who were on treatment for HIV/AIDS with some of them on antituberculosis drugs. METHOD:

  14. Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats

    International Nuclear Information System (INIS)

    Li, Zheng-Qian; Rong, Xiao-Ying; Liu, Ya-Jie; Ni, Cheng; Tian, Xiao-Sheng; Mo, Na; Chui, De-Hua; Guo, Xiang-Yang

    2013-01-01

    Highlights: •Isoflurane induces hippocampal IL-1β elevation and cognitive deficits in aged rats. •Isoflurane transiently activates the canonical NF-κB pathway in aged rat hippocampus. •NF-κB inhibitor mitigates isoflurane-induced IL-1β elevation and cognitive deficits. •We report a linkage between NF-κB signaling, IL-1β expression, and cognitive changes. -- Abstract: Although much recent evidence has demonstrated that neuroinflammation contributes to volatile anesthetic-induced cognitive deficits, there are few existing mechanistic explanations for this inflammatory process. This study was conducted to investigate the effects of the volatile anesthetic isoflurane on canonical nuclear factor (NF)-κB signaling, and to explore its association with hippocampal interleukin (IL)-1β levels and anesthetic-related cognitive changes in aged rats. After a 4-h exposure to 1.5% isoflurane in 20-month-old rats, increases in IκB kinase and IκB phosphorylation, as well as a reduction in the NF-κB inhibitory protein (IκBα), were observed in the hippocampi of isoflurane-exposed rats compared with control rats. These events were accompanied by an increase in NF-κB p65 nuclear translocation at 6 h after isoflurane exposure and hippocampal IL-1β elevation from 1 to 6 h after isoflurane exposure. Nevertheless, no significant neuroglia activation was observed. Pharmacological inhibition of NF-κB activation by pyrrolidine dithiocarbamate markedly suppressed the IL-1β increase and NF-κB signaling, and also mitigated the severity of cognitive deficits in the Morris water maze task. Overall, our results demonstrate that isoflurane-induced cognitive deficits may stem from upregulation of hippocampal IL-1β, partially via activation of the canonical NF-κB pathway, in aged rats

  15. Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one.

    Science.gov (United States)

    Nie, Lina; Di, Tianqi; Li, Yu; Cheng, Peng; Li, Ming; Gao, Jun

    2018-06-23

    Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D 2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT 2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT 2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT 2A receptors on dopamine D 2 -mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D 2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D 2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT 2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT 2A and D 2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT 2A receptors mediate maternal behavior is through

  16. Separating the roles of nitrogen and oxygen in high pressure-induced blood-borne microparticle elevations, neutrophil activation, and vascular injury in mice.

    Science.gov (United States)

    Yang, Ming; Bhopale, Veena M; Thom, Stephen R

    2015-08-01

    An elevation in levels of circulating microparticles (MPs) due to high air pressure exposure and the associated inflammatory changes and vascular injury that occur with it may be due to oxidative stress. We hypothesized that these responses arise due to elevated partial pressures of N2 and not because of high-pressure O2. A comparison was made among high-pressure air, normoxic high-pressure N2, and high-pressure O2 in causing an elevation in circulating annexin V-positive MPs, neutrophil activation, and vascular injury by assessing the leakage of high-molecular-weight dextran in a murine model. After mice were exposed for 2 h to 790 kPa air, there were over 3-fold elevations in total circulating MPs as well as subgroups bearing Ly6G, CD41, Ter119, CD31, and CD142 surface proteins-evidence of neutrophil activation; platelet-neutrophil interaction; and vascular injury to brain, omentum, psoas, and skeletal muscles. Similar changes were found in mice exposed to high-pressure N2 using a gas mixture so that O2 partial pressure was the same as that of ambient air, whereas none of these changes occurred after exposures to 166 kPa O2, the same partial pressure that occurs during high-pressure air exposures. We conclude that N2 plays a central role in intra- and perivascular changes associated with exposure to high air pressure and that these responses appear to be a novel form of oxidative stress. Copyright © 2015 the American Physiological Society.

  17. Moral elevation reduces prejudice against gay men.

    Science.gov (United States)

    Lai, Calvin K; Haidt, Jonathan; Nosek, Brian A

    2014-01-01

    Disgust is linked to social evaluation. People with higher disgust sensitivity exhibit more sexual prejudice, and inducing disgust increases sexual prejudice. We tested whether inducing moral elevation, the theoretical opposite of disgust, would reduce sexual prejudice. In four studies (N = 3622), we induced elevation with inspiring videos and then measured sexual prejudice with implicit and explicit measures. Compared to control videos that elicited no particular affective state, we found that elevation reduced implicit and explicit sexual prejudice, albeit very slightly. No effect was observed when the target of social evaluation was changed to race (Black-White). Inducing amusement, another positive emotion, did not significantly affect sexual prejudice. We conclude that elevation weakly but reliably reduces prejudice towards gay men.

  18. The hepatic Raldh1 expression is elevated in Zucker fatty rats and its over-expression introduced the retinal-induced Srebp-1c expression in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available The roles of vitamin A (VA in the development of metabolic diseases remain unanswered. We have reported that retinoids synergized with insulin to induce the expression of sterol-regulatory element-binding protein 1c gene (Srebp-1c expression in primary rat hepatocytes. Additionally, the hepatic Srebp-1c expression is elevated in Zucker fatty (ZF rats, and reduced in those fed a VA deficient diet. VA is metabolized to retinoic acid (RA for regulating gene expression. We hypothesized that the expression of RA production enzymes contributes to the regulation of the hepatic Srebp-1c expression. Therefore, we analyzed their expression levels in Zucker lean (ZL and ZF rats. The mRNA levels of retinaldehyde dehydrogenase family 1 gene (Raldh1 were found to be higher in the isolated and cultured primary hepatocytes from ZF rats than that from ZL rats. The RALDH1 protein level was elevated in the liver of ZF rats. Retinol and retinal dose- and time-dependently induced the expression of RA responsive Cyp26a1 gene in hepatocytes and hepatoma cells. INS-1 cells were identified as an ideal tool to study the effects of RA production on the regulation of gene expression because only RA, but not retinal, induced Srebp-1c mRNA expression in them. Recombinant adenovirus containing rat Raldh1 cDNA was made and used to infect INS-1 cells. The over-expression of RALDH1 introduced the retinal-mediated induction of Srebp-1c expression in INS-1 cells. We conclude that the expression levels of the enzymes for RA production may contribute to the regulation of RA responsive genes, and determine the responses of the cells to retinoid treatments. The elevated hepatic expression of Raldh1 in ZF rats may cause the excessive RA production from retinol, and in turn, result in higher Srebp-1c expression. This excessive RA production may be one of the factors contributing to the elevated lipogenesis in the liver of ZF rats.

  19. Response of a tundra ecosystem to elevated atmospheric carbon dioxide and CO{sub 2}-induced climate change. Annual technical report

    Energy Technology Data Exchange (ETDEWEB)

    Oechel, W.C.

    1992-04-01

    Northern ecosystems contain up to 455 Gt of C in the soil active layer and upper permafrost. The soil carbon in these layers is equivalent to approximately 60% of the carbon currently in the atmosphere as CO{sub 2}. Much of this carbon is stored in the soil as dead organic matter. Its fate is subject to the net effects of global change on the plant and soil systems of northern ecosystems. The arctic alone contains about 60 Gt C, 90% of which is present in the soil active layer and upper permafrost. The arctic is assumed to have been a sink for CO{sub 2} during the historic and recent geologic past. The arctic has the potential to be a very large, long-term source or sink of CO{sub 2} with respect to the atmosphere. In situ experimental manipulations of atmospheric CO{sub 2}, indicated that there is little effect of elevated atmospheric CO{sub 2} on leaf level photosynthesis or whole-ecosystem CO{sub 2} flux over the course of weeks to years, respectively. However, there may be longer- term ecosystem responses to elevated CO{sub 2} that could ultimately affect ecosystem CO{sub 2} balance. In addition to atmospheric CO{sub 2}, climate may affect net ecosystem carbon balance. Recent results indicate that the arctic has become a source of CO{sub 2} to the atmosphere. This change coincides with recent climatic variation in the arctic, and suggests a positive feedback of arctic ecosystems on atmospheric CO{sub 2} and global change. The research proposed in this application has four principal aspects: (A) Long-term response of arctic plants and ecosystems to elevated atmospheric CO{sub 2}; (B) Circumpolar patterns of net ecosystem CO{sub 2} flux; (C) In situ controls by temperature and moisture on net ecosystem CO{sub 2} flux; (D) Scaling of CO{sub 2} flux from plot, to landscape, to regional scales (In conjunction with research proposed for NSF support).

  20. Iowa Bedrock Surface Elevation

    Data.gov (United States)

    Iowa State University GIS Support and Research Facility — This Digital Elevation Model (DEM) of the bedrock surface elevation in Iowa was compiled using all available data, principally information from GEOSAM, supplemented...

  1. Diet-induced obesity elevates colonic TNF-alpha in mice and is accompanied by an activation of Wnt signaling: a mechanism for obesity-associated colorectal cancer

    Science.gov (United States)

    Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induce...

  2. Elevated VGKC-Complex Antibodies in a Boy with Fever-Induced Refractory Epileptic Encephalopathy in School-Age Children (FIRES)

    Science.gov (United States)

    Illingworth, Marjorie A.; Hanrahan, Donncha; Anderson, Claire E.; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J. Helen; Wright, Sukvhir; Dale, Russell C.; Vincent, Angela; Kurian, Manju A.

    2011-01-01

    Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and…

  3. Elevation of Plasma TGF-β1 During Radiation Therapy Predicts Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer: A Combined Analysis From Beijing and Michigan

    International Nuclear Information System (INIS)

    Zhao Lujun; Wang Luhua; Ji Wei; Wang Xiaozhen; Zhu Xiangzhi; Hayman, James A.; Kalemkerian, Gregory P.; Yang Weizhi; Brenner, Dean; Lawrence, Theodore S.; Kong, F.-M.

    2009-01-01

    Purpose: To test whether radiation-induced elevations of transforming growth factor-β1 (TGF-β1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power. Methods and Materials: Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-β1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was ≥ Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis. Results: A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-β1 ratio > 1 vs. 7.9% in patients with a TGF-β1 ratio ≤ 1 (p 20 Gy vs. 17.4% if MLD ≤ 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-β1 ratio ≤ 1 and MLD ≤ 20 Gy, 47.4% in those with a TGF-β1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-β1 ratio >1 and MLD > 20 Gy (p < 0.001). Conclusions: Radiation-induced elevation of plasma TGF-β1 level during RT is predictive of RILT. The combination of TGF- β1 and MLD may help stratify the patients for their risk of RILT.

  4. Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.

    Science.gov (United States)

    Su, Le; Zhao, BaoXiang; Lv, Xin; Wang, Nan; Zhao, Jing; Zhang, ShangLi; Miao, JunYing

    2007-02-20

    Neuronal apoptosis is a very important event in the development of the central nervous system (CNS), but the underlying mechanisms remain to be elucidated. We have previously shown that safrole oxide, a small molecule, induces integrin beta4 expression and promotes apoptosis in vascular endothelial cells. In this study, the effects of safrole oxide on cell growth and apoptosis have been examined in primary cultures of mouse neurons. Safrole oxide was found to significantly inhibit neuronal cell growth and to induce apoptosis. The inhibitory and apoptotic activities of safrole oxide followed a dose- and time-dependent manner. Interestingly, the expression of integrin beta4 was significantly inhibited with safrole oxide treatment. Furthermore, safrole oxide dramatically increases the level of intracellular reactive oxygen species (ROS) and the activity of NADPH oxidase. Moreover, manganese-dependent superoxide dismutase (MnSOD) activity was decreased significantly with safrole oxide treatment. Our study thus demonstrates that safrole oxide induces neuronal apoptosis through integrin beta4, ROS, NADPH, and MnSOD.

  5. Paroxetine-induced apoptosis in human osteosarcoma cells: Activation of p38 MAP kinase and caspase-3 pathways without involvement of [Ca2+]i elevation

    International Nuclear Information System (INIS)

    Chou, C.-T.; He Shiping; Jan, C.-R.

    2007-01-01

    Selective serotonin reuptake inhibitors (SSRIs), a group of antidepressants, are generally used for treatment of various mood and anxiety disorders. There has been much research showing the anti-tumor and cytotoxic activities of some antidepressants; but the detailed mechanisms were unclear. In cultured human osteosarcoma cells (MG63), paroxetine reduced cell viability in a concentration- and time-dependent manner. Paroxetine caused apoptosis as assessed by propidium iodide-stained cells and increased caspase-3 activation. Although immunoblotting data revealed that paroxetine could activate the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH 2 -terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor) partially prevented cells from apoptosis. Paroxetine also induced [Ca 2+ ] i increases which involved the mobilization of intracellular Ca 2+ stored in the endoplasmic reticulum and Ca 2+ influx from extracellular medium. However, pretreatment with BAPTA/AM, a Ca 2+ chelator, to prevent paroxetine-induced [Ca 2+ ] i increases did not protect cells from death. The results suggest that in MG63 cells, paroxetine caused Ca 2+ -independent apoptosis via inducing p38 MAPK-associated caspase-3 activation

  6. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

    Directory of Open Access Journals (Sweden)

    Thanos Manos

    2018-04-01

    Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

  7. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

    Science.gov (United States)

    Manos, Thanos; Zeitler, Magteld; Tass, Peter A

    2018-01-01

    In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long

  8. Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels.

    Directory of Open Access Journals (Sweden)

    Hei-Man Vincent Tang

    2009-10-01

    Full Text Available Peroxiredoxins are a family of antioxidant enzymes critically involved in cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is thought to play a role in the maintenance of genome integrity, but the underlying mechanism is not understood. In this study, we took a genetic approach to investigate the cause of genome instability in tsa1Delta cells. Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous base substitutions. An elevation in intracellular dNTP production was observed in tsa1Delta cells. This was associated with constitutive activation of the DNA damage checkpoint as indicated by phosphorylation of Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1 genes. In addition, defects in the DNA damage checkpoint did not modulate intracellular level of reactive oxygen species, but suppressed the mutator phenotype of tsa1Delta cells. On the contrary, overexpression of RNR1 exacerbated this phenotype by increasing dNTP levels. Taken together, our findings uncover a new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause of genome instability.

  9. Elevated hydrostatic pressures induce apoptosis and oxidative stress through mitochondrial membrane depolarization in PC12 neuronal cells: A cell culture model of glaucoma.

    Science.gov (United States)

    Tök, Levent; Nazıroğlu, Mustafa; Uğuz, Abdülhadi Cihangir; Tök, Ozlem

    2014-10-01

    Despite the importance of oxidative stress and apoptosis through mitochondrial depolarization in neurodegenerative diseases, their roles in etiology of glaucoma are poorly understood. We aimed to investigate whether oxidative stress and apoptosis formation are altered in rat pheochromocytoma-derived cell line-12 (PC12) neuronal cell cultures exposed to elevated different hydrostatic pressures as a cell culture model of glaucoma. Cultured PC12 cells were subjected to 0, 15 and 70 mmHg hydrostatic pressure for 1 and 24 h. Then, the following values were analyzed: (a) cell viability; (b) lipid peroxidation and intracellular reactive oxygen species production; (c) mitochondrial membrane depolarization; (d) cell apoptosis; (e) caspase-3 and caspase-9 activities; (f) reduced glutathione (GSH) and glutathione peroxidase (GSH-Px). The hydrostatic pressures (15 and 70 mmHg) increased oxidative cell damage through a decrease of GSH and GSH-Px values, and increasing mitochondrial membrane potential. Additionally, 70 mmHg hydrostatic pressure for 24 h indicated highest apoptotic effects, as demonstrated by plate reader analyses of apoptosis, caspase-3 and -9 values. The present data indicated oxidative stress, apoptosis and mitochondrial changes in PC12 cell line during different hydrostatic pressure as a cell culture model of glaucoma. This findings support the view that mitochondrial oxidative injury contributes early to glaucomatous optic neuropathy.

  10. Troponin elevation in subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Ioannis N. Mavridis

    2015-03-01

    Full Text Available Troponin (tr elevation in aneurysmal subarachnoid hemorrhage (SAH patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words: “troponin elevation” and “subarachnoid hemorrhage”. All of them, as well as relative neurosurgical books, were used for this review. Some type of cardiovascular abnormality develops in most SAH patients. Neurogenic stunned myocardium is a frequent SAH complication, due to catecholamine surge which induces cardiac injury, as evidenced by increased serum tr levels, electrocardiographic (ECG changes and cardiac wall motion abnormalities. Tr elevation, usually modest, is an early and specific marker for cardiac involvement after SAH and its levels peak about two days after SAH. Cardiac tr elevation predictors include poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, female sex, large body surface area, lower systolic blood pressure, higher heart rate and prolonged Q-Tc interval. Elevated tr levels are associated with disability and death (especially tr >1 μg/L, worse neurological grade, systolic and diastolic cardiac dysfunction, pulmonary congestion, longer intensive care unit stay and incidence of vasospasm. Tr elevation is a common finding in SAH patients and constitutes a rightful cause of worry about the patients' cardiac function and prognosis. It should be therefore early detected, carefully monitored and appropriately managed by clinicians.

  11. Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

    Science.gov (United States)

    Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

    2005-01-01

    To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic

  12. Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro.

    Science.gov (United States)

    Wang, Bao-Qiang; Yang, Quan-Hui; Xu, Rong-Kun; Xu, Jian-Ning

    2013-01-01

    Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma. In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods. Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells. There is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.

  13. Response of a tundra ecosystem to elevated atmospheric carbon dioxide and CO{sub 2}-induced climate change. Annual technical report

    Energy Technology Data Exchange (ETDEWEB)

    Oechel, W.C.

    1993-02-01

    Northern ecosystems contain up to 455 Gt of C in the soil active layer and upper permafrost, which is equivalent to approximately 60% of the carbon currently in the atmosphere as CO{sub 2}. Much of this carbon is stored in the soil as dead organic matter. Its fate is subject to the net effects of global change on the plant and soil systems of northern ecosystems. The arctic alone contains about 60 Gt C, 90% of which is present in the soil active layer and upper permafrost, and is assumed to have been a sink for CO{sub 2} during the historic and recent geologic past. Depending on the nature, rate, and magnitude of global environmental change, the arctic may have a positive or negative feedback on global change. Results from the DOE- funded research efforts of 1990 and 1991 indicate that the arctic has become a source of CO{sub 2} to the atmosphere. Measurements made in the Barrow, Alaska region during 1992 support these results. This change coincides with recent climatic variation in the arctic, and suggests a positive feedback of arctic ecosystems on atmospheric CO{sub 2} and global change. There are obvious potential errors in scaling plot level measurements to landscape, mesoscale, and global spatial scales. In light of the results from the recent DOE-funded research, and the remaining uncertainties regarding the change in arctic ecosystem function due to high latitude warming, a revised set of research goals is proposed for the 1993--94 year. The research proposed in this application has four principal aspects: (A) Long- term response of arctic plants and ecosystems to elevated atmospheric CO{sub 2}. (B) Circumpolar patterns of net ecosystem CO{sub 2} flux. (C) In situ controls by temperature and moisture on net ecosystem CO{sub 2} flux. (D) Scaling of CO{sub 2} flux from plot, to landscape, to regional scales.

  14. Feedback suppression of meal-induced glucagon-like peptide-1 (GLP-1) secretion mediated through elevations in intact GLP-1 caused by dipeptidyl peptidase-4 inhibition

    DEFF Research Database (Denmark)

    Baranov, Oleg; Kahle, Melanie; Deacon, Carolyn F

    2016-01-01

    AIM: To compare directly the clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L-cell feedback inhibition induced by dipeptidyl peptidase (DPP-4) inhibition. METHODS: A total of 24 patients (12 on a diet/exercise re......AIM: To compare directly the clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L-cell feedback inhibition induced by dipeptidyl peptidase (DPP-4) inhibition. METHODS: A total of 24 patients (12 on a diet....../exercise regimen, 12 on metformin) were treated, in randomized order, for 7-9 days, with either vildagliptin (50 mg twice daily = 100 mg/d), sitagliptin (100 mg once daily in those on diet, 50 mg twice daily in those on metformin treatment = 100 mg/d) or placebo (twice daily). A mixed-meal test was performed....... RESULTS: Intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide concentrations were doubled by both DPP-4 inhibitors. Meal-related total GLP-1 responses were reduced by vildagliptin and sitagliptin treatment alike in the majority of patients (vildagliptin: p = 0...

  15. Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells

    Directory of Open Access Journals (Sweden)

    Hyo-Jeong Lee

    2012-01-01

    Full Text Available Although cryptotanshinone (CT was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

  16. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.

    Science.gov (United States)

    Hussein, Abdelaziz M; Adel, Mohamed; El-Mesery, Mohamed; Abbas, Khaled M; Ali, Amr N; Abulseoud, Osama A

    2018-03-14

    l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score ( p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure ( p l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) ( p l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 ( p l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

  17. Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

    DEFF Research Database (Denmark)

    Parkinson, C; Kassem, M; Heickendorff, Lene

    2003-01-01

    Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...

  18. Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

    International Nuclear Information System (INIS)

    Al-Kafaji, Ghada; Malik, Afshan N.

    2010-01-01

    During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as μ-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 ± 50 vs 147 ± 54, p < 0.05), and hearts (1583 ± 277 vs 191 ± 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 ± 37 vs 18 ± 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

  19. Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

    Energy Technology Data Exchange (ETDEWEB)

    Al-Kafaji, Ghada [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom); Malik, Afshan N., E-mail: afshan.malik@kcl.ac.uk [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom)

    2010-01-22

    During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as {mu}-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 {+-} 50 vs 147 {+-} 54, p < 0.05), and hearts (1583 {+-} 277 vs 191 {+-} 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 {+-} 37 vs 18 {+-} 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

  20. Dietary docosahexaenoic acid-induced generation of liver lipid peroxides is not suppressed further by elevated levels of glutathione in ODS rats.

