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Sample records for atypical transient stress-induced

  1. Apoplastic reactive oxygen species transiently decrease auxin signaling and cause stress-induced morphogenic response in Arabidopsis.

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    Blomster, Tiina; Salojärvi, Jarkko; Sipari, Nina; Brosché, Mikael; Ahlfors, Reetta; Keinänen, Markku; Overmyer, Kirk; Kangasjärvi, Jaakko

    2011-12-01

    Reactive oxygen species (ROS) are ubiquitous signaling molecules in plant stress and development. To gain further insight into the plant transcriptional response to apoplastic ROS, the phytotoxic atmospheric pollutant ozone was used as a model ROS inducer in Arabidopsis (Arabidopsis thaliana) and gene expression was analyzed with microarrays. In contrast to the increase in signaling via the stress hormones salicylic acid, abscisic acid, jasmonic acid (JA), and ethylene, ROS treatment caused auxin signaling to be transiently suppressed, which was confirmed with a DR5-uidA auxin reporter construct. Transcriptomic data revealed that various aspects of auxin homeostasis and signaling were modified by apoplastic ROS. Furthermore, a detailed analysis of auxin signaling showed that transcripts of several auxin receptors and Auxin/Indole-3-Acetic Acid (Aux/IAA) transcriptional repressors were reduced in response to apoplastic ROS. The ROS-derived changes in the expression of auxin signaling genes partially overlapped with abiotic stress, pathogen responses, and salicylic acid signaling. Several mechanisms known to suppress auxin signaling during biotic stress were excluded, indicating that ROS regulated auxin responses via a novel mechanism. Using mutants defective in various auxin (axr1, nit1, aux1, tir1 afb2, iaa28-1, iaa28-2) and JA (axr1, coi1-16) responses, ROS-induced cell death was found to be regulated by JA but not by auxin. Chronic ROS treatment resulted in altered leaf morphology, a stress response known as "stress-induced morphogenic response." Altered leaf shape of tir1 afb2 suggests that auxin was a negative regulator of stress-induced morphogenic response in the rosette.

  2. [Takotsubo and surroundings. Step by step postpartum stress-induced cardiomyopathy shows its facet. A peculiar case of atypical takotasubo in the peripartum period].

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    Russo, Marco; Sappa, Roberta; Gianfagna, Enrico; Salame, Kareem; Sinagra, Gianfranco; Proclemer, Alessandro

    2014-01-01

    Takotsubo syndrome is an acquired cardiomyopathy with transient and reversible left ventricular dysfunction that can mimic an acute coronary syndrome. It is characterized by ECG abnormalities, including minimal ST-segment elevation and T-wave changes, mild troponin elevation, typical left ventricular regional wall motion abnormalities (apical ballooning) and atypical forms (midventricular or reverse apical ballooning) without significant coronary artery stenosis. Its etiology and pathophysiology remain unclear. The sympathetic system seems to play a central role: its exaggerated response to emotional or physical stress triggers may induce microvascular dysfunction and catecholamine-induced cardiotoxicity due to cyclic AMP-mediated calcium overload. We report our experience highlighting the possible pathophysiological and clinical overlap of emotional-triggered catecholamine cardiotoxicity, arterial hypertension and physiological cardiovascular overload in pregnancy describing an atypical case of takotsubo cardiomyopathy with diffuse left ventricular hypokinesia at onset and subsequent evolution to apical ballooning.

  3. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

    Institute of Scientific and Technical Information of China (English)

    Tong Liu; Ru-Rong Ji

    2012-01-01

    Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice,and furthermore,to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch.Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice.The mice were observed for 30 min.Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 μmol) elicited robust scratching behavior,displaying an inverted U-shaped dose-response curve.Naloxone,an opioid receptor antagonist,but not morphine,largely suppressed the oxidant-induced scratching.Chlorpheniramine,a histamine H 1 receptor antagonist,blocked histamine-but not oxidant-induced scratching,indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch.Further,resiniferatoxin treatment abolished oxidant-induced scratching,suggesting an essential role of C-fibers.Notably,blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031,or genetic deletion of Trpal but not Trpvl (subfamily V,member 1) resulted in a profound reduction in H2O2-evoked scratching.Finally,systemic administration of the antioxidant Nacety1-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.Conclusion Oxidative stress by different oxidants induces profound scratching behavior,which is largely histamine-and TRPV1-independent but TRPA1-dependent.Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.

  4. Atypical transient stress-induced cardiomyopathies with an inverted Takotsubo pattern in sepsis and in the postpartal state.

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    Lee, Sahng; Lee, Kyung Jin; Yoon, Hyeon Soo; Kang, Ki-Woon; Lee, Young Sook; Lee, Jun Wan

    2010-01-01

    Several cases of inverted Takotsubo cardiomyopathy--a variant form with hyperdynamic left ventricular apex and akinesia of the left ventricular base and mid-portion--have been reported recently, especially in association with cerebrovascular accidents and catecholamine cardiomyopathies. Herein, we describe 2 cases of inverted Takotsubo cardiomyopathy: one that occurred in a middle-aged woman who had a septic condition, and another in a young woman who was in the postpartal state. Such cases have not been reported previously.

  5. Stress-Induced Anxiety- and Depressive-Like Phenotype Associated with Transient Reduction in Neurogenesis in Adult Nestin-CreERT2/Diphtheria Toxin Fragment A Transgenic Mice.

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    Yun, Sanghee; Donovan, Michael H; Ross, Michele N; Richardson, Devon R; Reister, Robin; Farnbauch, Laure A; Fischer, Stephanie J; Riethmacher, Dieter; Gershenfeld, Howard K; Lagace, Diane C; Eisch, Amelia J

    2016-01-01

    Depression and anxiety involve hippocampal dysfunction, but the specific relationship between these mood disorders and adult hippocampal dentate gyrus neurogenesis remains unclear. In both humans with MDD and rodent models of depression, administration of antidepressants increases DG progenitor and granule cell number, yet rodents with induced ablation of DG neurogenesis typically do not demonstrate depressive- or anxiety-like behaviors. The conflicting data may be explained by the varied duration and degree to which adult neurogenesis is reduced in different rodent neurogenesis ablation models. In order to test this hypothesis we examined how a transient-rather than permanent-inducible reduction in neurogenesis would alter depressive- and anxiety-like behaviors. Transgenic Nestin-CreERT2/floxed diphtheria toxin fragment A (DTA) mice (Cre+DTA+) and littermates (Cre+DTA-; control) were given tamoxifen (TAM) to induce recombination and decrease nestin-expressing stem cells and their progeny. The decreased neurogenesis was transient: 12 days post-TAM Cre+DTA+ mice had fewer DG proliferating Ki67+ cells and fewer DCX+ neuroblasts/immature neurons relative to control, but 30 days post-TAM Cre+DTA+ mice had the same DCX+ cell number as control. This ability of DG neurogenesis to recover after partial ablation also correlated with changes in behavior. Relative to control, Cre+DTA+ mice tested between 12-30 days post-TAM displayed indices of a stress-induced anxiety phenotype-longer latency to consume highly palatable food in the unfamiliar cage in the novelty-induced hypophagia test, and a depression phenotype-longer time of immobility in the tail suspension test, but Cre+DTA+ mice tested after 30 days post-TAM did not. These findings suggest a functional association between adult neurogenesis and stress induced anxiety- and depressive-like behaviors, where induced reduction in DCX+ cells at the time of behavioral testing is coupled with stress-induced anxiety and a

  6. Repeated exposure of adult rats to transient oxidative stress induces various long-lasting alterations in cognitive and behavioral functions.

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    Yoshio Iguchi

    Full Text Available Exposure of neonates to oxidative stress may increase the risk of psychiatric disorders such as schizophrenia in adulthood. However, the effects of moderate oxidative stress on the adult brain are not completely understood. To address this issue, we systemically administrated 2-cyclohexen-1-one (CHX to adult rats to transiently reduce glutathione levels. Repeated administration of CHX did not affect the acquisition or motivation of an appetitive instrumental behavior (lever pressing rewarded by a food outcome under a progressive ratio schedule. In addition, response discrimination and reversal learning were not affected. However, acute CHX administration blunted the sensitivity of the instrumental performance to outcome devaluation, and this effect was prolonged in rats with a history of repeated CHX exposure, representing pro-depression-like phenotypes. On the other hand, repeated CHX administration reduced immobility in forced swimming tests and blunted acute cocaine-induced behaviors, implicating antidepressant-like effects. Multivariate analyses segregated a characteristic group of behavioral variables influenced by repeated CHX administration. Taken together, these findings suggest that repeated administration of CHX to adult rats did not cause a specific mental disorder, but it induced long-term alterations in behavioral and cognitive functions, possibly related to specific neural correlates.

  7. Disfunção ventricular esquerda transitória por cardiomiopatia induzida por estresse Transient left ventricular dysfunction due to stress-induced cardiomyopathy

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    Marcus Vinicius Simões

    2007-10-01

    Full Text Available Apresenta-se o caso de uma paciente de 71 anos que preencheu os critérios diagnósticos para cardiomiopatia induzida por estresse que foi desencadeada por intenso estresse emocional após atropelamento por bicicleta. O quadro clínico mimetizou o infarto agudo do miocárdio, manifestando-se com dor precordial, supradesnivelamento do segmento ST, seguido por ondas T profundas e prolongamento do intervalo QT, elevação discreta de enzimas cardíacas e cursando com disfunção sistólica apical do ventrículo esquerdo e hipercinesia das porções basais (conferindo o aspecto de "abaloamento apical", mas na ausência de obstrução coronariana subepicárdica. A função ventricular normalizou-se após a segunda semana de evolução.The case presented here is of a 71-yr-old female patient who met the diagnostic criteria for stress-induced cardiomyopathy, which was triggered by intense emotional stress after being hit by a bicycle. The clinical picture mimicked that of an acute myocardial infarction, manifesting as precordial pain, ST-segment depression followed by deep negative T waves and prolonging of the QT interval, slight increase in cardiac enzymes and coursing with transient apical ballooning of the left ventricle and hyperkinesis of the basal walls (conferring the aspect of "apical ballooning", although in the absence of subepicardial coronary obstruction. Ventricular function normalized after the second week of clinical evolution.

  8. Cold stress induces lower urinary tract symptoms.

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    Imamura, Tetsuya; Ishizuka, Osamu; Nishizawa, Osamu

    2013-07-01

    Cold stress as a result of whole-body cooling at low environmental temperatures exacerbates lower urinary tract symptoms, such as urinary urgency, nocturia and residual urine. We established a model system using healthy conscious rats to explore the mechanisms of cold stress-induced detrusor overactivity. In this review, we summarize the basic findings shown by this model. Rats that were quickly transferred from room temperature (27 ± 2°C) to low temperature (4 ± 2°C) showed detrusor overactivity including increased basal pressure and decreased voiding interval, micturition volume, and bladder capacity. The cold stress-induced detrusor overactivity is mediated through a resiniferatoxin-sensitve C-fiber sensory nerve pathway involving α1-adrenergic receptors. Transient receptor potential melastatin 8 channels, which are sensitive to thermal changes below 25-28°C, also play an important role in mediating the cold stress responses. Additionally, the sympathetic nervous system is associated with transient hypertension and decreases of skin surface temperature that are closely correlated with the detrusor overactivity. With this cold stress model, we showed that α1-adrenergic receptor antagonists have the potential to treat cold stress-exacerbated lower urinary tract symptoms. In addition, we showed that traditional Japanese herbal mixtures composed of Hachimijiogan act, in part, by increasing skin temperature and reducing the number of cold sensitive transient receptor potential melastatin channels in the skin. The effects of herbal mixtures have the potential to treat and/or prevent the exacerbation of lower urinary tract symptoms by providing resistance to the cold stress responses. Our model provides new opportunities for utilizing animal disease models with altered lower urinary tract functions to explore the effects of novel therapeutic drugs.

  9. Does stress induce bowel dysfunction?

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    Chang, Yu-Ming; El-Zaatari, Mohamad; Kao, John Y

    2014-08-01

    Psychological stress is known to induce somatic symptoms. Classically, many gut physiological responses to stress are mediated by the hypothalamus-pituitary-adrenal axis. There is, however, a growing body of evidence of stress-induced corticotrophin-releasing factor (CRF) release causing bowel dysfunction through multiple pathways, either through the HPA axis, the autonomic nervous systems, or directly on the bowel itself. In addition, recent findings of CRF influencing the composition of gut microbiota lend support for the use of probiotics, antibiotics, and other microbiota-altering agents as potential therapeutic measures in stress-induced bowel dysfunction.

  10. Atypical Depression

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    Diseases and Conditions Atypical depression By Mayo Clinic Staff Any type of depression can make you feel sad and keep you from enjoying life. However, atypical depression — also called depression with atypical features — means that ...

  11. Inhibition of conditioned stimulus pathway phosphoprotein 24 expression blocks the reduction in A-type transient K+ current produced by one-trial in vitro conditioning of Hermissenda.

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    Yamoah, Ebenezer N; Levic, Snezana; Redell, John B; Crow, Terry

    2005-05-11

    Long-term intrinsic enhanced excitability is a characteristic of cellular plasticity and learning-dependent modifications in the activity of neural networks. The regulation of voltage-dependent K+ channels by phosphorylation/dephosphorylation and their localization is proposed to be important in the control of cellular plasticity. One-trial conditioning in Hermissenda results in enhanced excitability in sensory neurons, type B photoreceptors, of the conditioned stimulus pathway. Conditioning also regulates the phosphorylation of conditioned stimulus pathway phosphoprotein 24 (Csp24), a cytoskeletal-related protein containing multiple beta-thymosin-like domains. Recently, it was shown that the downregulation of Csp24 expression mediated by an antisense oligonucleotide blocked the development of enhanced excitability in identified type B photoreceptors after one-trial conditioning without affecting short-term excitability. Here, we show using whole-cell patch recordings that one-trial in vitro conditioning applied to isolated photoreceptors produces a significant reduction in the amplitude of the A-type transient K+ current (I(A)) detected 1.5-16 h after conditioning. One-trial conditioning produced a depolarized shift in the steady-state activation curve of I(A) without altering the inactivation curve. The conditioning-dependent reduction in I(A) was blocked by preincubation of the photoreceptors with Csp antisense oligonucleotide. These results provide an important link between Csp24, a cytoskeletal protein, and regulation of voltage-gated ion channels associated with intrinsic enhanced excitability underlying pavlovian conditioning.

  12. Stress-induced cardiomyopathy in the absence of complaints

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    N. M. Butkevich

    2012-01-01

    Full Text Available Stress-induced cardiomyopathy or Takotsubo cardiomyopathy that generally runs with the clinical manifestations of acute coronary syndrome and left ventricular asynergy, which are caused by emotional, psychological, or physical stress, is most frequently encountered among the unclassified cardiomyopathies. A clinical case of this myocardial lesion without clinical manifestations, but with transient electrocardiographic changes and evident impairment of left ventricular contraction is described.

  13. Atypical pneumonia

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    Walking pneumonia; Community-acquired pneumonia - atypical ... Bacteria that cause atypical pneumonia include: Mycoplasma pneumonia is caused by the bacteria Mycoplasma pneumoniae . It often affects people younger than age 40. Pneumonia due ...

  14. Up-regulation of the transient A-type K+ current (IA) in the differentiation of neural stem cells of the early postnatal rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    GUO Hong-bo; HUANG Lian-yan; ZOU Yu-xi; ZOU Fei

    2010-01-01

    Background Neural stem cells (NSCs) not only are essential to cell replacement therapy and transplantation in clinical settings, but also provide a unique model for the research into neurogenesis and epigenesis. However, little attention has been paid to the electrophysiological characterization of NSC development. This work aimed to identify whether the morphological neuronal differentiation process in NSCs included changes in the electrophysiological properties of transient A-type K+ currents (IA).Methods NSCs were isolated from early postnatal rat hippocampus and were multiplied in basic serum-free medium containing basic fibroblast growth factor. Potassium currents were investigated and compared using whole-cell patch-clamp techniques and one-way analysis of variance (ANOVA), respectively.Results Compared with NSC-derived neurons, cloned NSCs (cNSCs) had a more positive resting membrane potential, a higher input resistance, and a lower membrane capacitance. Part of cNSCs and NSC-derived neurons possessed both delayed-rectifier K+ currents (IDR) and IA, steady-state activation of IA in cNSCs (half-maximal activation at (21.34±4.37) mV) occurred at a more positive voltage than in NSC-derived neurons at 1-6 days in vitro (half-maximal activation at (12.85±4.19) mV).Conclusions Our research revealed a developmental up-regulation of the IA component during differentiation of postnatal NSCs. Together with the marked developmental up-regulation of IDR in vitro neuronal differentiation we have previously found, the voltage-gated potassium channels may participate in neuronal maturation process.

  15. Atypical Cities

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    DiJulio, Betsy

    2011-01-01

    In this creative challenge, Surrealism and one-point perspective combine to produce images that not only go "beyond the real" but also beyond the ubiquitous "imaginary city" assignment often used to teach one-point perspective. Perhaps the difference is that in the "atypical cities challenge," an understanding of one-point perspective is a means…

  16. 上肢骨骼肌缺血再灌注对血小板聚集活性和血钠水平的影响%Impact of transient upper limb skeletal muscle ischemia and reperfusion on platelet reactivity and stress induced sodium retention in healthy subjects

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    宋冬林; 刘军翔; 刘新林

    2011-01-01

    Objective To determine whether or not skeletal muscle I/R procedure has clinically relevant impact on platelet aggregability, and to investigate its relationship to individuals ability of sodium retention under stress challenge, we serially measured platelet aggregation and related plasma biochemical changes before and after skeletal muscle I/R protocol in healthy subjects.Methods We enrolled 24 healthy subjects to receive a RIPC protocol consisting of a three 5 min cycles of unilateral upper arm I/R by blood pressure cuff to 200 mm Hg, and harvested the whole blood samples at baseline, 1 h after, and 24 h after I/R stress.Platelet aggregation was performed using a light transmission aggregometer in stirred platelet rich plasma.Results In general ,this limb I/R procedure did not result in significant change in platelet aggregation and blood biochemistry, except for a transient decrease of plasma glucose level 1 h after I/R stress(P <0.05).To further explore potential link between individuals responsiveness to stress-induced sodium retention and platelet reactivity, we dichotomized all subjects into sodium-retention responders [those with positive A plasma sodium level after ischemia, defined as plasma sodium (1 h after I/R) minus plasma sodium ( before I/R)]and non responders (the rest of subjects ).By this category, one third ( 8/24) of subjects were responders to I/R stress-induced sodium retention.Compared with non-responders, the responders had significantly increased platelet aggregation [(12.88±8.47)% vs (5.44±3.07)%, P < 0.05 )].Moreover, plasma sodium was positively correlated with platelet aggregation ( r = 0.488, P < 0.05 ).Conclusions In a subset of population characterized by increased plasma sodium retention after transient limb skeletal muscle I/R challenge, there is a transient increase of platelet aggregability.%目的 探讨骨骼肌缺血再灌注是否会影响血小板聚集率,以及血小板聚集与应激时血钠

  17. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation.

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    Bluett, R J; Gamble-George, J C; Hermanson, D J; Hartley, N D; Marnett, L J; Patel, S

    2014-07-08

    Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test. Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. FAAH inhibition does not significantly affect anxiety-like behaviors in non-stressed mice. Moreover, whole brain anandamide levels are reduced 24 h after acute foot-shock stress and are negatively correlated with anxiety-like behavioral measures in the light-dark box test. These data indicate that central anandamide levels predict acute stress-induced anxiety, and that reversal of stress-induced anandamide deficiency is a key mechanism subserving the therapeutic effects of FAAH inhibition. These studies provide further support that eCB-augmentation is a viable pharmacological strategy for the treatment of stress-related neuropsychiatric disorders.

  18. Stress induced phase transitions in silicon

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    Budnitzki, M.; Kuna, M.

    2016-10-01

    Silicon has a tremendous importance as an electronic, structural and optical material. Modeling the interaction of a silicon surface with a pointed asperity at room temperature is a major step towards the understanding of various phenomena related to brittle as well as ductile regime machining of this semiconductor. If subjected to pressure or contact loading, silicon undergoes a series of stress-driven phase transitions accompanied by large volume changes. In order to understand the material's response for complex non-hydrostatic loading situations, dedicated constitutive models are required. While a significant body of literature exists for the dislocation dominated high-temperature deformation regime, the constitutive laws used for the technologically relevant rapid low-temperature loading have severe limitations, as they do not account for the relevant phase transitions. We developed a novel finite deformation constitutive model set within the framework of thermodynamics with internal variables that captures the stress induced semiconductor-to-metal (cd-Si → β-Si), metal-to-amorphous (β-Si → a-Si) as well as amorphous-to-amorphous (a-Si → hda-Si, hda-Si → a-Si) transitions. The model parameters were identified in part directly from diamond anvil cell data and in part from instrumented indentation by the solution of an inverse problem. The constitutive model was verified by successfully predicting the transformation stress under uniaxial compression and load-displacement curves for different indenters for single loading-unloading cycles as well as repeated indentation. To the authors' knowledge this is the first constitutive model that is able to adequately describe cyclic indentation in silicon.

  19. Possible Biomarkers of Chronic Stress Induced Exhaustion - A Longitudinal Study.

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    Johanna Wallensten

    Full Text Available Vascular endothelial growth factor (VEGF, epidermal growth factor (EGF and monocyte chemotactic protein-1 (MCP-1 have previously been suggested to be potential biomarkers for chronic stress induced exhaustion. The knowledge about VEGF has increased during the last decades and supports the contention that VEGF plays an important role in stress and depression. There is scarce knowledge on the possible relationship of EGF and MCP-1 in chronic stress and depression. This study further examines the role of VEGF, EGF and MCP-1 in women with chronic stress induced exhaustion and healthy women during a follow-up period of two years.Blood samples were collected from 105 women with chronic stress induced exhaustion on at least 50% sick leave for at least three months, at inclusion (T0, after 12 months (T12 and after 24 months (T24. Blood samples were collected at inclusion (T0 in 116 physically and psychiatrically healthy women. The plasma levels of VEGF, EGF and MCP-1 were analyzed using Biochip Array Technology. Women with chronic stress induced exhaustion had significantly higher plasma levels of VEGF and EGF compared to healthy women at baseline, T12 and at T24. There was no significant difference in plasma levels of MCP-1. Plasma levels of VEGF and EGF decreased significantly in women with chronic stress induced exhaustion during the two years follow-up.The replicated findings of elevated levels of VEGF and EGF in women with chronic stress induced exhaustion and decreasing plasma levels of VEGF and EGF during the two years follow-up add important knowledge to the pathophysiology of chronic stress induced exhaustion.

  20. Atypical meningococcal meningitis with rashless presentation:A case report

    Institute of Scientific and Technical Information of China (English)

    Sunita; Singh Manpreet; Kapoor Dheeraj

    2012-01-01

    Meningococcal disease is the major health problem in developing world. The clinical presentation is varied, ranging from transient fever and bacteraemia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. The classical clinical manifestations of meningococcal disease have been well described, but atypical presentations if unrecognized, may lead to a delay in treatment and fatal outcome. We here report a case presented with atypical presentation of meningococcal meningitis without classical rash, which was diagnosed and managed successfully.

  1. Reproductive stage and modulation of stress-induced tau phosphorylation in female rats

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    Steinmetz, Danielle; Ramos, Eugenia; Campbell, Shannon N.; Morales, Teresa; Rissman, Robert A.

    2015-01-01

    Chronic stress is implicated as a risk factor for Alzheimer's disease (AD) and other neurodegenerative disorders. While the specific mechanisms linking stress exposure and AD vulnerability have yet to be fully elucidated, our lab and others have shown that acute and repeated restraint stress in rodents leads to an increase in hippocampal tau phosphorylation (tau-P) and tau insolubility, a critical component of tau pathology in AD. Tau phosphorylation induced by a psychological stressor is reversible and is thought to be dependent on intact signaling through the type 1 corticotropin-releasing factor receptor, but how sex steroids or other modulators may also modulate this effect are unknown. A naturally occurring attenuation of stress response is observed in female rats at the end of pregnancy and throughout lactation. To test the hypothesis that decreased sensitivity to stress during lactation modulates stress-induced tau-P, cohorts of virgin, lactating, and weaned female rats were subjected to 30 minutes of restraint stress or no stress (control), and were sacrificed at 20 minutes or 24 hours after the episode. Exposure to restraint stress induced a significant decrease in tau-P in the hippocampus of lactating rats sacrificed 20 minutes after stress compared to lactating controls and virgins subjected to stress treatment. Lactating rats sacrificed 24 hours after exposure to restraint stress showed a significant increase in tau-P compared to the restraint-stressed lactating rats sacrificed only 20 minutes after stress exposure, expressing phosphorylation levels similar to control animals. Further, GSK3-α levels were significantly decreased in stressed lactating animals at both timepoints. This suggests a steep, yet transient stress-induced dephosphorylation of tau, influenced by GSK3, in the hippocampus of lactating rats. PMID:26510116

  2. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

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    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas;

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...

  3. Implication of snail in metabolic stress-induced necrosis.

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    Cho Hee Kim

    Full Text Available BACKGROUND: Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

  4. Atypical charles bonnet syndrome.

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    Arun, Priti; Jain, Rajan; Tripathi, Vaibhav

    2013-10-01

    Charles Bonnet syndrome (CBS) is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  5. NOVEL ATYPICAL ANTIPSYCHOTIC AGENTS

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    Vijay Vinay

    2011-05-01

    Full Text Available Antipsychotics are a group of drugs commonly but not exclusively used to treat psychosis. Antipsychotic agents are grouped in two categories: Typical and Atypical antipsychotics. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s. Both typical and atypical antipsychotics are effective in reducing positive and negative symptoms of schizophrenia. Blockade of D2 receptor in mesolimbic pathway is responsible for antipsychotic action. Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects. Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2-receptor binding and high ratio of serotonin type 2 (5-HT2-receptor binding to D2. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, narcoleptic malignant syndrome, and hyperprolactinemia. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs and tardive dyskinesia (TD.

  6. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

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    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K. (Department of Cardiology, Postgraduate Medical School, Warsaw (Poland))

    1991-06-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 {times} 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications.

  7. Developmentally and stress-induced small heat shock proteins in cork oak somatic embryos.

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    Puigderrajols, Pere; Jofré, Anna; Mir, Gisela; Pla, Maria; Verdaguer, Dolors; Huguet, Gemma; Molinas, Marisa

    2002-06-01

    The timing and tissue localization of small heat shock proteins (sHSPs) during cork oak somatic embryo development was investigated under normal growing culture conditions and in response to stress. Western blot analyses using polyclonal antibodies raised against cork oak recombinant HSP17 showed a transient accumulation of class I sHSPs during somatic embryo maturation and germination. Moreover, the amount of protein increased at all stages of embryo development in response to exogenous stress. The developmentally accumulated proteins localized to early differentiating, but not the highly dividing, regions of the root and shoot apical meristems. By contrast, these highly dividing regions were strongly immunostained after heat stress. Findings support the hypothesis of a distinct control for developmentally and stress-induced accumulation of class I sHSPs. The possible role of sHSPs is discussed in relation to their tissue specific localization.

  8. Melatonin attenuates stress-induced defecation: lesson from a rat model of stress-induced gut dysfunction.

    Science.gov (United States)

    Song, G H; Gwee, K A; Moochhala, S M; Ho, K Y

    2005-10-01

    Melatonin is known to alleviate stress and modulate gut motility. We investigated the modulating effects of melatonin on stress-induced gut dysfunction. One hundred Wistar rats were randomly assigned to five equal groups, receiving intraperitoneal injections of 0, 1, 10, 100 or 1000 microg kg(-1) melatonin, respectively. Fifteen minutes later, each group was divided again into four subgroups receiving no treatment, 0.25 mg luzindole (a non-selective melatonin receptor antagonist) intraperitoneally, wrap-restraint stress, and 10 mg kg(-1) serotonin intraperitoneally, respectively. Two hours later, serum serotonin, corticotropin-releasing factor (CRF) and melatonin levels, and faecal output were recorded. Results showed that intraperitoneal melatonin increased faecal output, but this effect was abolished by luzindole. In wrap-restraint group, prior intraperitoneal melatonin at doses of 100 or 1000 microg kg(-1) significantly inhibited stress-induced defecation. This effect was associated with corresponding reductions in serum serotonin and CRF concentrations. In serotonin-treated group, serotonin-induced defecation was also inhibited by melatonin. In conclusion, melatonin exhibited an excitatory effect on bowel output in rats placed under resting state, while attenuated defecation in those subjected to wrap-restraint stress or serotonin treatment. The inhibitory effects of melatonin on stress-induced defecation may stem from its antagonistic effect on stress-induced enhancement of serotonin and CRF secretion.

  9. Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions?

    Directory of Open Access Journals (Sweden)

    Olivier Toussaint

    2002-01-01

    Full Text Available No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1. Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2. As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2 appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (pathophysiology and aging.

  10. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    DEFF Research Database (Denmark)

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric;

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...

  11. Stress-induced neuroinflammation: mechanisms and new pharmacological targets

    Directory of Open Access Journals (Sweden)

    C.D. Munhoz

    2008-12-01

    Full Text Available Stress is triggered by numerous unexpected environmental, social or pathological stimuli occurring during the life of animals, including humans, which determine changes in all of their systems. Although acute stress is essential for survival, chronic, long-lasting stress can be detrimental. In this review, we present data supporting the hypothesis that stress-related events are characterized by modifications of oxidative/nitrosative pathways in the brain in response to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO and an excess of pro-oxidants in various brain areas as responsible for both neuronal functional impairment and structural damage. Similarly, cyclooxygenase-2 (COX-2, another known source of oxidants, may account for stress-induced brain damage. Interestingly, some of the COX-2-derived mediators, such as the prostaglandin 15d-PGJ2 and its peroxisome proliferator-activated nuclear receptor PPARγ, are activated in the brain in response to stress, constituting a possible endogenous anti-inflammatory mechanism of defense against excessive inflammation. The stress-induced activation of both biochemical pathways depends on the activation of the N-methyl-D-aspartate (NMDA glutamate receptor and on the activation of the transcription factor nuclear factor kappa B (NFκB. In the case of inducible NO synthase (iNOS, release of the cytokine TNF-α also accounts for its expression. Different pharmacological strategies directed towards different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNF-α activation and release, inhibitors of NFκB, specific inhibitors of iNOS and COX-2 activities and PPARγ agonists. This article reviews recent contributions to this area addressing possible new pharmacological targets for the treatment of stress-induced neuropsychiatric disorders.

  12. Shear stress-induced improvement of red blood cell deformability

    OpenAIRE

    Meram, Ece; Yılmaz, Bahar D.; Bas, Ceren; Atac, Nazlı; Yalçın, Ö.; Başkurt, Oguz K.; Meiselman, Herbert J.

    2013-01-01

    Classically, it is known that red blood cell (RBC) deformability is determined by the geometric and material properties of these cells. Experimental evidence accumulated during the last decade has introduced the concept of active regulation of RBC deformability. This regulation is mainly related to altered associations between membrane skeletal proteins and integral proteins, with the latter serving to anchor the skeleton to the lipid matrix. It has been hypothesized that shear stress induces...

  13. Atypical Optic Neuritis.

    Science.gov (United States)

    Gaier, Eric D; Boudreault, Katherine; Rizzo, Joseph F; Falardeau, Julie; Cestari, Dean M

    2015-12-01

    Classic demyelinative optic neuritis is associated with multiple sclerosis and typically carries a good prognosis for visual recovery. This disorder is well characterized with respect to its presentation and clinical features by baseline data obtained through the optic neuritis treatment trial and numerous other studies. Atypical optic neuritis entails clinical manifestations that deviate from this classic pattern of features. Clinical signs and symptoms that deviate from the typical presentation should prompt consideration of less common etiologies. Atypical features to consider include lack of pain, simultaneous or near-simultaneous onset, lack of response to or relapse upon tapering from corticosteroids, or optic nerve head or peripapillary hemorrhages. The most important alternative etiologies to consider and the steps towards their respective diagnostic evaluations are suggested for these atypical features.

  14. Stress-induced changes in wheat grain composition and quality.

    Science.gov (United States)

    Ashraf, M

    2014-01-01

    Abiotic stresses such as drought, salinity, waterlogging, and high temperature cause a myriad of changes in the metabolism of plants, and there is a lot of overlap in these changes in plants in response to different stresses such as drought and salinity. These stress-induced metabolic changes cause impaired crop growth thereby resulting in poor yield. The metabolic changes taking place in several plant species due to a particular abiotic stress have been revealed from the whole plant to the molecular level by researchers, but most studies have focused on organs such as leaf, stem, and root. Information on such stress-induced changes in seed or grains is infrequent in the literature. From the information that is available, it is now evident that abiotic stress can induce considerable changes in the composition and quality of cereal grains including those of wheat, the premier staple food crop in the world. Thus, the present review discusses how far different types of stresses, mainly salinity, drought, high temperature, and waterlogging, can alter the wheat grain composition and quality. By fully uncovering the stress-induced changes in the nutritional values of wheat grains it would be possible to establish whether balanced supplies of essential nutrients are available to the human population from the wheat crop grown on stress-affected areas.

  15. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  16. Calnexin deficiency and endoplasmic reticulum stress-induced apoptosis.

    Science.gov (United States)

    Zuppini, Anna; Groenendyk, Jody; Cormack, Lori A; Shore, Gordon; Opas, Michal; Bleackley, R Chris; Michalak, Marek

    2002-02-26

    In this study, we used calnexin-deficient cells to investigate the role of this protein in ER stress-induced apoptosis. We found that calnexin-deficient cells are relatively resistant to ER stress-induced apoptosis. However, caspase 3 and 8 cleavage and cytochrome c release were unchanged in these cells, indicating that ER to mitochondria "communication" during apoptotic stimulation is not affected in the absence of calnexin. The Bcl-2:Bax ratio was also not significantly changed in calnexin-deficient cells regardless of whether the ER stress was induced with thapsigargin or not. Ca(2+) homeostasis and ER morphology were unaffected by the lack of calnexin, but ER stress-induced Bap31 cleavage was significantly inhibited. Immunoprecipitation experiments revealed that Bap31 forms complexes with calnexin, which may play a role in apoptosis. The results suggest that calnexin may not play a role in the initiation of the ER stress but that the protein has an effect on later apoptotic events via its influence on Bap31 function.

  17. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

    NARCIS (Netherlands)

    Legendre, C.M.; Licht, C.; Muus, P.; Greenbaum, L.A.; Babu, S.; Bedrosian, C.; Bingham, C.; Cohen, D.J.; Delmas, Y.; Douglas, K.; Eitner, F.; Feldkamp, T.; Fouque, D.; Furman, R.R.; Gaber, O.; Herthelius, M.; Hourmant, M.; Karpman, D.; Lebranchu, Y.; Mariat, C.; Menne, J.; Moulin, B.; Nurnberger, J.; Ogawa, M.; Remuzzi, G.; Richard, T.; Sberro-Soussan, R.; Severino, B.; Sheerin, N.S.; Trivelli, A.; Zimmerhackl, L.B.; Goodship, T.; Loirat, C.

    2013-01-01

    BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We

  18. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo;

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  19. Atypical charles bonnet syndrome

    Directory of Open Access Journals (Sweden)

    Priti Arun

    2013-01-01

    Full Text Available Charles Bonnet syndrome (CBS is not uncommon disorder. It may not present with all typical symptoms and intact insight. Here, a case of atypical CBS is reported where antipsychotics were not effective. Patient improved completely after restoration of vision.

  20. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders

    Directory of Open Access Journals (Sweden)

    Simeng Gu

    2016-01-01

    Full Text Available Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC/norepinephrine (NE system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty. The reason for this discrepancy might be that NE is not only for flight (fear, but also for fight (anger. Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders.

  1. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  2. Stress-induced cardiomyopathy (Takotsubo – broken heart and mind?

    Directory of Open Access Journals (Sweden)

    Redfors B

    2013-04-01

    Full Text Available Björn Redfors, Yangzhen Shao, Elmir Omerovic Department of Molecular and Clinical Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden Abstract: Stress-induced cardiomyopathy (SIC, also known as Takotsubo cardiomyopathy, is characterized by severe but potentially reversible regional left ventricular wall motion abnormalities, ie, akinesia, in the absence of explanatory angiographic evidence of a coronary occlusion. The typical pattern is that of an akinetic apex with preserved contractions in the base, but other variants are also common, including basal or midmyocardial akinesia with preserved apical function. The pathophysiology of SIC remains largely unknown but catecholamines are believed to play a pivotal role. The diverse array of triggering events that have been linked to SIC are arbitrarily categorized as either emotional or somatic stressors. These categories can be considered as different elements of a continuous spectrum, linked through the interface of neurology and psychiatry. This paper reviews our current knowledge of SIC, with focus on the intimate relationship between the brain and the heart. Keywords: stress-induced cardiomyopathy, takotsubo cardiomyopathy, catecholamine, cerebral injury, emotional stress, somatic stress

  3. Cellular and Molecular Basis for Stress-Induced Depression

    Science.gov (United States)

    Seo, Ji-Seon; Wei, Jing; Qin, Luye; Kim, Yong; Yan, Zhen

    2016-01-01

    Chronic stress plays a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2+) glutamatergic neurons. Viral expression of p11 in D2+ PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2+ neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2+ PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses. PMID:27457815

  4. Takotsubo syndrome with transient complete atrioventricular block

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Takotsubo syndrome (transient left ventricular apical ballooning syndrome) is a novel cardiac syndrome of left ventricular apical ballooning involving reversible left ventricular apical ballooning (during systole) of acute onset with chest pain, electrocardiographic changes, and minimal elevation of cardiac enzymes resembling acute myocardial infarction, but without evidence of myocardial ischemia or injury. Patients have no angiographic evidence of coronary artery stenosis and there is almost always a complete recovery of left ventricular function in days to weeks. The precise etiologic basic of this syndrome is not clear but most likely it is a non-ischemic, metabolic syndrome caused by stress-induced activation of the cardiac adrenoceptors in absence of ischemia and reperfusion.1-3 Reported here is a case of stress-induced transient left ventricular apical ballooning syndrome in an elderly Chinese woman.

  5. Stress-induced cardiomyopathy (Takotsubo)--broken heart and mind?

    Science.gov (United States)

    Redfors, Björn; Shao, Yangzhen; Omerovic, Elmir

    2013-01-01

    Stress-induced cardiomyopathy (SIC), also known as Takotsubo cardiomyopathy, is characterized by severe but potentially reversible regional left ventricular wall motion abnormalities, ie, akinesia, in the absence of explanatory angiographic evidence of a coronary occlusion. The typical pattern is that of an akinetic apex with preserved contractions in the base, but other variants are also common, including basal or midmyocardial akinesia with preserved apical function. The pathophysiology of SIC remains largely unknown but catecholamines are believed to play a pivotal role. The diverse array of triggering events that have been linked to SIC are arbitrarily categorized as either emotional or somatic stressors. These categories can be considered as different elements of a continuous spectrum, linked through the interface of neurology and psychiatry. This paper reviews our current knowledge of SIC, with focus on the intimate relationship between the brain and the heart.

  6. Stress-induced obesity and the emotional nervous system.

    Science.gov (United States)

    Dallman, Mary F

    2010-03-01

    Stress and emotional brain networks foster eating behaviors that can lead to obesity. The neural networks underlying the complex interactions among stressors, body, brain and food intake are now better understood. Stressors, by activating a neural stress-response network, bias cognition toward increased emotional activity and degraded executive function. This causes formed habits to be used rather than a cognitive appraisal of responses. Stress also induces secretion of glucocorticoids, which increases motivation for food, and insulin, which promotes food intake and obesity. Pleasurable feeding then reduces activity in the stress-response network, reinforcing the feeding habit. These effects of stressors emphasize the importance of teaching mental reappraisal techniques to restore responses from habitual to thoughtful, thus battling stress-induced obesity.

  7. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  8. [Atypical presentation of preeclampsia].

    Science.gov (United States)

    Ditisheim, A; Boulvain, M; Irion, O; Pechère-Bertschi, A

    2015-09-09

    Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia.

  9. STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

    Directory of Open Access Journals (Sweden)

    Zachary Robert Patterson

    2013-07-01

    Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress-induced

  10. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  11. Stress-induced cardiomyopathy following infection of the upper respiratory tract in an elderly female patient: A case report

    Science.gov (United States)

    Ding, Huaiyu; Huang, Rongchong; Shi, Xiaoli; Wu, Baolin

    2016-01-01

    Stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy (TTC), is a relatively newly-described condition, which has been increasingly reported in the literature. It is characterized by acute onset of symptoms and electrocardiogram changes mimicking myocardial infarction, with transient but completely reversible left ventricular (LV) dysfunction. SIC commonly occurs following physical or emotional stress. The present study discusses the case of a 68-year-old female patient who had suffered from infection of the upper respiratory tract for 10 days before admission to the hospital with symptoms of chest stuffiness and dyspnea that persisted for 2 days. Coronary angiography showed normal coronary artery function, while LV angiography demonstrated systolic apical ballooning. Based on these observed characteristics, the patient was diagnosed with SIC and was successfully treated. PMID:27882121

  12. Atypical manifestations of leptospirosis.

    Science.gov (United States)

    Rajapakse, Senaka; Rodrigo, Chaturaka; Balaji, Krishan; Fernando, Sumadhya Deepika

    2015-05-01

    Leptospirosis is an illness with a wide spectrum of clinical manifestations and severe illness affects nearly all organ systems. Serious and potentially life-threatening clinical manifestations of acute leptospirosis are caused by both direct tissue invasion by spirochaetes and by the host immune responses. In its severe form, leptospirosis can cause multi-organ dysfunction and death in a matter of days. Therefore it is critical to suspect and recognize the disease early, in order to initiate timely treatment. While the classical presentation of the disease is easily recognized by experienced clinicians practising in endemic regions, rarer manifestations can be easily missed. In this systematic review, we summarize the atypical manifestations reported in literature in patients with confirmed leptospirosis. Awareness of these unusual manifestations would hopefully guide clinicians towards early diagnosis.

  13. Tomato leaf spatial expression of stress-induced Asr genes.

    Science.gov (United States)

    Maskin, Laura; Maldonado, Sara; Iusem, Norberto D

    2008-12-01

    Asr1 and Asr2 are water stress-inducible genes belonging to the Asr gene family, which transcriptionally regulate a sugar transporter gene, at least in grape. Using an in situ RNA hybridization methodology, we determined that, in basal conditions, expression of Asr2 in tomato leaves is detected in the phloem tissue, particularly in companion phloem cells. When plants are exposed to water stress, Asr2 expression is contained in companion cells but expands occasionally to mesophyll cells. In contrast, Asr1 transcript localization seems to be sparse in leaf vascular tissue under both non-stress and stress conditions. The occurrence of Asr transcripts precisely in companion cells is in accordance with the cell type specificity reported for hexose-transporter protein molecules in grape encoded by the only Asr-target gene known to date. The results are discussed in light of the reported scarcity of plasmodesmata between companion cells and the rest of leaf tissue in the family Solanaceae.

  14. The stress-induced surface wave velocity variations in concrete

    Science.gov (United States)

    Spalvier, Agustin; Bittner, James; Evani, Sai Kalyan; Popovics, John S.

    2017-02-01

    This investigation studies the behavior of surface wave velocity in concrete specimens subjected to low levels of compressive and tensile stress in beams from applied flexural loads. Beam specimen is loaded in a 4-point-load bending configuration, generating uniaxial compression and tension stress fields at the top and bottom surfaces of the beam, respectively. Surface waves are generated through contactless air-coupled transducers and received through contact accelerometers. Results show a clear distinction in responses from compression and tension zones, where velocity increases in the former and decreases in the latter, with increasing load levels. These trends agree with existing acoustoelastic literature. Surface wave velocity tends to decrease more under tension than it tends to increase under compression, for equal load levels. It is observed that even at low stress levels, surface wave velocity is affected by acoustoelastic effects, coupled with plastic effects (stress-induced damage). The acoustoelastic effect is isolated by means of considering the Kaiser effect and by experimentally mitigating the viscoelastic effects of concrete. Results of this ongoing investigation contribute to the overall knowledge of the acoustoelastic behavior of concrete. Applications of this knowledge may include structural health monitoring of members under flexural loads, improved high order modelling of materials, and validation of results seen in dynamic acoustoelasticity testing.

  15. Stress inducible proteomic changes in Capsicum annuum leaves.

    Science.gov (United States)

    Mahajan, Neha S; Mishra, Manasi; Tamhane, Vaijayanti A; Gupta, Vidya S; Giri, Ashok P

    2014-01-01

    Herbivore attack induces defense responses in plants, activating several signaling cascades. As a result, molecules deterrent to the herbivores are produced and accumulated in plants. Expression of defense mechanism/traits requires reorganization of the plant metabolism, redirecting the resources otherwise meant for growth. In the present work, protein profile of Capsicum annuum leaves was examined after herbivore attack/induction. Majority of proteins identified as differentially accumulated, were having roles in redox metabolism and photosynthesis. For example, superoxide dismutase and NADP oxidoreductase were upregulated by 10- and 6-fold while carbonic anhydrase and fructose-1,6-bisphosphatase were downregulated by 9- and 4-fold, respectively. Also, superoxide dismutase, NADPH quinone oxidoreductase and NADP dependent isocitrate dehydrogenase transcripts showed a higher accumulation in induced leaf tissues at early time points. In general, proteins having role in defense and damage repair were upregulated while those involved in photosynthesis appeared downregulated. Thus metabolic reconfiguration to balance defense and tolerance was evident in the stress-induced leaves.

  16. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Gharib Ola

    2009-11-01

    Full Text Available Abstract Background Trichloroethylene (TCE may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1 the control group treated with vehicle, (2 Kombucha (KT-treated group, (3 TCE-treated group and (4 KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT and lactate dehydrogenase (LDH activities were also measured. Results TCE administration increased the malondiahyde (MDA and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  17. Brugada Syndrome with atypical characteristics: Case report

    Directory of Open Access Journals (Sweden)

    Hatem Ari

    2013-09-01

    Full Text Available The Brugada Syndrome (BrS is a heterogeneous genetic disease characterized by persistent or transient ST-segment elevation in the right precordial electrocardiography (ECG leads and a high incidence of sudden death and life-threatening ventricular tachyarrhythmias in patients with structurally normal hearts. The syndrome generally manifests in men during adulthood. The ECG manifestations can be overt or concealed. We report a case of BrS whose type 1 ECG pattern during febrile state converted to type 2 ECG after alleviation of fever with atypical characteristics (78-year-old woman with monomorphic ventricular tachycardia on holter monitoring, a history of the sudden infant death of her child, and without inducible ventricular arrhythmia by programed ventricular stimulation [PVS].

  18. Protective effect of nicotinamide adenine dinucleotide (NAD(+)) against spinal cord ischemia-reperfusion injury via reducing oxidative stress-induced neuronal apoptosis.

    Science.gov (United States)

    Xie, Lei; Wang, Zhenfei; Li, Changwei; Yang, Kai; Liang, Yu

    2017-02-01

    As previous studies demonstrate that oxidative stress and apoptosis play crucial roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD(+)) treatment attenuates oxidative stress-induced cell death among primary neurons and astrocytes as well as significantly reduce cerebral ischemic injury in rats. We used a spinal cord ischemia injury (SCII) model in rats to verify our hypothesis that NAD(+) could ameliorate oxidative stress-induced neuronal apoptosis. Adult male rats were subjected to transient spinal cord ischemia for 60min, and different doses of NAD(+) were administered intraperitoneally immediately after the start of reperfusion. Neurological function was determined by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick-end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF (apoptosis inducing factor). The results showed that NAD(+) at 50 or 100mg/kg significantly decreased the oxidative stress level and neuronal apoptosis in the spinal cord of ischemia-reperfusion rats compared with saline, as accompanied with the decreased oxidative stress, NAD(+) administration significantly restrained the neuronal apoptosis after ischemia injury while improved the neurological and motor function. These findings suggested that NAD(+) might protect against spinal cord ischemia-reperfusion via reducing oxidative stress-induced neuronal apoptosis.

  19. Atypical Odontalgia (Phantom Tooth Pain)

    Science.gov (United States)

    ... atypical facial pain, phantom tooth pain, or neuropathic orofacial pain, is characterized by chronic pain in a ... such as a specialist in oral medicine or orofacial pain. The information contained in this monograph is ...

  20. Atypical GTPases as drug targets.

    Science.gov (United States)

    Soundararajan, Meera; Eswaran, Jeyanthy

    2012-01-01

    The Ras GTPases are the founding members of large Ras superfamily, which constitutes more than 150 of these important class of enzymes. These GTPases function as GDP-GTP-regulated binary switches that control many fundamental cellular processes. There are a number of GTPases that have been identified recently, which do not confine to this prototype termed as "atypical GTPases" but have proved to play a remarkable role in vital cellular functions. In this review, we provide an overview of the crucial physiological functions mediated by RGK and Centaurin class of multi domain atypical GTPases. Moreover, the recently available atypical GTPase structures of the two families, regulation, physiological functions and their critical roles in various diseases will be discussed. In summary, this review will highlight the emerging atypical GTPase family which allows us to understand novel regulatory mechanisms and thus providing new avenues for drug discovery programs.

  1. Stress-induced core temperature changes in pigeons (Columba livia).

    Science.gov (United States)

    Bittencourt, Myla de Aguiar; Melleu, Fernando Falkenburger; Marino-Neto, José

    2015-02-01

    Changes in body temperature are significant physiological consequences of stressful stimuli in mammals and birds. Pigeons (Columba livia) prosper in (potentially) stressful urban environments and are common subjects in neurobehavioral studies; however, the thermal responses to stress stimuli by pigeons are poorly known. Here, we describe acute changes in the telemetrically recorded celomatic (core) temperature (Tc) in pigeons given a variety of potentially stressful stimuli, including transfer to a novel cage (ExC) leading to visual isolation from conspecifics, the presence of the experimenter (ExpR), gentle handling (H), sham intracelomatic injections (SI), and the induction of the tonic immobility (TI) response. Transfer to the ExC cage provoked short-lived hyperthermia (10-20 min) followed by a long-lasting and substantial decrease in Tc, which returned to baseline levels 2 h after the start of the test. After a 2-hour stay in the ExC, the other potentially stressful stimuli evoked only weak, marginally significant hyperthermic (ExpR, IT) or hypothermic (SI) responses. Stimuli delivered 26 h after transfer to the ExC induced definite and intense increases in Tc (ExpR, H) or hypothermic responses (SI). These Tc changes appear to be unrelated to modifications in general activity (as measured via telemetrically recorded actimetric data). Repeated testing failed to affect the hypothermic responses to the transference to the ExC, even after nine trials and at 1- or 8-day intervals, suggesting that the social (visual) isolation from conspecifics may be a strong and poorly controllable stimulus in this species. The present data indicated that stress-induced changes in Tc may be a consistent and reliable physiological parameter of stress but that they may also show stressor type-, direction- and species-specific attributes.

  2. Atypical Light Curves

    CERN Document Server

    Steenwyk, Steven D; Molnar, Lawrence A

    2013-01-01

    We have identified some two-hundred new variable stars in a systematic study of a data archive obtained with the Calvin-Rehoboth observatory. Of these, we present five close binaries showing behaviors presumably due to star spots or other magnetic activity. For context, we first present two new RS CVn systems whose behavior can be readily attribute to star spots. Then we present three new close binary systems that are rather atypical, with light curves that are changing over time in ways not easily understood in terms of star spot activity generally associated with magnetically active binary systems called RS CVn systems. Two of these three are contact binaries that exhibit gradual changes in average brightness without noticeable changes in light curve shape. A third system has shown such large changes in light curve morphology that we speculate this may be a rare instance of a system that transitions back and forth between contact and noncontact configurations, perhaps driven by magnetic cycles in at least o...

  3. A Rare Case: Atypical Measles

    OpenAIRE

    Ümmü Sena Sarı; Figen Kaptan

    2016-01-01

    Atypical measles has been described in persons who were exposed to wild measles virus several years after they were immunized with killed measles vaccine. Occasionally, it can be caused by live measles vaccines also. It is a clinical picture different from typical measles. In this report, an adult patient with a history of immunization, who presented with high fever, maculopapular rash starting at the palms and soles, and pneumonia, is presented. Atypical measles that was ...

  4. Phase Stability and Stress-Induced Transformations in Beta Titanium Alloys

    Science.gov (United States)

    Kolli, R. Prakash; Joost, William J.; Ankem, Sreeramamurthy

    2015-06-01

    In this article, we provide a brief review of the recent developments related to the relationship between phase stability and stress-induced transformations in metastable body-centered-cubic β-phase titanium alloys. Stress-induced transformations occur during tensile, compressive, and creep loading and influence the mechanical response. These transformations are not fully understood and increased understanding of these mechanisms will permit future development of improved alloys for aerospace, biomedical, and energy applications. In the first part of this article, we review phase stability and discuss a few recent developments. In the second section, we discuss the current status of understanding stress-induced transformations and several areas that require further study. We also provide our perspective on the direction of future research efforts. Additionally, we address the occurrence of the hcp ω-phase and the orthorhombic α″-martensite phase stress-induced transformations.

  5. Adolescent personality: associations with Basal, awakening, and stress-induced cortisol responses.

    Science.gov (United States)

    Laceulle, Odilia M; Nederhof, Esther; van Aken, Marcel A G; Ormel, Johan

    2015-06-01

    The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress-induced HPA-axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress-induced cortisol were not related to personality. Possibly due to its more trait-like nature, basal cortisol seems more informative than stress-induced cortisol when investigating trait-like characteristics such as personality facets.

  6. Catalase activity as a biomarker for mild-stress-induced robustness in Bacillus weihenstephanensis

    NARCIS (Netherlands)

    Besten, den H.M.W.; Effraimidou, S.; Abee, T.

    2013-01-01

    Microorganisms are able to survive and grow in changing environments by activating stress adaptation mechanisms which may enhance bacterial robustness. Stress-induced enhanced robustness complicates the predictability of microbial inactivation. Using psychrotolerant Bacillus weihenstephanensis strai

  7. Studies on effect of stress preconditioning in restrain stress-induced behavioral alterations.

    Science.gov (United States)

    Kaur, Rajneet; Jaggi, Amteshwar Singh; Singh, Nirmal

    2010-02-01

    Stress preconditioning has been documented to confer on gastroprotective effects on stress-induced gastric ulcerations. However, the effects of prior exposure of stress preconditioning episodes on stress-induced behavioral changes have not been explored yet. Therefore the present study was designed to investigate the ameliorative effects of stress preconditioning in immobilization stress-induced behavioral alterations in rats. The rats were subjected to restrain stress by placing in restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Stress preconditioning was induced by subjecting the rats to two cycles of restraint and restrain-free periods of 15 min each. Furthermore, a similar type of stress preconditioning was induced using different time cycles of 30 and 45 min. The extent and severity of the stress-induced behavioral alterations were assessed using different behavioral tests such as hole-board test, social interaction test, open field test, and actophotometer. Restrain stress resulted in decrease in locomotor activity, frequency of head dips and rearing in hole board, line crossing and rearing in open field, and decreased following and increased avoidance in social interaction test. Stress preconditioning with two cycles of 15, 30 or 45 min respectively, did not attenuate stress-induced behavioral changes to any extent. It may be concluded that stress preconditioning does not seem to confer any protective effect in modulating restrain stress-induced behavioral alterations.

  8. [Therapy for atypical facial pain].

    Science.gov (United States)

    Ishida, Satoshi; Kimura, Hiroko

    2009-09-01

    Atypical facial pain is a pain in the head, neck and the face, without organic causes. It is treated at departments of physical medicine, such as dental, oral and maxillofacial surgery, otolaryngology, cerebral surgery, or head and neck surgery. In primary care, it is considered to be a medically unexplained symptom (MUS), or a somatoform disorder, such as somatization caused by a functional somatic syndrome (FSS) by psychiatrists. Usually, patients consult departments of physical medicine complaining of physical pain. Therefore physicians in these departments should examine the patients from the holistic perspective, and identify organic diseases. As atypical facial pain becomes chronic, other complications, including psychiatric complaints other than physical pain, such as depression may develop. Moreover, physical, psychological, and social factors affect the symptoms by interacting with one another. Therefore, in examining atypical facial pain, doctors specializing in dental, oral and maxillofacial medicine are required to provide psychosomatic treatment that is based on integrated knowledge.

  9. Atypical moles: diagnosis and management.

    Science.gov (United States)

    Perkins, Allen; Duffy, R Lamar

    2015-06-01

    Atypical moles are benign pigmented lesions. Although they are benign, they exhibit some of the clinical and histologic features of malignant melanoma. They are more common in fair-skinned individuals and in those with high sun exposure. Atypical moles are characterized by size of 6 mm or more at the greatest dimension, color variegation, border irregularity, and pebbled texture. They are associated with an increased risk of melanoma, warranting enhanced surveillance, especially in patients with more than 50 moles and a family history of melanoma. Because an individual lesion is unlikely to display malignant transformation, biopsy of all atypical moles is neither clinically beneficial nor cost-effective. The ABCDE (asymmetry, border irregularity, color unevenness, diameter of 6 mm or more, evolution) mnemonic is a valuable tool for clinicians and patients to identify lesions that could be melanoma. Also, according to the "ugly duckling" concept, benign moles tend to have a similar appearance, whereas an outlier with a different appearance is more likely to be undergoing malignant change. Atypical moles with changes suggestive of malignant melanoma should be biopsied, using an excisional method, if possible.

  10. Full Quantum Theory of Transient-State Electromagnetically Induced Transparency

    Institute of Scientific and Technical Information of China (English)

    KUANGLe-Man; ZENGAi-Hua; KUANGZhen-Hua

    2004-01-01

    We develop a full quantum theory of transient-state electromagnetically induced transparency (EIT) in the vapor of three-level A-type atoms interacting with probe and coupling lasers. As applications of the full quantum theory, we show that transient-state EIT medium exhibits normal dispersion and find that group velocities of both coupling and probe lasers are greatly reduced. It is shown that the group velocity of the probe laser in the transient-state EIT case is equal to that in the adiabatic EIT case and that the coupling laser group velocity in the transient-state EIT is generally less than that in the adiabatic EIT.

  11. Full Quantum Theory of Transient-State Electromagnetically Induced Transparency

    Institute of Scientific and Technical Information of China (English)

    KUANG Le-Man; ZENG Ai-Hua; KUANG Zhen-Hua

    2004-01-01

    We develop a full quantum theory of transient-state electromagnetically induced transparency (EIT) in thevapor of three-level A-type atoms interacting with probe and coupling lasers. As applications of the full quantum theory,we show that transient-state EIT medium exhibits normal dispersion and find that group velocities of both coupling andprobe lasers are greatly reduced. It is shown that the group velocity of the probe laser in the transient-state EIT case isequal to that in the adiabatic EIT case and that the coupling laser group velocity in the transient-state EIT is generallyless than that in the adiabatic EIT.

