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Sample records for chronic unpredictable mild

  1. [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

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    Kudryashov, N V; Kalinina, T S; Voronina, T A

    2015-02-01

    The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

  2. Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress.

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    Chhillar, Ritu; Dhingra, Dinesh

    2013-08-01

    This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

  3. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.

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    Jia, Hong-Mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-Wu; Ding, Gang; Shang, Hai; Zou, Zhong-Mei

    2016-03-23

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.

  4. The link between unpredictable chronic mild stress model for depression and vascular inflammation?

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    Demirtaş, Tuğçe; Utkan, Tijen; Karson, Ayşe; Yazır, Yusufhan; Bayramgürler, Dilek; Gacar, Nejat

    2014-10-01

    Inflammation has been suggested to be associated with stress-induced depression and cardiovascular dysfunction. Tumor necrosis factor alpha (TNF-α) is a major cytokine in the activation of neuroendocrine, immune, and behavioral responses. In this study, we investigated the effects of infliximab (a TNF-α inhibitor) on endothelium-dependent vascular reactivity, systemic blood pressure, and endothelial nitric oxide synthase (eNOS) immunoreactivity in the unpredictable chronic mild stress (UCMS) model of depression in rats. There was no significant change between all groups in the systemic blood pressure. In UCMS, endothelium-dependent relaxation of the smooth muscle in response to carbachol was significantly decreased with 50 % maximal response (E max) and pD2 values compared with the controls. Infliximab was able to reverse this UCMS effect. Relaxation in response to the nitric oxide (NO) donor sodium nitroprusside and papaverine and KCl-induced contractile responses was similar between groups. In UCMS, decreased expression of eNOS was detected. Moreover, there was no significant change in UCMS + infliximab group with respect to control rats. Our results suggest that tumor necrosis factor-alpha (TNF-α) could be a major mediator of vascular dysfunction associated with UCMS, leading to decreased expression of eNOS.

  5. Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

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    López-López, Ana Laura; Jaime, Herlinda Bonilla; Escobar Villanueva, María Del Carmen; Padilla, Malinalli Brianza; Palacios, Gonzalo Vázquez; Aguilar, Francisco Javier Alarcón

    2016-07-01

    Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1β, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic

  6. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

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    Neetu Kushwah

    Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH in Unpredictable Chronic Mild Stress (UCMS induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM, open field test (OFT, force swim test (FST, as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.

  7. Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

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    Kolomin, Timur; Andreeva, Lyudmila; Bondarenko, Elena; Myasoedov, Nikolay; Slominsky, Petr; Shadrina, Maria

    2017-01-01

    It was shown that the anxiolytic effect of Selank is comparable to that of classical benzodiazepine drugs and that the basis of their mechanism of action may be similar. These data suggest that the presence of Selank may change the action of classical benzodiazepine drugs. To test this hypothesis, we evaluated the anxiolytic activity of Selank and diazepam in rats both under conditions of unpredictable chronic mild stress and in its absence, after the individual and combined administration of these compounds using the elevated plus maze test. We found that, even in the absence of chronic stress, the administration of a course of test substances changed anxiety indicators toward their deterioration, but the changes after the administration of a course of Selank were less pronounced. In conditions of chronic stress, anxiety indicator values after the simultaneous use of diazepam and Selank did not differ from the respective values observed before chronic stress exposure. The data obtained indicate that the individual administration of Selank was the most effective in reducing elevated levels of anxiety, induced by the administration of a course of test substances, whereas the combination of diazepam with Selank was the most effective in reducing anxiety in unpredictable chronic mild stress conditions. PMID:28280289

  8. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

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    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

  9. Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice.

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    Deng, Xue-Yang; Li, Hong-Yan; Chen, Jun-Jun; Li, Rui-Peng; Qu, Rong; Fu, Qiang; Ma, Shi-Ping

    2015-09-15

    Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT) in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with thymol significantly restored the CUMS-induced alterations of monoamine neurotransmitters in the hippocampus. Our results further demonstrated that thymol administration negatively regulated the induction of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1. In sum, our findings suggested that thymol played a potential antidepressant role in CUMS mice model through up-regulating the levels of central neurotransmitters and inhibiting the expressions of proinflammatory cytokines, which might provide potential for thymol in the light of opening up new therapeutic avenues for depression.

  10. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

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    Pei Jiang

    2014-01-01

    Full Text Available Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1 and peptides (VGF and NPY in rats exposed to chronic unpredictable mild stress (CUMS. Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS.

  11. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

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    Ru-Peng Liu

    2013-01-01

    Full Text Available To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA at the auricular concha region (ACR of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS, and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA axis hyperactivity.

  12. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice.

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    Kurhe, Yeshwant; Mahesh, Radhakrishnan

    2016-06-01

    Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15-28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  13. Chronic unpredicted mild stress-induced depression alter saxagliptin pharmacokinetics and CYP450 activity in GK rats

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    Zhengchao Xia

    2016-01-01

    Full Text Available Background. This study was to explore the pharmacokinetics of saxagliptin (Sax in Goto–Kakizaki (GK rats complicated with depression induced by chronic unpredicted mild stress (CUMS. The comorbidity of diabetic patients with depression is becoming more and more epidemic. Whether depression mental disorder alters the pharmacokinetics of hypoglycemic drugs in diabetes patients is not clear.Methods. Five-week-old male GK rats were kept in the cage for 7 weeks in a specific pathogen free (SPF-grade lab until the emergence of diabetes and were then divided into two groups: control group and depression model group. Rats in the CUMS-induced depression group were exposed to a series of stressors for 8 weeks. Plasma serotonin and dopamine levels and behavior of open-field test were used to confirm the establishment of the depression model. All rats were given 0.5 mg/kg Sax orally after 8 weeks and blood samples were collected at different time points. The Sax concentration was assayed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS. The CYP450 activity of the liver microsomes was determined by using cocktails of probe drugs in which the activities of CYP enzymes were assessed through the determination of the production of the probe drugs.Results. Statistically significant differences in Sax pharmacokinetics were observed for area under curve, clearance, peak concentration, peak time and mean residence time between the depression rats and the control rats, while no statistical differences were observed for half-time and distribution volume by HPLC-MS/MS analysis. The CYP450 activity had different changes in the depression group.Conclusions. These results indicated that CUMS-induced depression alters the drug metabolic process of Sax and CYP450 activity of the liver microsomal enzymes in GK rats.