    Science.gov (United States)

    Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

    2006-04-01

    We examined the effects of ascorbic acid (AsA) and glutathione (GSH; experiment 1) and of GSH in acetaminophen-fed rats (experiment 2) on dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation. In experiment 1, AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats were fed soybean protein diets containing DHA (10.0% total energy) and AsA at 50 (low) or 300 (normal) mg/kg without (low) or with (normal) methionine at 2 g/kg for 32 d. In experiment 2, ODS rats were fed diets containing DHA (7.8% total energy) and acetaminophen (4 g/kg) with different levels of dietary methionine (low, moderate, high, and excessive at 0, 3, 6, and 9 g/kg, respectively) for 30 d. Tissue lipid peroxides and antioxidant levels were determined. In experiment 1, liver lipid peroxide levels in the low-AsA group were lower than those in the normal-AsA group, but kidney and testis lipid peroxide levels in the low-AsA group were higher than those in the normal-AsA group. Dietary methionine tended to decrease tissue lipid peroxide levels but did not decrease vitamin E (VE) consumption. In experiment 2, a high level of methionine (6 g/kg) decreased liver lipid peroxide levels and VE consumption. However, generation of tissue lipid peroxides and VE consumption were not decreased further by a higher dose of methionine (9 g/kg). Higher than normal levels of dietary methionine are not necessarily associated with decreased dietary DHA-induced generation of tissue lipid peroxides and VE consumption except that the GSH requirement is increased in a condition such as acetaminophen feeding.

  1. De stille elever

    DEFF Research Database (Denmark)

    Winther-Lindqvist, Ditte Alexandra

    2012-01-01

    Det er blevet en afgørende samværskompetence i uddannelsessystemet at stå aktivt frem og deltage verbalt i skoleklassens liv både fagligt og socialt. Men ikke alle elever deltager lige villigt verbalt i plenum. Artiklen handler om de stille elever og konsekvenserne af stillehed i skolen. Det...... foreslås at skolesystemet sanktionerer ældre elever hårdere for stillehed end yngre elever og det forklares med at skolelivet også er en kultivering henimod elevhed som social identitet og denne er der forventning om at eleverne mestrer i udskolingen....

  2. Acrolein produces nitric oxide through the elevation of intracellular calcium levels to induce apoptosis in human umbilical vein endothelial cells: implications for smoke angiopathy.

    Science.gov (United States)

    Misonou, Yoshiko; Asahi, Michio; Yokoe, Shunichi; Miyoshi, Eiji; Taniguchi, Naoyuki

    2006-03-01

    Acrolein is a highly electrophilic alpha, beta-unsaturated aldehyde, the levels of which are increased in the blood of smokers. To determine if acrolein is involved in the pathology of smoke angiopathy, the effect of acrolein on human umbilical vein endothelial cells (HUVEC) was examined. Intracellular nitric oxide (NO) levels, determined using diaminofluorescein-2 diacetate (DAF-2 DA), an NO sensitive fluorescent dye, were found to be increased after treatment in HUVEC with 10 microM acrolein. The measurement of nitrite with 2,3-diaminonaphthalene and a Western blot analysis revealed that nitrite and S-nitroso-cysteine levels were increased in a dose-dependent manner, confirming that NO production is increased by acrolein. The increase was not reduced by treatment with 10mM N-acetyl-l-cysteine (NAC), an anti-oxidant, but was reduced with 10 microM of the intracellular calcium chelator, 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester. Acrolein-stimulated NO production was significantly reduced by pretreatment with 1mM N(G)-nitro-l-arginine-methyl ester (L-NAME), an NO synthase inhibitor. The cytotoxicity of acrolein was reduced by pretreatment with 10 microM 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO), an intracellular NO scavenger, or 1mM L-NAME, whereas it was not reduced by 10mM NAC, 20 microM Curcumin, another peroxide scavenger, or 100 microM Mn(III)TMPyP, a superoxide dismutase mimic. Nuclear staining and a Western blot analysis using an anti-cleaved caspase 3 antibody revealed that the reduced viability of HUVEC by acrolein was due to apoptosis, which was reversed after pretreatment with 0.1mM carboxy-PTIO or 1mM L-NAME. Thus, acrolein increases intracellular calcium production to induce intracellular NO production by a calcium-dependent NO synthase, possibly eNOS, and the excess and rapid increase in NO might lead to the apoptosis of HUVEC. These data suggest that acrolein might be

  3. Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

    Science.gov (United States)

    Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

    2011-06-01

    ). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2.

    Science.gov (United States)

    Le Bacquer, Olivier; Petroulakis, Emmanuel; Paglialunga, Sabina; Poulin, Francis; Richard, Denis; Cianflone, Katherine; Sonenberg, Nahum

    2007-02-01

    The most common pathology associated with obesity is insulin resistance, which results in the onset of type 2 diabetes mellitus. Several studies have implicated the mammalian target of rapamycin (mTOR) signaling pathway in obesity. Eukaryotic translation initiation factor 4E-binding (eIF4E-binding) proteins (4E-BPs), which repress translation by binding to eIF4E, are downstream effectors of mTOR. We report that the combined disruption of 4E-BP1 and 4E-BP2 in mice increased their sensitivity to diet-induced obesity. Increased adiposity was explained at least in part by accelerated adipogenesis driven by increased expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), C/EBPalpha, and PPARgamma coupled with reduced energy expenditure, reduced lipolysis, and greater fatty acid reesterification in the adipose tissue of 4E-BP1 and 4E-BP2 double KO mice. Increased insulin resistance in 4E-BP1 and 4E-BP2 double KO mice was associated with increased ribosomal protein S6 kinase (S6K) activity and impairment of Akt signaling in muscle, liver, and adipose tissue. These data clearly demonstrate the role of 4E-BPs as a metabolic brake in the development of obesity and reinforce the idea that deregulated mTOR signaling is associated with the development of the metabolic syndrome.

  5. Adenosine monophosphate is elevated in the bronchoalveolar lavage fluid of mice with acute respiratory toxicity induced by nanoparticles with high surface hydrophobicity.

    Science.gov (United States)

    Dailey, Lea Ann; Hernández-Prieto, Raquel; Casas-Ferreira, Ana Maria; Jones, Marie-Christine; Riffo-Vasquez, Yanira; Rodríguez-Gonzalo, Encarnación; Spina, Domenico; Jones, Stuart A; Smith, Norman W; Forbes, Ben; Page, Clive; Legido-Quigley, Cristina

    2015-02-01

    Inhaled nanomaterials present a challenge to traditional methods and understanding of respiratory toxicology. In this study, a non-targeted metabolomics approach was used to investigate relationships between nanoparticle hydrophobicity, inflammatory outcomes and the metabolic fingerprint in bronchoalveolar fluid. Measures of acute lung toxicity were assessed following single-dose intratracheal administration of nanoparticles with varying surface hydrophobicity (i.e. pegylated lipid nanocapsules, polyvinyl acetate nanoparticles and polystyrene beads; listed in order of increasing hydrophobicity). Broncho-alveolar lavage (BAL) fluid was collected from mice exposed to nanoparticles at a surface area dose of 220 cm(2) and metabolite fingerprints were acquired via ultra pressure liquid chromatography-mass spectrometry-based metabolomics. Particles with high surface hydrophobicity were pro-inflammatory. Multivariate analysis of the resultant small molecule fingerprints revealed clear discrimination between the vehicle control and polystyrene beads (p < 0.05), as well as between nanoparticles of different surface hydrophobicity (p < 0.0001). Further investigation of the metabolic fingerprints revealed that adenosine monophosphate (AMP) concentration in BAL correlated with neutrophilia (p < 0.01), CXCL1 levels (p < 0.05) and nanoparticle surface hydrophobicity (p < 0.001). Our results suggest that extracellular AMP is an intermediary metabolite involved in adenine nucleotide-regulated neutrophilic inflammation as well as tissue damage, and could potentially be used to monitor nanoparticle-induced responses in the lung following pulmonary administration.

  6. Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Nelli Giribabu

    2014-01-01

    Full Text Available P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO product, malondialdehyde (MDA, and the diminution of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes.

  7. Undervisning af tosprogede elever

    DEFF Research Database (Denmark)

    Horst, Christian

    2003-01-01

    Artiklen fremdrager hovedresultaterne fra Virginia P. Collier's og Wayne P. Thomas's længdeundersøgelser af tosprogede elever i USA, som formentlig er de mest omfattende undersøgelser af undervisningen af tosprogede elever overhovedet. Resultaterne diskuteres i relation til udviklingen af en...

  8. Effects of elevated CO

    NARCIS (Netherlands)

    Xue, Sha; Yang, Xiaomei; Liu, Guobin; Gai, Lingtong; Zhang, Changsheng; Ritsema, Coen J.; Geissen, Violette

    2017-01-01

    Elevated CO2 and drought are key consequences of climate change and affect soil processes and plant growth. This study investigated the effects of elevated CO2 and drought on the microbial biomass and enzymatic activities in the rhizospheres of Bothriochloa ischaemum and

  9. Dyslipidemic Diet-Induced Monocyte “Priming” and Dysfunction in Non-Human Primates Is Triggered by Elevated Plasma Cholesterol and Accompanied by Altered Histone Acetylation

    Directory of Open Access Journals (Sweden)

    John D. Short

    2017-08-01

    Full Text Available Monocytes and the recruitment of monocyte-derived macrophages into sites of inflammation play a key role in atherogenesis and other chronic inflammatory diseases linked to cardiometabolic syndrome and obesity. Previous studies from our group have shown that metabolic stress promotes monocyte priming, i.e., enhanced adhesion and accelerated chemotaxis of monocytes in response to chemokines, both in vitro and in dyslipidemic LDLR−/− mice. We also showed that metabolic stress-induced monocyte dysfunction is, at least to a large extent caused by the S-glutathionylation, inactivation, and subsequent degradation of mitogen-activated protein kinase phosphatase 1. Here, we analyzed the effects of a Western-style, dyslipidemic diet (DD, which was composed of high levels of saturated fat, cholesterol, and simple sugars, on monocyte (dysfunction in non-human primates (NHPs. We found that similar to mice, a DD enhances monocyte chemotaxis in NHP within 4 weeks, occurring concordantly with the onset of hypercholesterolemia but prior to changes in triglycerides, blood glucose, monocytosis, or changes in monocyte subset composition. In addition, we identified transitory decreases in the acetylation of histone H3 at the lysine residues 18 and 23 in metabolically primed monocytes, and we found that monocyte priming was correlated with the acetylation of histone H3 at lysine 27 after an 8-week DD regimen. Our data show that metabolic stress promotes monocyte priming and hyper-chemotactic responses in NHP. The histone modifications accompanying monocyte priming in primates suggest a reprogramming of the epigenetic landscape, which may lead to dysregulated responses and functionalities in macrophages derived from primed monocytes that are recruited to sites of inflammation.

  10. Laser-induced thermotherapy (LITT) elevates mRNA expression of connective tissue growth factor (CTGF) associated with reduced tumor growth of liver metastases compared to hepatic resection.

    Science.gov (United States)

    Isbert, Christoph; Ritz, Jörg-Peter; Roggan, André; Schuppan, Detlef; Ajubi, Navid; Buhr, Heinz Johannes; Hohenberger, Werner; Germer, Christoph-Thomas

    2007-01-01

    Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24-96 hours and 14 days after intervention. Volumes of the untreated tumors prior to intervention were 38+/-8 mm(3) in group I (laser), 39 +/- 7 mm(3) in group II (resection), and 42 +/- 12 mm(3) in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor+/-SEM volume of untreated tumor in group I (laser) [223 +/- 36] was smaller than in group II (resection) [1233.28 +/- 181.52; P tumor growth in comparison to hepatic resection. Accelerated tumor growth after hepatic resection is associated with higher mRNA level of HGF and reduced tumor growth after LITT with higher mRNA level of CTGF. The increased CTGF-mediated regulation of ECM may cause reduced residual tumor growth after LITT. (c) 2006 Wiley-Liss, Inc.

  11. Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons ( Papio anubis) With Experimentally-Induced Disease.

    Science.gov (United States)

    Nothnick, Warren B; Falcone, Tommaso; Joshi, Niraj; Fazleabas, Asgerally T; Graham, Amanda

    2017-08-01

    We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endometriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis.

  12. Elevator and hydraulics; Elevator to yuatsu

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, I. [Hitachi, Ltd., Tokyo (Japan)

    1994-07-15

    A hydraulic type elevator is installed in relatively lower buildings as compared with a rope type elevator, but the ratio in the number of installation of the former elevator is increasing. This paper explains from its construction and features to especially various control systems for the riding comfort and safety. A direct push-up system with hydraulic jacks arranged beneath a car, and an indirect push-up system that has hydraulic jacks arranged on flank of a car and transmits the movement of a plunger via a rope are available. The latter system eliminates the need of large holes to embed hydraulic jacks. While the speed is controlled by controlling flow rates of high-pressure oil, the speed, position, acceleration and even time differential calculus of the acceleration must be controlled severely. The system uses two-step control for the through-speed and the landing speed. Different systems that have been realized may include compensation for temperatures in flow rate control valves, load pressures, and oil viscosity, from learning control to fuzzy control for psychological effects, or control of inverters in motors. 13 refs., 12 figs., 1 tab.

  13. Is moral elevation an approach-oriented emotion?

    OpenAIRE

    Van de Vyver, Julie; Abrams, Dominic

    2016-01-01

    Abstract Two studies were designed to test whether moral elevation should be conceptualized as an approach-oriented emotion. The studies examined the relationship between moral elevation and the behavioral activation and inhibition systems. Study 1 (N?=?80) showed that individual differences in moral elevation were associated with individual differences in behavioral activation but not inhibition. Study 2 (N?=?78) showed that an elevation-inducing video promoted equally high levels of approac...

  14. Elevators or stairs?

    Science.gov (United States)

    Shah, Sachin; O’Byrne, Michael; Wilson, Merne; Wilson, Thomas

    2011-01-01

    Background: Staff in hospitals frequently travel between floors and choose between taking the stairs or elevator. We compared the time savings with these two options. Methods: Four people aged 26–67 years completed 14 trips ranging from one to six floors, both ascending and descending. We compared the amount of time per floor travelled by stairs and by two banks of elevators. Participants reported their fatigue levels using a modified Borg scale. We performed two-way analysis of variance to compare the log-transformed data, with participant and time of day as independent variables. Results: The mean time taken to travel between each floor was 13.1 (standard deviation [SD] 1.7) seconds by stairs and 37.5 (SD 19.0) and 35.6 (SD 23.1) seconds by the two elevators (F = 8.61, p elevator equaled about 15 minutes a day. Self-reported fatigue was less than 13 (out of 20) on the Borg scale for all participants, and they all stated that they were able to continue their duties without resting. The extra time associated with elevator use was because of waiting for its arrival. There was a difference in the amount of time taken to travel by elevator depending on the time of day and day of the week. Interpretation: Taking the stairs rather than the elevator saved about 15 minutes each workday. This 3% savings per workday could translate into improved productivity as well as increased fitness. PMID:22159365

  15. l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70

    Directory of Open Access Journals (Sweden)

    Abdelaziz M. Hussein

    2018-03-01

    Full Text Available l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal (negative control or pentylenetetrazole (PTZ 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car (100 mg/kg/day × 4 weeks (PTZ + l-Car, while the second group received saline (PTZ + Sal. Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score (p = 0.0002 that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure (p < 0.0001 and shortened seizure duration (p = 0.028. In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA (p < 0.0001 and reduced the activity of catalase enzyme (p = 0.0006 and increased antioxidant GSH activity (p < 0.0001. Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 (p < 0.0001 and β-catenin (p < 0.0001. Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

  16. Elevated temperature fracture mechanics

    International Nuclear Information System (INIS)

    Tomkins, B.

    1979-01-01

    The application of fracture mechanics concepts to cracks at elevated temperatures is examined. Particular consideration is given to the characterisation of crack tip stress-strain fields and parameters controlling crack extension under static and cyclic loads. (author)

  17. Indsatser for tosprogede elever

    DEFF Research Database (Denmark)

    Andersen, Dines; Jakobsen, Vibeke; Jensen, Vibeke Myrup

    Fagligt set klarer tosprogede elever sig dårligere i skolen og det videre uddannelsessystem end ’danske’ elever. Kommuner og folkeskoler har derfor sat en række tiltag i værk, som sigter mod at forbedre de tosprogede elevers skole- og uddannelsessituation. Rapporten kortlægger og analyserer...... af klasseundervisningen. Analysen viser, at de elever, der bliver taget ud af klassen for at få ekstra undervisning i dansk som andetsprog, klarer sig dårligere end elever, der modtager ekstraundervisningen i klassen eller uden for skoletid. Undersøgelsen er baseret på spørgeskemaundersøgelser blandt...... kommunale forvaltningschefer, skoleledere, lærere og forældre til børn i 2. klasse samt lærere til og elever i 9. klasse, SFI’s forløbsundersøgelse af årgang 1995 og registerdata. Undersøgelsen er via Ministeriet for Børn og Undervisning betalt med midler fra satspuljeaftalen 2009 om integration....

  18. Restoring the IL-1β/NF-κB-induced impaired chondrogenesis by diallyl disulfide in human adipose-derived mesenchymal stem cells via attenuation of reactive oxygen species and elevation of antioxidant enzymes.

    Science.gov (United States)

    Bahrampour Juybari, Kobra; Kamarul, Tunku; Najafi, Mohammad; Jafari, Davood; Sharifi, Ali Mohammad

    2018-03-26

    Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured articular cartilage are not effective enough in osteoarthritis (OA). Due to the enhanced inflammation and oxidative stress in OA microenvironment, differentiation of MSCs into chondrocytes would be impaired. This study aims to explore the effects of diallyl disulfide (DADS) on IL-1β-mediated inflammation and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs) during chondrogenesis. MTT assay was employed to examine the effects of various concentrations of DADS on the viability of hADSCs at different time scales to obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1β-induced intracellular ROS generation and lipid peroxidation were evaluated in hADSCs. Western blotting was used to analyze the protein expression levels of IκBα (np), IκBα (p), NF-κB (np) and NF-κB (p). Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and chondrogenic markers at days 7, 14 and 21 of differentiation were measured using qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid peroxidation, IκBα activation and NF-κB nuclear translocation in hADSCs treated with IL-1β. In addition, DADS could significantly increase the expression levels of IL-1β-induced impaired chondrogenic marker genes in differentiated hADSCs. Treatment with DADS may provide an effective approach to prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes of chondrocyte cell death and enhance the protective anabolic effects by promoting chondrogenesis associated gene expressions in hADSCs exposed to OA condition.

  19. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    International Nuclear Information System (INIS)

    Kwong, Raymond W.M.; Andres, Jose A.; Niyogi, Som

    2011-01-01

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  20. Effects of dietary cadmium exposure on tissue-specific cadmium accumulation, iron status and expression of iron-handling and stress-inducible genes in rainbow trout: Influence of elevated dietary iron

    Energy Technology Data Exchange (ETDEWEB)

    Kwong, Raymond W.M. [Toxicology Centre, University of Saskatchewan, Saskatoon, SK, S7N 5B3 (Canada); Andres, Jose A. [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, SK, S7N 5E2 (Canada)

    2011-03-15

    Recent evidences suggest that dietary cadmium (Cd) uptake likely occurs via the dietary iron (Fe) uptake pathway in freshwater fish, at least in part. The present study investigated the interactive effects of dietary Cd and Fe in juvenile rainbow trout (Oncorhynchus mykiss). Fish were treated for four weeks with four different diets: normal Fe, high Fe, normal Fe plus Cd, and high Fe plus Cd. Physiological parameters, tissue-specific Fe and Cd level, plasma Fe status, and tissue-specific mRNA expression of transferrin, metallothioneins (MT-A and MT-B) and heat shock proteins 70 (HSP70a and HSP70b) were analyzed. Exposure to dietary Cd increased Cd burden in the following order: intestine > kidney > stomach > liver > gill > carcass. Interestingly, high dietary Fe reduced Cd accumulation in the stomach and intestine as well as in the wholebody of fish. Dietary Cd increased hepatic transferrin mRNA expression and total Fe binding capacity in the plasma, indicating the effect of Cd on Fe handling in fish. The mRNA expression of MTs and HSP70s was also increased in various tissues following dietary Cd exposure, however the response profile of different MT and HSP70 genes was not consistent among different tissues. In general, MT-A was more responsive to Cd exposure in the intestine and liver, whereas MT-B was more responsive in the kidney. Similarly, HSP70a expression was more sensitive to Cd exposure than HSP70b, particularly in the intestine. Interestingly, high Fe diet suppressed Cd-induced induction of transferrin, MT and HSP70 genes in various tissues. Overall, our study suggests that elevated dietary Fe can reduce Cd accumulation and ameliorate Cd-induced stress responses in freshwater fish.

  1. Theobromine induced seminiferous tubular lesion with elevated ...

    African Journals Online (AJOL)

    Concentrations of serum testosterone, albumin, transferrin, total serum protein and testicular histology of male albino wistar rats were evaluated following administration of 700mg/kg body weight theobromine in 0.5ml 14% sodium acetate for seven days. Theobromine administration produced significant increase in serum ...

  2. [Pharmacology of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (II). Sleep-inducing activity and effect on the motor system].