  12. Structure-dependent behavior of stress-induced voiding in Cu interconnects

    Energy Technology Data Exchange (ETDEWEB)

    Wu Zhenyu, E-mail: wuzhenyu@xidian.edu.c [Key Laboratory of Ministry of Education for Band-Gap Semiconductor Materials and Devices, School of Microelectronics, Xidian University, Xi' an 710071 (China); Yang Yintang; Chai Changchun; Li Yuejin; Wang Jiayou; Li Bin; Liu Jing [Key Laboratory of Ministry of Education for Band-Gap Semiconductor Materials and Devices, School of Microelectronics, Xidian University, Xi' an 710071 (China)

    2010-05-03

    Stress modeling and cross-section failure analysis by focused-ion-beam have been used to investigate stress-induced voiding phenomena in Cu interconnects. The voiding mechanism and the effect of the interconnect structure on the stress migration have been studied. The results show that the most concentrated tensile stress appears and voids form at corners of vias on top surfaces of Cu M1 lines. A simple model of stress induced voiding in which vacancies arise due to the increase of the chemical potential under tensile stress and diffuse under the force of stress gradient along the main diffusing path indicates that stress gradient rather than stress itself determines the voiding rate. Cu interconnects with larger vias show less resistance to stress-induced voiding due to larger stress gradient at corners of vias.

  13. Magnetic indication of the stress-induced martensitic transformation in ferromagnetic Ni-Mn-Ga alloy

    Energy Technology Data Exchange (ETDEWEB)

    Heczko, O. [Laboratory of Materials Science, Helsinki University of Technology, Vuorimiehentie 2A, P.O. Box 6200, FIN-02015 TKK, Espoo (Finland); L' vov, V.A. [Radiophysics Department, Taras Shevchenko University, Glushkov str. 2, build. 5, 03022 Kiev (Ukraine); Straka, L. [Laboratory of Biomedical Engineering, Helsinki University of Technology, Rakentajanaukio 2C, P.O. Box 2200, FIN-02015, Espoo (Finland)]. E-mail: ladislav.straka@hut.fi; Hannula, S.-P. [Laboratory of Materials Science, Helsinki University of Technology, Vuorimiehentie 2A, P.O. Box 6200, FIN-02015 TKK, Espoo (Finland)

    2006-07-15

    A quantitative study of the stress-induced martensitic transformation in Ni{sub 49.7}Mn{sub 29.1}Ga{sub 21.2} magnetic shape memory alloy has been carried out in two different ways: the first way is based on the measurements of saturation magnetization under variable mechanical stress and the second one is founded on the quantitative theoretical treatment of experimental stress-strain loops. A functional dependence between the volume fraction of transformed martensite and applied stress has been determined from both magnetization and strain values. A quantitative agreement between the functions determined in two different ways has been observed, and hence, the effectiveness of the magnetic indication of the stress-induced martensitic transformations has been proved. This method can be used to monitor stress-induced transformations in martensitic films, needles and small specimens.

  14. Magnetic indication of the stress-induced martensitic transformation in ferromagnetic Ni Mn Ga alloy

    Science.gov (United States)

    Heczko, O.; L'vov, V. A.; Straka, L.; Hannula, S.-P.

    2006-07-01

    A quantitative study of the stress-induced martensitic transformation in Ni 49.7Mn 29.1Ga 21.2 magnetic shape memory alloy has been carried out in two different ways: the first way is based on the measurements of saturation magnetization under variable mechanical stress and the second one is founded on the quantitative theoretical treatment of experimental stress-strain loops. A functional dependence between the volume fraction of transformed martensite and applied stress has been determined from both magnetization and strain values. A quantitative agreement between the functions determined in two different ways has been observed, and hence, the effectiveness of the magnetic indication of the stress-induced martensitic transformations has been proved. This method can be used to monitor stress-induced transformations in martensitic films, needles and small specimens.

  15. Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced anxiety in rats: comparison with diazepam.

    Science.gov (United States)

    Mizoguchi, Kazushige; Ikeda, Ryuji; Shoji, Hirotaka; Tanaka, Yayoi; Jin, Xue-Long; Kase, Yoshio; Takeda, Shuichi; Maruyama, Wakako; Tabira, Takeshi

    2009-01-01

    Anxiety is frequently observed in several neuropsychiatric disorders, and stress is thought to precipitate or exacerbate anxiety. In this study, the anxiolytic action of a herbal medicine, saikokaryukotsuboreito, (SRBT) was examined in normal healthy rats using the elevated plus-maze test. Moreover, the improving effect of SRBT on chronic stress-induced anxiety was also examined. Single administration of SRBT did not have anxiolytic action in normal rats. Repeated administration of SRBT significantly improved chronic stress-induced anxiety. On the other hand, single administration of a typical anxiolytic, diazepam, had anxiolytic action in normal rats but repeated administration did not improve chronic stress-induced anxiety. These results suggest that SRBT does not have anxiolytic activity equivalent to that of diazepam but has potency for improving stress-related anxiety. This finding provides information important for the treatment of anxiety.

  16. (-)Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats.

    Science.gov (United States)

    Soung, Hung-Sheng; Wang, Mao-Hsien; Tseng, Hsiang-Chien; Fang, Hsu-Wei; Chang, Kuo-Chi

    2015-08-18

    Stress induces reactive oxygen species (ROS) and causes alterations in brain cytoarchitecture and cognition. Green tea has potent antioxidative properties especially the tea catechin (-) epigallocatechin-3-gallate (EGCG). These powerful antioxidative properties are able to protect against various oxidative damages. In this study we investigated the impact of stress on rats' locomotor activity, learning and memory. Many tea catechins, including EGCG, were examined for their possible therapeutic effects in treating stress-induced impairment. Our results indicated that locomotor activity was decreased, and the learning and memory were impaired in stressed rats (SRs). EGCG treatment was able to prevent the decreased locomotor activity as well as improve the learning and memory in SRs. EGCG treatment was also able to reduce the increased oxidative status in SRs' hippocampi. The above results suggest a therapeutic effect of EGCG in treating stress-induced impairment of learning and memory, most likely by means of its powerful antioxidative properties.

  17. The stress-inducible displacement detected through RSA in non-migrating UKR.

    Science.gov (United States)

    Bragonzoni, Laura; Russo, Alessandro; Loreti, Ivano; Montagna, Luisa; Visani, Andrea; Marcacci, Maurilio

    2005-08-01

    Roentgen stereophotogrammetric analysis (RSA) under stress conditions was used to investigate possible stress-inducible displacement of the tibial component of unicompartmental knee prostheses (UKR) in which the stability was previously assessed by radiographic evaluation and standard supine RSA examinations. Sixteen patients, implanted with Duracon UNI(R) prosthesis, were selected for this study. The RSA protocol included examinations in plain upright standing posture and during execution of stress-inducing tasks in weight-bearing stance. The first follow-up was performed at an average of 14 months, and the second one at 26 months. The results showed non-negligible stress-induced rotations of the prosthetic tibial component in all the patients in most of the stress tasks performed. Rotational stress tasks and squatting turned out to be the stress conditions in which induced displacement reached the most significant values (p<0.05). These micromotions occurred mainly around the transverse axis of the knee joint and in one examination around the sagittal axis. Stress-induced translations were negligible in all the examinations. Moreover, we focused our attention on two patients suffering from inexplicable pain, and we observed a significant difference in the inducible rotation around the x-axis between these patients and the remaining fourteen. Stress-inducible displacement is a common finding in knee prostheses, but we observed that in patients with inexplicable pain, these micromotions reached values greater than the median calculated on patients without any pain. This result suggests the introduction of the stress-inducible displacement as a new parameter to be taken into consideration when analyzing the outcome of patients treated by UKR.

  18. Atypical centromeres in plants – what they can tell us

    Directory of Open Access Journals (Sweden)

    Maria eCuacos

    2015-10-01

    Full Text Available The centromere, visible as the primary constriction of condensed metaphase chromosomes, is a defined chromosomal locus essential for genome stability. It mediates transient assembly of a multi-protein complex, the kinetochore, which enables interaction with spindle fibers and thus faithful segregation of the genetic information during nuclear divisions. Centromeric DNA varies in extent and sequence composition among organisms, but a common feature of almost all active eukaryotic centromeres is the presence of the centromeric histone H3 variant cenH3 (a.k.a. CENP-A.These typical centromere features apply to most studied species. However, a number of species display atypical centromeres, such as holocentromeres (centromere extension along almost the entire chromatid length or neocentromeres (ectopic centromere activity.In this review, we provide an overview of different atypical centromere types found in plants including holocentromeres, de novo formed centromeres and terminal neocentromeres as well as di-, tri- and metapolycentromeres (more than one centromere per chromosomes. We discuss their specific and common features and compare them to centromere types found in other eukaryotic species. We also highlight new insights into centromere biology gained in plants with atypical centromeres such as distinct mechanisms to define a holocentromere, specific adaptations in species with holocentromeres during meiosis or various scenarios leading to neocentromere formation.

  19. Atypical Steatocystoma Multiplex with Calcification

    Science.gov (United States)

    Rahman, Muhammad Hasibur; Islam, Muhammad Saiful; Ansari, Nazma Parvin

    2011-01-01

    A 60-year-old male reported to us with an atypical case of giant steatocystoma multiplex in the scrotum with calcification. There was no family history of similar lesions. Yellowish, creamy material was expressed from a nodule during punch biopsy. The diagnosis was based on clinical as well as histological findings. Successful surgical excision was done to cure the case without any complications. PMID:22363850

  20. Atypical Centrioles During Sexual Reproduction

    Directory of Open Access Journals (Sweden)

    Tomer eAvidor-Reiss

    2015-04-01

    Full Text Available Centrioles are conserved, self-replicating, microtubule-based 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, the proximal centriole-like structure (PCL. We also discuss another type of atypical centriole, the zombie centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology.

  1. Atypical Imaging Appearances of Meningioma

    Directory of Open Access Journals (Sweden)

    Ahmad Soltani shirazi

    2009-01-01

    Full Text Available "nIntroduction: Meningiomas are the commonest primary non-glial intracranial tumors. The diagnosis is usually correctly established on characteristic imaging appearances. Atypical meningiomas may be difficult to diagnose because of their similarity to other brain tumors. This paper presents one case of atypical meningioma, misdiagnosed primarily as glioblastoma multiforms (GBM by radiological techniques. "nCase report: A 15-year-old girl presented with a severe intermittent generalized headache that on occasion localized to retro-orbital and vertex. Other manifestations were blurred vision, photophobia, diplopia, weakness and clumsiness of the right hand. The result of systemic and neurological examinations was normal, except for a positive right hand drift test. MRI showed a large lobulated mass with peripheral edema, central necrosis and a heterogenous enhancement at the central part of the parietal lobe inducing to subfalcian herniation. Glioblastoma multiforms (GBM was misdiagnosed for the patient on the basis of MRI appearance. Pathology evaluation was compatible with meningioma (WHO grade I to II. The patient was operated and discharged with minimal right hand weakness. Physiotherapy was recommended to improve the remaining problems. "nConclusion: Atypical meningiomas may mimic other intracranical brain lesions and may cause misdiagnosis. It is important to be aware of these features in order to avoid misdiagnosis. "n"n  

  2. GABA(A)-benzodiazepine receptor complex ligands and stress-induced hyperthermia in singly housed mice.

    NARCIS (Netherlands)

    Olivier, B.; Bouwknecht, J.A.; Pattij, T.; Leahy, C.; Oorschot, R. van; Zethof, T.J.

    2002-01-01

    Stress-induced hyperthermia (SIH) in singly housed mice, in which the rectal temperature of a mouse is measured twice with a 10-min interval, enables to study the effects of a drug on the basal (T(1)) and on the stress-enhanced temperature (T(2)), 10 min later, using the rectal procedure as stressor

  3. Adolescent Personality : Associations With Basal, Awakening, and Stress-Induced Cortisol Responses

    NARCIS (Netherlands)

    Laceulle, Odilia M.; Nederhof, Esther; van Aken, Marcel A. G.; Ormel, Johan

    2015-01-01

    The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning w

  4. Investigations into mild electric foot shock stress-induced cognitive enhancement: possible role of angiotensin neuropeptides.

    Science.gov (United States)

    Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2013-09-01

    This study was designed to investigate the role of angiotensin neuropeptides in mild electric foot shock stress-induced cognitive enhancement in mice. Mild stress was induced by applying mild electric foot shocks of 0.15 mA intensity for 0.5 s. The stress-induced alteration in cognition was assessed using a Morris water maze test. The animals were subjected to mild electric foot shocks 5 min before we recorded escape latency time (ELT), an index of learning, during the first 4 days of a 5-day trial in the Morris water maze. The time spent in target quadrant (TSTQ), an index of retrieval, was noted on the fifth day without prior administration of electric foot shock. The angiotensin-converting enzyme inhibitor lisinopril (5, 10 and 20 mg/kg), and telmisartan (1, 2 and 5 mg/kg), an angiotensin II receptor blocker, were employed to assess the role of angiotensin neuropeptides. The application of mild electric shocks significantly decreased ELT and increased TSTQ, indicating enhancement in stress-induced learning and memory. However, administration of lisinopril and telmisartan significantly attenuated the stress-induced decrease in ELT and increase in TSTQ. It may be concluded that mild electric foot shock-induced stress triggers the release of angiotensin neuropeptides that may be responsible for memory enhancement.

  5. Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis

    Directory of Open Access Journals (Sweden)

    Maria Razzoli

    2016-01-01

    Conclusion: Our findings demonstrate that thermogenesis and BAT function are determinant of the resilience or vulnerability to stress-induced obesity. Our data support a model in which adrenergic and purinergic pathways exert complementary/synergistic functions in BAT, thus suggesting an alternative to βARs agonists for the activation of human BAT.

  6. Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

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    Lim Sung-Chul

    2011-09-01

    Full Text Available Abstract Background In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1, and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood. Results In the present study, we show that Distal-less 2 (Dlx-2, a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS in response to glucose deprivation (GD, one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH release, indicating the important role(s of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis. Conclusions These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.

  7. C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.

    Science.gov (United States)

    Nath, Ravi D; Chow, Elly S; Wang, Han; Schwarz, Erich M; Sternberg, Paul W

    2016-09-26

    The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep-pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus-and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides.

  8. Individual differences in the locus coeruleus-norepinephrine system: Relevance to stress-induced cardiovascular vulnerability.

    Science.gov (United States)

    Wood, Christopher S; Valentino, Rita J; Wood, Susan K

    2017-04-01

    Repeated exposure to psychosocial stress is a robust sympathomimetic stressor and as such has adverse effects on cardiovascular health. While the neurocircuitry involved remains unclear, the physiological and anatomical characteristics of the locus coeruleus (LC)-norepinephrine (NE) system suggest that it is poised to contribute to stress-induced cardiovascular vulnerability. A major theme throughout is to review studies that shed light on the role that the LC may play in individual differences in vulnerability to social stress-induced cardiovascular dysfunction. Recent findings are discussed that support a unique plasticity in afferent regulation of the LC, resulting in either excitatory or inhibitory input to the LC during establishment of different stress coping strategies. This contrasting regulation of the LC by either afferent regulation, or distinct differences in stress-induced neuroinflammation would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The goal of this review is to highlight recent developments in the interplay between the LC-NE and cardiovascular systems during repeated stress in an effort to advance therapeutic treatments for the development of stress-induced cardiovascular vulnerability.

  9. Oxidative stress induces transient O-GlcNAc elevation and tau dephosphorylation in SH-SY5Y cells.

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    Kátai, Emese; Pál, József; Poór, Viktor Soma; Purewal, Rupeena; Miseta, Attila; Nagy, Tamás

    2016-12-01

    O-linked β-N-acetlyglucosamine or O-GlcNAc modification is a dynamic post-translational modification occurring on the Ser/Thr residues of many intracellular proteins. The chronic imbalance between phosphorylation and O-GlcNAc on tau protein is considered as one of the main hallmarks of Alzheimer's disease. In recent years, many studies also showed that O-GlcNAc levels can elevate upon acute stress and suggested that this might facilitate cell survival. However, many consider chronic stress, including oxidative damage as a major risk factor in the development of the disease. In this study, using the neuronal cell line SH-SY5Y we investigated the dynamic nature of O-GlcNAc after treatment with 0.5 mM H2 O2 for 30 min. to induce oxidative stress. We found that overall O-GlcNAc quickly increased and reached peak level at around 2 hrs post-stress, then returned to baseline levels after about 24 hrs. Interestingly, we also found that tau protein phosphorylation at site S262 showed parallel, whereas at S199 and PHF1 sites showed inverse dynamic to O-Glycosylation. In conclusion, our results show that temporary elevation in O-GlcNAc modification after H2 O2 -induced oxidative stress is detectable in cells of neuronal origin. Furthermore, oxidative stress changes the dynamic balance between O-GlcNAc and phosphorylation on tau proteins.

  10. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    Science.gov (United States)

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  11. Influenza a virus host shutoff disables antiviral stress-induced translation arrest.

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    Denys A Khaperskyy

    2014-07-01

    Full Text Available Influenza A virus (IAV polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5' caps and poly(A tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs. It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1 non-structural protein 1 (NS1 inactivates the antiviral double-stranded RNA (dsRNA-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2 nucleoprotein (NP inhibits SG formation without affecting eIF2α phosphorylation; 3 host-shutoff protein polymerase-acidic protein-X (PA-X strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A RNA and nuclear accumulation of poly(A-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.

  12. Influenza a virus host shutoff disables antiviral stress-induced translation arrest.

    Science.gov (United States)

    Khaperskyy, Denys A; Emara, Mohamed M; Johnston, Benjamin P; Anderson, Paul; Hatchette, Todd F; McCormick, Craig

    2014-07-01

    Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5' caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.

  13. Rapid stress-induced corticosterone rise in the hippocampus reverses serial memory retrieval pattern.

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    Chauveau, F; Tronche, C; Piérard, C; Liscia, P; Drouet, I; Coutan, M; Béracochéa, D

    2010-01-01

    We previously showed that an acute stress (electric footshocks) induced both a rapid plasma corticosterone rise and a reversal of serial memory retrieval pattern in a contextual serial discrimination (CSD) task. This study is aimed at determining (i) if the rapid stress effects on CSD performance are mediated by the hippocampus; (ii) if hippocampal corticosterone membrane receptor activation is involved in the rapid stress effects on CSD performance. In experiment 1, microdialysis in the dorsal hippocampus (dHPC) was used to measure the stress-induced corticosterone rise; in parallel, the effect of acute stress on CSD performance was evaluated. In addition, the functional involvement of corticosterone in the behavioral effects of stress was assessed by administering metyrapone, a corticosterone synthesis inhibitor, before stress. In experiment 2, the involvement of hippocampal corticosterone membrane receptors in the stress-induced reversal of CSD performance was studied by injecting corticosterone-bovine serum albumin (BSA) (a membrane-impermeable complex) in the dHPC in non stressed mice. Results showed that (i) the acute stress induced a rapid (15 min) and transitory (90 min) corticosterone rise into the hippocampus dHPC, and a reversal of serial memory retrieval pattern; (ii) both the endocrinal and memory stress-induced effects were blocked by metyrapone; (iii) corticosterone-BSA injection into the dHPC in non stressed mice mimicked the effects of stress on serial retrieval pattern. Overall, our study is first to show that (i) a rapid stress-induced corticosterone rise into the dHPC transitorily reverses serial memory retrieval pattern and (ii) hippocampal corticosterone membrane receptors activation is involved in the rapid effects of acute stress on serial memory retrieval.

  14. Treatment options for atypical optic neuritis

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    Amina Malik

    2014-01-01

    Full Text Available Context: Optic neuritis (ON is defined as inflammation of the optic nerve and can have various etiologies. The most common presentation in the US is demyelinating, or "typical" ON, usually associated with multiple sclerosis. This is in contrast to "atypical" causes of ON, which differ in their clinical presentation, management, and prognosis. These atypical cases are characterized by lack of eye pain, exudates, and hemorrhages on exam, very severe, bilateral or progressive visual loss, or with failure to recover vision. Aims: The aim was to describe the clinical presentations of atypical ON and their treatments. Settings and Design: Review article. Materials and Methods: Literature review. Results: Types of atypical ON identified include neuromyelitis optica, autoimmune optic neuropathy, chronic relapsing inflammatory optic neuropathy, idiopathic recurrent neuroretinitis, and optic neuropathy associated with systemic diseases. Atypical ON usually requires corticosteroid treatment and often will require aggressive immunosuppression. Conclusions: Unlike demyelinating ON, atypical ON requires treatment to preserve vision.

  15. Stress induced cardiomyopathy presenting as acute coronary syndrome: Tako-Tsubo in Mercogliano, Southern Italy

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    Salemme L

    2007-10-01

    Full Text Available Abstract Background Tako-tsubo syndrome (TTS in its typical (apical and atypical (non-apical forms is being increasingly recognized in the West owing to early systematic coronary angiography in acute coronary syndromes (ACS. Aim of the study To assess the incidence, the clinical characteristics and the outcome of TTS in a single high volume cath lab in Southern Italy over the last 6 years. Methods Among 1674 consecutive patients (pts referred to our coronary care units in the last 6 years (2001–2006 for ACS we selected 6 (0.5% pts (6 women; age 57 ± 6 years who fulfilled the following 4 criteria: 1 transient left ventricular wall motion abnormalities resulting in ballooning at contrast ventricolographic or echocardiographic evaluation; 2 normal coronary artery on coronary angiography performed 5 ± 9 hours from hospitalization; 3 new electrocardiographic ischemic-like abnormalities (either ST-segment elevation or T-wave inversion and 4 emotional or physical trigger event. Results At admission all pts had presumptive diagnosis of ACS and ECG revealed ST elevation in 3 (50% and T wave inversion with QT elongation in 3 (50%. In the acute phase cardiogenic shock occurred in 2 (33% and heart failure in 1(16%. Presenting symptoms were chest pain in 6 (100%, dyspnoea in 2 (33% and lipotimia in 1 (16%. At echocardiographic-ventricolographic assessment, the mechanical dysfunction (ballooning was apical in all 6 pts ("classic" TTS. In all patients wall motion abnormalities completely reversed within 4.5 ± 1.5 days. The region of initial recovery was the anterior and lateral wall in 4 cases and the lateral wall in 2 cases. Ejection fraction was 35 ± 8% in the acute phase and increased progressively at discharge (55 ± 6% and at 41 ± 20 months follow-up (60 ± 4%, p Conclusion Classic TTS is a frequent serendipitous diagnosis after coronary angiography showed "surprisingly" normal findings in a clinical setting mimicking an ACS. Despite its long

  16. Atypical Manifestation of Vestibular Schwannoma

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    Webster, Guilherme

    2013-09-01

    Full Text Available Introduction: Vestibular schwannoma (also known as acoustic neuroma is a benign tumor whose cells are derived from Schwann sheaths, which commonly occurs from the vestibular portion of the eighth cranial nerve. Furthermore, vestibular schwannomas account for ∼8% of intracranial tumors in adults and 80 to 90% of tumors of the cerebellopontine angle. Its symptoms are varied, but what stands out most is a unilateral sensorineural hearing loss, with a low index of speech recognition. Objective: Describe an atypical manifestation of vestibular schwannoma. Case Report: The 46-year-old woman had vertigo and binaural hearing loss and fullness, with ear, nose, and throat examination suggestive of cochlear injury. After 6 months, the patient developed worsening of symptoms and onset of right unilateral tinnitus. In further exams the signs of cochlear damage remained, except for the vestibular test (hyporeflexia. Magnetic resonance imaging showed an expansive lesion in the right cerebellopontine angle. Discussion: This report warns about the atypical manifestations of vestibular schwannoma, which must always be remembered in investigating and diagnosing hearing loss.

  17. Atypical Presentation of Atypical Teratoid Rhabdoid Tumor in a Child

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    Y. T. Udaka

    2013-01-01

    Full Text Available Atypical Teratoid Rhabdoid Tumor (ATRT is a rare malignant intracranial neoplasm more commonly diagnosed in young children. The authors report the case of an 11-year-old boy with a long standing history of slowly progressive weight loss, fatigue, and weakness over 1.5 years whose magnetic resonance imaging revealed a large heterogeneous enhancing dorsally exophytic lower brainstem mass. Examination revealed extreme cachexia, gaze-evoked nystagmus, dysphagia, dysarthria, bilateral dysmetria, and global weakness without ambulation. The protracted history and neuroimaging features were most suggestive of a low grade glioma. However, pathology revealed a hypercellular tumor with large hyperchromatic nucleoli and loss of INI-1 staining on immunohistochemistry consistent with a diagnosis of an ATRT. The child died shortly after surgery due to complications from his brainstem infiltrative disease. This case illustrates the diverse presentation of ATRT in childhood that can clinically and radiographically mimic that of low grade glioma.

  18. Opioid and nonopioid interactions in two forms of stress-induced analgesia.

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    Grisel, J E; Fleshner, M; Watkins, L R; Maier, S F

    1993-05-01

    Stressful environmental events activate endogenous mechanisms of pain inhibition. Under some circumstances the analgesia is blocked by naloxone/naltrexone ("opioid"), while under others it is not ("nonopioid"). The existence of these two categories of analgesia leads to the question of how they are related. In a collateral inhibition model proposed by Kirshgessner, Bodnar, and Pasternak (1982), opiate and nonopiate mechanisms were viewed as acting in a mutually inhibitory fashion. In the present experiments, rats were exposed to either of two environmental stressors that produce a nonopioid stress-induced analgesia (SIA) following injections of the opiate antagonist naltrexone or agonist morphine. In the presence of naltrexone, SIA produced by either cold water swim (CWS) or social defeat was enhanced. These same SIAs were found to attenuate the analgesic effect of morphine, demonstrating that an activation of opioid systems can inhibit nonopioid analgesias. These results support an inhibitory interaction of opioid and nonopioid mechanisms in some forms of stress-induced analgesia.

  19. A study on anti-stress property of Nardostachys jatamamsi on stress induced Drosophila melanogaster

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    Shilpashree R.

    2011-09-01

    Full Text Available Stress is a feeling that’s created when we react to particular events. It s the body’s way of rising to a challenge and preparing to meet a tough situation with focus, strength, stamina, and heightened alertness. As a result of the stress immune system can be suppressed by chronic stress opening to increased infections and increasing the risk of autoimmune diseases. So one has to learn away to overcome stress. Here is an attempt made to overcome the stress induced in Drosophila melanogaster a model organism, in this study. Methotrexate is used to induce the stress at different concentration taking different group of flies and a Nardostachys jatamamsi plant extract having antistress property is used to relieve the stress induced. This stress relieve measured by the various stress related enzymes like catalase and Superoxide dismutase by this antistress property of the plant Nardostachys jatamamsi was shown.

  20. Endoplasmic reticulum stress-induced autophagy determines the susceptibility of melanoma cells to dabrafenib

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    Ji, Chao; Zhang, Ziping; Chen, Lihong; Zhou, Kunli; Li, Dongjun; Wang, Ping; Huang, Shuying; Gong, Ting; Cheng, Bo

    2016-01-01

    Melanoma is one of the deadliest skin cancers and accounts for most skin-related deaths due to strong resistance to chemotherapy drugs. In the present study, we investigated the mechanisms of dabrafenib-induced drug resistance in human melanoma cell lines A375 and MEL624. Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy. PMID:27536070

  1. Nordihydroguaiaretic Acid Attenuates the Oxidative Stress-Induced Decrease of CD33 Expression in Human Monocytes

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    Silvia Guzmán-Beltrán

    2013-01-01

    Full Text Available Nordihydroguaiaretic acid (NDGA is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs. Oxidative stress was induced by iodoacetate (IAA or hydrogen peroxide (H2O2 and was evaluated using reactive oxygen species (ROS production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H2O2 in human MNs. It was also shown that NDGA (20 μM attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H2O2. These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  2. Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death.

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    Liao, Yajin; Hao, Yumin; Chen, Hong; He, Qing; Yuan, Zengqiang; Cheng, Jinbo

    2015-06-01

    Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca(2+) uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.

  3. A Method for Psychosocial Stress-Induced Reinstatement of Cocaine Seeking in Rats.

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    Manvich, Daniel F; Stowe, Taylor A; Godfrey, Jodi R; Weinshenker, David

    2016-06-01

    We describe a novel preclinical model of stress-induced relapse to cocaine use in rats using social defeat stress, an ethologically valid psychosocial stressor in rodents that closely resembles stressors that promote craving and relapse in humans. Rats self-administered cocaine for 20 days. On days 11, 14, 17, and 20, animals were subjected to social defeat stress or a nonstressful control condition following the session, with discrete environmental stimuli signaling the impending event. After extinction training, reinstatement was assessed following re-exposure to these discrete cues. Animals re-exposed to psychosocial stress-predictive cues exhibited increased serum corticosterone and significantly greater reinstatement of cocaine seeking than the control group, and active coping behaviors during social defeat episodes were associated with subsequent reinstatement magnitude. These studies are the first to describe an operant model of psychosocial stress-induced relapse in rodents and lay the foundation for future work investigating its neurobiological underpinnings.

  4. Stress-induced cardiac autonomic reactivity and preclinical atherosclerosis: does arterial elasticity modify the association?

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    Chumaeva, Nadja; Hintsanen, Mirka; Pulkki-Råback, Laura; Merjonen, Päivi; Elovainio, Marko; Hintsa, Taina; Juonala, Markus; Kähönen, Mika; Raitakari, Olli T; Keltikangas-Järvinen, Liisa

    2015-01-01

    The effect of acute mental stress on atherosclerosis can be estimated using arterial elasticity measured by carotid artery distensibility (Cdist). We examined the interactive effect of acute stress-induced cardiac reactivity and Cdist to preclinical atherosclerosis assessed by carotid intima-media thickness (IMT) in 58 healthy adults aged 24-39 years participated in the epidemiological Young Finns Study. Cdist and IMT were measured ultrasonographically. Impedance electrocardiography was used to measure acute mental stress-induced cardiac autonomic responses: heart rate (HR), respiratory sinus arrhythmia and pre-ejection period after the mental arithmetic and the public speaking tasks. Interactions between HR reactivity and Cdist in relation to preclinical atherosclerosis were found. The results imply that elevated HR reactivity to acute mental stress is related to less atherosclerosis among healthy participants with higher arterial elasticity. Possibly, increased cardiac reactivity in response to challenging tasks is an adaptive reaction related to better cardiovascular health.

  5. Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger.

    Science.gov (United States)

    Frank, Matthew G; Watkins, Linda R; Maier, Steven F

    2013-10-01

    A considerable number of studies demonstrate that acute and chronic stressors prime CNS innate immune responses to subsequent pro-inflammatory challenges and that glucocorticoids mediate, in part, stress-induced sensitization of pro-inflammatory immune responses. Here, we explore the notion that GCs produce a persisting sensitization of CNS innate immune effectors (e.g. microglia) so that they will generate a potentiated pro-inflammatory response after the GC rise has dissipated, thereby enhancing the sickness response to infection or injury and maximizing the animal's ability to neutralize danger. The stress-induced GC response is conceptualized here as an neuroendocrine warning signal or alarmin to the innate immune system, which prepares or sensitizes the innate immune response to potential danger. Thus, a new understanding of the stress response and its function (priming CNS innate immune responses to infection or injury during a fight/flight emergency) would be suggested.

  6. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction

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    Stevie Struiksma

    2009-06-01

    Full Text Available Background: Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood. Methods: Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP 70 was evaluated. The intestinal epithelial permeability was examined with Ussing chamber technique. Results: HSP70 was detected in normal intestinal epithelial cells. Psychological stress decreased HSP70 in the intestinal epithelial cells that correlated with the stress-induced intestinal epithelial hyperpermeability. Pretreatment with HSP70 abrogated stress-induced intestinal barrier dysfunction. Conclusions: Chronic stress inhibits HSP70 activity in rat intestinal epithelial layer that is associated with intestinal epithelial barrier dysfunction, which can be prevented by pretreatment with HSP70 protein.

  7. Nordihydroguaiaretic acid attenuates the oxidative stress-induced decrease of CD33 expression in human monocytes.

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    Guzmán-Beltrán, Silvia; Pedraza-Chaverri, José; Gonzalez-Reyes, Susana; Hernández-Sánchez, Fernando; Juarez-Figueroa, Ulises E; Gonzalez, Yolanda; Bobadilla, Karen; Torres, Martha

    2013-01-01

    Nordihydroguaiaretic acid (NDGA) is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs). Oxidative stress was induced by iodoacetate (IAA) or hydrogen peroxide (H(2)O(2)) and was evaluated using reactive oxygen species (ROS) production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H(2)O(2) in human MNs. It was also shown that NDGA (20  μ M) attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H(2)O(2). These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  8. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice

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    Yoshinori Kobayashi

    2014-01-01

    Full Text Available Background: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae and is a known component of the nitric oxide (NO cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. Objective: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model. Materials and Methods: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C. A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice, and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. Results: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. Conclusions: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.

  9. EVALUATION OF ANXIOLYTIC POTENTIAL OF ETHANOLIC EXTRACT HYPERICUM HOOKERIANUM IN STRESS INDUCED SWISS ALBINO MICE

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    S.Subakanmani

    2012-04-01

    Full Text Available The aim of the present work is evaluate to Anxiolytic profile of Hypericum hookerianum in stress induced Swiss albino mice. The study was carried out using Swiss albino mice (25- 30 g. The Anxiolytic effect of aerial parts of ethanolic extract of Hypericum hookerianum was evaluated by using behavioral analysis like Elevated plus maze (EPM test, Open Field Test (OFT, Hole Board Test (HBT, Light dark exploration Test (LDE in restraint stress induced animals. Behavioral test parameters for anxiety were assessed followed by biochemical parameters (lipid per oxidation, super oxide dismutase, catalase, glutathione per oxidase, reduced glutathione, etc. and Diazepam 1 mg/kg served as a standard Anxiolytic drug, administered intraperitonealy. The results were shown that, ethanolic extract of H.hookerianum (Hh 100mg/kg and Hh 200 mg/kg, p.o. significantly increased the percentage of time spent and number of entries in open arm in EPM. In LDE, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. Biochemical analyses revealed an increase in lipid per oxidation, depletion of super oxide dismutase, reduced glutathione, catalase activity and glutathione per oxidase in stress induced animals as compared to unstressed animal. Six days treatment of Hh (100 mg/kg, 200 mg/kg comparable with Diazepam, significantly attenuated restraint stress-induced behavioral and oxidative damage. The results of the present study suggest that an ethanolic extract of H.hookerianum may possess Anxiolytic activity in stressed animals and provide a scientific evidence for its traditional claim.

  10. Bias-stress-induced instability of polymer thin-film transistor based on poly(3-hexylthiophene)

    OpenAIRE

    Liu, YR; Liao, R.; Lai, PT; Yao, RH

    2012-01-01

    A polymer thin-film transistor (PTFT) based on poly(3-hexylthiophene) (P3HT) is fabricated by a spin-coating process and characterized. Its bias-stress-induced instability during operation is investigated as a function of time and temperature. For negative gate-bias stress, the carrier mobility remains unchanged, the off-state current decreases, and the threshold voltage shifts toward the negative direction. On the other hand, for negative drain-bias stress, the carrier mobility decreases sli...

  11. Glutamatergic mechanisms associated with stress-induced amygdala excitability and anxiety-related behavior.

    Science.gov (United States)

    Masneuf, Sophie; Lowery-Gionta, Emily; Colacicco, Giovanni; Pleil, Kristen E; Li, Chia; Crowley, Nicole; Flynn, Shaun; Holmes, Andrew; Kash, Thomas

    2014-10-01

    The neural factors underlying individual differences in susceptibility to chronic stress remain poorly understood. Preclinical studies demonstrate that mouse strains vary greatly in anxiety-related responses to chronic stress in a manner paralleled by differential stress-induced changes in glutamatergic signaling in the basolateral amygdala (BLA). Previous work has also shown that alterations in the amygdala gene expression of the GluN1 NMDA and the GluK1 kainate receptors are associated with stress-induced alterations in anxiety-like behavior in the C57BL/6J mouse strain. Using in vivo behavioral pharmacological and ex vivo physiological approaches, the aim of the current study was to further elucidate changes in glutamate neurotransmission in the BLA caused by stress and to test the functional roles of GluN1 and GluK1 in mediating stress-related changes in behavior. Results showed that stress-induced alterations in anxiety-like behavior (light/dark exploration test) were absent following bilateral infusion of the GluK1 agonist ATPA into the BLA. Intra-BLA infusion of the competitive NMDA antagonist AP5 produced a generalized behavioral disinhibition/locomotor hyperactivity, irrespective of stress. Slice electrophysiological recordings showed that ATPA augmented BLA GABAergic neurotransmission and that stress increased the amplitude of network-dependent spontaneous excitatory postsynaptic currents and amplitude of GABAergic miniature inhibitory postsynaptic currents in BLA. These findings could indicate stress-induced BLA glutamatergic neuronal network hyperexcitability and a compensatory increase in GABAergic neurotransmission, suggesting that GluK1 agonism augmented GABAergic inhibition to prevent behavioral sequelae of stress. Current data could have implications for developing novel therapeutic approaches, including GluK1 agonists, for stress-related anxiety disorders.

  12. Stress-induced Nuclear Bodies Are Sites of Accumulation of Pre-mRNA Processing Factors

    Science.gov (United States)

    Denegri, Marco; Chiodi, Ilaria; Corioni, Margherita; Cobianchi, Fabio; Riva, Silvano; Biamonti, Giuseppe

    2001-01-01

    Heterogeneous nuclear ribonucleoprotein (hnRNP) HAP (hnRNP A1 interacting protein) is a multifunctional protein with roles in RNA metabolism, transcription, and nuclear structure. After stress treatments, HAP is recruited to a small number of nuclear bodies, usually adjacent to the nucleoli, which consist of clusters of perichromatin granules and are depots of transcripts synthesized before stress. In this article we show that HAP bodies are sites of accumulation for a subset of RNA processing factors and are related to Sam68 nuclear bodies (SNBs) detectable in unstressed cells. Indeed, HAP and Sam68 are both present in SNBs and in HAP bodies, that we rename “stress-induced SNBs.” The determinants required for the redistribution of HAP lie between residue 580 and 788. Different portions of this region direct the recruitment of the green fluorescent protein to stress-induced SNBs, suggesting an interaction of HAP with different components of the bodies. With the use of the 580–725 region as bait in a two-hybrid screening, we have selected SRp30c and 9G8, two members of the SR family of splicing factors. Splicing factors are differentially affected by heat shock: SRp30c and SF2/ASF are efficiently recruited to stress-induced SNBs, whereas the distribution of SC35 is not perturbed. We propose that the differential sequestration of splicing factors could affect processing of specific transcripts. Accordingly, the formation of stress-induced SNBs is accompanied by a change in the splicing pattern of the adenovirus E1A transcripts. PMID:11694584

  13. Differential Effects of Stress-induced Cortisol Responses on Recollection and Familiarity-based Recognition Memory

    OpenAIRE

    McCullough, Andrew M.; Ritchey, Maureen; Ranganath, Charan; Yonelinas, Andrew

    2015-01-01

    Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol o...

  14. 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...

  15. Oxidative stress-induced epigenetic changes associated with malignant transformation of human kidney epithelial cells.

    Science.gov (United States)

    Mahalingaiah, Prathap Kumar S; Ponnusamy, Logeswari; Singh, Kamaleshwar P

    2016-09-17

    Renal Cell Carcinoma (RCC) in humans is positively influenced by oxidative stress status in kidneys. We recently reported that adaptive response to low level of chronic oxidative stress induces malignant transformation of immortalized human renal tubular epithelial cells. Epigenetic alterations in human RCC are well documented, but its role in oxidative stress-induced malignant transformation of kidney cells is not known. Therefore, the objective of this study was to evaluate the potential role of epigenetic changes in chronic oxidative stress-induced malignant transformation of HK-2, human renal tubular epithelial cells. The results revealed aberrant expression of epigenetic regulatory genes involved in DNA methylation (DNMT1, DNMT3a and MBD4) and histone modifications (HDAC1, HMT1 and HAT1) in HK-2 cells malignantly transformed by chronic oxidative stress. Additionally, both in vitro soft agar assay and in vivo nude mice study showing decreased tumorigenic potential of malignantly transformed HK-2 cells following treatment with DNA de-methylating agent 5-aza 2' dC further confirmed the crucial role of DNA hypermethyaltion in oxidative stress-induced malignant transformation. Changes observed in global histone H3 acetylation (H3K9, H3K18, H3K27 and H3K14) and decrease in phospho-H2AX (Ser139) also suggest potential role of histone modifications in increased survival and malignant transformation of HK-2 cells by oxidative stress. In summary, the results of this study suggest that epigenetic reprogramming induced by low levels of oxidative stress act as driver for malignant transformation of kidney epithelial cells. Findings of this study are highly relevant in potential clinical application of epigenetic-based therapeutics for treatments of kidney cancers.

  16. Opto-Electronically Efficient Conjugated Polymers by Stress-Induced Molecular Constraints

    Science.gov (United States)

    2012-07-15

    Final Report for AOARD Grant FA2386-11-1-4055 Opto-Electronically Efficient Conjugated Polymers by Stress-Induced Molecular Constraints... polymers . The effects of molecular flows triggered in thin film dewetting were further studied to reveal the mechanisms of chain stretching...to increase. Finally, the efficiency enhancement can be produced in solid films of conjugated polymers using simple imprints under good control

  17. Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis.

    Science.gov (United States)

    Kreisel, T; Frank, M G; Licht, T; Reshef, R; Ben-Menachem-Zidon, O; Baratta, M V; Maier, S F; Yirmiya, R

    2014-06-01

    The limited success in understanding the pathophysiology of major depression may result from excessive focus on the dysfunctioning of neurons, as compared with other types of brain cells. Therefore, we examined the role of dynamic alterations in microglia activation status in the development of chronic unpredictable stress (CUS)-induced depressive-like condition in rodents. We report that following an initial period (2-3 days) of stress-induced microglial proliferation and activation, some microglia underwent apoptosis, leading to reductions in their numbers within the hippocampus, but not in other brain regions, following 5 weeks of CUS exposure. At that time, microglia displayed reduced expression of activation markers as well as dystrophic morphology. Blockade of the initial stress-induced microglial activation by minocycline or by transgenic interleukin-1 receptor antagonist overexpression rescued the subsequent microglial apoptosis and decline, as well as the CUS-induced depressive-like behavior and suppressed neurogenesis. Similarly, the antidepressant drug imipramine blocked the initial stress-induced microglial activation as well as the CUS-induced microglial decline and depressive-like behavior. Treatment of CUS-exposed mice with either endotoxin, macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, all of which stimulated hippocampal microglial proliferation, partially or completely reversed the depressive-like behavior and dramatically increased hippocampal neurogenesis, whereas treatment with imipramine or minocycline had minimal or no anti-depressive effects, respectively, in these mice. These findings provide direct causal evidence that disturbances in microglial functioning has an etiological role in chronic stress-induced depression, suggesting that microglia stimulators could serve as fast-acting anti-depressants in some forms of depressive and stress-related conditions.

  18. Protective effect of Labisia pumila on stress-induced behavioral, biochemical, and immunological alterations.

    Science.gov (United States)

    Kour, Kiranjeet; Sharma, Neelam; Chandan, Bal Krishan; Koul, Surrinder; Sangwan, Payare Lal; Bani, Sarang

    2010-10-01

    The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 (+) and CD8 (+) T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis.

  19. Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor.

    Science.gov (United States)

    Vogel, Susanne; Klumpers, Floris; Schröder, Tobias Navarro; Oplaat, Krista T; Krugers, Harm J; Oitzl, Melly S; Joëls, Marian; Doeller, Christian F; Fernández, Guillén

    2016-12-21

    Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.Neuropsychopharmacology advance online publication, 21 December 2016; doi:10.1038/npp.2016.262.

  20. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6

    Directory of Open Access Journals (Sweden)

    Rong Liu

    2014-01-01

    Full Text Available Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated retinoblastoma (Rb protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.

  1. Secondary aerosol formation from stress-induced biogenic emissions and possible climate feedbacks

    Directory of Open Access Journals (Sweden)

    Th. F. Mentel

    2013-09-01

    Full Text Available Atmospheric aerosols impact climate by scattering and absorbing solar radiation and by acting as ice and cloud condensation nuclei. Biogenic secondary organic aerosols (BSOAs comprise an important component of atmospheric aerosols. Biogenic volatile organic compounds (BVOCs emitted by vegetation are the source of BSOAs. Pathogens and insect attacks, heat waves and droughts can induce stress to plants that may impact their BVOC emissions, and hence the yield and type of formed BSOAs, and possibly their climatic effects. This raises questions of whether stress-induced changes in BSOA formation may attenuate or amplify effects of climate change. In this study we assess the potential impact of stress-induced BVOC emissions on BSOA formation for tree species typical for mixed deciduous and Boreal Eurasian forests. We studied the photochemical BSOA formation for plants infested by aphids in a laboratory setup under well-controlled conditions and applied in addition heat and drought stress. The results indicate that stress conditions substantially modify BSOA formation and yield. Stress-induced emissions of sesquiterpenes, methyl salicylate, and C17-BVOCs increase BSOA yields. Mixtures including these compounds exhibit BSOA yields between 17 and 33%, significantly higher than mixtures containing mainly monoterpenes (4–6% yield. Green leaf volatiles suppress SOA formation, presumably by scavenging OH, similar to isoprene. By classifying emission types, stressors and BSOA formation potential, we discuss possible climatic feedbacks regarding aerosol effects. We conclude that stress situations for plants due to climate change should be considered in climate–vegetation feedback mechanisms.

  2. Cordyceps militaris Extract Protects Human Dermal Fibroblasts against Oxidative Stress-Induced Apoptosis and Premature Senescence

    Science.gov (United States)

    Park, Jun Myoung; Lee, Jong Seok; Lee, Ki Rim; Ha, Suk-Jin; Hong, Eock Kee

    2014-01-01

    Oxidative stress induced by reactive oxygen species (ROS) is the major cause of degenerative disorders including aging and disease. In this study, we investigated whether Cordyceps militaris extract (CME) has in vitro protective effects on hydrogen peroxide-induced oxidative stress in human dermal fibroblasts (HDFs). Our results showed that the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity of CME was increased in a dose-dependent manner. We found that hydrogen peroxide treatment in HDFs increased ROS generation and cell death as compared with the control. However, CME improved the survival of HDFs against hydrogen peroxide-induced oxidative stress via inhibition of intracellular ROS production. CME treatment inhibited hydrogen peroxide-induced apoptotic cell death and apoptotic nuclear condensation in HDFs. In addition, CME prevented hydrogen peroxide-induced SA-β-gal-positive cells suggesting CME could inhibit oxidative stress-induced premature senescence. Therefore, these results suggest that CME might have protective effects against oxidative stress-induced premature senescence via scavenging ROS. PMID:25230212

  3. Cordyceps militaris Extract Protects Human Dermal Fibroblasts against Oxidative Stress-Induced Apoptosis and Premature Senescence

    Directory of Open Access Journals (Sweden)

    Jun Myoung Park

    2014-09-01

    Full Text Available Oxidative stress induced by reactive oxygen species (ROS is the major cause of degenerative disorders including aging and disease. In this study, we investigated whether Cordyceps militaris extract (CME has in vitro protective effects on hydrogen peroxide-induced oxidative stress in human dermal fibroblasts (HDFs. Our results showed that the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging activity of CME was increased in a dose-dependent manner. We found that hydrogen peroxide treatment in HDFs increased ROS generation and cell death as compared with the control. However, CME improved the survival of HDFs against hydrogen peroxide-induced oxidative stress via inhibition of intracellular ROS production. CME treatment inhibited hydrogen peroxide-induced apoptotic cell death and apoptotic nuclear condensation in HDFs. In addition, CME prevented hydrogen peroxide-induced SA-β-gal-positive cells suggesting CME could inhibit oxidative stress-induced premature senescence. Therefore, these results suggest that CME might have protective effects against oxidative stress-induced premature senescence via scavenging ROS.

  4. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

    Science.gov (United States)

    Viswanathan, Kavitha; Dhabhar, Firdaus S.

    2005-04-01

    Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

  5. Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

    Science.gov (United States)

    Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

    2004-03-01

    Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

  6. Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition.

    Science.gov (United States)

    Wang, Qian; Guo, Wenjing; Hao, Baixia; Shi, Xianli; Lu, Yingying; Wong, Connie W M; Ma, Victor W S; Yip, Timothy T C; Au, Joseph S K; Hao, Quan; Cheung, King-Ho; Wu, Wutian; Li, Gui-Rong; Yue, Jianbo

    2016-08-02

    Reactive oxygen species (ROS) have been commonly accepted as inducers of autophagy, and autophagy in turn is activated to relieve oxidative stress. Yet, whether and how oxidative stress, generated in various human pathologies, regulates autophagy remains unknown. Here, we mechanistically studied the role of TRPM2 (transient receptor potential cation channel subfamily M member 2)-mediated Ca(2+) influx in oxidative stress-mediated autophagy regulation. On the one hand, we demonstrated that oxidative stress triggered TRPM2-dependent Ca(2+) influx to inhibit the induction of early autophagy, which renders cells more susceptible to death. On the other hand, oxidative stress induced autophagy (and not cell death) in the absence of the TRPM2-mediated Ca(2+) influx. Moreover, in response to oxidative stress, TRPM2-mediated Ca(2+) influx activated CAMK2 (calcium/calmodulin dependent protein kinase II) at levels of both phosphorylation and oxidation, and the activated CAMK2 subsequently phosphorylated BECN1/Beclin 1 on Ser295. Ser295 phosphorylation of BECN1 in turn decreased the association between BECN1 and PIK3C3/VPS34, but induced binding between BECN1 and BCL2. Clinically, acetaminophen (APAP) overdose is the most common cause of acute liver failure worldwide. We demonstrated that APAP overdose also activated ROS-TRPM2-CAMK2-BECN1 signaling to suppress autophagy, thereby causing primary hepatocytes to be more vulnerable to death. Inhibiting the TRPM2-Ca(2+)-CAMK2 cascade significantly mitigated APAP-induced liver injury. In summary, our data clearly demonstrate that oxidative stress activates the TRPM2-Ca(2+)-CAMK2 cascade to phosphorylate BECN1 resulting in autophagy inhibition.

  7. The genome-wide early temporal response of Saccharomyces cerevisiae to oxidative stress induced by cumene hydroperoxide.

    Science.gov (United States)

    Sha, Wei; Martins, Ana M; Laubenbacher, Reinhard; Mendes, Pedro; Shulaev, Vladimir

    2013-01-01

    Oxidative stress is a well-known biological process that occurs in all respiring cells and is involved in pathophysiological processes such as aging and apoptosis. Oxidative stress agents include peroxides such as hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide, the thiol oxidant diamide, and menadione, a generator of superoxide, amongst others. The present study analyzed the early temporal genome-wide transcriptional response of Saccharomyces cerevisiae to oxidative stress induced by the aromatic peroxide cumene hydroperoxide. The accurate dataset obtained, supported by the use of temporal controls, biological replicates and well controlled growth conditions, provided a detailed picture of the early dynamics of the process. We identified a set of genes previously not implicated in the oxidative stress response, including several transcriptional regulators showing a fast transient response, suggesting a coordinated process in the transcriptional reprogramming. We discuss the role of the glutathione, thioredoxin and reactive oxygen species-removing systems, the proteasome and the pentose phosphate pathway. A data-driven clustering of the expression patterns identified one specific cluster that mostly consisted of genes known to be regulated by the Yap1p and Skn7p transcription factors, emphasizing their mediator role in the transcriptional response to oxidants. Comparison of our results with data reported for hydrogen peroxide identified 664 genes that specifically respond to cumene hydroperoxide, suggesting distinct transcriptional responses to these two peroxides. Genes up-regulated only by cumene hydroperoxide are mainly related to the cell membrane and cell wall, and proteolysis process, while those down-regulated only by this aromatic peroxide are involved in mitochondrial function.

  8. The genome-wide early temporal response of Saccharomyces cerevisiae to oxidative stress induced by cumene hydroperoxide.

    Directory of Open Access Journals (Sweden)

    Wei Sha

    Full Text Available Oxidative stress is a well-known biological process that occurs in all respiring cells and is involved in pathophysiological processes such as aging and apoptosis. Oxidative stress agents include peroxides such as hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide, the thiol oxidant diamide, and menadione, a generator of superoxide, amongst others. The present study analyzed the early temporal genome-wide transcriptional response of Saccharomyces cerevisiae to oxidative stress induced by the aromatic peroxide cumene hydroperoxide. The accurate dataset obtained, supported by the use of temporal controls, biological replicates and well controlled growth conditions, provided a detailed picture of the early dynamics of the process. We identified a set of genes previously not implicated in the oxidative stress response, including several transcriptional regulators showing a fast transient response, suggesting a coordinated process in the transcriptional reprogramming. We discuss the role of the glutathione, thioredoxin and reactive oxygen species-removing systems, the proteasome and the pentose phosphate pathway. A data-driven clustering of the expression patterns identified one specific cluster that mostly consisted of genes known to be regulated by the Yap1p and Skn7p transcription factors, emphasizing their mediator role in the transcriptional response to oxidants. Comparison of our results with data reported for hydrogen peroxide identified 664 genes that specifically respond to cumene hydroperoxide, suggesting distinct transcriptional responses to these two peroxides. Genes up-regulated only by cumene hydroperoxide are mainly related to the cell membrane and cell wall, and proteolysis process, while those down-regulated only by this aromatic peroxide are involved in mitochondrial function.

  9. Atypical presentations of celiac disease

    Directory of Open Access Journals (Sweden)

    Balasa Adriana Luminita

    2016-08-01

    Full Text Available In this study we evaluated the association of celiac disease in 81 children with autoimmune disease and genetic syndromes over a two years periods (January 2014 to July 2016 in Pediatric Clinic in Constanta. Because the extraintestinal symptoms are an atypical presentation of celiac disease we determined in these children the presence of celiac disease antibodies: Anti-tissue Transglutaminase Antibody IgA and IgA total serum level as a screening method followeds in selective cases by Anti-tissue Transglutaminase Antibody IgG, anti-endomysial antibodies, deamidated gliadin antibodies IgA and IgG and intestinal biopsia. In our study 8 patients had been diagnosed with celiac disease with extraintestinal symptoms, of which 4 with type 1 diabetes, 1 patient with ataxia, 2 patients with dermatitis herpetiformis and 1 patient with Down syndrome that associate also autoimmune thyroiditis, alopecia areata, enamel hypoplasia.

  10. Differential response of A 68930 and sulpiride in stress-induced gastric ulcers in rats.

    Science.gov (United States)

    Rasheed, Naila; Ahmad, Ausaf; Singh, Neetu; Singh, Pratibha; Mishra, Vaibhav; Banu, Naheed; Lohani, Mohtashim; Sharma, Sharad; Palit, Gautam

    2010-09-15

    Dopamine is linked to gastrointestinal functions. However, its exact nature in stress-induced gastric pathology is still not clear. In the present study, an attempt has been made to identify the effects of dopamine in stress-induced gastric ulcers, and concurrent alterations in various ulcer-influencing factors such as plasma corticosterone levels, gastric mucosal PGE(2) content and proton pump activity. The dopamine D(1) receptor agonist (A 68930) and antagonist (SCH 23390), and D(2) receptor agonist (quinpirole) and antagonist (sulpiride) were used to evaluate their effects on acute stress (single immobilization for 150 min) and chronic unpredictable stress (two different types of stressors for 7 days) induced gastric ulcers in rats. Acute and chronic unpredictable stress significantly increased the gastric ulcer severity, adrenal hypertrophy and corticosterone levels, while gastric mucosal dopamine levels were decreased. Pretreatment of sulpiride (60 mg/kg) significantly reverted the acute stress-induced alterations, while A 68930 (0.25mg/kg) significantly restored the acute and chronic unpredictable stress-induced alterations. In contrast, administration of SCH 23390 (0.1-0.5mg/kg) and quinpirole (0.1-0.5mg/kg) failed to alter acute stress-induced alterations. Further, A 68930 and sulpiride showed different response on proton pump inhibition under in-vitro condition. A 68930 (10-50 microg/ml) inhibited the gastric H(+) K(+)-ATPase activity comparable to positive control omeprazole, while sulpiride (10-50 microg/ml) had no effect. A 68930 also normalized the decreased gastric PGE2 content observed during chronic unpredictable stress. The histopathological evaluation of gastric mucosal tissue supported the observations regarding the gastroprotective effect of sulpiride during acute stress and of A 68930 during both acute and chronic unpredictable stress conditions. Our results provide important insights into the mechanism of dopamine-regulated pathways, which

  11. Pseudoarthrosis in atypical femoral fracture: case report.

    Science.gov (United States)

    Giannotti, S; Bottai, V; Dell'Osso, G; De Paola, G; Ghilardi, M; Guido, G

    2013-11-01

    Atypical femoral fractures can be subsequent to a long-term biphosphonates treatment; they have a high frequency of delayed healing. The authors describe a femoral pseudoarthrosis of an atypical fracture treated with intramedullary nailing in a female after prolonged alendronate therapy. Atypical femoral fractures can be subsequent to a long-term biphosphonates treatment even if, in the literature, there is no clarity on the exact pathogenetic mechanism. The Task Force of the American Society for Bone and Mineral Research described the major and minor features to define atypical fractures and recommends that all the five major features must be present while minor features are not necessary. Another controversial aspect regarding the atypical femoral fractures is the higher frequency of the delayed healing that can be probably related to a suppressed bone turnover caused by a prolonged period of bisphosphonates treatment. This concept could be corroborated by the Spet Tc exam. In the case of a pseudoarthrosis, there is not a standardization of the treatment. In this report, the authors describe a femoral pseudoarthrosis of an atypical fracture treated with intramedullary nailing in a female after prolonged alendronate therapy; the patient was studied with clinical, bioumoral end SPECT-Tc exam of both femurs. Many studies show the relationship between bisphosphonates and the presence of atypical fractures. These fractures should be monitored more closely due to the risk of nonunion and they require considering an initial treatment with pharmacological augmentation to reduce the complications for the patient and the health care costs.

  12. Influence of Momordica charantia on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats

    Directory of Open Access Journals (Sweden)

    Ch. Naga Kavitha

    2011-01-01

    Conclusions: This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.