  14. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

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    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  15. Serum metabonomics study of anti-depressive effect of Xiao-Chai-Hu-Tang on rat model of chronic unpredictable mild stress.

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    Xiong, Zhili; Yang, Jie; Huang, Yue; Zhang, Kuo; Bo, Yunhai; Lu, Xiumei; Su, Guangyue; Ma, Jie; Yang, Jingyu; Zhao, Longshan; Wu, Chunfu

    2016-09-01

    Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment.

  16. Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS.

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    Longshan Zhao

    Full Text Available Hydrophilic interaction-ultra high performance liquid chromatography (HILIC-UHPLC allows the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP chromatography. By optimization of the preparation and analytical conditions in HILIC mode, HILIC-UHPLC/MS was applied for the global metabolic profiling of rat plasma samples generated in an experimental model of chronic unpredictable mild stress (CUMS, and the concomitant investigation of the protective effect of fluoxetine was also evaluated. Identification of plasma metabolic profiles indicated that significant changes in specific metabolites occurred after fluoxetine exposure, including increased phenylalanine, serine, acetyl-L-carnitine, carnitine and decreased creatine, betaine, proline, tryptophan, tyrosine, C16:0 LPC. Some novel biomarkers from this HILIC-UHPLC/MS approach were betaine, proline, tyrosine creatine and serine compared with the results of RP-UHPLC/MS. The complementary nature of this technique is confirmed and is on agreement with previously published studies.

  17. TNF-alpha inhibition prevents cognitive decline and maintains hippocampal BDNF levels in the unpredictable chronic mild stress rat model of depression.

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    Şahin, Tuğçe Demirtaş; Karson, Ayşe; Balcı, Fuat; Yazır, Yusufhan; Bayramgürler, Dilek; Utkan, Tijen

    2015-10-01

    Previous findings have shown that patients with depression express higher levels of proinflammatory cytokines such as TNF-α and IL-6. We have recently found that Infliximab (a TNF-α inhibitor) decreased anhedonia and despair-like behavior in the rat unpredictable chronic mild stress (UCMS) model of depression suggesting that inflammation might play an important role in depression. An increasing number of studies suggest that inflammation is also associated with cognitive impairments. The current study aimed to investigate the effect of UCMS on the cognitive performance of rats and their hippocampal BDNF levels and the effect of chronic Infliximab (5mg/kg/weekly, i.p.) treatment on these measures. Rats were subjected to different types of stressors daily for a period of 56 days to induce depression-like state. The UCMS resulted in impairments in spatial and emotional memory acquisition and retention with no effect on the level of locomotor activity. These behavioral effects of UCMS were accompanied by reduction in the level of BDNF in the CA1 and CA3 regions of the hippocampus. Chronic Infliximab treatment prevented the UCMS-induced cognitive impairments as well as the reduction in the levels of hippocampal brain-derived neurotrophic factor (BDNF). These results suggest that Infliximab improves the spatial and emotional memory impairments induced by chronic stress in rats likely through its effects on hippocampal function by modulating inflammation.

  18. The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine--Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model.

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    Lingling Ding

    Full Text Available Jie Yu Chu Fan capsule (JYCF is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE, 5-hydroxytryptamine (5-HT, dopamine (DA, 5-hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA and 3,4-dihydroxyphenylacetic acid (DOPAC in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC. The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg and fluoxetine (20 mg/kg significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively and 5-HT in hippocampus (P < 0.05. In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.

  19. The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

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    Jun Shen

    2016-01-01

    Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.

  20. Cytisine, a Partial Agonist of α4β2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors.

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    Han, Jing; Wang, Dong-Sheng; Liu, Shui-Bing; Zhao, Ming-Gao

    2016-05-01

    Cytisine (CYT), a partial agonist of α4β2-nicotinic receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress.

  1. Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced rats by attenuating neuronal apoptosis via regulating ROCK/Akt pathway.

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    Qin, Tingting; Fang, Fang; Song, Meiting; Li, Ruipeng; Ma, Zhanqiang; Ma, Shiping

    2017-01-15

    There is increasing evidence that major depressive disorder (MDD) is also a progressive neurodegeneration disorder and neuronal damage is the major pathology of MDD. Umbelliferone, a coumarin derivative, was found in a range of plants with proved anti-oxidative, anti-inflammatory and neuroprotective effects. The primary purpose of this investigation was to evaluate whether umbelliferone could confer an antidepressant-like effect on the depressive model in rats developed by chronic unpredictable mild stress (CUMS) and explore the possible mechanism involved in its neuroprotective effects. We found that treatments with umbelliferone (15mg/kg, 30mg/kg) significantly ameliorated CUMS-induced depressive-like behaviors, such as decreased sucrose consumption, reduced locomotor activity and prolonged immobility time. Rats under CUMS stimulation treated with umbelliferone (15mg/kg, 30mg/kg) showed reduced neuronal apoptosis, as well as inhibited inflammatory cytokines levels by down-regulating Rho-associated protein kinase (ROCK) signaling and up-regulating protein kinase B (Akt) signaling. In conclusion, umbelliferone showed neuroprotective effects on CUMS-induced model of depression, which was associated with the inhibition of neuronal apoptosis modulated by ROCK/Akt pathway.

  2. Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress-Induced Oxidative Stress in Hippocampus by Upregulation of BDNF-TrkB Pathway

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    Min Hu

    2016-01-01

    Full Text Available Chronic unpredictable mild stress (CUMS induces hippocampal oxidative stress. H2S functions as a neuroprotectant against oxidative stress in brain. We have previously shown the upregulatory effect of H2S on BDNF protein expression in the hippocampus of rats. Therefore, we hypothesized that H2S prevents CUMS-generated oxidative stress by upregulation of BDNF-TrkB pathway. We showed that NaHS (0.03 or 0.1 mmol/kg/day ameliorates the level of hippocampal oxidative stress, including reduced levels of malondialdehyde (MDA and 4-hydroxy-2-trans-nonenal (4-HNE, as well as increased level of glutathione (GSH and activity of superoxide dismutase (SOD in the hippocampus of CUMS-treated rats. We also found that H2S upregulated the level of BDNF and p-TrkB protein in the hippocampus of CUMS rats. Furthermore, inhibition of BDNF signaling by K252a, an inhibitor of the BDNF receptor TrkB, blocked the antioxidant effects of H2S on CUMS-induced hippocampal oxidative stress. These results reveal the inhibitory role of H2S in CUMS-induced hippocampal oxidative stress, which is through upregulation of BDNF/TrkB pathway.