    Science.gov (United States)

    Yamamoto, K; Matsushita, A; Sawada, T; Naito, Y; Yoshimura, K; Takesue, H; Utsumi, S; Kawasaki, K; Hirono, S; Koshida, H

    1984-07-01

    The sleep-inducing activity and effect on the motor system of the 1H-1,2,4-triazolyl benzophenone derivative 450191-S were examined behaviorally, electroencephalographically and electro-physiologically with various species of animals and were compared with those of diazepam, nitrazepam, estazolam and triazolam. In the rhesus monkey, rabbit and rat with chronically indwelling brain electrodes, 0.6 to 3 mg/kg, p.o. of 450191-S caused a shorter latency of sleep onset, an increase of and a stable continuity of slow wave deep sleep (SWDS) with higher amplitude, and the appearance of clear spindle bursts in the slow wave light sleeping (SWLS) state with little muscle relaxation. Animals treated with nitrazepam and/or estazolam showed a smaller increase in SWDS and its unstable continuity with remarkable disturbance of gait. The doses needed to induce sleep in the rhesus monkey were 0.6 to 1 mg/kg p.o. for 450191-S, 3 mg/kg for nitrazepam, 1 mg/kg for estazolam and 0.3 mg/kg for triazolam. The cat treated with 450191-S showed the phenomena caused by benzodiazepines (BDZ), i.e., behavioral excitation and decrease of frequencies in the hippocampal theta waves. The suppressive effects of 450191-S on the EEG arousal reaction and/or blood pressure elevation induced by hypothalamic stimulation in the rabbit suggested that the inhibitory effects acted on the posterior hypothalamus to the limbic system. The inhibitory effect of 450191-S on the amygdaloid kindling in the rat was as potent as those of diazepam and nitrazepam. Successive daily oral administration of both 3 mg/kg of 450191-S and/or 3 to 6 mg/kg of nitrazepam for 15 days in the rabbit caused slight decrease of SWDS and increase of fast wave (REM) sleep (FWS). During the withdrawal period of both compounds, a slight but insignificant increase in the waking state was noticed for 1 to 2 days, but not a rebound increase of FWS. Intravenously administered 450191-S showed the same action as BDZ on the spinal reflex and the

  3. National Elevation Dataset

    Science.gov (United States)

    ,

    2002-01-01

    The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey. NED is designed to provide National elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, perform edge matching, and fill sliver areas of missing data. NED has a resolution of one arc-second (approximately 30 meters) for the conterminous United States, Hawaii, Puerto Rico and the island territories and a resolution of two arc-seconds for Alaska. NED data sources have a variety of elevation units, horizontal datums, and map projections. In the NED assembly process the elevation values are converted to decimal meters as a consistent unit of measure, NAD83 is consistently used as horizontal datum, and all the data are recast in a geographic projection. Older DEM's produced by methods that are now obsolete have been filtered during the NED assembly process to minimize artifacts that are commonly found in data produced by these methods. Artifact removal greatly improves the quality of the slope, shaded-relief, and synthetic drainage information that can be derived from the elevation data. Figure 2 illustrates the results of this artifact removal filtering. NED processing also includes steps to adjust values where adjacent DEM's do not match well, and to fill sliver areas of missing data between DEM's. These processing steps ensure that NED has no void areas and artificial discontinuities have been minimized. The artifact removal filtering process does not eliminate all of the artifacts. In areas where the only available DEM is produced by older methods, then "striping" may still occur.

  4. Interaktive tavler - interaktive elever

    DEFF Research Database (Denmark)

    Reusch, Charlotte F.; Otzen, Elsebeth

    Abstract, Poster-præsentation 13.-14. juni 2012, Pilotprojekt: Interaktive tavler – interaktive elever Lektor, cand. pæd., Elsebeth Otzen og Lektor, cand. mag., Charlotte Reusch, Institut for Skole og Læring, Læreruddannelsen, Professionshøjskolen Metropol, København Hvordan motiverer en interaktiv...... tavle lærere og elever? Hvad sker der mellem elev, stof og lærer, når læreren bliver i stand til at billedliggøre og dynamisere sine oplæg på tavlen? Bliver læreroplæg prioriteret? Bliver eleverne aktive, eller ender den interaktive tavle med blot at understøtte lærerens envejskommunikation til klassen......? Og hvad sker der mellem eleverne? Disse spørgsmål var igangsættende for arbejdet med pilotprojektet Interaktive tavler – interaktive elever, som blev afviklet i skoleåret 2010-2011. Projektet blev udført af en tværfaglig gruppe, bestående af lektorer i matematik, biologi og dansk i læreruddannelsen...

  5. Udeskole og elevers handlekompetence

    DEFF Research Database (Denmark)

    Breiting, Søren

    2011-01-01

    Elever elsker at komme væk fra undervisningen i skolen. Er det positivt eller negativt? Og hvad har betydning for, at eleverne får mest muligt ud af oplevelserne uden for skolen? Forskellige former for udeskole giver nogle oplagte muligheder, så eleverne udvikler sig som engagerede borgere i et...

  6. Interaktive tavler - interaktive elever

    DEFF Research Database (Denmark)

    Reusch, Charlotte; Otzen, Elsebeth

    Abstract, Poster-præsentation 13.-14. juni 2012, Pilotprojekt: Interaktive tavler ? interaktive elever Lektor, cand. pæd., Elsebeth Otzen og Lektor, cand. mag., Charlotte Reusch, Institut for Skole og Læring, Læreruddannelsen, Professionshøjskolen Metropol, København Hvordan motiverer en interaktiv...... tavle lærere og elever? Hvad sker der mellem elev, stof og lærer, når læreren bliver i stand til at billedliggøre og dynamisere sine oplæg på tavlen? Bliver læreroplæg prioriteret? Bliver eleverne aktive, eller ender den interaktive tavle med blot at understøtte lærerens envejskommunikation til klassen......? Og hvad sker der mellem eleverne? Disse spørgsmål var igangsættende for arbejdet med pilotprojektet Interaktive tavler ? interaktive elever, som blev afviklet i skoleåret 2010-2011. Projektet blev udført af en tværfaglig gruppe, bestående af lektorer i matematik, biologi og dansk i læreruddannelsen...

  7. Skuldertesten "Kombineret Elevation"

    DEFF Research Database (Denmark)

    Clausen, Mikkel Bek; Overkær, Brian

    2010-01-01

    Formål: At udarbejde en testprotokol for testen Kombineret Elevation (KE) og undersøge test-retest variationen ved test af elite svømmere, samt diskutere testens relevans og validitet. Materiale og Metode: 9 elite og 10 sub-elite svømmere, heraf var 11 mænd og 8 kvinder, gennemførte testen KE 2...

  8. Elevated ammonium levels

    DEFF Research Database (Denmark)

    Søgaard, Rikke; Novak, Ivana; MacAulay, Nanna

    2012-01-01

    was not enhanced. The ammonium-induced stimulation of EAAT3 increased with increasing extracellular pH, suggesting that the gaseous form NH(3) mediates the effect. An ammonium-induced intracellular alkalinization was excluded as the cause of the enhanced EAAT3 activity because 1) ammonium acidified the oocyte...

  9. A spider elevator

    Energy Technology Data Exchange (ETDEWEB)

    Butylkin, A.V.; Butylkin, V.A.; Izosimov, A.M.

    1983-01-01

    A spider elevator is proposed which contains a body, a wedge clamp with wedges hinged to each other, a subassembly for holding the wedge clamp in the open and closed positions and a mechanism for changing the wedge clamp, which is made in the form of levers with ears for cleats and installed in the body with the capability of turning. To increase reliability in the operational mode through using the external force for clamping the pipe, the free ends of the levers are hinged with the body by a power cylinder.

  10. Elevator Control Strategies

    OpenAIRE

    Ceder, Frederick; Nordin, Alexandra

    2013-01-01

    The purpose of this essay is to investigate if it is eective to switch strategies for elevators during one day in an oce building. This essay describes some of the strategies in use today, followed by a comparison and analysis of two of the strategies described. We have also implemented optimizations to one of these strategies. From our test results we can conclude that our optimized strategy worked and produced better results on average waiting time and total traveling time than the two stra...

  11. Automatic pipe elevator

    Energy Technology Data Exchange (ETDEWEB)

    Haney, K.M.; Willis, C.A.

    1987-03-17

    This patent describes an elevator adapted for use with a power swivel for supporting a drilling or production tubular, the elevator comprising: at least two jaws, each jaw having a clamping surface; a connector member for supporting the jaws, the connector member comprising an upper end, a lower end, means for coupling the upper end to the power swivel, means for coupling the lower end to a tubular. The member also comprises means for defining a passageway extending from the upper end to the lower end through the connector member to allow drilling mud to be passed from the power swivel through the bore, into the tubular; and linkage means mounted between the connector member and the jaws for coupling the jaws to the connector member and for maintaining the clamping surfaces of the jaws in clamping engagement with the tubular when the connector member and the tubular are urged apart relative to one another. The linkage means is configured such that the force by which the clamping surfaces clamp the tubular increases as the force urging the connector member and the tubular apart increases.

  12. Elevation data for floodplain mapping

    National Research Council Canada - National Science Library

    Committee on Floodplain Mapping Technologies; National Research Council; Division on Earth and Life Studies; National Research Council

    2007-01-01

    .... Elevation Data for Floodplain Mapping shows that there is sufficient two-dimensional base map imagery to meet FEMA's flood map modernization goals, but that the three-dimensional base elevation data...

  13. An elevator wheel

    Energy Technology Data Exchange (ETDEWEB)

    Zhornik, V.I.; Cherkov, Ye.M.; Simonov, A.A.

    1982-01-01

    This invention deals with mineral enrichment and is primarily for unloading submerged products of enrichment during separation in heavy mediums. An elevator wheel is proposed for unloading the submerged product from the bath of a heavy to medium separator which includes ladle disks with internal walls and overlapping sheets hinged to the ends. In order to increase the degree of dehydration of the unloaded product, the internal wall of each ladle is made of sheets installed in stages with clearances relative to each other. The advantages of the proposed device include an improvement in the degree of dehydration of the submerged product in the ladles and a reduction in the carry away of the heavy medium with the enrichment products.

  14. Plastic responses to elevated temperature in low and high elevation populations of three grassland species.

    Science.gov (United States)

    Frei, Esther R; Ghazoul, Jaboury; Pluess, Andrea R

    2014-01-01

    Local persistence of plant species in the face of climate change is largely mediated by genetic adaptation and phenotypic plasticity. In species with a wide altitudinal range, population responses to global warming are likely to differ at contrasting elevations. In controlled climate chambers, we investigated the responses of low and high elevation populations (1200 and 1800 m a.s.l.) of three nutrient-poor grassland species, Trifolium montanum, Ranunculus bulbosus, and Briza media, to ambient and elevated temperature. We measured growth-related, reproductive and phenological traits, evaluated differences in trait plasticity and examined whether trait values or plasticities were positively related to approximate fitness and thus under selection. Elevated temperature induced plastic responses in several growth-related traits of all three species. Although flowering phenology was advanced in T. montanum and R. bulbosus, number of flowers and reproductive allocation were not increased under elevated temperature. Plasticity differed between low and high elevation populations only in leaf traits of T. montanum and B. media. Some growth-related and phenological traits were under selection. Moreover, plasticities were not correlated with approximate fitness indicating selectively neutral plastic responses to elevated temperature. The observed plasticity in growth-related and phenological traits, albeit variable among species, suggests that plasticity is an important mechanism in mediating plant responses to elevated temperature. However, the capacity of species to respond to climate change through phenotypic plasticity is limited suggesting that the species additionally need evolutionary adaptation to adjust to climate change. The observed selection on several growth-related and phenological traits indicates that the study species have the potential for future evolution in the context of a warming climate.

  15. Group control of elevators

    Energy Technology Data Exchange (ETDEWEB)

    Umeda, Yasukazu; Hikita, Shiro; Tuji, Sintaro (Mitsubishi Electric Corp., Tokyo (Japan))

    1988-09-05

    Items to be evaluated in the group control of elevators, and a typical control system are described. A new system in which the fuzzy rule base is employed is introduced together with the configuration. The items to be evaluated are waiting time, riding time, accuracy of forecasting, energy saving, and ease of usage. The everage waiting time of less than 20 seconds with less than 3% waiting rate of more than 60 seconds is accepted as a satisfactory service condition. There are many conflicting matters in group-controlling, and the study for the controlling must deal with the optimization of multi-purpose problems. The standards for group-control evaluation differ according to building structures and the tastes of users, and an important problem is where to give emphasis of the evaluation. The TRAFFIC PATTERN LEARNING METHOD has been applied in the system for careful control to accommodate the traffic. No specific function is provided for the evaluation, but the call allocation is made by fuzzy rule-base. The configuration of a new group-control system is introduced. 7 references, 7 figures, 1 table.

  16. Lærer-elev-relationer

    DEFF Research Database (Denmark)

    Laursen, Per Fibæk; Nielsen, Anne Maj

    2015-01-01

    I kapitlet belyser vi relationskompetence i forholdet mellem lærer og elever og hvordan læreren kan arbejde med forhold til elever og med sin opmærksomhed på relationsarbejdet. Afslutningsvis ser vi på hvordan lærere fortsat kan udvikle deres relationskompetence.......I kapitlet belyser vi relationskompetence i forholdet mellem lærer og elever og hvordan læreren kan arbejde med forhold til elever og med sin opmærksomhed på relationsarbejdet. Afslutningsvis ser vi på hvordan lærere fortsat kan udvikle deres relationskompetence....

  17. Tanzania Elevation and Surface Characteristics

    Data.gov (United States)

    US Agency for International Development — The dataset displays Elevation, Slope, Aspect, Topographic Position Index, Terrain Ruggedness, and Roughness based on Shuttle Radar Topography Mission (SRTM) (3...

  18. Elevated carbon dioxide increases salicylic acid in Glycine max.

    Science.gov (United States)

    Casteel, Clare L; Segal, Lauren M; Niziolek, Olivia K; Berenbaum, May R; DeLucia, Evan H

    2012-12-01

    Concentrations of carbon dioxide (CO(2)) are increasing in the atmosphere, affecting soybean (Glycine max L.) phytohormone signaling and herbivore resistance. Whether the impact of elevated CO(2) on phytohormones and induced defenses is a generalized response within this species is an open question. We examined jasmonic acid (JA) and salicylic acid (SA) under ambient and elevated CO(2) concentrations with and without Japanese beetle (Popillia japonica Newman) damage and artificial damage across six soybean cultivars (HS93-4118, Pana, IA 3010, Loda, LN97-15076, and Dwight). Elevated CO(2) reduced constitutive levels of JA and related transcripts in some but not all soybean cultivars. In contrast to the variation in JA, constitutive levels of salicylic were increased universally among soybean cultivars grown under elevated CO(2). Variation in hormonal signaling may underpin observed variation in the response of insect herbivores and pathogens to plants grown under elevated CO(2).

  19. Elevation of the diaphragmatic cupola

    International Nuclear Information System (INIS)

    Semenov, V.M.; Talesnik, M.R.

    1988-01-01

    Altogether 45 patients with elevation of the diaphragmatic cupola were examined. A high frequency of erroneous initial interpretation of examination results was noted in inflammatory and tumorous lesions and congenital conditions. Routine and contrast methods (pneumoperitoneum, bronchography, pleurography and fistulography) were used. Disease-related methods of X-ray investigation were proposed. A variety of causes of diaphragm elevation was indicated

  20. Seizures induced by carbachol, morphine, and leucine-enkephalin: a comparison.

    Science.gov (United States)

    Snead, O C

    1983-04-01

    The electrical, behavioral, and pharmacological properties of seizures induced by morphine, leucine-enkephalin, and the muscarinic cholinergic agonist carbachol were examined and compared. Low-dose carbachol given intracerebroventricularly (ICV) produced seizures similar electrically to those produced by ICV morphine and leucine-enkephalin, although there was some difference in site of subcortical origin of onset. Carbachol and morphine were similar in that they had the same anticonvulsant profile, produced similar behavioral changes, caused generalized absence seizures in low doses and generalized convulsive seizures in high doses, and were capable of chemical kindling. However, opiate-induced seizures were not overcome by cholinergic antagonists, nor were carbachol seizures blocked by opiate antagonists. These data suggest that there may be a common noncholinergic, nonopiatergic system involved in mediating carbachol- and morphine-induced seizures but not enkephalin seizures.

  1. Space Station tethered elevator system

    Science.gov (United States)

    Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

  2. Elevation of blood levels of zinc protoporphyrin by radiomimetic drugs and friend leukemia virus

    International Nuclear Information System (INIS)

    Walden, T.L.; Al-Ansari, H.M.; Farkas, W.R.; Tennessee Univ., Knoxville; Tennessee Univ., Knoxville

    1987-01-01

    Sublethal doses of whole-body irradiation induced the elevation of zinc protoporphyrin (ZPP). Experiments were conducted to determine if recovery from radiomimetic drugs also resulted in elevation of ZPP. Daily injections with hydroxyurea and other cytotoxic drugs for 10 days caused ZPP elevation and a dose of radiation too low to cause ZPP elevation by itself caused ZPP elevation when hydroxyurea was administered prior to irradiation. Friend leukemia virus also brought about an elevation of ZPP. However, not all factors that increased erythropoiesis brought about ZPP elevation. The elevated erythropoiesis in response to hypoxia and the enhanced erythropoiesis that followed administration of folic acid to folic acid-deficient mice was not accompanied by ZPP elevation. (orig.)

  3. Elevation of blood levels of zinc protoporphyrin by radiomimetic drugs and friend leukemia virus

    Energy Technology Data Exchange (ETDEWEB)

    Walden, T.L.; Al-Ansari, H.M.; Farkas, W.R.

    1987-01-01

    Sublethal doses of whole-body irradiation induced the elevation of zinc protoporphyrin (ZPP). Experiments were conducted to determine if recovery from radiomimetic drugs also resulted in elevation of ZPP. Daily injections with hydroxyurea and other cytotoxic drugs for 10 days caused ZPP elevation and a dose of radiation too low to cause ZPP elevation by itself caused ZPP elevation when hydroxyurea was administered prior to irradiation. Friend leukemia virus also brought about an elevation of ZPP. However, not all factors that increased erythropoiesis brought about ZPP elevation. The elevated erythropoiesis in response to hypoxia and the enhanced erythropoiesis that followed administration of folic acid to folic acid-deficient mice was not accompanied by ZPP elevation.

  4. Context-Aware Elevator Scheduling

    OpenAIRE

    Strang, Thomas; Bauer, Christian

    2007-01-01

    Research on context-aware systems is usually user-centric and thus focussed on the context of a specific user to serve his or her needs in an optimized way. In this paper, we want to apply core concepts developed in research on context-awareness in a system-centric way, namely to elevator systems. We show with three different examples that the performance of an elevator system can be significantly improved if the elevator control has access to contextual knowledge. The first example demons...

  5. FEMA DFIRM Base Flood Elevations

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally,...

  6. Advanced energy saving hydraulic elevator

    Energy Technology Data Exchange (ETDEWEB)

    Garrido, A.; Sevilleja, J.; Servia, A.

    1993-08-24

    An hydraulic elevator is described comprising: a counterweighted elevator comprising a car, a counterweight, and a rope connecting the car and the counterweight; a ram having a first reaction surface for driving one of the car or the counterweight upwardly and a second reaction surface for driving one of the car or the counterweight downwardly; multiplier means for moving the car a distance greater than a stroke of the ram, the multiplier means connecting the ram to the counterweighted elevator, the multiplier means comprising: a first pulley; a second pulley; means for rigidly connecting the first and second pulley, the means having a length corresponding to a rise of the hydraulic elevator, the means attaching to the ram; and a pulley rope which: has a first end attaching to a first fixed point, extends about the first pulley, extends about the second pulley, and has a second end attaching to a second fixed point.

  7. Space Elevators Preliminary Architectural View

    Science.gov (United States)

    Pullum, L.; Swan, P. A.

    Space Systems Architecture has been expanded into a process by the US Department of Defense for their large scale systems of systems development programs. This paper uses the steps in the process to establishes a framework for Space Elevator systems to be developed and provides a methodology to manage complexity. This new approach to developing a family of systems is based upon three architectural views: Operational View OV), Systems View (SV), and Technical Standards View (TV). The top level view of the process establishes the stages for the development of the first Space Elevator and is called Architectural View - 1, Overview and Summary. This paper will show the guidelines and steps of the process while focusing upon components of the Space Elevator Preliminary Architecture View. This Preliminary Architecture View is presented as a draft starting point for the Space Elevator Project.

  8. Coastal Digital Elevation Models (DEMs)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Digital elevation models (DEMs) of U.S. and other coasts that typically integrate ocean bathymetry and land topography. The DEMs support NOAA's mission to understand...

  9. Base Flood Elevation (BFE) Lines

    Data.gov (United States)

    Department of Homeland Security — The Base Flood Elevation (BFE) table is required for any digital data where BFE lines will be shown on the corresponding Flood Insurance Rate Map (FIRM). Normally if...

  10. Elevated Fixed Platform Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Elevated Fixed Platform (EFP) is a helicopter recovery test facility located at Lakehurst, NJ. It consists of a 60 by 85 foot steel and concrete deck built atop...