  13. Lanthanum Prevents Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells by Controlling Early Induction Events

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In a previous study, a salt stress-induced programmed cell death (PCD) model was established in rice root tip cells. Here,by using Wuyunjing 8th rice seedlings, the effects of lanthanum on salt stress-induced PCD early events were studied. The peroxidase (APX). Imidazole (20 mmol/L), the inhibitor of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), could alleviate the occurrence of PCD obviously, and such alleviation could be enhanced by the addition of La3+,indicating the involvement of NADPH oxidase in the salt stress-induced PCD process. Taken together, lanthanum could prevent salt stress-induced PCD occurrence in the rice root tip cells by blocking the calcium influx under stress, which was followed by inhibiting calcium-dependent NADPH oxidase activity to prevent O2·-production and, enhancing the cytosolic antioxidative enzyme activities to scavenge the reactive oxygen species.

  14. Atypical measles syndrome: unusual hepatic, pulmonary, and immunologic aspects.

    Science.gov (United States)

    Frey, H M; Krugman, S

    1981-01-01

    The atypical measles syndrome is a relatively new disease that was first recognized 15 years ago. Initially, it occurred in children who were exposed to wild measles virus several years after they were immunized with killed measles vaccine. It was characterized by a two- to three-day prodrome of high fever, cough, headache, and myalgia followed by a rash that resembled Rocky Mountain spotted fever, scarlet fever, or varicella and associated with roentgenographic evidence of pneumonia with or without pleural effusion. This report highlights three unusual manifestations of this syndrome: 1) transient hepatitis, 2) persistence of pulmonary lesions for several years, and 3) occurrence of excessively high measles hemagglutination-inhibition antibody titers. Today, this syndrome occurs predominantly in adolescents and young adults.

  15. Bisphosphonate-associated atypical subtrochanteric femur fracture.

    Science.gov (United States)

    Wolin, Ely A; Banks, Kevin P; Vroman, Penny J

    2015-03-01

    Bisphosphonates help prevent progressive bone mineralization loss and subsequent osteoporotic fractures. However, long-term bisphosphonate therapy paradoxically increases the risk of a unique injury called an atypical subtrochanteric femur fracture. Despite this, the benefits of bisphosphonates outweigh the risks, because far more pathologic fractures are prevented than induced. The early identification of atypical subtrochanteric femur fractures is important as there is high associated morbidity and mortality. We describe a case of a 76-y-old woman with a completed bisphosphonate-associated atypical subtrochanteric femur fracture.

  16. Atypical imaging appearances of intracranial meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    O' Leary, S. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Adams, W.M. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Parrish, R.W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom); Mukonoweshuro, W. [Radiology Department, Derriford Hospital, Plymouth (United Kingdom)]. E-mail: William.mukonoweshuro@phnt.swest.nhs.uk

    2007-01-15

    Meningiomas are the commonest primary, non-glial intracranial tumours. The diagnosis is often correctly predicted from characteristic imaging appearances. This paper presents some examples of atypical imaging appearances that may cause diagnostic confusion.

  17. Atypical disease phenotypes in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Levine, Arie; de Bie, Charlotte I; Turner, Dan

    2013-01-01

    Definitive diagnosis of pediatric ulcerative colitis (UC) may be particularly challenging since isolated colitis with overlapping features is common in pediatric Crohn's disease (CD), while atypical phenotypes of UC are not uncommon. The Paris classification allows more accurate phenotyping...

  18. Pharmacological evaluation of the stress-induced social avoidance model of anxiety.

    Science.gov (United States)

    Leveleki, Cs; Sziray, N; Levay, G; Barsvári, B; Soproni, K; Mikics, E; Haller, J

    2006-03-31

    We have shown earlier that mild electric shocks induce a lasting social avoidance in male rats. Here we investigated whether shock-induced social avoidance can be developed into a laboratory model of stress-induced anxiety. The putative new model would assess sub-chronic, stress-induced anxiety (as opposed to tests based on natural fear) in a heterologous context (as opposed to classical fear conditioning). A single exposure to mild electric shocks induced a robust social avoidance that lasted more than 5 days. Low doses of chlordiazepoxide (0.5, 1 mg/kg), diazepam (0.5, 1, 5 mg/kg), buspirone (0.3, 1 mg/kg), and fluoxetine (1, 3, 5 mg/kg) abolished this effect, whereas the anxiogenic compound m-chlorophenylpiperazine (0.5-3 mg/kg) induced social avoidance in unshocked rats. These effects were produced at doses that did not affect locomotion in the open field. Haloperidol (0.05, 0.1, 1, 5 mg/kg) influenced social avoidance at sedative doses only. The sensitivity of the model to anxiolytic agents was compromised at high (sedating) doses. Taken conjointly, these data show that shock-induced social avoidance can be used to assess the anxiolytic potential of compounds. In addition to predictive validity, the model appears to show construct and face validity as well: stress is among the etiological factors of, whereas social avoidance simulates the social deficits seen in, a variety of anxiety disorders. The model may be used to study the effects of anxiolytics on sub-chronic states of stress-induced anxiety.

  19. GAD65 haplodeficiency conveys resilience in animal models of stress-induced psychopathology

    Directory of Open Access Journals (Sweden)

    Iris eMüller

    2014-08-01

    Full Text Available GABAergic mechanisms are critically involved in the control of fear and anxiety, but their role in the development of stress-induced psychopathologies, including post-traumatic stress disorder (PTSD and mood disorders is not sufficiently understood. We studied these functions in two established mouse models of risk factors for stress-induced psychopathologies employing variable juvenile stress and/or social isolation. A battery of emotional tests in adulthood revealed the induction of contextually generalized fear, anxiety, hyperarousal and depression-like symptoms in these paradigms. These reflect the multitude and complexity of stress effects in human PTSD patients. With factor analysis we were able to identify parameters that reflect these different behavioral domains in stressed animals and thus provide a basis for an integrated scoring of affectedness more closely resembling the clinical situation than isolated parameters. To test the applicability of these models to genetic approaches we further tested the role of GABA using heterozygous mice with targeted mutation of the GABA synthesizing enzyme GAD65 (GAD65+/- mice, which show a delayed postnatal increase in tissue GABA content in limbic and cortical brain areas. Unexpectedly, GAD65(+/- mice did not show changes in exploratory activity regardless of the stressor type and were after the variable juvenile stress procedure protected from the development of contextual generalization in an auditory fear conditioning experiment. Our data demonstrate the complex nature of behavioral alterations in rodent models of stress-related psychopathologies and suggest that GAD65 haplodeficiency, likely through its effect on the postnatal maturation of GABAergic transmission, conveys resilience to some of these stress-induced effects.

  20. Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

    Science.gov (United States)

    Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

    2016-05-01

    Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress

  1. Differential effects of stress-induced cortisol responses on recollection and familiarity-based recognition memory.

    Science.gov (United States)

    McCullough, Andrew M; Ritchey, Maureen; Ranganath, Charan; Yonelinas, Andrew

    2015-09-01

    Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response.

  2. An animal model of stress-induced cardiomyopathy utilizing the social defeat paradigm.

    Science.gov (United States)

    Wideman, Cyrilla H; Cierniak, Kayla H; Sweet, Wendy E; Moravec, Christine S; Murphy, Helen M

    2013-08-15

    Stress-induced cardiomyopathy (SIC) is a form of acute heart disease triggered by extreme psychological stress. In patients who develop SIC, the outward symptoms are almost indistinguishable from acute myocardial infarction (AMI). However, some important criteria differentiate patients with SIC from those with AMI. Patients with SIC: (1) experience some form of extreme psychological stress from minutes to hours before developing heart disease, (2) do not suffer from atherosclerosis or coronary artery obstruction, and 3) exhibit abnormal ballooning of the left ventricle. In the present study, the resident-intruder (RI) social defeat test was investigated as a potential rat model for stressed-induced cardiomyopathy. Adult Long-Evans rats were implanted with a biotelemetry transmitter for ECG recordings and habituated for two weeks. An intruder rat was placed in the cage of a resident rat behind a wire-mesh partition for 5 min. The partition was then removed for 5 min to allow direct contact between the intruder and resident rats. After this interval, the wire-mesh partition was replaced and the intruder rat remained behind the partition for an additional 50 min. Behavioral responses were noted and ECG recordings were collected during the entire 60-min testing period. Upon completion of the test, the intruder rat was removed from the cage of the resident rat and sacrificed. The heart was examined and blood was collected. Heart weight/body weight ratio, left ventricle/body weight ratio, heart length, plasma corticosterone levels, and plasma troponin I levels of intruder rats were significantly higher as compared to control rats. Intruder rats significantly increased their heart rate during the first 5 min of the RI test. It is concluded that the RI test to induce social defeat is a novel rodent paradigm for modeling stress-induced cardiomyopathy in the human.

  3. Atypical presentations of Wolframs syndrome

    Directory of Open Access Journals (Sweden)

    S Saran

    2012-01-01

    Full Text Available Background: Wolfram syndrome is a rare hereditary or sporadic neurodegenerative disorder also known as DIDMOAD. The classically described presentation is of insulin-dependent diabetes, followed by optic atrophy, central diabetes insipidus, and sensory neural deafness. Also included are less well-described presentations of Wolframs syndrome. We here present three cases of atypical presentation of this syndrome. Case 1: A 15-year-old boy with insulin-dependent diabetes was presented for evaluation of depressive symptoms associated with suicidal tendency. Neuropsychiatric manifestations are described with Wolframs syndrome, and wolframin gene, in recessive inheritance, is associated with psychiatric illnesses without other manifestations of Wolframs syndrome. Case 2: A 17-year-old diabetic boy on insulin with good control of blood sugar presented for evaluation of delayed puberty. Central hypogonadism and other anterior pituitary hormone dysfunctions are the less publicized hormone dysfunctions in Wolframs syndrome. Case 3: A 23-year-old female who was on insulin for diabetes for the past 14 years, got admitted for evaluation of sudden loss of vision. This patient had developed a vitreous hemorrhage and, on evaluation, was found to have optic atrophy, sensory neural hearing loss, and diabetes insipidus, and presented differently from the gradual loss of vision described in Wolframs syndrome. Conclusion: Wolframs syndrome being a multisystem degenerative disorder can have myriad other manifestations than the classically described features. Neuropsychiatric manifestations, depression with suicidal risk, central hypogonadism, and secondary adrenal insufficiency are among the less well-described manifestations of this syndrome.

  4. Atypical presentations of neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Douglas Sato

    2011-10-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4 has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks.

  5. ATYPICAL ANTIPSYCHOTICS FROM SCRATCH TO THE PRESENT

    Directory of Open Access Journals (Sweden)

    Ashish Chauhan*, Amit Mittal, Pradeep Kumar Arora

    2013-01-01

    Full Text Available Mental illness constitutes the second-largest disease burden in the United States. Psychosis is one of the most common and severe mental illnesses. It is an extremely devastating condition characterised by delusions, hallucinations, distortion of thoughts and deteriorating social functioning experiences. Psychosis in all human societies has approximately same incidence of occurrence as in accordance to “anthropo-parity principle.” It has large economic impact on various aspects of cognition, health, and quality of life which has devastated effects on its sufferers and facing them large economic burden. Psychosis (Schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyper-stimulation of dopamine function in the brain, particularly in the mesolimbic pathway. Consequences of antipsychotic treatment are far reaching and expensive. Detrimental extrapyramidal side effects associated with conventional antipsychotics and non-compliance among patients limits long term treatment with conventional antipsychotics. It gives rise to a new class, atypical antipsychotics owning low propensity to cause EPS, efficacy against refractory cases and better control over negative symptoms, better tolerance and compliance along with lower relapse rate and safer adverse effect profile. Atypical antipsychotics have revolutionized the treatment of psychosis, now being the treatment of choice for patients with psychosis. The positive therapeutic experience with the atypical antipsychotics in the treatment of psychosis and their favourable effects outweighs their unfavourable adverse effects. Though atypical antipsychotics are widely prescribed in the treatment of schizophrenia, however not a single atypical antipsychotic drug having any exceptional efficacy and safety profile. Thus, there is still a lot of research needed to be carried out in the development of novel atypical antipsychotics. This review is comprehensive appraisal about

  6. Stress-Induced Phase Transformation in Incompressible Materials and Stability of Multi-Phase Deformation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The stress-induced phase transformation in incompressible materials and the interfacial stability of multi-phase deformation were studied. The existence of multi-phase deformation was determined through exploring whether the material would lose the strong ellipticity at some deformation gradient.Then, according to the stability criterion which is based on a quasi-static approach, the stability of the multi-phase deformation in incompressible materials was investigated by studying the growth/decay behaviour of the interface in the undeformed configuration when it is perturbed. At last, the way to define multi-phase deformation in incompressible materials was concluded and testified by a corresponding numerical example.

  7. Thermal Stress-Induced Birefringence in Borate Glass Irradiated by Femtosecond Laser Pulses

    Institute of Scientific and Technical Information of China (English)

    DAI Ye; YU Bing-Kun; LU Bo; QIU Jian-Rong; YAN Xiao-Na; JIANG Xiong-Wei; ZHU Cong-Shan

    2005-01-01

    @@ Thermal stress-induced birefringence in borate glass which has been irradiated by 800-nm femtosecond laser pulses is observed under cross-polarized light. Due to the high temperature and pressure formed in the focal volume, the material at the edge of the micro-modified region is compressed between the expanding region and the unheated one, then stress emerges. Raman spectroscopy is used to investigate the stress distribution in the micro-modified region and indicates the redistributions of density and refractive index by Raman peak shift. We suggest that this technique can develop waveguide polarizers and Fresnel zone plates in integrated optics.

  8. Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Motoharu Hayashi

    Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

  9. The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia.

    Science.gov (United States)

    Yesilyurt, Ozgur; Seyrek, Melik; Tasdemir, Serdar; Kahraman, Serdar; Deveci, Mehmet Salih; Karakus, Emre; Halici, Zekai; Dogrul, Ahmet

    2015-09-05

    The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia. Stress-induced analgesia was induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception. Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone did not produce analgesia in unstressed mice. These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia.

  10. Current interruption transients calculation

    CERN Document Server

    Peelo, David F

    2014-01-01

    Provides an original, detailed and practical description of current interruption transients, origins, and the circuits involved, and how they can be calculated Current Interruption Transients Calculationis a comprehensive resource for the understanding, calculation and analysis of the transient recovery voltages (TRVs) and related re-ignition or re-striking transients associated with fault current interruption and the switching of inductive and capacitive load currents in circuits. This book provides an original, detailed and practical description of current interruption transients, origins,

  11. Role of Glia in Stress-Induced Enhancement and Impairment of Memory

    Science.gov (United States)

    Pearson-Leary, Jiah; Osborne, Danielle Maria; McNay, Ewan C.

    2016-01-01

    Both acute and chronic stress profoundly affect hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesia. Often overlooked in consideration of the impact of stress on cognitive processes, and specifically memory, is the important contribution of glia as a target for stress-induced changes. Astrocytes, microglia, and oligodendrocytes all have unique contributions to learning and memory. Furthermore, these three types of glia express receptors for both norepinephrine and glucocorticoids and are hence immediate targets of stress hormone actions. It is becoming increasingly clear that inflammatory cytokines and immunomodulatory molecules released by glia during stress may promote many of the behavioral effects of acute and chronic stress. In this review, the role of traditional genomic and rapid hormonal mechanisms working in concert with glia to affect stress-induced learning and memory will be emphasized. PMID:26793072

  12. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  13. Role of glia in stress-induced enhancement and impairment of memory

    Directory of Open Access Journals (Sweden)

    Jiah ePearson-Leary

    2016-01-01

    Full Text Available Both acute and chronic stress profoundly affects hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesia. Often overlooked in consideration of the impact of stress on cognitive processes, and specifically memory, is the important contribution of glia as a target for stress-induced changes. Astrocytes, microglia, and oligodendrocytes all have unique contributions to learning and memory. Furthermore, these three types of glia express receptors for both norepinephrine and glucocorticoids and are hence immediate targets of stress hormone actions. It is becoming increasingly clear that inflammatory cytokines and immunomodulatory molecules released by glia during stress may promote many of the behavioral effects of acute and chronic stress. In this review, the role of traditional genomic and rapid hormonal mechanisms working in concert with glia to affect stress-induced learning and memory will be emphasized.

  14. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

    Directory of Open Access Journals (Sweden)

    Antonio Aubry

    2016-10-01

    Full Text Available Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR and norepinephrine release within the amygdala leads to the mobilization of AMPA receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  15. Effects of (-)-Sesamin on Chronic Stress-Induced Anxiety Disorders in Mice.

    Science.gov (United States)

    Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Yi, Bo Ram; Lee, Kyung Eun; Lee, Myung Koo

    2016-12-19

    This study investigated the effects of (-)-sesamin on chronic electric footshock (EF) stress-induced anxiety disorders in mice. Mice were treated with (-)-sesamin (25 and 50 mg/kg) orally once a day for 21 days prior to exposure to EF stress (0.6 mA, 1 s every 5 s, 3 min). Mice treated with (-)-sesamin (25 and 50 mg/kg) exhibited less severe decreases in the number of open arm entries and time spent on open arms in the elevated plus-maze test and the distance traveled in the open field test following exposure to chronic EF stress. Similarly, mice treated with (-)-sesamin exhibited significantly less severe decreases in brain levels of dopamine, norepinephrine, and serotonin following exposure to chronic EF stress. Increases in serum levels of corticosterone and expression of c-Fos were also less pronounced in mice treated with (-)-sesamin (25 and 50 mg/kg). These results suggest that (-)-sesamin may protect against the effects of chronic EF stress-induced anxiety disorders by modulating dopamine, norepinephrine, and serotonin levels, c-Fos expression, and corticosterone levels.

  16. Mitofusin-2 protects against cold stress-induced cell injury in HEK293 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenbin; Chen, Yaomin; Yang, Qun; Che, Honglei; Chen, Xiangjun; Yao, Ting; Zhao, Fang; Liu, Mingchao; Ke, Tao [Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2010-06-25

    Mitochondrial impairment is hypothesized to contribute to cell injury during cold stress. Mitochondria fission and fusion are closely related in the function of the mitochondria, but the precise mechanisms whereby these processes regulate cell injury during cold stress remain to be determined. HEK293 cells were cultured in a cold environment (4.0 {+-} 0.1 {sup o}C) for 2, 4, 8, or 12 h. Western blot analyses showed that these cells expressed decreased fission-related protein Drp1 and increased fusion-related protein Mfn2 at 4 h; meanwhile, electron microscopy analysis revealed large and long mitochondrial morphology within these cells, indicating increased mitochondrial fusion. With silencing of Mfn2 but not of Mfn1 by siRNA promoted cold-stress-induced cell death with decreased ATP production in HEK293 cells. Our results show that increased expression of Mfn2 and mitochondrial fusion are important for mitochondrial function as well as cell survival during cold stress. These findings have important implications for understanding the mechanisms of mitochondrial fusion and fission in cold-stress-induced cell injury.

  17. Stress-induced martensitic transformation in metastable austenitic stainless steels: Effect on fatigue crack growth rate

    Science.gov (United States)

    Khan, Z.; Ahmed, M.

    1996-04-01

    This paper addresses the influence of cyclic stress-induced martensitic transformation on fatigue crack growth rates in metastable austenitic stainless steels. At low applied stress and mean stress values in AISI type 301 stainless steel, fatigue crack growth rate is substantially retarded due to a cyclic stress-induced γ-α' and γ-ɛ martensitic transformation occurring at the crack-tip plastic zone. It is suggested that the transformation products produce a compressive residual stress at the tip of the fatigue crack, which essentially lowers the effective stress intensity and hence retards the fatigue crack growth rate. At high applied stress or mean stress values, fatigue crack growth rates in AISI type 301 steels become almost equal to those of stable AISI type 302 alloy. As the amount of transformed products increases (with an increase in applied or mean stress), the strain-hardening effect brought about by the transformed martensite phase appears to accelerate fatigue crack growth, offsetting the contribution from the compressive residual stress produced by the positive volume change of γ → α' or ɛ transformation.

  18. Thermal Stress-Induced Depolarization Loss in Conventional and Panda-Shaped Photonic Crystal Fiber Lasers

    Science.gov (United States)

    Mousavi, Seyedeh Laleh; Sabaeian, Mohammad

    2016-10-01

    We report on the modeling of the depolarization loss in the conventional and panda-shaped photonic crystal fiber lasers (PCFLs) due to the self-heating of the fiber, which we call it thermal stress-induced depolarization loss (TSIDL). We first calculated the temperature distribution over the fiber cross sections and then calculated the thermal stresses/strains as a function of heat load per meter. Thermal stress-induced birefringence (TSIB), which is defined as | n x - n y |, in the core and cladding regions was calculated. Finally, TSIDL was calculated for the conventional and panda-shaped PCFLs as a function of fiber length and, respectively, saturated values of 22 and 25 % were obtained which were independent of heat load per meter. For panda-shaped PCFLs, prior to being saturated, an oscillating and damping behavior against the fiber length was seen where in some lengths reached 35 %. The results are close to an experimental value of 30 % reported for a pulsed PCFL (Limpert et al., Opt Express 12:1313-1319, 2004) where the authors reported a degree of polarization of 70 % (i.e., a depolarization of 30 %). The most important result of this work is a saturation behavior of TSIDL at long-enough lengths of the fiber laser which is independent of heat load per meter. To our knowledge, this the first report of TSIBL for PCFLs.

  19. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala.

    Science.gov (United States)

    Aubry, Antonio V; Serrano, Peter A; Burghardt, Nesha S

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR) and norepinephrine release within the amygdala leads to the mobilization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  20. Role of Glia in Stress-Induced Enhancement and Impairment of Memory.

    Science.gov (United States)

    Pearson-Leary, Jiah; Osborne, Danielle Maria; McNay, Ewan C

    2015-01-01

    Both acute and chronic stress profoundly affect hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesia. Often overlooked in consideration of the impact of stress on cognitive processes, and specifically memory, is the important contribution of glia as a target for stress-induced changes. Astrocytes, microglia, and oligodendrocytes all have unique contributions to learning and memory. Furthermore, these three types of glia express receptors for both norepinephrine and glucocorticoids and are hence immediate targets of stress hormone actions. It is becoming increasingly clear that inflammatory cytokines and immunomodulatory molecules released by glia during stress may promote many of the behavioral effects of acute and chronic stress. In this review, the role of traditional genomic and rapid hormonal mechanisms working in concert with glia to affect stress-induced learning and memory will be emphasized.

  1. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Directory of Open Access Journals (Sweden)

    Penny J Tricker

    2015-09-01

    Full Text Available The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defence ‘priming’ and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity’s adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  2. A new murine model of stress-induced complex atherosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Amir H. Najafi

    2013-03-01

    The primary purpose of this investigation was to determine whether ApoE−/− mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE−/− mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.

  3. Expression of HSF2 decreases in mitosis to enable stress-inducible transcription and cell survival.

    Science.gov (United States)

    Elsing, Alexandra N; Aspelin, Camilla; Björk, Johanna K; Bergman, Heidi A; Himanen, Samu V; Kallio, Marko J; Roos-Mattjus, Pia; Sistonen, Lea

    2014-09-15

    Unless mitigated, external and physiological stresses are detrimental for cells, especially in mitosis, resulting in chromosomal missegregation, aneuploidy, or apoptosis. Heat shock proteins (Hsps) maintain protein homeostasis and promote cell survival. Hsps are transcriptionally regulated by heat shock factors (HSFs). Of these, HSF1 is the master regulator and HSF2 modulates Hsp expression by interacting with HSF1. Due to global inhibition of transcription in mitosis, including HSF1-mediated expression of Hsps, mitotic cells are highly vulnerable to stress. Here, we show that cells can counteract transcriptional silencing and protect themselves against proteotoxicity in mitosis. We found that the condensed chromatin of HSF2-deficient cells is accessible for HSF1 and RNA polymerase II, allowing stress-inducible Hsp expression. Consequently, HSF2-deficient cells exposed to acute stress display diminished mitotic errors and have a survival advantage. We also show that HSF2 expression declines during mitosis in several but not all human cell lines, which corresponds to the Hsp70 induction and protection against stress-induced mitotic abnormalities and apoptosis.

  4. Novel targets for endoplasmic reticulum stress-induced apoptosis in B-CLL.

    Science.gov (United States)

    Rosati, Emanuela; Sabatini, Rita; Rampino, Giuliana; De Falco, Filomena; Di Ianni, Mauro; Falzetti, Franca; Fettucciari, Katia; Bartoli, Andrea; Screpanti, Isabella; Marconi, Pierfrancesco

    2010-10-14

    A better understanding of apoptotic signaling in B-chronic lymphocytic leukemia (B-CLL) cells may help to define new therapeutic strategies. This study investigated endoplasmic reticulum (ER) stress signaling in spontaneous apoptosis of B-CLL cells and whether manipulating ER stress increases their apoptosis. Results show that a novel ER stress-triggered caspase cascade, initiated by caspase-4 and involving caspase-8 and -3, plays an important role in spontaneous B-CLL cell apoptosis. ER stress-induced apoptosis in B-CLL cells also involves CHOP/GADD153 up-regulation, increased JNK1/2 phosphorylation, and caspase-8-mediated cleavage of Bap31 to Bap20, known to propagate apoptotic signals from ER to mitochondria. In ex vivo B-CLL cells, some apoptotic events associated with mitochondrial pathway also occur, including mitochondrial cytochrome c release and caspase-9 processing. However, pharmacologic inhibition studies show that caspase-9 plays a minor role in B-CLL cell apoptosis. ER stress also triggers survival signals in B-CLL cells by increasing BiP/GRP78 expression. Manipulating ER signaling by siRNA down-regulation of BiP/GRP78 or treating B-CLL cells with 2 well-known ER stress-inducers, tunicamycin and thapsigargin, increases their apoptosis. Overall, our findings show that ER triggers an essential pathway for B-CLL cell apoptosis and suggest that genetic and pharmacologic manipulation of ER signaling could represent an important therapeutic strategy.

  5. Stress-induced crack path in Aji granite under tensile stress

    Science.gov (United States)

    Kudo, Yozo; Sano, Osam; Murashige, Naokuni; Mizuta, Yoshiaki; Nakagawa, Koji

    1992-12-01

    The double-torsion test using Aji granite was carried out to investigate the interaction between stress-induced crack path and mineral grains. Crack velocities were controlled at range 10-7 m/s to 10-1 m/s. After the stressed specimens were dyed, we checked the crack path by thin section analysis, using an optical microscope. The stress-induced crack path was divided into two types, transgranular and intergranular cracks, and each path was subdivided with respect to mineral grains. In spite of the extensive range of crack velocities, the ratios between the transgranular and intergranular crack lengths did not change. The crack paths were all jagged, and often showed detour around the grain boundary when faced with obstacles like hard grains or preexisting cracks. That is to say, quartz grain played an important role as an obstacle. Feldspar grain could change the crack path because of its cleavage plane. Biolite grain had a serious effect on the path even if its constitution ratio is very small. Fractal dimensions of the crack paths were calculated by three methods, as indicators of surface roughness. The fractal dimensions were shown in a slight trend with the change of crack velocity. This trend can be explained from the point of limited cracking rate in stress corrosion.

  6. Solcoseryl in prevention of stress-induced gastric lesions and healing of chronic ulcers.

    Science.gov (United States)

    Konturek, S J; Drozdowicz, D; Pytko-Polonczyk, J; Brzozowski, T; Bielański, W

    1991-03-01

    Solcoseryl, a deproteinized extract of calf blood, protects the gastric mucosa against various topical irritants and enhances the healing of chronic gastric ulcerations but the mechanisms of these effects have been little studied. This study was designed to elucidate the active principle in Solcoseryl and to determine the role of prostaglandins (PG) and polyamines in the antiulcer properties of this agent. Using both, the radioimmunoassay and radioreceptor assay, EGF-like material was detected in Solcoseryl preparation. Solcoseryl given s.c. prevented the formation of stress-induced gastric lesions and this was accompanied by an increase in the generation of PGE2 in the gastric mucosa. Similar effects were obtained with EGF. Pretreatment with indomethacin, to suppress mucosal generation of prostaglandins (PG), greatly augmented stress-induced gastric ulcerations and antagonized the protection exerted by both Solcoseryl and EGF. Solcoseryl, like EGF, enhanced the healing of chronic gastro-duodenal ulcerations. This effect was abolished by the pretreatment with difluoromethylornithine, an inhibitor of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines. The healing effects of Solcoseryl and EGF was also reduced by prednisolone which decreased the angiogenesis in the granulation tissue in the ulcer area. These results indicate that Solcoseryl 1. contains EGF-like material, 2. displays the protective and ulcer healing effects similar to those of EGF and involving both PG and polyamines and 3. acts via similar mechanism as does EGF.

  7. Involvement of Protein Phosphorylation in Water Stress-induced Antioxidant Defense in Maize Leaves

    Institute of Scientific and Technical Information of China (English)

    Shu-cheng Xu; Hai-dong Ding; Feng-xia Su; A-ying Zhang; Ming-yi Jiang

    2009-01-01

    Using pharmacological and biochemical approaches, the role of protein phosphorylation and the interrelationship between water stress-enhanced kinase activity, antioxidant enzyme activity, hydrogen peroxide (H2O2) accumulation and endogenous abscisic acid in maize (Zea mays L.) leaves were investigated. Water-stress upregulated the activities of total protein phosphorylation and Ca2+ -dependent protein kinase, and the upregulation was blocked in abscisic acid-deficient vp5 mutant. Furthermore, pretreatments with a nicotinamide adenine dinucleotide phosphate oxidase inhibitor and a scavenger of H2O2 significantly reduced the increased activities of total protein kinase and Ca2+-dependent protein kinase in maize leaves exposed to water stress. Pretreatments with different protein kinase inhibitors also reduced the water stress-induced H2O2 production and the water stress-enhanced activities of antioxidant enzymes such as superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase. The data suggest that protein phosphorylation and H2O2 generation are required for water stress-induced antioxidant defense in maize leaves and that crosstalk between protein phosphorylation and H2O2 generation may occur.

  8. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Science.gov (United States)

    Zhu, Li-Juan; Liu, Meng-Ying; Li, Huan; Liu, Xiao; Chen, Chen; Han, Zhou; Wu, Hai-Yin; Jing, Xing; Zhou, Hai-Hui; Suh, Hoonkyo; Zhu, Dong-Ya; Zhou, Qi-Gang

    2014-01-01

    Hypothalamus-pituitary-adrenal (HPA) hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR) - neuronal nitric oxide synthesis enzyme (nNOS) - nitric oxide (NO) pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  9. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  10. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway

    Science.gov (United States)

    Jung, T.W.; Lee, M.W.; Lee, Y.-J.; Kim, S.M.

    2012-01-01

    Type 2 diabetes mellitus is thought to be partially associated with endoplasmic reticulum (ER) stress toxicity on pancreatic beta cells and the result of decreased insulin synthesis and secretion. In this study, we showed that a well-known insulin sensitizer, metformin, directly protects against dysfunction and death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase activation. We also showed that exposure of NIT-1 cells to metformin (5mM) increases cellular resistance against ER stress-induced NIT-1 cell dysfunction and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on cell function and death. Metformin-mediated protective effects on ER stress-induced apoptosis were not a result of an unfolded protein response or the induced inhibitors of apoptotic proteins. In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.

  11. Clinical Presentation of Atypical Genital Herpes

    Institute of Scientific and Technical Information of China (English)

    李俊杰; 梁沛杨; 罗北京

    2002-01-01

    Objective: To make a clinical analysis on the basis of 36cases of atypical genital herpes (GH) patients. Methods: Thirty-six cases of atypical GH were diagnosedclinically, and their case histories, symptoms and signs wererecorded in detail and followed up. Polymerase chain reaction(PCR) was adopted for testing HSV2-DNA with cotton-tippedswabs. Enzyme-linked immuno sorbent assay (ELISA) forserum anti-HSV2-IgM was done to establish a definfiivediagnosis. Other diagnoses were excluded at the same time bytesting for related pathogens including fungi, Chlamydia,Mycoplasma, Treponema pallidum, gonococci, Trichomonas,etc. Results: The main clinical manifestations of atypical GHwere: (1) small genital ulcers; (2) inflammation of urethralmeatus; (3) nonspecific genital erythema; (4) papuloid noduleson the glands; (5) nonspecific vaginitis. Twenty-three cases(64%) tested by PCR were HSV2-DNA sera-positive, and 36cases (100 %) anti-HSV2-IgM sera-positive by ELISA. Conclusion: atypical HSV is difficult to be diagnosed. Butthe combination of PCR and ELIAS will be helpful to thediagnosis of atypical HSV.

  12. Atypical aging in Down syndrome.

    Science.gov (United States)

    Zigman, Warren B

    2013-01-01

    divided into two sections. The first section will review typical and atypical aging patterns in somatic issues in elder adults with DS; the second section will review the multifaceted relationship between AD and DS.

  13. Protective role of metallothionein in stress-induced gastric ulcer in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Jiang; Lin Chang; Chun-Shui Pan; Yong-Fen Qi; Chao-Shu Tang

    2005-01-01

    AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced

  14. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  15. Neuroleptic malignant syndrome induced by atypical antipsychotics.

    Science.gov (United States)

    Farver, Debra K

    2003-01-01

    A review of the English literature confirms that neuroleptic malignant syndrome (NMS) occurs with both traditional and atypical antipsychotic medications. Published reports of NMS induced by the traditional antipsychotics have given the practitioner valuable information on the prevention and treatment of this adverse effect. Case reports have also been published concerning NMS and clozapine, risperidone, olanzapine and quetiapine. By evaluating the case reports of atypical antipsychotic-induced NMS, valuable information may be obtained concerning similarities or differences from that induced by the traditional antipsychotics. The case reports of NMS with atypical antipsychotics were evaluated for diagnosis, age/sex of patient, risk factors, antipsychotic doses and duration of use, symptoms of NMS, and clinical course.

  16. [Atypical antipsychotic-induced weight gain].

    Science.gov (United States)

    Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.

  17. A Detailed Observation on Successive Stress-Induced Martensite Transformation in CuAlMnZnZr Alloy Polycrystalline Above Af

    Institute of Scientific and Technical Information of China (English)

    Li Zhou; Wang Ming-pu; Tang Wang; Guo Ming-xing

    2004-01-01

    The successive stress-induced martensite morphologies and mechanisms in polycrystalline CuAlMnZnZr samples have been examined. By applying stress to the uniform β1 matrix, two or more orientation plates of M18R martensite are stress-induced in a grain. With further increasing stress, one orientation plate depletes the other and coalesces into a single region in some view field. The mechanisms by which these are developed have been ascertained, and include variant-variant coalescence, stress-induced martensite to martensite transformation and the complicated cross-like stress-induced martensite formation.

  18. Resistance of LaCl3 to Oxidative Stress Induced by 2, 4-Dichlorophenoxy

    Institute of Scientific and Technical Information of China (English)

    Jia Yanxia; Gao Yongsheng; Zeng Fuli

    2005-01-01

    Cucumber seedlings were sprayed with different concentrations of LaCl3 for 3 d continuously. After 7 d of this treatment, the plants were treated with 1200 mg·L-1 2,4-dichlorophennoxy(2,4-D) for 24 h. The leaves were harvested and rinsed with 5 mmol · L-1 EDTA. The concentrations of photosynthetic pigments, soluble protein and metabolites related to oxidative stress and the activities of antioxidant enzymes in leaves were assayed. The results show that the treatment with appropriate concentration of LaCl3 has resistant effect on oxidative stress induced by 2, 4-D. Proper concentration of LaCl3 promotes the activity of antioxidant system in plants and alleviates the damage caused by 2, 4-D.

  19. Deep-Trap Stress Induced Leakage Current Model for Nominal and Weak Oxides

    Science.gov (United States)

    Kamohara, Shiro; Hu, Chenming; Okumura, Tsugunori

    2008-08-01

    We have developed a model of the stress-induced leakage current (SILC) based on the inelastic trap-assisted tunneling (ITAT) by introducing a trap with a deep energy level of 3.6 eV from the bottom of the conduction band. This model can explain both of two field dependencies, i.e., a field dependence of the direct tunneling (DT) for A-mode SILC and that of the Fowler-Nordheim (FN) tunneling for B-mode SILC by analytical equations of a common form. For simple analytical equations, we introduce the most favorable trap position (MFTP), which gives the largest contribution to the leakage current. The trap area density for A-mode SILC of around 1×1010 cm-2 and the area density of the leakage paths for B-mode SILC of 1×102 cm-2 were obtained by comparisons between the experimental results and the present model.

  20. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  1. Nutritional stress induces exchange of cell material and energetic coupling between bacterial species.

    Science.gov (United States)

    Benomar, Saida; Ranava, David; Cárdenas, María Luz; Trably, Eric; Rafrafi, Yan; Ducret, Adrien; Hamelin, Jérôme; Lojou, Elisabeth; Steyer, Jean-Philippe; Giudici-Orticoni, Marie-Thérèse

    2015-02-23

    Knowledge of the behaviour of bacterial communities is crucial for understanding biogeochemical cycles and developing environmental biotechnology. Here we demonstrate the formation of an artificial consortium between two anaerobic bacteria, Clostridium acetobutylicum (Gram-positive) and Desulfovibrio vulgaris Hildenborough (Gram-negative, sulfate-reducing) in which physical interactions between the two partners induce emergent properties. Molecular and cellular approaches show that tight cell-cell interactions are associated with an exchange of molecules, including proteins, which allows the growth of one partner (D. vulgaris) in spite of the shortage of nutrients. This physical interaction induces changes in expression of two genes encoding enzymes at the pyruvate crossroads, with concomitant changes in the distribution of metabolic fluxes, and allows a substantial increase in hydrogen production without requiring genetic engineering. The stress induced by the shortage of nutrients of D. vulgaris appears to trigger the interaction.

  2. CHARACTERISTICS OF STRESS-INDUCED TRANSFORMATION AND MICROSTRUCTURE EVOLUTION IN Cu-BASED SMA

    Institute of Scientific and Technical Information of China (English)

    Cheng Peng; Xingyao Wang; Yongzhong Huo

    2008-01-01

    The mechanical behavior of shape memory alloys (SMAs) is closely related to the formation and evolution of its microstructures. Through theoretical analysis and experimental ob-servations, it was found that the stress-induced martensitic transformation process of single crys-tal Cu-based SMA under uniaxial tension condition consisted of three periods: nucleation, mixed nucleation and growth, and merging due to growth. During the nucleation, the stress dropped rapidly and the number of interfaces increased very fast while the phase fraction increased slowly.In the second period, both the stress and the interface number changed slightly but the phase fraction increased dramatically. Finally, the stress and the phase fraction changed slowly while the number of interfaces decreased quickly. Moreover, it was found that the transformation could be of multi-stage: sharp stress drops at several strains and correspondingly, the nucleation and growth process occurred quasi-independently in several parts of the sample.

  3. Effect of loading speed on the stress-induced magnetic behavior of ferromagnetic steel

    Science.gov (United States)

    Bao, Sheng; Gu, Yibin; Fu, Meili; Zhang, Da; Hu, Shengnan

    2017-02-01

    The primary goal of this research is to investigate the effect of loading speed on the stress-induced magnetic behavior of a ferromagnetic steel. Uniaxial tension tests on Q235 steel were carried out with various stress levels under different loading speeds. The variation of the magnetic signals surrounding the tested specimen was detected by a fluxgate magnetometer. The results indicated that the magnetic signal variations depended not only on the tensile load level but on the loading speed during the test. The magnetic field amplitude seemed to decrease gradually with the increase in loading speed at the same tensile load level. Furthermore, the evolution of the magnetic reversals is also related to the loading speed. Accordingly, the loading speed should be considered as one of the influencing variables in the Jies-Atherton model theory of the magnetomechanical effect.

  4. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Science.gov (United States)

    Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302

  5. Inhibition of stress induced hyperglucagonemia by administration of glucose in normal and alloxan-diabetic rat.

    Science.gov (United States)

    Klimes, I; Jurcovicová, J; Németh, S; Jezová, D; Vigas, M

    1981-01-01

    The increase in plasma pancreatic glucagon which is known to occur under several stress conditions was confirmed in fed and 18 h prefasted rats subjected to a low, "stress producing" dose of the Noble-collip drum procedure (400 revolutions per 400 s). A single dose of exogenous glucose ( 1 g kg-1) injected 3 min and 20 s before stress into the jugular vein of intact fasted or fed animals anesthetized with pentobarbital 930 mg kg-1) completely abolished their hyperglucagonemic response in stress. In alloxan-diabetic hyperglycemic rats the stress-hyperglucagonemia was exaggerated, but was also suppressible by exogenous glucose. It was concluded that: 1. the stress induced hyperglucagonemic response of both intact and alloxan-diabetic rats was completely suppressible by administration of i.v. bolus of exogenous glucose; 2. the site inhibiting effect of glucose might be located either at the level of A cell or at the level of "'glucoreceptors" in hypothalamus.

  6. Heat stress induced changes in metabolic regulators of donkeys from arid tracts in India

    Directory of Open Access Journals (Sweden)

    Kataria N.

    2012-05-01

    Full Text Available To find out heat stress induced changes in metabolic regulators of donkeys from arid tracts in India, blood samples were collected to harvest the serum during moderate and extreme hot ambiences. The metabolic enzymes determined were sorbitol dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, ornithine carbamoyl transferase, gammaglutamayl transferase, 5’nucleotidase, glucose-6-phosphatase, arginase, and aldolase. The mean values of all the serum enzymes increased significantly (p≤0.05 during hot ambience as compared to respective values during moderate ambience. It was concluded that increased activity of all the enzymes in the serum was due to modulation of metabolic reactions to combat the effect of hot ambience on the animals. Activation of gluconeogenesis along with hexose monophosphate shunt and urea cycle probably helped the animals to combat the heat stress.

  7. Stress induced martensite at the crack tip in NiTi alloys during fatigue loading

    Directory of Open Access Journals (Sweden)

    E. Sgambitterra

    2014-10-01

    Full Text Available Crack tip stress-induced phase transformation mechanisms in nickel-titanium alloys (NiTi were analyzed by Digital Image Correlation (DIC, under fatigue loads. In particular, Single Edge Crack (SEC specimens, obtained from a commercial pseudoelastic NiTi sheet, and an ad-hoc experimental setup were used, for direct measurements of the near crack tip displacement field by the DIC technique. Furthermore, a fitting procedure was developed to calculate the mode I Stress Intensity Factor (SIF, starting from the measured displacement field. Finally, cyclic tensile tests were performed at different operating temperature, in the range 298-338 K, and the evolution of the SIF was studied, which revealed a marked temperature dependence.

  8. Lysosome dysfunction enhances oxidative stress-induced apoptosis through ubiquitinated protein accumulation in Hela cells.

    Science.gov (United States)

    Yu, Chunyan; Huang, Xiaowei; Xu, Ye; Li, Hongyan; Su, Jing; Zhong, Jiateng; Kang, Jinsong; Liu, Yuhe; Sun, Liankun

    2013-01-01

    The role of lysosomal system in oxidative stress-induced apoptosis in cancer cells is not fully understood. Menadione is frequently used as oxidative stress model. It is indicated that menadione could induce autophagy in Hela cells. In the present study, we examined whether the lysosomal inhibitor, ammonium chloride (NH(4)Cl) could prevent the autophagy flux by inhibiting the fusion of autophagosomes with lysosomes and enhance apoptosis induced by menadione via mitochondrial pathway. The results demonstrated generation and accumulation of reactive oxygen species and increased levels of ubiquitinated proteins and GRP78 in cells treated with both menadione and NH(4)Cl. Our data indicates that lysosomal system through autophagy plays an important role in preventing menadione-induced apoptosis in Hela cells by clearing misfolded proteins, which alleviates endoplasmic reticulum stress.

  9. Protective Effect of Strawberry Extract against Inflammatory Stress Induced in Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Massimiliano Gasparrini

    2017-01-01

    Full Text Available A protracted pro-inflammatory state is a major contributing factor in the development, progression and complication of the most common chronic pathologies. Fruit and vegetables represent the main sources of dietary antioxidants and their consumption can be considered an efficient tool to counteract inflammatory states. In this context an evaluation of the protective effects of strawberry extracts on inflammatory stress induced by E. coli LPS on human dermal fibroblast cells was performed in terms of viability assays, ROS and nitrite production and biomarkers of oxidative damage of the main biological macromolecules. The results demonstrated that strawberry extracts exerted an anti-inflammatory effect on LPS-treated cells, through an increase in cell viability, and the reduction of ROS and nitrite levels, and lipid, protein and DNA damage. This work showed for the first time the potential health benefits of strawberry extract against inflammatory and oxidative stress in LPS-treated human dermal fibroblast cells.

  10. Stress-induced hemorrhagic gastric ulcer after successful Helicobacter pylori eradication: two case reports

    Directory of Open Access Journals (Sweden)

    Miyamoto Mitsuaki

    2011-06-01

    Full Text Available Abstract Introduction Helicobacter pylori infection is a major cause of gastric ulcers, and Helicobacter pylori eradication drastically reduces ulcer recurrence. It has been reported, however, that severe physical stress is closely associated with gastric ulceration even in Helicobacter pylori -negative patients. Case presentation We report the cases of a 47-year-old Japanese man and a 69-year-old Japanese man who developed psychological stress-induced hemorrhagic gastric ulcers, in both of whom Helicobacter pylori had been successfully eradicated. Conclusion Our cases strongly suggest that not only physical but also psychological stress is still an important pathogenic factor for peptic ulceration and accordingly that physicians should pay attention to the possible presence of psychological stress in the management of patients with peptic ulcers.

  11. Reno-protective effect of garlic extract against immobilization stress induced changes in rats

    Institute of Scientific and Technical Information of China (English)

    Syed; Kashif; Zaidi; Shakeel; Ahmed; Ansari; Ghulam; Md.Ashraf; Mohammad; Alam; Jafri; Shams; Tabrez; Naheed; Banu

    2015-01-01

    Objective: To examine immobilization stress-induced antioxidant defense alterations in rat kidney and the antioxidant effects of aqueous garlic extract in pre and post stress extract treatments. Methods: Albino rats were treated with aqueous extract of garlic both before and 6 h of immobilization stress. Pro-oxidant eminence of rat kidney was assessed by determining the levels of glutathione, thiobarbituric acid reactive substances, aspartate aminotransferase, alanine aminotransferase, glucose, uric acid, alkaline phosphatase and antioxidant enzymes activities. Results: In response to 6 h of immobilization stress, a significant rise in the level of kidney enzymes was recorded. However, antioxidant enzyme activities showed a sharp decline. Conclusions: The extract treatment before and after the stress reverted the activities of above mentioned enzymes towards their control values. Hence, garlic extract can be given as nutritional supplement for scavenging the free radicals generated in rat kidney.

  12. Atypical RNAs in the coelacanth transcriptome.

    Science.gov (United States)

    Nitsche, Anne; Doose, Gero; Tafer, Hakim; Robinson, Mark; Saha, Nil Ratan; Gerdol, Marco; Canapa, Adriana; Hoffmann, Steve; Amemiya, Chris T; Stadler, Peter F

    2014-09-01

    Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.

  13. Transient tachypnea - newborn

    Science.gov (United States)

    ... lungs - newborns; Retained fetal lung fluid; Transient RDS; Prolonged transition; Neonatal - transient tachypnea ... The mother's pregnancy and labor history are important to make the diagnosis. Tests performed on the baby may include: Blood count ...

  14. Dispositional optimism and stress-induced changes in immunity and negative mood.

    Science.gov (United States)

    Brydon, Lena; Walker, Cicely; Wawrzyniak, Andrew J; Chart, Henrik; Steptoe, Andrew

    2009-08-01

    Evidence suggests that optimism may be protective for health during times of heightened stress, yet the mechanisms involved remain unclear. In a double-blind placebo-controlled study, we recently showed that acute psychological stress and an immune stimulus (Typhim-Vi typhoid vaccine) synergistically increased serum levels of interleukin-6 (IL-6) and negative mood in 59 healthy men. Here we carried out further analysis of this sample to investigate the relationship between dispositional optimism and stress-induced changes in immunity and mood. Volunteers were randomly assigned to one of four experimental conditions in which they received either typhoid vaccine or saline placebo, and then rested or completed two mental tasks. In the stress condition, optimism was inversely related to IL-6 responses, independent of age, BMI, trait CES-D depression and baseline IL-6. This relationship was present across both stress groups (combining vaccine and placebo) and was not present in the vaccine/stress group alone, suggesting that optimism protects against the inflammatory effects of stress rather than vaccine per se. Typhoid vaccine induced a significant increase in participants' circulating anti-Vi antibody levels. Stress had no effect on antibody responses overall. However, in the vaccine/stress group, there was a strong positive association between optimism and antibody responses, indicating that stress accentuated the antibody response to vaccine in optimists. Across the complete sample, more optimistic individuals had smaller increases in negative mood and less reduction in mental vigour. Together these findings suggest that optimism may promote health, by counteracting stress-induced increases in inflammation and boosting the adjuvant effects of acute stress.

  15. Effects of cerebrolysin administration on oxidative stress-induced apoptosis in lymphocytes from CADASIL patients.

    Science.gov (United States)

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

    2013-04-01

    Cerebrolysin (Cere) is a peptidergic nootropic drug with neurotrophic properties which has been used to treat dementia and sequelae of stroke. Use of Cere prevents nuclear structural changes typical of apoptosis and significantly reduces the number of apoptotic cells after several apoptotic stimuli. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis. The aim of this study was to evaluate the in vitro protective effects of Cere against oxidative stress-induced apoptosis in cells from CADASIL patients. We used peripheral blood lymphocytes (PBLs) from 15 CADASIL patients (age range 34-70 years); 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analyzed by flow cytometry and fluorescence microscopy. Administration of Cere to PBLs from CADASIL patients cultured under standard conditions had no effect on the percentage of apoptotic cells. Administration of Cere to PBLs cultured with dRib caused a significant decrease in apoptosis after 48 h of culture in only 5 patients, whereas in the other 10 patients, Cere treatment was not associated with any significant difference in the percentage of apoptosis. This result showed a protective effect of Cere against oxidative stress-induced apoptosis only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably does not influence the anti-apoptotic properties of Cere in vitro.

  16. Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gebhard, Catherine; Staehli, Barbara E. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Shi, Yi; Camici, Giovanni G.; Akhmedov, Alexander; Hoegger, Lisa; Lohmann, Christine [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Matter, Christian M. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Hassa, Paul O.; Hottiger, Michael O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Malinski, Tadeusz [Department of Chemistry and Biochemistry, Ohio University, Athens, OH (United States); Luescher, Thomas F. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); and others

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer The nuclear enzyme PARP-1 is a downstream effector of oxidative stress. Black-Right-Pointing-Pointer PARP-1 protects from oxidative stress induced endothelial dysfunction. Black-Right-Pointing-Pointer This effect is mediated through inhibition of vasoconstrictor prostanoid production. Black-Right-Pointing-Pointer Thus, PARP-1 may play a protective role as antioxidant defense mechanism. -- Abstract: Background: Generation of reactive oxygen species (ROS) is a key feature of vascular disease. Activation of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) is a downstream effector of oxidative stress. Methods: PARP-1(-/-) and PARP-1(+/+) mice were injected with paraquat (PQ; 10 mg/kg i.p.) to induce intracellular oxidative stress. Aortic rings were suspended in organ chambers for isometric tension recording to analyze vascular function. Results: PQ treatment markedly impaired endothelium-dependent relaxations to acetylcholine in PARP-1(-/-), but not PARP-1(+/+) mice (p < 0.0001). Maximal relaxation was 45% in PQ treated PARP-1(-/-) mice compared to 79% in PARP-1(+/+) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (SNP) were not altered. After PQ treatment, L-NAME enhanced contractions to norepinephrine by 2.0-fold in PARP-1(-/-) mice, and those to acetylcholine by 3.3-fold, respectively, as compared to PARP-1(+/+) mice. PEG-superoxide dismutase (SOD) and PEG-catalase prevented the effect of PQ on endothelium-dependent relaxations to acetylcholine in PARP-1(-/-) mice (p < 0.001 vs. PQ treated PARP-1(+/+) mice. Indomethacin restored endothelium-dependent relaxations to acetylcholine in PQ treated PARP-1(-/-) mice (p < 0.05 vs. PQ treated PARP-1(+/+). Conclusion: PARP-1 protects from acute intracellular oxidative stress induced endothelial dysfunction by inhibiting ROS induced production of vasoconstrictor prostanoids.

  17. Repeated stress-induced stimulation of catecholamine response is not followed by altered immune cell redistribution.

    Science.gov (United States)

    Imrich, Richard; Tibenska, Elena; Koska, Juraj; Ksinantova, Lucia; Kvetnansky, Richard; Bergendiova-Sedlackova, Katarina; Blazicek, Pavol; Vigas, Milan

    2004-06-01

    Stress response is considered an important factor in the modulation of immune function. Neuroendocrine hormones, including catecholamines, affect the process of immune cell redistribution, important for cell-mediated immunity. This longitudinal investigation was aimed at evaluating the effect of repeated stress-induced elevation of catecholamines on immune cell redistribution and expression of adhesive molecules. We assessed the responses of epinephrine (EPI), norepinephrine (NE), cortisol, changes in lymphocytes subpopulations, and percentages of CD11a+, CD11b+, and CD62L+ lymphocytes to a 20-min treadmill exercise of an intensity equal to 80% of the individual's Vo(2)max. The exercise was performed before and after 6 weeks of endurance training consisting of a 1-h run 4 times a week (ET) and after 5 days of bed rest (HDBR) in 10 healthy males. We did not observe any significant changes in the basal levels of EPI, NE, and cortisol in the plasma, nor in the immune parameters after ET and HDBR. The exercise test led to a significant (P <.001) elevation of EPI and NE levels after both ET and HDBR, a significant elevation (P <.01) of cortisol after HDBR, an increase in the absolute numbers of leukocytes, granulocytes, monocytes, CD3+, CD4+, CD8+, CD16+, CD19+ lymphocytes, percentage of CD11a+ and CD11b+ lymphocytes, and to a decrease of CD62L1 before, after ET, and after HDBR. We found comparable changes in all measured immune parameters after ET and HDBR. In conclusion, repeated stress-induced elevation of EPI and NE was not associated with an alteration in immune cell redistribution found in response to the single bout of exercise.

  18. 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

  19. Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

    Full Text Available BACKGROUND/AIMS: Hepcidin (gene name HAMP, an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. METHODS: Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and -blotting, while prohepcidin levels in human bile were determined by ELISA. RESULTS: Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03. In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively. In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05. CONCLUSION: Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.

  20. Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Jingkai Wei

    Full Text Available Depression is an adverse prognostic factor after an acute myocardial infarction (MI, and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.We studied 98 patients (49 women and 49 men age 38-60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task, and after exercise or pharmacological stress. A summed difference score (SDS, obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30, p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56, p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological stress.

  1. PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy.

    Science.gov (United States)

    Tan, S; Wei, X; Song, M; Tao, J; Yang, Y; Khatoon, S; Liu, H; Jiang, J; Wu, B

    2014-03-13

    Mucosal apoptosis has been demonstrated to be an essential pathological feature in portal hypertensive gastropathy (PHG). p53-upregulated modulator of apoptosis (PUMA) was identified as a BH3-only Bcl-2 family protein that has an essential role in apoptosis induced by a variety of stimuli, including endoplasmic reticulum (ER) stress. However, whether PUMA is involved in mucosal apoptosis in PHG remains unclear, and whether PUMA induces PHG by mediating ER stress remains unknown. The aim of the study is to investigate whether PUMA is involved in PHG by mediating ER stress apoptotic signaling. To identify whether PUMA is involved in PHG by mediating ER stress, gastric mucosal injury and apoptosis were studied in both PHG patients and PHG animal models using PUMA knockout (PUMA-KO) and PUMA wild-type (PUMA-WT) mice. The induction of PUMA expression and ER stress signaling were investigated, and the mechanisms of PUMA-mediated apoptosis were analyzed. GES-1 and SGC7901 cell lines were used to further identify whether PUMA-mediated apoptosis was induced by ER stress in vitro. Epithelial apoptosis and PUMA were markedly induced in the gastric mucosa of PHG patients and mouse PHG models. ER stress had a potent role in the induction of PUMA and apoptosis in PHG models, and the apoptosis was obviously attenuated in PUMA-KO mice. Although the targeted deletion of PUMA did not affect ER stress, mitochondrial apoptotic signaling was downregulated in mice. Meanwhile, PUMA knockdown significantly ameliorated ER stress-induced mitochondria-dependent apoptosis in vitro. These results indicate that PUMA mediates ER stress-induced mucosal epithelial apoptosis through the mitochondrial apoptotic pathway in PHG, and that PUMA is a potentially therapeutic target for PHG.

  2. Transient drainage summary report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-01

    This report summarizes the history of transient drainage issues on the Uranium Mill Tailings Remedial Action (UMTRA) Project. It defines and describes the UMTRA Project disposal cell transient drainage process and chronicles UMTRA Project treatment of the transient drainage phenomenon. Section 4.0 includes a conceptual cross section of each UMTRA Project disposal site and summarizes design and construction information, the ground water protection strategy, and the potential for transient drainage.

  3. Expression of human telomerase (hTERT) does not prevent stress-induced senescence in normal human fibroblasts but protects the cells from stress-induced apoptosis and necrosis.

    Science.gov (United States)

    Gorbunova, Vera; Seluanov, Andrei; Pereira-Smith, Olivia M

    2002-10-11

    Cells subjected to sub-lethal doses of stress such as irradiation or oxidative damage enter a state that closely resembles replicative senescence. What triggers stress-induced premature senescence (SIPS) and how similar this mechanism is to replicative senescence are not well understood. It has been suggested that stress-induced senescence is caused by rapid telomere shortening resulting from DNA damage. In order to test this hypothesis directly, we examined whether overexpression of the catalytic subunit of human telomerase (hTERT) can protect cells from SIPS. We therefore analyzed the response of four different lines of normal human fibroblasts with and without hTERT to stress induced by UV, gamma-irradiation, and H(2)O(2). SIPS was induced with the same efficiency in normal and hTERT-immortalized cells. This suggests that SIPS is not triggered by telomere shortening and that nonspecific DNA damage serves as a signal for induction of SIPS. Although telomerase did not protect cells from SIPS, fibroblasts expressing hTERT were more resistant to stress-induced apoptosis and necrosis. We hypothesize that healing of DNA breaks by telomerase inhibits the induction of cell death, but because healing does not provide legitimate DNA repair, it does not protect cells from SIPS.

  4. Biochemical and molecular studies of atypical nevi

    NARCIS (Netherlands)

    Nieuwpoort, Arno Frans van

    2011-01-01

    The results obtained in this thesis suggest that the most explicit differences between normal and atypical melanocytes are subtle changes in pigment biosynthesis and the functioning of the antioxidant system. Impairment of the antioxidant system and increased levels of pheomelanin result in increase

  5. Non-diabetic atypical necrobiosis lipoidica

    Directory of Open Access Journals (Sweden)

    Mittal R

    1994-01-01

    Full Text Available One 8 year female child had asymptomatic, anaesthetic, hypohidrotic, atrophic, yellowish, waxy plaque on the front of left thigh since 2 months. No nerve thickening was observed clinically or histopathologically. Hyperkeratosis, follicular keratosis, epidermal atrophy, degeneration of collagen, mononuclear granulomas and perivascular mononuclear infiltrate confirmed the clinical diagnosis of atypical necrobiosis lipoidica.