  3. Association between Repeated Unpredictable Chronic Mild Stress (UCMS) Procedures with a High Fat Diet: A Model of Fluoxetine Resistance in Mice

    Science.gov (United States)

    Isingrini, Elsa; Camus, Vincent; Le Guisquet, Anne-Marie; Pingaud, Maryse; Devers, Séverine; Belzung, Catherine

    2010-01-01

    Major depressive disorder is a debilitating disease. Unfortunately, treatment with antidepressants (ADs) has limited therapeutic efficacy since resistance to AD is common. Research in this field is hampered by the lack of a reliable natural animal model of AD resistance. Depression resistance is related to various factors, including the attendance of cardiovascular risk factors and past depressive episodes. We aimed to design a rodent model of depression resistance to ADs, associating cardiovascular risk factors with repeated unpredicted chronic mild stress (UCMS). Male BALB/c mice were given either a regular (4% fat) or a high fat diet (45% fat) and subjected to two 7-week periods of UCMS separated by 6 weeks. From the second week of each UCMS procedure, vehicle or fluoxetine (10 mg/kg, i.p.) was administrated daily. The effects of the UCMS and fluoxetine in both diet conditions were assessed using physical (coat state and body weight) and behavioural tests (the reward maze test and the splash test). The results demonstrate that during the second procedure, UCMS induced behavioural changes, including coat state degradation, disturbances in self-care behaviour (splash test) and anhedonia (reward maze test) and these were reversed by fluoxetine in the regular diet condition. In contrast, the high-fat diet regimen prevented the AD fluoxetine from abolishing the UCMS-induced changes. In conclusion, by associating UCMS—an already validated animal model of depression—with high-fat diet regimen, we designed a naturalistic animal model of AD resistance related to a sub-nosographic clinical entity of depression. PMID:20436931

  4. Association between repeated unpredictable chronic mild stress (UCMS procedures with a high fat diet: a model of fluoxetine resistance in mice.

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    Elsa Isingrini

    Full Text Available Major depressive disorder is a debilitating disease. Unfortunately, treatment with antidepressants (ADs has limited therapeutic efficacy since resistance to AD is common. Research in this field is hampered by the lack of a reliable natural animal model of AD resistance. Depression resistance is related to various factors, including the attendance of cardiovascular risk factors and past depressive episodes. We aimed to design a rodent model of depression resistance to ADs, associating cardiovascular risk factors with repeated unpredicted chronic mild stress (UCMS. Male BALB/c mice were given either a regular (4% fat or a high fat diet (45% fat and subjected to two 7-week periods of UCMS separated by 6 weeks. From the second week of each UCMS procedure, vehicle or fluoxetine (10 mg/kg, i.p. was administrated daily. The effects of the UCMS and fluoxetine in both diet conditions were assessed using physical (coat state and body weight and behavioural tests (the reward maze test and the splash test. The results demonstrate that during the second procedure, UCMS induced behavioural changes, including coat state degradation, disturbances in self-care behaviour (splash test and anhedonia (reward maze test and these were reversed by fluoxetine in the regular diet condition. In contrast, the high-fat diet regimen prevented the AD fluoxetine from abolishing the UCMS-induced changes. In conclusion, by associating UCMS-an already validated animal model of depression-with high-fat diet regimen, we designed a naturalistic animal model of AD resistance related to a sub-nosographic clinical entity of depression.

  5. Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress.

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    Xian-cang Ma

    Full Text Available BACKGROUND: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS, an animal model of depression. METHODOLOGY/PRINCIPAL FINDINGS: C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST and forced swimming test (FST, the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice. CONCLUSIONS/SIGNIFICANCE: These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

  6. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  7. 慢性应激引起的大鼠海马神经细胞形态结构的改变%The pathological change in the neurons of hippocampus of rat after chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    林志雄; 殷静雯; 罗旭东

    2014-01-01

    Objective:To identify The Change in the neurons of Hippocampus of Rat and depressive-like behavior after Chronic Unpredictable Mild Stress ( CUMS). Method: The mice were subjected to various unpredictable stressors during the 21 days CUMS procedures. The depressive-like behavior and pathological change was observed.Results:The number of neurons of hippocampus after stress was significantly different (P<0.01).Conclusion:Rats after chronic unpredictable mild stress appeared depressive-like behavior correlated with decreased of neurons hippocampus.%目的:探讨慢性应激引起的抑郁样行为与海马神经细胞形态结构的变化。方法:建立慢性轻度不可预见性应激大鼠抑郁模型,检测大鼠快感缺乏,行为活动减少,体质量减轻等抑郁样症状,观察海马区病理改变。结果:实验组和对照组大鼠行为学评分存在显著差异(P<0.01),实验组海马椎体细胞萎缩,神经细胞层数减少,细胞数目明显减少(P<0.01)。结论:应激可导致大鼠抑郁样行为的发生,同时影响神经细胞的生长和存活。

  8. 抑郁模型大鼠再应激后海马细胞支架蛋白的改变%Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    杨灿; 王高华; 王惠玲; 刘忠纯; 王晓萍; 朱志先