  11. Energy efficient elevators and escalators

    Energy Technology Data Exchange (ETDEWEB)

    Patrao, Carlos; Fong, Joao; Almeida, Anibal de (Dep. Electrical Engineering, Univ. of Coimbra, Coimbra (Portugal)); Rivet, Luc

    2009-07-01

    Elevators and escalators are the crucial element that makes it practical to live and work several floors above ground - more than 4,3 million units are installed in Europe. Due to ageing of the European population the installation of elevators in single family houses is experiencing a significant growth, as well as equipping existing buildings. Elevators use about 4% of the electricity in tertiary sector buildings. High untapped saving potentials exist with respect to energy-efficient technologies, investment decisions and behavioural approaches, in these sectors. This paper presents preliminary results from the IEE project E4, whose overall objective is the improvement of the energy performance of elevators and escalators, in tertiary sector buildings and in multi family residential buildings. The project is characterizing people conveyors electricity consumption in the tertiary sector and in residential buildings in the EU. The installed park is characterised by a survey among elevators national associations in each country. An assessment of the barriers has been made in the first phase of the project and will be presented. Monitoring campaigns in elevators and escalators are being conducted in each country according to a common developed methodology. More than fifty elevators and escalators will be audited. This will allow the collection of load curves (start up, travel up and down, travel full and empty), including the characterization of standby consumption. Standby consumption of an elevator can represent up to 80% of the total energy consumed per year, and can be drastically reduced. This paper presents the preliminary results of the first ten audits performed in Portugal by Isr-UC.

  12. MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE

    DEFF Research Database (Denmark)

    Thyagabhavan Mony, Jyothi; Khorooshi, Reza; Owens, Trevor

    2014-01-01

    Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-l...

  13. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  14. Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

    Directory of Open Access Journals (Sweden)

    Saima Mahmood Malhi

    2014-01-01

    Full Text Available Brain-derived neurotrophic factor (BDNF and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ- induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n=12 animals/group is presented as means ± S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P<0.003 and c-Fos (P<0.01 protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS.

  15. Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

    Science.gov (United States)

    Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

    2017-06-01

    The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Complex behavior of elevators in peak traffic

    Science.gov (United States)

    Nagatani, Takashi

    2003-08-01

    We study the dynamical behavior of elevators in the morning peak traffic. We present a stochastic model of the elevators to take into account the interactions between elevators through passengers. The dynamics of the elevators is expressed in terms of a coupled nonlinear map with noises. The number of passengers carried by an elevator and the time-headway between elevators exhibit the complex behavior with varying elevator trips. It is found that the behavior of elevators exhibits a deterministic chaos even if there are no noises. The chaotic motion depends on the loading parameter, the maximum capacity of an elevator, and the number of elevators. When the loading parameter is superior to the threshold, each elevator carries a full load of passengers throughout its trip. The dependence of the threshold (transition point) on the elevator capacity is clarified.

  17. Vessels for elevated temperature service

    International Nuclear Information System (INIS)

    O'Donnell, W.J.; Porowski, J.S.

    1983-01-01

    The subject is covered in chapters, entitled: introduction (background; elevated temperature concerns; design tools); design of pressure vessels for elevated temperature per ASME code; basic elevated temperature failure modes; allowable stresses and strains per ASME code (basic allowable stress limits; ASME code limits for bending; time-fraction summations; strain limits; buckling and instability; negligible creep and stress-rupture effects); combined membrane and bending stresses in creep regime; thermal stress cycles; bounding methods based on elastic core concept (bounds on accumulated strains; more accurate bounds; strain ranges; maximum stresses; strains at discontinuities); elastic follow-up; creep strain concentrations; time-dependent fatigue (combined creep rupture and fatigue damage; limits for inelastic design analyses; limits for elastic design analyses); flaw evaluation techniques; type 316 stainless steel; type 304 stainless steel; steel 2 1/4Cr1Mo; Inconel 718; Incolloy 800; Hastelloy X; detailed inelastic design analyses. (U.K.)

  18. Elevated environmental temperature and methamphetamine neurotoxicity

    International Nuclear Information System (INIS)

    Miller, Diane B.; O'Callaghan, James P.

    2003-01-01

    Amphetamines have been of considerable research interest for the last several decades. More recent work has renewed interest in the role of ambient temperature in both the toxicity and neurotoxicity of these drugs. We have determined that the striatal dopaminergic neurotoxicity observed in the mouse is linked in some fashion to both body and environmental temperature. Most studies of d-methamphetamine (d-METH) neurotoxicity are conducted at standard laboratory ambient temperatures (e.g., ∼21-22 deg. C) and utilizing a repeated dosage regimen (e.g., three to four injections spaced 2 h apart). A lowering of the ambient temperature provides neuro protection, while an elevation increases neurotoxicity. d-METH causes long-term depletions of triatal dopamine (DA) that are accompanied by other changes that are indicative of nerve terminal degeneration. These include argyrophilia, as detected by silver degeneration stains, and an elevation in glial fibrillary acidic protein (GFAP), a marker of reactive gliosis in response to injury, as well as a long-term decrease in tyrosine hydroxylase (TH) protein levels. here we show that increasing the ambient temperature during and for some time following dosing increases the neurotoxicity of d-METH. Mice (female 57BL6/J) given a single dosage of d-METH (20 mg/kg s.c.) and maintained at the usual laboratory ambient temperature show minimal striatal damage (an ∼15% depletion of DA and an ∼ 86% increase in GFAP). substantial striatal damage (e.g., an ∼70% depletion of DA and an ∼200% elevation in GFAP) was induced by this regimen if mice were maintained at 27 deg. C for 24 or 72 h following dosing. An increase in neurotoxicity was also apparent in mice kept at an elevated temperature for only 5 or 9 h, but keeping animals at 27 deg. C for 24 or 72 h was the most effective in increasing the neurotoxicity of d-METH. Our data show how a relatively minor change in ambient temperature can have a major impact on the degree of

  19. Historie i spillefilm - for elever

    DEFF Research Database (Denmark)

    Tønnesen, Lone Guldbrandt

    2016-01-01

    MOOC om historiebrug i spillefilm, hvor elever kan lære om, hvordan spillefilm bruger fortiden, og om hvordan vores opfattelse af historien både sætter sig spor i filmene og bliver påvirket af dem.......MOOC om historiebrug i spillefilm, hvor elever kan lære om, hvordan spillefilm bruger fortiden, og om hvordan vores opfattelse af historien både sætter sig spor i filmene og bliver påvirket af dem....

  20. Tether Elevator Crawler Systems (TECS)

    Science.gov (United States)

    Swenson, Frank R.

    1987-01-01

    One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

  1. Dannelsen af den ansvarlige elev

    DEFF Research Database (Denmark)

    Larsen, Jesper

    2010-01-01

    Denne artikel handler om den del af lærergerningen, der har at gøre med udarbejdelse af elevplaner. Der tages udgangspunkt i en foucaultsk forståelse, hvor beskrivelsen af den enkelte elev udtrykker et særligt normativt ideal om, hvilke former for elevhed der er de ønskværdige i den danske...

  2. Methylphenidatinduceret ST-elevations-myokardieinfarkt

    DEFF Research Database (Denmark)

    Ruwald, Martin Huth; Ruwald, Anne-Christine Huth; Tønder, Niels

    2012-01-01

    Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly diagnosed and treated with methylphenidate. We present the case of an 20 year-old man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial infarction due to coronary vasospasm related to an overdose...

  3. Elevated lactate during psychogenic hyperventilation

    NARCIS (Netherlands)

    ter Avest, E.; Patist, F. M.; ter Maaten, J. C.; Nijsten, M. W. N.

    Study objective Elevated arterial lactate levels are closely related to morbidity and mortality in various patient categories. In the present retrospective study, the relation between arterial lactate, partial pressure of carbon dioxide (Pco(2)) and pH was systematically investigated in patients who

  4. Climate change, elevational range shifts, and bird extinctions.

    Science.gov (United States)

    Sekercioglu, Cagan H; Schneider, Stephen H; Fay, John P; Loarie, Scott R

    2008-02-01

    Limitations imposed on species ranges by the climatic, ecological, and physiological effects of elevation are important determinants of extinction risk. We modeled the effects of elevational limits on the extinction risk of landbirds, 87% of all bird species. Elevational limitation of range size explained 97% of the variation in the probability of being in a World Conservation Union category of extinction risk. Our model that combined elevational ranges, four Millennium Assessment habitat-loss scenarios, and an intermediate estimate of surface warming of 2.8 degrees C, projected a best guess of 400-550 landbird extinctions, and that approximately 2150 additional species would be at risk of extinction by 2100. For Western Hemisphere landbirds, intermediate extinction estimates based on climate-induced changes in actual distributions ranged from 1.3% (1.1 degrees C warming) to 30.0% (6.4 degrees C warming) of these species. Worldwide, every degree of warming projected a nonlinear increase in bird extinctions of about 100-500 species. Only 21% of the species predicted to become extinct in our scenarios are currently considered threatened with extinction. Different habitat-loss and surface-warming scenarios predicted substantially different futures for landbird species. To improve the precision of climate-induced extinction estimates, there is an urgent need for high-resolution measurements of shifts in the elevational ranges of species. Given the accelerating influence of climate change on species distributions and conservation, using elevational limits in a tested, standardized, and robust manner can improve conservation assessments of terrestrial species and will help identify species that are most vulnerable to global climate change. Our climate-induced extinction estimates are broadly similar to those of bird species at risk from other factors, but these estimates largely involve different sets of species.

  5. Elevator deflections on the icing process

    Science.gov (United States)

    Britton, Randall K.

    1990-01-01

    The effect of elevator deflection of the horizontal stabilizer for certain icing parameters is investigated. Elevator deflection can severely change the lower and upper leading-edge impingement limits, and ice can accrete on the elevator itself. Also, elevator deflection had practically no effect on the maximum local collection efficiency. It is shown that for severe icing conditions (large water droplets), elevator deflections that increase the projected height of the airfoil can significantly increase the total collection efficiency of the airfoil.

  6. Elevated Expression of Fractalkine (CX3CL1 and Fractalkine Receptor (CX3CR1 in the Dorsal Root Ganglia and Spinal Cord in Experimental Autoimmune Encephalomyelitis: Implications in Multiple Sclerosis-Induced Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Wenjun Zhu

    2013-01-01

    Full Text Available Multiple sclerosis (MS is a central nervous system (CNS disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP. Molecular signaling through fractalkine (CX3CL1, a nociceptive chemokine, via its receptor (CX3CR1 is thought to be associated with MS-induced NPP. An experimental autoimmune encephalomyelitis (EAE model of MS was utilized to assess time dependent gene and protein expression changes of CX3CL1 and CX3CR1. Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG and spinal cord (SC 12 days after EAE induction compared to controls. This increased expression correlated with behavioural thermal sensory abnormalities consistent with NPP. Furthermore, this increased expression correlated with the peak neurological disability caused by EAE induction. This is the first study to identify CX3CL1 signaling through CX3CR1 via the DRG /SC anatomical connection that represents a critical pathway involved in NPP induction in an EAE model of MS.

  7. Når elever producerer

    DEFF Research Database (Denmark)

    Bremholm, Jesper; Hansen, Rune; Slot, Marie Falkesgaard

    2017-01-01

    Dette kapitel præsenterer centrale resultater fra studiet Elevopgaver og elevproduktion i det 21. århundrede der blandt andet rummer den første større kvantitative undersøgelse af opgavedidaktik og elevers produktive arbejde i den danske grundskole. Studiet omfatter også en kvalitativ del, og i...... undersøgelsen præsenteres og diskuteres gennem en række konkrete eksempler fra de berørte fag. I forhold til elevers produktive arbejde peger undersøgelsens resultater både på potentialer og særlige barrierer i forbindelse med at udvikle en kompetenceorienteret undervisning. I kapitlet argumenteres desuden...

  8. Læring mellem elever

    DEFF Research Database (Denmark)

    Georgsen, Marianne; Davidsen, Jacob

    2010-01-01

    I denne rapport præsenteres resultater fra følgeforskningen til projektet Læring gennem Bevægelse, som er gennemført på Søndervangskolen i Hammel i perioden august 2009 - maj 2010. Projektet er gennemført i samspil mellem lærere, it-vejleder, elever og skolens ledelse. Projektets overordnede formål...

  9. Science on a space elevator

    Energy Technology Data Exchange (ETDEWEB)

    Laubscher, B. E. (Bryan E.); Jorgensen, A. M. (Anders M.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. If the SE's promise of low cost access can be realized, everything becomes economically more feasible to accomplish in space. In this paper we describe in-situ science stations mounted on a science-dedicated space elevator tether. The concept presented here involves a carbon nanotube ribbon that is constructed by an existing space elevator and then science sensors are stationed along the ribbon at differing altitudes. The finished ribbon can be moved across the earth to the position at which its scientific measurements are to be taken. The ability to station scientific, in-situ instrumentation at different altitudes for round-the-clock observations is a unique capability of the SE. The environments that the science packages sense range from the troposphere out beyond the magnetopause of the magnetosphere on the solar side of the earth. Therefore, the very end of the SE can sense the solar wind. The measurements at various points along its length include temperature, pressure, density, sampling, chemical analyses, wind speed, turbulence, free oxygen, electromagnetic radiation, cosmic rays, energetic particles and plasmas in the earth's magnetosphere and the solar wind. There exist some altitudes that are difficult to access with aircraft or balloons or rockets and so remain relatively unexplored. The space elevator solves these problems and opens these regions up to in-situ measurements. Without the need for propulsion, the SE provides a more benign and pristine environment for atmospheric measurements than available with powered aircraft. Moreover, replacing and upgrading instrumentation is expected to be very cost effective with the SE. Moving and stationing the science SE affords the opportunity to sense multiple regions of the atmosphere. The SE's geosynchronous, orbital motion through the magnetosphere, albeit nominally with Earth's magnetic field, will trace a plane

  10. Elevation of blood levels of zinc protoporphyrin in mice following whole-body irradiation

    International Nuclear Information System (INIS)

    Walden, T.L. Jr.

    1983-01-01

    Elevation of zinc protoporphyrin (ZPP) levels in the blood has served as an indicator of lead poisoning and iron deficiency anemia for many years. The author has discovered that sublethal doses of whole body irradiation with X-rays also elevates ZPP two- to three-fold over normal levels. The ZPP level does not begin to increase until days 12 to 14 post-irradiation and peaks between days 18 to 20 before returning to normal levels between days 28 to 35. Increasing the radiation dose delays the onset of the rise in ZPP but does not affect the magnitude of the elevation. At lethal doses, ZPP elevation is not observed. Neither of the two previously described mechanisms which cause elevations of ZPP, namely iron deficiency and inhibition of ferrochelatase, are responsible for the radiation induced elevation of ZPP. The elevation of ZPP appears to be correlated with the recovery of the hematopoietic system from radiation injury

  11. The elevation of blood levels of zinc protoporphyrin in mice following whole body irradiation

    International Nuclear Information System (INIS)

    Walden, T.L.; Draganac, P.S.; Farkas, W.R.

    1984-01-01

    Elevation of zinc protoporphyrin (ZPP) levels in the blood has served as an indicator of lead poisoning and iron deficiency anemia for many years. We have discovered that sublethal doses of whole body irradiation with x-rays also elevates ZPP 2-3-fold over normal levels. The ZPP level does not begin to increase until days 12-14 postirradiation and peaks between days 18 and 20 before returning to normal levels between days 28 and 35. Increasing the radiation dose delays the onset of the rise in ZPP, but does not affect the magnitude of the elevation. At lethal doses, ZPP elevation is not observed. Neither of the two previously described mechanisms that cause elevations of ZPP, namely iron deficiency and inhibition of ferrochelatase, are responsible for the radiation-induced elevation of ZPP. The elevation of ZPP appears to be correlated with the recovery of the hematopoietic system from radiation injury

  12. Comparing trapezius muscle activity in the different planes of shoulder elevation.

    Science.gov (United States)

    Ishigaki, Tomonobu; Ishida, Tomoya; Samukawa, Mina; Saito, Hiroshi; Hirokawa, Motoki; Ezawa, Yuya; Sugawara, Makoto; Tohyama, Harukazu; Yamanaka, Masanori

    2015-05-01

    [Purpose] The purpose of this study was to compare the upper, middle, and lower trapezius muscles' activity in the different planes of shoulder elevation. [Subjects] Twenty male subjects volunteered for this study. [Methods] Surface electromyographic (EMG) activity for each of the three regions of the trapezius muscles in the three different planes of elevation were collected while the participants maintained 30, 60, and 90 degrees of elevation in each plane. The EMG data were normalized with maximum voluntary isometric contraction (%MVIC), and compared among the planes at each angle of elevation. [Results] There were significantly different muscle activities among the elevation planes at each angle. [Conclusion] This study found that the three regions of the trapezius muscles changed their activity depending on the planes of shoulder elevation. These changes in the trapezius muscles could induce appropriate scapular motion to face the glenoid cavity in the correct directions in different planes of shoulder elevation.

  13. Retinal Ganglion Cell Loss in Diabetes Associated with Elevated Homocysteine

    Directory of Open Access Journals (Sweden)

    Kenneth S. Shindler

    2009-11-01

    Full Text Available A number of studies have suggested that homocysteine may be a contributing factor to development of retinopathy in diabetic patients based on observed correlations between elevated homocysteine levels and the presence of retinopathy. The significance of such a correlation remains to be determined, and potential mechanisms by which homocysteine might induce retinopathy have not been well characterized. Ganapathy and colleagues1 used mutant mice that have endogenously elevated homocysteine levels due to heterozygous deletion of the cystathionine-β-synthase gene to examine changes in retinal pathology following induction of diabetes. Their finding that elevated homocysteine levels hastens loss of cells in the retinal ganglion cell layer suggests that toxicity to ganglion cells may warrant further investigation as a potential mechanism of homocysteine enhanced susceptibility to diabetic retinopathy.

  14. Mechanism for elevated temperature leaching

    International Nuclear Information System (INIS)

    Kenna, B.T.; Murphy, K.D.

    1979-01-01

    Long-term, elevated temperature leaching and subsequent electron microprobe analysis of simulated waste glass and ceramic materials have been completed. A cyclic leaching pattern was found in all systems over a 20-month period. It appears that the leaching of mobile ions by simple diffusional processes is modified by more complex chemical interactions. The release of immobile ions is primarily a function of their chemical interactions in the matrix which suggests that these ions may be complex species when released into solution. A mechanism is proposed which incorporates these ideas and the cyclic phenomenon observed

  15. PLC VVVF Elevator Control System

    OpenAIRE

    Tang, Yujian; Gui, Tianyu

    2016-01-01

    The aim of the thesis is to introduce the PLC VVVF elevator and its control system. The thesis can be divided into three parts. The first part is about the overview of the lift: the kinds of the lift and the structure of the lift, it shows the knowledge about the components and the operating systems of the lift. The second part is about the PLC control system, it’s about the operations of the lift from the introduction about the hardware and software of the PLC control system. And the thi...

  16. Amorphisation during elevated temperature implantation

    International Nuclear Information System (INIS)

    Carter, G.; Nobes, M.J.; Elliman, R.G.

    1994-01-01

    Transition state theory is employed to predict the rates of amorphous zone recrystallization by direct thermal and radiation mediated thermal annealing processes. These rates are functions of zone radius and are employed to describe the competition between amorphous zone generation and annealing during elevated temperature heavy ion implantation of, particularly, Si and the accumulation of amorphousness with increasing ion fluence. This analysis predicts a change from monotonic to sigmoidal to biexponential accumulation functions with increasing annealing rate or substrate temperature in agreement with experiments. A logarithmic dependence of ion flux density upon substrate temperature for the achievement of defined fractional amorphisation is predicted and is also in agreement with the experiment. (author)

  17. The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation

    Science.gov (United States)

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-01-01

    Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing. PMID:28413186

  18. The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.

    Science.gov (United States)

    Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Fung, Kwok-Pui; Lam, Francis Fu-Yuen; Ng, Ethel Sau-Kuen; Lau, Kit-Man; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

    2017-08-05

    Delayed foot wound healing is a major complication attributed to hyperglycemia in type 2 diabetes mellitus (DM) patients, and these wounds may develop into foot ulcers. There are at least two types of DM wound models used in rodents to study delayed wound healing. However, clinically relevant animal models are not common. Most models use type 1 DM rodents or wounds created on the back rather than on the foot. An open full-thickness excision wound on the footpad of type 2 DM rats is more clinically relevant, but such a model has not yet been characterized systematically. The objective of this study was to investigate and characterize how DM affected a full-thickness excision open foot wound in n5-streptozotocin (n5-STZ)-induced type 2 DM rats. We hypothesized that elevated inflammation, reduced blood circulation, and cell proliferation due to hyperglycemia could delay the wound healing of DM rats. The wounds of DM rats were compared with those of non-DM rats (Ctrl) at Days 1 and 8 post wounding. The wound healing process of the DM rats was significantly delayed compared with that of the Ctrl rats. The DM rats also had higher C-reactive protein (CRP) and lower blood circulation and proliferating cell nuclear antigen (PCNA) in DM wounds. This confirmed that elevated inflammation and reduced blood flow and cell proliferation delayed foot wound healing in the n5-STZ rats. Hence, this open foot wound animal model provides a good approach to study the process of delayed wound healing.

  19. Kindle : how gamification can motivate jobseekers

    NARCIS (Netherlands)

    van der Kruys, B.; Khan, J.V.; Nah, F.F.-H.; Tan, C.-H.

    Prolonged unemployment can lead to depression and a loss of self-esteem. Gamification is a strategy that engages and motivates groups of people by implementing game mechanics and dynamics in an existing non-gaming system. This paper studies the possibility of using gamification to motivate job

  20. Impact of iso-osmolar versus low-osmolar contrast agents on contrast-induced nephropathy and tissue reperfusion in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (from the Contrast Media and Nephrotoxicity Following Primary Angioplasty for Acute Myocardial Infarction [CONTRAST-AMI] Trial).