  6. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    Directory of Open Access Journals (Sweden)

    Derek To

    2014-01-01

    Full Text Available We present a patient with atypical pyoderma gangrenosum (APG, which involved the patient’s arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  7. Atypical pyoderma gangrenosum mimicking an infectious process.

    Science.gov (United States)

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  8. Atypical Alpha Asymmetry in Adults with ADHD

    Science.gov (United States)

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  9. Atypical fractures on long term bisphosphonates therapy.

    LENUS (Irish Health Repository)

    Hussein, W

    2011-01-01

    Bisphosphonates reduce fractures risk in patients with osteoporosis. A new pattern of fractures is now being noted in patients on prolonged bisphosphonate therapy. We report a case of an atypical femoral fracture with preceding pain and highlight the characteristics of these fractures.

  10. Atypical visuomotor performance in children with PDD

    NARCIS (Netherlands)

    Schlooz, W.A.J.M.; Hulstijn, W.

    2012-01-01

    Children with autism spectrum disorders (ASD) frequently encounter difficulties in visuomotor tasks, which are possibly caused by atypical visuoperceptual processing. This was tested in children (aged 9–12 years) with pervasive developmental disorder (PDD; including PDD-NOS and Asperger syndrome), a

  11. Psychiatric syndromes associated with atypical chest pain

    Directory of Open Access Journals (Sweden)

    Nikolić Gordana

    2010-01-01

    Full Text Available Background/Aim. Chest pain often indicates coronary disease, but in 25% of patients there is no evidence of ischemic heart disease using standard diagnostic tests. Beside that, cardiologic examinations are repeated several times for months. If other medical causes could not be found, there is a possibility that chest pain is a symptom of psychiatric disorder. The aim of this study was to determine the presence of psychiatric syndromes, increased somatization, anxiety, stress life events exposure and characteristic of chest pain expression in persons with atypical chest pain and coronary patients, as well as to define predictive parameters for atypical chest pain. Method. We compared 30 patients with atypical chest pain (E group to 30 coronary patients (K group, after cardiological and psychiatric evaluation. We have applied: Mini International Neuropsychiatric Interview (MINI, The Symptom Checklist 90-R (SCL-90 R, Beck Anxiety Inventory (BAI, Holms-Rahe Scale of stress life events (H-R, Questionnaire for pain expression Pain-O-Meter (POM. Significant differences between groups and predictive value of the parameters for atypical chest pain were determined. Results. The E group participants compared to the group K were younger (33.4 ± 5.4 : 48.3 ± 6,4 years, p < 0.001, had a moderate anxiety level (20.4 ± 11.9 : 9.6 ± 3.8, p < 0.001, panic and somatiform disorders were present in the half of the E group, as well as eleveted somatization score (SOM ≥ 63 -50% : 10%, p < 0.01 and a higher H-R score level (102.0 ± 52.2 : 46.5 ± 55.0, p < 0.001. Pain was mild, accompanied with panic. The half of the E group subjects had somatoform and panic disorders. Conclusion. Somatoform and panic disorders are associated with atypical chest pain. Pain expression is mild, accompained with panic. Predictive factors for atypical chest pain are: age under 40, anxiety level > 20, somatization ≥ 63, presence of panic and somatoform disorders, H-R score > 102

  12. 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...

  13. Ameliorative potential of sodium cromoglycate and diethyldithiocarbamic acid in restraint stress-induced behavioral alterations in rats.

    Science.gov (United States)

    Manchanda, Rajneet K; Jaggi, Amteshwar S; Singh, Nirmal

    2011-01-01

    The present study was designed to investigate the ameliorative effects of sodium cromoglycate and diethyldithiocarbamic acid in acute stress-induced behavioral alterations in rats subjected to restraint stress. The rats were placed in the restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Restraint stress-induced behavioral alterations were assessed using the hole-board, social interactions and open field tests. Restraint stress resulted in a decrease in the frequency of head dips, rearing in the hole board, line crossings and rearings in the open field, and an increase in avoidance behaviors in the social interaction tests. Sodium cromoglycate (25 mg/kg and 50 mg/kg, ip), a mast cell stabilizer, and diethyldithiocarbamic acid (75 mg/kg and 150 mg/kg, ip), a selective NF-κB inhibitor, were employed to modulate restraint stress-induced behavioral changes. The administration of sodium cromoglycate and diethyldithiocarbamic acid significantly attenuated the restraint stress-induced behavioral changes. The noted beneficial effects of sodium cromoglycate and diethyldithiocarbamic acid may possibly be attributed to mast cell stabilization and inhibition of NF-κB activity, respectively.

  14. Blocking the mineralocorticoid receptor in humans prevents the stress-induced enhancement of centromedial amygdala connectivity with the dorsal striatum

    NARCIS (Netherlands)

    Vogel, S.; Klumpers, F.; Krugers, H.J.; Fang, Z.; Oplaat, K.T.; Oitzl, M.S.; Joels, M.; Fernandez, G.S.E.

    2015-01-01

    Two research lines argue for rapid stress-induced reallocations of neural network activity involving the amygdala. One focuses on the role of norepinephrine (NE) in mediating a shift towards the salience network and improving vigilance processing, whereas the other focuses on the role of cortisol in

  15. Effect of "rose essential oil" inhalation on stress-induced skin-barrier disruption in rats and humans.

    Science.gov (United States)

    Fukada, Mika; Kano, Eri; Miyoshi, Michio; Komaki, Ryoichi; Watanabe, Tatsuo

    2012-05-01

    In stressed animals, several brain regions (e.g., hypothalamic paraventricular nucleus [PVN]) exhibit neuronal activation, which increases plasma adrenocorticotropic hormone (ACTH) and glucocorticoids. We previously reported that so-called "green odor" inhibits stress-induced activation of the hypothalamo-pituitary-adrenocortical axis (HPA axis) and thereby prevents the chronic stress-induced disruption of the skin barrier. Here, we investigated whether rose essential oil, another sedative odorant, inhibits the stress-induced 1) increases in PVN neuronal activity in rats and plasma glucocorticoids (corticosterone [CORT] in rats and cortisol in humans) and 2) skin-barrier disruption in rats and humans. The results showed that in rats subjected to acute restraint stress, rose essential oil inhalation significantly inhibited the increase in plasma CORT and reduced the increases in the number of c-Fos-positive cells in PVN. Inhalation of rose essential oil significantly inhibited the following effects of chronic stress: 1) the elevation of transepidermal water loss (TEWL), an index of the disruption of skin-barrier function, in both rats and humans and 2) the increase in the salivary concentration of cortisol in humans. These results suggest that in rats and humans, chronic stress-induced disruption of the skin barrier can be limited or prevented by rose essential oil inhalation, possibly through its inhibitory effect on the HPA axis.

  16. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus.

    Science.gov (United States)

    Pawlak, Robert; Rao, B S Shankaranarayana; Melchor, Jerry P; Chattarji, Sumantra; McEwen, Bruce; Strickland, Sidney

    2005-12-13

    Repeated stress can impair function in the hippocampus, a brain structure essential for learning and memory. Although behavioral evidence suggests that severe stress triggers cognitive impairment, as seen in major depression or posttraumatic stress disorder, little is known about the molecular mediators of these functional deficits in the hippocampus. We report here both pre- and postsynaptic effects of chronic stress, manifested as a reduction in the number of NMDA receptors, dendritic spines, and expression of growth-associated protein-43 in the cornu ammonis 1 region. Strikingly, the stress-induced decrease in NMDA receptors coincides spatially with sites of plasminogen activation, thereby predicting a role for tissue plasminogen activator (tPA) in this form of stress-induced plasticity. Consistent with this possibility, tPA-/- and plasminogen-/- mice are protected from stress-induced decrease in NMDA receptors and reduction in dendritic spines. At the behavioral level, these synaptic and molecular signatures of stress-induced plasticity are accompanied by impaired acquisition, but not retrieval, of hippocampal-dependent spatial learning, a deficit that is not exhibited by the tPA-/- and plasminogen-/- mice. These findings establish the tPA/plasmin system as an important mediator of the debilitating effects of prolonged stress on hippocampal function at multiple levels of neural organization.

  17. A critical role for the melanocortin 4 receptor in stress-induced relapse to nicotine seeking in rats.

    Science.gov (United States)

    Qi, Xiaoli; Yamada, Hidetaka; Corrie, Lu W; Ji, Yue; Bauzo, Rayna M; Alexander, Jon C; Bruijnzeel, Adrie W

    2015-03-01

    Tobacco addiction is characterized by a lack of control over smoking and relapse after periods of abstinence. Smoking cessation leads to a dysphoric state that contributes to relapse to smoking. After the acute withdrawal phase, exposure to stressors increases the risk for relapse. Blockade of melanocortin 4 (MC4 ) receptors has anxiolytic and antidepressant-like effects in animal models. The aim of these studies was to investigate the role of MC4 receptors in the dysphoria associated with nicotine withdrawal and stress-induced reinstatement of nicotine seeking. To study stress-induced reinstatement, rats self-administered nicotine for 16 days and then nicotine seeking was extinguished by substituting saline for nicotine. Nicotine seeking was reinstated by intermittent footshock stress. The intracranial self-stimulation (ICSS) procedure was used to assess the negative mood state associated with nicotine withdrawal. Elevations in the ICSS thresholds are indicative of a dysphoric state. The selective MC4 receptor antagonists HS014 and HS024 prevented stress-induced reinstatement of extinguished nicotine seeking. Drug doses that prevented stress-induced relapse did not affect responding for food pellets, which indicates that the drugs did not induce sedation or motor impairments. In the ICSS experiments, the nicotinic acetylcholine receptor antagonist mecamylamine elevated the ICSS thresholds of the nicotine-dependent rats. Pre-treatment with HS014 or HS024 did not prevent the elevations in ICSS thresholds. These studies indicate that MC4 receptors play a critical role in stress-induced reinstatement of nicotine seeking, but these receptors may not play a role in the dysphoria associated with acute nicotine withdrawal.

  18. Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni).

    Science.gov (United States)

    Dupoué, Andréaz; Angelier, Frédéric; Lourdais, Olivier; Bonnet, Xavier; Brischoux, François

    2014-02-01

    Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis.

  19. Dependence of stress-induced omega transition and mechanical twinning on phase stability in metastable β Ti–V alloys

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.L.; Li, L.; Mei, W.; Wang, W.L.; Sun, J., E-mail: jsun@sjtu.edu.cn

    2015-09-15

    Tensile properties and deformation microstructures of a series of binary β Ti–16–22V alloys have been investigated. The results show that the plastic deformation mode changes from the plate-like stress-induced ω phase transformation with a special habit plane of (− 5052){sub ω}//(3 − 3 − 2){sub β} to (332)<113> type deformation twinning with increasing the content of vanadium in the β Ti–16–22 wt.% V alloys. The plate-like stress-induced ω phase has a special orientation relationship with the β phase matrix, i.e., [110]{sub β}//[− 12 − 10]{sub ω}, (3 − 3 − 2){sub β}//(− 5052){sub ω} and (− 55 − 4){sub β}//(30 − 31){sub ω}. The alloys plastically deformed by stress-induced ω phase transformation exhibit relatively higher yield strength than those deformed via (332)<113> type deformation twinning. It can be concluded that the stability of β phase plays a significant role in plastic deformation mode, i.e., stress-induced ω phase transformation or (332)<113> type deformation twinning, which governs the mechanical property of the β Ti–16–22 wt.% V alloys. - Highlights: • Tensile properties and deformed microstructures of β Ti–16–22V alloys were studied. • Stress-induced ω phase transformation and (332)<113> twinning occur in the alloys. • Stability of β phase plays a significant role in plastic deformation mode. • Plastic deformation mode governs the mechanical property of the alloys.

  20. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

    Directory of Open Access Journals (Sweden)

    Tomiki eSumiyoshi

    2013-10-01

    Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  1. An intergenic region shared by At4g35985 and At4g35987 in Arabidopsis thaliana is a tissue specific and stress inducible bidirectional promoter analyzed in transgenic arabidopsis and tobacco plants.

    Directory of Open Access Journals (Sweden)

    Joydeep Banerjee

    Full Text Available On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985 are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85 showed stronger expression (about 3.5 fold compared to the At4g35987 promoter (P87. The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications.

  2. Transient Voltage Recorder

    Science.gov (United States)

    Medelius, Pedro J. (Inventor); Simpson, Howard J. (Inventor)

    2002-01-01

    A voltage transient recorder can detect lightning induced transient voltages. The recorder detects a lightning induced transient voltage and adjusts input amplifiers to accurately record transient voltage magnitudes. The recorder stores voltage data from numerous monitored channels, or devices. The data is time stamped and can be output in real time, or stored for later retrieval. The transient recorder, in one embodiment, includes an analog-to-digital converter and a voltage threshold detector. When an input voltage exceeds a pre-determined voltage threshold, the recorder stores the incoming voltage magnitude and time of arrival. The recorder also determines if its input amplifier circuits clip the incoming signal or if the incoming signal is too low. If the input data is clipped or too low, the recorder adjusts the gain of the amplifier circuits to accurately acquire subsequent components of the lightning induced transients.

  3. Antistress property of Glycyrrhiza glabra (Athimadhura on stress induced Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Sowmya M.

    2010-11-01

    Full Text Available Stress is defined as a condition that disturbs the normal function of the biological system or a condition that decreases fitness. The present study was to evaluate the antistress property of Glycyrrhiza glabra (Athimadura. Here the Antistress property was experimented on Drosophila melanogaster. Stress was induced by adding methotrixate (MTX to the media. The 4 groups of Drosophila melanogaster were cultured in the laboratory. In the first group only control flies. In the second group MTX induced flies, in the third group MTX along with plant powder induced flies. In the fourth group only plant powder induced flies were cultured. Stress related enzymes like Catalase (CAT and Super Oxide Dismutase (SOD are most widely used paradigm for the evaluation of enzyme activity . SOD and CAT Activity in Stress induced flies was increased compared to that of normal flies. After incorporation of the plant powder to the media fed for Drosophila melanogaster, both SOD and CAT Activity was decreased indicating the reduction in Stress by the plant powder. Thus Glycyrrhiza glabra may have Antistress property, as it has reduced stress in Drosophila melanogaster induced by MTX at different concentration.

  4. Analysis of thermal stresses induced in silicon during xenon arc lamp flash annealing

    Science.gov (United States)

    Bentini, G. G.; Correra, L.

    1983-04-01

    Evaluation of thermal stresses induced on silicon wafers during flash annealing with incoherent light from a xenon lamp has been performed. The thermally induced stresses have been computed taking into account that the slip planes, in silicon crystal, are {111} and the slip directions in the plane are . The computed stresses have been compared with the yield stress of the material, to determine the threshold of damage introduction by the annealing process. For the light flash durations shorter than 500 μsec, a preheating of the sample is necessary to obtain a good annealing of a 1000 Å implanted layer without defects introduction. A relationship among flash duration, preheating temperature and flash energy density has been established allowing the identification of the best annealing conditions. The computed results have been compared with experimental annealing data obtained on silicon, phosphorus implanted at 10 keV, 1.5×1015 at/cm2 and irradiated with an original flash annealing system set up in our laboratory.

  5. Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells

    Institute of Scientific and Technical Information of China (English)

    Jian-You Li; Ai-Liang Jiang; Wei Zhang

    2007-01-01

    Salt stressed rice root tips were used to investigate the changes of reactive oxygen species (ROS) and antioxidant enzymes at the early stages of programmed cell death (PCD). The results indicated that 500 mmol/L NaCl treatment could lead to specific features of PCD in root tips, such as DNA ladder, nuclear condense and deformation, and transferase mediated dUTP nick end labeling positive reaction, which were initiated at 4 h of treatment and progressed thereafter. Cytochrome c release from mitochondria into cytoplasm was also observed, which occurred at 2 h and was earlier than the above nuclear events. In the very early phase of PCD, an immediate burst in hydrogen peroxide and superoxide anion production rate was accompanied by two-phase changes of superoxide dismutases and ascorbate peroxidase. A short period of increase in the activity was followed by prolonged impairment. Thus,we conclude that salt can induce PCD in rice root tip cells, and propose that in the early phase of rice root tip cell PCD, salt stress-induced oxidative burst increased the antioxidant enzyme activity, which, In turn, scavenged the ROS and abrogated PCD. Also, when the stress is prolonged, the antioxidant system is damaged and accumulated ROS induces the PCD process, which leads to cytochrome c release and nuclear change.

  6. The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans

    Science.gov (United States)

    Iannacone, Michael J; Beets, Isabel; Lopes, Lindsey E; Churgin, Matthew A; Fang-Yen, Christopher; Nelson, Matthew D; Schoofs, Liliane; Raizen, David M

    2017-01-01

    In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, stress-induced sleep(SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1, which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo, is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness. DOI: http://dx.doi.org/10.7554/eLife.19837.001 PMID:28094002

  7. Influence of reaction stresses induced by dislocation slips on the orientation evolution in bcc metals

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A plastic deformation model for bcc metals is proposed in consideration of reaction stresses. The shear strains and the corresponding reaction stresses induced by the activation of dislocations are calculated in the model, which will influence the following dislocation activation. The rolling texture in bcc metals is simulated up to 80% reduction, while the ratio of critical resolved shear stresses between the dislocations slipping on the {110} and {112} planes is chosen as 0.95. The corresponding calculation is also conducted with the activation of second dislocation, if the difference between the orientation factor of the two dislocations with maximal orientation factors is lower than 5%. It is shown that the simulated texture is closer to that of the 80% rolled interstitial free steels than other modeling. It is believed that the new model can give more attention to both of the strain and stress continuities during the plastic deformation of polycrystalline metals, and therefore approaches closer to the real deformation process in bcc metals.

  8. Stress induced anisotropy in CoFeMn soft magnetic nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Leary, A. M., E-mail: leary@cmu.edu; Keylin, V.; McHenry, M. E. [Materials Science and Engineering Department, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, Pennsylvania 15213 (United States); Ohodnicki, P. R. [Functional Materials Development Division, National Energy Technology Laboratory (NETL), 626 Cochrans Mill Road, Pittsburgh, Pennsylvania 15236 (United States)

    2015-05-07

    The use of processing techniques to create magnetic anisotropy in soft magnetic materials is a well-known method to control permeability and losses. In nanocomposite materials, field annealing below the Curie temperature results in uniaxial anisotropy energies up to ∼2 kJ/m{sup 3}. Higher anisotropies up to ∼10 kJ/m{sup 3} result after annealing Fe-Si compositions under stress due to residual stress in the amorphous matrix acting on body centered cubic crystals. This work describes near zero magnetostriction Co{sub 80−x−y}Fe{sub x}Mn{sub y}Nb{sub 4}B{sub 14}Si{sub 2} soft magnetic nanocomposites, where x and y < 8 at.% with close packed crystalline grains that show stress induced anisotropies up to ∼50 kJ/m{sup 3} and improved mechanical properties with respect to Fe-Si compositions. Difference patterns measured using transmission X-ray diffraction show evidence of affine strain with respect to the stress axis.

  9. Stress induced anisotropy in CoFeMn soft magnetic nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Leary, AM; Keylin, V; Ohodnicki, PR; McHenry, ME

    2015-05-07

    The use of processing techniques to create magnetic anisotropy in soft magnetic materials is a well-known method to control permeability and losses. In nanocomposite materials, field annealing below the Curie temperature results in uniaxial anisotropy energies up to similar to 2 kJ/m(3). Higher anisotropies up to similar to 10 kJ/m(3) result after annealing Fe-Si compositions under stress due to residual stress in the amorphous matrix acting on body centered cubic crystals. This work describes near zero magnetostriction Co80-x-yFexMnyNb4B14Si2 soft magnetic nanocomposites, where x and y < 8 at. % with close packed crystalline grains that show stress induced anisotropies up to similar to 50 kJ/m(3) and improved mechanical properties with respect to Fe-Si compositions. Difference patterns measured using transmission X-ray diffraction show evidence of affine strain with respect to the stress axis. (C) 2015 AIP Publishing LLC.

  10. Antioxidative effect of ginseng stem-leaf saponins on oxidative stress induced by cyclophosphamide in chickens.

    Science.gov (United States)

    Yu, J; Chen, Y; Zhai, L; Zhang, L; Xu, Y; Wang, S; Hu, S

    2015-05-01

    Previous investigation demonstrated that oral administration of ginseng stem-leaf saponins in chickens could enhance the immune response. The present study was designed to evaluate the effects of ginseng stem-leaf saponins on oxidative stress induced by cyclophosphamide in chickens. One hundred and twenty chickens were randomly divided into 5 groups. Groups 1 to 4 received intramuscular injection of cyclophosphamide to induce oxidative stress while group 5 was injected with saline solution and served as control. Following administration of cyclophosphamide, groups 1 to 3 were orally administered ginseng stem-leaf saponins at 2.5, 5, and 10 mg/kg BW in drinking water for 7 d, respectively. After that, the spleen, thymus, bursa, and serum were collected to measure the indices of the organs and oxidative parameters. The results showed that ginseng stem-leaf saponins significantly inhibited cyclophosphamide-induced oxidative stress by increasing the organ indices, total antioxidant capacity, and the levels of glutathione, ascorbic acid, and α-tocopherol, while elevating the activity of total superoxide dismutase, catalase, and glutathione peroxidase, as well as decreasing the protein carbonyl content and malondialdehyde. Therefore, ginseng stem-leaf saponins could be a promising agent against oxidative stress in the poultry industry.

  11. Peripheral relays in stress-induced activation of visceral afferents in the gut.

    Science.gov (United States)

    van den Wijngaard, René M; Klooker, Tamira K; de Jonge, Wouter J; Boeckxstaens, Guy E

    2010-02-16

    Multiple organs are targeted by the stress response, but the focus of this article is on stress-induced activation of visceral afferents in the gut. During recent years it became apparent that mast cells are pivotal in this response. Peripheral corticotrophin releasing factor (CRF) induces their degranulation whereupon mast cell mediators activate visceral afferents. In addition, these mediators are responsible for gut barrier dysfunction and subsequent influx of luminal antigens and bacteria. Some research groups have begun to investigate the possible importance of barrier dysfunction for enhanced visceral sensitivity. After reviewing the current knowledge on CRF-induced mast cell degranulation we will discuss these groundbreaking papers in a more elaborate way. They form the basis for a hypothesis in which not only CRF-induced but also antigen-mediated mast cell degranulation is relevant to stress-related afferent activation. Part of this hypothesis is certainly speculative and needs further investigation. At the end of this article we sum up some of the unanswered questions raised by others and during this review.

  12. Tau Deletion Prevents Stress-Induced Dendritic Atrophy in Prefrontal Cortex: Role of Synaptic Mitochondria.

    Science.gov (United States)

    Lopes, Sofia; Teplytska, Larysa; Vaz-Silva, Joao; Dioli, Chrysoula; Trindade, Rita; Morais, Monica; Webhofer, Christian; Maccarrone, Giuseppina; Almeida, Osborne F X; Turck, Christoph W; Sousa, Nuno; Sotiropoulos, Ioannis; Filiou, Michaela D

    2016-04-12

    Tau protein in dendrites and synapses has been recently implicated in synaptic degeneration and neuronal malfunction. Chronic stress, a well-known inducer of neuronal/synaptic atrophy, triggers hyperphosphorylation of Tau protein and cognitive deficits. However, the cause-effect relationship between these events remains to be established. To test the involvement of Tau in stress-induced impairments of cognition, we investigated the impact of stress on cognitive behavior, neuronal structure, and the synaptic proteome in the prefrontal cortex (PFC) of Tau knock-out (Tau-KO) and wild-type (WT) mice. Whereas exposure to chronic stress resulted in atrophy of apical dendrites and spine loss in PFC neurons as well as significant impairments in working memory in WT mice, such changes were absent in Tau-KO animals. Quantitative proteomic analysis of PFC synaptosomal fractions, combined with transmission electron microscopy analysis, suggested a prominent role for mitochondria in the regulation of the effects of stress. Specifically, chronically stressed animals exhibit Tau-dependent alterations in the levels of proteins involved in mitochondrial transport and oxidative phosphorylation as well as in the synaptic localization of mitochondria in PFC. These findings provide evidence for a causal role of Tau in mediating stress-elicited neuronal atrophy and cognitive impairment and indicate that Tau may exert its effects through synaptic mitochondria.

  13. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress.

  14. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

    Science.gov (United States)

    Fey, Theres; Schubert, Kai Michael; Schneider, Holger; Fein, Evelyn; Kleinert, Eike; Pohl, Ulrich; Dendorfer, Andreas

    2016-08-01

    Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

  15. Capsaicin ameliorates stress-induced Alzheimer's disease-like pathological and cognitive impairments in rats.

    Science.gov (United States)

    Jiang, Xia; Jia, Lin-Wei; Li, Xiao-Hong; Cheng, Xiang-Shu; Xie, Jia-Zhao; Ma, Zhi-Wei; Xu, Wei-Jie; Liu, Yue; Yao, Yun; Du, Lai-Ling; Zhou, Xin-Wen

    2013-01-01

    Hyperphosphorylated tau aggregated into neurofibrillary tangles is a hallmark lesion of Alzheimer's disease (AD) and is linked to synaptic and cognitive impairments. In animal models, cold water stress (CWS) can cause cognitive disorder and tau hyperphosphorylation. Capsaicin (CAP), a specific TRPV1 agonist, is neuroprotective against stress-induced impairment, but the detailed mechanisms are still elusive. Here, we investigated whether CAP mitigates CWS-induced cognitive and AD-like pathological alterations in rats. The animals were administered CAP (10 mg/kg in 0.2 ml, 0.1% ethanol) or a control (0.2 ml normal saline, 0.1% ethanol) by intragastric infusion 1 h before CWS treatment. Our results showed that CAP significantly attenuated CWS-induced spatial memory impairment and suppression of PP-DG long-term potentiation; CAP abolished CWS-induced dendritic regression and enhanced several memory-associated proteins decreased by CWS, such as synapsin I and PSD93; CAP also prevented CWS-induced tau hyperphosphorylation by abolishing inhibition of protein phosphatase 2A. Taken together, this study demonstrated that activation of TRPV1 can mitigate CWS-induced AD-like neuropathological alterations and cognitive impairment and may be a promising target for therapeutic intervention in AD.

  16. Recurrence of Postoperative Stress-Induced Cardiomyopathy Resulting from Status Epilepticus

    Science.gov (United States)

    Ahmed, Yousef M.; Tarant, Nicki S.

    2017-01-01

    Introduction. Classically, stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy, displays the pathognomonic feature of reversible left ventricular apical ballooning without coronary artery stenosis following stressful event(s). Temporary reduction in ejection fraction (EF) resolves spontaneously. Variants of SIC exhibiting mid-ventricular regional wall motion abnormalities have been identified. Recent case series present SIC as a finding in association with sudden unexplained death in epilepsy (SUDEP). This case presents a patient who develops recurrence of nonapical cardiomyopathy secondary to status epilepticus. Case Report. Involving a postoperative, postmenopausal woman having two distinct episodes of status epilepticus (SE) preceding two incidents of SIC. Preoperative transthoracic echocardiogram (TTE) confirms the patient's baseline EF of 60% prior to the second event. Postoperatively, SE occurs, and the initial electrocardiogram exhibits T-wave inversions with subsequent elevation of troponin I. Postoperative TTE shows an EF of 30% with mid-ventricular wall akinesia restoring baseline EF rapidly. Conclusion. This case identifies the need to understand SIC and its diagnostic criteria, especially when cardiac catheterization is neither indicated nor available. Sudden cardiac death should be considered as a possible complication of refractory status epilepticus. The pathophysiology in SUDEP is currently unknown; yet a correlation between SUDEP and SIC is hypothesized to exist. PMID:28210509

  17. Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function

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    Omary Chillo

    2016-08-01

    Full Text Available The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.

  18. Analytical Modeling of Surface Roughness, Hardness and Residual Stress Induced by Deep Rolling

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    Magalhães, Frederico C.; Abrão, Alexandre M.; Denkena, Berend; Breidenstein, Bernd; Mörke, Tobias

    2016-12-01

    Deep rolling is a mechanical surface treatment that can significantly alter the features of metallic components and despite the fact that it has been used for a long time, to date the influence of the interaction among the principal process parameters has not been thoroughly understood. Aiming to fulfill this gap, this work addresses the effect of deep rolling on surface finish and mechanical properties from the analytical and experimental viewpoints. More specifically, the influence of deep rolling pressure and number of passes on surface roughness, hardness and residual stress induced on AISI 1060 steel is investigated. The findings indicate that the surface roughness after deep rolling is closely related to the yield strength of the work material and the available models can satisfactorily predict the former parameter. Better agreement between the mathematical and experimental hardness values is achieved when a single deep rolling pass is employed, as well as when the yield strength of the work material increases. Compressive residual stress is generally induced after deep rolling, irrespectively of the selected heat treatment and deep rolling parameters. Finally, the model proposed to predict residual stress provides results closest to the experimental data especially when the annealed material is considered.

  19. A method for tracking subsurface fronts of stress-induced permeability enhancement

    Science.gov (United States)

    Lewis, K. C.

    2012-12-01

    The coupled interactions in fractured geological media between thermal-hydrologic-mechanical (THM) and chemical effects are expected to be important in many engineering applications including CO2 sequestration, geothermal energy production, oil and gas production, nuclear waste isolation, and arctic permafrost. Large changes in pressures, temperatures, and saturations can result due to injection/withdrawal of fluids or emplaced heat sources. Phase changes or rock failure often occur in an abrupt fashion, characterized by a sharp front of discontinuity with relatively small changes in properties on either side of the front. These changes can modify the formation permeability in a manner that can often be approximated by a step-function-like dependence. Such behavior has motivated us to use an analogy to the classical Stefan problem; we construct evolution equations for the fluid pore pressure on both sides of a propagating stress induced damage front for the case of planar front geometry. Closed form expressions are derived for the position of the damage front and the observable surface mass flow rate as functions of time for planar, spherical, and cylindrical damage front geometries. Isothermal, pressure induced damage is discussed as well as damage dominated by thermal effects. Model predictions are shown to agree with those of a less general fracture model as well as with field data consisting of measured mass flow rates over a two week period. Finally, we discuss extensions of the basic model to more complex damage front geometries.

  20. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.

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    Farrar, Conrad A; Tran, David; Li, Ke; Wu, Weiju; Peng, Qi; Schwaeble, Wilhelm; Zhou, Wuding; Sacks, Steven H

    2016-05-01

    Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

  1. Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance.

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    Ramirez, Karol; Shea, Daniel T; McKim, Daniel B; Reader, Brenda F; Sheridan, John F

    2015-05-01

    Psychosocial stress is associated with altered immunity, anxiety and depression. Previously we showed that repeated social defeat (RSD) promoted microglia activation and social avoidance behavior that persisted for 24days after cessation of RSD. The aim of the present study was to determine if imipramine (a tricyclic antidepressant) would reverse RSD-inducedsocial avoidance and ameliorate neuroinflammatory responses. To test this, C57BL/6 mice were divided into treatment groups. One group from RSD and controls received daily injections of imipramine for 24days, following 6 cycles of RSD. Two other groups were treated with saline. RSD mice spent significantly less time in the interaction zone when an aggressor was present in the cage. Administration of imipramine reversed social avoidance behavior, significantly increasing the interaction time, so that it was similar to that of control mice. Moreover, 24days of imipramine treatment in RSD mice significantly decreased stress-induced mRNA levels for IL-6 in brain microglia. Following ex vivo LPS stimulation, microglia from mice exposed to RSD, had higher mRNA expression of IL-6, TNF-α, and IL-1β, and this was reversed by imipramine treatment. In a second experiment, imipramine was added to drinking water confirming the reversal of social avoidant behavior and decrease in mRNA expression of IL-6 in microglia. These data suggest that the antidepressant imipramine may exert its effect, in part, by down-regulating microglial activation.

  2. Anesthetic ketamine counteracts repetitive mechanical stress-induced learning and memory impairment in developing mice.

    Science.gov (United States)

    Peng, Sheng; Zhang, Yan; Wang, Hua; Ren, Bingxu; Zhang, Jiannan

    2011-10-01

    The aim of this study is to investigate whether ketamine, a noncompetitive N-methyl-D: -aspartate receptor (NMDAR) antagonist, had an influence on learning and memory in developing mice. Fifty Kunming mice aged 21 days were randomly divided into 5 subgroups (n = 10 for each) to receive intraperitoneal injection of equal volume of saline (S group) or ketamine (25, 50 or 100 mg/kg of body weight/day) for 7 consecutive days, or to be left untreated (C group). A step-down passive avoidance test was performed to evaluate learning and memory in these mice on days 8 and 9. Additionally, the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined. Rats receiving saline or sub-anesthetic dose of ketamine (25 mg/kg) showed significantly decreased abilities of learning and memory and reduced expression of BDNF, compared to the normal controls (P learning and memory and expression of BDNF were found for anesthetic doses of ketamine (50 or 100 mg/kg)-treated rats and controls (P > 0.05). Repetitive mechanical stress impairs learning and memory performance in developing mice, which may be associated with decreased BDNF expression. The stress-induced learning and memory impairment can be prevented by anesthetic doses of ketamine.

  3. The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-) : cystine supplier and beyond.

    Science.gov (United States)

    Conrad, Marcus; Sato, Hideyo

    2012-01-01

    The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.

  4. Prevalence and risk factors of stress-induced gastrointestinal bleeding in critically ill children

    Institute of Scientific and Technical Information of China (English)

    Chookhuan Nithiwathanapong; Sanit Reungrongrat; Nuthapong Ukarapol

    2005-01-01

    AIM: To assess the frequency and the risk factors of stress-induced gastrointestinal (GI) bleeding in children admitted to a pediatric intensive care unit (PICU).METHODS: The medical records of children aged between 1 month and 15 years admitted to the PICU between January 2002 and December 2002 were reviewed.Demographic data, indications for PICU admission, principle diagnosis, and basic laboratory investigations were recorded. Previously described factors for stress ulcer bleeding (mechanical ventilation, sepsis, acute respiratory distress syndrome, renal insufficiency, coagulopathy,thrombocytopenia, and intracranial pathology) were used as independent variables in a multivariate analysis.RESULTS: One hundred and seventy of two hundred and five medical records were eligible for review. The most common indication for PICU admission was respiratory failure (48.8%). Twenty-five children received stress ulcer bleeding prophylaxis with ranitidine. The incidence of stress ulcer bleeding was 43.5%, in which 5.3% were clinically significant bleeding. Only mechanical ventilation and thrombocytopenia were significantly associated with stress ulcer bleeding using the univariate analysis.The odds ratio and 95% confidence intervals were 5.13(1.86-14.12) and 2.26 (1.07-4.74), respectively. However, the logistic regression analysis showed that mechanicai ventilation was the only significant risk factor with the odds ratio of 14.1.CONCLUSION: The incidence of gastrointestinal bleeding was high in critically ill children. Mechanical ventilation was an important risk factor for gastrointestinal bleeding.

  5. Genome wide transcriptional response of Saccharomyces cerevisiae to stress-induced perturbations

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    Hilal eTaymaz-Nikerel

    2016-02-01

    Full Text Available Cells respond to environmental and/or genetic perturbations in order to survive and proliferate. Characterization of the changes after various stimuli at different -omics levels is crucial to comprehend the adaptation of cells to changing conditions. Genome wide quantification and analysis of transcript levels, the genes affected by perturbations, extends our understanding of cellular metabolism by pointing out the mechanisms that play role in sensing the stress caused by those perturbations and related signaling pathways, and in this way guides us to achieve endeavors such as rational engineering of cells or interpretation of disease mechanisms. Saccharomyces cerevisiae as a model system has been studied in response to different perturbations and corresponding transcriptional profiles were followed either statically or/and dynamically, short- and long- term. This review focuses on response of yeast cells to diverse stress inducing perturbations including nutritional changes, ionic stress, salt stress, oxidative stress, osmotic shock, as well as to genetic interventions such as deletion and over-expression of genes. It is aimed to conclude on common regulatory phenomena that allow yeast to organize its transcriptomic response after any perturbation under different external conditions.

  6. Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine.

    Science.gov (United States)

    Koriem, Khaled M M; Soliman, Rowan E

    2014-01-01

    Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective.

  7. L -sulpiride, at antidepressant dosage, prevents conditioned-fear stress-induced gastric lesions in rats.

    Science.gov (United States)

    Benelli, A; De Pol A; Poggioli, R; Cavazzuti, E; Arletti, R; Bertolini, A; Vergoni, A V

    2000-08-01

    It has been previously shown that long-term treatment with low doses of l-sulpiride is highly effective in rat models of depression and of anticipatory anxiety/panic behavior. The present study was aimed at investigating whether the same treatment can prevent the ulcerogenic effect of repeated inescapable stresses. In adult rats, the repeated (7 consecutive days) exposure to an uncontrollable stressful condition (inescapable 2.5 mA scrambled shock for 60 s) produced the development of gastric lesions (multiple punctiform telangiectasias in all rats, with superficial erosions or more severe ulcerations in 10 out 13 rats; score 4.67 +/- 0.44). l-sulpiride, intraperitoneally injected once a day at an antidepressant dose level (4 mg kg(-1) per day), starting 21 days before the beginning of the 7-day sequence of inescapable punishments ( = 28 daily treatments), almost completely prevented the stress-induced gastric injury (score 1.67 +/- 0.29; Psulpiride prevents the development of gastric lesions induced by chronic exposure to uncontrollable stress.

  8. Effects of (-)-sesamin on chronic stress-induced memory deficits in mice.

    Science.gov (United States)

    Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Kim, Kyung Sook; Lee, Kung Eun; Cho, Yoon Jeong; Lee, Myung Koo

    2016-11-10

    This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element binding protein (CREB), which were reduced by chronic EF stress, were increased by treatment with (-)-sesamin. Retention latencies in the passive avoidance test and dopamine levels in the substantia nigra-striatum were also reduced by chronic EF stress, and similarly recovered with (-)-sesamin treatment. These results suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced spatial and habit learning memory deficits by modulating both NMDA receptor and dopaminergic neuronal systems.

  9. Binary Stress Induces an Increase in Indole Alkaloid Biosynthesis in Catharanthus roseus

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    Wei eZhu

    2015-07-01

    Full Text Available Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to that in control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress.

  10. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Wang; Qian Wang; Yong Chen; Qiang Lin; Hui-Bao Gao; Ping Zhang

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells.In a pattern similar to the normal process of Leydig cell ageing,stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion.We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells.To test this hypothesis,we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally,intracellular lipofuscin levels,reactive oxygen species (ROS)levels and DNA damage were assessed.The results showed that chronic stress accelerated ageing-related changes:ultrastructural alterations associated with ageing,cellular lipofuscin accumulation,increased ROS levels and more extensive DNA damage were observed.Additionally,testosterone levels were decreased.This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

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

    Science.gov (United States)

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

    2012-11-01

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

  12. Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes

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    Zhang, Yue; Han, Jun; Zhu, Cheng-Cheng; Tang, Feng; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2016-01-01

    T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence. T-2 toxin has posed various toxic effects on human and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues, while HT-2 toxin is the major metabolite which is deacetylated by T-2 toxin. In this study, we focused on the toxic effects of HT-2 on porcine oocyte maturation. We treated the porcine oocyte with HT-2 toxin in vitro, and we first found that HT-2 treatment inhibited porcine oocyte polar body extrusion and cumulus cell expansion. We observed the disrupted meiotic spindle morphology after treatment, which might be due to the reduced p-MAPK protein level. Actin distribution was also disturbed, indicating that HT-2 affects cytoskeleton of porcine oocytes. We next explored the causes for the failure of oocyte maturation after HT-2 treatment. We found that HT-2 treated oocytes showed the increased ROS level, which indicated that oxidative stress had occurred. We also detected autophagy as well as early apoptosis in the treatment oocytes. Due to the fact that oxidative stress could induced apoptosis, our results indicated that HT-2 toxin caused oxidative stress induced apoptosis and autophagy, which further affected porcine oocyte maturation. PMID:27658477

  13. Evaluation of Stress-Inducing Factors of Educational Environment in Hamadan Dentistry School’s Students

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    M. Dalband

    2007-01-01

    Full Text Available ntroduction & Objective: The aim of this study was to evaluate stressor factors of educational environment in Hamadan dental school’s students in year 2002.Materials & Methods: The study design was descriptive, cross-sectional and it was accomplished using a questionnaire which was taken from DES (dental environment stress questionnaire. According to restricted number of statistical population all members of population (154 students were evaluated as samples and this study was a survey one. Results: The results of this study indicated that most stressfull factors in dental students has been related to class work with mean score 3.18±0.83 and faculty-student relationship with mean score 3.05±0.83. Female students showed more total stress than male students (2.73 vs. 2.44. The fourth-year students had the most stress rate in all students of different years (3.05 and preclinical and clinical factors were the most stress-inducing factors of these students (3.63.Conclusion: It is concluded that the environment of Hamadan dental school and the process of education in the field of dentistry is potentially stressful. Also there is a reverse relationship between level of stress in students and their academic efficiencies.

  14. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

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    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  15. Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

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    Eva Klinman

    2015-07-01

    Full Text Available Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5 activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration.

  16. Moesin and stress-induced phosphoprotein-1 are possible sero-diagnostic markers of psoriasis.

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    Hideki Maejima

    Full Text Available To identify diagnostic markers for psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from psoriasis vulgaris and psoriatic arthritis patients were screened by two-dimensional immunoblotting (2D-IB. Based on 2D-IB and MADLI TOF/TOF-MS analyses, eleven proteins each in psoriasis vulgaris and psoriatic arthritis were identified as autoantigens. Furthermore, serum levels of moesin, keratin 17 (K17, annexin A1 (ANXA1, and stress-induced phophoprotein-1 (STIP1, which were detected as autoantigens, were studied by dot blot analysis with psoriasis patients and healthy controls. The levels of moesin and STIP1 were significantly higher in sera from patients with psoriasis vulgaris than in the controls (moesin: P<0.05, STIP1: P<0.005. The area under the curve (AUC for moesin and STIP1 between patients with psoraisis vulgaris and controls was 0.747 and 0.792, respectively. STIP1 and K17 levels were significantly higher in sera from patients with psoriatic arthritis than in those with psoriasis vulgaris (P<0.05 each. The AUC for STIP1 and K17 between patients with psoriatic arthritis and psoriasis vulgaris was 0.69 and 0.72, respectively. The STIP1 or moesin, CK17 serum level was not correlated with disease activity of psoriasis patients. These data suggest that STIP1 and moesin may be novel and differential sero-diagnostic markers for psoriasis vulgaris and psoriatic arthritis.

  17. Arabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling

    Science.gov (United States)

    Brzezinka, Krzysztof; Altmann, Simone; Czesnick, Hjördis; Nicolas, Philippe; Gorka, Michal; Benke, Eileen; Kabelitz, Tina; Jähne, Felix; Graf, Alexander; Kappel, Christian; Bäurle, Isabel

    2016-01-01

    Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the FORGETTER1 (FGT1) locus, with fgt1 mutants displaying reduced maintenance of heat-induced gene expression. FGT1 encodes the Arabidopsis thaliana orthologue of Strawberry notch (Sno), and the protein globally associates with the promoter regions of actively expressed genes in a heat-dependent fashion. FGT1 interacts with chromatin remodelers of the SWI/SNF and ISWI families, which also display reduced heat stress memory. Genomic targets of the BRM remodeler overlap significantly with FGT1 targets. Accordingly, nucleosome dynamics at loci with altered maintenance of heat-induced expression are affected in fgt1. Together, our results suggest that by modulating nucleosome occupancy, FGT1 mediates stress-induced chromatin memory. DOI: http://dx.doi.org/10.7554/eLife.17061.001 PMID:27680998

  18. Chaperone-Targeting Cytotoxin and Endoplasmic Reticulum Stress-Inducing Drug Synergize to Kill Cancer Cells

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    Joseph M. Backer

    2009-11-01

    Full Text Available Diverse physiological and therapeutic insults that increase the amount of unfolded or misfolded proteins in the endoplasmic reticulum (ER induce the unfolded protein response, an evolutionarily conserved protective mechanism that manages ER stress. Glucose-regulated protein 78/immunoglobulin heavy-chain binding protein (GRP78/BiP is an ER-resident protein that plays a central role in the ER stress response and is the only known substrate of the proteolytic A subunit (SubA of a novel bacterial AB5 toxin. Here, we report that an engineered fusion protein, epidermal growth factor (EGF-SubA, combining EGF and SubA, is highly toxic to growing and confluent epidermal growth factor receptor-expressing cancer cells, and its cytotoxicity is mediated by a remarkably rapid cleavage of GRP78/BiP. Systemic delivery of EGF-SubA results in a significant inhibition of human breast and prostate tumor xenografts in mouse models. Furthermore, EGF-SubA dramatically increases the sensitivity of cancer cells to the ER stress-inducing drug thapsigargin, and vice versa, demonstrating the first example of mechanism-based synergism in the action of a cytotoxin and an ER-targeting drug.

  19. Micromechanical modeling of stress-induced strain in polycrystalline Ni–Mn–Ga by directional solidification

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Yuping, E-mail: zhuyuping@126.com [Seismic Observation and Geophysical Imaging Laboratory, Institute of Geophysics, China Earthquake Administration, Beijing 100081 (China); Shi, Tao; Teng, Yao [Faculty of Civil Engineering and Mechanics, Jiangsu University, Zhenjiang 212013 (China)

    2015-10-05

    Highlights: • A micromechanical model of directional solidification Ni–Mn–Ga is developed. • The stress–strain curves in different directions are tested. • The martensite Young’s moduli in different directions are predicted. • The macro reorientation strains in different directions are investigated. - Abstract: Polycrystalline ferromagnetic shape memory alloy Ni–Mn–Ga produced by directional solidification possess unique properties. Its compressive stress–strain behaviors in loading–unloading cycle show nonlinear and anisotropic. Based on the self-consistent theory and thermodynamics principle, a micromechanical constitutive model of polycrystalline Ni–Mn–Ga by directional solidification is developed considering the generating mechanism of the macroscopic strain and anisotropy. Then, the stress induced strains at different angles to solidification direction are calculated, and the results agree well with the experimental data. The predictive curves of martensite Young’s modulus and macro reorientation strain in different directions are investigated. It may provide theoretical guidance for the design and use of ferromagnetic shape memory alloy.

  20. The effect of beta blockade on stress-induced cognitive dysfunction in adolescents.

    Science.gov (United States)

    Faigel, H C

    1991-07-01

    Test anxiety is severely disabling to students whose fear of examinations causes cognitive dysfunction that paralyzes their thinking the way stage fright impairs actors ability to act. In studies using subjective evaluations among actors and musicians, beta-blockade relieved stage fright and has been used informally to treat test anxiety in students without objective measures of effectiveness. The Scholastic Aptitude Test (SAT) was chosen as an objective test instrument to confirm the effect of beta-blockade on test anxiety and performance. Thirty-two high school students who had already taken the SAT before enrolling in this study and who had stress-induced cognitive dysfunction on exams were given 40 mg of propranolol one hour before they retook those tests. Mean SAT scores with beta-blockade were 130 points higher than on the initial SAT done before entering the study without medication (p = less than .01). A single dose of propranolol immediately before the SAT permitted improved performance in students prone to cognitive dysfunction due to test anxiety.

  1. Saffron (Crocus sativus) aqueous extract and its constituent crocin reduces stress-induced anorexia in mice.

    Science.gov (United States)

    Halataei, Bahar-al-Sadat; Khosravi, Maryam; Arbabian, Sedigheh; Sahraei, Hedayat; Golmanesh, Leila; Zardooz, Homeira; Jalili, Cyrus; Ghoshooni, Hassan

    2011-12-01

    In the present study, the effects of an ethanol and aqueous extract of saffron Crocus sativus and its constituents safranal and crocin on the stress-induced reduction in food intake, weight gain and anorexic time in mice were investigated. Male albino mice (20-25 g) were irregularly exposed to a trial of electroshock stress for 7 days. Then, the anorexic time as well as the animal's food intake and weight were recorded. In addition, blood samples were obtained on days 1 and 7 for corticosterone determination. Intraperitoneal (i.p.) administration of the aqueous but not the ethanol extract (10, 50 and 100 mg/kg) significantly reduced the anorexic time. The results were similar for crocin (1, 5 and 10 mg/kg; i.p.). In addition, a reduction in weight gain was observed in the controls as well as in the groups that received alcohol extract or safranal. However, this was not observed in animals treated with aqueous extract or crocin. The plasma corticosterone level did not increase in the aqueous extract and crocin treated animals. It can be concluded that the saffron aqueous extract and its constituent crocin reduce side effects of electroshock stress in mice.

  2. Stress-induced endocrine response and anxiety: the effects of comfort food in rats.

    Science.gov (United States)

    Ortolani, Daniela; Garcia, Márcia Carvalho; Melo-Thomas, Liana; Spadari-Bratfisch, Regina Celia

    2014-05-01

    The long-term effects of comfort food in an anxiogenic model of stress have yet to be analyzed. Here, we evaluated behavioral, endocrine and metabolic parameters in rats submitted or not to chronic unpredictable mild stress (CUMS), with access to commercial chow alone or to commercial chow and comfort food. Stress did not alter the preference for comfort food but decreased food intake. In the elevated plus-maze (EPM) test, stressed rats were less likely to enter/remain in the open arms, as well as being more likely to enter/remain in the closed arms, than were control rats, both conditions being more pronounced in the rats given access to comfort food. In the open field test, stress decreased the time spent in the centre, independent of diet; neither stress nor diet affected the number of crossing, rearing or grooming episodes. The stress-induced increase in serum corticosterone was attenuated in rats given access to comfort food. Serum concentration of triglycerides were unaffected by stress or diet, although access to comfort food increased total cholesterol and glucose. It is concluded that CUMS has an anorexigenic effect. Chronic stress and comfort food ingestion induced an anxiogenic profile although comfort food attenuated the endocrine stress response. The present data indicate that the combination of stress and access to comfort food, common aspects of modern life, may constitute a link among stress, feeding behavior and anxiety.

  3. Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

    Directory of Open Access Journals (Sweden)

    Popović Nataša

    2010-01-01

    Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

  4. Reduction of spinal PGE2 concentrations prevents swim stress-induced thermal hyperalgesia.

    Science.gov (United States)

    Guevara, Coram; Fernandez, Ana Cristina; Cardenas, Ricardo; Suarez-Roca, Heberto

    2015-03-30

    We evaluated the association between spinal PGE2 and thermal hyperalgesia following repeated stress. Thermal nociception was determined in male Sprague-Dawley rats using the hot-plate test, before and after forced-swimming; non-conditioned rats served as controls. Animals were pretreated with ketoprofen or meloxicam, preferential COX-1 and COX-2 inhibitors, respectively. After the second hot-plate test, we measured serum corticosterone (stress marker), and lumbar spinal PGE2 (neuroinflammation marker) under peripheral inflammation (1% formalin plantar injection). Stressed rats displayed response latencies 40% shorter and inflammatory spinal PGE2 levels 95% higher than controls. Pretreatment with ketoprofen or meloxicam prevented hyperalgesia and elevation of spinal PGE2, increasing the escape behavior time during forced swimming 95% respect to saline-treated rats. Corticosterone levels in stressed rats were 97% higher than controls; COX inhibitors reduced them by 84%. PGE2 could participate in stress-induced hyperalgesia, learned helplessness, and corticosterone production, supporting the use of non-steroidal anti-inflammatory drugs (NSAIDs) for persistent pain associated with chronic stress and depression.

  5. Antioxidant effect of pomegranate against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Anahita Aboonabi

    2014-01-01

    Full Text Available Oxidative stress attributes a crucial role in chronic complication of diabetes. The aim of this study was to determine the most effective part of pomegranate on oxidative stress markers and antioxidant enzyme activities against streptozotocin-nicotinamide (STZ-NA-induced diabetic rats. Male Sprague-Dawley rats were randomly divided into six groups. Experimental diabetes was induced by a single intraperitoneal injection (i.p, 15 min after the i.p administration of NA. Diabetic rats showed significant increase in plasma glucose level, and the significant decrease in plasma insulin level. The activities of antioxidant enzymes such as total antioxidant status (TAS, superoxide dismutase (SOD, and catalase (CAT reduced while the levels of biomarkers of oxidative stress such as gamma-glutamyle transferase (GGT, and malondialdehyde (MDA increased in diabetic control rats as compared to normal control rats. Oral treatment with pomegranate seed-juice for 21 days demonstrated significant protective effects on all the biochemical parameters studied. Besides, biochemical findings were supported by histopathological study. These results revealed that pomegranate has potential protective effect against oxidative stress induced diabetic rats.

  6. Cross-country differences in basal and stress-induced cortisol secretion in older adults.

    Directory of Open Access Journals (Sweden)

    Juliana N Souza-Talarico

    Full Text Available Several studies have emphasized the association between socioeconomic status (SES and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries.Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST in both populations.Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants.These findings suggest that country context may modulate cortisol secretion and could impact the population health.

  7. The Zwicky Transient Facility

    CERN Document Server

    Bellm, Eric C

    2014-01-01

    The Zwicky Transient Facility (ZTF) is a next-generation optical synoptic survey that builds on the experience and infrastructure of the Palomar Transient Factory (PTF). Using a new 47 deg$^2$ survey camera, ZTF will survey more than an order of magnitude faster than PTF to discover rare transients and variables. I describe the survey and the camera design. Searches for young supernovae, fast transients, counterparts to gravitational-wave detections, and rare variables will benefit from ZTF's high cadence, wide area survey.

  8. An atypical presentation of antiphospholipid antibody syndrome.

    Science.gov (United States)

    D'souza, Deepti; Dandakeri, Sukumar; Bhat, M Ramesh; Srinath, M K

    2015-01-01

    Cutaneous manifestations in antiphospholipid antibody syndrome (APS) though common, are extremely diverse and it is important to know which dermatological finding should prompt consideration of antiphospholipid syndrome. The cutaneous manifestations of APS vary from livedo reticularis to cutaneous necrosis, and systemic involvement is invariably an accomplice in APS. Cutaneous ulcers with sharp margins can be seen in APS and they are usually seen on the legs. This case had an atypical presentation, as the initial presentation was painful necrotic ulcers over the legs, which resembled pyoderma gangrenosum and she had no systemic manifestations. There was no history of any arterial or venous thrombosis or any abortions. Antiphospholipid syndrome can be tricky to diagnose when cutaneous lesions are atypical. Nonetheless, it is very important to pin down this syndrome early due to its systemic complications.

  9. An atypical presentation of antiphospholipid antibody syndrome

    Directory of Open Access Journals (Sweden)

    Deepti D′Souza

    2015-01-01

    Full Text Available Cutaneous manifestations in antiphospholipid antibody syndrome (APS though common, are extremely diverse and it is important to know which dermatological finding should prompt consideration of antiphospholipid syndrome. The cutaneous manifestations of APS vary from livedo reticularis to cutaneous necrosis, and systemic involvement is invariably an accomplice in APS. Cutaneous ulcers with sharp margins can be seen in APS and they are usually seen on the legs. This case had an atypical presentation, as the initial presentation was painful necrotic ulcers over the legs, which resembled pyoderma gangrenosum and she had no systemic manifestations. There was no history of any arterial or venous thrombosis or any abortions. Antiphospholipid syndrome can be tricky to diagnose when cutaneous lesions are atypical. Nonetheless, it is very important to pin down this syndrome early due to its systemic complications.

  10. Primary atypical sacral meningioma- not always benign

    Energy Technology Data Exchange (ETDEWEB)

    Bhadra, A.K.; Casey, A.T.H.; Saifuddin, A.; Briggs, T.W. [Royal National Orthopaedic Hospital, Stanmore, London (United Kingdom)

    2007-06-15

    We present a case of an atypical recurrent meningioma of the sacrum with pulmonary metastasis in a 31-year-old man. He presented with deep-seated buttock pain and urinary hesitancy for 3 months. MRI revealed a lesion occupying the central and left side of the sacral canal at the S1-S2 level. Surgical excision of the lesion via a posterior approach was undertaken, and the patient became symptom-free post-operatively. Histology confirmed atypical meningioma. Eight months later he re-presented with similar symptoms, and MRI confirmed local recurrence. The patient underwent left hemisacrectomy. Six months later he again presented with low back pain and MRI confirmed a second local recurrence. A CT scan of the chest showed multiple lung metastases. The patient died of a severe chest infection 18 months later. (orig.)

  11. Atypical reactive histiocytosis. A case report.

    Directory of Open Access Journals (Sweden)

    Jorge E. Barleta del Castillo

    2004-08-01

    Full Text Available This paper presents the case of a 50 year old chronic alcoholic and heavy smoker female that was assisted at the provincial university hospital ¨Dr. Gustavo Aldereguía Lima¨ in Cienfuegos city due to a severe adenic syndrome and who was diagnosed as a case of atypical reactive histiocytosis , problem which disappeared with the abstinence of toxic habits, improving her health.

  12. Bisphosphonate-induced atypical subtrochanteric femoral fracture

    OpenAIRE

    2013-01-01

    The use of bisphosphonates (BPs) is universally accepted in the management of osteoporosis. However, a small percentage of patients have been recognised to develop atypical subtrochanteric fractures of the femur with the prolonged use of BPs. We report a rare case of bilateral insufficiency lesions in the proximal femora, where a major subtrochanteric fracture developed with a minor fall. This was successfully treated with internal fixation using proximal femoral nail.

  13. An atypical case of segmental spinal dysgenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zana, Elodie; Chalard, Francois; Sebag, Guy [Hopital Robert Debre, Department of Paediatric Imaging, Paris (France); Mazda, Keyvan [Hopital Robert Debre, Department of Paediatric Orthopaedic Surgery, Paris (France)

    2005-09-01

    Spinal segmental dysgenesis is a complex closed dysraphism. The diagnostic criteria are: lumbar or thoracolumbar vertebral dysgenesis causing kyphosis, focal spinal cord narrowing without exiting roots, deformity of the lower limbs and paraplegia or paraparesis. We present a newborn who showed atypical features of bifocal spinal cord narrowing, without any vertebral abnormality at the proximal level. This seems to be a variant of this rare entity, whose early diagnosis is important, as surgical stabilisation of the spine is required. (orig.)