    2011-01-01

    目的 研究抑郁模型大鼠接受再次急性和慢性应激后细胞支架微管系统的动态性改变,并探讨可能的机制.方法 将40只大鼠按随机数字表法分为5组:对照组(空白对照+生理盐水),CUMS组(CUMS+生理盐水),氟西汀组(CUMS+氟西汀),急性再应激组(CUMS+氟西汀+药物清洗期+急性游泳应激),CUMS再应激组(CUMS+氟西汀+药物清洗期+CUMS).实验结束后进行行为学观察,并使用免疫印迹法( western blotting)检测大鼠海马乙酰化微管蛋白(Acet-Tub),酪氨酸化微管蛋白(Tyr-Tub),微管结合蛋白2(MAP-2)及磷酸化微管结合蛋白2(phospho-MAP-2).结果 (1)CUMS再应激组糖水偏好[ (43.38±7.84)%],总行程[(859.21±653.62)cm],运动平均速度[(2.05±0.60)cm/s]及直立次数[(0.12±0.30)次]均减少,与对照组及CUMS组相比均差异有显著性(P<0.01).急性再应激组行为与对照组比较差异无显著性.氟西汀组糖水偏好和旷场实验相关指标与对照组差异无显著性,与CUMS组差异有显著性(P<0.01).(2) CUMS再应激组Acet-Tub表达升高[(244.24±8.90)%],Tyr-Tub表达降低[ (30.92±11.00)%],与对照组及CUMS组差异均有显著性(P<0.01).MAP-2的表达与对照组及CUMS组比较差异无显著性,phospho-M AP-2的表达减少[(24.75±8.83)%],与对照组及CUMS组均差异有显著性(P<0.01).急性再应激组各蛋白水平与对照组比较差异无显著性.氟西汀组各蛋白的表达与对照组比较差异无显著性(P>0.05),与CUMS组比较差异有显著性(P<0.01).结论 动物再次暴露于CUMS后,其行为和微管动态性损害更严重,同时伴随微管相关蛋白磷酸化的变化,提示临床抑郁症的发生以及复发的町能机制.%Objective To investigate behavior and hippocampal cytoskeletal alterations following re-exposure to chronic unpredictable mild stress(CUMS) and acute swimming stress,and explore the possible mechanism.Methods 40 Male Sprague-Dawley (SD) rats were

  9. Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

    Institute of Scientific and Technical Information of China (English)

    Shuang Liang; Renbin Huang; Xing Lin; Jianchun Huang; Zhongshi Huang; Huagang Liu

    2012-01-01

    The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

  10. Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (6g on chronic unpredictable mild stress-induced changes in behavioural and brain oxidative stress parameters in mice

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    Shvetank Bhatt

    2014-01-01

    Full Text Available Aim: The aim of the study was to evaluate a novel 5 HT 3 receptor antagonist (6g on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body′s reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants. Materials and Methods: In the present study, a novel and potential 5-HT 3 receptor antagonist (4-benzylpiperazin-1-yl(3-methoxyquinoxalin-2-yl methanone (6g with good Log P (3.08 value and pA 2 (7.5 values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour. Results: The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05 decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05 increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. ′6g′ (1 and 2 mg/kg, p.o., 21 days and fluoxetine treatment (20 mg/kg, p.o., 21 days significantly (P < 0.05 reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities. However fluoxetine treatment (20 mg/kg, p.o., 21 days significantly decreased the nitrite level in the brain while ′6g′ (1 and 2 mg/kg, p.o., 21 days did not show significant (P < 0

  11. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

    Science.gov (United States)

    Tao, Weiwei; Dong, Yu; Su, Qiang; Wang, Hanqing; Chen, Yanyan; Xue, Wenda; Chen, Chang; Xia, Baomei; Duan, Jinao; Chen, Gang

    2016-07-15

    Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. The main purpose of the current study was to verify whether liquiritigenin conferred an antidepressant-like effect on the depressive mouse model established by unpredictable chronic mild stress (UCMS) and explore its possible mechanism. The results of depression-related behaviors including sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) indicated that both liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) dramatically improved the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) revealed that treatment with liquiritigenin significantly reduced the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus. Compared with the UCMS group, the administrations of liquiritigenin, increased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and decreased Malondialdehyde (MDA) content. Meanwhile, glucocorticoids (GC) content was reduced in the liquiritigenin group, which suggested that liquiritigenin exhibiting the ameliorative effect on activated hypothalamic-pituitary-adrenal (HPA) axis stimulated with UCMS. Mice treated with liquiritigenin showed restored levels of neurotransmitter norepinephrine (NE) and serotonin (5-HT). Western blot analysis displayed up-regulated expressions of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p- mammalian target of rapamycin (mTOR), p-tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF). Thus, it was supposed that liquiritigenin might be useful for the treatment of chronic depression possibly through PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

  12. Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.

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    Hong-Mei Jia

    Full Text Available Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36 were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36 involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC and indoleamine 2, 3-dioxygenase (IDO in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify

  13. 海马BDNF和iNOS与慢性应激性抑郁的关系%Sequental Involvement of Hippocampal BDNF and Inducible Nitric Oxide in Depression Induced by Chronic Unpredicted Mild Stress

    Institute of Scientific and Technical Information of China (English)

    王丹

    2010-01-01

    建立慢性不可预见性抑郁动物模型,采用液体消耗实验(fluid consumption test,FCT)、敞箱实验(Open field test,OFT)和强迫游泳(Forced swimming test,FST)等方法进行行为学测试,并用免疫组织化学的方法检测海马BDNF和iNOS的表达,运用腹腔注射药物的方法探索BDNF和iNOS的作用与关系.探讨了海马脑源性神经营养因子(BDNF)和诱导型一氧化氮合酶(iNOS)在慢性应激诱导的抑郁症中的关系,及抑郁症的发病机制.与对照组相比,慢性不可预见性应激(Chronic unpredicted mild stress ,CUMS)组大鼠的行为学表现能力下降,BDNF表达下降(n=8,P<0.01),iNOS的表达升高(n=8,P<0.01);阻断内源性BDNF大鼠的行为学表现能力也下降,iNOS的表达升高(n=7,P<0.01);而海马微量注射iNOS的抑制剂SMT均可反转CUMS和BDNF抑制剂所导致的行为学表现能力下降的现象.慢性不可预见性应激引起海马BDNF表达下降,NO过高而导致抑郁.BDNF对神经元具有保护作用, BDNF的抗抑郁作用可能是通过抑制iNOS的表达而起作用的.提示BDNF等神经保护因子通过抑制iNOS的过量表达而保护脑组织可能是治疗抑郁症的一个重要途径.