    Science.gov (United States)

    Bolognese, Leonardo; Falsini, Giovanni; Schwenke, Carsten; Grotti, Simone; Limbruno, Ugo; Liistro, Francesco; Carrera, Arcangelo; Angioli, Paolo; Picchi, Andrea; Ducci, Kenneth; Pierli, Carlo

    2012-01-01

    Conflicting data have been reported on the effects of low-osmolar and iso-osmolar contrast media on contrast-induced acute kidney injury (CI-AKI). In particular, no clinical trial has yet focused on the effect of contemporary contrast media on CI-AKI, epicardial flow, and microcirculatory function in patients with ST-segment elevation acute myocardial infarction who undergo primary percutaneous coronary intervention. The Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty for Acute Myocardial Infarction (CONTRAST-AMI) trial is a prospective, randomized, single-blind, parallel-group, noninferiority study aiming to evaluate the effects of the low-osmolar contrast medium iopromide compared to the iso-osmolar agent iodixanol on CI-AKI and tissue-level perfusion in patients with ST-segment elevation acute myocardial infarction. Four hundred seventy-five consecutive, unselected patients who underwent primary percutaneous coronary intervention were randomized to iopromide (n = 239) or iodixanol (n = 236). All patients received high-dose N-acetylcysteine and hydration. The primary end point was the proportion of patients with serum creatinine (sCr) increases ≥25% from baseline to 72 hours. Secondary end points were Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, increase in sCr ≥50%, increase in sCr ≥0.5 or ≥1 mg/dl, and 1-month major adverse cardiac events. The primary end point occurred in 10% of the iopromide group and in 13% of the iodixanol group (95% confidence interval -9% to 3%, p for noninferiority = 0.0002). A TIMI myocardial perfusion grade of 0 or 1 was present in 14% of patients in the 2 groups. No differences between the 2 groups were found in any of the secondary analyses of sCr increase. No significant difference in 1-month major adverse cardiac events was found (8% vs 6%, p = 0.37). In conclusion, in a population of unselected patients with ST-segment elevation acute myocardial infarction

  1. 马桑内酯致痫大鼠海马IL-2免疫反应性的变化%Study of Changes of Cytokines (Interleukin-2) in Hippocampus Following Coriaria Lactone-induced Kindling in Rats

    Institute of Scientific and Technical Information of China (English)

    向赟; 董大翠; 刘庆莹; 文若剑; 朱长庚; 魏英; 蔡秋云

    2003-01-01

    目的:探求细胞因子中的白细胞介素2(Interleukin-2,IL-2)与癫痫发病之间的关系.方法:将Wistar大鼠分成三组,第一组侧脑室注入马桑内酯(Coriari Lactone,CL)2μL,第二组注入等量的生理盐水,第三组不做任何处理.然后运用免疫组织化学方法,对大鼠海马IL-2的免疫反应性进行分析;同时对实验中大鼠的行为及脑电图(eletroencepalograph,EEG)进行观察和记录.结果:第一组大鼠侧脑室注射CL过程中即诱发癫痫,且测到痫性脑电图,第二组、第三组无癫痫症状且未记录到痫性脑电图;第一组大鼠海马IL-2免疫反应性较第二组及第三组显著增强(P<0.01),表现在其海马CA1、CA2、CA3区细胞数目增多,突起及其分支增多,着色明显加深;而第二、三组之间无明显差别(P<0.05).结论:IL-2参与癫痫的发病过程,二者之间存在着一定的联系.

  2. Diffusion rates for elevated releases

    International Nuclear Information System (INIS)

    Ramsdell, J.V.

    1983-11-01

    A search of the literature related to diffusion from elevated sources has determined that an adequate data base exists for use in developing parameterizations for estimating diffusion rates for material released from free standing stacks at nuclear power plants. A review of published data analyses indicates that a new parameterization of horizontal diffusion rates specifically for elevated releases is not likely to significantly change the magnitudes of horizontal diffusion coefficients on the average. However, the uncertainties associated with horizontal diffusion coefficient estimates under any given set of atmospheric conditions could be reduced by a new parameterization. Similarly, a new parameterization of vertical diffusion rates would be unlikely to significantly alter the magnitudes of diffusion coefficients for unstable atmospheric conditons. However, for neutral and stable atmospheric conditions, a new parameterization of vertical diffusion rates might increase vertical diffusion coefficients significantly. The increase would move ground-level time-integrated concentration maxima closer to the plant and would increase the maxima. 55 references, 2 figures, 4 tables

  3. Operation experience with elevated ammonia

    International Nuclear Information System (INIS)

    Vankova, Katerina; Kysela, Jan; Malac, Miroslav; Petrecky, Igor; Svarc, Vladimir

    2011-01-01

    The 10 VVER units in the Czech and Slovak Republics are all in very good water chemistry and radiation condition, yet questions have arisen regarding the optimization of cycle chemistry and improved operation in these units. To address these issues, a comprehensive experimental program for different water chemistries of the primary circuit was carried out at the Rez Nuclear Research Institute, Czech Republic, with the goal of judging the influence of various water chemistries on radiation build-up. Four types of water chemistries were compared: standard VVER water chemistry (in common use), direct hydrogen dosing without ammonia, standard VVER water chemistry with elevated ammonia levels, and zinc dosing to standard VVER water chemistry. The test results showed that the types of water chemistry other than the common one have benefits for the operation of the nuclear power plant (NPP) primary circuit. Operation experience with elevated ammonia at NPP Dukovany Units 3 and 4 is presented which validates the experimental results, demonstrating improved corrosion product volume activity. (orig.)

  4. Digitial Elevation Model (DEM) 100K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USG to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  5. Digtial Elevation Model (DEM) 250K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  6. Digital Elevation Model (DEM) 24K

    Data.gov (United States)

    Kansas Data Access and Support Center — Digital Elevation Model (DEM) is the terminology adopted by the USGS to describe terrain elevation data sets in a digital raster form. The standard DEM consists of a...

  7. Bucket elevator type continuous unloader; Basket elevator gata renzokushiki anroda

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-04-20

    This unloader was delivered to Wakayama branch of Sumikin Butsuryu in the site of Wakayama steel plant of Sumitomo Metal Industries Ltd. for landing sub-materials for ironworks. Main specifications: (1) Capacity: 400t/h for limestone, 280t/h for gypsum, (2) Kinds of ships: 5,000DWT maximum, (3) Boom swing radius: 20m. Features: (1) Simple light-weight unloader for not large ships for main materials but small coastal service ships which works with not swing motion but only traveling and normal-directional motion of the under structure of a bucket elevator unit, (2) Various useful functions such as ground conveyance, truck loading, back yard stacking and back yard shipment for handling of various sub-materials. (translated by NEDO)

  8. History of Elevators and Related Research

    Science.gov (United States)

    Abe, Shigeru; Watanabe, Eiki

    The history of traction drive elevators in Japan is described. The electrical technologies such as the microprocessor car control and the VVVF motor control made remarkable progress leading to higher reliability and energy savings. Then, the various machine-room-less elevators have been developed and the space saving technology, such as the shuttle and the double-deck elevators become important, too. The elevators used for evacuation in case of emergencies are also discussed.

  9. Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus

    Energy Technology Data Exchange (ETDEWEB)

    Schartl, M.; Schmidt, C.R.; Anders, A.; Barnekow, A.

    1985-08-15

    In the fish Xiphophorus the authors have detected elevated levels of pp60c-src kinase activity in a variety of tumors (n = 34) of neurogenic, epithelial, and mesenchymal origin either of hereditary etiology or induced by carcinogens. This elevation ranged from 2-fold up to 50-fold compared to the corresponding non-tumorous tissue and up to 6-fold compared to the highest activities found in any of the normal organs. The level of elevation parallels the degree of malignancy in melanoma and in tumors of mesenchymal origin. In fish bearing tumors of hereditary etiology kinase activity was also elevated in the non-tumorous brain, while in fish bearing induced tumors, kinase activity was elevated only in the cells of the neoplasia.

  10. 21 CFR 890.3930 - Wheelchair elevator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Wheelchair elevator. 890.3930 Section 890.3930 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... elevator. (a) Identification. A wheelchair elevator is a motorized lift device intended for medical...

  11. 46 CFR 183.540 - Elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Elevators. 183.540 Section 183.540 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) ELECTRICAL INSTALLATION Miscellaneous Systems and Requirements § 183.540 Elevators. Each elevator on a vessel must meet the requirements of ANSI A 17.1 ...

  12. Global variation in elevational diversity patterns

    Science.gov (United States)

    Qinfeng Guo; Douglas A. Kelt; Zhongyu Sun; Hongxiao Liu; Liangjun Hu; Hai Ren; Jun We

    2013-01-01

    While horizontal gradients of biodiversity have been examined extensively in the past, vertical diversity gradients (elevation, water depth) are attracting increasing attention. We compiled data from 443 elevational gradients involving diverse organisms worldwide to investigate how elevational diversity patterns may vary between the Northern and Southern hemispheres...

  13. [Children with hyperthyroidism due to elevated hCG levels].

    Science.gov (United States)

    Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

    2014-01-01

    We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

  14. Myocarditis with ST elevation and elevated cardiac enzymes misdiagnosed as an ST-elevation myocardial infarction.

    Science.gov (United States)

    Sheldon, Seth H; Crandall, Mark A; Jaffe, Allan S

    2012-12-01

    Acute myocarditis can mimic ST-elevation myocardial infarction (STEMI). Quickly determining the correct diagnosis is critical given the "time is muscle" implication with a STEMI and the potential adverse effects associated with use of fibrinolytic therapy. A 46-year-old man presented to a rural emergency department with chest pain, and an electrocardiogram (ECG) read as showing 0.1 mV of ST-segment elevation in leads III and aVF. His initial cardiac troponin T was 0.44 ng/mL. He received fibrinolytic therapy for presumed STEMI. Cardiac magnetic resonance imaging was later performed and showed epicardial delayed enhancement consistent with myocarditis. Upon further questioning, he acknowledged 3 days of stuttering chest discomfort and a recent upper respiratory infection, as well as similar chest pain in his wife. A systematic evaluation is essential for acute chest pain, including a focused history, identification of cardiac risk factors, and ECG interpretation. A history of recent viral illness, absence of cardiac risk factors, or ECG findings inconsistent with a single anatomic lesion would suggest a potential alternate diagnosis to STEMI. This case emphasizes the importance of a focused history in the initial evaluation of chest pain. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Plants increase laccase activity in soil with long-term elevated CO2 legacy

    DEFF Research Database (Denmark)

    Partavian, Asrin; Mikkelsen, Teis Nørgaard; Vestergård, Mette

    2015-01-01

    [CO2] stimulate laccase activity. We incubated soil exposed to seven years of elevated or ambient field [CO2] in ambient or elevated [CO2] chambers for six months either with or without plants (Deschampsia flexuosa). Elevated chamber [CO2] increased D. flexuosa production and belowground respiration....... Interestingly, plants also grew larger in soil with an elevated [CO2] legacy. Plants stimulated soil microbial biomass, belowground respiration and laccase activity, and the plant-induced laccase stimulation was particularly apparent in soil exposed to long-term elevated [CO2] in the field, whereas laccase......Actively growing plants can stimulate mineralization of recalcitrant soil organic matter (SOM), and increased atmospheric [CO2] can further enhance such plant-mediated SOM degradation. Laccases are central for recalcitrant SOM decomposition, and we therefore hypothesized that plants and elevated...

  16. Community and ecosystem responses to elevational gradients

    DEFF Research Database (Denmark)

    Sundqvist, Maja K.; Sanders, Nate; Wardle, David A.

    2013-01-01

    Community structure and ecosystem processes often vary along elevational gradients. Their responses to elevation are commonly driven by changes in temperature, and many community- and ecosystem-level variables therefore frequently respond similarly to elevation across contrasting gradients...... elevational gradients for understanding community and ecosystem responses to global climate change at much larger spatial and temporal scales than is possible through conventional ecological experiments. However, future studies that integrate elevational gradient approaches with experimental manipulations...... will provide powerful information that can improve predictions of climate change impacts within and across ecosystems....

  17. Cytomegalovirus Antibody Elevation in Bipolar Disorder: Relation to Elevated Mood States

    Directory of Open Access Journals (Sweden)

    A. R. Prossin

    2015-01-01

    Full Text Available The neurobiology of mood states is complicated by exposure to everyday stressors (e.g., psychosocial, ubiquitous environmental infections like CMV, each fluctuating between latency and reactivation. CMV reactivation induces proinflammatory cytokines (e.g., TNF-α associated with induction of neurotoxic metabolites and the presence of mood states in bipolar disorder (BD. Whether CMV reactivation is associated with bipolar diagnoses (trait or specific mood states is unclear. We investigated 139 BD type I and 99 healthy controls to determine if concentrations of IgG antibodies to Herpesviridae (e.g., CMV, HSV-1, and HSV-2 were associated with BD-I diagnosis and specific mood states. We found higher CMV antibody concentration in BD-I than in healthy controls (T234=3.1, Puncorr=0.002; Pcorr=0.006 but no difference in HSV-1 (P>0.10 or HSV-2 (P>0.10. Compared to euthymic BD-I volunteers, CMV IgG was higher in BD-I volunteers with elevated moods (P0.10. While relationships presented between BD-I diagnosis, mood states, and CMV antibodies are encouraging, they are limited by the study’s cross sectional nature. Nevertheless, further testing is warranted to replicate findings and determine whether reactivation of CMV infection exacerbates elevated mood states in BD-I.

  18. Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol ...

    African Journals Online (AJOL)

    olayemitoyin

    Plasma glucose was significantly (p<0.05) reduced in all the sleep deprived groups compared ... of 12hr light-dark cycle after which they were subjected to Paradoxical .... Wakefulness involves high neuronal metabolism to maintain neuronal ...

  19. Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

    DEFF Research Database (Denmark)

    Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

    2010-01-01

    Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...... and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of Y2 receptors (alone or in combination with neuropeptide Y) could be an alternative strategy for epilepsy treatment....

  20. Dynamic multibody modeling for tethered space elevators

    Science.gov (United States)

    Williams, Paul

    2009-08-01

    This paper presents a fundamental modeling strategy for dealing with powered and propelled bodies moving along space tethers. The tether is divided into a large number of discrete masses, which are connected by viscoelastic springs. The tether is subject to the full range of forces expected in Earth orbit in a relatively simple manner. Two different models of the elevator dynamics are presented. In order to capture the effect of the elevator moving along the tether, the elevator dynamics are included as a separate body in both models. One model treats the elevator's motion dynamically, where propulsive and friction forces are applied to the elevator body. The second model treats the elevator's motion kinematically, where the distance along the tether is determined by adjusting the lengths of tether on either side of the elevator. The tether model is used to determine optimal configurations for the space elevator. A modal analysis of two different configurations is presented which show that the fundamental mode of oscillation is a pendular one around the anchor point with a period on the order of 160 h for the in-plane motion, and 24 h for the out-of-plane motion. Numerical simulation results of the effects of the elevator moving along the cable are presented for different travel velocities and different elevator masses.

  1. Predictors of backrest elevation in critical care.

    Science.gov (United States)

    Grap, Mary Jo; Munro, Cindy L; Bryant, Sandra; Ashtiani, Brooke

    2003-04-01

    Low backrest and supine positions are associated with increased mortality and ventilator associated pneumonia (VAP). Data are not available across ICU settings about the level of backrest position used and its relationship to enteral feeding and hemodynamic status. The purpose of this descriptive study was to document the level of backrest elevation and position and identify factors associated with and predict positioning in a medical, surgical and neuroscience intensive care unit. Data were collected randomly in each unit over a 6-week period, resulting in 506 observations for170 patients. Backrest elevation was determined by electronic bed read-out or bed frame elevation gauge. BP, HR and enteral feeding status were retrieved from the medical record. Results showed that mean backrest elevation was 19.2 degrees and 70% of subjects were supine. No difference in backrest elevation among units was found. Significant correlations between backrest elevation and systolic BP (r=0.15, P=0.006); and backrest and diastolic BP (r=0.13, P=0.02) were found. There was no difference in backrest elevation between patients being fed and not being fed. Differences in backrest elevation for intubated versus nonintubated patients approached significance (P=0.07) with intubated patients at lower backrest elevations. In summary, use of higher backrest elevations (>30 degrees ) is minimal, is not related to feeding and minimally related to hemodynamic status. Strategies to meet published recommendations for backrest elevation (30-45 degrees ) must include repeated feedback about nurse's use of backrest elevation and estimates of elevation.

  2. The space station tethered elevator system

    Science.gov (United States)

    Anderson, Loren A.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The elevator is an unmanned mobile structure which operates on a ten kilometer tether spanning the distance between the Space Station and a tethered platform. Elevator capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The potential uses, parameters, and evolution of the spacecraft design are discussed. Engineering development of the tethered elevator is the result of work conducted in the following areas: structural configurations; robotics, drive mechanisms; and power generation and transmission systems. The structural configuration of the elevator is presented. The structure supports, houses, and protects all systems on board the elevator. The implementation of robotics on board the elevator is discussed. Elevator robotics allow for the deployment, retrieval, and manipulation of tethered objects. Robotic manipulators also aid in hooking the elevator on a tether. Critical to the operation of the tethered elevator is the design of its drive mechanisms, which are discussed. Two drivers, located internal to the elevator, propel the vehicle along a tether. These modular components consist of endless toothed belts, shunt-wound motors, regenerative power braking, and computer controlled linear actuators. The designs of self-sufficient power generation and transmission systems are reviewed. Thorough research indicates all components of the elevator will operate under power provided by fuel cells. The fuel cell systems will power the vehicle at seven kilowatts continuously and twelve kilowatts maximally. A set of secondary fuel cells provides redundancy in the unlikely event of a primary system failure. Power storage exists in the form of Nickel-Hydrogen batteries capable of powering the elevator under maximum loads.

  3. Space elevator systems level analysis

    Energy Technology Data Exchange (ETDEWEB)

    Laubscher, B. E. (Bryan E.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. It involves new, untried technologies in most of its subsystems. Thus the successful construction of the SE requires a significant amount of development, This in turn implies a high level of risk for the SE. This paper will present a systems level analysis of the SE by subdividing its components into their subsystems to determine their level of technological maturity. such a high-risk endeavor is to follow a disciplined approach to the challenges. A systems level analysis informs this process and is the guide to where resources should be applied in the development processes. It is an efficient path that, if followed, minimizes the overall risk of the system's development. systems level analysis is that the overall system is divided naturally into its subsystems, and those subsystems are further subdivided as appropriate for the analysis. By dealing with the complex system in layers, the parameter space of decisions is kept manageable. Moreover, A rational way to manage One key aspect of a resources are not expended capriciously; rather, resources are put toward the biggest challenges and most promising solutions. This overall graded approach is a proven road to success. The analysis includes topics such as nanotube technology, deployment scenario, power beaming technology, ground-based hardware and operations, ribbon maintenance and repair and climber technology.

  4. Phase-preserved optical elevator.

    Science.gov (United States)

    Luo, Yuan; Zhang, Baile; Han, Tiancheng; Chen, Zhi; Duan, Yubo; Chu, Chia-Wei; Barbastathis, George; Qiu, Cheng Wei

    2013-03-25

    The unique superiority of transformation optics devices designed from coordinate transformation is their capability of recovering both ray trajectory and optical path length in light manipulation. However, very few experiments have been done so far to verify this dual-recovery property from viewpoints of both ray trajectory and optical path length simultaneously. The experimental difficulties arise from the fact that most previous optical transformation optics devices only work at the nano-scale; the lack of intercomparison between data from both optical path length and ray trajectory measurement in these experiments obscured the fact that the ray path was subject to a subwavelength lateral shift that was otherwise not easily perceivable and, instead, was pointed out theoretically [B. Zhang et al. Phys. Rev. Lett. 104, 233903, 2010]. Here, we use a simple macroscopic transformation optics device of phase-preserved optical elevator, which is a typical birefringent optical phenomenon that can virtually lift an optical image by a macroscopic distance, to demonstrate decisively the unique optical path length preservation property of transformation optics. The recovery of ray trajectory is first determined with no lateral shift in the reflected ray. The phase preservation is then verified with incoherent white-light interferometry without ambiguity and phase unwrapping.

  5. Defense of a space elevator

    Energy Technology Data Exchange (ETDEWEB)

    Laubscher, B. E. (Bryan E.)

    2004-01-01

    The Space Elevator (SE) represents a major paradigm shift in space access. If the SE's promise of low-cost access is to be realized, everything becomes economically more feasible to accomplish in space. In this paper we describe a defensive system of the SE. The primary scenario adopted for this analysis is the SE based on a floating platform in the ocean along the equator. A second possible scenario is the SE stationed on land (island or continent) on or near the equator. The SE will capture the imaginations of people around the world. It will become a symbol of power, capability, wealth and prestige for the country that builds it. As such, it will become a prime terrorist target. Moreover, the tremendous economic leverage afforded by the SE might motivate rogue nations to plot its destruction. Therefore, it is necessary to consider the requirements for defense of the SE. For the purposes of this paper it is assumed that the SE is to be deployed by the United States or one of its companies, and the resources of the US are available for its defense.

  6. Global warming leads to more uniform spring phenology across elevations.

    Science.gov (United States)

    Vitasse, Yann; Signarbieux, Constant; Fu, Yongshuo H

    2018-01-30

    One hundred years ago, Andrew D. Hopkins estimated the progressive delay in tree leaf-out with increasing latitude, longitude, and elevation, referred to as "Hopkins' bioclimatic law." What if global warming is altering this well-known law? Here, based on ∼20,000 observations of the leaf-out date of four common temperate tree species located in 128 sites at various elevations in the European Alps, we found that the elevation-induced phenological shift (EPS) has significantly declined from 34 d⋅1,000 m -1 conforming to Hopkins' bioclimatic law in 1960, to 22 d⋅1,000 m -1 in 2016, i.e., -35%. The stronger phenological advance at higher elevations, responsible for the reduction in EPS, is most likely to be connected to stronger warming during late spring as well as to warmer winter temperatures. Indeed, under similar spring temperatures, we found that the EPS was substantially reduced in years when the previous winter was warmer. Our results provide empirical evidence for a declining EPS over the last six decades. Future climate warming may further reduce the EPS with consequences for the structure and function of mountain forest ecosystems, in particular through changes in plant-animal interactions, but the actual impact of such ongoing change is today largely unknown.