  14. Atypical presentations of methemoglobinemia from benzocaine spray.

    Science.gov (United States)

    Tantisattamo, Ekamol; Suwantarat, Nuntra; Vierra, Joseph R; Evans, Samuel J

    2011-06-01

    Widely used for local anesthesia, especially prior to endoscopic procedures, benzocaine spray is one of the most common causes of iatrogenic methemoglobinemia. The authors report an atypical case of methemoglobinemia in a woman presenting with pale skin and severe hypoxemia, after a delayed repeat exposure to benzocaine spray. Early recognition and prompt management of methemoglobinemia is needed in order to lessen morbidity and mortality from this entity.

  15. An atypical mycobacterial infection of the shoulder

    Directory of Open Access Journals (Sweden)

    Christopher L Talbot

    2012-01-01

    Full Text Available Mycobacterium malmoense is an acid-fast non-tuberculous organism that most commonly causes pulmonary infection. Extrapulmonary infection has also been reported. With an increased emphasis being placed on the clinical importance of this organism, especially within Europe, we report the first case of septic arthritis of the shoulder caused by this organism. We also highlight the importance of considering atypical mycobacterium infection in the differential diagnosis of shoulder infection and issues surrounding the management of this entity.

  16. Atypical manifestations of multiple myeloma: Radiological appearance

    Energy Technology Data Exchange (ETDEWEB)

    Hess, Thomas [Department of Radiology, St-Vincenz Hospital, Auf dem Schafsberg, D-65549 Limburg (Germany)]. E-mail: t.hess@st-vincenz.de; Egerer, Gerlinde [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kasper, Bernd [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Rasul, Kakil Ibrahim [Hamad Medical Center, Moha (Qatar); Goldschmidt, Hartmut [Department of Internal Medicine V, Haematology/Oncology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kauffmann, G.W. [Department of Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany)

    2006-05-15

    Diagnostic procedures performed on patients with multiple myeloma typically reveal lytic bone lesions, osteopenia or osteoporosis, bone marrow infiltration by plasma cells as well as overproduction of immunoglobulin or light chains in the serum or urine. Skeletal manifestations are extremely variable and the unusual forms have been described extensively. Extramedullary plasma-cell tumours (plasmocytoma) are found in about 5% of newly diagnosed patients with multiple myelomas. In this paper we present eight patients with atypical forms of multiple myeloma.

  17. Atypical retroperitoneal extension of iliopsoas bursitis

    Energy Technology Data Exchange (ETDEWEB)

    Coulier, B.; Cloots, V. [Department of Diagnostic Imaging, Cliniques St. Luc, Rue St Luc 8, 5004, Bouge, Namur (Belgium)

    2003-05-01

    We report two rare cases of iliopsoas bursitis extending into the retroperitoneal space. The first lesion contained much gas, mimicking a retroperitoneal abscess, and the second was responsible for atypical inguinal pain. The diagnosis was made by contrast-enhanced CT in both cases and arthrography in the first case. Iliopsoas bursitis in these two patients, it is hypothesized, extended into the retroperitoneum, at least in part, by way of intraneural or perineural structures. (orig.)

  18. Prophylactic Nailing of Incomplete Atypical Femoral Fractures

    Directory of Open Access Journals (Sweden)

    Chang-Wug Oh

    2013-01-01

    Full Text Available Introduction. Recent reports have described the occurrence of low-energy subtrochanteric and femoral shaft fractures associated with long-term bisphosphonate use. Although information regarding the surgical treatment of these atypical femoral fractures is increasing, it is unclear if the preventive operation is useful in incomplete fractures. This study examined the results of preventive intramedullary nailing for incomplete atypical femoral fractures. Material and Methods. A retrospective search was conducted for patients older than 50 years receiving bisphosphonate therapy, with incomplete, nondisplaced fractures in either the subtrochanteric or diaphyseal area of the femur. Seventeen patients with a total of 20 incomplete, non-displaced lesions were included. The mean duration of bisphosphonate use was 50.5 months. Eleven of the 17 (64.7% patients had complete or incomplete fractures on the contralateral femur. All were treated with prophylactic fixation of an intramedullary (IM nail. The minimum followup was 12 months. Results. All cases healed with a mean period of 14.3 weeks. Nineteen of the 20 cases healed with the dissolution of incomplete fractures of the lateral aspect. A complete fracture developed at the time of nailing in one patient, but it healed with callus bridging. Conclusion. IM nailing appears to be a reliable way of preventing the progress of incomplete atypical femoral fractures.

  19. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Kawamura R

    2012-01-01

    Full Text Available Ryosuke Kawamura1,2, Hidenao Ideta1, Hideyuki Hori1, Kenya Yuki2, Tsuyoshi Uno1, Tatsurou Tanabe1, Kazuo Tsubota2, Tsutomu Kawasaki11Ideta Eye Hospital, Kumamoto, Japan; 2Keio University, School of Medicine, Department of Ophthalmology, Tokyo, JapanBackground: Central serous chorioretinopathy (CSC has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC.Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 µm, and exposure time of 13–60 seconds to minimize retinal damage.Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30. Final BCVA

  20. Stress-induced deformation at Ap~Mp and thermal cycling behavior of Cu-Al-Ni single crystals

    Institute of Scientific and Technical Information of China (English)

    陈庆福; 蔡伟; 赵连城

    2001-01-01

    Stress-induced deformation in Ap~Mp and concomitant shape recovery behavior of Cu-13.4Al-4.0Ni single crystals were studied. Abnormal high stress-induced deformation exists in Ap~Mp under the conditions of either heating with load or cooling with load. The recovered deformation is successively composed of four parts, the recoveries from superelasticity, normal reverse transformation, thermally activated reverse transformation of partially stabilized martensite and reverse transformation of stabilized martensite by over-heating. With increasing cycling number, the recovery part from normal reverse transformation decreases, while that from reverse transformation of stabilized martensite by over-heating increases, which shows a typical stabilization of martensite.

  1. Molecular dynamics simulations of stress-induced phase transformations and grain nucleation at crack tips in Fe

    Science.gov (United States)

    Latapie, A.; Farkas, D.

    2003-09-01

    The molecular dynamics simulation technique is used to study a stress-induced new grain formation mechanism at the crack tip of a nanocrystalline alpha-iron sample at temperatures ranging from 100 to 600 K. The stress-induced formation of new bcc grains, created inside existing grains, is found to occur through a metastable bcc to fcc phase transformation at the crack tip of the sample. A Nishiyama-Wassermann orientation relationship is found between the original bcc grain and the fcc phase and a Kurdjumov-Sachs orientation relationship is found between the new bcc grain created and the fcc transition phase. The new grain nucleation is observed to increase with increasing temperature and stacking faults associated with the fcc phase are observed at the higher temperatures.

  2. Stress-induced cortisol secretion impairs detection performance in x-ray baggage screening for hidden weapons by screening novices.

    Science.gov (United States)

    Thomas, Livia; Schwaninger, Adrian; Heimgartner, Nadja; Hedinger, Patrik; Hofer, Franziska; Ehlert, Ulrike; Wirtz, Petra H

    2014-09-01

    Aviation security strongly depends on screeners' performance in the detection of threat objects in x-ray images of passenger bags. We examined for the first time the effects of stress and stress-induced cortisol increases on detection performance of hidden weapons in an x-ray baggage screening task. We randomly assigned 48 participants either to a stress or a nonstress group. The stress group was exposed to a standardized psychosocial stress test (TSST). Before and after stress/nonstress, participants had to detect threat objects in a computer-based object recognition test (X-ray ORT). We repeatedly measured salivary cortisol and X-ray ORT performance before and after stress/nonstress. Cortisol increases in reaction to psychosocial stress induction but not to nonstress independently impaired x-ray detection performance. Our results suggest that stress-induced cortisol increases at peak reactivity impair x-ray screening performance.

  3. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

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

    Science.gov (United States)

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

    2016-08-18

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

  5. Caspase-4 directly activates caspase-9 in endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells.

    Science.gov (United States)

    Yamamuro, Akiko; Kishino, Takashi; Ohshima, Yu; Yoshioka, Yasuhiro; Kimura, Tomoki; Kasai, Atsushi; Maeda, Sadaaki

    2011-01-01

    The present study investigated the function of caspase-4 in endoplasmic reticulum (ER) stress-induced apoptosis in human neuronal cell line SH-SY5Y. Tunicamycin, which is known to induce ER stress, activated both caspase-9 and caspase-4, and the activation of caspase-4 preceded that of caspase-9. The caspase-4 inhibitor LEVD-CHO suppressed both the apoptosis and caspase-9 activation. In addition, human recombinant active caspase-4 cleaved wild type and D330A mutant substituted Asp-330 for alanine of human recombinant procaspase-9, but did not cleave D315A mutant substituted Asp-315 for alanine. These results suggest that caspase-4 directly activates caspase-9 by the processing of procaspase-9 at Asp-315 in ER stress-induced neuronal apoptosis.

  6. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression

    DEFF Research Database (Denmark)

    Agudelo, Leandro Z; Femenía, Teresa; Orhan, Funda

    2014-01-01

    Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which...... skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid......, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration...

  7. Downregulation of the stress-induced ligand ULBP1 following SV40 infection confers viral evasion from NK cell cytotoxicity.

    Science.gov (United States)

    Bauman, Yoav; Drayman, Nir; Ben-Nun-Shaul, Orly; Vitenstein, Alon; Yamin, Rachel; Ophir, Yael; Oppenheim, Ariella; Mandelboim, Ofer

    2016-03-29

    Polyomaviruses are a diverse family of viruses which are prevalent in the human population. However, the interactions of these viruses with the immune system are not well characterized. We have previously shown that two human polyomaviruses, JC and BK, use an identical microRNA to evade immune attack by Natural Killer (NK) cells. We showed that this viral microRNA suppresses ULBP3 expression, a stress induced ligand for the killer receptor NKG2D. Here we show that Simian Virus 40 (SV40) also evades NK cell attack through the down regulation of another stress-induced ligand of NKG2D, ULBP1. These findings indicate that NK cells play an essential role in fighting polyomavirus infections and further emphasize the importance of various members of the ULBP family in controlling polyomavirus infection.

  8. Systematic control of stress-induced anisotropy in pseudomorphic iron garnet thin films

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, M., E-mail: Masashi.Kubota@dsn.rohm.co.jp [Correlated Electron Research Group (CERG) and Cross-Correlated Materials Research Group (CMRG), RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Power Electronics R and D Unit, ROHM Co., Ltd., Kyoto 615-8585 (Japan); Shibuya, K.; Tokunaga, Y. [Correlated Electron Research Group (CERG) and Cross-Correlated Materials Research Group (CMRG), RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Kagawa, F. [Department of Applied Physics and Quantum Phase Electronics Center (QPEC), University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan); CREST, Japan Science and Technology Agency, Bunkyo, Tokyo 113-8656 (Japan); Tsukazaki, A. [Department of Applied Physics and Quantum Phase Electronics Center (QPEC), University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan); PRESTO, Japan Science and Technology Agency, Bunkyo, Tokyo 113-8656 (Japan); Tokura, Y.; Kawasaki, M. [Correlated Electron Research Group (CERG) and Cross-Correlated Materials Research Group (CMRG), RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Department of Applied Physics and Quantum Phase Electronics Center (QPEC), University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan)

    2013-08-15

    Iron garnets are one of the most well-studied magnetic materials that enabled magnetic bubble memories and magneto-optical devices employing films with a perpendicular easy axis. However, most studies have been conducted on rather thick films (>1 μm), and it has not been elucidated whether it is possible to align the magnetic easy axis perpendicular to the film plane for much thinner (<100 nm) films by overcoming shape anisotropy. We studied the effects of epitaxial strain and film composition on the magnetic properties of 50-nm-thick garnet thin films grown by pulsed-laser deposition. Y{sub 3}Fe{sub 5}O{sub 12} was selected as the most prototypical garnet and Sm{sub 3−x}Tm{sub x}Fe{sub 5}O{sub 12} (x=1, 2, 3) was selected in view of its negatively large magnetostriction constants. We employed (111) planes of single crystalline Gd{sub 3}Ga{sub 5}O{sub 12} and (CaGd){sub 3}(MgGaZr){sub 5}O{sub 12} substrates to tune the epitaxial strain. Thin films with a pseudomorphic structure were fabricated with the in-plane strain (ε{sub //}) ranging from −1.5% to +0.5%, corresponding to the stress-induced anisotropy field (H{sub A}) ranging from −40 kOe to +25 kOe, respectively. The magnetization ratio of the out-of-plane to in-plane component (M{sub ⊥}/M{sub //}) systematically varied in accord with H{sub A}, yielding M{sub ⊥}/M{sub //} >1 for thin films with H{sub A} values larger than 20 kOe. Among the films grown, Tm{sub 3}Fe{sub 5}O{sub 12} on Gd{sub 3}Ga{sub 5}O{sub 12} showed the largest ε{sub //} and H{sub A} values of +0.5% and +25 kOe, respectively, to realize an apparently perpendicular easy axis, confirmed by a large M{sub ⊥}/M{sub //} value of 7.8. Further, magnetic force microscope images showed a maze pattern typical of a perpendicularly magnetized film. These results reveal a method for tailoring the magnetic anisotropy of garnet ultrathin films by utilizing epitaxial strain. These thin films may be utilized to obtain nanoscale magnetic bubbles

  9. Effects of Red Wine Tannat on Oxidative Stress Induced by Glucose and Fructose in Erythrocytes in Vitro

    OpenAIRE

    Pazzini, Camila Eliza Fernandes; Oliveira, Ana zilda Ceolin Colpo Simões; Poetini, Márcia Rósula; Pires, Cauê Ferreira; de Camargo, Vanessa Brum; Mendez, Andreas Sebastian Loureiro; Azevedo, Miriane Lucas; Soares, Júlio César Mendes; Folmer, Vanderlei

    2015-01-01

    The literature indicates that red wine presents in its composition several substances that are beneficial to health. This study has investigated the antioxidant effects of Tannat red wine on oxidative stress induced by glucose and fructose in erythrocytes in vitro, with the purpose to determine some of its majoritarian phenolic compounds and its antioxidant capacity. Erythrocytes were incubated using different concentrations of glucose and fructose in the presence or absence of wine. From the...

  10. Nitric Oxide Reduces Hydrogen Peroxide Accumulation Involved in Water Stress-induced Subcellular Anti-oxidant Defense in Maize Plants

    Institute of Scientific and Technical Information of China (English)

    Jianrong Sang; Mingyi Jiang; Fan Lin; Shucheng Xu; Aying Zhang; Mingpu Tan

    2008-01-01

    Nitric oxide (NO) Is a bioactive molecule involved in many biological events, and has been reported as pro-oxidant as well as anti-oxidant in plants. In the present study, the sources of NO production under water stress, the role of NO in water stress-induced hydrogen peroxide (H2O2) accumulation and subcellular activities of anti-oxidant enzymes in leaves of maize (Zea mays L.) plants were investigated. Water stress Induced defense increases in the generation of NO In maize mesphyll cells and the activity of nitric oxide synthase (NOS) in the cytosolic and microsomal fractions of maize leaves. Water stress-induced defense increases in the production of NO were blocked by pretreatments with Inhibitors of NOS and nitrate reductase (NR), suggesting that NO is produced from NOS and NR in leaves of maize plants exposed to water stress. Water stress also induced increases in the activities of the chloroplastic and cytosolic anti-oxidant enzymes superoxide dismutase (SOD), ascorbate peroxidass (APX), and glutathione reductase (GR), and the increases in the activities of anti-oxidant enzymes were reduced by pretreatments with inhibitors of NOS and NR. Exogenous NO increases the activities of water stress-induced subcellular anti-oxidant enzymes, which decreases accumulation of H2O2. Our results suggest that NOS and NR are involved in water strese-induced NO production and NOS is the major source of NO. The potential ability of NO to scavenge H2O2 is, at least in part, due to the induction of a subcellular anti-oxidant defense.

  11. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

    Directory of Open Access Journals (Sweden)

    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  12. Deformation behavior after stress-induced martensite transformation in a Ti-50.8 at.% Ni alloy

    Directory of Open Access Journals (Sweden)

    Wang Xiebin

    2015-01-01

    Full Text Available In this study, the deformation behavior of a Ti-50.8 at.% Ni thin wire, which was subjected to different heat treatments, was investigated by means of uniaxial tensile tests. Considerable ductility (tensile elongation >50% and a large variation of the stress-strain relations are observed after different heat treatments, especially in the stage after the stress-induced martensite transformation plateau. A possible explanation for the observed phenomenon is discussed in this work.

  13. Stress induced a shift from dorsal hippocampus to prefrontal cortex dependent memory retrieval: role of regional corticosterone

    OpenAIRE

    Gaelle eDominguez; Pierre eFaucher; Nadia eHenkous; Ali eKrazem; Christophe ePierard; Daniel eBeracochea

    2014-01-01

    Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1...

  14. TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors.

    Science.gov (United States)

    Choi, Juli; Kim, Ji-eun; Kim, Tae-Kyung; Park, Jin-Young; Lee, Jung-Eun; Kim, Hannah; Lee, Eun-Hwa; Han, Pyung-Lim

    2015-10-01

    Chronic stress is a potent risk factor for depression, but the mechanism by which stress causes depression is not fully understood. To investigate the molecular mechanism underlying stress-induced depression, C57BL/6 inbred mice were treated with repeated restraint to induce lasting depressive behavioral changes. Behavioral states of individual animals were evaluated using the forced swim test, which measures psychomotor withdrawals, and the U-field test, which measures sociability. From these behavioral analyses, individual mice that showed depression-like behaviors in both psychomotor withdrawal and sociability tests, and individuals that showed a resiliency to stress-induced depression in both tests were selected. Among the neuropeptides expressed in the amygdala, thyrotropin-releasing hormone (TRH) was identified as being persistently up-regulated in the basolateral amygdala (BLA) in individuals exhibiting severe depressive behaviors in the two behavior tests, but not in individuals displaying a stress resiliency. Activation of TRH receptors by local injection of TRH in the BLA in normal mice produced depressive behaviors, mimicking chronic stress effects, whereas siRNA-mediated suppression of either TRH or TRHR1 in the BLA completely blocked stress-induced depressive symptoms. The TRHR1 agonist, taltirelin, injection in the BLA increased the level of p-ERK, which mimicked the increased p-ERK level in the BLA that was induced by treatment with repeated stress. Stereotaxic injection of U0126, a potent inhibitor of the ERK pathway, within the BLA blocked stress-induced behavioral depression. These results suggest that repeated stress produces lasting depression-like behaviors via the up-regulation of TRH and TRH receptors in the BLA.

  15. Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner.

    Science.gov (United States)

    Ulrich-Lai, Yvonne M; Figueiredo, Helmer F; Ostrander, Michelle M; Choi, Dennis C; Engeland, William C; Herman, James P

    2006-11-01

    The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly increases adrenal weight, but it is not known to what extent this growth is due to cellular hyperplasia or hypertrophy and whether it is subregion specific. Moreover, it is not clear whether increased production of adrenal glucocorticoid after chronic stress is due to increased sensitivity to adrenocorticotropic hormone (ACTH) vs. increased maximal output. The present studies use a 14-day chronic variable stress (CVS) paradigm in adult male rats to assess the effects of chronic stress on adrenal growth and corticosterone steroidogenesis. Exogenous ACTH administration (0-895 ng/100 g body wt) to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity. This enhanced function was associated with increased adrenal weight, DNA and RNA content, and RNA/DNA ratio after CVS, suggesting that both cellular hyperplasia and hypertrophy occurred. Unbiased stereological counting of cells labeled for Ki67 (cell division marker) or 4,6-diamidino-2-phenylindole (nuclear marker), combined with zone specific markers, showed that CVS induced hyperplasia in the outer zona fasciculata, hypertrophy in the inner zona fasciculata and medulla, and reduced cell size in the zona glomerulosa. Collectively, these results demonstrate that increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal corticosterone responses to ACTH. These chronic stress-induced changes in adrenal growth and function may have implications for patients with stress-related disorders.

  16. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dan, E-mail: danw@bjmu.edu.cn [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Liu, Jing; Wu, Baiyan [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Tu, Bo; Zhu, Weiguo [Department of Biochemistry and Molecular Biology, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Luo, Jianyuan, E-mail: jluo@som.umaryland.edu [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Department of Medical and Research Technology, School of Medicine, University of Maryland, Baltimore 21201 (United States)

    2014-04-25

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.

  17. Expression and regulation of phosphate stress inducible genes in Sinorhizobium meliloti.

    Science.gov (United States)

    Summers, M L; Elkins, J G; Elliott, B A; McDermott, T R

    1998-11-01

    Sinorhizobium meliloti 104A14 was mutated with transposon Tn5B22, which creates lacZ transcriptional fusions when inserted in the correct orientation relative to the promoter. This promoter reporter allowed us to identify six phosphate stress inducible (psi) genes in S. meliloti that are up-regulated in response to inorganic phosphate (Pi) starvation. The transposon and flanking DNA were cloned from each psi::Tn5B22 reporter mutant and the junction DNA sequenced. High identity/similarity of the inferred peptides with those in major data bases allowed identification of the following genes: dnaK, expC, pssB, ackA, vipC, and prkA. The prkA homolog was also found to be up-regulated in response to carbon starvation and when nitrate replaced ammonium as the nitrogen source. Through allele replacement techniques, PhoB- mutants were generated for the expC, ackA, vipC, and pssB reporter strains. Loss of a functional PhoB resulted in the absence of Pi-sensitive induction in all four genes. These experiments suggest the Pho regulon in S. meliloti includes genes that presumably are not directly linked to Pi acquisition or assimilation. The psi strains were tested for their symbiotic properties under growth conditions that were Pi-limiting or Pi-nonlimiting for the host plant. All were Nod+ and Fix+ except the reporter strain of dnaK transcription, which was less effective than the wild-type strain under both P treatments, indicating DnaK is required for optimum symbiotic function.

  18. Body mass index and risk for mental stress induced ischemia in coronary artery disease.

    Science.gov (United States)

    Soufer, Robert; Fernandez, Antonio B; Meadows, Judith; Collins, Dorothea; Burg, Matthew M

    2016-05-19

    Acute emotionally reactive mental stress (MS) can provoke prognostically relevant deficits in cardiac function and myocardial perfusion, and chronic inflammation increases risk for this ischemic phenomenon. We have described parasympathetic withdrawal and generation of inflammatory factors in MS. Adiposity is also associated with elevated markers of chronic inflammation. High body mass index (BMI) is frequently used as a surrogate for assessment of excess adiposity, and associated with traditional CAD risk factors, and CAD mortality. BMI is also associated with autonomic dysregulation, adipose tissue derived proinflammatory cytokines, which are also attendant to emotion provoked myocardial ischemia. Thus, we sought to determine if body mass index (BMI) contributes to risk of developing myocardial ischemia provoked by mental stress. We performed a prospective interventional study in a cohort of 161 patients with stable CAD. They completed an assessment of myocardial blood flow with single photon emission computed tomography (SPECT) simultaneously during 2 conditions: laboratory mental stress and at rest. Multivariate logistic regression determined the independent contribution of BMI to the occurrence of mental-stress induced ischemia. Mean age was 65.6±9.0 years; 87.0% had a history of hypertension, and 28.6% had diabetes. Mean BMI was 30.4±4.7. Prevalence of mental stress ischemia was 39.8%. BMI was an independent predictor of mental stress ischemia, OR=1.10, 95% CI [1.01-1.18] for one-point increase in BMI and OR=1.53, 95% CI [1.06-2.21] for a 4.7 point increase in BMI (one standard deviation beyond the cohort BMI mean), p=0.025 for all. These data suggest that BMI may serve as an independent risk marker for mental stress ischemia. The factors attendant with greater BMI, which include autonomic dysregulation and inflammation, may represent pathways by which high BMI contribute to this risk and serve as a conceptual construct to replicate these findings in larger

  19. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  20. FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory.

    Science.gov (United States)

    Zoladz, Phillip R; Dailey, Alison M; Nagle, Hannah E; Fiely, Miranda K; Mosley, Brianne E; Brown, Callie M; Duffy, Tessa J; Scharf, Amanda R; Earley, McKenna B; Rorabaugh, Boyd R

    2017-03-01

    FK506 binding protein 51 (FKBP5) is a co-chaperone of heat shock protein 90 and significantly influences glucocorticoid receptor sensitivity. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events. The mechanisms underlying these associations are largely unknown, but it has been speculated that the influence of these SNPs on emotional memory systems may play a role. In the present study, 112 participants were exposed to the socially evaluated cold pressor test (stress) or control (no stress) conditions immediately prior to learning a list of 42 words. Participant memory was assessed immediately after learning (free recall) and 24 h later (free recall and recognition). Participants provided a saliva sample that enabled the genotyping of three FKBP5 polymorphisms: rs1360780, rs3800373 and rs9296158. Results showed that stress impaired immediate recall in risk allele carriers. More importantly, stress enhanced long-term recall and recognition memory in non-carriers of the risk alleles, effects that were completely absent in risk allele carriers. Follow-up analyses revealed that memory performance was correlated with salivary cortisol levels in non-carriers, but not in carriers. These findings suggest that FKBP5 risk allele carriers may possess a sensitized stress response system, perhaps specifically for stress-induced changes in corticosteroid levels, which might aid our understanding of how SNPs in the FKBP5 gene confer increased risk for stress-related psychological disorders and their related phenotypes.

  1. Raman spectroscopic study of acute oxidative stress induced changes in mice skeletal muscles

    Science.gov (United States)

    Sriramoju, Vidyasagar; Alimova, Alexandra; Chakraverty, Rahul; Katz, A.; Gayen, S. K.; Larsson, L.; Savage, H. E.; Alfano, R. R.

    2008-02-01

    The oxidative stress due to free radicals is implicated in the pathogenesis of tissue damage in diseases such as muscular dystrophy, Alzheimer dementia, diabetes mellitus, and mitochrondrial myopathies. In this study, the acute oxidative stress induced changes in nicotinamide adenine dinucleotides in mouse skeletal muscles are studied in vitro using Raman spectroscopy. Mammalian skeletal muscles are rich in nicotinamide adenine dinucleotides in both reduced (NADH) and oxidized (NAD) states, as they are sites of aerobic and anaerobic respiration. The relative levels of NAD and NADH are altered in certain physiological and pathological conditions of skeletal muscles. In this study, near infrared Raman spectroscopy is used to identify the molecular fingerprints of NAD and NADH in five-week-old mice biceps femoris muscles. A Raman vibrational mode of NADH is identified in fresh skeletal muscle samples suspended in buffered normal saline. In the same samples, when treated with 1% H IIO II for 5 minutes and 15 minutes, the Raman spectrum shows molecular fingerprints specific to NAD and the disappearance of NADH vibrational bands. The NAD bands after 15 minutes were more intense than after 5 minutes. Since NADH fluoresces and NAD does not, fluorescence spectroscopy is used to confirm the results of the Raman measurements. Fluorescence spectra exhibit an emission peak at 460 nm, corresponding to NADH emission wavelength in fresh muscle samples; while the H IIO II treated muscle samples do not exhibit NADH fluorescence. Raman spectroscopy may be used to develop a minimally invasive, in vivo optical biopsy method to measure the relative NAD and NADH levels in muscle tissues. This may help to detect diseases of muscle, including mitochondrial myopathies and muscular dystrophies.

  2. Effect of brain-derived neurotrophic factor haploinsufficiency on stress-induced remodeling of hippocampal neurons.

    Science.gov (United States)

    Magariños, A M; Li, C J; Gal Toth, J; Bath, K G; Jing, D; Lee, F S; McEwen, B S

    2011-03-01

    Chronic restraint stress (CRS) induces the remodeling (i.e., retraction and simplification) of the apical dendrites of hippocampal CA3 pyramidal neurons in rats, suggesting that intrahippocampal connectivity can be affected by a prolonged stressful challenge. Since the structural maintenance of neuronal dendritic arborizations and synaptic connectivity requires neurotrophic support, we investigated the potential role of brain derived neurotrophic factor (BDNF), a neurotrophin enriched in the hippocampus and released from neurons in an activity-dependent manner, as a mediator of the stress-induced dendritic remodeling. The analysis of Golgi-impregnated hippocampal sections revealed that wild type (WT) C57BL/6 male mice showed a similar CA3 apical dendritic remodeling in response to three weeks of CRS to that previously described for rats. Haploinsufficient BDNF mice (BDNF(±) ) did not show such remodeling, but, even without CRS, they presented shorter and simplified CA3 apical dendritic arbors, like those observed in stressed WT mice. Furthermore, unstressed BDNF(±) mice showed a significant decrease in total hippocampal volume. The dendritic arborization of CA1 pyramidal neurons was not affected by CRS or genotype. However, only in WT mice, CRS induced changes in the density of dendritic spine shape subtypes in both CA1 and CA3 apical dendrites. These results suggest a complex role of BDNF in maintaining the dendritic and spine morphology of hippocampal neurons and the associated volume of the hippocampal formation. The inability of CRS to modify the dendritic structure of CA3 pyramidal neurons in BDNF(±) mice suggests an indirect, perhaps permissive, role of BDNF in mediating hippocampal dendritic remodeling.

  3. Effect of temperature on oxidative stress induced by lead in the leaves of Plantago major L.

    Science.gov (United States)

    Balakhnina, Tamara I.; Borkowska, Aneta; Nosalewicz, Magdalena; Nosalewicz, Artur; Włodarczyk, Teresa M.; Kosobryukhov, Anatoly A.; Fomina, Irina R.

    2016-07-01

    Fluctuation of the summer day-time temperatures in the mid-latitudes in a range from 16 to 30°C should not have irreversible negative effects on plants, but may influence metabolic processes including the oxidative stress. To test the effect of moderately high temperature on oxidative stress induced by lead in the leaves of Plantago major L.; the plants were incubated in a water solution of 0, 150, 450, and 900 μM Pb (NO3)2 at 20 and 28°C. Plant reactions were evaluated by the content of thiobarbituric acid reactive substances and ascorbate peroxidase and glutathione reductase activities in leaves after 2, 24, 48, and 72 h. The Pb concentration in the leaves rose with the increase in the Pb content and was higher at 20°C. The increase in stomatal resistance caused by Pb was higher at 28°C. The contents of TBARS increased after 2 h of plant exposure to Pb and the increase was the highest at 900 μM Pb, 28°C. The AsP activity increased up to 50% after 24 h of Pb-treatment at 28°C; the highest increase in glutathione reductase activity was observed after 72 h at 20°C. Thus, the moderately high temperature 28°C compared with optimal 20°C caused a decrease in Pb accumulation in Plantago leaves but amplified the negative effects of lead, especially in the beginning of stress development.

  4. Isolation and Expression Analysis of a Novel Abiotic Stress-Induced Gene W89 from Wheat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Rui-yue; XU Zhao-shi; LI Lian-cheng; CHEN Ming; MA You-zhi

    2007-01-01

    Water stress and cold stress are important factors restricting plant growth. However, there is little knowledge on the function of stress-responsive genes in plants. Therefore, it is necessary to clone some important genes to study the mechanism of plant adaptation to abiotic stress for improvement of plant resistance. A putative water stress-induced gene, W89, was cloned from the cDNA library of drought-treated wheat seedlings by phage hybridization in situ, and its entire length was obtained using 5'-rapid amplification of cDNA ends (RACE) and reverse transcription-polymerase chain reaction (RT-PCR). The full-length cDNA of W89 consists of 2 392 bp and contains a 1 896 bp open reading frame (ORF) encoding a 631 amino acid protein. Southern blot analysis indicated that W89 was a single-copy gene. RT-PCR analysis revealed that the expression of W89 was upregulated by drought, cold, and abscisic acid (ABA). Amino acid sequence analysis discovered that W89 had a conserved region of DUF248 (pfam03141), which contained a methyltransferase domain with a sterile alpha motif (SAM)-binding motif. Phylogenetic analysis showed that W89 was 66% identical to Oryza sativa dehydration-responsive protein (BAD67956). It was supposed that W89 was a novel dehydration-responsive protein encoding gene. On the basis of the functions of methyltransferase and the SAM-binding motif, the SAM-binding motif of W89 was supposed to be connected with other proteins or transcription factors to transduce stress signals and finally regulate the expression of stress-responsive genes on the early stage of drought stress.

  5. Post-training reward partially restores chronic stress induced effects in mice.

    Directory of Open Access Journals (Sweden)

    Sergiu Dalm

    Full Text Available Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact over the course of two weeks. Following novelty exploration, (non- spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1 the effects of chronic stress persisted beyond the period of the actual rat exposure. (2 Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3 in stressed mice sugar partially "normalized" the impaired performance to the level of controls without sugar. Chronic stress (4 increased behavioral inhibition in response to novelty; (5 induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6 increased the intake of sucrose and water. (7 Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory.

  6. Effect of single and paired metal inputs in soil on a stress-inducible transgenic nematode.

    Science.gov (United States)

    Power, R S; de Pomerai, D I

    1999-11-01

    A toxicity test using a transgenic strain of the free-living soil nematode Caenorhabditis elegans carrying a stress-inducible beta-galactosidase reporter has been adapted for use in soil biomonitoring. High concentrations (250 microg. g(-1)) of cadmium are required to induce the stress response in worms exposed to Lufa 2.2 soil. Even at relatively high concentrations, the response to copper and zinc additions alone is minimal, yet combinations of cadmium and copper in the test soil induce a larger response than with cadmium alone at the same concentration. In contrast, the addition of both zinc and cadmium induces a lower response than cadmium additions alone. Analysis of the interstitial water suggests that there is preferential occupation by copper of sorption sites in the soil, allowing more cadmium to remain in solution. Conversely, cadmium and zinc would appear to interact similarly with the soil constituents, resulting in an increase of both metals in solution with increased additions to the soil. Aquatic tests mimic the results of the soil test, so it is not increased cadmium availability alone that causes an increased stress response when both cadmium and copper are present. The presence of other metals could reduce the amount of cadmium available, which may be one factor in the zinc moderation of the stress response to cadmium. Intracellular mechanisms may also contribute to the copper enhancement of the stress response to cadmium.http://link. springer-ny.com/link/service/journals/00244/bibs/37n4p503.++ +html

  7. Divergent Stress-Induced Neuroendocrine and Behavioral Responses Prior to Puberty

    Science.gov (United States)

    Lui, Patina; Padow, Victoria A.; Franco, Daly; Hall, Baila S.; Park, Brian; Klein, Zoe A.; Romeo, Russell D.

    2012-01-01

    Following an acute stressor, pre-adolescent rats exhibit a protracted hormonal response compared to adults, while after repeated exposure to the same stressor (i.e., homotypic stress) prepubertal males fail to habituate like adults. Though the neurobehavioral implications of these changes are unknown, studying pubertal shifts in stress reactivity may help elucidate the mechanisms that underlie the increase in stress-related psychological and physiological disorders often observed during adolescence. Here, we investigated hormonal, behavioral, and neural responses of prepubertal (30d) and adult (77d) male rats before, during, or after acute stress (restraint), homotypic stress (repeated restraint) or heterotypic stress (repeated cold exposure followed by restraint). We found that prepubertal males exhibit prolonged corticosterone responses following acute and heterotypic stress, and higher adrenocorticotropic hormone and corticosterone responses after homotypic stress, compared to adults. Despite these significant age-dependent changes in hormonal responsiveness, we found struggling behavior during restraint was similar at both ages, such that both prepubertal and adult animals exposed to homotypic stress struggled less than animals exposed to either acute or heterotypic stress. Across these different stress paradigms, we found greater neural activation, as indexed by FOS immunostaining, in the prepubertal compared to adult paraventricular nucleus of the hypothalamus, a nucleus integral for initiating the hormonal stress response. Interestingly, however, we did not find any influence of pubertal development on stress-induced activation of the posterior paraventricular thalamic nucleus, a brain region involved in experience-dependent changes in stress reactivity. Collectively, our data indicate prepubertal and adult males display divergent hormonal, behavioral, and neural responses following a variety of stressful experiences, as well as a distinct dissociation

  8. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

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    Petra eSántha

    2016-01-01

    Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

  9. Role of melatonin in modulation of oxidative stress induced by delta-

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    El-Sawi, MR, Badawy, ME and El-Gharieb, NM.

    2007-09-01

    Full Text Available Backgrounds: Delta-aminolevulinic acid (ALA is a heme precursor that accumulates in acute intermittent porphyria (AIP due to enzymatic deficiencies in the heme biosynthetic pathway, its accumulation has been associated with several symptoms because it works as an endogenous source of reactive oxygen species, which can exert oxidative damage to cell structures. The present work was designed to examine the ability of melatonin, a well known antioxidant and a free radical scavenger secreted from the pineal gland, to revert ALA-promoted damage in brain, liver and kidney of rats. Results: The present data demonstrated that chronically ALA-treated rats (40 mg / kg body wt day after day for 14 days exhibited very highly significant increases in malondialdehyde (MDA and protein carbonyl (PC whereas the level of glutathione (GSH was significantly diminished in the tissue homogenates of all tested organs (brain, kidney & liver. Among antioxidant enzymes, superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GSH-Rd, glutathione-S-transferase (GST activities were significantly diminished by ALA treatment. Intraperitoneal injection of melatonin (10 mg / kg body weight, every day for 14 consecutive days significantly ameliorated all the tested parameters. Melatonin moderately increased SOD, CAT, GSH-Rd and GST activities, thereby counteracting the oxidative stress induced by ALA. Nevertheless, exogenous ALA caused a strong net rise in MDA and PC and a significant decrease in GSH when given together with ALA, melatonin antagonized these effects and largely protected the integrity of tissue structures. From the present data, the protection of melatonin against ALA oxidative stress is obviously, so it is well recommended to use melatonin in patients suffering from symptoms related to ALA accumulation

  10. Thermoelastic stresses induced by non-isothermal fluid injection into fractured rock

    Science.gov (United States)

    Mossop, A.; Matthai, S. K.

    2003-04-01

    The injection of cold water into hot fractured rock occurs in a number of industrial scenarios, most commonly in the recharge of geothermal reservoirs and during waterflood operations in hydrocarbon reservoirs. The cold water cools the rock local to the fracture flow pathways, the cooled rock contracts, causing localised stress perturbations. Essentially analogous physical processes are involved in the injection of hot fluids into cooler rock such as occur in steam flood operations in viscous oil recovery. In this study we investigate such thermoelastic stresses induced by non-isothermal injection into a three dimensional fractured rock mass. The starting point of our analysis is an idealized model of injection into a single, uniform, horizontal fracture. For this case we have previously found semi-analytic solutions and analytic estimates of the stress perturbation and these are in turn used for cross-verification of an isoparametric, quadratic, finite element model of the system. In the numerical model the fractures are treated as discrete conductive channels within the matrix and an additional feature is that the matrix itself can be assigned a non-zero permeability. As the numerical simulator follows a fundamentally different methodology for solving these thermoelastic problems, the results help to validate some of the scaling relationships and non-intuitive behaviour deduced from the analytic estimates (e.g. for a broad range of flow rates, fracture normal stress perturbations decrease with increasing injection rates). The finite element model is then used to explore progressively more complex fracture geometries and networks. Finally we investigate the validity of a continuum limit as fracture densities increase to the point that fracture separation length scales are comparable with thermal diffusion length scales.

  11. Adiponectin is protective against oxidative stress induced cytotoxicity in amyloid-beta neurotoxicity.

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    Koon-Ho Chan

    Full Text Available Beta-amyloid (Aβ neurotoxicity is important in Alzheimer's disease (AD pathogenesis. Aβ neurotoxicity causes oxidative stress, inflammation and mitochondrial damage resulting in neuronal degeneration and death. Oxidative stress, inflammation and mitochondrial failure are also pathophysiological mechanisms of type 2 diabetes (T(2DM which is characterized by insulin resistance. Interestingly, T(2DM increases risk to develop AD which is associated with reduced neuronal insulin sensitivity (central insulin resistance. We studied the potential protective effect of adiponectin (an adipokine with insulin-sensitizing, anti-inflammatory and anti-oxidant properties against Aβ neurotoxicity in human neuroblastoma cells (SH-SY5Y transfected with the Swedish amyloid precursor protein (Sw-APP mutant, which overproduced Aβ with abnormal intracellular Aβ accumulation. Cytotoxicity was measured by assay for lactate dehydrogenase (LDH released upon cell death and lysis. Our results revealed that Sw-APP transfected SH-SY5Y cells expressed both adiponectin receptor 1 and 2, and had increased AMP-activated protein kinase (AMPK activation and enhanced nuclear factor-kappa B (NF-κB activation compared to control empty-vector transfected SH-SY5Y cells. Importantly, adiponectin at physiological concentration of 10 µg/ml protected Sw-APP transfected SH-SY5Y cells against cytotoxicity under oxidative stress induced by hydrogen peroxide. This neuroprotective action of adiponectin against Aβ neurotoxicity-induced cytotoxicity under oxidative stress involved 1 AMPK activation mediated via the endosomal adaptor protein APPL1 (adaptor protein with phosphotyrosine binding, pleckstrin homology domains and leucine zipper motif and possibly 2 suppression of NF-κB activation. This raises the possibility of novel therapies for AD such as adiponectin receptor agonists.

  12. Thermal stress induced voids in nanoscale copper interconnects by in-situ TEM heating

    Science.gov (United States)

    An, Jin Ho

    Stress induced void formation in Cu interconnects, due to thermal stresses generated during the processing of semiconductors, is an increasing reliability issue in the semiconductor industry as Cu interconnects are being downscaled to follow the demand for faster chip speed. In this work, 1.8 micron and 180 nm wide Cu interconnects, fabricated by Freescale Semiconductors, were subjected to thermal cycles, in-situ in the TEM, to investigate the stress relaxation mechanisms as a function of interconnect linewidth. The experiments show that the 1.8 micron Cu interconnect lines relax the thermal stresses through dislocation nucleation and motion while the Cu interconnect 180 nm lines exhibit void formation. Void formation in 180 nm lines occurs predominantly at triple junctions where the Ta diffusion barrier meets a Cu grain boundary. In order to understand void formation in 180 nm lines, the grain orientation and local stresses are determined. In particular, Nanobeam Diffraction (NBD) in the TEM is used to obtain the diffraction pattern of each grain, from which the crystal orientation is evaluated by the ACT (Automated Crystallography for TEM) software. In addition, 2D Finite Element Method (FEM) simulations are performed using the Object Oriented Finite Modeling (OOF2) software to correlate grain orientation with local stresses, and consequently void formation. According to the experimental and simulation results obtained, void formation in 180nm Cu interconnects does not seem to be solely dependent on local stresses, but a combination of diffusion paths available, stress gradients and possibly the presence of defects. In addition, based on the in-situ TEM observations, void growth seems to occur through grain boundary and/or interfacial diffusion. However, in-situ STEM observations of fully opened voids post-failure show pileup of material at the Cu grain surfaces. This means that surface or interface diffusion is also very active during void growth in the presence

  13. Seagrass proliferation precedes mortality during hypo-salinity events: a stress-induced morphometric response.

    Directory of Open Access Journals (Sweden)

    Catherine J Collier

    Full Text Available Halophytes, such as seagrasses, predominantly form habitats in coastal and estuarine areas. These habitats can be seasonally exposed to hypo-salinity events during watershed runoff exposing them to dramatic salinity shifts and osmotic shock. The manifestation of this osmotic shock on seagrass morphology and phenology was tested in three Indo-Pacific seagrass species, Halophila ovalis, Halodule uninervis and Zostera muelleri, to hypo-salinity ranging from 3 to 36 PSU at 3 PSU increments for 10 weeks. All three species had broad salinity tolerance but demonstrated a moderate hypo-salinity stress response--analogous to a stress induced morphometric response (SIMR. Shoot proliferation occurred at salinities <30 PSU, with the largest increases, up to 400% increase in shoot density, occurring at the sub-lethal salinities <15 PSU, with the specific salinity associated with peak shoot density being variable among species. Resources were not diverted away from leaf growth or shoot development to support the new shoot production. However, at sub-lethal salinities where shoots proliferated, flowering was severely reduced for H. ovalis, the only species to flower during this experiment, demonstrating a diversion of resources away from sexual reproduction to support the investment in new shoots. This SIMR response preceded mortality, which occurred at 3 PSU for H. ovalis and 6 PSU for H. uninervis, while complete mortality was not reached for Z. muelleri. This is the first study to identify a SIMR in seagrasses, being detectable due to the fine resolution of salinity treatments tested. The detection of SIMR demonstrates the need for caution in interpreting in-situ changes in shoot density as shoot proliferation could be interpreted as a healthy or positive plant response to environmental conditions, when in fact it could signal pre-mortality stress.

  14. Stress-induced chemical detection using flexible metal-organic frameworks.

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    Allendorf, Mark D.; Hesketh, Peter J. (Georgia Institute of Technology, Atlanta, GA); Gall, Kenneth A. (Georgia Institute of Technology, Atlanta, GA); Choudhury, A. (Georgia Institute of Technology, Atlanta, GA); Pikarsky, J. (Georgia Institute of Technology, Atlanta, GA); Andruszkiewicz, Leanne (Georgia Institute of Technology, Atlanta, GA); Houk, Ronald J. T.; Talin, Albert Alec (National Institute of Standards & Technology, Gaithersburg, MD)

    2009-09-01

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be efficiently converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N{sub 2} or O{sub 2}. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO{sub 2}. We also report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes. A force field model is described that successfully predicts changes in MOF properties and the uptake of gases. This model is used to predict adsorption isotherms for a number of representative compounds, including explosives, nerve agents, volatile organic compounds, and polyaromatic hydrocarbons. The results show that, as a result of relatively large heats of adsorption (> 20 kcal mol{sup -1}) in most cases, we expect an onset of adsorption by MOF as low as 10{sup -6} kPa, suggesting the potential to detect compounds such as RDX at levels as low as 10 ppb at atmospheric pressure.

  15. Studying the cytotoxicity and oxidative stress induced by two kinds of bentonite particles on human B lymphoblast cells in vitro.

    Science.gov (United States)

    Zhang, Meibian; Lu, Yezhen; Li, Xiaoxue; Chen, Qing; Lu, Longxi; Xing, Mingluan; Zou, Hua; He, Jiliang

    2010-02-12

    The aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by native and active bentonite particles (BPs) on human B lymphoblast cells using seven assays. Our results showed that the order of cytotoxicity was: active BPs>native BPs>quartz particles (DQ-12)>gypsum, according to the IC50 values in CCK-8 assay and neutral red uptake (NRU) assay. The lactate dehydrogenase (LDH) leakage, the proportions of early apoptotic cells, the reactive oxygen species (ROS) generation, the superoxide dismutase (SOD) inhibition and the malondialdehyde (MDA) release in the native and active BPs groups were significantly higher than those in the gypsum and DQ-12 groups (Pstress induced by active BPs was significantly higher than that induced by native BPs (Pstress on human B lymphoblast cells in vitro. The cytotoxic difference between active BPs and native BPs may be associated with the adsorption capacity of BPs and oxidative stress induced by BPs to a certain extent. The insoluble particle fractions may play a main role in the cytotoxic effects and oxidative stress induced by BPs.

  16. Neuropeptide FF and related peptides attenuates warm-, but not cold-water swim stress-induced analgesia in mice.

    Science.gov (United States)

    Li, Ning; Han, Zheng-lan; Fang, Quan; Wang, Zi-long; Tang, Hong-zhu; Ren, Hui; Wang, Rui

    2012-08-01

    Neuropeptide FF (NPFF) belongs to a neuropeptide family including two receptors (NPFF(1) and NPFF(2)). NPFF system has been reported to play important roles in pain transmission. The aim of the present study was to investigate the roles of NPFF related peptides and their receptors in swim stress-induced analgesia (SIA). Nociceptive test was performed in mice stressed by forced swimming in water at 15 °C (cold water swimming) or 32 °C (warm water swimming). Warm water swimming produced a naloxone-mediated antinociceptive effect. This warm water swim SIA was dose-dependently antagonized by i.c.v. injection of NPFF and two related peptides (3-30 nmol), NPVF and dNPA, which exhibited the highest selectivities for NPFF(1) and NPFF(2) receptors, respectively. Moreover, the selective NPFF receptor antagonist RF9 (30 nmol) was inactive by itself, but prevented the effects of NPFF and related peptides. Cold-water swimming produced a wilder analgesic effect that was blocked by MK-801, but not naloxone. However, NPFF system failed to modify the cold water swim stress-induced analgesia. These findings demonstrated that NPFF and related peptides attenuated opioid-mediated form of SIA via NPFF receptors in the brain, but not non-opioid swim stress-induced analgesia. These data further support an anti-opioid character of NPFF system.

  17. Effect of St. John's Wort (Hypericum perforatum treatment on restraint stress-induced behavioral and biochemical alteration in mice

    Directory of Open Access Journals (Sweden)

    Prakash Atish K

    2010-05-01

    Full Text Available Abstract Background A stressful stimulus is a crucial determinant of health and disease. Antidepressants are used to manage stress and their related effects. The present study was designed to investigate the effect of St. John's Wort (Hypericum perforatum in restraint stress-induced behavioral and biochemical alterations in mice. Methods Animals were immobilized for a period of 6 hr. St. John's Wort (50 and 100 mg/kg was administered 30 minutes before the animals were subjecting to acute immobilized stress. Various behavioral tests parameters for anxiety, locomotor activity and nociceptive threshold were assessed followed by biochemical assessments (malondialdehyde level, glutathione, catalase, nitrite and protein subsequently. Results 6-hr acute restraint stress caused severe anxiety like behavior, antinociception and impaired locomotor activity as compared to unstressed animals. Biochemical analyses revealed an increase in malondialdehyde, nitrites concentration, depletion of reduced glutathione and catalase activity as compared to unstressed animal brain. Five days St. John's Wort treatment in a dose of 50 mg/kg and 100 mg/kg significantly attenuated restraint stress-induced behavioral (improved locomotor activity, reduced tail flick latency and antianxiety like effect and oxidative damage as compared to control (restraint stress. Conclusion Present study highlights the modest activity of St. John's Wort against acute restraint stress induced modification.

  18. Shear stress induces cell apoptosis via a c-Src-phospholipase D-mTOR signaling pathway in cultured podocytes

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chunfa, E-mail: chunfa.huang@case.edu [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States); Bruggeman, Leslie A. [Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States); Hydo, Lindsey M. [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Miller, R. Tyler [Louis Stokes Cleveland Veteran Affairs Medical Center, Case Western Reserve University (United States); Department of Medicine, Case Western Reserve University (United States); Rammelkamp Center for Research and Education, MetroHealth System Campus, Cleveland, OH 44106 (United States)

    2012-06-10

    The glomerular capillary wall, composed of endothelial cells, the glomerular basement membrane and the podocytes, is continually subjected to hemodynamic force arising from tractional stress due to blood pressure and shear stress due to blood flow. Exposure of glomeruli to abnormal hemodynamic force such as hyperfiltration is associated with glomerular injury and progressive renal disease, and the conversion of mechanical stimuli to chemical signals in the regulation of the process is poorly understood in podocytes. By examining DNA fragmentation, apoptotic nuclear changes and cytochrome c release, we found that shear stress induced cell apoptosis in cultured podocytes. Meanwhile, podocytes exposed to shear stress also stimulated c-Src phosphorylation, phospholipase D (PLD) activation and mammalian target of rapamycin (mTOR) signaling. Using the antibodies against c-Src, PLD{sub 1}, and PLD{sub 2} to perform reciprocal co-immunoprecipitations and in vitro PLD activity assay, our data indicated that c-Src interacted with and activated PLD{sub 1} but not PLD{sub 2}. The inhibition of shear stress-induced c-Src phosphorylation by PP{sub 2} (a specific inhibitor of c-Src kinase) resulted in reduced PLD activity. Phosphatidic acid, produced by shear stress-induced PLD activation, stimulated mTOR signaling, and caused podocyte hypertrophy and apoptosis.

  19. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  20. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    Directory of Open Access Journals (Sweden)

    Fu-Wei Liu

    Full Text Available Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system.

  1. [Advances in molecular mechanisms of bacterial resistance caused by stress-induced transfer of resistance genes--a review].

    Science.gov (United States)

    Sun, Dongchang; Wang, Bing; Zhu, Lihong

    2013-07-04

    The transfer of resistance gene is one of the most important causes of bacterial resistance. Recent studies reveal that stresses induce the transfer of antibiotic resistance gene through multiple mechanisms. DNA damage stresses trigger bacterial SOS response and induce the transfer of resistance gene mediated by conjugative DNA. Antibiotic stresses induce natural bacterial competence for transformation in some bacteria which lack the SOS system. In addition, our latest studies show that the general stress response regulator RpoS regulates a novel type of resistance gene transfer which is mediated by double-stranded plasmid DNA and occurs exclusively on the solid surface. In this review, we summarized recent advances in SOS dependent and independent stress-induced DNA transfer which is mediated by conjugation and transformation respectively, and the transfer of double-stranded plasmid DNA on the solid surface which is regulated by RpoS. We propose that future work should address how stresses activate the key regulators and how these regulators control the expression of gene transfer related genes. Answers to the above questions would pave the way for searching for candidate targets for controlling bacterial resistance resulted from the transfer of antibiotic genes.

  2. HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative stress-induced neuronal cell death.

    Science.gov (United States)

    Peng, Shengyi; Zhao, Siqi; Yan, Feng; Cheng, Jinbo; Huang, Li; Chen, Hong; Liu, Qingsong; Ji, Xunming; Yuan, Zengqiang

    2015-01-21

    All neurodegenerative diseases are associated with oxidative stress-induced neuronal death. Forkhead box O3a (FOXO3a) is a key transcription factor involved in neuronal apoptosis. However, how FOXO3a forms complexes and functions in oxidative stress processing remains largely unknown. In the present study, we show that histone deacetylase 2 (HDAC2) forms a physical complex with FOXO3a, which plays an important role in FOXO3a-dependent gene transcription and oxidative stress-induced mouse cerebellar granule neuron (CGN) apoptosis. Interestingly, we also found that HDAC2 became selectively enriched in the promoter region of the p21 gene, but not those of other target genes, and inhibited FOXO3a-mediated p21 transcription. Furthermore, we found that oxidative stress reduced the interaction between FOXO3a and HDAC2, leading to an increased histone H4K16 acetylation level in the p21 promoter region and upregulated p21 expression in a manner independent of p53 or E2F1. Phosphorylation of HDAC2 at Ser 394 is important for the HDAC2-FOXO3a interaction, and we found that cerebral ischemia/reperfusion reduced phosphorylation of HDAC2 at Ser 394 and mitigated the HDAC2-FOXO3a interaction in mouse brain tissue. Our study reveals the novel regulation of FOXO3a-mediated selective gene transcription via epigenetic modification in the process of oxidative stress-induced cell death, which could be exploited therapeutically.

  3. Nitric Oxide Plays a Central Role in Water Stress-Induced Tanshinone Production in Salvia miltiorrhiza Hairy Roots

    Directory of Open Access Journals (Sweden)

    Xuhong Du

    2015-04-01

    Full Text Available Nitric oxide (NO, a well-known signaling molecule plays an important role in abiotic and biotic stress-induced production of plant secondary metabolites. In this study, roles of NO in water stress-induced tanshinone production in Salvia miltiorrhiza hairy roots were investigated. The results showed that accumulations of four tanshinone compounds in S. miltiorrhiza hairy roots were significantly stimulated by sodium nitroprusside (SNP, a NO donor at 100 μM. Effects of SNP were just partially arrested by the mevalonate (MVA pathway inhibitor (mevinolin, but were completely inhibited by the 2-C-methyl-d-erythritol-4-phosphate pathway (MEP inhibitor (fosmidomycin. The increase of tanshinone accumulation and the up-regulation of HMGR and DXR expression by PEG and ABA treatments were partially inhibited by an inhibitor of NO biosynthesis (Nω-nitro-L-arginine methyl ester (L-NAME and a NO scavenger (2-(4-Carboxyphenyl- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO. Simultaneously, NO generation in the hairy roots was triggered by PEG and ABA, and the effects were also arrested by c-PTIO and L-NAME. These results indicated that NO signaling probably plays a central role in water stress-induced tanshinone production in S. miltiorrhiza hairy roots. SNP mainly stimulated the MEP pathway to increase tanshinone accumulation.

  4. Nitric Oxide Plays a Central Role in Water Stress-Induced Tanshinone Production in Salvia miltiorrhiza Hairy Roots.

    Science.gov (United States)

    Du, Xuhong; Zhang, Chenlu; Guo, Wanli; Jin, Weibo; Liang, Zongsuo; Yan, Xijun; Guo, Zhixin; Liu, Yan; Yang, Dongfeng

    2015-04-24

    Nitric oxide (NO), a well-known signaling molecule plays an important role in abiotic and biotic stress-induced production of plant secondary metabolites. In this study, roles of NO in water stress-induced tanshinone production in Salvia miltiorrhiza hairy roots were investigated. The results showed that accumulations of four tanshinone compounds in S. miltiorrhiza hairy roots were significantly stimulated by sodium nitroprusside (SNP, a NO donor) at 100 μM. Effects of SNP were just partially arrested by the mevalonate (MVA) pathway inhibitor (mevinolin), but were completely inhibited by the 2-C-methyl-d-erythritol-4-phosphate pathway (MEP) inhibitor (fosmidomycin). The increase of tanshinone accumulation and the up-regulation of HMGR and DXR expression by PEG and ABA treatments were partially inhibited by an inhibitor of NO biosynthesis (Nω-nitro-L-arginine methyl ester (L-NAME)) and a NO scavenger (2-(4-Carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO)). Simultaneously, NO generation in the hairy roots was triggered by PEG and ABA, and the effects were also arrested by c-PTIO and L-NAME. These results indicated that NO signaling probably plays a central role in water stress-induced tanshinone production in S. miltiorrhiza hairy roots. SNP mainly stimulated the MEP pathway to increase tanshinone accumulation.

  5. Prickly Pear Cactus (Opuntia ficus indica var. saboten) Protects Against Stress-Induced Acute Gastric Lesions in Rats

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha

    2012-01-01

    Abstract The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague–Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800–1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production. PMID:23062184

  6. Post-traumatic and stress-induced osteolysis of the distal clavicle: MR imaging findings in 17 patients

    Energy Technology Data Exchange (ETDEWEB)

    Puente, R. de la [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States)]|[Servicio de Radioloxia, CXH Cristal Pinor, Ourense (Spain); Boutin, R.D. [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States)]|[Department of Radiology, Veterans Affairs Medical Center, San Diego, CA (United States); Theodorou, D.J.; Hooper, A.; Resnick, D. [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States); Schweitzer, M. [Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA (United States)

    1999-04-01

    Objective. To describe the MR imaging findings in patients with osteolysis of the distal clavicle and to compare the MR imaging appearance of clavicular osteolysis following acute injury with that related to chronic stress. Design and patients. MR imaging examinations were reviewed in 17 patients (14 men, 3 women; ages 16-55 years) with the diagnosis of post-traumatic or stress-induced osteolysis of the clavicle. A history of a single direct injury was present in seven patients and a history of weight-lifting, participation in sports, or repetitive microtrauma was present in 10 patients. Results. MR imaging showed edema in the distal clavicle in 17 patients and, of these, eight also had edema in the acromion. The edema was most evident in STIR and fat-suppressed T2-weighted pulse sequences. Other findings about the acromioclavicular (AC) joint were prominence of the joint capsule in 14, joint fluid in eight, cortical irregularity in 12, and bone fragmentation in six patients. No differences in the MR imaging features of post-traumatic and stress-induced osteolysis of the distal clavicle were observed. Conclusion. Post-traumatic and stress-induced osteolysis of the distal clavicle have similar appearances on MR imaging, the most common and conspicuous MR imaging feature being increased T2 signal intensity in the distal clavicle. (orig.) With 5 figs., 1 tab., 19 refs.