  14. Behavioral and hippocampal cytoskeletal alterations in rats following chronic unpredictable mild stress and fluoxetine treatment%慢性应激及氟西汀治疗后大鼠海马细胞支架的改变

    Institute of Scientific and Technical Information of China (English)

    杨灿; 王高华; 王惠玲; 王晓萍; 刘忠纯; 朱志先

    2010-01-01

    目的 探讨慢性不可预见性应激及氟西汀治疗后大鼠细胞支架微管系统的动态性变化及其可能机制.方法 将24只大鼠按随机数字表法分为对照组(空白对照+生理盐水)、慢性不可预见性温和应激(CUMS)组(CUMS+生理盐水)和氟西汀组(CUMS+氟西汀),每组8只.对大鼠进行连续21 d CUMS后,氟西汀组给予氟西汀(10 mg/kg)治疗21 d,对照组和CUMS组给予生理盐水.实验结束后进行行为学观察,并使用免疫印迹法(western blot)检测大鼠海马乙酰化微管蛋白(Acet-Tub),酪氨酸化微管蛋白(Tyr-Tub),微管结合蛋白2(MAP-2)及磷酸化微管结合蛋白2(phospho-MAP-2).结果 (1)CUMS组糖水偏好[(55.13±11.80)%],总行程[(2736.59±511.20)cm],运动平均速度[(5.69±1.08)cm/s]及直立次数[(2.50±2.00)次]均低于对照组,差异有统计学意义(P<0.01);氟西汀组上述指标与对照组比较差异无统计学意义(P>0.05).(2)CUMS组与对照组相比,Acet-Tub表达升高[(171.84±10.34)%],Tyr-Tub[(62.06±9.24)%]和phospho-MAP-2[(68.81±8.93)%]的表达降低,差异有统计学意义(P均<0.01),MAP-2的表达与对照组比较无统计学意义(P>0.05);经氟西汀治疗后,Acet-Tub的表达降低为[(96.18±8.92)%],Tyr-Tub和phospho-MAP-2的表达分别升高为[(95.06±8.00)%]、[(100.60±7.30)%],与对照组比较均无统计学意义(P>0.05).结论 慢性应激后微管动态性减低,神经可塑性受损,氟西汀可以逆转海马的这些损伤,上述过程可能与微管相关蛋白磷酸化水平的变化有关.%Objective To investigate behavior and hippocampal cytoskeletal alterations in rats following chronic unpredictable mild stress and fluoxetine treatment, and explore the possible mechanism. Methods Twenty four male Sprague-Dawley (SD) rats were divided into three groups, with 8 exposed to 21 consecutive days of chronic unpredicted mild stresses (CUMS) and treated with vehicle, 8 exposed to CUMS and treated with fluoxetine, and 8 as

  15. A PET study on brain of chronic unpredictable mild stimulations (CUMS)-induced depressive rats%慢性不可预见性温和刺激抑郁症模型大鼠的脑PET成像研究

    Institute of Scientific and Technical Information of China (English)

    刘金鹏; 刘华; 高峻钰; 刘少君

    2015-01-01

    目的:通过PET成像技术研究慢性不可预见性温和刺激( CUMS)致抑郁症大鼠的全脑代谢特点。方法实验组大鼠给予CUMS 4周后,通过糖水偏嗜度、自发活动距离、体质量等指标分为刺激后抑郁大鼠( D组)及刺激后非抑郁大鼠( ND组),并与正常对照组大鼠( CON组)一起行PET检查,比较不同组大鼠之间全脑的代谢变化。结果(1)D组大鼠的双侧S1、丘脑、苍白球、岛叶、M2、左屏状核较CON组代谢升高,右侧下丘、胼胝体压部、小脑则代谢降低;(2)D组大鼠双侧海马CA3区、M1、M2、纹状体、S1、嗅球等区较ND组代谢增高,左侧楔状核及海马则代谢降低;(3) ND组大鼠与CON组相比,无代谢升高的脑区,而外侧隔核、双侧纹状体、下丘脑室旁核、双侧S1、右侧苍白球则代谢降低。结论以前囟后4 mm处为界,抑郁大鼠脑代谢特点是前高后低,左右大致对称。抑郁症的发生可能与多个脑区功能的异常相互作用有关。%Objective To observe the metabolic changes in the whole brain of chronic unpredictable mild stimulations ( CUMS)-induced depressive rats using PET imaging technology.Methods After 4 weeks’ of CUMS, rats of experimental group were divided into two groups:Group D( depression) and Group ND( no depression) , according to the degree of sugar addiction, distance of spontaneous activity and relative body mass.Then metabolic changes in the whole brain of these rats and those in control group ( CON) were observed using PET technology, and the differences were companred between the threegroups.Results (1)ComparedwithGroupCON,metabolismofGroupDwaselevatedinbilateralS1,thalamus, globus pallidus, insula, M2 and left claustrum, but descended in right inferior colliculus, splenium of corpus callosum and cerebellum.(2) Metabolism of Group D increased in the bilateral CA3 region of hippocampus, M1, M2, striatum, S1 and olfactory bulb

  16. NEUROPROTECTIVE EFFECT OF CURCUMIN ON RATS UNDER CHRONIC UNPREDICTABLE MILD STRESS%姜黄素预处理对慢性心理应激大鼠中枢神经的保护作用

    Institute of Scientific and Technical Information of China (English)