  7. Nitrogen Deifciency Limited the Improvement of Photosynthesis in Maize by Elevated CO2 Under Drought

    Institute of Scientific and Technical Information of China (English)

    ZONG Yu-zheng; SHANGGUAN Zhou-ping

    2014-01-01

    Global environmental change affects plant physiological and ecosystem processes. The interaction of elevated CO2, drought and nitrogen (N) deficiency result in complex responses of C4 species photosynthetic process that challenge our current understanding. An experiment of maize (Zea mays L.) involving CO2 concentrations (380 or 750 µmol mol-1, climate chamber), osmotic stresses (10% PEG-6000, -0.32 MPa) and nitrogen constraints (N deficiency treated since the 144th drought hour) was carried out to investigate its photosynthesis capacity and leaf nitrogen use efficiency. Elevated CO2 could alleviate drought-induced photosynthetic limitation through increasing capacity of PEPC carboxylation (Vpmax) and decreasing stomatal limitations (SL). The N deifciency exacerbated drought-induced photosynthesis limitations in ambient CO2. Elevated CO2 partially alleviated the limitation induced by drought and N deifciency through improving the capacity of Rubisco carboxylation (Vmax) and decreasing SL. Plants with N deifciency transported more N to their leaves at elevated CO2, leading to a high photosynthetic nitrogen-use efifciency but low whole-plant nitrogen-use efifciency. The stress mitigation by elevated CO2 under N deifciency conditions was not enough to improving plant N use efifciency and biomass accumulation. The study demonstrated that elevated CO2 could alleviate drought-induced photosynthesis limitation, but the alleviation varied with N supplies.

  8. Broadband phase-preserved optical elevator

    OpenAIRE

    Luo, Yuan; Han, Tiancheng; Zhang, Baile; Qiu, Cheng-Wei; Barbastathis, George

    2011-01-01

    Phase-preserved optical elevator is an optical device to lift up an entire plane virtually without distortion in light path or phase. Using transformation optics, we have predicted and observed the realization of such a broadband phase-preserved optical elevator, made of a natural homogeneous birefringent crystal without resorting to absorptive and narrowband metamaterials involving time-consuming nano-fabrication. In our demonstration, the optical elevator is designed to lift a sheet upwards...

  9. Soil nematodes show a mid-elevation diversity maximum and elevational zonation on Mt. Norikura, Japan.

    Science.gov (United States)

    Dong, Ke; Moroenyane, Itumeleng; Tripathi, Binu; Kerfahi, Dorsaf; Takahashi, Koichi; Yamamoto, Naomichi; An, Choa; Cho, Hyunjun; Adams, Jonathan

    2017-06-08

    Little is known about how nematode ecology differs across elevational gradients. We investigated the soil nematode community along a ~2,200 m elevational range on Mt. Norikura, Japan, by sequencing the 18S rRNA gene. As with many other groups of organisms, nematode diversity showed a high correlation with elevation, and a maximum in mid-elevations. While elevation itself, in the context of the mid domain effect, could predict the observed unimodal pattern of soil nematode communities along the elevational gradient, mean annual temperature and soil total nitrogen concentration were the best predictors of diversity. We also found nematode community composition showed strong elevational zonation, indicating that a high degree of ecological specialization that may exist in nematodes in relation to elevation-related environmental gradients and certain nematode OTUs had ranges extending across all elevations, and these generalized OTUs made up a greater proportion of the community at high elevations - such that high elevation nematode OTUs had broader elevational ranges on average, providing an example consistent to Rapoport's elevational hypothesis. This study reveals the potential for using sequencing methods to investigate elevational gradients of small soil organisms, providing a method for rapid investigation of patterns without specialized knowledge in taxonomic identification.

  10. On a lunar space elevator

    Science.gov (United States)

    Lemke, E. H.

    We consider a space elevator system for lunar surface access that consists of a space station in circumlunar orbit, a cable reaching down to some meters above the surface and a magnetically levitated vehicle driven by a linear motor. It accelerates the load to be lifted to the speed of the cable end. Loads to be delivered are either put on the vehicle and slowed down by it or they are slowed down by a sand braking technique in a mare terrain. It is technically possible to operate this transport system nearly without fuel supply from Earth. We calculate various steel cable dimensions for a static stress maximum of 1/5th of the tensile strength. The process of takeover is considered in detail. Five ways of eliminating the adverse large cable elongation due to the load are described. The touchdown process and behaviour of the cable after disconnection are analysed. The positive difference between the speed of the load at takeover and cable end can excite a large inplane swing motion. We propose to damp it by a dissipative pulley that hangs in a loop of wire leading to the ends of two beams mounted on the space station tangentially to the orbit, the pulley's core being connected with the load. Roll librations are damped by energy losses in the elastic beams; damping can be reinforced by viscous beam elements and/or controlled out-of-plane motions of the beams. We argue in favour of the possibility of fast deployment. The problems of vehicle vibrations and agglutination at sand braking blades are underlined and their combined experimental investigation is suggested.

  11. An Automatic System for Elevator Monitoring

    OpenAIRE

    Md. Haidar Sharif; Ibrahim Furkan Ince

    2015-01-01

    An elevator is a conveyor device or transport equipment that moves people or goods between floors or levels or decks of a building, vessel, or other structures. It has become a part and parcel of modern life in developed countries. The number of floors in high buildings, skyscrapers, and towers generate the usage of elevators. If it is simply assumed that each floor has at least two elevators in a thirty-floor building, people call the elevators in each floor even they are already occupied in...

  12. National requirements for improved elevation data

    Science.gov (United States)

    Snyder, Gregory I.; Sugarbaker, Larry J.; Jason, Allyson L.; Maune, David F.

    2014-01-01

    This report presents the results of surveys, structured interviews, and workshops conducted to identify key national requirements for improved elevation data for the United States and its territories, including coastlines. Organizations also identified and reported the expected economic benefits that would be realized if their requirements for improved elevation were met (appendixes 1–3). This report describes the data collection methodology and summarizes the findings. Participating organizations included 34 Federal agencies, 50 States and two territories, and a sampling of local governments, tribes, and nongovernmental orgnizations. The nongovernmental organizations included The Nature Conservancy and a sampling of private sector businesses. These data were collected in 2010-2011 as part of the National Enhanced Elevation Assessment (NEEA), a study to identify program alternatives for better meeting the Nation’s elevation data needs. NEEA tasks included the collection of national elevation requirements; analysis of the benefits and costs of meeting these requirements; assessment of emerging elevation technologies, lifecycle data management needs, and costs for managing and distributing a national-scale dataset and derived products; and candidate national elevation program alternatives that balance costs and benefits in meeting the Nation’s elevation requirements. The NEEA was sponsored by the National Digital Elevation Program (NDEP), a government coordination body with the U.S. Geological Survey (USGS) as managing partner that includes the National Geospatial-Intelligence Agency (NGA), the Federal Emergency Management Agency (FEMA), the Natural Resources Conservation Service (NRCS), the U.S. Army Corps of Engineers (USACE), and the National Oceanic and Atmospheric Administration (NOAA), among the more than a dozen agencies and organizations. The term enhanced elevation data as used in this report refers broadly to three-dimensional measurements of land or

  13. Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

    Directory of Open Access Journals (Sweden)

    Ali Tahir

    2015-01-01

    Full Text Available Patients with diabetes mellitus (DM develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC. Serotonin was observed to elevate reactive oxygen species (ROS and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT, superoxide dismutase (SOD, B-type natriuretic peptide (BNP expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

  14. 78 FR 14697 - Final Flood Elevation Determinations

    Science.gov (United States)

    2013-03-07

    ... Communities affected elevation above ground [caret] Elevation in meters (MSL) Modified Cecil County, Maryland... 1 to Stone Run At the Stone Run +271 Town of Rising Sun, confluence. Unincorporated Areas of Cecil County. Approximately 460 feet +359 downstream of Pierce Road. Tributary 2 to Stone Run At the Stone Run...

  15. 75 FR 31361 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-06-03

    ... source(s) elevation ground [caret] Elevation Communities affected in meters (MSL) Effective Modified... American Vertical Datum. Depth in feet above ground. [caret] Mean Sea Level, rounded to the nearest 0.1.... Stone County, Mississippi, and Incorporated Areas Church House Branch Approximately 0.5 mile None +211...

  16. High elevation white pines educational website

    Science.gov (United States)

    Anna W. Schoettle; Michele Laskowski

    2011-01-01

    The high elevation five-needle white pines are facing numerous challenges ranging from climate change to invasion by a non-native pathogen to escalation of pest outbreaks. This website (http://www.fs.fed.us/rm/highelevationwhitepines/) serves as a primer for managers and the public on the high elevation North American five-needle pines. It presents information on each...

  17. 46 CFR 120.540 - Elevators.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Elevators. 120.540 Section 120.540 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150 PASSENGERS OR WITH OVERNIGHT ACCOMMODATIONS FOR MORE THAN 49 PASSENGERS ELECTRICAL INSTALLATION Miscellaneous Systems and Requirements § 120.540 Elevators....

  18. Insect Population Dynamics in Commercial Grain Elevators

    Science.gov (United States)

    Data were collected in 1998-2002 from wheat stored in commercial grain elevators in south-central Kansas. Storage bins at these elevators had concrete walls and were typically 6-9 m in diameter and 30-35 m tall. A vacuum-probe sampler was used to collect ten 3-kg grain samples in the top 12 m of the...

  19. 75 FR 69892 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-11-16

    ...: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth... county +899 City of Norwich, Town boundary. of Greene, Town of North Norwich, Town of Oxford, Town of...). Susquehanna River At the downstream county +965 Town of Afton, Town of boundary. Bainbridge, Village of Afton...

  20. 77 FR 6980 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-02-10

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Nowata County... Bayou An area bounded by the +100 Town of Mayersville, county boundary to the Unincorporated Areas of...

  1. 76 FR 1535 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-01-11

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Poinsett County... with the St. Francis River...... +212 Areas of Poinsett County. Approximately 0.45 mile downstream of...

  2. 75 FR 29253 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-05-25

    ...: * Elevation in feet (NGVD) + Elevation in feet (NAVD) Depth in feet above State City/town/county Source of... +21 Town of Ebro, upstream of the Unincorporated Areas confluence with the of Washington County. East... County, Colorado, and Incorporated Areas Willow Creek At the confluence with None +8,154 Unincorporated...

  3. 75 FR 68710 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-11-09

    ...: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth... County, California Docket Nos.: FEMA-B-7762, FEMA-B-7795, and FEMA-B-1053 California Unincorporated Oregon Slough..... City of Montague +2503 Areas of Siskiyou and County. Unincorporated Siskiyou County...

  4. 76 FR 50918 - Final Flood Elevation Determinations

    Science.gov (United States)

    2011-08-17

    ... in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source of flooding... affected [caret] Elevation in meters (MSL) Modified Jones County, Texas, and Incorporated Areas Docket No.: FEMA-B-1122 Lake Fort Phantom Hill Just downstream of County +1642 City of Abilene, Highway 1082...

  5. 78 FR 10066 - Final Flood Elevation Determinations

    Science.gov (United States)

    2013-02-13

    ... follows: * Elevation in feet (NGVD) + Elevation in feet (NAVD) Depth in feet State City/town/county Source...). Scriba Creek Approximately 0.90 mile +546 Town of Amboy. upstream of County Route 23 (Potter Road.... Town of Palermo Maps are available for inspection at the Palermo Town Municipal Offices, 53 County...

  6. 77 FR 49379 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-08-16

    ... in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding Location Depth in feet above ground [caret] Elevation in meters (MSL) Modified Unincorporated Areas of Washington County... of the +35 Areas of railroad. Washington County. Approximately 2.1 miles upstream of the railroad...

  7. 75 FR 43418 - Final Flood Elevation Determinations

    Science.gov (United States)

    2010-07-26

    ... follows: * Elevation in feet (NGVD) + Elevation in feet (NAVD) State City/town/county Source of flooding... +869 Town of Peoria, upstream of Main Street. Unincorporated Areas of Ottawa County. Approximately 1.... Town of Peoria Maps are available for inspection at the Ottawa County Courthouse, 102 East Central...

  8. 78 FR 21272 - Final Flood Elevation Determinations

    Science.gov (United States)

    2013-04-10

    ... below for the modified BFEs for each community listed. These modified elevations have been published in... [Amended] 0 2. The tables published under the authority of Sec. 67.11 are amended as follows: * Elevation... Austin. upstream of 29th Avenue Southwest (County Highway 28). At the downstream side of +1205 I and M...

  9. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

    OpenAIRE

    Egerton, A.; Howes, O. D.; Houle, S.; McKenzie, K.; Valmaggia, L. R.; Bagby, M. R.; Tseng, H-H; Bloomfield, M. A. P.; Kenk, M.; Bhattacharyya, S.; Suridjan, I.; Chaddock, C. A.; Winton-Brown, T. T.; Allen, P.; Rusjan, P.

    2017-01-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capaci...

  10. The benefits of improved national elevation data

    Science.gov (United States)

    Snyder, Gregory I.

    2013-01-01

    This article describes how the National Enhanced Elevation Assessment (NEEA) has identified substantial benefits that could come about if improved elevation data were publicly available for current and emerging applications and business uses such as renewable energy, precision agriculture, and intelligent vehicle navigation and safety. In order to support these diverse needs, new national elevation data with higher resolution and accuracy are needed. The 3D Elevation Program (3DEP) initiative was developed to meet the majority of these needs and it is expected that 3DEP will result in new, unimagined information services that would result in job growth and the transformation of the geospatial community. Private-sector data collection companies are continuously evolving sensors and positioning technologies that are needed to collect improved elevation data. An initiative of this scope might also provide an opportunity for companies to improve their capabilities and produce even higher data quality and consistency at a pace that might not have otherwise occurred.

  11. Ethanol Induced Urine Acidification is Related with Early Acetaldehyde Concentration

    Directory of Open Access Journals (Sweden)

    Soon Kil Kwon

    2014-06-01

    Conclusion: In conclusion, urine acidification after ethanol ingestion is related with serum acetaldehyde concentration. Early elevation of acetaldhyde could induce urine acidification, but the urine pH was elevated after a few hours, that might make prolonged acidemia.

  12. Exercise-induced rhabdomyolysis.

    Science.gov (United States)

    Lee, George

    2014-11-03

    Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and pain out of proportion to the expected fatigue post exercise. The diagnosis is confirmed by myoglobinuria, and an elevated serum Creatinine Phosphokinase (CPK) level, usually 10 times the normal range. However, an elevation in CPK is seen in most forms of strenuous exercise, up to 20 times the upper normal range. Therefore, there is no definitive pathologic CPK cut-off. Fortunately the dreaded complication of acute renal failure is rare compared to other forms rhabdomyolysis. We review the risks, diagnosis, clinical course and treatment for exercise- induced rhabdomyolysis.

  13. Investigations of Sooting Laminar Coflow Diffusion Flames at Elevated Pressures

    KAUST Repository

    Steinmetz, Scott A.

    2016-12-01

    Soot is a common byproduct of hydrocarbon based combustion systems. It poses a risk to human and environmental health, and can negatively or positively affect combustor performance. As a result, there is significant interest in understanding soot formation in order to better control it. More recently, the need to study soot formation in engine relevant conditions has become apparent. One engine relevant parameter that has had little focus is the ambient pressure. This body of work focuses on the formation of soot in elevated pressure environments, and a number of investigations are carried out with this purpose. Laminar coflow diffusion flames are used as steady, simple soot producers. First, a commonly studied flame configuration is further characterized. Coflow flames are frequently used for fundamental flame studies, particularly at elevated pressures. However, they are more susceptible to buoyancy induced instabilities at elevated pressures. The velocity of the coflow is known to have an effect on flame stability and soot formation, though these have not been characterized at elevated pressures. A series of flames are investigated covering a range of flowrates, pressures, and nozzle diameters. The stability limits of coflow flames in this range is investigated. Additionally, an alternative strategy for scaling these flames to elevated pressures is proposed. Finally, the effect of coflow rate on soot formation is evaluated. Identification of fundamental flames for coordinated research can facilitate our understanding of soot formation. The next study of this work focuses on adding soot concentration and particle size information to an existing fundamental flame dataset for the purpose of numerical model validation. Soot volume fraction and average particle diameters are successfully measured in nitrogen-diluted ethylene-air laminar coflow flames at pressures of 4, 8, 12, and 16 atm. An increase in particle size with pressure is found up to 12 atm, where particle

  14. Early-Onset Oligohydramnios Complicated with Hypertension, Hyperthyroidism and Coexisting Elevated Urine Vanillylmandelic Acid of Unknown Origin, Mimicking a Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Joung-Liang Wu

    2004-12-01

    Conclusion: A combination of hypertension, oligohydramnios and hyperthyroidism is rare. An elevated 24- hour urine vanillylmandelic acid of unknown origin is a previously unreported finding, to the best of our knowledge, associated with hyperthyroidism and pregnancy-induced hypertension.

  15. Turbulent burning characteristics of FACE-C gasoline and TPRF blend associated with the same RON at elevated pressures

    KAUST Repository

    Mannaa, Ossama; Brequigny, P.; Mounaim-Rousselle, C.; Foucher, F.; Chung, Suk-Ho; Roberts, William L.

    2018-01-01

    morphology induced by the simultaneous existences of different turbulent length scales and the susceptibility to develop cellular structures at elevated pressures (through the Darrieus-Landau instability). Measurements were performed in a well

  16. Thermodynamic and structural characteristics of cement minerals at elevated temperature

    International Nuclear Information System (INIS)

    Bruton, C.J.; Meike, A.; Viani, B.E.; Martin, S.; Phillips, B.L.

    1994-05-01

    We have instituted an experimental and including program designed to elucidate the structural and thermodynamic response of cement minerals to elevated temperature. Components of the program involve: (a) synthesis of hydrated Ca-silicates; (b) structural analysis of cement phases induced by heating and dehydration/rehydration; (c) mechanistic and thermodynamic descriptions of the hydration/dehydration behavior of hydrated Ca-silicates as a function of temperature, pressure and relative humidity; (d) study of naturally occurring hydrated Ca-silicates; and (e) measurements of thermodynamic data for hydrated Ca-silicates

  17. Elevated tumour marker: an indication for imaging?

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

  18. ST Elevations and Elevated Cardiac Enzymes Not Always a STEMI: Two Case Reports.

    Science.gov (United States)

    Fernández Fernández, Juan; Deliz-Guzmán, Claudia; Andino-Colón, César; Claudio-Hernández, Héctor; Lugo-Amador, Nannette

    2016-01-01

    Chest pain is a common complaint in the emergency department (ED). Besides a careful history and physical exam; electrocardiogram, laboratory tests and imaging studies are widely available diagnostic tests that are used for patient assessment. When ST elevation and elevated cardiac enzymes are present the most likely diagnosis are ST elevation myocardial infarction (STEMI) or myocarditis. In this case report we present two low risk patients for major adverse cardiac event with ST elevation and elevated cardiac enzymes and how a careful risk assessment and detailed electrocardiogram evaluation could help differentiating between these two diagnoses.

  19. Conservation status affects elevational gradient in bird diversity in the Himalaya: A new perspective

    Directory of Open Access Journals (Sweden)

    Prakash Kumar Paudel

    2014-12-01

    Full Text Available Understanding diversity patterns along altitudinal gradients, and their underlying causes are important for conserving biodiversity. Previous studies have focused on climatic, energetic, and geographic variables (e.g., mid-domain effects, with less attention paid to human-induced habitat modifications. We used published data of bird distributions along an elevational gradient (0–4900 m in the Nepalese Himalaya and interpolated species presence between elevational limits. The relationship between species richness and environmental variables was analyzed using generalized linear models. A low plateau relationship between bird richness and elevation was observed, with a main peak at intermediate elevations (2800 m. Across the total gradient, interpolated bird species richness had a unimodal relationship to maximum monthly precipitation and a linear response to seasonal variation in temperature, proportion of forest cover, and proportion of protected area. In lower elevations (0–2800 m, interpolated species richness had a positive and linear response to the proportion of Ramsar sites and a unimodal response to habitat heterogeneity. At higher elevations (2900–4900 m, interpolated bird richness had a positive linear response to monthly variation in temperature and a negative linear response to proportion forest cover. We conclude that factors related to human management are important drivers of elevational gradients in bird species richness. Keywords: Elevational gradient, Biogeography, Bird species richness, Conservation, Himalaya, Nepal

  20. Plasma sphingosine-1-phosphate is elevated in obesity.

    Directory of Open Access Journals (Sweden)

    Greg M Kowalski

    Full Text Available BACKGROUND: Dysfunctional lipid metabolism is a hallmark of obesity and insulin resistance and a risk factor for various cardiovascular and metabolic complications. In addition to the well known increase in plasma triglycerides and free fatty acids, recent work in humans and rodents has shown that obesity is associated with elevations in the bioactive class of sphingolipids known as ceramides. However, in obesity little is known about the plasma concentrations of sphinogsine-1-phosphate (S1P, the breakdown product of ceramide, which is an important signaling molecule in mammalian biology. Therefore, the purpose of this study was to examine the impact of obesity on circulating S1P concentration and its relationship with markers of glucose metabolism and insulin sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Plasma S1P levels were determined in high-fat diet (HFD-induced and genetically obese (ob/ob mice along with obese humans. Circulating S1P was elevated in both obese mouse models and in obese humans compared with lean healthy controls. Furthermore, in humans, plasma S1P positively correlated with total body fat percentage, body mass index (BMI, waist circumference, fasting insulin, HOMA-IR, HbA1c (%, total and LDL cholesterol. In addition, fasting increased plasma S1P levels in lean healthy mice. CONCLUSION: We show that elevations in plasma S1P are a feature of both human and rodent obesity and correlate with metabolic abnormalities such as adiposity and insulin resistance.