  7. Characterization of the atypical lymphocytes in African swine fever

    Science.gov (United States)

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  8. Characterization of the atypical lymphocytes in African swine fever

    Directory of Open Access Journals (Sweden)

    Z. A. Karalyan

    2016-07-01

    Full Text Available Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection.

  9. Client Proteins and Small Molecule Inhibitors Display Distinct Binding Preferences for Constitutive and Stress-Induced HSP90 Isoforms and Their Conformationally Restricted Mutants.

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    Thomas L Prince

    Full Text Available The two cytosolic/nuclear isoforms of the molecular chaperone HSP90, stress-inducible HSP90α and constitutively expressed HSP90β, fold, assemble and maintain the three-dimensional structure of numerous client proteins. Because many HSP90 clients are important in cancer, several HSP90 inhibitors have been evaluated in the clinic. However, little is known concerning possible unique isoform or conformational preferences of either individual HSP90 clients or inhibitors. In this report, we compare the relative interaction strength of both HSP90α and HSP90β with the transcription factors HSF1 and HIF1α, the kinases ERBB2 and MET, the E3-ubiquitin ligases KEAP1 and RHOBTB2, and the HSP90 inhibitors geldanamycin and ganetespib. We observed unexpected differences in relative client and drug preferences for the two HSP90 isoforms, with HSP90α binding each client protein with greater apparent affinity compared to HSP90β, while HSP90β bound each inhibitor with greater relative interaction strength compared to HSP90α. Stable HSP90 interaction was associated with reduced client activity. Using a defined set of HSP90 conformational mutants, we found that some clients interact strongly with a single, ATP-stabilized HSP90 conformation, only transiently populated during the dynamic HSP90 chaperone cycle, while other clients interact equally with multiple HSP90 conformations. These data suggest different functional requirements among HSP90 clientele that, for some clients, are likely to be ATP-independent. Lastly, the two inhibitors examined, although sharing the same binding site, were differentially able to access distinct HSP90 conformational states.

  10. Atypical meningioma and extensive calvarium defects in neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Simsek, Enver [Department of Paediatrics, Duzce Medical Faculty, Abant Izzet Baysal University, Konuralp-Duzce (Turkey); Yavuz, Cevdet [Department of Neurosurgery, Duzce Medical Faculty, Abant Izzet Baysal University, Konuralp-Duzce (Turkey); Ustundag, Nil [Department of Pathology, Abant Izzet Baysal University School of Medicine, Konuralp-Duzce (Turkey)

    2003-08-01

    A 9-year-old girl with neurofibromatosis type 1 (NF1) presented with a massive atypical meningioma and calvarial defect. Skull radiographs and cranial CT showed an extensive lytic bone lesion at the vertex. MRI demonstrated a large mass invading the calvarium and sagittal sinus. The histopathological and immunohistochemical diagnosis of the resected mass was atypical meningioma. To our knowledge, this is the first case of NF1 associated with atypical meningioma and massive calvarial defect in a child. (orig.)

  11. Transient stress cardiomyopathies in the elderly: Clinical & Pathophysiologic considerations

    Institute of Scientific and Technical Information of China (English)

    Michael A Chen

    2012-01-01

    Transient stress-induced cardiomyopathies have been increasingly recognized and while rare,they tend to affect elderly women more than other demographic groups.One type,often called tako-tsubo cardiomyopathy (TTC),is typically triggered by significant emotional or physical stress and is associated with chest pain,electrocardiogram (ECG) changes and abnormal cardiac enzymes.Significant left ventricular regional wall motion abnormalities usually include an akinetic "ballooning" apex with normal or hyperdynamic function of the base.A second type,often called neurogenic stunned myocardium,typically associated with subarachnoid hemorrhage,also usually presents with ECG changes and positive enzymes,but the typical wall motion abnormalities seen include normal basal and apical left ventricular contraction with akinesis of the mid-cavity in a circumferential fashion.The pathophysiology,clinical care and typical courses,are reviewed.

  12. Hematological Side Effects of Atypical Antipsychotic Drugs

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    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  13. Atypical And Severe Enlargement Of Right Atrium.

    Science.gov (United States)

    Siniscalchi, Carmine; Rossetti, Pietro; Rocci, Anna; Rubino, Pasquale; Basaglia, Manuela; Gaibazzi, Nicola; Quintavalla, Roberto

    2016-09-13

    A 76 year-old woman was admitted to the Emergency Department for recent-onset dyspnea and cough. The electrocardiogram was considered inconclusive. A thoracic X-ray showed global cardiac profile enlargement. Computed tomography, acutely performed in the clinical suspicion of atypical pneumonia/myocarditis or pericardial effusion, showed cardiac enlargement especially of the right chambers. In order to investigate Ebstein's anomaly, pericardial cysts, tumors or other conditions of the right heart a simple trans-thoracic echocardiogram was performed. Four chambers view showed a giant right atrium aneurysm with moderate tricuspid regurgitation without stenosis or typical Ebstein's echocardiographic pattern.

  14. Wilson’s disease: Atypical imaging features

    Directory of Open Access Journals (Sweden)

    Venugopalan Y Vishnu

    2016-10-01

    Full Text Available Wilson’s disease is a genetic movement disorder with characteristic clinical and imaging features. We report a 17- year-old boy who presented with sialorrhea, hypophonic speech, paraparesis with repeated falls and recurrent seizures along with cognitive decline. He had bilateral Kayser Flescher rings. Other than the typical features of Wilson’s disease in cranial MRI, there were extensive white matter signal abnormalities (T2 and FLAIR hyperintensities and gyriform contrast enhancement which are rare imaging features in Wilson's disease. A high index of suspicion is required to diagnose Wilson’s disease when atypical imaging features are present.

  15. Atypical outcome in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Schmidt, K; Freidson, S

    1990-07-01

    This report describes the course of psychiatric illness in two boys. Both presented with attention deficit hyperactivity disorder (ADHD) in midchildhood; after puberty, one boy developed a schizophrenic illness while the other boy developed a major affective illness. Although the major ADHD outcome studies have found no link between the childhood occurrence of ADHD and psychosis in adulthood, occasionally such a link may exist. The theoretical and practical implications of this finding are discussed. It should be noted, however, that such outcome is highly atypical and very rare.

  16. Atypical Log D profile of rifampicin

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    Mariappan T

    2007-01-01

    Full Text Available The distribution coefficient (log D values of rifampicin, an essential first-line antitubercular drug, at gastrointestinal pH conditions are not reported in literature. Hence determinations were made using n-octanol and buffers ranging between pH 1-7. Also, log D values were predicted using Prolog D. Both the determinations showed opposite behaviour. The atypical experimental log D profile of rifampicin could be attributed to its surface-active properties, which also explained the reported permeability behaviour of the drug in various gastrointestinal tract segments.

  17. Atypical giant chondroblastoma mimicking a chondrosarcoma.

    Science.gov (United States)

    Dhanda, Sunita; Menon, Santosh; Gulia, Ashish

    2015-01-01

    Chondroblastoma is a rare, benign tumor derived from chondroblasts, commonly presenting in the second decade of life. It is usually found in the epiphysis or apophysis of long bones; however, it may rarely affect flat bones like scapula. Occasionally a histologically typical chondroblastoma may exhibit an aggressive behavior that is not normally associated with benign tumors such as a large size, pulmonary metastases, joint and soft-tissue infiltration and local recurrence. We present a case report of a patient with chondroblastoma showing atypical radiological presentation and non-concordance with age.

  18. Bisphosphonates and Atypical Fractures of Femur

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    Tero Yli-Kyyny

    2011-01-01

    Full Text Available Bisphosphonates are the most widely prescribed medicines for the treatment of osteoporosis and have generally been regarded as well-tolerated and safe drugs. Since 2005, there have been numerous case reports about atypical fractures of the femur linked to long-term treatment of osteoporosis with bisphosphonates. Some attempts to characterize pathophysiology and epidemiology of these fractures have been published as well. However, as the American Society for Bone and Mineral Research (ASBMR concluded in their task force report, the subject warrants further studies.

  19. Atypical calcific tendinitis with cortical erosions

    Energy Technology Data Exchange (ETDEWEB)

    Kraemer, E.J. [College of Medicine, Univ. of Iowa, Iowa City, IA (United States); El-Khoury, G.Y. [Dept. of Radiology and Orthopaedics, Univ. of Iowa, Iowa City, IA (United States)

    2000-12-01

    Objective. To present and discuss six cases of calcific tendinitis in atypical locations (one at the insertion of the pectoralis major and five at the insertion of the gluteus maximus).Patients and results. All cases were associated with cortical erosions, and five had soft tissue calcifications. The initial presentation was confusing and the patients were suspected of having infection or neoplastic disease.Conclusion. Calcific tendinitis is a self-limiting condition. It is important to recognize the imaging features of this condition to avoid unnecessary investigation and surgery. (orig.)

  20. Gorlin’s syndrome: Atypical case report

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    Sanjay N. Agrawal

    2014-10-01

    Full Text Available Gorlin syndrome or basal cell nevus syndrome (BCNS is a rare autosomal dominant disorder. The condition appears to have complete penetrance and variable expressivity, which makes clinilcal presentation among families variable. All known BCNS carry mutations in PATCHED gene. A 65 years old male patient presented with complaints of characteristic skin lesions on his face, back, palms since early adulthood. The lesions were pigmented nodules with characteristic border. The histopathology showed characteristic features suggestive of Basal Cell Carcinoma (BCC. This case was atypical due to appearance of lesions quite later in life.

  1. Atypical presentation of childhood obsessive compulsive disorder

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    Satyakam Mohapatra

    2016-01-01

    Full Text Available Obsessive-compulsive disorder (OCD is one of the most prevalent psychiatric disorders in children and adolescents. The phenomenology of OCD in children and adolescent is strikingly similar to that of adults. But at times, the presentation of OCD may be so atypical or unusual in children and adolescents that may lead to misdiagnosis or delay in diagnosis. We report a case of 10-year-old child who was initially misdiagnosed with schizophrenia, and treated with antipsychotic for 2 months. But once the core symptoms were recognized as obsessions and compulsions and appropriately treated in the line of OCD, the symptoms resolved significantly.

  2. Measurement of elastic nonlinearity of soft solid with transient elastography.

    Science.gov (United States)

    Catheline, S; Gennisson, J L; Fink, M

    2003-12-01

    Transient elastography is a powerful tool to measure the speed of low-frequency shear waves in soft tissues and thus to determine the second-order elastic modulus mu (or the Young's modulus E). In this paper, it is shown how transient elastography can also achieve the measurement of the nonlinear third-order elastic moduli of an Agar-gelatin-based phantom. This method requires speed measurements of polarized elastic waves measured in a statically stressed isotropic medium. A static uniaxial stress induces a hexagonal anisotropy (transverse isotropy) in solids. In the special case of uniaxially stressed isotropic media, the anisotropy is not caused by linear elastic coefficients but by the third-order nonlinear elastic constants, and the medium recovers its isotropic properties as soon as the uniaxial stress disappears. It has already been shown how transient elastography can measure the elastic (second-order) moduli in a media with transverse isotropy such as muscles. Consequently this method, based on the measurement of the speed variations of a low-frequency (50-Hz) polarized shear strain waves as a function of the applied stress, allows one to measure the Landau moduli A, B, C that completely describe the third-order nonlinearity. The several orders of magnitude found among these three constants can be justified from the theoretical expression of the internal energy.

  3. Searches for radio transients

    CERN Document Server

    Bhat, N D R

    2011-01-01

    Exploration of the transient Universe is an exciting and fast-emerging area within radio astronomy. Known transient phenomena range in time scales from sub-nanoseconds to years or longer, thus spanning a huge range in time domain and hinting a rich diversity in their underlying physical processes. Transient phenomena are likely locations of explosive or dynamic events and they offer tremendous potential to uncover new physics and astrophysics. A number of upcoming next-generation radio facilities and recent advances in computing and instrumentation have provided a much needed impetus for this field which has remained a relatively uncharted territory for the past several decades. In this paper we focus mainly on the class of phenomena that occur on very short time scales (i.e. from $\\sim$ milliseconds to $\\sim$ nanoseconds), known as {\\it fast transients}, the detections of which involve considerable signal processing and data management challenges, given the high time and frequency resolutions required in the...

  4. Transient Ischemic Attack

    Medline Plus

    Full Text Available ... TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an ... a short time. The only difference between a stroke and TIA is that with TIA the blockage ...

  5. Voluntary exercise protects against stress-induced decreases in brain-derived neurotrophic factor protein expression.

    Science.gov (United States)

    Adlard, P A; Cotman, C W

    2004-01-01

    Exercise is increasingly recognized as an intervention that can reduce CNS dysfunctions such as cognitive decline, depression and stress. Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) is increased in the hippocampus following exercise. In this study we tested the hypothesis that exercise can counteract a reduction in hippocampal BDNF protein caused by acute immobilization stress. Since BDNF expression is suppressed by corticosterone (CORT), circulating CORT levels were also monitored. In animals subjected to 2 h immobilization stress, CORT was elevated immediately following, and at 1 h after the cessation of stress, but remained unchanged from baseline up to 24 h post-stress. The stress protocol resulted in a reduction in BDNF protein at 5 and 10 h post-stress that returned to baseline at 24 h. To determine if exercise could prevent this stress-induced reduction in BDNF protein, animals were given voluntary access to running wheels for 3 weeks prior to the stress. Stressed animals, in the absence of exercise, again demonstrated an initial elevation in CORT (at 0 h) and a subsequent decrease in hippocampal BDNF at the 10 h time point. Exercising animals, both non-stressed and stressed, demonstrated circulating CORT and hippocampal BDNF protein levels that were significantly elevated above control values at both time points examined (0 and 10 h post-stress). Thus, the persistently high CORT levels in exercised animals did not affect the induction of BDNF with exercise, and the effect of immobilization stress on BDNF protein was overcome. To examine the role of CORT in the stress-related regulation of BDNF protein, experiments were carried out in adrenalectomized (ADX) animals. BDNF protein was not downregulated as a result of immobilization stress in ADX animals, while there continued to be an exercise-induced upregulation of BDNF. This study demonstrates that CORT modulates stress-related alterations in BDNF protein. Further, exercise

  6. Stress induced alterations in pre-pubertal ovarian follicular development in rat

    Directory of Open Access Journals (Sweden)

    Yajurvedi H.N.

    2011-12-01

    Full Text Available The objective of the study was to find out whether stress experienced during neo-natal period alters the timing of formation of pre-antral and antral follicles and if so, whether pre-treatment with CRH receptor antagonist prevents these effects in rats. New born rat pups (n= 15 were exposed to maternal separation (6 hours/ day from post-natal day (PND 1 to 7 and were killed on PND 8, 11 and 15. The time of exposure was randomly changed every day during light phase (7Am to 7Pm of the day to avoid habituation. There was a significant increase in serum corticosterone levels on PND 8 and 11 in stress group rats compared to controls indicating stress response in these pups. The ovary of both control and stressed rats contained oocytes and primary follicles on PND 8 and 11 and in showed progress of follicular development upto to pre-antral and early antral follicle formation on PND 11 and 15. However, mean number of healthy oocytes and all categories of follicles at all ages studied were significantly lower in stressed rats compared to controls. Concomitant with these changes, number of atreatic follicles showed an increase over control values in stressed rats. The increase in atresia of follicles was due to apoptosis as shown by increase in the percentage of granulosa cells showing TUNEL positive staining and caspase 3 activity. On the other hand, pre-treatment with CRH- receptor antagonist (CRH 9-41 2ng/ 0.1 ml/ rat prior to undergoing stress regime on PND 1 to 7, prevented alterations in pre- pubertal follicular development thereby indicating that the ovarian changes were due to effects of stress induced activation of HPA axis. The results indicate that, stress during neonatal phase, though does not affect timing of formation of pre-antral and antral follicles, it does enhance atresia of follicles of all categories, including follicular reserve, which may affect the reproductive potential of adults. The results, for the first time reveal that CRF

  7. Chemical stress induced by heliotrope (Heliotropium europaeum L.) allelochemicals and increased activity of antioxidant enzymes.

    Science.gov (United States)

    Abdulghader, Kalantar; Nojavan, Majid; Naghshbandi, Nabat

    2008-03-15

    The aims of this study were to evaluate the allelopathic potential of heliotrope on some biochemical processes of dodder. The preliminary experiments revealed that the effect of aqueous extract of leaves of heliotrope is higher than its seeds and roots. So, the aqueous extract of leaves was used in remaining experiments. Leaf extracts of 5 g powder per 100 mL H2O inhibited the germination of dodder seeds up to 95% and that of radish up to 100%. While, the aqueous extract of vine leaves which is a non-allelopathic plant did not have any inhibitory effect on these seeds. Vine leaf was used as a control to show that the inhibitory effect of heliotrope is due to an inhibitory compound but not due to the concentration. The leaf extract of heliotrope at 0.0, 0.1, 1.0, 2, 3, 4 and 5 g powder per 100 mL H2O reduced the radish seedling growth from 14 cm to about 0.5 cm and that of dodder from 7.5 cm to about 0.25 cm. The effects of heliotrope allelochemicals on some physiological and biochemical processes of radish was also Investigated. The activity of auxin oxidase increased in leaves and roots of radish. Suggesting that the reduced radish growth is due to the decreased active auxin levels in its leaves and roots. The activity of alpha-amylase was reduced, so reduction of starch degradation and lack of respiratory energy is the prime reason of germination inhibition in dodder and radish seeds. The level of soluble sugars increased. This is an indication of reduction of the activity of some respiratory enzymes and reduced consumption of these sugars. Proline levels were also increased, indicating that, the chemical stress is induced by leaf extract. Finally, the activities of GPX and CAT which are antioxidant enzymes were increased, along with increased extract concentration. These finding shows that the chemical stress induced by leaf extract produces super oxide (O2*) and H2O2, which is neutralized to H2O and O2 by these enzymes.

  8. LRRK2 enhances oxidative stress-induced neurotoxicity via its kinase activity.

    Science.gov (United States)

    Heo, Hye Young; Park, Ji-Min; Kim, Cy-Hyun; Han, Baek Soo; Kim, Kwang-Soo; Seol, Wongi

    2010-02-15

    LRRK2 is an autosomal dominant gene whose mutations cause familial Parkinson's disease (PD). The LRRK2 protein contains a functional kinase and a GTPase domain. PD phenotypes caused by LRRK2 mutations are similar to those of idiopathic PD, implying that LRRK2 is an important participant in PD pathogenesis. Of LRRK2's PD-specific mutations, the G2019S is the most frequently observed one. Its over-expression is known to increase kinase activity and neurotoxicity compared to wild type (WT) LRRK2. Here, using a simple colorimetric cell viability assay, we analyzed LRRK2's neurotoxicity in dopaminergic SN4741 cells following treatment with hydrogen peroxide. When WT, G2019S, or empty vector was expressed in SN4741 cells, cell death was modestly and significantly increased in the order of G2019S>WT>vector. When these transfected cells were treated with hydrogen peroxide to mimic oxidative stress, cellular neurotoxicity was enhanced in the same order (i.e. G2019S>WT>vector). Moreover, incubation of SN4741 cells with conditioned medium from cells expressing G2019S and subjected to hydrogen peroxide treatment exhibited 10-15% more cell death than conditioned medium from cells transfected with vector or WT, suggesting that G2019S-expressing cells secrete a factor(s) affecting viability of neighboring cells. The kinase domain was mapped to be responsible for oxidative stress-induced neurotoxicity. In addition, over-expression of WT and G2019S LRRK2 lead to a weak, but significant, increase in intracellular reactive oxygen species (ROS) in the order of G2019S>WT as measured by DCFH-DA assay in both the presence and absence of H(2)O(2) treatment. Furthermore, in G2019S-expressing cells, co-expression of the anti-oxidant protein DJ-1 or ERK inhibitor treatment restored survival rate to a level similar to that of cells transfected with control vector under H(2)O(2) treatment. Taken together, our data suggest that the LRRK2 kinase domain increases the generation of ROS and causes

  9. Stress induced lipid production in Chlorella vulgaris: relationship with specific intracellular reactive species levels.

    Science.gov (United States)

    Menon, Kavya R; Balan, Ranjini; Suraishkumar, G K

    2013-06-01

    Microalgae have significant potential to be an important alternative energy source, but the challenges to the commercialization of bio-oil from microalgae need to be overcome for the potential to be realized. The application of stress can be used to improve bio-oil yields from algae. Nevertheless, the understanding of stress effects is fragmented due to the lack of a suitable, direct quantitative marker for stress. The lack of understanding seems to have limited the development of stress based strategies to improve bio-oil yields, and hence the commercialization of microalgae-based bio-oil. In this study, we have proposed and used the specific intracellular reactive species levels (siROS) particularly hydroxyl and superoxide radical levels, separately, as direct, quantitative, markers for stress, irrespective of the type of stress induced. Although ROS reactions are extremely rapid, the siROS level can be assumed to be at pseudo-steady state compared to the time scales of metabolism, growth and production, and hence they can be effective stress markers at particular time points. Also, the specific intracellular (si-) hydroxyl and superoxide radical levels are easy to measure through fluorimetry. Interestingly, irrespective of the conditions employed in this study, that is, nutrient excess/limitation or different light wavelengths, the cell concentrations are correlated to the siROS levels in an inverse power law fashion. The composite plots of cell concentration (y) and siROS (x) yielded the correlations of y = k1  · x(-0.7) and y = k2  · x(-0.79) , for si-hydroxyl and si-superoxide radical levels, respectively. The specific intracellular (si-) neutral lipid levels, which determine the bio-oil productivity, are related in a direct power law fashion to the specific hydroxyl radical levels. The composite plot of si-neutral lipid levels (z) and si-hydroxyl radical level (x) yielded a correlation of z = k3  · x(0.65) . More interestingly, a

  10. High susceptibility of activated lymphocytes to oxidative stress-induced cell death

    Directory of Open Access Journals (Sweden)

    Giovanna R. Degasperi

    2008-03-01

    Full Text Available The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.O presente estudo demonstra que linfócitos ativados de baço de ratos portadores do tumor de Walker 256 são mais susceptíveis à morte celular necrótica induzida por tert-butil hidroperóxido (t-BOOH in vitro quando comparados aos controles. O quelante de ferro e antioxidante deferoxamina, o quelante intracelular de Ca2+ BAPTA, o antagonista de canal de Ca2+ nifedipina ou o inibidor da transição de permeabilidade mitocondrial ciclosporina-A, mas não o inibidor de calcineurina FK-506, inibiram de maneira similar a morte celular induzida por t-BOOH em linfócitos ativados e controles. Os linfócitos ativados apresentaram redução do potencial de membrana mitocondrial induzida por t-BOOH num mecanismo sensível a ciclosporina-A. Nossos resultados indicam que o aumento da concentração de Ca2+ citosólico em linfócitos ativados aumenta a susceptibilidade dos mesmos à morte celular induzida por estresse oxidativo, num mecanismo envolvendo a participação do poro de transição de permeabilidade mitocondrial.

  11. Effect of pinaverium bromide on stress-induced colonic smooth muscle contractility disorder in rats

    Institute of Scientific and Technical Information of China (English)

    Yun Dai; Jian-Xiang Liu; Jun-Xia Li; Yun-Feng Xu

    2003-01-01

    AIM: To investigate the effect of pinaverium bromide, a Ltype calcium channel blocker with selectivity for the gastrointestinal tract on contractile activity of colonic circular smooth muscle in normal or cold-restraint stressed rats and its possible mechanism.METHODS: Cold-restraint stress was conducted on rats to increase fecal pellets output. Each isolated colonic circular muscle strip was suspended in a tissue chamber containing warm oxygenated Tyrode-Ringer solution. The contractile response to ACh or KCl was measured isometrically on inkwriting recorder. Incubated muscle in different concentrations of pinaverium and the effects of pinaverium were investigated on ACh or KCl-induced contraction. Colon smooth muscle cells were cultured from rats and [Ca2+]i was measured in cell suspension using the Ca2+ fluorescent dye fura-2/AlMl.RESULTS: During stress, rats fecal pellet output increased 61% (P<0.01). Stimulated with ACh or KCl, the muscle contractility was higher in stress than that in control. Pinaverium inhibited the increment of [Ca2+]i and the muscle contraction in response to ACh or KCl in a dose dependent manner. A significant inhibition of pinaverium to ACh or KCl induced [Ca2+]i increment was observed at 10-6 mol/L. The IC50 values for inhibition of ACh induced contraction for the stress and control group were 1.66×10-6 mol/L and 0.91×10-6mol/L, respectively. The ICs0 values for inhibition of KCl induced contraction for the stress and control group were 8.13×10-7 mol/L and 3.80×10-7 mol/L, respectively.CONCLUSION: Increase in [Ca2+]i of smooth muscle cells is directly related to the generation of contraction force in colon. L-type Ca2+ channels represent the main route of Ca2+ entry.Pinaverium inhibits the calcium influx through L-type channels;decreases the contractile response to many kinds of agonists and regulates the stress-induced colon hypermotility.

  12. Transient multivariable sensor evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Vilim, Richard B.; Heifetz, Alexander

    2017-02-21

    A method and system for performing transient multivariable sensor evaluation. The method and system includes a computer system for identifying a model form, providing training measurement data, generating a basis vector, monitoring system data from sensor, loading the system data in a non-transient memory, performing an estimation to provide desired data and comparing the system data to the desired data and outputting an alarm for a defective sensor.

  13. Endoplasmic Reticulum Stress-Induced Autophagy Provides Cytoprotection from Chemical Hypoxia and Oxidant Injury and Ameliorates Renal Ischemia-Reperfusion Injury.

    Directory of Open Access Journals (Sweden)

    Bhavya B Chandrika

    Full Text Available We examined whether endoplasmic reticulum (ER stress-induced autophagy provides cytoprotection from renal tubular epithelial cell injury due to oxidants and chemical hypoxia in vitro, as well as from ischemia-reperfusion (IR injury in vivo. We demonstrate that the ER stress inducer tunicamycin triggers an unfolded protein response, upregulates ER chaperone Grp78, and activates the autophagy pathway in renal tubular epithelial cells in culture. Inhibition of ER stress-induced autophagy accelerated caspase-3 activation and cell death suggesting a pro-survival role of ER stress-induced autophagy. Compared to wild-type cells, autophagy-deficient MEFs subjected to ER stress had enhanced caspase-3 activation and cell death, a finding that further supports the cytoprotective role of ER stress-induced autophagy. Induction of autophagy by ER stress markedly afforded cytoprotection from oxidants H2O2 and tert-Butyl hydroperoxide and from chemical hypoxia induced by antimycin A. In contrast, inhibition of ER stress-induced autophagy or autophagy-deficient cells markedly enhanced cell death in response to oxidant injury and chemical hypoxia. In mouse kidney, similarly to renal epithelial cells in culture, tunicamycin triggered ER stress, markedly upregulated Grp78, and activated autophagy without impairing the autophagic flux. In addition, ER stress-induced autophagy markedly ameliorated renal IR injury as evident from significant improvement in renal function and histology. Inhibition of autophagy by chloroquine markedly increased renal IR injury. These studies highlight beneficial impact of ER stress-induced autophagy in renal ischemia-reperfusion injury both in vitro and in vivo.

  14. Atypical Celiac Disease: From Recognizing to Managing

    Directory of Open Access Journals (Sweden)

    B. Admou

    2012-01-01

    Full Text Available The nonclassic clinical presentation of celiac disease (CD becomes increasingly common in physician’s daily practice, which requires an awareness of its many clinical faces with atypical, silent, and latent forms. Besides the common genetic background (HLA DQ2/DQ8 of the disease, other non-HLA genes are now notably reported with a probable association to atypical forms. The availability of high-sensitive and specific serologic tests such as antitissue transglutuminase, antiendomysium, and more recent antideamidated, gliadin peptide antibodies permits to efficiently uncover a large portion of the submerged CD iceberg, including individuals having conditions associated with a high risk of developing CD (type 1 diabetes, autoimmune diseases, Down syndrome, family history of CD, etc., biologic abnormalities (iron deficiency anemia, abnormal transaminase levels, etc., and extraintestinal symptoms (short stature, neuropsychiatric disorders, alopecia, dental enamel hypoplasia, recurrent aphtous stomatitis, etc.. Despite the therapeutic alternatives currently in developing, the strict adherence to a GFD remains the only effective and safe therapy for CD.

  15. NMDA antagonist MK 801 in nucleus accumbens core but not shell disrupts the restraint stress-induced reinstatement of extinguished cocaine-conditioned place preference in rats.

    Science.gov (United States)

    De Giovanni, Laura N; Guzman, Andrea S; Virgolini, Miriam B; Cancela, Liliana M

    2016-12-15

    Relapse is a common feature of cocaine addiction. In rodents, it can be elicited by cues, stress or the drug. Restraint stress-induced reinstatement of cocaine-conditioned place preference (CPP) is a useful model to study the mechanisms involved in stress-induced relapse of drug-seeking behavior. There is evidence that the glutamate NMDA receptors are critically involved in drug- and cue-induced reinstatement of seeking behavior and drug-CPP responses. The aim of this study was to investigate the contribution of NMDA receptors within core vs. shell nucleus accumbens (NAc) subregions to restraint stress-induced reinstatement of extinguished cocaine-CPP. After extinction of cocaine-conditioned preference, animals were administered MK 801 systemically or directly into intra-core or intra-shell, and restrained for 30min or left undisturbed in their home-cages. First, we demonstrated that restraint stress-induced reinstatement of extinguished cocaine-CPP depends on the duration of restraint as well as on the context in which it is applied. Second, this effect was blocked by systemic MK 801 administration either before or after restraint. Third, intra-core but not intra-shell administration abrogated the restraint stress-induced reinstatement. These findings show that NMDA receptors within NAc core, but not shell, play a critical role in restraint stress-induced reinstatement of cocaine-CPP.

  16. Atypical relapse of hemolytic uremic syndrome after transplantation.

    NARCIS (Netherlands)

    Olie, K.H.; Florquin, S.; Groothoff, J.W.; Verlaak, R.; Strain, L.; Goodship, T.H.; Weening, J.J.; Davin, J.C.

    2004-01-01

    Atypical hemolytic uremic syndrome (HUS) frequently leads to end-stage renal failure and can relapse after transplantation. A 12-year-old girl presenting with familial atypical HUS with a factor H mutation was successfully transplanted 6 years after a first transplant that had failed because of imme

  17. Inversed relationship between CD44 variant and c-Myc due to oxidative stress-induced canonical Wnt activation

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Go J., E-mail: medical21go@yahoo.co.jp; Saya, Hideyuki

    2014-01-10

    Highlights: •CD44 variant8–10 and c-Myc are inversely expressed in gastric cancer cells. •Redox-stress enhances c-Myc expression via canonical Wnt signal. •CD44v, but not CD44 standard, suppresses redox stress-induced Wnt activation. •CD44v expression promotes both transcription and proteasome degradation of c-Myc. •Inversed expression pattern between CD44v and c-Myc is often recognized in vivo. -- Abstract: Cancer stem-like cells express high amount of CD44 variant8-10 which protects cancer cells from redox stress. We have demonstrated by immunohistochemical analysis and Western blotting, and reverse-transcription polymerase chain reaction, that CD44 variant8-10 and c-Myc tend to show the inversed expression manner in gastric cancer cells. That is attributable to the oxidative stress-induced canonical Wnt activation, and furthermore, the up-regulation of the downstream molecules, one of which is oncogenic c-Myc, is not easily to occur in CD44 variant-positive cancer cells. We have also found out that CD44v8-10 expression is associated with the turn-over of the c-Myc with the experiments using gastric cancer cell lines. This cannot be simply explained by the model of oxidative stress-induced Wnt activation. CD44v8-10-positive cancer cells are enriched at the invasive front. Tumor tissue at the invasive area is considered to be composed of heterogeneous cellular population; dormant cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup high}/ c-Myc {sup low} and proliferative cancer stem-like cells with CD44v8-10 {sup high}/ Fbw7 {sup low}/ c-Myc {sup high}.

  18. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  19. Maternal chewing during prenatal stress ameliorates stress-induced hypomyelination, synaptic alterations, and learning impairment in mouse offspring.

    Science.gov (United States)

    Suzuki, Ayumi; Iinuma, Mitsuo; Hayashi, Sakurako; Sato, Yuichi; Azuma, Kagaku; Kubo, Kin-Ya

    2016-11-15

    Maternal chewing during prenatal stress attenuates both the development of stress-induced learning deficits and decreased cell proliferation in mouse hippocampal dentate gyrus. Hippocampal myelination affects spatial memory and the synaptic structure is a key mediator of neuronal communication. We investigated whether maternal chewing during prenatal stress ameliorates stress-induced alterations of hippocampal myelin and synapses, and impaired development of spatial memory in adult offspring. Pregnant mice were divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube, and was initiated on day 12 of pregnancy and continued until delivery. Mice in the stress/chewing group were given a wooden stick to chew during restraint. In 1-month-old pups, spatial memory was assessed in the Morris water maze, and hippocampal oligodendrocytes and synapses in CA1 were assayed by immunohistochemistry and electron microscopy. Prenatal stress led to impaired learning ability, and decreased immunoreactivity of myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in the hippocampal CA1 in adult offspring. Numerous myelin sheath abnormalities were observed. The G-ratio [axonal diameter to axonal fiber diameter (axon plus myelin sheath)] was increased and postsynaptic density length was decreased in the hippocampal CA1 region. Maternal chewing during stress attenuated the prenatal stress-induced impairment of spatial memory, and the decreased MBP and CNPase immunoreactivity, increased G-ratios, and decreased postsynaptic-density length in the hippocampal CA1 region. These findings suggest that chewing during prenatal stress in dams could be an effective coping strategy to prevent hippocampal behavioral and morphologic impairments in their offspring.

  20. The Bcl-2 proteins Noxa and Bcl-xL co-ordinately regulate oxidative stress-induced apoptosis.

    Science.gov (United States)

    Eno, Colins O; Zhao, Guoping; Olberding, Kristen E; Li, Chi

    2012-05-15

    Because the detailed molecular mechanisms by which oxidative stress induces apoptosis are not completely known, we investigated how the complex Bcl-2 protein network might regulate oxidative stress-induced apoptosis. Using MEFs (mouse embryonic fibroblasts), we found that the endogenous anti-apoptotic Bcl-2 protein Bcl-xL prevented apoptosis initiated by H(2)O(2). The BH3 (Bcl-2 homology 3)-only Bcl-2 protein Noxa was required for H(2)O(2)-induced cell death and was the single BH3-only Bcl-2 protein whose pro-apoptotic activity was completely antagonized by endogenous Bcl-xL. Upon H(2)O(2) treatment, Noxa mRNA displayed the greatest increase among BH3-only Bcl-2 proteins. Expression levels of the anti-apoptotic Bcl-2 protein Mcl-1 (myeloid cell leukaemia sequence 1), the primary binding target of Noxa, were reduced in H(2)O(2)-treated cells in a Noxa-dependent manner, and Mcl-1 overexpression was able to prevent H(2)O(2)-induced cell death in Bcl-xL-deficient MEF cells. Importantly, reduction of the expression of both Mcl-1 and Bcl-xL caused spontaneous cell death. These studies reveal a signalling pathway in which H(2)O(2) activates Noxa, leading to a decrease in Mcl-1 and subsequent cell death in the absence of Bcl-xL expression. The results of the present study indicate that both anti- and pro-apoptotic Bcl-2 proteins co-operate to regulate oxidative stress-induced apoptosis.

  1. Hypothermia enhances bcl-2 expression and protects against oxidative stress-induced cell death in Chinese hamster ovary cells.

    Science.gov (United States)

    Slikker, W; Desai, V G; Duhart, H; Feuers, R; Imam, S Z

    2001-08-01

    Oxidative stress is one of the major causes of cellular injury. Various reactive oxygen (ROS) and nitrogen (RNS) species such as superoxide, hydroxyl radical, peroxynitrite, and nitric oxide are involved in the manifestations of different types of organ toxicity and the resultant syndromes, symptoms, or diseases. Hypothermic conditions have been reported to reduce the oxidative stress in various in vitro and in vivo studies. In the present study, we sought to determine the effect of lowered temperatures on oxidative stress-induced cell death in Chinese hamster ovary (CHO) cells. We also investigated the oxidative stress-induced alterations in the expression of anti-apoptotic protein, bcl-2, in CHO cells at lowered temperatures. CHO cells were incubated at four different temperatures of 30, 32, 35, and 37 degrees C (control temperature) from 1 to 4 d. In another set, the cells were incubated with 100 microM hydrogen peroxide (H(2)O(2)) for 30 min before harvesting at different time points. The cells were harvested at 1, 2, 3, and 4 d. Cell survival was significantly higher at 30 degrees C as compared to 37 degrees C over 4 d of incubation. In cells incubated with H(2)O(2), significantly higher cell viability was observed at lower temperatures as compared to the cells incubated at 37 degrees C. The activity of glutathione peroxidase (GSH-Px) also increased significantly at lower temperatures. Lowered temperature also provided a significant increase in the expression of anti-apoptotic protein, bcl-2 after 4 d of incubation. These data suggest that hypothermic conditions lowers the risk of oxidative stress-induced cellular damage and programmed cell death by increasing the activity of GSH-Px and by the induction in the expression of the anti-apoptotic protein, bcl-2.

  2. Central noradrenergic depletion by DSP-4 prevents stress-induced memory impairments in the object recognition task.

    Science.gov (United States)

    Scullion, G A; Kendall, D A; Sunter, D; Marsden, C A; Pardon, M-C

    2009-12-01

    Environmental stress produces adverse affects on memory in humans and rodents. Increased noradrenergic neurotransmission is a major component of the response to stress and noradrenaline (NA) plays an important role in modulating processes involved in learning and memory. The present study investigated the effect of NA depletion on stress-induced changes on memory performance in the mouse. Central NA depletion was induced using the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP-4) and verified by high performance liquid chromatography (HPLC). A novel cage stress procedure involving exposure to a new clean cage for 1 h per day, 4 days per week for 4 weeks, was used to produce stress-induced memory deficits measured using the object recognition task. 50 mg/kg DSP-4 produced large and sustained reductions in NA levels in the frontal cortex and hippocampus measured 24 h, 1 week and 5 weeks after treatment. Four weeks of exposure to novel cage stress induced a memory deficit in the object recognition task which was prevented by DSP-4 pre-treatment (50 mg/kg 1 week before the commencement of stress).These findings indicate that chronic environmental stress adversely affects recognition memory and that this effect is, in part, mediated by the noradrenergic stress response. The implication of these findings is that drugs targeting the noradrenergic system to reduce over-activity may be beneficial in the treatment of stress-related mental disorders such as post-traumatic stress disorder or anxiety in which memory is affected.

  3. 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.

  4. Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Lulu Fan

    Full Text Available BACKGROUND: Endoplasmic reticulum stress (ER stress is generally activated in solid tumors and results in tumor cell anti-apoptosis and drug resistance. Paeonol (Pae, 2-hydroxy-4-methoxyacetophenone, is a natural product extracted from the root of Paeonia Suffruticosa Andrew. Although Pae displays anti-neoplastic activity and increases the efficacy of chemotherapeutic drugs in various cell lines and in animal models, studies related to the effect of Pae on ER stress-induced resistance to chemotherapeutic agents in hepatocellular carcinoma (HCC are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the effect of the endoplasmic reticulum (ER stress response during resistance of human hepatocellular carcinoma cells to doxorubicin. Treatment with the ER stress-inducer tunicamycin (TM before the addition of doxorubicin reduced the rate of apoptosis induced by doxorubicin. Interestingly, co-pretreatment with tunicamycin and Pae significantly increased apoptosis induced by doxorubicin. Furthermore, induction of ER stress resulted in increasing expression of COX-2 concomitant with inactivation of Akt and up-regulation of the pro-apoptotic transcription factor CHOP (GADD153 in HepG2 cells. These cellular changes in gene expression and Akt activation may be an important resistance mechanism against doxorubicin in hepatocellular carcinoma cells undergoing ER stress. However, co-pretreatment with tunicamycin and Pae decreased the expression of COX-2 and levels of activation of Akt as well as increasing the levels of CHOP in HCC cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Pae reverses ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by targeting COX-2 mediated inactivation of PI3K/AKT/CHOP.

  5. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Srisuttee, Ratakorn [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Jhun, Byung Hak [Department of Applied Nanoscience, Pusan National University, Busan 609-735 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  6. Stress induced a shift from dorsal hippocampus to prefrontal cortex dependent memory retrieval: role of regional corticosterone.

    Science.gov (United States)

    Dominguez, Gaelle; Faucher, Pierre; Henkous, Nadia; Krazem, Ali; Piérard, Christophe; Béracochéa, Daniel

    2014-01-01

    Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each) delivered before memory testing reversed the memory retrieval pattern (MRP) in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non-stress condition) to mPFC-dependent MRP and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  7. β-carotene treatment alters the cellular death process in oxidative stress-induced K562 cells.

    Science.gov (United States)

    Akçakaya, Handan; Tok, Sabiha; Dal, Fulya; Cinar, Suzan Adin; Nurten, Rustem

    2017-03-01

    Oxidizing agents (e.g., H2 O2 ) cause structural and functional disruptions of molecules by affecting lipids, proteins, and nucleic acids. As a result, cellular mechanisms related to disrupted macro molecules are affected and cell death is induced. Oxidative damage can be prevented at a certain point by antioxidants or the damage can be reversed. In this work, we studied the cellular response against oxidative stress induced by H2 O2 and antioxidant-oxidant (β-carotene-H2 O2 ) interactions in terms of time, concentration, and treatment method (pre-, co-, and post) in K562 cells. We showed that co- or post-treatment with β-carotene did not protect cells from the damage of oxidative stress furthermore co- and post-β-carotene-treated oxidative stress induced cells showed similar results with only H2 O2 treated cells. However, β-carotene pre-treatment prevented oxidative damage induced by H2 O2 at concentrations lower than 1,000 μM compared with only H2 O2 -treated and co- and post-β-carotene-treated oxidative stress-induced cells in terms of studied cellular parameters (mitochondrial membrane potential [Δψm ], cell cycle and apoptosis). Prevention effect of β-carotene pre-treatment was lost at concentrations higher than 1,000 μM H2 O2 (2-10 mM). These findings suggest that β-carotene pre-treatment alters the effects of oxidative damage induced by H2 O2 and cell death processes in K562 cells.

  8. Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-A [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Shim, Sang Hee [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Ahn, Hong Ryul [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Jung, Sang Hoon, E-mail: shjung507@gmail.com [Functional Food Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 210-340 (Korea, Republic of)

    2013-06-01

    The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with L-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca{sup 2+} was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-D-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7 days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage, and may be considered as an agent for treating or preventing retinal degeneration. - Highlights: • Psoralea corylifolia have neuroprotective effects in vitro and in vivo. • Bakuchiol attenuated the increase of apoptotic proteins induced by oxidative

  9. Stress-induced martensite variant reorientation in magnetic shape memory Ni Mn Ga single crystal studied by neutron diffraction

    Science.gov (United States)

    Molnar, P.; Sittner, P.; Lukas, P.; Hannula, S.-P.; Heczko, O.

    2008-06-01

    Stress-induced martensite variant reorientation in magnetic shape memory Ni-Mn-Ga single crystal was studied in situ by the neutron diffraction technique. Principles of determination of individual tetragonal martensitic variants in shape memory alloys are explained. Using neutron diffraction we show that the macroscopic strain originates solely from the martensite structure reorientation or variant redistribution. Neutron diffraction also reveals that the reorientation of martensite is not fully completed even at a stress value of 25 MPa, which is about 20 times larger than the mean stress needed for reorientation. Only one twinning system is active during the reorientation process.

  10. Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance

    DEFF Research Database (Denmark)

    Emanuelli, Brice; Eberlé, Delphine; Suzuki, Ryo

    2008-01-01

    Insulin resistance, a hallmark of type 2 diabetes and obesity, is associated with increased activity of MAP and stress-activated protein (SAP) kinases, which results in decreased insulin signaling. Our goal was to investigate the role of MAP kinase phosphatase-4 (MKP-4) in modulating this process......, improved glucose intolerance, decreased expression of gluconeogenic and lipogenic genes, and reduced hepatic steatosis. Thus, MKP-4 has a protective effect against the development of insulin resistance through its ability to dephosphorylate and inactivate crucial mediators of stress-induced insulin...... resistance, such as ERK and JNK, and increasing MKP-4 activity might provide a therapy for insulin-resistant disorders....

  11. A Stress-Induced Martensitic Transformation in Aged Ti49Ni51 Alloy after High-Velocity Impact

    Directory of Open Access Journals (Sweden)

    Yingying Zhu

    2016-06-01

    Full Text Available The effects of a high-velocity impact on the microstructure, phase transformation and mechanical property of aged Ti49Ni51 alloy are investigated. The transformation behavior and microstructure along the impact direction after impact emerge with regionalization characteristics, including a deformed region near the crater (0–4 mm and an un-deformed region of the distal crater (5–6 mm. Stress-induced martensite is the main deformation mechanism in the deforming region of aged Ti49Ni51 alloy under high-velocity impact.

  12. Role of TFF in healing of stress-induced gastric lesions

    Institute of Scientific and Technical Information of China (English)

    Shi-Nan Nie; Hai-Chen Sun; Zhao-Shen Li; Xiao-Ming Qian; Xue-Hao Wu; Shi-Yu Yang; Wen-Jie Tang; Bao-Hua Xu; Fang Huang; Xin Lin; Dong-Yan Sun

    2003-01-01

    AIM: To determine the changes of pS2 and ITF of TFF expression in gastric mucosa and the effect on ulcer healing of pS2, ITF to Water-immersion and restraint stress (WRS)in rats.METHODS: Wistar rats were exposed to single or repeated WRS for 4 h every other day for up to 6 days. Gastric mucosal blood flow (GMBF) was measured by LDF-3 flowmeter and the extent of gastric mucosal lesions were evaluated grossly and histologically. Expression of pS2 and ITF mRNA was determined by RT-PCR. Immunohistochemistry was used to further detect the expression of pS2 and ITF.RESULTS: WRS applied once produced numerous gastric mucosal erosions, but the number of these lesions gradually declined and GMBF restored at 2, 4, 8 h after stress. The area of gastric mucosal lesion was reduced by 64.9 % and GMBF was increased by 89.8 % at 8 h. The healing of stress-induced ulcerations was accompanied by increased expression of pS2 (0.51±0.14 vs0.77±0.11, P<0.01) and ITF (0.022±0.001 vs 0.177±0.010, P<0.01). The results were demonstrated further by immunohistochemistry of pS2(0.95±0.11 vs1.41±0.04, P<0.01) and ITF (0.134±0.001 vs 0.253±0.01,P<0.01). With repeated WRS, adaptation to this WRS developed, the area of gastric mucosal lesions was reduced by 22.0 % after four consecutive WRS. This adaptation to WRS was accompanied by increased GMBF (being increased by 94.2 %), active cell proliferation in the neck region of gastric glands, and increased expression of pS2 (0.37±0.02 vs 0.77±0.01, P<0.01) and ITF (0.040±0.001 vs0.372±0.010, P<0.01). The result was demonstrated further by immunohistochemistry of pS2 (0.55±0.04 vs 2.46±0.08, P<0.01) and ITF (0.134±0.001 vs0.354±0.070,P<0.01).CONCLUSION: TFF may not only participate in the early phase of epithelial repair known as restitution(maked by increased cell migration),but also play an important role in the subsequent, protracted phase of glandular renewal(made by cell proliferation).

  13. Modeling and inversion of stress-induced multicomponent seismic time shifts

    Science.gov (United States)

    Smith, Steven Shawn

    Subsurface pressure and temperature variations can alter rock properties both near and relatively far from the disturbance, causing detectable changes in seismic traveltimes. In this thesis, I first use traveltime variations to study velocity changes around a heated prototype nuclear waste storage tunnel. Then I model and invert compaction-induced multicomponent time shifts from depressurizing petroleum reservoirs. Heaters inside the tunnel replicate the thermal output of decaying radioactive waste, heating the tunnel over two years and maintaining a constant temperature for another two years. Time-lapse velocity models were constructed using temperature-dependent velocity data for granite and thermal profiles from boreholes in the tunnel wall. Matching check-shot and modeled waveforms indicate that the tunnel temperature can be monitored using seismic data. Further, the smooth, unperturbed velocity field lacks spatial perturbations, suggesting that no fluid or steam was present around the tunnel near the receiver array during the experiment. However, the combination of changing velocities and non-elastic, stress-induced acoustic emissions near the tunnel crown suggest that damage to the rock may occur. To study time shifts around a compacting reservoir, I employ geomechanical modeling of the compaction-induced stress/strain fields. Strain-dependent stiffness perturbations are obtained from the nonlinear theory of elasticity. Then full-waveform multicomponent seismic data are generated by finite-differences and used to estimate the time shifts of P-, S-, and PS-waves. P-wave time shifts are strongly influenced by compaction-induced velocity anisotropy around the reservoir. S-wave anisotropy is almost negligible, but S-wave shifts are 2-3 times larger than those of P-waves. PS-wave time-shift behavior significantly varies with the reflection point. Spatial time-shift distributions are exploited to study the sensitivity of each wave type to reservoir pressure ( Delta

  14. Imaging the neurobiological substrate of atypical depression by SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Salmaso, Dario [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Nardo, Davide [University of Rome La Sapienza, Department of Psychology, Rome (Italy); Jonsson, Cathrine; Larsson, Stig A. [Karolinska University Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Jacobsson, Hans [Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Gardner, Ann [Karolinska University Hospital Huddinge, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm (Sweden)

    2007-01-15

    Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in {sup 99m}Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders. (orig.)

  15. Clinical grand rounds: atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Hodgkins, Kavita S; Bobrowski, Amy E; Lane, Jerome C; Langman, Craig B

    2012-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

  16. Atypical Cogan's syndrome associated with coronary disease

    Institute of Scientific and Technical Information of China (English)

    Ivanovic Branislava; Tadic Marijana; Damjanov Nemanja; Simic Dragan; Zlatanovic Maja

    2011-01-01

    Cogan's syndrome (CS) is a rare inflammatory disorder characterized by interstitial keratitis and vestibuloauditory abnormalities often associated with various systemic manifestations. Involvement of cardiovascular system resembling systemic vasculitis may lead to severe complications and death. The present report describes a case of a female patient with atypical Cogan's syndrome presented with systemic manifestations and severe coronary and femoral artery stenosis.Despite the clinical improvement after glucocorticoids and cyclophosphamide, the patient required double aortocoronal bypass grafting one year letter. During three years follow-up, she was in stable condition, without stenocardial symptoms and claudication and her inflammatory parameters remain normal. This case highlights the rare involvement of coronary arteries without associated large-vessel vasculitis of the aortic arch in CS.

  17. Pulmonary Atypical Adenomatous Hyperplasia And Bronchioloalveolar Carcinoma

    Institute of Scientific and Technical Information of China (English)

    MeilinXu; XiaYang; ZhiyaoZhang

    2004-01-01

    OBJECTIVE To study the relationship between atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). METHODS Morphometric, immunohistochemical and ultrastructural analyses were performed in 4 patients with low grade AAH, 5 with high grade AAH and 7 with BAC. RESULTS The mean nuclear areas of high grade AAH and BAC were greater than those of low grade AAH (P<0.05); p53 protein expression was negative in 4 cases of low grade AAH,while the positive rates in high grade AAH and BAC were 40% (2/5) and 57% (4/7), respectively. CONCLUSION The development of BAC is stepwise. AAH appears to be a lesion closely related with BAC, probably as its genuine precursor.

  18. Indications of atypical antipsychotics in the elderly.

    Science.gov (United States)

    McKean, Andrew; Monasterio, Erik

    2015-01-01

    Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.

  19. Atypical parakeratosis: a marker of dysplasia?

    Science.gov (United States)

    Voytek, T M; Kannan, V; Kline, T S

    1996-11-01

    The Bethesda System categorizes atypical parakeratosis (APK) as "ASCUS or SIL depending on the degree of cellular abnormalities." APK, however, is not well-defined. We retrospectively reviewed 68 cervicovaginal specimens with follow-up material to identify specific criteria and clinical significance of APK. APK cells were small cells, 2-3 times the diameter of neutrophil, with dense, orangeophilic cytoplasm, high nuclear cytoplasmic ratio, dense, often uneven chromatin, and irregular nuclear contour. Of 62 cases with APK, 37 had accompanying dysplastic cells. Of 25 cases with APK alone, follow-up revealed 12 with squamous intraepithelial lesion (5 HSIL and 7 LSIL) and 13 with benign changes. A major diagnostic pitfall of APK was inflammation with degeneration. Abundant APK cells, minimal inflammation and degeneration, and previous history of dysplasia frequently were associated with follow-up SIL. The findings of this study identify APK as an important marker for dysplasia that warrants careful evaluation and follow-up.

  20. Atypical Radiological Manifestation of Pulmonary Metastatic Calcification

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Hae; Kim, Eun Sun; Kim, Chul Hwan; Ham, Soo Youn; Oh, Yu Whan [Korea University College of Medicine, Seoul (Korea, Republic of)

    2008-04-15

    Metastatic pulmonary calcification is a condition of calcium deposition in the normal pulmonary parenchyma, and this is secondary to abnormal calcium metabolism without any prior soft tissue damage. The predisposing factors for this condition include chronic renal failure, hypercalcemia and increased tissue alkalinity. The most common radiologic manifestation consists of poorly defined nodular opacities in the upper lung zone. These opacities reflect the deposition of calcium salts in the pulmonary interstitium. We present here a case of metastatic pulmonary calcification in a patient who recovered from pneumonia with sepsis and whose high-resolution CT (HRCT) images demonstrated localized parenchymal airspace calcification that was limited to the bilateral lower lobes. These lower lobes had been involved with pneumonic consolidation without calcification, as seen on the previous CT scan. In summary, we report here on an atypical presentation of metastatic pulmonary calcification that showed dense airspace consolidation localized to the bilateral lower lobes in a patient with primary hyperparathyroidism and pneumonia.

  1. Emphysematous Cystitis: Report of an Atypical Case

    Directory of Open Access Journals (Sweden)

    Karen De Baets

    2011-01-01

    Full Text Available We report the atypical case of a nondiabetic 66-year old male with severe abdominal pain and vomiting who was found to have emphysematous cystitis. Of all gas-forming infections of the urinary tract emphysematous cystitis is the most common and the least severe. The major risk factors are diabetes mellitus and urinary tract obstruction. Most frequent causative pathogens are Escherichia coli and Klebsiella pneumoniae. The clinical presentation is nonspecific and ranges from asymptomatic urinary tract infection to urosepsis and septic shock. The diagnosis is made by abdominal imaging. Treatment consists of broad-spectrum antibiotics, bladder drainage, and management of the risk factors. Surgery is reserved for severe cases. Overall mortality rate of emphysematous cystitis is 7%. Immediate diagnosis and treatment is necessary because of the rapid progression to bladder necrosis, emphysematous pyelonephritis, urosepsis, and possibly fatal evolution.

  2. A case of atypical progressive supranuclear palsy

    Directory of Open Access Journals (Sweden)

    Spaccavento S

    2013-12-01

    Full Text Available Simona Spaccavento, Marina Del Prete, Angela Craca, Anna Loverre IRCCS Salvatore Maugeri Foundation, Cassano Murge, Bari, Italy Background: Progressive supranuclear palsy (PSP is a neurodegenerative extrapyramidal syndrome. Studies have demonstrated that PSP can present clinically as an atypical dementing syndrome dominated by a progressive apraxia of speech (AOS and aphasia. Aim: We aimed to investigate the clinical presentation of PSP, using a comprehensive multidimensional evaluation, and the disease response to various pharmacological treatments. Methods: A 72-year-old right-handed male, with 17 years education, who first presented with aphasia, AOS, depression, apathy, and postural instability at 69 years; a complete neuropsychological evaluation, tapping the different cognitive domains, was performed. Results: Testing revealed a moderate global cognitive deficit (Mini-Mental State Examination test score =20, low memory test scores (story recall, Rey’s 15-word Immediate and Delayed Recall, and poor phonemic and semantic fluency. The patient’s language was characterized by AOS, with slow speech rate, prolonged intervals between syllables and words, decreased articulatory accuracy, sound distortions, and anomia. Behavioral changes, such as depression, anxiety, apathy, and irritability, were reported. The neurological examination revealed supranuclear vertical gaze palsy, poor face miming, and a mild balance deficit. Magnetic resonance imaging showed only widespread cortical atrophy. Single photon emission computed tomography demonstrated left > right frontotemporal cortical abnormalities. After 6 months, a further neuropsychological assessment showed a progression in cognitive deficits, with additional attention deficits. The patient reported frequent falls, but the neurological deficits remained unchanged. Neuroimaging tests showed the same brain involvement. Conclusion: Our case highlights the heterogeneity of the clinical features in

  3. Preventing the stress-induced shift from goal-directed to habit action with a β-adrenergic antagonist.

    Science.gov (United States)

    Schwabe, Lars; Höffken, Oliver; Tegenthoff, Martin; Wolf, Oliver T

    2011-11-23

    Stress modulates instrumental action in favor of habit processes that encode the association between a response and preceding stimuli and at the expense of goal-directed processes that learn the association between an action and the motivational value of the outcome. Here, we asked whether this stress-induced shift from goal-directed to habit action is dependent on noradrenergic activation and may therefore be blocked by a β-adrenoceptor antagonist. To this end, healthy men and women were administered a placebo or the β-adrenoceptor antagonist propranolol before they underwent a stress or a control procedure. Shortly after the stress or control procedure, participants were trained in two instrumental actions that led to two distinct food outcomes. After training, one of the food outcomes was selectively devalued by feeding participants to satiety with that food. A subsequent extinction test indicated whether instrumental behavior was goal-directed or habitual. As expected, stress after placebo rendered participants' behavior insensitive to the change in the value of the outcome and thus habitual. After propranolol intake, however, stressed participants behaved, same as controls, goal-directed, suggesting that propranolol blocked the stress-induced bias toward habit behavior. Our findings show that the shift from goal-directed to habitual control of instrumental action under stress necessitates noradrenergic activation and could have important clinical implications, particularly for addictive disorders.