    安改红; 陈学伟; 王静; 刘洪涛; 张娜; 徐传香; 佘晓俊; 崔博; 马强

    2013-01-01

    目的 观察姜黄素预处理对慢性应激大鼠行为学、单胺类递质水平及血清糖皮质激素的影响,为评价姜黄素对慢性心理应激大鼠中枢神经的保护作用提供依据.方法 48只Wistar大鼠随机分为对照组、慢性应激组、氟西汀干预组、姜黄素(低、中、高剂量)干预组,每天应激前1h灌胃给药.对大鼠进行28 d应激刺激建立慢性不可预知性慢性应激模型.旷场试验测定大鼠行为学指标;糖水试验测定大鼠“快感缺乏”;高效液相-电化学检测法测定海马单胺类递质;ELISA检测血清糖皮质激素.结果 慢性应激组大鼠的体质量、旷场活动性和糖水偏嗜度均明显低于对照组(P<0.05,P<0.01);海马5-HT含量下降(P<0.05),血清糖皮质激素水平升高(P<0.01).3个剂量姜黄素组大鼠体质量于第4周分别为(310.60±21.35)、(315.60±23.73)和(319.91±18.76)g,高于慢性应激组[(270.24±19.60)g,P<0.05];旷场竖立时间分别为(18.86±9.49)、(24.14±4.38)和(24.14±5.41)s,高于慢性应激组[(11.00±9.20)s,P<0.05];血清糖皮质激素水平分别为(567.94±22.54)、(338.62±63.79)和(259.96± 17.79)ng/L,低于慢性应激组[(908.57±22.86) ng/L,P<0.01].实验后低、中剂量组海马5-HT含量分别为(1063.89±149.61)和(1340.96±42.62) ng/g,高于慢性应激组[(941.23±80.00) ng/g,P<0.05].结论 姜黄素预处理可改善慢性不可预知性应激大鼠抑郁状态,起到中枢神经保护作用,其作用机制可能与单胺类递质水平的增加和调节HPA轴活性有关.%Objective To observe the effect of curcumin on behavior,monoamine neurotransmitter,and serum glucocorticoid of rats under chronic unpredictable mild stress (CUMS) ,in order to provide theoretical basis for assessing the neuroprotection of curcumin. Methods Forty-eight male Wistar rats were randomly divided into six groups: normal control group, stress group, curcumin groups (low, moderate, high dose) ,and

  17. Chronic unpredictable stress during adolescence causes long-term anxiety.

    Science.gov (United States)

    Chaby, L E; Cavigelli, S A; Hirrlinger, A M; Caruso, M J; Braithwaite, V A

    2015-02-01

    Exposure to stress during adolescence can cause long-term changes in behavior and cognition. Anxiety diagnoses rise during adolescence and are increased by adverse experiences. Currently, it is unknown how long stress during adolescence alters anxiety in adulthood. We found that rats exposed to chronic unpredictable stress during adolescence expressed altered behavior 6.5 months later; showing increased anxiety in a feeding test in a novel environment. Although behavioral changes indicative of anxiety were detected in late adulthood, the basal levels of fecal corticoid metabolites in prior-stressed rats did not differ from unstressed, control rats.

  18. 慢性应激抑郁型黄褐斑动物模型建立与现有模型的比较研究%Establishment of Chloasma Guinea pig Model with chronic unpredictable mild stress depression and comparative study of it with existent models

    Institute of Scientific and Technical Information of China (English)

    杨鹏; 杨慧兰; 麦跃; 戴勇; 孙林潮; 鲁东平

    2013-01-01

    Objective To establish and authenticate the Chloasma Guinea pig Model with chronic unpredictable mild stress depression and comparative study of it with existent models. Methods After the injection of progesterone,chronic unpredictable sequence of mild stressors stimulated them and gave them partially ultraviolet radiation. Results The Guinea pig model of depression had been established successfully at 28th day.Multiple models of progesterone injection and ultraviolet radiation compounding with chronic unpredictable sequence of mild stressors can heighten MDA,depress SOD,and increase melanocytes of skin. Meanwhile,the ethology of this model showed it's syndrome of Depressive position.The guinea pig showed reduced squares crossing and rearing in open-field test, a significantly reduced consumption of preference for sucrose solutions and an increased pure water consumption as compared with control group. Conclusion The multiple factor Chloasma model of chronic unpredictable mild stress depression has been built successfully. Compared with other existing models of MDA,SOD and skin melanocytes objective indicators of change closer to human Chloasma lesions.%目的:建立并验证慢性应激抑郁型黄褐斑动物模型,并与现有其他模型进行比较.方法:在注射黄体酮同时,进行慢性轻度不可预见的应激刺激,并紫外线局部照射.结果:黄体酮+紫外线+慢性应激抑郁法造模较其他方法更能导致皮肤丙二醛(Malondialdehyde,MDA)升高和超氧化物歧化酶(Superoxide dismutase,SOD)降低以及皮肤黑素细胞的增加,并且具有抑郁症的行动学表现.与空白组比较,经慢性轻度不可预见性应激刺激的动物体重显著下降,敞箱试验中穿格次数、理毛时间和次数、直立次数得分显著下降,液体消耗试验中糖水消耗和糖水偏爱百分比明显下降,而纯水消耗显著提高.结论:黄体酮+紫外线+慢性应激抑郁法建立的抑郁型黄褐斑豚鼠多因素模型

  19. A comparative study on behavior changes and cerebral morphology and function of chronic restraint stress mice and chronic unpredictable mild stress mice%慢性束缚与慢性不可预期温和应激抑郁模型小鼠的行为学比较及其发生机制研究

    Institute of Scientific and Technical Information of China (English)

    廖莎; 周佳; 平锋锋; 王倩; 郝娣; 尚靖

    2012-01-01

    【Objective】 The aim of this study was to explore the pathogenesis of depression by comparing the effects of chronic restraint stress(CRS) and chronic unpredictable mild stress(CUMS) on behavior and cerebral morphology of C57BL/6 mice.【Method】 Mice were randomly divided into the normal control(NC) group,CRS group,and CUMS group.After 3 weeks of stress exposure,open-field test,tail suspension test,and forced swimming test were taken to evaluate the behavior changes of mice.In addition,the cerebral morphology and function changes were investigated by HE staining and immuno-histochemistry analysis.The MAO activity of mice hippocampus was analyzed by fluorescence spectrophotometry.【Result】 The results showed that compared to the NC group,the crossing frequency,hearing frequency and body weight were all decreased significantly in the CRS group,whereas no significant changes in the CUMS group(P0.05).However,the results of tail suspension test and forced swimming test showed that there was a significant increase in the percent of immobility time in the CUMS group compared to the NC group(P0.01).In addition,except the hippocampus CA1 region in the CRS group,the CA1,CA3 and dentate gyrus regions of hippocampus were all atrophied in both stressed groups.Furthermore,the expression of 5-HT1A receptor in hippocampus was decreased and the MAO activity was up-regulated in both CRS and CUMS group.【Conclusion】 The results showed that both CRS and CUMS can induce depressive-like behaviors in C57BL/6 mice.CRS mainly suppresses the exploratory behavior while CUMS induced typical behavioral despair.This praxiology distinction may be relative to the differences in cerebral morphology and function of treated mice between two stressed groups.%【目的】通过比较慢性束缚应激(Chronic restraint stress,CRS)与慢性不可预期温和应激(Chronic unpredictable mild stress,CUMS)对C57BL/6小鼠行为学指标及大脑海马区相关功能的影响,探讨抑