  1. Keauhou, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  2. Atka, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  3. King Cove, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  4. Chenega, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  5. Juneau, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  6. Lahaina, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  7. Kawaihae, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Shaded Relief of Minnesota Elevation - Color

    Data.gov (United States)

    Minnesota Department of Natural Resources — This file is a product of a shaded relief process on the 30 meter resolution Digital Elevation Model data (dem30im3). This image was created using a custom AML...

  9. Shaded Relief of Minnesota Elevation - Black & White

    Data.gov (United States)

    Minnesota Department of Natural Resources — This file is a product of a shaded relief process on the 30 meter resolution Digital Elevation Model data (dem30im3). This image was created using a custom AML...

  10. Tatitlek, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  11. Hoonah, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  12. Whittier, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  13. Gustavus, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  14. Taholah, Washington Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  15. Chignik, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  16. Panama City, Florida Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  17. Mariana Trench Bathymetric Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) created a bathymetric digital elevation model (DEM) for the Mariana Trench and adjacent seafloor in the Western...

  18. Nikolski, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  19. Battling against Marginalisation: Towards the Elevation of ...

    African Journals Online (AJOL)

    This paper questions the rationale of having Zimbabwean local languages and in ... The study adopts a qualitative methodology and a case study design to ... and possibly future intervention strategies of elevating indigenous languages.

  20. HCF + LCF Interactions at Elevated Temperature

    National Research Council Canada - National Science Library

    Byrne, James; Hall, R. F; Ding, J

    2005-01-01

    ...) crack propagation in Ti- 6Al-4V will be studied under combined HCF/low cycle fatigue (LCF) loading conditions at elevated temperatures up to 350 deg C where creep stress ratcheting and environmental effects may arise...

  1. Elevator mechanism and method for scintillation detectors

    International Nuclear Information System (INIS)

    Frank, E.

    1975-01-01

    An elevator mechanism and method for raising and lowering radioactive samples through a shielded vertical counting chamber in a benchtop scintillation detector is described. The elevator mechanism adds little or nothing to the height of the detector by using an elongated flexible member such as a metal tape secured to the bottom of the elevator platform and extending downwardly through the counting chamber and its bottom shielding, where the tape is bent laterally for connection to a drive means. In the particular embodiment illustrated, the tape is bent laterally below the bottom shielding for the counting chamber, and then upwardly along or through one side of the shielding to a reel at the top of the shielding. The tape is wound onto the reel, and the reel is driven by a reversible motor which winds and unwinds the tape on the reel to raise and lower the elevator platform

  2. Elevated temperature erosive wear of metallic materials

    International Nuclear Information System (INIS)

    Roy, Manish

    2006-01-01

    Solid particle erosion of metals and alloys at elevated temperature is governed by the nature of the interaction between erosion and oxidation, which, in turn, is determined by the thickness, pliability, morphology, adhesion characteristics and toughness of the oxide scale. The main objective of this paper is to critically review the present state of understanding of the elevated temperature erosion behaviour of metals and alloys. First of all, the erosion testing at elevated temperature is reviewed. This is followed by discussion of the essential features of elevated temperature erosion with special emphasis on microscopic observation, giving details of the erosion-oxidation (E-O) interaction mechanisms. The E-O interaction has been elaborated in the subsequent section. The E-O interaction includes E-O maps, analysis of transition criteria from one erosion mechanism to another mechanism and quantification of enhanced oxidation kinetics during erosion. Finally, the relevant areas for future studies are indicated. (topical review)

  3. United States Interagency Elevation Inventory (USIEI)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The U.S. Interagency Elevation Inventory displays high-accuracy topographic and bathymetric data for the United States and its territories. The project is a...

  4. Monterey, California Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  5. Garibaldi, Oregon Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  6. ASTER Digital Elevation Model V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The ASTER Digital Elevation Model (DEM) product is generated using bands 3N (nadir-viewing) and 3B (backward-viewing) of an ASTER Level-1A image acquired by the...

  7. Hanalei, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Ocean City, Maryland Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  9. Southeast Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  10. Kachemak Bay, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  11. New Orleans, Louisiana Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions in the Gulf of Mexico....

  12. Virginia Beach, Virginia Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  13. Galveston, Texas Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  14. Savannah, Georgia Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  15. Biloxi, Mississippi Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  16. Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  17. Santa Barbara, California Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  18. Hilo, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  19. Corpus Christi, Texas Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  20. Port Alexander Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  1. Grain Elevators: New Source Performance Standards (NSPS)

    Science.gov (United States)

    The New Source Performance Standards (NSPS) for Grain Elevators aims to reduce particulate matter pollution. The new amendments seek to clarify definitions, and requirements, as well as propose new regulations on particulate matter emissions

  2. 77 FR 21471 - Final Flood Elevation Determinations

    Science.gov (United States)

    2012-04-10

    ... elevations have been published in newspapers of local circulation and ninety (90) days have elapsed since... School Creek. Approximately 0.61 mile +605 upstream of the confluence with School Creek. Arkansas River...

  3. Arecibo, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  4. Craig, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  5. Midway Atoll Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  6. Guayama, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  7. Fajardo, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  8. Montauk, New York Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  9. Sand Point, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  10. Shemya, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  11. La Push, Washington Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  12. Portland, Maine Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  13. Arena Cove, California Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  14. Port Orford, Oregon Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  15. An elevator for cobalt-60 source

    International Nuclear Information System (INIS)

    Tang Zaimin; Liang Donghu

    1990-07-01

    The elevator used for cobalt-60 source is a key device in the irradiation industry. It plays an important role in the safety and control of irradiation operation as well as the utilization rate of radiation source. From 1983 to 1986, Beijing Institute of Nuclear Engineering undertook designing of various size irradiation projects for different uses. Since then a kind of cobalt-60 source elevator suited for the irradiator of wet-source-storage has been chosen. It is reliable in the operation and complete in the function. An automatic control circuit brings the systems of cobalt-60 source elevator into an interlock system which ensures the irradiation operation safety. Besides introducing the structural features and performance of this elevator, the conditions of safety interlocking in raising or lowering the cobalt-60 source is also discussed. The discussion is from the safety viewpoint of operating an irradiator and irradiation technology

  16. 2 minute Southcentral Alaska Elevation Grid

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The 2-minute Southcentral Alaska Elevation Grid provides bathymetric data in ASCII raster format of 2-minute resolution in geographic coordinates. This grid is...

  17. Adak, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  18. Dutch Harbor, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  19. Unalaska, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) to support individual coastal States as part of the...

  20. Ponce, Puerto Rico Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  1. ASTER Global Digital Elevation Model V002

    Data.gov (United States)

    National Aeronautics and Space Administration — The Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM) was developed jointly by the U.S. National...

  2. Cordova, Alaska Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  3. Nantucket, Massachusetts Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  4. Daytona Beach, Florida Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  5. Oahu, Hawaii Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  6. Central Oregon Coastal Digital Elevation Model

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA's National Geophysical Data Center (NGDC) is building high-resolution digital elevation models (DEMs) for select U.S. coastal regions. These integrated...

  7. Estimating Elevation Angles From SAR Crosstalk

    Science.gov (United States)

    Freeman, Anthony

    1994-01-01

    Scheme for processing polarimetric synthetic-aperture-radar (SAR) image data yields estimates of elevation angles along radar beam to target resolution cells. By use of estimated elevation angles, measured distances along radar beam to targets (slant ranges), and measured altitude of aircraft carrying SAR equipment, one can estimate height of target terrain in each resolution cell. Monopulselike scheme yields low-resolution topographical data.

  8. Elevator Illusion and Gaze Direction in Hypergravity

    Science.gov (United States)

    Cohen, Malcolm M.; Hargens, Alan (Technical Monitor)

    1995-01-01

    A luminous visual target in a dark hypergravity (Gz greater than 1) environment appears to be elevated above its true physical position. This "elevator illusion" has been attributed to changes in oculomotor control caused by increased stimulation of the otolith organs. Data relating the magnitude of the illusion to the magnitude of the changes in oculomotor control have been lacking. The present study provides such data.

  9. Electrostatic Climber for Space Elevator and Launcher

    OpenAIRE

    Bolonkin, A.

    2007-01-01

    Author details research on the new, very prospective, electrostatic Space Elevator climber based on a new electrostatic linear engine previously offered at the 42nd Joint Propulsion Conference (AIAA-2006-5229) and published in AEAT, Vol.78, No.6, 2006, pp. 502-508. The electrostatic climber discussed can have any speed (and braking), the energy for climber movement is delivered by a lightweight high-voltage line into a Space Elevator-holding cable from Earth electric generator. This electric ...

  10. Energy considerations in the partial space elevator

    Science.gov (United States)

    Woo, Pamela; Misra, Arun K.

    2014-06-01

    The space elevator has been proposed as an alternate method for space transportation. A partial elevator is composed of a tether of several hundreds of kilometres, held vertically in tension between two end masses, with its centre of orbit placed at the geosynchronous orbit. A spacecraft can dock at the lower end, and then use the climber on the elevator to ascend to higher altitudes. In this paper, energy calculations are performed, to determine whether a partial elevator can provide sufficient savings in operational costs, compared to the traditional rocket-powered launch. The energy required to launch a spacecraft from a Low Earth Orbit (LEO) to the geostationary orbit (GEO) is calculated for two trajectories. In the first trajectory, the spacecraft travels from LEO to GEO via a Hohmann transfer. In the second trajectory, the spacecraft travels from LEO to the lower end of the partial space elevator with a Hohmann transfer, and then uses the elevator to climb to GEO. The total energy required is compared between the two trajectories. The effects of tether length, spacecraft-to-climber mass ratio, altitude of LEO, and tether material are investigated.

  11. Michelson-Morley in Einstein's elevators

    Science.gov (United States)

    Pierce, Fred; Pierce, Ayal

    2010-02-01

    Experiments are proposed in which a Michelson-Morley interferometer is placed in Einstein's thought experiments where elevators are subjected to varied accelerated fields. Unbeknownst to the observers inside the elevators, they are placed in different circumstances: on the surface of the Earth, in free fall, in space distant from any mass, and inside a rotating space station. By use of not one, but two objects, the observer will be challenged to determine the nature and shape of the accelerated field, if any, inside the elevator. It will be demonstrated that the nature of the accelerated field can be determined easily from inside the elevator by the motion of the two objects released by the observer. It will also be shown that, for the elevator on the space station which is generating an ``artificial gravity'' field by rotation, Michelson-Morley would have the same null result as on Earth. However, the Michelson-Morley experiment is adapted so that in addition to the two horizontal arms of the interferometer (parallel to the floor of the elevator) a vertical arm is added perpendicular to the floor facing towards the ceiling. Such a vertical arm added to the Michelson-Morley experiment adds a new dimension to examining each accelerated field, including gravity. )

  12. Global elevational diversity and diversification of birds.

    Science.gov (United States)

    Quintero, Ignacio; Jetz, Walter

    2018-03-08

    Mountain ranges harbour exceptionally high biodiversity, which is now under threat from rapid environmental change. However, despite decades of effort, the limited availability of data and analytical tools has prevented a robust and truly global characterization of elevational biodiversity gradients and their evolutionary origins. This has hampered a general understanding of the processes involved in the assembly and maintenance of montane communities. Here we show that a worldwide mid-elevation peak in bird richness is driven by wide-ranging species and disappears when we use a subsampling procedure that ensures even species representation in space and facilitates evolutionary interpretation. Instead, richness corrected for range size declines linearly with increasing elevation. We find that the more depauperate assemblages at higher elevations are characterized by higher rates of diversification across all mountain regions, rejecting the idea that lower recent diversification rates are the general cause of less diverse biota. Across all elevations, assemblages on mountains with high rates of past temperature change exhibit more rapid diversification, highlighting the importance of climatic fluctuations in driving the evolutionary dynamics of mountain biodiversity. While different geomorphological and climatic attributes of mountain regions have been pivotal in determining the remarkable richness gradients observed today, our results underscore the role of ongoing and often very recent diversification processes in maintaining the unique and highly adapted biodiversity of higher elevations.

  13. P Elevator: An Innovatively Designed Elevator for Extraction of Third Molars.

    Science.gov (United States)

    Singh, Pradeep; Xiao, Shui Sheng; Ajmera, Deepal Haresh

    2015-01-01

    To modify the conventional straight elevator with a unique and innovative design in respect to approach and accessibility during extraction for patients with abrasions around corners of the mouth and with thick buccal mucosa, without causing overstretching of angles of the mouth. The shank of the straight elevator in the shape of a 'U' was modified, giving it a shape similar to 'P' in the English alphabet hence it is named the P Elevator. The P elevator utilises a 'U' shaped bend in the shank of the conventional straight elevator making space for the buccal soft tissues and the angle of the mouth, to accommodate properly in the 'U' shank. The application of this elevator in the successful removal of third molars is described. Two hundred patients underwent extraction of third molars with the P elevator including 166 patients with disimpaction of all third molars, 23 patients with abrasion around the angle of the mouth, and 11 patients with thick buccal mucosa. Satisfactory results were obtained in all the cases with no postoperative complications. The P elevator permits prudent, meticulous, innovative and proficient extraction of third molars in patients with thick buccal mucosa and abrasions around the angle of the mouth, without overstretching the corners of the mouth. We introduce novel applications of the P elevator in third molar extraction that provide substantial advantages over a conventional straight elevator.

  14. The Dialectic: Not just the Absolute Recoil, but the World’s Living Fire that Extinguishes and Kindles Itself. Reflections on Slavoj Žižek’s Version of Dialectical Philosophy in "Absolute Recoil: Towards a New Foundation of Dialectical Materialism".

    Directory of Open Access Journals (Sweden)

    Christian Fuchs

    2014-10-01

    Full Text Available Slavoj Žižek shows in his book Absolute Recoil (and previous Hegelian works such as Less than Nothing the importance of repeating Hegel’s dialectical philosophy in contemporary capitalism. Žižek contributes especially to a reconceptualisation of dialectical logic and based on it the dialectic of history. The reflections in this paper stress that the dialectic is only the absolute recoil, a sublation that posits its own presuppositions, by working as a living fire that extinguishes and kindles itself. I point out that a new foundation of dialectical materialism needs a proper Heraclitusian foundation. I discuss Žižek’s version of the dialectic that stresses the absolute recoil and the logic of retroactivity and point out its implications for the concept of history as well as Žižek’s own theoretical ambiguities that oscillate between postmodern relativism and mechanical materialism. I argue that Žižek’s version of the dialectic should be brought into a dialogue with the dialectical philosophies of the German Marxists Hans Heinz Holz and Herbert Hörz. Žižek’s achievement is that he helps keeping alive the fire of dialectical materialism in the 21st century. Such a dialectical fire is needed for a proper revolutionary theory.

  15. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance

    Science.gov (United States)

    Loh, Kim; Fukushima, Atsushi; Zhang, Xinmei; Galic, Sandra; Briggs, Dana; Enriori, Pablo J.; Simonds, Stephanie; Wiede, Florian; Reichenbach, Alexander; Hauser, Christine; Sims, Natalie A.; Bence, Kendra K.; Zhang, Sheng; Zhang, Zhong-Yin; Kahn, Barbara B.; Neel, Benjamin G.; Andrews, Zane B.; Cowley, Michael A.; Tiganis, Tony

    2011-01-01

    SUMMARY In obesity, anorectic responses to leptin are diminished, giving rise to the concept of ‘leptin resistance’. Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high fat diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity. PMID:22000926

  16. Lunar transportation scenarios utilising the Space Elevator.

    Science.gov (United States)

    Engel, Kilian A

    2005-01-01

    The Space Elevator (SE) concept has begun to receive an increasing amount of attention within the space community over the past couple of years and is no longer widely dismissed as pure science fiction. In light of the renewed interest in a, possibly sustained, human presence on the Moon and the fact that transportation and logistics form the bottleneck of many conceivable lunar missions, it is interesting to investigate what role the SE could eventually play in implementing an efficient Earth to Moon transportation system. The elevator allows vehicles to ascend from Earth and be injected into a trans-lunar trajectory without the use of chemical thrusters, thus eliminating gravity loss, aerodynamic loss and the need of high thrust multistage launch systems. Such a system therefore promises substantial savings of propellant and structural mass and could greatly increase the efficiency of Earth to Moon transportation. This paper analyzes different elevator-based trans-lunar transportation scenarios and characterizes them in terms of a number of benchmark figures. The transportation scenarios include direct elevator-launched trans-lunar trajectories, elevator launched trajectories via L1 and L2, as well as launch from an Earth-based elevator and subsequent rendezvous with lunar elevators placed either on the near or on the far side of the Moon. The benchmark figures by which the different transfer options are characterized and evaluated include release radius (RR), required delta v, transfer times as well as other factors such as accessibility of different lunar latitudes, frequency of launch opportunities and mission complexity. The performances of the different lunar transfer options are compared with each other as well as with the performance of conventional mission concepts, represented by Apollo. c2005 Elsevier Ltd. All rights reserved.

  17. Elevational distribution and extinction risk in birds.

    Directory of Open Access Journals (Sweden)

    Rachel L White

    Full Text Available Mountainous regions are hotspots of terrestrial biodiversity. Unlike islands, which have been the focus of extensive research on extinction dynamics, fewer studies have examined mountain ranges even though they face increasing threats from human pressures - notably habitat conversion and climate change. Limits to the taxonomic and geographical extent and resolution of previously available information have precluded an explicit assessment of the relative role of elevational distribution in determining extinction risk. We use a new global species-level avian database to quantify the influence of elevational distribution (range, maximum and midpoint on extinction risk in birds at the global scale. We also tested this relationship within biogeographic realms, higher taxonomic levels, and across phylogenetic contrasts. Potential confounding variables (i.e. phylogenetic, distributional, morphological, life history and niche breadth were also tested and controlled for. We show that the three measures of elevational distribution are strong negative predictors of avian extinction risk, with elevational range comparable and complementary to that of geographical range size. Extinction risk was also found to be positively associated with body weight, development and adult survival, but negatively associated with reproduction and niche breadth. The robust and consistent findings from this study demonstrate the importance of elevational distribution as a key driver of variation in extinction dynamics in birds. Our results also highlight elevational distribution as a missing criterion in current schemes for quantifying extinction risk and setting species conservation priorities in birds. Further research is recommended to test for generality across non-avian taxa, which will require an advance in our knowledge of species' current elevational ranges and increased efforts to digitise and centralise such data.

  18. Lunar transportation scenarios utilising the Space Elevator

    Science.gov (United States)

    Engel, Kilian A.

    2005-07-01

    The Space Elevator (SE) concept has begun to receive an increasing amount of attention within the space community over the past couple of years and is no longer widely dismissed as pure science fiction. In light of the renewed interest in a, possibly sustained, human presence on the Moon and the fact that transportation and logistics form the bottleneck of many conceivable lunar missions, it is interesting to investigate what role the SE could eventually play in implementing an efficient Earth to Moon transportation system. The elevator allows vehicles to ascend from Earth and be injected into a trans-lunar trajectory without the use of chemical thrusters, thus eliminating gravity loss, aerodynamic loss and the need of high thrust multistage launch systems. Such a system therefore promises substantial savings of propellant and structural mass and could greatly increase the efficiency of Earth to Moon transportation. This paper analyzes different elevator-based trans-lunar transportation scenarios and characterizes them in terms of a number of benchmark figures. The transportation scenarios include direct elevator-launched trans-lunar trajectories, elevator-launched trajectories via L1 and L2, as well as launch from an Earth-based elevator and subsequent rendezvous with lunar elevators placed either on the near or on the far side of the Moon. The benchmark figures by which the different transfer options are characterized and evaluated include release radius (RR), required Δv, transfer times as well as other factors such as accessibility of different lunar latitudes, frequency of launch opportunities and mission complexity. The performances of the different lunar transfer options are compared with each other as well as with the performance of conventional mission concepts, represented by Apollo.

  19. Creating a Coastal National Elevation Database (CoNED) for science and conservation applications

    Science.gov (United States)

    Thatcher, Cindy A.; Brock, John C.; Danielson, Jeffrey J.; Poppenga, Sandra K.; Gesch, Dean B.; Palaseanu-Lovejoy, Monica; Barras, John; Evans, Gayla A.; Gibbs, Ann

    2016-01-01

    The U.S. Geological Survey is creating the Coastal National Elevation Database, an expanding set of topobathymetric elevation models that extend seamlessly across coastal regions of high societal or ecological significance in the United States that are undergoing rapid change or are threatened by inundation hazards. Topobathymetric elevation models are raster datasets useful for inundation prediction and other earth science applications, such as the development of sediment-transport and storm surge models. These topobathymetric elevation models are being constructed by the broad regional assimilation of numerous topographic and bathymetric datasets, and are intended to fulfill the pressing needs of decision makers establishing policies for hazard mitigation and emergency preparedness, coastal managers tasked with coastal planning compatible with predictions of inundation due to sea-level rise, and scientists investigating processes of coastal geomorphic change. A key priority of this coastal elevation mapping effort is to foster collaborative lidar acquisitions that meet the standards of the USGS National Geospatial Program's 3D Elevation Program, a nationwide initiative to systematically collect high-quality elevation data. The focus regions are located in highly dynamic environments, for example in areas subject to shoreline change, rapid wetland loss, hurricane impacts such as overwash and wave scouring, and/or human-induced changes to coastal topography.