  4. Delayed degradation of chlorophylls and photosynthetic proteins in Arabidopsis autophagy mutants during stress-induced leaf yellowing.

    Science.gov (United States)

    Sakuraba, Yasuhito; Lee, Sang-Hwa; Kim, Ye-Sol; Park, Ohkmae K; Hörtensteiner, Stefan; Paek, Nam-Chon

    2014-07-01

    Plant autophagy, one of the essential proteolysis systems, balances proteome and nutrient levels in cells of the whole plant. Autophagy has been studied by analysing Arabidopsis thaliana autophagy-defective atg mutants, but the relationship between autophagy and chlorophyll (Chl) breakdown during stress-induced leaf yellowing remains unclear. During natural senescence or under abiotic-stress conditions, extensive cell death and early yellowing occurs in the leaves of atg mutants. A new finding is revealed that atg5 and atg7 mutants exhibit a functional stay-green phenotype under mild abiotic-stress conditions, but leaf yellowing proceeds normally in wild-type leaves under these conditions. Under mild salt stress, atg5 leaves retained high levels of Chls and all photosystem proteins and maintained a normal chloroplast structure. Furthermore, a double mutant of atg5 and non-functional stay-green nonyellowing1-1 (atg5 nye1-1) showed a much stronger stay-green phenotype than either single mutant. Taking these results together, it is proposed that autophagy functions in the non-selective catabolism of Chls and photosynthetic proteins during stress-induced leaf yellowing, in addition to the selective degradation of Chl-apoprotein complexes in the chloroplasts through the senescence-induced STAY-GREEN1/NYE1 and Chl catabolic enzymes.

  5. Differential stress-induced alterations of colonic corticotropin-releasing factor receptors in the Wistar Kyoto rat.

    Science.gov (United States)

    o'malley, D; Julio-Pieper, M; Gibney, S M; Gosselin, R D; Dinan, T G; Cryan, J F

    2010-03-01

    BACKGROUND A growing body of data implicates increased life stresses with the initiation, persistence and severity of symptoms associated with functional gut disorders such as irritable bowel syndrome (IBS). Activation of central and peripheral corticotropin-releasing factor (CRF) receptors is key to stress-induced changes in gastrointestinal (GI) function. METHODS This study utilised immunofluorescent and Western blotting techniques to investigate colonic expression of CRF receptors in stress-sensitive Wistar Kyoto (WKY) and control Sprague Dawley (SD) rats. KEY RESULTS No intra-strain differences were observed in the numbers of colonic CRFR1 and CRFR2 positive cells. Protein expression of functional CRFR1 was found to be comparable in control proximal and distal colon samples. Sham levels of CRFR1 were also similar in the proximal colon but significantly higher in WKY distal colons (SD: 0.38 +/- 0.14, WKY: 2.06 +/- 0.52, P CRF receptor expression and further support a role for local colonic CRF signalling in stress-induced changes in GI function.

  6. The Effect of Exercise on Learning and Spatial Memory Following Stress-Induced Sleep Deprivation (Sleep REM in Rats

    Directory of Open Access Journals (Sweden)

    Darkhah

    2016-04-01

    Full Text Available Background Stress induced by sleep deprivation can cause degradation of learning in the acquisition phase, and low-intensity exercise can prevent the negative effects of stress. Objectives The aim of this study was to investigate the moderating role of aerobic exercise on spatial memory and learning following stress-induced insomnia (sleep REM in animal models. Materials and Methods This experimental study was conducted on adult male Wistar rats that were randomly divided into two groups. Both groups were exposed to sleep deprivation induced stress, following which the experimental group was exposed to exercise training (experimental, n = 8; control, n = 8. The stress intervention was undertaken through 24 hours of sleep deprivation using a modified sleep deprivation platform (MMD. The exercise protocol included mild aerobic exercise on a treadmill (30 minutes a day, seven days, and Morris Water Maze (MWM protocols were applied to assess spatial memory and learning. Data were analyzed by an independent t-test and dependent t-test. Results The results showed that, after seven days of aerobic exercise on a treadmill, the experimental group showed better performance escape latency (P < 0.05 and distance traveled (P < 0.05 than the control group in the MWM, while there was no difference between these two groups in the pre-test. Conclusions The role of exercise is greater in the retention than the acquisition phase for recalling past experiences.

  7. Effect of Celastrus paniculatus seed oil (Jyothismati oil on acute and chronic immobilization stress induced in swiss albino mice

    Directory of Open Access Journals (Sweden)

    George Lekha

    2010-01-01

    Full Text Available Stress alters the homeostasis and is produced by several factors. Immobilization stress induced due to reduced floor area provided for the mobility results in the imbalance of oxidant and antioxidant status. The modern computer savvy world decreases human mobility in the working environment, leading to the formation of oxygen free radicals and if left untreated might result in severe health problems like hypertension, cardiovascular disease, premature aging and brain dysfunction. Hence, modern medicines rely upon the medicinal plants for some drugs with zero side effects. In this context, Jyothismati oil (JO, extracted from Celastrus paniculatus seeds, was used to treat acute and chronic immobilization induced experimentally. C. paniculatus plant is considered to be rich in antioxidant content and so the seed oil extract′s efficacy was tested against immobilization stress in albino mice. The animals were kept in a restrainer for short and long durations, grouped separately and fed with the drug. Animals were sacrificed and the samples were analyzed. The antioxidant enzyme levels of the animals regained and markedly increased in the acute and chronic immobilized groups, respectively. The results suggested that the extract of C. paniculatus seed was highly efficacious in reducing the stress induced by least mobility for hours.

  8. Unpredictable chronic stress-induced reproductive suppression associated with the decrease of kisspeptin immunoreactivity in male mice.

    Science.gov (United States)

    Hirano, Tetsushi; Kobayashi, Yoshihiro; Omotehara, Takuya; Tatsumi, Atsutoshi; Hashimoto, Rie; Umemura, Yuria; Nagahara, Daichi; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2014-09-01

    Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.

  9. Isolation and functional characterization of salt-stress induced RCI2-like genes from Medicago sativa and Medicago truncatula.

    Science.gov (United States)

    Long, Ruicai; Zhang, Fan; Li, Zhenyi; Li, Mingna; Cong, Lili; Kang, Junmei; Zhang, Tiejun; Zhao, Zhongxiang; Sun, Yan; Yang, Qingchuan

    2015-07-01

    Salt stress is one of the most significant adverse abiotic factors, causing crop failure worldwide. So far, a number of salt stress-induced genes, and genes improving salt tolerance have been characterized in a range of plants. Here, we report the isolation and characterization of a salt stress-induced Medicago sativa (alfalfa) gene (MsRCI2A), which showed a high similarity to the yeast plasma membrane protein 3 gene (PMP3) and Arabidopsis RCI2A. The sequence comparisons revealed that five genes of MtRCI2(A-E) showed a high similarity to MsRCI2A in the Medicago truncatula genome. MsRCI2A and MtRCI2(A-E) encode small, highly hydrophobic proteins containing two putative transmembrane domains, predominantly localized in the plasma membrane. The transcript analysis results suggest that MsRCI2A and MtRCI2(A-D) genes are highly induced by salt stress. The expression of MsRCI2A and MtRCI2(A-C) in yeast mutants lacking the PMP3 gene can functionally complement the salt sensitivity phenotype resulting from PMP3 deletion. Overexpression of MsRCI2A in Arabidopsis plants showed improved salt tolerance suggesting the important role of MsRCI2A in salt stress tolerance in alfalfa.

  10. Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells transplantation.

    Science.gov (United States)

    Wang, Chao; Shi, Dongling; Song, Xinghui; Chen, Yingying; Wang, Linlin; Zhang, Xiaoming

    2016-07-01

    Bone marrow mesenchymal stem cells (BMSCs) therapy for tissue repair is limited by low survival of cells transplanted in the recipient sites after spinal cord injury (SCI). Here, we investigated the effects of a calpain inhibitor (MDL28170) on BMSCs survival by a rat model of spinal cord injury in vitro and in vivo. Conditioned medium from hypoxia injured VSC4.1 motor neurons (Hypoxia-CM) were collected to mimic the micro-environment of injured spinal cord. Tunicamycin was also applied to induce endoplasmic reticulum (ER) stress in BMSCs. The CCK-8 assay, LDH leakage assay and flow cytometer assay demonstrated that MDL28170 could enhance BMSCs survival in response to Hypoxia-CM and tunicamycin. Moreover, MDL28170 significantly enhanced GFP-positive BMSCs survival in vivo after transplantation into the contused spinal cord of SCI rats. The protective effects of MDL28170 on BMSCs survival may inhibit the activation of calpain and the downstream ER stress-induced apoptosis. The present results suggested for the first time that MDL28170 with BMSCs transplant helped to rescue cells in injured spinal cord by modulating the ER stress-induced apoptosis. The calpain inhibitor, MDL28170 may have the promising new strategies for promoting the survival of transplanted BMSCs on cell-based regenerative medicine.

  11. Protective effects of ginsenoside Rg1 on chronic restraint stress induced learning and memory impairments in male mice.

    Science.gov (United States)

    Wang, Yuchan; Kan, Hongwei; Yin, Yanyan; Wu, Wangyang; Hu, Wen; Wang, Mingming; Li, Weiping; Li, Weizu

    2014-05-01

    Alzheimer's disease (AD) is one of the major neurological diseases of the elderly. Chronic stress, which can induce atrophy and functional impairments in several key brain areas such as the frontal cortex and hippocampus, plays an important role in the generation and progression of AD. Currently, there are no effective drug treatment options for preventing chronic stress induced learning and memory impairments and neuronal damage. Ginsenoside Rg1 (Rg1) is a steroidal saponin abundantly contained in ginseng. This study explored the neuroprotective effects of Rg1 on chronic restraint stress (CRS) induced learning and memory impairments in a mouse model. Our results showed that Rg1 (5mg/kg) significantly protected against learning and memory impairments induced by CRS in a Morris water maze. Besides, Rg1 (2, 5mg/kg) was able to decrease ROS generation and attenuate the neuronal oxidative damage in the frontal cortex and hippocampus CA1 in mice. Additionally, the inhibition of NOX2, p47phox and RAC1 expression is also involved in the action mechanisms of Rg1 in this experimental model. This study provided an experimental basis for the clinical application of Rg1 in chronic stress induced neuronal oxidative damage.

  12. Integrin-like Protein Is Involved in the Osmotic Stress-induced Abscisic Acid Biosynthesis in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Bing Lü; Feng Chen; Zhong-Hua Gong; Hong Xie; Jian-Sheng Liang

    2007-01-01

    We studied the perception of plant cells to osmotic stress that leads to the accumulation of abscisic acid (ABA) in stressed Arabidopsis thaliana L. cells. A significant difference was found between protoplasts and cells in terms of their responses to osmotic stress and ABA biosynthesis, implying that cell wall and/or cell wall-plasma membrane interaction are essential in identifying osmotic stress. Western blotting and immunofluorescence localization experiments, using polyclonal antibody against human integrin β1, revealed the existence of a protein similar to the integrin protein of animals in the suspension-cultured cells located in the plasma membrane fraction.Treatment with a synthetic pentapeptide, Gly-Arg-Gly-Asp-Ser (GRGDS), which contains an RGD domain and interacts specifically with integrin protein and thus blocks the cell wall-plasma membrane interaction, significantly inhibited osmotic stress-induced ABA biosynthesis in cells, but not in protoplasts. These results demonstrate that cell wall and/or cell wall-plasma membrane interaction mediated by integrin-like proteins played important roles in osmotic stress-induced ABA biosynthesis in Arabidopsis thaliana.

  13. Protein phosphorylation is involved in the water stress induced ABA accumulation in the roots of Malus hupehensis Rehd

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Water stress-induced ABA accumulation plays a key role in the root to shoot communication and/or the cell to cell signaling under the soil stresses. The signaling of the water stress itself that leads to the accumulation, however, is less known. In this study, we subjected the roots of Malus hupehensis seedlings to water stress treatment and investigated the ABA accumulation in relation to protein phosphorylation. Our results showed that ABA accumulation could be substantially triggered in 40 min and reached 4 folds in 100 min after treatment with 30% PEG 6000 (polyethylene glycol). The water stress treatment also led to a substantial enhancement of total kinase activity, assessed with histone-Ⅲ as substrate, in 15 min and a maximum enhancement in 30 min before it declined to initial level. The Ca2+-dependent kinase activity showed a similar, if not more sensitive, trend. When the roots were fed with labeled 32pATP, water stress enhanced the labeling of proteins, which showed a maximum labeling at 40 min. Two inhibitors of protein kinases, Quercetin and H7, effectively diminished or completely blocked the ABA accumulation under the stress treatment. It is therefore suggest that protein phosphorylation is involved in the signaling of the water stress-induced ABA accumulation.

  14. The shear stress-induced transcription factor KLF2 affects dynamics and angiopoietin-2 content of Weibel-Palade bodies.

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    Ellen L van Agtmaal

    Full Text Available BACKGROUND: The shear-stress induced transcription factor KLF2 has been shown to induce an atheroprotective phenotype in endothelial cells (EC that are exposed to prolonged laminar shear. In this study we characterized the effect of the shear stress-induced transcription factor KLF2 on regulation and composition of Weibel-Palade bodies (WPBs using peripheral blood derived ECs. METHODOLOGY AND PRINCIPAL FINDINGS: Lentiviral expression of KLF2 resulted in a 4.5 fold increase in the number of WPBs per cell when compared to mock-transduced endothelial cells. Unexpectedly, the average length of WPBs was significantly reduced: in mock-transduced endothelial cells WPBs had an average length of 1.7 µm versus 1.3 µm in KLF2 expressing cells. Expression of KLF2 abolished the perinuclear clustering of WPBs observed following stimulation with cAMP-raising agonists such as epinephrine. Immunocytochemistry revealed that WPBs of KLF2 expressing ECs were positive for IL-6 and IL-8 (after their upregulation with IL-1β but lacked angiopoietin-2 (Ang2, a regular component of WPBs. Stimulus-induced secretion of Ang2 in KLF2 expressing ECs was greatly reduced and IL-8 secretion was significantly lower. CONCLUSIONS AND SIGNIFICANCE: These data suggest that KLF2 expression leads to a change in size and composition of the regulated secretory compartment of endothelial cells and alters its response to physiological stimuli.

  15. The gender difference of selective serotonin reuptake inhibitor, fluoxetine in adult rats with stress-induced gastric ulcer.

    Science.gov (United States)

    Abdel-Sater, Khaled A; Abdel-Daiem, Wafaa M; Sayyed Bakheet, Mohamad

    2012-08-01

    We investigated the gender difference of selective serotonin reuptake inhibitor, fluoxetine in adult rats with stress-induced gastric ulcer. The rats were randomly divided into six groups: Group I, control males and group II, control females; group III, acute cold restraint stressed males and group IV, acute cold restraint stressed females; group V, fluoxetine-treated stressed males and group VI, fluoxetine-treated stressed females. Acute cold restraint stress was established by fixing the four limbs of the rat and placing it in a refrigerator at 4°C for 3h. Fluoxetine was given intraperitoneal in a single dose of 10mg/kg/day. After 2 weeks, stomach and brain tissues were collected for the assay of gastric malonaldehyde (MDA), catalase, nitric oxide (NO) and cortical gamma aminobutyric acid (GABA). Stressed animals exhibited increased total acidity in association with decreased gastric secretion volume. Gastric MDA was increased while gastric catalase, NO, and cortical GABA were decreased in stressed male rats when compared to stressed females. However, fluoxetine administration attenuated these stress-induced changes especially in stressed male animals. Stressed male rats were more responsive to the antiulcer effect of fluoxetine more than stressed females. However, fluoxetine might be considered to be the first-choice drug in depressive patients with gastric ulcers in the future.

  16. Nicotine blocks stress-induced impairment of spatial memory and long-term potentiation of the hippocampal CA1 region.

    Science.gov (United States)

    Aleisa, Abdulaziz M; Alzoubi, Karem H; Gerges, Nashaat Z; Alkadhi, Karim A

    2006-08-01

    The effect of chronic nicotine treatment on chronic psychosocial stress-induced impairment of short-term memory and long-term potentiation (LTP) was determined. An "intruder" stress model was used to induce psychosocial stress for 4-6 wk, during which rats were injected with saline or nicotine (1 mg/kg s.c.) twice a day. The radial arm water maze memory task was used to test hippocampus-dependent spatial memory. Chronic psychosocial stress impaired short-term memory without affecting the learning phase or long-term memory. Concurrent chronic nicotine treatment prevented stress-induced short-term memory impairment. In normal rats chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anaesthetized rats showed severe reduction of LTP magnitude in stressed rats, which was normalized in nicotine-treated stressed rats. Nicotine had no effect on LTP in control animals. These results showed that chronic nicotine treatment improved hippocampus-dependent spatial memory and LTP only when impaired by stress.

  17. Effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression in male albino Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Tabassum Imrana

    2010-01-01

    Full Text Available Objective : The aim of this study was to study the ameliorative effects of Ocimum sanctum and Camellia sinensis on stress-induced anxiety and depression. Materials and Methods : The study was carried out using male albino rats (200 ± 50 g. The effect of O. sanctum and C. sinensis was evaluated for anxiety and depression using elevated plus maze (EPM test, open field test (OFT, forced swim test (FST, and tail suspension test (TST. Result : Restraint stress (3 h/day for six consecutive days induced a significant reduction in both the percentage number of entries and time spent in open arms in EPM, and these changes were reversed with post-treatment of aqueous extract of O. sanctum and C. sinensis (100 mg/kg for 6 days. Restraint stress-induced (a increased latency and (b decreased ambulation and rearing were also reversed by O. sanctum and C. sinensis in OFT. A significant increase in immobility period was observed in FST and TST after restraint stress. O. sanctum and C. sinensis significantly reduced the immobility times of rats in FST and TST. Conclusion : O. sanctum and C. sinensis possess anxiolytic and antidepressant activities.

  18. Effects of the α1-adrenoceptor agonist phenylephrine on SART stress-induced orthostatic hypotension in rats

    Directory of Open Access Journals (Sweden)

    Wada Tetsuyuki

    2010-10-01

    Full Text Available Abstract Background Specific alternation of rhythm in temperature (SART-stressed rats, an animal model of autonomic imbalance, exhibit low blood pressure and tachycardia during consciousness and under anesthesia. In addition, these rats easily develop orthostatic hypotension (OH as a response to postural manipulation. Hence, we studied the influence of the adrenalin α1-receptor agonist phenylephrine on stress-induced OH in SART-stressed rats and unstressed rats. Methods Male Wistar rats weighing 250-300 g were used. Rats were fixed in the supine position under urethane anesthesia. Blood pressure was directly measured from the left common carotid artery and ECG was recorded simultaneously. Results The maximum decrease in blood pressure and the area under the blood pressure-time curve were both large, while the %reflex was small in the SART-stressed rats compared with unstressed rats. In the SART-stressed rats, prolonged intravenous administration of phenylephrine reduced OH at a dose that barely affected unstressed rats. Conclusion The results suggested that sympathetic dysfunction is a factor underlying SART stress-induced OH.

  19. Effect of stress-induced grain growth during room temperature tensile deformation on ductility in nanocrystalline metals

    Indian Academy of Sciences (India)

    Weichang Xu; Pinqiang Dai; Xiaolei Wu

    2010-10-01

    In the present study defect-free nanocrystalline (nc) Ni–Co alloys with the Co content ranging from 2.4–59.3% (wt.%) were prepared by pulse electrodeposition. X-ray diffraction analysis shows that only a single face-centred cubic solid solution is formed for each alloy and that the grain size reduces monotonically with increasing Co content, which is consistent with transmission electron microscopy (TEM) observations. In the nc Ni–Co alloys, both the ultimate tensile strength and the elongation to failure increase as the Co content increases. The TEM observations reveal that stress-induced grain growth during tensile deformation is significantly suppressed for the nc Ni–Co alloys rich in Co in sharp contrast to those poor in Co. We believe that sufficient solutes could effectively pin grain boundaries making grain boundary motions (e.g. grain boundary migration and/or grain rotation) during deformation more difficult. Thus, stress-induced grain growth is greatly suppressed. At the same time, shear banding plasticity instability is correspondingly delayed leading to the enhanced ductility.

  20. The profile of lysosomal exoglycosidases in replicative and stress-induced senescence in early passage human fibroblasts

    Directory of Open Access Journals (Sweden)

    Małgorzata Knaś

    2012-07-01

    Full Text Available The aim of the present study was to assess the profiles of the exoglycosidases: N-acetyl-β-hexosoaminidase, β glucuronidase and β galactosidase, α mannosidase and α fucosidase in fibroblast culture undergoing replicative and stress-induced senescence. Half of the cell culture was grown in normal conditions, without the stressor, and the other half of the cell was treated with 0.15 mM tert-butylhydroperoxide. The activities of total N-acetyl-β-hexosoaminidase as well as β glucuronidase in the cell lysate were determined in duplicates using the method of Marciniak et al. The activities of β galactosidase, α mannosidase and α fucosidase in the cell lysate were determined in duplicates using the method of Chatteriee et al. with the modification by Zwierz et al. The activities of the exoglycosidases examined, with the exception of β glucuronidase, showed a significant increase between individual days of the experiment in both non-stressed and stressed fibroblast cell culture. On each day of the experiment, in the cell lysate of stressed fibroblasts, the activities of exoglycosidases were significantly higher compared to the non-stressed cells. There were very strong correlations between SA-β-GAL staining and b galactosidase activity on individual days of the experiment in both non-stressed and stressed fibroblast cell culture. Replicative and stress-induced senescence results in significant changes to the level of lysosomal exoglycosidases, and results in enhanced lysosomal degradative capacity.

  1. Effects of Red Wine Tannat on Oxidative Stress Induced by Glucose and Fructose in Erythrocytes in Vitro.

    Science.gov (United States)

    Pazzini, Camila Eliza Fernandes; Colpo, Ana Ceolin; Poetini, Márcia Rósula; Pires, Cauê Ferreira; de Camargo, Vanessa Brum; Mendez, Andreas Sebastian Loureiro; Azevedo, Miriane Lucas; Soares, Júlio César Mendes; Folmer, Vanderlei

    2015-01-01

    The literature indicates that red wine presents in its composition several substances that are beneficial to health. This study has investigated the antioxidant effects of Tannat red wine on oxidative stress induced by glucose and fructose in erythrocytes in vitro, with the purpose to determine some of its majoritarian phenolic compounds and its antioxidant capacity. Erythrocytes were incubated using different concentrations of glucose and fructose in the presence or absence of wine. From these erythrocytes were determined the production of thiobarbituric acid reactive species (TBARS), glucose consumption, and osmotic fragility. Moreover, quantification of total phenolic, gallic acid, caffeic acid, epicatechin, resveratrol, and DPPH scavenging activity in wine were also assessed. Red wine showed high levels of polyphenols analyzed, as well as high antioxidant potential. Erythrocytes incubated with glucose and fructose had an increase in lipid peroxidation and this was prevented by the addition of wine. The wine increased glucose uptake into erythrocytes and was able to decrease the osmotic fragility of erythrocytes incubated with fructose. Altogether, these results suggest that wine leads to a reduction of the oxidative stress induced by high concentrations of glucose and fructose.

  2. Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum stress-induced apoptosis in MCF-7 cells.

    Science.gov (United States)

    Delom, Frédéric; Fessart, Delphine; Chevet, Eric

    2007-02-01

    The endoplasmic reticulum (ER) is the cellular compartment where proteins enter the secretory pathway, undergo post-translational modifications and acquire a correct conformation. If these functions are chronically altered, specific ER stress signals are triggered to promote cell death through the intrinsic apoptotic pathway. Here, we show that tunicamycin causes significant alteration of calnexin sub-cellular distribution in MCF-7 cells. Interestingly, this correlates with the absence of both tunicamycin-induced calnexin phosphorylation as well as tunicamycin-induced cell death. Under these conditions, calnexin-associated Bap31, an ER integral membrane protein, is subjected to a caspase-8 cleavage pattern within a specific sub-compartment of the ER. These results suggest that MCF-7 resistance to ER stress-induced apoptosis is partially mediated by the expression level of calnexin which in turn controls its sub-cellular localization, and its association with Bap31. These data may delineate a resistance mechanism to the ER stress-induced intrinsic apoptotic pathway.

  3. Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

    Directory of Open Access Journals (Sweden)

    Yumie Ono

    2015-01-01

    Full Text Available The present study examined the effects of chewing on stress-induced long-term depression (LTD and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

  4. Blockade of glucocorticoid receptors with ORG 34116 does not normalize stress-induced symptoms in male tree shrews.

    Science.gov (United States)

    Van Kampen, Marja; De Kloet, E Ronald; Flügge, Gabriele; Fuchs, Eberhard

    2002-12-20

    Glucocorticoid receptors play an important role in the regulation of the activity of the hypothalamo-pituitary-adrenal axis, and are thought to be involved in the pathophysiology of depressive disorders. The present study investigated the effect of the specific glucocorticoid receptor antagonist ORG 34116 (a substituted 11,21 bisarylsteroid compound) in the tree shrew (Tupaia belangeri) chronic psychosocial stress model, an established animal model for depressive disorders. Animals were stressed for 10 days before treatment with ORG 34116 started (25 mg/kg p.o. for 28 days). Stress induced a decrease in body weight, which just failed significance, whereas ORG 34116 did not affect body weight in stress and control animals. ORG 34116 enhanced the stress-induced increase in the concentration of urinary-free cortisol, although no differences between the different experimental groups existed during the last week of treatment. In stressed animals, ORG 34116 did not affect marking behavior, but decreased locomotor activity. Post mortem analysis of 5-HT(1A) receptors revealed a decreased affinity of 3[H]-8-OH-DPAT (3[H]-8-hydroxy-2-[di-n-propylamino]tetralin) binding sites in the hippocampus of animals treated with the glucocorticoid receptor antagonist. In conclusion, under our experimental conditions, the glucocorticoid receptor antagonist ORG 34116 did not normalize the depressive-like symptoms in the psychosocial stress model of male tree shrews. This finding, however, does not exclude that specific central, neuroendocrine and behavioral features are affected by the compound.

  5. PEG-mediated osmotic stress induces premature differentiation of the root apical meristem and outgrowth of lateral roots in wheat.

    Science.gov (United States)

    Ji, Hongtao; Liu, Ling; Li, Kexue; Xie, Qingen; Wang, Zhijuan; Zhao, Xuhua; Li, Xia

    2014-09-01

    Water stress is one of the major environmental stresses causing growth retardation and yield loss of plants. In the past decades, osmotic adjustment, antioxidant protection, and stomatal movement have been extensively studied, but much less attention has been paid to the study of root system reprogramming to maximize water absorption and survival under water stress. Here, it is shown that polyethylene glycol (PEG)-simulated mild and moderate osmotic stress induced premature differentiation of the root apical meristem (RAM). It is demonstrated that RAM premature differentiation is a conserved adaptive mechanism that is widely adopted by various plants to cope with osmotic stress simulated by PEG 8000, and the occurrence of RAM premature differentiation is directly related to stress tolerance of plants. It is shown that the osmotic stress-induced premature differentiation caused growth cessation of primary roots allowing outgrowth of lateral roots. This work has uncovered a key mechanism for controlling the plastic development of the root system by which plants are capable of survival, growth, or reproduction under water stress.

  6. Pseudocataplexy and transient functional paralysis: a spectrum of psychogenic motor disorder.

    Science.gov (United States)

    Shankar, Rohit; Jalihal, Virupakshi; Walker, Matthew; Zeman, Adam

    2010-01-01

    The authors describe and discuss a syndrome of transient psychogenic weakness usually mistaken for cataplexy but which has a close association with a depressive mental state. Four patients were referred to the authors with suspected neurological causes of transient weakness, including cataplexy in three cases, for whom the eventual diagnosis was of a functional or psychogenic motor disorder, related in most cases to depression. This variety of transient functional weakness is related to conditions such as nonepileptic attack disorder, persistent functional weakness, catatonia, and depressive motor retardation. These cases point to the existence of a syndrome of transient motor weakness which resembles cataplexy and has features in common with other forms of mood induced psychogenic weakness such as psychomotor retardation and catatonia. Psychogenic "pseudocataplexy" is a diagnostic consideration in patients with atypical cataplexy, especially in the context of mood disturbance. Despite its close resemblance to cataplexy, pseudocataplexy has a different pathogenesis and requires a different approach to management.

  7. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

    Science.gov (United States)

    Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat

    2017-01-01

    Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets. PMID:28195122

  8. Malignant atypical cell in urine cytology: a diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Kakkar Nandita

    2006-01-01

    Full Text Available Abstract Aims The aim of this study was to find out the characteristic morphology of malignant atypical cells which were missed on routine cytology of urine. Materials and methods In this retrospective study, we examined detailed cytomorphology of 18 cases of atypical urinary cytology which were missed on routine examination and were further proved on histopathology as transitional cell carcinoma (TCC of bladder. The cytological features of these cases were compared with 10 cases of benign urine samples. Results There were 11 cases of high grade TCC and 7 cases of low grade TCC on histopathology of the atypical urine samples. Necrosis in the background and necrosed papillae were mostly seen in malignant atypical cells. The comet cells and cells with India ink nuclei (single cells with deep black structure-less nuclei were only observed in malignant atypical cells. The most consistent features in malignant atypical cells were: i high nuclear and cytoplasmic (N/C ratio ii nuclear pleomorphism iii nuclear margin irregularity iv hyperchromasia and v chromatin abnormalities Conclusion The present study emphasizes that nuclear features such as high N/C ratio, hyperchromasia and chromatin abnormalities are particularly useful for assessing the malignant atypical cells. Other cytological features such as comet cells and cells with India ink nuclei are also helpful for diagnosis but have limited value because they are less frequently seen.

  9. Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes.

    Science.gov (United States)

    Mojtabai, Ramin; Lavelle, Janet; Gibson, P Joseph; Bromet, Evelyn J

    2003-01-01

    This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.

  10. On Detecting Transients

    CERN Document Server

    Belanger, G

    2013-01-01

    Transient phenomena are interesting and potentially highly revealing of details about the processes under observation and study that could otherwise go unnoticed. It is therefore important to maximise the sensitivity of the method used to identify such events. In this article we present a general procedure based on the use of the likelihood function for identifying transients that is particularly suited for real-time applications because it requires no grouping or pre-processing of the data. The method is optimal in the sense that all the information that is available in the data is used in the statistical decision making process, and is suitable for a wide range of applications. We here consider those most common in astrophysics which involve searching for transient sources, events or features in images, time series, energy spectra and power spectra, and demonstrate the use of the method in the cases of a transient in a time series or in a power spectrum. We derive a fit statistic that is ideal for fitting a...

  11. Transient Heat Conduction

    DEFF Research Database (Denmark)

    Rode, Carsten

    1998-01-01

    Analytical theory of transient heat conduction.Fourier's law. General heat conducation equation. Thermal diffusivity. Biot and Fourier numbers. Lumped analysis and time constant. Semi-infinite body: fixed surface temperature, convective heat transfer at the surface, or constant surface heat flux...

  12. Transient lingual papillitis.

    Science.gov (United States)

    Kornerup, Ida M; Senye, Mireya; Peters, Edmund

    2016-01-01

    A case of recurrent, clinically innocuous, but painful papules involving the tongue dorsum of a 25-year-old man is presented. The lesions were interpreted to represent a transient lingual papillitis. This a poorly understood, but benign and self-limited condition involving the tongue fungiform papillae, which does not appear to be widely recognized.

  13. The LOFAR Transients Pipeline

    NARCIS (Netherlands)

    Swinbank, J.; Staley, T.; Molenaar, G.; Rol, E.; Rowlinson, A.; Scheers, L.H.A.; Spreeuw, H.; Bell, M.E.; Broderick, J.; Carbone, D.; Garsden, H.; Horst, A. van der; Law, C.J.; Wise, M.W.; Breton, R.P.; Cendes, Y.; Corbel, S.; Eisloeffel, J.; Falcke, H.; Fender, R.P.; Griessmeier, J.-M.; Hessels, J.W.T.; Stappers, B.W.; Stewart, A.; Wijers, R.A.M.J.; Wijnands, R.; Zarka, P.

    2015-01-01

    Current and future astronomical survey facilities provide a remarkably rich opportunity for transient astronomy, combining unprecedented fields of view with high sensitivity and the ability to access previously unexplored wavelength regimes. This is particularly true of LOFAR, a recently-commissione

  14. Absorptive reduction and width narrowing in A-type atoms confined between two dielectric walls

    Institute of Scientific and Technical Information of China (English)

    Li Yuan-Yuan; Hou Xun; Bai Jin-Tao; Yan Jun-Feng; Gan Chen-Li; Zhang Yan-Peng

    2008-01-01

    This paper investigates the absorptive reduction and the width narrowing of electromagnetically induced trans- parency (EIT) in a thin vapour film of A-type atoms confined between two dielectric walls whose thickness is comparable with the wavelength of the probe field. The absorptive lines of the weak probe field exhibit strong reductions and very narrow EIT dips, which mainly results from the velocity slow-down effects and transient behaviour of atoms in a con-fined system. It is also shown that the lines are modified by the strength of the coupling field and the ratio of L/λ, with L the film thickness and A the wavelength of the probe field. A simple robust recipe for EIT in a thin medium is achievable in experiment.

  15. Results of surgical treatment of atypical endometrial hyperplasia

    Directory of Open Access Journals (Sweden)

    O. A. Gornykh

    2014-01-01

    Full Text Available The results of surgical treatment in 132 patients with atypical endometrial hyperplasia have been studied. Post-operative diagnosis was: en- dometrial cancer – in 19 %, atypical hyperplasia – in 35 %, simple and complex hyperplasia – in 33 %, only atrophic endometrial changes – in 13 % of patients. The tumor was within the endometrium in 5 patients, the superficial invasion of the myometrium (1–2 mm were in 8 patients, invasion to half of the myometrium – in 9 patients, invasion of more than half of the myometrium – in 3 patients. The questions of tactics of treatment of atypical endometrial hyperplasia is under discussion.

  16. Intracranial Tuberculoma Presenting as Atypical Eclampsia: A Case Report

    Science.gov (United States)

    Murugesan, Sharmila; Pradeep, Sunitha; John, Lopamudra; Kolluru, Vasavi

    2016-01-01

    Occurrence of eclampsia before 20 weeks of pregnancy and after 48 hours of delivery in the absence of typical signs of hypertension and or proteinuria is termed as atypical eclampsia. Atypical or non-classic eclampsia will have some symptoms of eclampsia but without the usual proteinuria or hypertension. All patients with atypical onset should undergo neurological evaluation to rule out neurologic causes of seizures. Cerebral tuberculosis is a rare and serious form of disease secondary to haematogenous spread of Mycobacterium tuberculosis. Here we present a case of cerebral tuberculoma with seizures in late pregnancy mimicking eclampsia. PMID:27504359

  17. Systemic and local responses to repeated HL stress-induced retrograde signaling in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Matthew John Gordon

    2013-01-01

    Full Text Available Chloroplasts of leaves under high light stress initiate signals to the nuclei of both exposed and distal leaves in order to acclimate against the potential threat of oxidative damage: a process known as high light systemic acquired acclimation (HL SAA. This study explores the nature of HL SAA, synergistic interactions with other environmental stresses, and the impact of repeated HL stress on the acclimation response of exposed and distal leaves. This necessitated the development of novel experimental systems to investigate the initiation, perception and response to HL SAA. These systems were used to investigate the HL SAA response by monitoring the induction of mRNA in distal leaves not exposed to the HL stress. Acclimation to HL is induced within minutes and the response is proportionally dependent on the quality and quantity of light. HL SAA treatments in conjunction with variations in temperature and humidity reveal HL SAA is influenced by fluctuations in humidity. These treatments also result in changes in auxin accumulation and auxin-responsive genes. A key question in retrograde signaling is the extent to which transient changes in light intensity result in a memory of the event leading to acclimation responses. Repeated exposure to short term HL resulted in acclimation of the exposed tissue and that of emerging and young leaves (but not older leaves to HL and oxidative stress.

  18. Effects of glucocorticoid and glucocorticoid receptors on stress-induced neurogenesis suppression

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Jiapei Dai; Dan Liu; Shangxun Li; Yiwu Zhou

    2010-01-01

    Studies have shown that cerebral ischemia activates neurogenesis and that stress inhibits neurogenesis.However,the role of stress hormone levels on neurogenesis following cerebral ischemia remains poorly understood.The present study explored the possible regulatory mechanisms of adult neurogenesis under pathological conditions by examining changes and regulation of glucocorticoid receptors in adult rats subjected to transient unilateral middle cerebral artery suture occlusion.Corticosterone levels gradually increased following middle cerebral artery occlusion,and the number of glucocorticoid receptor-positive cells decreased.The number of5-bromodeoxyuridine-and nestin-positive cells significantly increased at 1 and 2 weeks after ischemia.A large number of doublecortin-positive cells migrated from the hippocampus to the cortex.At 3 weeks post-surgery,the number of 5-bromodeoxyuridine-and nestin-positive cells significantly reduced in the subventricular zone.Increased corticosterone levels decreased vascular endothelial cell proliferation and neurogenesis,and the number of glucocorticoid receptor-positive cells decreased.In the sham surgery group,vascular endothelial cell proliferation related to post-ischemic cerebral rehabilitation was not detected.Corticosterone levels increased,but the number and distribution of glucocorticoid receptor-positive cells were not changed.However,normal neuregenesis and migration of neural stem cells existed in the adult rat brain in the sham surgery group.Results suggested that glucocorticoid receptors influenced neurogenesis and were negatively regulated by glucocorticoid levels following focal cerebral ischemia and reperfusion.

  19. Targeted Deletion of MicroRNA-22 Promotes Stress-Induced Cardiac Dilation and Contractile Dysfunction

    Science.gov (United States)

    Gurha, Priyatansh; Abreu-Goodger, Cei; Wang, Tiannan; Ramirez, Maricela O.; Drumond, Ana L.; van Dongen, Stijn; Chen, Yuqing; Bartonicek, Nenad; Enright, Anton J.; Lee, Brendan; Kelm, Robert J.; Reddy, Anilkumar K.; Taffet, George E.; Bradley, Allan; Wehrens, Xander H.; Entman, Mark L.; Rodriguez, Antony

    2012-01-01

    Background Delineating the role of microRNAs (miRNAs) in the posttranscriptional gene regulation offers new insights into how the heart adapts to pathological stress. We developed a knockout of miR-22 in mice and investigated its function in the heart. Methods and Results Here, we show that miR-22–deficient mice are impaired in inotropic and lusitropic response to acute stress by dobutamine. Furthermore, the absence of miR-22 sensitized mice to cardiac decompensation and left ventricular dilation after long-term stimulation by pressure overload. Calcium transient analysis revealed reduced sarcoplasmic reticulum Ca2+ load in association with repressed sarcoplasmic reticulum Ca2+ ATPase activity in mutant myocytes. Genetic ablation of miR-22 also led to a decrease in cardiac expression levels for Serca2a and muscle-restricted genes encoding proteins in the vicinity of the cardiac Z disk/titin cytoskeleton. These phenotypes were attributed in part to inappropriate repression of serum response factor activity in stressed hearts. Global analysis revealed increased expression of the transcriptional/translational repressor purine-rich element binding protein B, a highly conserved miR-22 target implicated in the negative control of muscle expression. Conclusion These data indicate that miR-22 functions as an integrator of Ca2+ homeostasis and myofibrillar protein content during stress in the heart and shed light on the mechanisms that enhance propensity toward heart failure. PMID:22570371

  20. Systemic and Local Responses to Repeated HL Stress-Induced Retrograde Signaling in Arabidopsis.

    Science.gov (United States)

    Gordon, Matthew J; Carmody, Melanie; Albrecht, Verónica; Pogson, Barry

    2012-01-01

    CHLOROPLASTS OF LEAVES UNDER HIGH LIGHT STRESS INITIATE SIGNALS TO THE NUCLEI OF BOTH EXPOSED AND DISTAL LEAVES IN ORDER TO ACCLIMATE AGAINST THE POTENTIAL THREAT OF OXIDATIVE DAMAGE: a process known as high light systemic acquired acclimation (HL SAA). This study explores the nature of HL SAA, synergistic interactions with other environmental stresses, and the impact of repeated HL stress on the acclimation response of exposed and distal leaves. This necessitated the development of novel experimental systems to investigate the initiation, perception, and response to HL SAA. These systems were used to investigate the HL SAA response by monitoring the induction of mRNA in distal leaves not exposed to the HL stress. Acclimation to HL is induced within minutes and the response is proportionally dependent on the quality and quantity of light. HL SAA treatments in conjunction with variations in temperature and humidity reveal HL SAA is influenced by fluctuations in humidity. These treatments also result in changes in auxin accumulation and auxin-responsive genes. A key question in retrograde signaling is the extent to which transient changes in light intensity result in a "memory" of the event leading to acclimation responses. Repeated exposure to short term HL resulted in acclimation of the exposed tissue and that of emerging and young leaves (but not older leaves) to HL and oxidative stress.

  1. Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence

    Science.gov (United States)

    Crowe, Elizabeth P.; Tuzer, Ferit; Gregory, Brian D.; Donahue, Greg; Gosai, Sager J.; Cohen, Justin; Leung, Yuk Y.; Yetkin, Emre; Nativio, Raffaella; Wang, Li-San; Sell, Christian; Bonini, Nancy M.; Berger, Shelley L.; Johnson, F. Brad; Torres, Claudio

    2016-01-01

    Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders. PMID:27630559

  2. Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-induced Senescence

    Directory of Open Access Journals (Sweden)

    Elizabeth P. Crowe

    2016-08-01

    Full Text Available Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including GFAP and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.

  3. First case of atypical takotsubo cardiomyopathy in a bilateral lung-transplanted patient due to acute respiratory failure.

    Science.gov (United States)

    Ghadri, Jelena R; Bataisou, Roxana D; Diekmann, Johanna; Lüscher, Thomas F; Templin, Christian

    2015-10-01

    Takotsubo cardiomyopathy which is characterised by a transient left ventricular wall motion abnormality was first described in 1990. The disease is still not well known, and as such it is suggested that an emotional trigger is mandatory in this disease. We present the case of a 51-year old female patient seven years after bilateral lung transplantation, who developed acute respiratory distress syndrome and subsequently suffered from atypical takotsubo cardiomyopathy with transient severe reduction of ejection fraction and haemodynamic instability needing acute intensive care treatment. Acute respiratory failure has emerged as an important physical trigger factor in takotsubo cardiomyopathy. Little is known about the association of hypoxia and takotsubo cardiomyopathy which can elicit a life-threatening condition requiring acute intensive care. Therefore, experimental studies are needed to investigate the role of hypoxia in takotsubo cardiomyopathy.

  4. Oxidative stress induced by chlorine dioxide as an insecticidal factor to the Indian meal moth, Plodia interpunctella.

    Science.gov (United States)

    Kumar, Sunil; Park, Jiyeong; Kim, Eunseong; Na, Jahyun; Chun, Yong Shik; Kwon, Hyeok; Kim, Wook; Kim, Yonggyun

    2015-10-01

    A novel fumigant, chlorine dioxide (ClO2) is a commercial bleaching and disinfection agent. Recent study indicates its insecticidal activity. However, its mode of action to kill insects is yet to be understood. This study set up a hypothesis that an oxidative stress induced by ClO2 is a main factor to kill insects. The Indian meal moth, Plodia interpunctella, is a lepidopteran insect pest infesting various stored grains. Larvae of P. interpunctella were highly susceptible to ClO2 gas, which exhibited an acute toxicity. Physiological damages by ClO2 were observed in hemocytes. At high doses, the larvae of P. interpunctella suffered significant reduction of total hemocytes. At low doses, ClO2 impaired hemocyte behaviors. The cytotoxicity of ClO2 was further analyzed using two insect cell lines, where Sf9 cells were more susceptible to ClO2 than High Five cells. The cells treated with ClO2 produced reactive oxygen species (ROS). The produced ROS amounts increased with an increase of the treated ClO2 amount. However, the addition of an antioxidant, vitamin E, significantly attenuated the cytotoxicity of ClO2 in a dose-dependent manner. To support the oxidative stress induced by ClO2, two antioxidant genes (superoxide dismutase (SOD) and thioredoxin-peroxidase (Tpx)) were identified from P. interpunctella EST library using ortholog sequences of Bombyx mori. Both SOD and Tpx were expressed in larvae of P. interpunctella especially under oxidative stress induced by bacterial challenge. Exposure to ClO2 gas significantly induced the gene expression of both SOD and Tpx. RNA interference of SOD or Tpx using specific double stranded RNAs significantly enhanced the lethality of P. interpunctella to ClO2 gas treatment as well as to the bacterial challenge. These results suggest that ClO2 induces the production of insecticidal ROS, which results in a fatal oxidative stress in P. interpunctella.

  5. Translational profiling of stress-induced neuroplasticity in the CA3 pyramidal neurons of BDNF Val66Met mice.

    Science.gov (United States)

    Gray, J D; Rubin, T G; Kogan, J F; Marrocco, J; Weidmann, J; Lindkvist, S; Lee, F S; Schmidt, E F; McEwen, B S

    2016-12-13

    Genetic susceptibility and environmental factors (such as stress) can interact to affect the likelihood of developing a mood disorder. Stress-induced changes in the hippocampus have been implicated in mood disorders, and mutations in several genes have now been associated with increased risk, such as brain-derived neurotrophic factor (BDNF). The hippocampus has important anatomical subdivisions, and pyramidal neurons of the vulnerable CA3 region show significant remodeling after chronic stress, but the mechanisms underlying their unique plasticity remain unknown. This study characterizes stress-induced changes in the in vivo translating mRNA of this cell population using a CA3-specific enhanced green fluorescent protein (EGFP) reporter fused to the L10a large ribosomal subunit (EGFPL10a). RNA-sequencing after isolation of polysome-bound mRNAs allows for cell-type-specific, genome-wide characterization of translational changes after stress. The data demonstrate that acute and chronic stress produce unique translational profiles and that the stress history of the animal can alter future reactivity of CA3 neurons. CA3-specific EGFPL10a mice were then crossed to the stress-susceptible BDNF Val66Met mouse line to characterize how a known genetic susceptibility alters both baseline translational profiles and the reactivity of CA3 neurons to stress. Not only do Met allele carriers exhibit distinct levels of baseline translation in genes implicated in ion channel function and cytoskeletal regulation, but they also activate a stress response profile that is highly dissimilar from wild-type mice. Closer examination of genes implicated in the mechanisms of neuroplasticity, such as the NMDA and AMPA subunits and the BDNF pathway, reveal how wild-type mice upregulate many of these genes in response to stress, but Met allele carriers fail to do so. These profiles provide a roadmap of stress-induced changes in a genetically homogenous population of hippocampal neurons and

  6. Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608).

    Science.gov (United States)

    Spooren, Will P J M; Schoeffter, Philippe; Gasparini, Fabrizio; Kuhn, Rainer; Gentsch, Conrad

    2002-01-25

    The stress-induced hyperthermia test is a paradigm developed several years ago to model the expression of autonomic hyperactivity in anxiety. Whereas in the classical stress-induced hyperthermia, cohort removal was used, in a recently described modification of the stress-induced hyperthermia model singly housed mice rather than groups of mice were used. The modification of this model can be summarized as follows: rectal temperature is recorded in singly housed animals at two consecutive time-points (T1 and T2) which are interspaced by a defined time-interval (15 min). Since the value at the second temperature-recording exceeds the value of the initial measure it is the difference between these two core-temperatures which reflects stress-induced hyperthermia. In the present study, the stress-induced hyperthermia paradigm, in its modified design, was evaluated in OF1/IC mice. By comparing the effect of various compounds in both the modified as well as the classical (cohort removal) stress-induced hyperthermia paradigm, a very high correlation was found for the pharmacological sensitivity of the two paradigms. Furthermore, it was demonstrated that other anxiolytics, all known to be active in the classical stress-induced hyperthermia paradigm, such as the benzodiazepines chlordiazepoxide (0.3, 1, 3, 10 mg/kg, p.o.), diazepam (0.1, 0.3, 1, 3 mg/kg, p.o.), clobazam (5 or 10 mg/kg, p.o.) and oxazepam (5 or 10 mg/kg, p.o.) as well as the non-benzodiazepines buspirone (7.5 or 15 mg/kg, p.o.) and ethanol (15% or 30%, 10 ml/kg, p.o.), showed a marked reduction in stress-induced hyperthermia in the modified design. New candidate anxiolytics, i.e. the metabotropic glutamate (mGlu) receptor group 2 agonist LY314582 (1 or 10 mg/kg, p.o.; racemic mixture of LY354740 ((2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid), the metabotropic glutamate 5 receptor antagonist MPEP (1, 7.5, 15 or 30 mg/kg, p.o.; 2-methyl-6-(phenylethynyl)pyridine) and the neurokinin 1 (NK1

  7. Teaching strategies for atypical presentation of illness in older adults.

    Science.gov (United States)

    Gray-Miceli, Deanna; Aselage, Melissa; Mezey, Mathy

    2010-07-01

    Atypical presentation of illness is a phenomenon where "seeing is believing." Expert geriatric nurses and clinicians know all too well the early signs and symptoms of this phenomenon, which frequently masquerades bacterial infections, pain, acute myocardial infarction, heart failure, or other serious medical ailments in older adults. Students, however, as novices to clinical practice, require interactive learning approaches to reflect on the patient's illness presentations, help with developing the necessary skills to analyze and synthesize clinically relevant data, and witness resolution of an atypical presentation when found and treated. Use of a case study as an educational tool can facilitate critical thinking about a clinical problem, such as atypical presentation of illness, for students within a problem-based learning format. Furthermore, we highlight strategies for teaching students atypical presentation of illness with consideration of student learning preferences, which include visual, auditory, reading, and kinesthetic modes of learning.

  8. Atypical presentation of mucopolysaccharidosis type IVA.

    Science.gov (United States)

    Rush, Eric T

    2016-09-01

    A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease.

  9. Atypical clinical response patterns to ipilimumab.

    Science.gov (United States)

    Ledezma, Blanca; Binder, Sandra; Hamid, Omid

    2011-08-01

    Patients with advanced melanoma have few treatment options, and survival is poor. However, improved understanding of how the immune system interacts with cancer has led to the development of novel therapies. Ipilimumab is a monoclonal antibody that inhibits cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key negative regulator of host T-cell responses. This article presents cases of patients receiving ipilimumab in clinical trials along with a discussion of their significance and relevance to nursing practice. The patients showed different response patterns to ipilimumab and also had various typical immune-related adverse events (irAEs), which were managed successfully. The atypical response patterns produced by ipilimumab likely reflect its mechanism of action, which requires time for the immune system to mount an effective antitumor response. Meanwhile, lesions may appear to enlarge as a consequence of enhanced T-cell infiltration, although this may not necessarily be true disease progression. Patients receiving ipilimumab may respond very differently compared to how they might react to chemotherapy. Responses can take weeks or months to develop; therefore, clinicians should not terminate treatment prematurely, providing the patient's condition allows for continuation. Early recognition of irAEs combined with prompt management will ensure that events are more likely to resolve without serious consequences.

  10. Atypical Takotsubo syndrome during anagrelide therapy.

    Science.gov (United States)

    Proietti, Riccardo; Rognoni, Andrea; Ardizzone, Fabio; Maccio, Sergio; Santagostino, Alberto; Rognoni, Giorgio

    2009-07-01

    Anagrelide is a phosphodiesterase III inhibitor utilized in the treatment of essential thrombocythemia. Anagrelide can be responsible for positive inotropic and chonotropic activity of the cardiovascular system. Moreover, it can induce vasospam directly on the epicardial coronary arteries. In the literature, it is well reported that this inhibitor can determine serious cardiovascular side effects, including congestive heart failure, arrhythmia and acute coronary syndrome. We describe the case of a 75-year-old woman who developed a mid-ventricular Takotsubo syndrome while on anagrelide therapy. Takotsubo cardiomyopathy, also known as left ventricular ballooning syndrome, is characterized by a reversible ventricular contractile dysfunction with akinesis and expansion of apical segments and hyperkinesis of the basal segments. Recently, atypical cases with akinesia and dilation of mid-ventricular segment and hypercontraction of the apical segments, also called mid-ventricular and inverted Takotsubo syndrome, have been described. Even though the pathogenesis of Takotsubo syndrome is poorly understood, several mechanisms have been proposed, including catecholamine-induced myocardial stunning, and ischemia-mediated stunning due to multivessel epicardial or microvascular spasm. We think that in our case, the adverse response of anagrelide therapy was determined, by accumulated dosage of the drug, through an intensive inotropic stimulation and a sympathetic hyperactivation in a vulnerable myocardium. To our knowledge, this is one of the first reports of an association between anagrelide therapy and Takotsubo cardiomyopathy.

  11. Atypical focal nodular hyperplasia of the liver

    Institute of Scientific and Technical Information of China (English)

    Muhammad Rizwan Khan; Taimur Saleem; Tanveer Ul Haq; Kanwal Aftab

    2011-01-01

    BACKGROUND: Focal nodular hyperplasia, a benign hepatic tumor, is usually asymptomatic. However, rarely the entity can cause symptoms, mandating intervention. METHOD: We present a case of focal nodular hyperplasia of the liver, which caused a considerable diagnostic dilemma due to its atypical presentation. RESULTS: A 29-year-old woman presented with a 15-year history of a progressively increasing mass in the right upper quadrant which was associated with pain and emesis. Examination showed a firm, mobile mass palpable below the right subcostal margin. A computed tomography scan of the abdomen showed an exophytic mass arising from hepatic segments III and IVb. Trucut biopsy of the hepatic mass was equivocal. Angiography showed a vascular tumor that was supplied by a tortuous branch of the proper hepatic artery. Surgical intervention for removal of the mass was undertaken. Intra-operatively, two large discrete tumors were found and completely resected. Histopathological examination showed features consistent with focal nodular hyperplasia. CONCLUSION: This description of an unusual case of focal nodular hyperplasia of the liver highlights the point that the diagnosis of otherwise benign hepatic tumors may be difficult despite extensive work-up in some cases.

  12. Atypical moral judgment following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Angelica Muresan

    2012-07-01

    Full Text Available Previous research has shown an association between emotions, particularly social emotions, and moral judgments. Some studies suggested an association between blunted emotion and the utilitarian moral judgments observed in patients with prefrontal lesions. In order to investigate how prefrontal brain damage affects moral judgment, we asked a sample of 29 TBI patients (12 females and 17 males and 41 healthy participants (16 females and 25 males to judge 22 hypothetical dilemmas split into three different categories (non-moral, impersonal and personal moral. The TBI group presented a higher proportion of affirmative (utilitarian responses for personal moral dilemmas when compared to controls, suggesting an atypical pattern of utilitarian judgements. We also found a negative association between the performance on recognition of social emotions and the proportion of affirmative responses on personal moral dilemmas. These results suggested that the preference for utilitarian responses in this type of dilemmas is accompanied by difficulties in social emotion recognition. Overall, our findings suggest that deontological moral judgments are associated with normal social emotion processing and that frontal lobe plays an important role in both emotion and moral judgment.

  13. Nocturnal manifestations of atypical parkinsonian disorders.

    Science.gov (United States)

    Bhidayasiri, Roongroj; Jitkritsadakul, Onanong; Colosimo, Carlo

    2014-01-01

    Although nocturnal disturbances are increasingly recognized as an integral part of the continuum of daytime manifestations of Parkinson's disease (PD), there is still little evidence in the medical literature to support the occurrence of these complex phenomena in patients with atypical parkinsonian disorders (APDs). Based on the anatomical substrates in APDs, which are considered to be more extensive outside the basal ganglia than in PD, we might expect that patients with APDs encounter the whole range of nocturnal disturbances, including motor, sleep disorders, autonomic dysfunctions, and neuropsychiatric manifestations at a similar, or even greater, frequency than in PD. This article is a review of the current literature on the problems at nighttime of patients with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. MEDLINE, life science journals and online books were searched by querying appropriate key words. Reports were included if the studies were related to nocturnal manifestations in APDs. Forty articles fulfilled the selection criteria. Differences between these symptoms in APDs and PD are highlighted, given the evidence available about each manifestation. This analysis of nocturnal manifestations of APDs suggests the need for future studies to address these issues to improve the quality of life not only of patients with APDs but the caregivers who encounter the challenges of supporting these patients on a daily basis.

  14. Persistent consequences of atypical early number concepts

    Directory of Open Access Journals (Sweden)

    Michèle M. M. Mazzocco

    2013-09-01

    Full Text Available How does symbolic number knowledge performance help identify young children at risk for poor mathematics achievement outcomes? In research and practice, classification of mathematics learning disability (MLD, or dyscalculia is typically based on composite scores from broad measures of mathematics achievement. These scores do predict later math achievement levels, but do not specify the nature of math difficulties likely to emerge among students at greatest risk for long-term mathematics failure. Here we report that gaps in 2nd and 3rd graders’ number knowledge predict specific types of errors made on math assessments at Grade 8. Specifically, we show that early whole number misconceptions predict slower and less accurate performance, and atypical computational errors, on Grade 8 arithmetic tests. We demonstrate that basic number misconceptions can be detected by idiosyncratic responses to number knowledge items, and that when such misconceptions are evident during primary school they persist throughout the school age years, with variable manifestation throughout development. We conclude that including specific qualitative assessments of symbolic number knowledge in primary school may provide greater specificity of the types of difficulties likely to emerge among students at risk for poor mathematics outcomes.

  15. Atypical mitochondrial inheritance patterns in eukaryotes.

    Science.gov (United States)

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  16. DENGUE WITH ATYPICAL MANIFESTATIONS AND WHO CLASSIFICATION

    Directory of Open Access Journals (Sweden)

    Jayant Mahadeorao

    2015-09-01

    Full Text Available Dengue fever and dengue haemorrhagic fever are important arboviral diseases. Dengue virus belongs to family Flaviviridae , has four serotypes that spread by the bite of infected Aedes mosquitoes . Dengue epidemics can have a significant economic and health t oll. Worldwide, an estimated 3.6 billion people are at risk of infection with about 50 - 100 million new cases each year Illness produced by any of the four dengue virus serotypes varies from mild asymptomatic illness to severe fatal dengue haemorrhagic fe ver/dengue shock syndrome (DHF/DSS. During the early febrile stage clinicians cannot predict which patients will progress to severe disease. Atypical manifestations were reported are associated with high risk of mortality. The existing WHO dengue classific ation scheme and case definitions have some drawbacks. A global strategy to reduce the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently un der development could also make an important contribution to dengue control in the future

  17. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    Science.gov (United States)

    Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

    2006-12-01

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  18. Atypical presentations among Medicare beneficiaries with unstable angina pectoris.