  20. Improvement ofSchisandrae Fructusprocessed products on depressive mice induced by chronic unpredictable mild stress%五味子不同炮制品对小鼠慢性不可预知性应激抑郁的改善作用

    Institute of Scientific and Technical Information of China (English)

    荆然; 李慧峰; 程艳刚; 裴妙荣

    2016-01-01

    Objective To evaluate the improvement ofSchisandrae Fructusprocessed products on depression of mice induced by chronic unpredictable mild stress.Methods ICR mice were randomly divided into control group, model group, fluoxetine group, andSchisandrae Fructus,Schisandrae Fructusprocessed with alcohol, andSchisandrae Fructusprocessed with wine groups, and each group had 10 mice. Mice in the control and model groups were ig administered with distilled water. Mice in the fluoxetine group were ig administered with Fluoxetine Hydrochloride Dispersible Tablets 3.3 mg/kg. Mice in the Schisandrae Fructus groups were ig administered withSchisandrae Fructus1.0 g/kg with volume of 10 mL/kg. Ten kinds of unpredictable stimulations were adopted to establish the model of chronic unpredictable mild stress after last administration 1 h for 28 d. Behaviors of depressive mice in open field test, tail suspression test, and forced swimming test were observed. The contents of 5-HT, DA, and CORT in serum were determined by Enzyme-linked immunosorbent assay (ELISA) method. Results were analyzed by comprehensive analysis method. Results Compared with the model group, the open field stand times and open central grid crossing times were increased, but the time of hanging tail and room temperature forced swimming were decreased in theSchisandrae Fructus group (P< 0.05, 0.01). There were no differences on open field stand times and open central grid crossing times inSchisandrae Fructusprocessed with alcohol and wine groups, but the time of hanging tail and room temperature forced swimming were decreased (P< 0.05). Compared with the model group, contents of 5-HT and DA in serum of depressive mice were increased, but the contents of CORT in serum were decreased in the Schisandrae Fructus group (P< 0.01). The contents of 5-HT in serum of depressive mice were increased, but the contents of CORT in serum were decreased in theSchisandrae Fructusprocessed with alcohol and wine groups (P< 0.05, 0

  1. Role of Hippocampal 5-HT1A Receptor and Its Modulation to NMDA Receptor and AMPA Receptor in Depression Induced by Chronic Unpredictable Mild Stress%应激性抑郁样行为发生中海马5-羟色胺1A受体的作用及其对NMDA受体和AMPA受体的调节

    Institute of Scientific and Technical Information of China (English)

    问黎敏; 安书成; 刘慧

    2012-01-01

    为探讨慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)诱发抑郁样行为发生中海马5-羟色胺1A受体(5-hydroxytryptamine receptor 1A,5-HT1AR)表达与作用,及其对谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体和α-氨基羟甲基异恶唑丙酸(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid,AMPA)受体的影响.通过建立CUMS动物模型,给应激抑郁模型大鼠海马微量注射5-HT1A受体激动剂、给正常大鼠海马微量注射5-HT1A受体拮抗剂,测量大鼠体重变化率,并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测,运用Western blot和ELISA方法检测大鼠海马组织中5-HT1AR和NMDAR和AMPAR的关键亚基的表达以及磷酸化水平.结果显示,与对照组相比,CUMS组大鼠表现出抑郁样行为,海马5-HT1AR、AMPA受体的GluR2/3亚基表达及磷酸化明显降低,NMDA受体的NR1和NR2B亚基表达及磷酸化显著增加;正常大鼠海马微量注射5-HT1A受体拮抗剂WAY100635,动物行为学表现及AMPA受体、NMDA受体表达及磷酸化水平均与CUMS组相同;注射5-HT1A受体激动剂8-OH-DPAT能逆转应激诱导的上述改变.以上结果表明,CUMS诱发抑郁榉行为与海马5-HT1AR表达下降,AMPAR表达量及磷酸化水平降低,NMDAR表达量及磷酸化水平升高有关.5-HT通过5-HT1AR产生抗抑郁作用.5-HT1AR激动剂抗抑郁作用与降低NMDAR表达量及磷酸化水平,提高AMPAR表达量及磷酸化水平密切相关.%Stressors markedly influence central neurochemical and hormonal processes and thus play a pivotal role in the occurrence of depressive illnesses. As the center for stress response and the potential target for stressfulprovocation, the hippocampus is becoming a focus in depression research. Although a large number of behavioral paradigms have been proposed as animal models of depression, only a few are considered potentially useful research tools with

  2. Expression of 11β-hydroxysteroid dehydrogenase type 1 on hippocampus of rat with chronic unpredictable mild stress%11β-羟基类固醇脱氢酶-1在慢性温和应激抑郁大鼠海马组织中的表达

    Institute of Scientific and Technical Information of China (English)

    程世翔; 涂悦; 张赛; 文立; 刘晓智

    2012-01-01

    Objective To investigate the roles of 11 β-hydroxysteroid dehydrogenase type 1 ( 11 β-HSD1 )on hippocampus of rat with chronic unpredictable mild stress (CUMS).Methods Twenty-four male SpragueDawley rats were randomly divided into control group and depressive model group. Chronic unpredictable mild stress (CUMS) was used to make up depressive animal model.Behavioral changes were recorded by body weight measuring,sucrose consumption test (SCT) and open field test (OFT),respectively.The mRNA transcription of 11β-HSD1 in hippocampus tissues of the rats were detected by real-time RT-PCR,and the protein expression of 11β-HSD1 were detected by western blot and immunofluorescence.Results Bcforc starting CUMS protocol,the rats exhibited equivalent weight and sucrose consumption.Twenty-eight days after CUMS protocol,behavior parameters such as body weight,sucrose consumption,nunber of crossing,and number of rearing were significantly decreased in rats exposed to CUMS group compared with control group (P < 0.05,P < 0.01 ).Correspondingly,realtime RT-PCR assays showed the mRNA expression of 11 β-HSD1 in the hippocampus of CUMS group,which was (31 ±9) % lower than that of control group.Meanwhile,the protein expression of it in CUMS group was lower than that of control group (P < 0.05 ).Inmunofluorescence revealed that the number of positive 11 3-HSD1 cells was high (223 ± 13) in the control group,while the number was decreased prominently (92 ± 11 ) in the CUMS group (P < 0.01 ).Conclusion Depressive behavior of rats is induced and the expression of 11 β-HSD1 in the hippocampus is decreased prominently by CUMS,the mechanism of which is at least related to the low expression of 11β-HSD1 and disturbance of glucocorticoid metabolism caused by CUMS.%目的 应用慢性温和不可预知刺激( CUMS)建立抑郁症动物模型,探讨大鼠海马组织中11β-羟基类固醇脱氢酶-1(11β-HSD1)蛋白表达以及抑郁症的发病机制.方法 将24只Sprague