  20. Photosynthesis and metabolite responses of Isatis indigotica Fortune to elevated [CO2

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Hongying Li; Yuzheng Zong; Frank Yonghong Li; Yuanhuai Han; Xingyu Hao

    2017-01-01

    Climate change is affecting global crop productivity, food quality, and security. However, few studies have addressed the mechanism by which elevated CO2 may affect the growth of medicinal plants. Isatis indigotica Fortune is a widely used Chinese medicinal herb with multiple pharmacological properties. To investigate the physiological mechanism of I. indigotica response to elevated [CO2], plants were grown at either ambient [CO2] (385μmol mol?1) or elevated [CO2] (590μmol mol?1) in an open-top chamber (OTC) experimental facility in North China. A significant reduction in transpiration rate (Tr) and stomatal conductance (gs) and a large increase in water-use efficiency contributed to an increase in net photosynthetic rate (Pn) under elevated [CO2] 76 days after sowing. Leaf non-photochemical quenching (NPQ) was decreased, so that more energy was used in effective quantum yield of PSII photochemistry (ΦPSI ) under elevated [CO2]. High ΦPSI , meaning high electron transfer efficiency, also increased Pn. The [CO2]-induced increase in photosynthesis significantly increased biomass by 36.8%. Amounts of metabolic compounds involved in sucrose metabolism, pyrimidine metabolism, flavonoid biosynthesis, and other processes in leaves were reduced under elevated [CO2]. These results showed that the fertilization effect of elevated [CO2] is conducive to increasing dry weight but not secondary metabolism in I. indigotica.

  1. Shake Table Testing of an Elevator System in a Full-Scale Five-Story Building.

    Science.gov (United States)

    Wang, Xiang; Hutchinson, Tara C; Astroza, Rodrigo; Conte, Joel P; Restrepo, José I; Hoehler, Matthew S; Ribeiro, Waldir

    2017-03-01

    This paper investigates the seismic performance of a functional traction elevator as part of a full-scale five-story building shake table test program. The test building was subjected to a suite of earthquake input motions of increasing intensity, first while the building was isolated at its base, and subsequently while it was fixed to the shake table platen. In addition, low-amplitude white noise base excitation tests were conducted while the elevator system was placed in three different configurations, namely, by varying the vertical location of its cabin and counterweight, to study the acceleration amplifications of the elevator components due to dynamic excitations. During the earthquake tests, detailed observation of the physical damage and operability of the elevator as well as its measured response are reported. Although the cabin and counterweight sustained large accelerations due to impact during these tests, the use of well-restrained guide shoes demonstrated its effectiveness in preventing the cabin and counterweight from derailment during high-intensity earthquake shaking. However, differential displacements induced by the building imposed undesirable distortion of the elevator components and their surrounding support structure, which caused damage and inoperability of the elevator doors. It is recommended that these aspects be explicitly considered in elevator seismic design.

  2. Competition and habitat filtering jointly explain phylogenetic structure of soil bacterial communities across elevational gradients.

    Science.gov (United States)

    Zhang, Qian; Goberna, Marta; Liu, Yuguo; Cui, Ming; Yang, Haishui; Sun, Qixiang; Insam, Heribert; Zhou, Jinxing

    2018-04-24

    The importance of assembly processes in shaping biological communities is poorly understood, especially for microbes. Here we report on the forces that structure soil bacterial communities along a 2000 m elevational gradient. We characterized the relative importance of habitat filtering and competition on phylogenetic structure and turnover in bacterial communities. Bacterial communities exhibited a phylogenetically clustered pattern and were more clustered with increasing elevation. Biotic factors (i.e. relative abundance of dominant bacterial lineages) appeared to be most important to the degree of clustering, evidencing the role of the competitive ability of entire clades in shaping the communities. Phylogenetic turnover showed the greatest correlation to elevation. After controlling for elevation, biotic factors showed greater correlation to phylogenetic turnover than all the habitat variables (i.e. climate, soil and vegetation). Structural equation modelling also identified that elevation and soil organic matter exerted indirect effects on phylogenetic diversity and turnover by determining the dominance of microbial competitors. Our results suggest that competition among bacterial taxa induced by soil carbon contributes to the phylogenetic pattern across elevational gradient in the Tibetan Plateau. This highlights the importance of considering not only abiotic filtering but also biotic interactions in soil bacterial communities across stressful elevational gradients. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Effect of elevated CO2, O3, and UV radiation on soils.

    Science.gov (United States)

    Formánek, Pavel; Rejšek, Klement; Vranová, Valerie

    2014-01-01

    In this work, we have attempted to review the current knowledge on the impact of elevated CO2, O3, and UV on soils. Elevated CO2 increases labile and stabile soil C pool as well as efficiency of organic pollutants rhizoremediation and phytoextraction of heavy metals. Conversely, both elevated O3 and UV radiation decrease inputs of assimilates to the rhizosphere being accompanied by inhibitory effects on decomposition processes, rhizoremediation, and heavy metals phytoextraction efficiency. Contrary to elevated CO2, O3, or UV-B decreases soil microbial biomass, metabolisable C, and soil N t content leading to higher C/N of soil organic matter. Elevated UV-B radiation shifts soil microbial community and decreases populations of soil meso- and macrofauna via direct effect rather than by induced changes of litter quality and root exudation as in case of elevated CO2 or O3. CO2 enrichment or increased UV-B is hypothesised to stimulate or inhibit both plant and microbial competitiveness for soluble soil N, respectively, whereas O3 favours only microbial competitive efficiency. Understanding the consequences of elevated CO2, O3, and UV radiation for soils, especially those related to fertility, phytotoxins inputs, elements cycling, plant-microbe interactions, and decontamination of polluted sites, presents a knowledge gap for future research.

  4. Effect of Elevated CO2, O3, and UV Radiation on Soils

    Directory of Open Access Journals (Sweden)

    Pavel Formánek

    2014-01-01

    Full Text Available In this work, we have attempted to review the current knowledge on the impact of elevated CO2, O3, and UV on soils. Elevated CO2 increases labile and stabile soil C pool as well as efficiency of organic pollutants rhizoremediation and phytoextraction of heavy metals. Conversely, both elevated O3 and UV radiation decrease inputs of assimilates to the rhizosphere being accompanied by inhibitory effects on decomposition processes, rhizoremediation, and heavy metals phytoextraction efficiency. Contrary to elevated CO2, O3, or UV-B decreases soil microbial biomass, metabolisable C, and soil Nt content leading to higher C/N of soil organic matter. Elevated UV-B radiation shifts soil microbial community and decreases populations of soil meso- and macrofauna via direct effect rather than by induced changes of litter quality and root exudation as in case of elevated CO2 or O3. CO2 enrichment or increased UV-B is hypothesised to stimulate or inhibit both plant and microbial competitiveness for soluble soil N, respectively, whereas O3 favours only microbial competitive efficiency. Understanding the consequences of elevated CO2, O3, and UV radiation for soils, especially those related to fertility, phytotoxins inputs, elements cycling, plant-microbe interactions, and decontamination of polluted sites, presents a knowledge gap for future research.

  5. Effects of oxygen on responses to heating in two lizard species sampled along an elevational gradient.

    Science.gov (United States)

    DuBois, P Mason; Shea, Tanner K; Claunch, Natalie M; Taylor, Emily N

    2017-08-01

    Thermal tolerance is an important variable in predictive models about the effects of global climate change on species distributions, yet the physiological mechanisms responsible for reduced performance at high temperatures in air-breathing vertebrates are not clear. We conducted an experiment to examine how oxygen affects three variables exhibited by ectotherms as they heat-gaping threshold, panting threshold, and loss of righting response (the latter indicating the critical thermal maximum)-in two lizard species along an elevational (and therefore environmental oxygen partial pressure) gradient. Oxygen partial pressure did not impact these variables in either species. We also exposed lizards at each elevation to severely hypoxic gas to evaluate their responses to hypoxia. Severely low oxygen partial pressure treatments significantly reduced the gaping threshold, panting threshold, and critical thermal maximum. Further, under these extreme hypoxic conditions, these variables were strongly and positively related to partial pressure of oxygen. In an elevation where both species overlapped, the thermal tolerance of the high elevation species was less affected by hypoxia than that of the low elevation species, suggesting the high elevation species may be adapted to lower oxygen partial pressures. In the high elevation species, female lizards had higher thermal tolerance than males. Our data suggest that oxygen impacts the thermal tolerance of lizards, but only under severely hypoxic conditions, possibly as a result of hypoxia-induced anapyrexia. Copyright © 2017. Published by Elsevier Ltd.

  6. Effect of Elevated CO2, O3, and UV Radiation on Soils

    Science.gov (United States)

    Rejšek, Klement; Vranová, Valerie

    2014-01-01

    In this work, we have attempted to review the current knowledge on the impact of elevated CO2, O3, and UV on soils. Elevated CO2 increases labile and stabile soil C pool as well as efficiency of organic pollutants rhizoremediation and phytoextraction of heavy metals. Conversely, both elevated O3 and UV radiation decrease inputs of assimilates to the rhizosphere being accompanied by inhibitory effects on decomposition processes, rhizoremediation, and heavy metals phytoextraction efficiency. Contrary to elevated CO2, O3, or UV-B decreases soil microbial biomass, metabolisable C, and soil Nt content leading to higher C/N of soil organic matter. Elevated UV-B radiation shifts soil microbial community and decreases populations of soil meso- and macrofauna via direct effect rather than by induced changes of litter quality and root exudation as in case of elevated CO2 or O3. CO2 enrichment or increased UV-B is hypothesised to stimulate or inhibit both plant and microbial competitiveness for soluble soil N, respectively, whereas O3 favours only microbial competitive efficiency. Understanding the consequences of elevated CO2, O3, and UV radiation for soils, especially those related to fertility, phytotoxins inputs, elements cycling, plant-microbe interactions, and decontamination of polluted sites, presents a knowledge gap for future research. PMID:24688424

  7. Space Elevator Concept Considered a Reality

    Science.gov (United States)

    2000-01-01

    The `once upon a time' science fiction concept of a space elevator has been envisioned and studied as a real mass transportation system in the latter part of the 21st century. David Smitherman of NASA's Marshall Space Flight Center's Advanced Projects Office has compiled plans for such an elevator. The space elevator concept is a structure extending from the surface of the Earth to geostationary Earth orbit (GEO) at 35,786 km in altitude. The tower would be approximately 50 km tall with a cable tethered to the top. Its center mass would be at GEO such that the entire structure orbits the Earth in sync with the Earth's rotation maintaining a stationary position over its base attachment at the equator. Electromagnetic vehicles traveling along the cable could serve as a mass transportation system for transporting people, payloads, and power between space and Earth. This illustration by artist Pat Rawling shows the concept of a space elevator as viewed from the geostationary transfer station looking down the length of the elevator towards the Earth.

  8. Operation of a hydraulic elevator system

    Energy Technology Data Exchange (ETDEWEB)

    Lazarev, G.A.; Li, Yu.V.; Bezuglov, N.N.

    1983-03-01

    The paper describes the hydraulic elevator system in the im. 50-letiya Oktyabr'skoi Revolutsii mine in the Karaganda basin. The system removes water and coal from the sump of a skip mine shaft. Water influx rate per day to the sump does not exceed 120 m/sup 3/, weight of coal falling from the skip is about 5,000 kg per day. The sump, 85 m deep, is closed by a screen. The elevator system consists of two pumps (one is used as a reserve pump) with a capacity of 300 m/sup 3/h. When water level exceeds the maximum permissive limit the pump is activated by an automatic control system. The coal and water mixture pumped from the sump bottom is directed to a screen which separates coal from water. Coal is fed to a coal hopper and water is pumped to a water tank. The hydraulic elevator has a capacity of 80 m/sup 3/ of mixture per hour. The slurry is tranported by a pipe of 175 mm diameter. Specifications of the pumps and pipelines are given. A scheme of the hydraulic elevator system is also shown. Economic aspects of hydraulic elevator use for removal of water and coal from deep sumps of skip shafts in the Karaganda basin also are discussed.

  9. False elevation of carboxyhemoglobin: case report.

    Science.gov (United States)

    Mehrotra, Shruti; Edmonds, Marcia; Lim, Rodrick K

    2011-02-01

    Carbon monoxide toxicity in infants and children, like adults, produce nonspecific symptoms with normal vital signs necessitating the serum measurement of carboxyhemoglobin (COHb). In infants, the COHb may be falsely elevated. Our goal was to report a case of suspected carbon monoxide toxicity in an infant and the likely cause of the falsely elevated serum COHb. A previously healthy 3-month-old girl presented to the pediatric emergency department (ED) with smoke inhalation from a defective furnace. She was asymptomatic. On examination, she was alert, with Glasgow Coma Scale of 15 and normal vital signs. Cardiorespiratory and neurological examinations were completely normal. Because of concern regarding carbon monoxide poisoning, she was treated with normobaric oxygen therapy. Initial and subsequent serum COHb levels were persistently elevated, despite treatment and the infant appearing clinically well. As such, she had a prolonged stay in the ED. Further investigations found that fetal hemoglobin interferes with the spectrophotometric method used to analyze serum COHb levels. Carboxyhemoglobin serum level, in infants, may be falsely elevated due to the fetal hemoglobin interfering with standard methods of analysis. Knowledge of the false elevation using standard spectrophotometric methods of COHb in clinically well-appearing infants can decrease unnecessary oxygen therapy and monitoring time in the ED.

  10. Elevation in Type I Interferons Inhibits HCN1 and Slows Cortical Neuronal Oscillations

    NARCIS (Netherlands)

    Stadler, Konstantin; Bierwirth, Claudia; Stoenica, Luminita; Battefeld, Arne; Reetz, Olivia; Mix, Eilhard; Schuchmann, Sebastian; Velmans, Tanja; Rosenberger, Karen; Bräuer, Anja U.; Lehnardt, Seija; Nitsch, Robert; Budt, Matthias; Wolff, Thorsten; Kole, Maarten H. P.; Strauss, Ulf

    2014-01-01

    Central nervous system (CNS) inflammation involves the generation of inducible cytokines such as interferons (IFNs) and alterations in brain activity, yet the interplay of both is not well understood. Here, we show that in vivo elevation of IFNs by viral brain infection reduced

  11. Effect of elevated atmospheric CO2 and vegetation type on microbiota associated with decomposing straw

    DEFF Research Database (Denmark)

    Frederiksen, Helle B.; Ronn, R.; Christensen, S.

    2001-01-01

    Straw from wheat plants grown at ambient and elevated atmospheric CO2 concentrations was placed in litterbags in a grass fallow field and a wheat field. The CO2 treatment induced an increase in straw concentration of ash-free dry mass from 84% to 93% and a decrease in nitrogen concentration from ...

  12. Scientific return of a lunar elevator

    Science.gov (United States)

    Eubanks, T. M.; Radley, C. F.

    2016-11-01

    The concept of a space elevator dates back to Tsilokovsky, but they are not commonly considered in near-term plans for space exploration, perhaps because a terrestrial elevator would not be possible without considerable improvements in tether material. A Lunar Space Elevator (LSE), however, can be built with current technology using commercially available tether polymers. This paper considers missions leading to infrastructure capable of shortening the time, lowering the cost and enhancing the capabilities of robotic and human explorers. These missions use planetary scale tethers, strings many thousands of kilometers long stabilized either by rotation or by gravitational gradients. These systems promise major reduction in transport costs versus chemical rockets, in a rapid timeframe, for a modest investment. Science will thus benefit as well as commercial activities.

  13. Advanced composite elevator for Boeing 727 aircraft

    Science.gov (United States)

    1979-01-01

    Detail design activities are reported for a program to develop an advanced composites elevator for the Boeing 727 commercial transport. Design activities include discussion of the full scale ground test and flight test activities, the ancillary test programs, sustaining efforts, weight status, and the production status. Prior to flight testing of the advanced composites elevator, ground, flight flutter, and stability and control test plans were reviewed and approved by the FAA. Both the ground test and the flight test were conducted according to the approved plan, and were witnessed by the FAA. Three and one half shipsets have now been fabricated without any significant difficulty being encountered. Two elevator system shipsets were weighed, and results validated the 26% predicted weight reduction. The program is on schedule.

  14. 3D Elevation Program: summary for Vermont

    Science.gov (United States)

    Carswell, William J.

    2015-01-01

    Elevation data are essential to a broad range of applications, including forest resources management, wildlife and habitat management, national security, recreation, and many others. For the State of Vermont, elevation data are critical for hazard mitigation, geologic resource assessment, natural resources conservation, agriculture and precision farming, flood risk management, infrastructure and construction management, and other business uses. Today, high-density light detection and ranging (lidar) data are the primary sources for deriving elevation models and other datasets. Federal, State, Tribal, and local agencies work in partnership to (1) replace data that are older and of lower quality and (2) provide coverage where publicly accessible data do not exist. A joint goal of State and Federal partners is to acquire consistent, statewide coverage to support existing and emerging applications enabled by lidar data.

  15. Vertical vibration analysis for elevator compensating sheave

    International Nuclear Information System (INIS)

    Watanabe, Seiji; Nakazawa, Daisuke; Fukui, Daiki; Okawa, Takeya

    2013-01-01

    Most elevators applied to tall buildings include compensating ropes to satisfy the balanced rope tension between the car and the counter weight. The compensating ropes receive tension by the compensating sheave, which is installed at the bottom space of the elevator shaft. The compensating sheave is only suspended by the compensating ropes, therefore, the sheave can move vertically while the car is traveling. This paper shows the elevator dynamic model to evaluate the vertical motion of the compensating sheave. Especially, behavior in emergency cases, such as brake activation and buffer strike, was investigated to evaluate the maximum upward motion of the sheave. The simulation results were validated by experiments and the most influenced factor for the sheave vertical motion was clarified

  16. 3D Elevation Program: summary for Nebraska

    Science.gov (United States)

    Carswell, William J.

    2015-01-01

    Elevation data are essential to a broad range of applications, including forest resources management, wildlife and habitat management, national security, recreation, and many others. For the State of Nebraska, elevation data are critical for agriculture and precision farming, natural resources conservation, flood risk management, infrastructure and construction management, geologic resource assessment and hazard mitigation, and other business uses. Today, high-density light detection and ranging (lidar) data are the primary sources for deriving elevation models and other datasets. Federal, State, Tribal, and local agencies work in partnership to (1) replace data that are older and of lower quality and (2) provide coverage where publicly accessible data do not exist. A joint goal of State and Federal partners is to acquire consistent, statewide coverage to support existing and emerging applications enabled by lidar data.

  17. Vertical vibration analysis for elevator compensating sheave

    Science.gov (United States)

    Watanabe, Seiji; Okawa, Takeya; Nakazawa, Daisuke; Fukui, Daiki

    2013-07-01

    Most elevators applied to tall buildings include compensating ropes to satisfy the balanced rope tension between the car and the counter weight. The compensating ropes receive tension by the compensating sheave, which is installed at the bottom space of the elevator shaft. The compensating sheave is only suspended by the compensating ropes, therefore, the sheave can move vertically while the car is traveling. This paper shows the elevator dynamic model to evaluate the vertical motion of the compensating sheave. Especially, behavior in emergency cases, such as brake activation and buffer strike, was investigated to evaluate the maximum upward motion of the sheave. The simulation results were validated by experiments and the most influenced factor for the sheave vertical motion was clarified.

  18. A new bed elevation dataset for Greenland

    Directory of Open Access Journals (Sweden)

    J. L. Bamber

    2013-03-01

    Full Text Available We present a new bed elevation dataset for Greenland derived from a combination of multiple airborne ice thickness surveys undertaken between the 1970s and 2012. Around 420 000 line kilometres of airborne data were used, with roughly 70% of this having been collected since the year 2000, when the last comprehensive compilation was undertaken. The airborne data were combined with satellite-derived elevations for non-glaciated terrain to produce a consistent bed digital elevation model (DEM over the entire island including across the glaciated–ice free boundary. The DEM was extended to the continental margin with the aid of bathymetric data, primarily from a compilation for the Arctic. Ice thickness was determined where an ice shelf exists from a combination of surface elevation and radar soundings. The across-track spacing between flight lines warranted interpolation at 1 km postings for significant sectors of the ice sheet. Grids of ice surface elevation, error estimates for the DEM, ice thickness and data sampling density were also produced alongside a mask of land/ocean/grounded ice/floating ice. Errors in bed elevation range from a minimum of ±10 m to about ±300 m, as a function of distance from an observation and local topographic variability. A comparison with the compilation published in 2001 highlights the improvement in resolution afforded by the new datasets, particularly along the ice sheet margin, where ice velocity is highest and changes in ice dynamics most marked. We estimate that the volume of ice included in our land-ice mask would raise mean sea level by 7.36 m, excluding any solid earth effects that would take place during ice sheet decay.

  19. Strength properties of concrete at elevated temperatures

    International Nuclear Information System (INIS)

    Freskakis, G.N.; Burrow, R.C.; Debbas, E.B.

    1979-01-01

    A study is presented concerning the compressive strength, modulus of elasticity, and stress-strain relationships of concrete at elevated temperatures. A review of published results provides information for the development of upper and lower bound relationships for compressive strength and the modulus of elasticity and establishes exposure conditions for a lower bound thermal response. The relationships developed from the literature review are confirmed by the results of a verification test program. The strength and elasticity relationships provide a basis for the development of design stress-strain curves for concrete exposed to elevated temperatures

  20. Forest succession at elevated CO2; TOPICAL

    International Nuclear Information System (INIS)

    Clark, James S.; Schlesinger, William H.

    2002-01-01

    We tested hypotheses concerning the response of forest succession to elevated CO2 in the FACTS-1 site at the Duke Forest. We quantified growth and survival of naturally recruited seedlings, tree saplings, vines, and shrubs under ambient and elevated CO2. We planted seeds and seedlings to augment sample sites. We augmented CO2 treatments with estimates of shade tolerance and nutrient limitation while controlling for soil and light effects to place CO2 treatments within the context of natural variability at the site. Results are now being analyzed and used to parameterize forest models of CO2 response