    Science.gov (United States)

    Canto, John G; Fincher, Contessa; Kiefe, Catarina I; Allison, Jeroan J; Li, Qing; Funkhouser, Ellen; Centor, Robert M; Selker, Harry P; Weissman, Norman W

    2002-08-01

    Chest pain is a hallmark symptom in patients with unstable angina pectoris (UAP). However, little is known regarding the prevalence of an atypical presentation among these patients and its relation to subsequent care. We examined the medical records of 4,167 randomly sampled Medicare patients hospitalized with unstable angina at 22 Alabama hospitals between 1993 and 1999. We defined typical presentation as (1) chest pain located substernally in the left or right chest, or (2) chest pain characterized as squeezing, tightness, aching, crushing, arm discomfort, dullness, fullness, heaviness, pressure, or pain aggravated by exercise or relieved with rest or nitroglycerin. Atypical presentation was defined as confirmed UAP without typical presentation. Among patients with confirmed UAP, 51.7% had atypical presentations. The most frequent symptoms associated with atypical presentation were dyspnea (69.4%), nausea (37.7%), diaphoresis (25.2%), syncope (10.6%), or pain in the arms (11.5%), epigastrium (8.1%), shoulder (7.4%), or neck (5.9%). Independent predictors of atypical presentation for patients with UAP were older age (odds ratio 1.09, 95% confidence interval 1.01 to 1.17/decade), history of dementia (odds ratio 1.49, 95% confidence interval 1.10 to 2.03), and absence of prior myocardial infarction, hypercholesterolemia, or family history of heart disease. Patients with atypical presentation received aspirin, heparin, and beta-blocker therapy less aggressively, but there was no difference in mortality. Thus, over half of Medicare patients with confirmed UAP had "atypical" presentations. National educational initiatives may need to redefine the classic presentation of UAP to include atypical presentations to ensure appropriate quality of care.

  19. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    LENUS (Irish Health Repository)

    Ryan, Aisling M

    2012-02-03

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  20. An Atypical Case of Pityriasis Rosea Gigantea after Influenza Vaccination

    Directory of Open Access Journals (Sweden)

    Dimitrios Papakostas

    2014-04-01

    Full Text Available Pityriasis rosea is a common erythematosquamous eruption, typically presenting along the cleavage lines of the skin. A wide spectrum of atypical manifestations may challenge even the most experienced physician. Here we report a rare case of a suberythrodermic pityriasis rosea with gigantic plaques after an influenza vaccination, and we discuss the possible triggers of atypical manifestations of such a common dermatological disease in the setting of an altered immunity.

  1. The Rapid Transient Surveyor

    Science.gov (United States)

    Baranec, Christoph; Tonry, John; Wright, Shelley; Tully, R. Brent; Lu, Jessica R.; Takamiya, Marianne Y.; Hunter, Lisa

    2016-01-01

    The next decade of astronomy will be dominated by large area surveys (see the detailed discussion in the Astro-2010 Decadal survey and NRC's recent OIR System Report). Ground-based optical transient surveys, e.g., LSST, ZTF and ATLAS and space-based exoplanet, supernova, and lensing surveys such as TESS and WFIRST will join the Gaia all-sky astrometric survey in producing a flood of data that will enable leaps in our understanding of the universe. There is a critical need for further characterization of these discoveries through high angular resolution images, deeper images, spectra, or observations at different cadences or periods than the main surveys. Such follow-up characterization must be well matched to the particular surveys, and requires sufficient additional observing resources and time to cover the extensive number of targets.We describe plans for the Rapid Transient Surveyor (RTS), a permanently mounted, rapid-response, high-cadence facility for follow-up characterization of transient objects on the U. of Hawai'i 2.2-m telescope on Maunakea. RTS will comprise an improved robotic laser adaptive optics system, based on the prototype Robo-AO system (formerly at the Palomar 1.5-m and now at the Kitt Peak 2.2-m telescope), with simultaneous visible and near-infrared imagers as well as a near-infrared integral field spectrograph (R~100, λ = 850 - 1830 nm, 0.15″ spaxels, 8.7″×6.0″ FoV). RTS will achieve an acuity of ~0.07″ in visible wavelengths and automated detection and characterization of astrophysical transients during a sustained observing campaign will yield the necessary statistics to precisely map dark matter in the local universe.

  2. Coherent Transient Systems Evaluation

    Science.gov (United States)

    1993-06-17

    manuscript is submitted for publication with the understanding that the United States Government is authorized to reproduce and distribute reprints...for governmental purposes. 1.0 Introduction The continuous optical correlator presented here is based on the phenomena of coherent transients, also...Gating the Continuous Processor Programming the continuous processor is accomplished by illuminati , n, the material with ,.’ modulated light pulses: a

  3. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs.

    Science.gov (United States)

    Trollor, Julian N; Chen, Xiaohua; Sachdev, Perminder S

    2009-01-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially severe idiosyncratic adverse reaction usually seen in the context of treatment with antipsychotic drugs. Although NMS is historically associated with the classic or 'typical' antipsychotic drugs, it is also a potential adverse effect of atypical antipsychotic drugs. The widespread use of atypical antipsychotic drugs highlights the need to examine the data relating to the symptomatology, diagnosis, classification and management of NMS with these newer agents. We used MEDLINE and EMBASE to identify NMS case reports and systematic reviews published to June 2008 related to the atypical antipsychotic drugs clozapine, olanzapine, risperidone, paliperidone, aripiprazole, ziprasidone, amisulpride and quetiapine. Case reports and reviews were systematically examined. Our review suggests that, in general, NMS associated with atypical antipsychotic drugs manifests in a typical manner. One notable exception is clozapine-induced NMS, which appears less likely to manifest with extrapyramidal features, including rigidity and tremor. The available literature highlights the divergence of opinion relating to the core diagnostic features of NMS and its conceptualization as a categorical versus dimensional disorder. Both these issues have relevance for the identification of atypical or milder forms of NMS, which are sometimes seen with atypical antipsychotic drugs.

  4. Mitochondrial DNA sequence analysis of patients with 'atypical psychosis'.

    Science.gov (United States)

    Kazuno, An-A; Munakata, Kae; Mori, Kanako; Tanaka, Masashi; Nanko, Shinichiro; Kunugi, Hiroshi; Umekage, Tadashi; Tochigi, Mamoru; Kohda, Kazuhisa; Sasaki, Tsukasa; Akiyama, Tsuyoshi; Washizuka, Shinsuke; Kato, Nobumasa; Kato, Tadafumi

    2005-08-01

    Although classical psychopathological studies have shown the presence of an independent diagnostic category, 'atypical psychosis', most psychotic patients are currently classified into two major diagnostic categories, schizophrenia and bipolar disorder, by the Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria. 'Atypical psychosis' is characterized by acute confusion without systematic delusion, emotional instability, and psychomotor excitement or stupor. Such clinical features resemble those seen in organic mental syndrome, and differential diagnosis is often difficult. Because patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) sometimes show organic mental disorder, 'atypical psychosis' may be caused by mutations of mitochondrial DNA (mtDNA) in some patients. In the present study whole mtDNA was sequenced for seven patients with various psychotic disorders, who could be categorized as 'atypical psychosis'. None of them had known mtDNA mutations pathogenic for mitochondrial encephalopathy. Two of seven patients belonged to a subhaplogroup F1b1a with low frequency. These results did not support the hypothesis that clinical presentation of some patients with 'atypical psychosis' is a reflection of subclinical mitochondrial encephalopathy. However, the subhaplogroup F1b1a may be a good target for association study of 'atypical psychosis'.

  5. Atypical sonographic patterns of fibroadenoma of the breast : pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kook, Shin Ho; Kim, Myung Sook; Pae, Won Kil [Kangbuk Samsung Hospital, Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-03-01

    To correlate the atypical sonographic patterns of fibroadenoma of the breast with the pathologic findings. Among 203 surgically proven 43 which were sonographically atypical fibroadenomas, were retrospectively reviewed. The diagnostic criteria for atypical variety, as seen on sonography, were an ill-defined margin, microlobulated or irregular shape, heterogeneous internal echo-pattern, posterior shadowing, microcalcification, and clefts. The atypical sonographic patterns of these 43 fibroadenomas were analysed and compared with the pathologic findings. Among 43 lesions, ill-defined margins or irregular shapes were seen in 15 cases, heterogeneous internal echo-patterns in 27, posterior attenuation in nine, and clefts in seven. Thirty-seven (86%) of the 43 were predominantly ductal or had a mixed ductal and stromal component. Eleven (73.3%) of fifteen ill-defined margin or irregular shaped lesions were caused by interdigitation of surrounding normal breast parenchyma and mass. Twenty two (81.5%) of 27 heterogeneous internal echo-pat-terns were related to dilated ducts, phyllodes features, collagen bundles, adenosis, microcalcification, or fat vacuoles. Eight (88.9%) of nine posterior attenuations were caused by collagen bundles, microcalcification, ductal proliferation or dilatation. All seven cases showing clefts revealed phyllodes features and dilated ducts. Most atypical fibroadenomas had a predominantly ductal or mixed component. Ill-defined margin or irregular shape was mainly due to interdigitation of normal surrounding parenchyma. Variable histologic features were related to the heterogeneous internal echo-pattern, posterior shadowing, and the clefts revealed by atypical sonographic findings.

  6. Usefulness of latent left ventricular dysfunction assessed by Bowditch Treppe to predict stress-induced pulmonary hypertension in minimally symptomatic severe mitral regurgitation secondary to mitral valve prolapse.

    Science.gov (United States)

    Agricola, Eustachio; Bombardini, Tonino; Oppizzi, Michele; Margonato, Alberto; Pisani, Matteo; Melisurgo, Giulio; Picano, Eugenio

    2005-02-01

    We assessed whether the presence of latent myocardial dysfunction, evaluated by echocardiographic derived force-frequency relationship (FFR) during exercise, predicts the appearance of stress-induced pulmonary hypertension in minimally symptomatic patients with severe mitral regurgitation (MR). Two groups of patients were identified: group I with normal (40 mm Hg) peak stress systemic pulmonary artery pressure. Group I had normal and upsloping FFR and group II had abnormal flat or biphasic FFR. Therefore, in patients with severe MR and apparently normal left ventricular function, the stress-induced pulmonary hypertension seems to be related to the presence of latent left ventricular dysfunction.

  7. STRESS-INDUCED MARTENSITIC TRANSFORMATION AND A NEW 7-LAYER MARTENSITE PHASE IN THE 63.1Ni-Al ALLOY

    OpenAIRE

    Martynov, V.; Enami, K.; Khandros, L.; Tkachenko, A.; Nenno, S.

    1982-01-01

    It is well known that the nickel-rich Ni-Al β phase alloy exhibits the martensitic transformation and the crystal structures of the as-quenched martensites are Llo(α'2) and 2H, (1,2). However, there is no systematic investigation on the deformation behaviour and stress-induced martensitic transformation in this alloy system, other than the deformation behaviour of the α'2 martensite (3). Recently we investigated the deformation behaviour and the stress-induced martensitic transformation of th...

  8. Uniaxial compressive stress induced nuclear quadrupole interaction at the {sup 111}Cd nucleus in n-doped silicon

    Energy Technology Data Exchange (ETDEWEB)

    Tessema, Genene [Faculty of Science, Department of Physics, Addis Ababa University, P.O. Box 1176, Addis Ababa (Ethiopia) and Helmholtz-Institut fuer Strahlen und Kernphysik, Nussalle 14-16, 53115 Bonn (Germany)]. E-mail: genene@gmx.net

    2006-03-01

    Stress induced quadrupole interaction at the probe nucleus ({sup 111}Cd) in silicon has been studied using the perturbed {gamma}-{gamma} angular correlation (PAC) method. The extra nuclear field, at the sites of the nuclei, is produced via the disturbances of the surrounding charges by the action of a uniaxial compressive stress on the samples. However, the probes situated at various lattice locations in the sample showed different responses for the same value of stress. The various lattice environments are mainly caused by the involvement of either tellurium or antimony donor atoms in the samples. As a result, the donor free substitutional probe atoms experience a finite nuclear quadrupole interaction due to the broken symmetry of the charge distribution upon uniaxial compression; those probe atoms, which form pairs with donors, exhibit a strong electric-field gradient (EFG) that appears to be pressure independent.

  9. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

    Science.gov (United States)

    Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

    2014-02-01

    Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized.

  10. The conduction mechanism of stress induced leakage current through ultra-thin gate oxide under constant voltage stresses

    Institute of Scientific and Technical Information of China (English)

    Wang Yan-Gang; Xu Ming-Zhen; Tan Chang-Hua; Zhang Zhang J.F; Duan Xiao-Rong

    2005-01-01

    The conduction mechanism of stress induced leakage current (SILC) through 2nm gate oxide is studied over a gate voltage range between 1.7V and stress voltage under constant voltage stress (CVS). The simulation results show that the SILC is formed by trap-assisted tunnelling (TAT) process which is dominated by oxide traps induced by high field stresses. Their energy levels obtained by this work are approximately 1.9eV from the oxide conduction band, and the traps are believed to be the oxygen-related donor-like defects induced by high field stresses. The dependence of the trap density on stress time and oxide electric field is also investigated.

  11. Dose-dependent Cytotoxicity and Oxidative Stress Induced by "Naked" Fe3O4 Nanoparticles in Human Hepatocyte

    Institute of Scientific and Technical Information of China (English)

    LIN Xin-li; ZHAO Shu-hua; ZHANG Long; HU Gui-qin; SUN Zhi-wei; YANG Wen-sheng

    2012-01-01

    The dose-dependent cytotoxicity effect on human hepatocyte(HL-7702 cells) induced by "naked" Fe3O4 nanoparticles was assessed through cell viabilities and lactate dehydrogenase(LDH) activities.Three important oxidative indexes of the cells by glutathione peroxidase(GSH-Px),superoxide dismutase(SOD) and malondialdehyde(MDA) were determined.The good correlation of the cell viabilities with their GSH-Px,SOD and MDA levels indicated that the cytotoxicity is related to activation of oxidative stress induced by Fe3O4 nanoparticles.The oxidative stress also leads to corresponding DNA damage in a similar dose-dependent manner,followed by the changes of cell cycle and cell apoptosis.Such work provides important experimental data for the safety evaluation of superparamagnetic Fe3O4 nanoparticles.

  12. Effect of Si on the reversibility of stress-induced martensite in Fe-Mn-Si shape memory alloys

    Energy Technology Data Exchange (ETDEWEB)

    Stanford, N. [Centre for Material and Fibre Innovation, Deakin University, Geelong, Victoria 3217 (Australia); Dunne, D.P., E-mail: druce_dunne@uow.edu.au [Faculty of Engineering, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2010-12-15

    Fe-Mn-Si is a well-characterized ternary shape memory alloy. Research on this alloy has consistently shown that the addition of 5-6 wt.% Si is desirable to enhance the reversibility of stress-induced martensite vis-a-vis shape memory. This paper examines the effect of Si on the morphology and the crystallography of the martensite in the Fe-Mn-Si system. It is concluded that the addition of Si increases the c/a ratio of the martensite, reduces the transformation volume change and decreases the atomic spacing difference between the parallel close-packed directions in the austenite-martensite interface (habit) plane. It is proposed that, in addition to austenite strengthening, Si enhances reversibility by reducing the volume change and the interfacial atomic mismatch between the martensite and the austenite. Although shape memory is improved, transformation reversibility remains limited by the necessary misfit dislocations that accommodate the atomic spacing differences in the interface.

  13. ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells.

    Science.gov (United States)

    Arduino, Daniela M; Esteves, A Raquel; Domingues, A Filipa; Pereira, Claudia M F; Cardoso, Sandra M; Oliveira, Catarina R

    2009-11-30

    Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

  14. Electrical-stress-induced transport and surface potential characterizations of metal/ TiO 2/metal planar junctions

    Science.gov (United States)

    Kim, Haeri; Kim, Dong-Wook

    2011-03-01

    Electric-field-induced resistive switching (RS) phenomena in metal oxides have attracted considerable research interest due to their potential use in nonvolatile memory device applications. Intensive investigations have revealed that coupled electron ion dynamics play a key role the RS mechanism. Metal/single crystal junction can be an ideal model system to study how the ionic drift and diffusion can affect the resistance. We investigated transport and local electrical properties of Pt/ Ti O2 single crystal/Ti planar junctions with micron- sized gaps between the electrodes. Scanning Kelvin probe microscopy (SKPM) showed that negative (positive) electrical stress to the Pt electrodes significantly reduced (hardly affected) the Pt/ Ti O2 contact resistance. The SKPM results also revealed that the electrical stress caused alteration of the local work function of Ti O2 . The comparative investigations of the transport and SKPM results suggested that the electrical stress induced redistribution of ions, resulting in the change of the junction resistance.

  15. Measurement of lattice rotations and internal stresses in over one hundred individual grains during a stress-induced martensitic transformation

    Directory of Open Access Journals (Sweden)

    Hachi Younes El

    2015-01-01

    Full Text Available To better understand the properties of polycrystals at a microscopic scale during cyclic mechanical loading we have measured the relationship between grain orientations, their positions inside the sample and their internal stresses. In this work, in-situ 3DXRD technique was performed on over hundred grains during the stress-induced martensitic transformation in a Cu-Al-Be shape memory alloy. Information about the position, orientation, and stress field was obtained for each austenitic grain. These results have been used to develop a procedure that allows automatic processing for a large number of grains, matching them during loading and leads to a quantitative stress field. A strong heterogeneity of stress state between the grains at the surface and in the volume is evident.

  16. Direct evidence for stress-induced transformation between coexisting multiple martensites in a Ni-Mn-Ga multifunctional alloy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, L.; Cong, D. Y.; Wang, Z. L.; Nie, Z. H.; Dong, Y. H.; Zhang, Y.; Ren, Yang; Wang, Y. D.

    2015-07-08

    The structural response of coexisting multiple martensites to stress field in a Ni-Mn-Ga multifunctional alloy was investigated by the in situ high-energy x-ray diffraction technique. Stress-induced transformation between coexisting multiple martensites was observed at 110 K, at which five-layered modulated (5M), seven-layered modulated (7M) and non-modulated (NM) martensites coexist. We found that a tiny stress of as low as 0.5 MPa could trigger the transformation from 5M and 7M martensites to NM martensite and this transformation is partly reversible. Besides the transformation between coexisting multiple martensites, rearrangement of martensite variants also occurs during loading, at least at high stress levels. The present study is instructive for designing advanced multifunctional alloys with easy actuation.

  17. Direct evidence for stress-induced transformation between coexisting multiple martensites in a Ni-Mn-Ga multifunctional alloy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, L.; Cong, D. Y.; Wang, Z. L.; Nie, Z. H.; Dong, Y. H.; Zhang, Y.; Ren, Yang; Wang, Y. D.

    2015-06-03

    The structural response of coexisting multiple martensites to stress field in a Ni-Mn-Ga multifunctional alloy was investigated by the in situ high-energy x-ray diffraction technique. Stress-induced transformation between coexisting multiple martensites was observed at 110 K, at which five-layered modulated (5M), seven-layered modulated (7M) and non-modulated (NM) martensites coexist. We found that a tiny stress of as low as 0.5 MPa could trigger the transformation from 5M and 7M martensites to NM martensite and this transformation is partly reversible. Besides the transformation between coexisting multiple martensites, rearrangement of martensite variants also occurs during loading, at least at high stress levels. The present study is instructive for designing advanced multifunctional alloys with easy actuation.

  18. Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo.

    Science.gov (United States)

    Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

    2016-03-01

    Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo.

  19. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.

    Science.gov (United States)

    Xie, Fang; Zhao, Yun; Ma, Jing; Gong, Jing-Bo; Wang, Shi-Da; Zhang, Liang; Gao, Xiu-Jie; Qian, Ling-Jia

    2016-09-01

    Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.

  20. Heat-Stress and Light-Stress Induce Different Cellular Pathologies in the Symbiotic Dinoflagellate during Coral Bleaching

    Science.gov (United States)

    Downs, C. A.; McDougall, Kathleen E.; Woodley, Cheryl M.; Fauth, John E.; Richmond, Robert H.; Kushmaro, Ariel; Gibb, Stuart W.; Loya, Yossi; Ostrander, Gary K.; Kramarsky-Winter, Esti

    2013-01-01

    Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m−2 s−1 PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching. PMID:24324575

  1. Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

    Science.gov (United States)

    Downs, C A; McDougall, Kathleen E; Woodley, Cheryl M; Fauth, John E; Richmond, Robert H; Kushmaro, Ariel; Gibb, Stuart W; Loya, Yossi; Ostrander, Gary K; Kramarsky-Winter, Esti

    2013-01-01

    Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

  2. Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

    Directory of Open Access Journals (Sweden)

    C A Downs

    Full Text Available Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex, usually by expulsion or xenophagy (symbiophagy of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2 s(-1 PAR at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

  3. BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

    Science.gov (United States)

    Nowacka, Marta; Obuchowicz, Ewa

    2013-01-01

    Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

  4. Activation of cannabinoid CB1 receptors in the ventral hippocampus improved stress-induced amnesia in rat.

    Science.gov (United States)

    Mohammadmirzaei, Negin; Rezayof, Ameneh; Ghasemzadeh, Zahra

    2016-09-01

    The ventral hippocampus (VH) has a high distribution of cannabinoid CB1 receptors which are important in modulating stress responses. Stress exposure activates the hypothalamic-pituitary-adrenal axis (HPA) which can impact hippocampal formation to change hippocampus-based memories. The purpose of the present study was to determine the possible role of the VH cannabinoid CB1 receptors in stress-induced amnesia using a step-through passive avoidance procedure in male Wistar rats. In order to induce acute stress, the animals were placed on an elevated platform for different time periods (10, 20 and 30min). Our results indicated that post-training 20 and 30min exposure to stress, but not 10min, induced amnesia. Post-training microinjection of a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 2.5-7.5ng/rat) into the VH (intra-VH) induced amnesia. Interestingly, post-training intra-VH microinjection of the same doses of ACPA improved stress-induced amnesia. On the other hand, post-training intra-VH microinjection of a selective CB1 receptor antagonist, AM-251 (20-50ng/rat) with exposure to an ineffective stress (10min) potentiated the effect of stress on memory consolidation and induced amnesia. It should be noted that post-training intra-VH microinjection of the same doses of AM-251 alone had no effect on memory consolidation. Our results revealed that post-training intra-VH microinjection of AM-251, prior to ACPA microinjection, inhibited the reversal effect of ACPA on acute elevated platform stress. Taken together, it can be concluded that exposure to post-training inescapable stress impaired memory consolidation. The impairing effects of stress on memory retrieval may be mediated by the VH cannabinoid CB1 receptors.

  5. Persistent ER stress induces the spliced leader RNA silencing pathway (SLS, leading to programmed cell death in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Hanoch Goldshmidt

    2010-01-01

    Full Text Available Trypanosomes are parasites that cycle between the insect host (procyclic form and mammalian host (bloodstream form. These parasites lack conventional transcription regulation, including factors that induce the unfolded protein response (UPR. However, they possess a stress response mechanism, the spliced leader RNA silencing (SLS pathway. SLS elicits shut-off of spliced leader RNA (SL RNA transcription by perturbing the binding of the transcription factor tSNAP42 to its cognate promoter, thus eliminating trans-splicing of all mRNAs. Induction of endoplasmic reticulum (ER stress in procyclic trypanosomes elicits changes in the transcriptome similar to those induced by conventional UPR found in other eukaryotes. The mechanism of up-regulation under ER stress is dependent on differential stabilization of mRNAs. The transcriptome changes are accompanied by ER dilation and elevation in the ER chaperone, BiP. Prolonged ER stress induces SLS pathway. RNAi silencing of SEC63, a factor that participates in protein translocation across the ER membrane, or SEC61, the translocation channel, also induces SLS. Silencing of these genes or prolonged ER stress led to programmed cell death (PCD, evident by exposure of phosphatidyl serine, DNA laddering, increase in reactive oxygen species (ROS production, increase in cytoplasmic Ca(2+, and decrease in mitochondrial membrane potential, as well as typical morphological changes observed by transmission electron microscopy (TEM. ER stress response is also induced in the bloodstream form and if the stress persists it leads to SLS. We propose that prolonged ER stress induces SLS, which serves as a unique death pathway, replacing the conventional caspase-mediated PCD observed in higher eukaryotes.

  6. Inhibition of immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion by injected leptin in rats.

    Science.gov (United States)

    Haque, Zeba; Akbar, Nazia; Yasmin, Farzana; Haleem, Muhammad A; Haleem, Darakhshan J

    2013-05-01

    Leptin, originally identified as an anti-obesity hormone, also has an important role in the regulation of mood and emotion. The present study was designed to monitor effects of injected leptin on immobilization stress-induced anorexia, behavioral deficits, and plasma corticosterone secretion in rats. Exposure to 2 h immobilization stress decreased food intake and body weight in saline-injected animals. Animals exposed to open field, elevated plus maze, and light-dark transition tests the day following immobilization exhibited anxiety-like behavior. Leptin injected at doses of 0.1 and 0.5 mg/kg also decreased food intake and body weight in unstressed animals and elicited anxiolytic effects at dose of 0.5 mg/kg, monitored on the following day. Immobilization-induced decreases in food intake, body weight, as well as stress-induced behavioral deficits in the open field, elevated plus maze, and light-dark transition test were reversed by exogenous leptin in a dose-dependent (0.1-0.5 mg/kg) manner. Acute exposure to 2 h immobilization produced a fourfold rise in plasma levels of corticosterone. Animals injected with leptin at a dose of 0.1 mg/kg, but not at dose of 0.5 mg/kg, exhibited a marginal increase in plasma corticosterone. Immobilization-induced increases of plasma corticosterone were reversed by leptin injected at doses of 0.1 or 0.5 mg/kg. The data suggest that exogenous leptin can reduce stress perception, resulting in an inhibition of stress effects on the activity of hypothalamic-pituitary-adrenal axis and behavior. The reported pharmacological effects of leptin represent an innovative approach for the treatment of stress-related disorders.

  7. Poor sleep quality potentiates stress-induced cytokine reactivity in postmenopausal women with high visceral abdominal adiposity.

    Science.gov (United States)

    Prather, Aric A; Puterman, Eli; Epel, Elissa S; Dhabhar, Firdaus S

    2014-01-01

    Sleep disturbance is a key behavioral risk factor for chronic medical conditions observed at high rates among overweight and obese individuals. Systemic inflammation, including that induced by stress, may serve as a common biological mechanism linking sleep, adiposity, and disease risk. To investigate these relationships, 48 postmenopausal women (mean age=61.8) completed a standardized laboratory stress task during which time blood was collected at baseline and 30, 50 and 90+ min after stressor onset to assess circulating levels of interleukin (IL)-6, IL-10, and IL-6/IL-10 ratio. Self-reported global sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) while adiposity was estimated by body mass index. Sagittal diameter was obtained in clinic to estimate visceral abdominal adiposity. Multi-level growth curve models revealed that poorer self-reported sleep quality was associated with greater stress-induced increases in IL-6/IL-10 ratio. In terms of adiposity, higher sagittal diameter, but not BMI, was associated with greater IL-6 reactivity (p's<0.05). Further, associations between sleep quality and cytokine reactivity varied as a function of sagittal diameter. Among poor sleepers (1 SD above mean of PSQI score), stress-induced increases in IL-6 and IL-6/IL-10 ratio were significantly steeper in those with high visceral adiposity (1 SD above the mean of sagittal diameter) compared to those with low visceral adiposity (1 SD below the mean of sagittal diameter). In sum, poorer sleep quality and greater visceral adiposity, separately and especially in combination, are associated with greater stress-related increases in systemic inflammation. This research may help elucidate the complex link between sleep, obesity and inflammatory disease risk.

  8. Isolation and analysis of water stress induced genes in maize seedlings by subtractive PCR and cDNA macroarray.

    Science.gov (United States)

    Zheng, Jun; Zhao, Jinfeng; Tao, Yazhong; Wang, Jianhua; Liu, Yunjun; Fu, Junjie; Jin, Ying; Gao, Peng; Zhang, Jinpeng; Bai, Yunfeng; Wang, Guoying

    2004-08-01

    In order to identify genes induced during the water stress response in maize (Zea mays) seedlings, suppression subtractive hybridization (SSH) was performed using mixed cDNAs prepared from maize seedlings treated with 20% PEG as testers and cDNAs from unstressed maize seedlings as drivers. A forward subtractive cDNA library was constructed, from which 960 recombinant colonies were picked and amplified. Through differential screening of the subtractive cDNA library, 533 clones were identified as water stress induced. After sequencing, 190 unique expressed sequence tags (ESTs) were obtained by clustering and blast analysis, which included transcripts that had previously been reported as responsive to stress as well as some functionally unknown transcripts. The ESTs with significant protein homology were sorted into 13 functional categories. A cDNA marcoarray containing the 190 unique ESTs was used to analyze their expression profiles in maize seedling during both PEG treatment and natural drought. The results indicated that 67 ESTs in leaves and 113 ESTs in roots were significantly up-regulated by PEG-stress. 123 ESTs were found to be up-regulated for at least one time-course point in either maize leaves or roots. Correspondingly, 163 ESTs were significantly up-regulated by drought stress. Results from the hierarchical cluster analysis suggest that the leaves and roots of maize seedlings had different expression profiles after PEG treatment and that there was a lot of overlap between PEG- and drought-stress induced up-regulated transcripts. A set of transcripts has been identified, which have significantly increased expression and probably involved in water stress signaling pathway based on data analysis.

  9. Auxin Biosynthesis, Accumulation, Action and Transport are Involved in Stress-Induced Microspore Embryogenesis Initiation and Progression in Brassica napus.

    Science.gov (United States)

    Rodríguez-Sanz, Héctor; Solís, María-Teresa; López, María-Fernanda; Gómez-Cadenas, Aurelio; Risueño, María C; Testillano, Pilar S

    2015-07-01

    Isolated microspores are reprogrammed in vitro by stress, becoming totipotent cells and producing embryos and plants via a process known as microspore embryogenesis. Despite the abundance of data on auxin involvement in plant development and embryogenesis, no data are available regarding the dynamics of auxin concentration, cellular localization and the expression of biosynthesis genes during microspore embryogenesis. This work involved the analysis of auxin concentration and cellular accumulation; expression of TAA1 and NIT2 encoding enzymes of two auxin biosynthetic pathways; expression of the PIN1-like efflux carrier; and the effects of inhibition of auxin transport and action by N-1-naphthylphthalamic acid (NPA) and α-(p-chlorophenoxy) isobutyric acid (PCIB) during Brassica napus microspore embryogenesis. The results indicated de novo auxin synthesis after stress-induced microspore reprogramming and embryogenesis initiation, accompanying the first cell divisions. The progressive increase of auxin concentration during progression of embryogenesis correlated with the expression patterns of TAA1 and NIT2 genes of auxin biosynthetic pathways. Auxin was evenly distributed in early embryos, whereas in heart/torpedo embryos auxin was accumulated in apical and basal embryo regions. Auxin efflux carrier PIN1-like gene expression was induced in early multicellular embryos and increased at the globular/torpedo embryo stages. Inhibition of polar auxin transport (PAT) and action, by NPA and PCIB, impaired embryo development, indicating that PAT and auxin action are required for microspore embryo progression. NPA also modified auxin embryo accumulation patterns. These findings indicate that endogenous auxin biosynthesis, action and polar transport are required in stress-induced microspore reprogramming, embryogenesis initiation and progression.

  10. Toll-like receptor 4 protects against stress-induced ulcers via regulation of glucocorticoid production in mice.

    Science.gov (United States)

    Wang, Liang; Luo, Pengfei; Zhang, Fang; Zhang, Yuelu; Wang, Xingtong; Chang, Fei; Zhang, Yuechan; Tang, Hongtai; Xia, Zhaofan

    2017-01-01

    Stress-induced gastric ulcer is an important life-threatening condition, while the molecular basis of its development is incompletely understood. Toll-like receptor 4 (TLR4), an innate immune pattern recognition receptor, can induce pro-inflammatory transcription, aggravating a stress ulcer. The present study found that TLR4 played a protective role in a mouse model of water immersion (23 °C) restraint stress. Wild-type (WT) and TLR4(-/-) male mice were respectively divided into five groups (5 per group), and exposed to the stressor for 0, 0.5, 1, 2, or 4 hours. Gastric ulcer index, determined post mortem, increased with time in both types of mice but was greater in TLR4(-/-) mice. Furthermore, increased serum cortisol and corticosterone concentrations were observed in WT mice only, and such increases were detected only in WT mice 4 h after lipopolysaccharide (LPS) treatment (2 mg/kg, intraperitoneal injection). Moreover, the administration of cortisol alleviated the gastric injury in TLR4(-/-) mice. Western blotting showed expression in the adrenal of P450scc (CYP11A1), the first rate-limiting enzyme in the synthesis of steroids, was increased 4 h after water immersion restraint stress or LPS treatment in WT mice, but was conversely decreased in TLR4(-/-) mice after either stressor. Furthermore, in adrenal glands of TLR4(-/-) mice, structural distortion of mitochondria (which contain CYP11A1) was found with electron microscopy, and lack of lipid-storing droplets was found using light microscopy on adrenal cryosections stained with Oil red O. These data indicate that TLR4 plays a protective role in stress-induced gastric ulcer that is exerted via impacting synthesis of glucocorticoid in the adrenal gland.

  11. FBXO6-Mediated Ubiquitination and Degradation of Ero1L Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2016-11-01

    Full Text Available Background/Aims: FBXO6 is the substrate recognition component of a Skp1-Cullin1-F-box protein (SCF ubiquitin E3 ligase complex, recognizing the chitobiose in unfolded N-glycoprotein to target glycoproteins for polyubiquitination and degradation. Although how FBXO6 recognizes glycoprotein has been fully investigated, the ubiquitination substrates of FBXO6 remain largely unknown. Previously, we have systematically identified the glycoproteins that interact with FBXO6 in an N-glycan dependent manner by LC/MS spectrum and confirmed the interaction between FBXO6 and glycosylated Ero1L, a protein disulfide oxidase in endoplasmic reticulum (ER. Methods: The relationship between endogenous Ero1L and exogenous Flag-FBXO6 were determined by Western blot. In vivo ubiquitination assay was used to detect the direct effect of FBXO6 in the regulation of Ero1L. Both CCK8 and FACS assays were used to determine the apoptosis ratio of cells after treatments. Results: Ero1L is a ubiquitination substrate of FBXO6. FBXO6 mediates the degradation of Ero1L through a ubiquitylation-dependent pathway. Overexpression of FBXO6 increased the polyubiquitination and decreased the stability of Ero1L, whereas inhibition of FBXO6 prolonged the half-life of Ero1L. Functionally, we show that FBXO6 inhibits ER stress-induced apoptosis by modulating the protein level of Ero1L. Conclusion: Collectively, our results demonstrate FBXO6 as a functional E3 ubiquitin ligase for Ero1L that plays a critical role in inhibiting ER stress-induced apoptosis.

  12. N-acetyl-L-cysteine prevents stress-induced desmin aggregation in cellular models of desminopathy.

    Directory of Open Access Journals (Sweden)

    Bertrand-David Segard

    Full Text Available Mutations within the human desmin gene are responsible for a subcategory of myofibrillar myopathies called desminopathies. However, a single inherited mutation can produce different phenotypes within a family, suggesting that environmental factors influence disease states. Although several mouse models have been used to investigate organ-specific desminopathies, a more general mechanistic perspective is required to advance our knowledge toward patient treatment. To improve our understanding of disease pathology, we have developed cellular models to observe desmin behaviour in early stages of disease pathology, e.g., upon formation of cytoplasmic desmin aggregates, within an isogenic background. We cloned the wildtype and three mutant desmin cDNAs using a Tet-On Advanced® expression system in C2C12 cells. Mutations were selected based on positioning within desmin and capacity to form aggregates in transient experiments, as follows: DesS46Y (head domain; low aggregation, DesD399Y (central rod domain; high aggregation, and DesS460I (tail domain; moderate aggregation. Introduction of these proteins into a C2C12 background permitted us to compare between desmin variants as well as to determine the role of external stress on aggregation. Three different types of stress, likely encountered during muscle activity, were introduced to the cell models-thermal (heat shock, redox-associated (H2O2 and cadmium chloride, and mechanical (stretching stresses-after which aggregation was measured. Cells containing variant DesD399Y were more sensitive to stress, leading to marked cytoplasmic perinuclear aggregations. We then evaluated the capacity of biochemical compounds to prevent this aggregation, applying dexamethasone (an inducer of heat shock proteins, fisetin or N-acetyl-L-cysteine (antioxidants before stress induction. Interestingly, N-acetyl-L-cysteine pre-treatment prevented DesD399Y aggregation during most stress. N-acetyl-L-cysteine has recently been

  13. First Japanese case of atypical progeroid syndrome/atypical Werner syndrome with heterozygous LMNA mutation.

    Science.gov (United States)

    Motegi, Sei-ichiro; Yokoyama, Yoko; Uchiyama, Akihiko; Ogino, Sachiko; Takeuchi, Yuko; Yamada, Kazuya; Hattori, Tomoyasu; Hashizume, Hiroaki; Ishikawa, Yuichi; Goto, Makoto; Ishikawa, Osamu

    2014-12-01

    Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a progeroid syndrome involving heterozygous mutations in the LMNA gene encoding the nuclear protein lamin A/C. We report the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). A 53-year-old Japanese man had a history of recurrent severe cardiovascular diseases as well as brain infarction and hemorrhages. Although our APS/AWS patient had overlapping features with Werner syndrome (WS), such as high-pitched voice, scleroderma, lipoatrophy and atherosclerosis, several cardinal features of WS, including short stature, premature graying/alopecia, cataract, bird-like face, flat feet, hyperkeratosis on the soles and diabetes mellitus, were absent. In immunofluorescence staining and electron microscopic analyses of the patient's cultured fibroblasts, abnormal nuclear morphology, an increase in small aggregation of heterochromatin and a decrease in interchromatin granules in nuclei of fibroblasts were observed, suggesting that abnormal nuclear morphology and chromatin disorganization may be associated with the pathogenesis of APS/AWS.

  14. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2007-08-01

    Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics

  15. Atypical/Nor98 scrapie infectivity in sheep peripheral tissues.

    Directory of Open Access Journals (Sweden)

    Olivier Andréoletti

    Full Text Available Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrP(Sc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed.

  16. Childhood Learning Disabilities and Atypical Dementia: A Retrospective Chart Review.

    Directory of Open Access Journals (Sweden)

    Alon Seifan

    Full Text Available To further our understanding of the association between self-reported childhood learning disabilities (LDs and atypical dementia phenotypes (Atypical Dementia, including logopenic primary progressive aphasia (L-PPA, Posterior Cortical Atrophy (PCA, and Dysexecutive-type Alzheimer's Disease (AD.This retrospective case series analysis of 678 comprehensive neuropsychological assessments compared rates of self-reported LD between dementia patients diagnosed with Typical AD and those diagnosed with Atypical Dementia. 105 cases with neuroimaging or CSF data available and at least one neurology follow-up were identified as having been diagnosed by the neuropsychologist with any form of neurodegenerative dementia. These cases were subject to a consensus diagnostic process among three dementia experts using validated clinical criteria for AD and PPA. LD was considered Probable if two or more statements consistent with prior LD were documented within the Social & Developmental History of the initial neuropsychological evaluation.85 subjects (Typical AD n=68, Atypical AD n=17 were included in the final analysis. In logistic regression models adjusted for age, gender, handedness, education and symptom duration, patients with Probable LD, compared to patients without Probable LD, were significantly more likely to be diagnosed with Atypical Dementia vs. Typical AD (OR 13.1, 95% CI 1.3-128.4. All three of the L-PPA cases reporting a childhood LD endorsed childhood difficulty with language. By contrast, both PCA cases reporting Probable childhood LD endorsed difficulty with attention and/or math.In people who develop dementia, childhood LD may predispose to atypical phenotypes. Future studies are required to confirm whether atypical neurodevelopment predisposes to regional-specific neuropathology in AD and other dementias.

  17. Thermal transient anemometer

    Science.gov (United States)

    Bailey, James L.; Vresk, Josip

    1989-01-01

    A thermal transient anemometer having a thermocouple probe which is utilized to measure the change in temperature over a period of time to provide a measure of fluid flow velocity. The thermocouple probe is located in the fluid flow path and pulsed to heat or cool the probe. The cooling of the heated probe or the heating of the cooled probe from the fluid flow over a period of time is measured to determine the fluid flow velocity. The probe is desired to be locally heated near the tip to increase the efficiency of devices incorporating the probe.

  18. DSN Transient Observatory

    Science.gov (United States)

    Kuiper, T. B. H.; Monroe, R. M.; White, L. A.; Garcia Miro, C.; Levin, S. M.; Majid, W. A.; Soriano, M.

    2016-11-01

    The Deep Space Network (DSN) Transient Observatory (DTO) is a signal processing facility that can monitor up to four DSN downlink bands for astronomically interesting signals. The monitoring is done commensally with reception of deep space mission telemetry. The initial signal processing is done with two CASPERa ROACH1 boards, each handling one or two baseband signals. Each ROACH1 has a 10 GBe interface with a GPU-equipped Debian Linux workstation for additional processing. The initial science programs include monitoring Mars for electrostatic discharges, radio spectral lines, searches for fast radio bursts and pulsars and SETI. The facility will be available to the scientific community through a peer review process.

  19. Lysosomal membrane permeabilization is involved in oxidative stress-induced apoptotic cell death in LAMP2-deficient iPSCs-derived cerebral cortical neurons

    Directory of Open Access Journals (Sweden)

    Cheuk-Yiu Law

    2016-03-01

    Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury.

  20. Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model.

    Science.gov (United States)

    Kim, So Mi; Hwang, In Koo; Yoo, Dae Young; Eum, Won Sik; Kim, Dae Won; Shin, Min Jea; Ahn, Eun Hee; Jo, Hyo Sang; Ryu, Eun Ji; Yong, Ji In; Cho, Sung-Woo; Kwon, Oh-Shin; Lee, Keun Wook; Cho, Yoon Shin; Han, Kyu Hyung; Park, Jinseu; Choi, Soo Young

    2015-06-01

    Oxidative stress-induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat-Atox1 and examined the roles of Tat-Atox1 in oxidative stress-induced hippocampal HT-22 cell death and an ischaemic injury animal model. Tat-Atox1 effectively transduced into HT-22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)-induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat-Atox1 regulated cellular survival signalling such as p53, Bad/Bcl-2, Akt and mitogen-activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat-Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat-Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat-Atox1 protects against oxidative stress-induced HT-22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat-Atox1 has potential as a therapeutic agent for the treatment of oxidative stress-induced ischaemic damage.

  1. A novel transcription factor, ERD15 (Early Responsive to Dehydration 15), connects endoplasmic reticulum stress with an osmotic stress-induced cell death signal.

    Science.gov (United States)

    Alves, Murilo S; Reis, Pedro A B; Dadalto, Silvana P; Faria, Jerusa A Q A; Fontes, Elizabeth P B; Fietto, Luciano G

    2011-06-03

    As in all other eukaryotic organisms, endoplasmic reticulum (ER) stress triggers the evolutionarily conserved unfolded protein response in soybean, but it also communicates with other adaptive signaling responses, such as osmotic stress-induced and ER stress-induced programmed cell death. These two signaling pathways converge at the level of gene transcription to activate an integrated cascade that is mediated by N-rich proteins (NRPs). Here, we describe a novel transcription factor, GmERD15 (Glycine max Early Responsive to Dehydration 15), which is induced by ER stress and osmotic stress to activate the expression of NRP genes. GmERD15 was isolated because of its capacity to stably associate with the NRP-B promoter in yeast. It specifically binds to a 187-bp fragment of the NRP-B promoter in vitro and activates the transcription of a reporter gene in yeast. Furthermore, GmERD15 was found in both the cytoplasm and the nucleus, and a ChIP assay revealed that it binds to the NRP-B promoter in vivo. Expression of GmERD15 in soybean protoplasts activated the NRP-B promoter and induced expression of the NRP-B gene. Collectively, these results support the interpretation that GmERD15 functions as an upstream component of stress-induced NRP-B-mediated signaling to connect stress in the ER to an osmotic stress-induced cell death signal.

  2. Stress-Induced Leakage Current in p+ Poly MOS Capacitors with Poly-Si and Poly-Si0.7Ge0.3 Gate Material

    NARCIS (Netherlands)

    Houtsma, V.E.; Holleman, J.; Salm, C.; Widdershoven, F.P.; Woerlee, P.H.

    1999-01-01

    The gate bias polarity dependence of stress-induced leakage current (SILC) of PMOS capacitors with a p+ polycrystalline silicon (poly-Si) and polycrystalline Silicon-Germanium (poly-Si0.7 Ge0.3) gate on 5.6-nm thick gate oxides has been investigated. It is shown that the SILC characteristics are hig

  3. Hyperosmotic stress induces Rho/Rho kinase/LIM kinase-mediated cofilin phosphorylation in tubular cells: key role in the osmotically triggered F-actin response

    DEFF Research Database (Denmark)

    Thirone, Ana C P; Speight, Pam; Zulys, Matthew;

    2009-01-01

    we investigated whether hyperosmolarity regulates cofilin, a key actin-severing protein, whose activity is inhibited by phosphorylation. Since the small GTPases Rho and Rac are sensitive to cell volume changes, and can regulate cofilin phosphorylation, we also asked if they might link osmostress...... in the hyperosmotic stress-induced F-actin increase. Key words: cytoskeleton, hypertonicity, cell volume, small GTPases....

  4. Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

    Science.gov (United States)

    Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of...

  5. Stress-induced martensitic transformation in (Ni47Ti44)100-xNbx shape memory alloys with wide hysteresis

    Institute of Scientific and Technical Information of China (English)

    HE Xiang-ming; ZHAO Long-zhi; DUO Shu-wang; ZHANG Rong-fa; RONG Li-jian

    2006-01-01

    The effect of deformation via stress-induced martensitic transformation on the reverse transformation behavior of the (Ni47Ti44)100-xNbx (x=3,9,15,20,30,mole fraction,%) shape memory alloys was investigated in detail by differential scanning calorimetry (DSC) after performing cryogenic tensile tests at a temperature of Ms+30 ℃. The results show that Nb-content has obvious effect on the process of stress-induced martensitic transformation. It is also observed that the stress-induced martensite is stabilized relative to the thermally-induced martensite (TIM) formed on cooling,and Nb-content in Ni-Ti-Nb alloy has great influence on the reverse transformation start temperature and transformation temperature hysteresis of stress-induced martensite(SIM). The mechanism of wide transformation temperature hysteresis was fully explained based on the microscopic structure and the distribution of the elastic strain energy of (Ni47Ti44)100-xNbx alloys.

  6. Antidepressant imipramine diminishes stress-induced inflammation in the periphery and central nervous system and related anxiety- and depressive- like behaviors.

    Science.gov (United States)

    Ramirez, Karol; Sheridan, John F

    2016-10-01

    In order to relieve anxiety and depression accompanying stress, physicians resort to tricyclic antidepressants, such as imipramine. We had previously shown that imipramine reversed stress-induced social avoidance behavior, and down-regulated microglial activation 24days after stress cessation. To further characterize the effects of imipramine on stress induced neuroimmune dysregulation and associated changes in behavior, the aims of this study were to determine if imipramine 1) ameliorated stress-induced inflammation in the periphery and central nervous system, and 2) prevented stress related anxiety- and depressive-like behaviors. C57BL/6 mice were treated with imipramine (15mg/kg) in their drinking water, and exposed to repeated social defeat (RSD). Imipramine attenuated stress-induced corticosterone and IL-6 responses in plasma. Imipramine decreased the percentage of monocytes and granulocytes in the bone marrow and circulation. However, imipramine did not prevent splenomegaly, stress-related increased percentage of granulocytes in this organ, and the production of pro-inflammatory cytokines in the spleen, following RSD. Moreover, imipramine abrogated the accumulation of macrophages in the brain in mice exposed to RSD. Imipramine blocked neuroinflammatory signaling and prevented stress-related anxiety- and depressive-like behaviors. These data support the notion that pharmacomodulation of the monoaminergic system, besides exerting anxiolytic and antidepressant effects, may have therapeutic effects as a neuroimmunomodulator during stress.

  7. Translational and posttranslational regulation of XIAP by eIF2α and ATF4 promotes ER stress-induced cell death during the unfolded protein response.

    Science.gov (United States)

    Hiramatsu, Nobuhiko; Messah, Carissa; Han, Jaeseok; LaVail, Matthew M; Kaufman, Randal J; Lin, Jonathan H

    2014-05-01

    Endoplasmic reticulum (ER) protein misfolding activates the unfolded protein response (UPR) to help cells cope with ER stress. If ER homeostasis is not restored, UPR promotes cell death. The mechanisms of UPR-mediated cell death are poorly understood. The PKR-like endoplasmic reticulum kinase (PERK) arm of the UPR is implicated in ER stress-induced cell death, in part through up-regulation of proapoptotic CCAAT/enhancer binding protein homologous protein (CHOP). Chop((-)/(-)) cells are partially resistant to ER stress-induced cell death, and CHOP overexpression alone does not induce cell death. These findings suggest that additional mechanisms regulate cell death downstream of PERK. Here we find dramatic suppression of antiapoptosis XIAP proteins in response to chronic ER stress. We find that PERK down-regulates XIAP synthesis through eIF2α and promotes XIAP degradation through ATF4. Of interest, PERK's down-regulation of XIAP occurs independently of CHOP activity. Loss of XIAP leads to increased cell death, whereas XIAP overexpression significantly enhances resistance to ER stress-induced cell death, even in the absence of CHOP. Our findings define a novel signaling circuit between PERK and XIAP that operates in parallel with PERK to CHOP induction to influence cell survival during ER stress. We propose a "two-hit" model of ER stress-induced cell death involving concomitant CHOP up-regulation and XIAP down-regulation both induced by PERK.

  8. Characterizing Nanoscale Transient Communication.

    Science.gov (United States)

    Chen, Yifan; Anwar, Putri Santi; Huang, Limin; Asvial, Muhamad

    2016-04-01

    We consider the novel paradigm of nanoscale transient communication (NTC), where certain components of the small-scale communication link are physically transient. As such, the transmitter and the receiver may change their properties over a prescribed lifespan due to their time-varying structures. The NTC systems may find important applications in the biomedical, environmental, and military fields, where system degradability allows for benign integration into life and environment. In this paper, we analyze the NTC systems from the channel-modeling and capacity-analysis perspectives and focus on the stochastically meaningful slow transience scenario, where the coherence time of degeneration Td is much longer than the coding delay Tc. We first develop novel and parsimonious models to characterize the NTC channels, where three types of physical layers are considered: electromagnetism-based terahertz (THz) communication, diffusion-based molecular communication (DMC), and nanobots-assisted touchable communication (TouchCom). We then revisit the classical performance measure of ϵ-outage channel capacity and take a fresh look at its formulations in the NTC context. Next, we present the notion of capacity degeneration profile (CDP), which describes the reduction of channel capacity with respect to the degeneration time. Finally, we provide numerical examples to demonstrate the features of CDP. To the best of our knowledge, the current work represents a first attempt to systematically evaluate the quality of nanoscale communication systems deteriorating with time.

  9. Transient Black Hole Binaries

    CERN Document Server

    Belloni, T M

    2016-01-01

    The last two decades have seen a great improvement in our understand- ing of the complex phenomenology observed in transient black-hole binary systems, especially thanks to the activity of the Rossi X-Ray Timing Explorer satellite, com- plemented by observations from many other X-ray observatories and ground-based radio, optical and infrared facilities. Accretion alone cannot describe accurately the intricate behavior associated with black-hole transients and it is now clear that the role played by different kinds of (often massive) outflows seen at different phases of the outburst evolution of these systems is as fundamental as the one played by the accretion process itself. The spectral-timing states originally identified in the X-rays and fundamentally based on the observed effect of accretion, have acquired new importance as they now allow to describe within a coherent picture the phenomenology observed at other wave- length, where the effects of ejection processes are most evident. With a particular focu...

  10. Ichthyosiform mycosis fungoides with alopecia and atypical membranous nephropathy

    Directory of Open Access Journals (Sweden)

    Qiang Zhou

    2011-01-01

    Full Text Available We describe here a rare case of variant of mycosis fungoides (MF: ichthyosiform MF with alopecia and atypical membranous nephropathy. The diagnosis was made based on the following findings: generalized ichthyosis-like eruption, alopecia, enlarged superficial lymph nodes, proteinuria, and hematuria, the histological features of the skin biopsy from both ichthyotic and alopecic lesions with immunohistochemical staining, and the renal biopsy examination with immunofluorescence. The histological examination of ichthyotic and alopecic lesions displayed a predominant infiltration of atypical lymphocytes in the upper dermis with the characteristics of epidermotropism and folliculotropism. Immunohistochemical studies demonstrated that most infiltrated atypical lymphocytes were CD3, CD4, and CD45RO positive, whereas negative for CD5, CD7, CD20, CD30, and CD56. A renal biopsy examination revealed atypical membranous nephropathy with deposition of immunoglobulin G (IgG, IgM, IgA, C1q, and C3. In this case atypical membranous nephropathy was involved, which is very uncommon and has never been presented in the literature to date. Although ichthyosiform MF usually features a relatively favorable course, diffuse alopecia and the renal involvement in this case might indicate aggressive disease and poor prognosis.

  11. Atypical periprosthetic acetabular fracture in long-term alendronate therapy

    Science.gov (United States)

    Marongiu, Giuseppe; Capone, Antonio

    2016-01-01

    Summary Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing. PMID:28228784

  12. Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ.

    Science.gov (United States)

    Clauser, Paola; Marino, Maria A; Baltzer, Pascal A T; Bazzocchi, Massimo; Zuiani, Chiara

    2016-01-01

    Atypical hyperplasia and lobular carcinoma in situ are rare proliferative breast lesions, growing inside ducts and terminal ducto-lobular units. They represent a marker of increased risk for breast cancer and a non-obligate precursor of malignancy. Evidence available on diagnosis and management is scarce. They are frequently found incidentally associated with other lesions, but can be visible through mammography, ultrasound or magnetic resonance. Due to the risk of underestimation, surgical excision is often performed. The analysis of imaging and histopathological characteristics could help identifying low-risk cases, for which surgery is not necessary. Chemopreventive agents can be used for risk reduction. Careful imaging follow up is mandatory; the role of breast MRI as screening modality is under discussion.

  13. Orbitofrontal cortex action of 5-hydroxytryptamine and its receptor in an acute forced swimming stress-induced depression model

    Institute of Scientific and Technical Information of China (English)

    Huipeng Li; Fengli An; Shucheng An

    2009-01-01

    BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion.5-hydroxytryptamine (5-HT) has been shown to be involved in human depression.OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR)in stress-induced depression.DESIGN, TIME AND SEI-rlNG: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008.MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) andspiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tlanjin Haoyang Biological Manufacture.METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone+5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5μL of 5-HT (12.5μg/pL),PCPA (20μg/μL), spiperone (1.3 μg/μL)+5-HT (12.5μg/μL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone+5-HT, and model groups, respectively.The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC,cingulate cortex, and piriform cortex.RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress),immobility time in forced swimming test increased dramatically (P<0.01), locomotion and rearing inopen field test declined (P<0.05 and P<0

  14. Calculating transient rates from surveys

    CERN Document Server

    Carbone, Dario; Wijers, Ralph A M J; Rowlinson, Antonia

    2016-01-01

    We have developed a method to determine the transient surface density and transient rate for any given survey, using Monte-Carlo simulations. This method allows us to determine the transient rate as a function of both the flux and the duration of the transients in the whole flux-duration plane rather than one or a few points as currently available methods do. It is applicable to every survey strategy that is monitoring the same part of the sky, regardless the instrument or wavelength of the survey, or the target sources. We have simulated both top-hat and Fast Rise Exponential Decay light curves, highlighting how the shape of the light curve might affect the detectability of transients. Another application for this method is to estimate the number of transients of a given kind that are expected to be detected by a survey, provided that their rate is known.

  15. Calculating transient rates from surveys

    Science.gov (United States)

    Carbone, D.; van der Horst, A. J.; Wijers, R. A. M. J.; Rowlinson, A.

    2017-03-01

    We have developed a method to determine the transient surface density and transient rate for any given survey, using Monte Carlo simulations. This method allows us to determine the transient rate as a function of both the flux and the duration of the transients in the whole flux-duration plane rather than one or a few points as currently available methods do. It is applicable to every survey strategy that is monitoring the same part of the sky, regardless the instrument or wavelength of the survey, or the target sources. We have simulated both top-hat and Fast Rise Exponential Decay light curves, highlighting how the shape of the light curve might affect the detectability of transients. Another application for this method is to estimate the number of transients of a given kind that are expected to be detected by a survey, provided that their rate is known.

  16. Crucial role of membrane potential in heat stress-induced overproduction of reactive oxygen species in avian skeletal muscle mitochondria.

    Science.gov (United States)

    Kikusato, Motoi; Toyomizu, Masaaki

    2013-01-01

    Heat stress is an environmental factor that causes oxidative stress. We found previously that acute heat stress stimulates the production of reactive oxygen species (ROS) in the skeletal muscle mitochondria of birds, and that this was accompanied by an increase of the mitochondrial membrane potential (ΔΨ) due to increased substrate oxidation by the electron transport chain. We also showed that avian uncoupling protein (avUCP) expression is decreased by the heat exposure. The present study clarifies whether ΔΨ is a major determinant of the overproduction of ROS due to acute heat stress, and if the decrease in avUCP expression is responsible for the elevation in ΔΨ. Control (24°C) and acute heat-stressed (34°C for 12 h) birds exhibited increased succinate-driven mitochondrial ROS production as indicated by an elevation of ΔΨ, with this increase being significantly higher in the heat-stressed group compared with the control group. In glutamate/malate-energized mitochondria, no difference in the ROS production between the groups was observed, though the mitochondrial ΔΨ was significantly higher in the heat-stressed groups compared with the control group. Furthermore, mitochondria energized with either succinate/glutamate or succinate/malate showed increased ROS production and ΔΨ in the heat-stressed group compared with mitochondria from the control group. These results suggest that succinate oxidation could play an important role in the heat stress-induced overproduction of mitochondrial ROS in skeletal muscle. In agreement with the notion of a decrease in avUCP expression in response to heat stress, proton leak, which was likely mediated by UCP (that part which is GDP-inhibited and arachidonic acid-sensitive), was reduced in the heat-exposed group. We suggest that the acute heat stress-induced overproduction of mitochondrial ROS may depend on ΔΨ, which may in turn result not only from increased substrate oxidation but also from a decrease in the

  17. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

    Science.gov (United States)

    Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

    2016-10-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition

  18. Baseline and stress-induced glucocorticoid concentrations are not repeatable but covary within individual great tits (Parus major).