  3. Influence on the Expression of TRH in Hypothalamus of Rats with Chronic Unpredictable Mild Stress-induced Depression by Different Electro-acupuncture Treatment%不同电针对慢性应激抑郁模型大鼠下丘脑促甲状腺激素释放激素表达的影响

    Institute of Scientific and Technical Information of China (English)

    莫雨平; 李志刚; 姚海江; 宋洪涛; 陈万顺; 王鑫; 加吾拉·阿不力孜; 许安萍; 唐银杉; 韩向博

    2014-01-01

    目的:观察不同电针对慢性应激抑郁模型( CUMS)大鼠下丘脑中促甲状腺激素释放激素( TRH)表达的影响,探讨TRH在大鼠实验性抑郁症发病过程中的作用机制及不同电针干预对其的影响。方法:将60只清洁健康雄性SD大鼠,随机分为正常组、模型组、脉冲电针组、音乐电针组及氟西汀组,每组12只。孤养结合CUMS21天复制抑郁症模型,通过开野试验观察大鼠行为学变化,采用免疫组织化学法、酶联免疫吸附法及荧光实时定量PCR分别检测TRH在大鼠下丘脑中的表达情况。结果:模型组大鼠开野实验水平运动及垂直运动明显减少,脉冲电针组、音乐电针组及氟西汀组均可改善此变化;模型组大鼠下丘脑内TRH表达均明显降低,脉冲电针组、音乐电针组及氟西汀组可逆转此病理变化,但氟西汀组治疗效果较两组电针治疗效果略胜一筹;两组电针治疗之间无明显统计学差异。结论:抑郁大鼠的TRH含量低于正常;电针治疗抑郁症可能是通过升高TRH的含量而发挥抗抑郁作用。音乐电针与脉冲电针治疗抑郁症效果差异不明显。%Objective:To investigate the influence on the expression of TRH in the hypothalamus of rats with chronic un-predictable mild stress by different electro-acupuncture( EA) treatments, to elucidate the possible role of TRH in the development of experimental depression and the effect of different EA for them.Methods:Adult male SD rats were ran-domly divided into a normal control group(n=12),a model group (n=12),a pulsed EA group(n=12),a music EA group( n=12) and a fluoxetine group( n=12) .Depression models were established by lonely raising and chronic unpre-dictable mild stress for 21 days.Open-field test was performed to test the behavior of rats.The expression of hypothala-mus TRH was detected by using immunohistochemistry , enzyme linked immunosorbent assay( ELISA) and real

  4. 音乐电针和脉冲电针对慢性应激抑郁模型大鼠不同脑区单胺类神经递质表达的影响%Influence of Music Electro-acupuncture and Pulsed Electro-acupuncture on the Different Encephalic Regions of Monoamine Neurotransmitter Chronic Unpredictable Mild Stress Depression Model Rats

    Institute of Scientific and Technical Information of China (English)

    唐银杉; 纪倩; 曹瑾; 滕金艳; 邓晓丰; 李静; 李志刚

    2014-01-01

    目的:对比观察不同电针对慢性应激抑郁模型大鼠额叶和海马5-HT、DA和NE表达的影响,进一步研究音乐电针与脉冲电针干预治疗抑郁症的疗效差异以及其生物学机制。方法:雄性SD大鼠,随机分为5组:正常对照组、模型组、百忧解组、音乐电针组、脉冲电针组,每组10只。除正常对照组外,其余均采用慢性应激结合孤养的方式造模。采用开野实验、糖水消耗实验和体重检测进行各组的行为学评价;采用放射免疫法分别检测大鼠额叶和海马5-HT、DA和NE的表达。结果:实验第21天后,模型组大鼠行为学指标较正常对照组有明显降低(P<0.01);百忧解组、音乐电针组和脉冲电针组与模型组比较,大鼠活动度、糖水消耗量和体重明显升高(P<0.05)。与正常对照组比较,模型组大鼠额叶和海马组织5-HT、DA和NE的表达量明显降低(P<0.01);与模型组相比,百忧解组、脉冲电针组和音乐电针组能提高额叶和海马组织的5-HT、DA、NE的表达量(P<0.05);与脉冲电针组比较,音乐电针组海马和额叶组织的5-HT的表达量有显著性差异(P<0.05)。结论:百忧解、脉冲电针和音乐电针均可改善慢性应激抑郁大鼠的行为学症状,具有一定的抗抑郁作用;音乐电针在提高慢性应激模型大鼠中枢单胺类的神经水平方面优于百忧解和脉冲电针,这可能是音乐电针发挥抗抑郁治疗作用的途径之一。%Objective:To observe the influence of different electro -acupuncture on frontal lobe and hippocampus to 5-HT,DA,NE neurotransmitter ’ s expression of chronic unpredictable mild stress depression model rats , to probe into the mechanism for treating depression .Methods:Fifty male SD rats were randomly divided into five groups:Nor-mal control group, Model group, Fluoxetine group, music electro-acupuncture group and pulsed

  5. Orbitofrontal Cortex 5-HT1A Receptor Modulate Glutamate and GABA in Depression Induced by Chronic Unpredictable Mild Stress%应激性抑郁样行为发生中眶额叶5-HT1A受体对谷氨酸和γ-氨基丁酸的调节

    Institute of Scientific and Technical Information of China (English)

    李江娜; 安书成; 李珍

    2015-01-01

    Stress response and depression have a crucial impact on modern society. Although the symptoms are well characterized, the molecular mechanisms underlying depression are largely unknown. Currently, the monoaminergic systems, especially serotonergic systems, have received the most attention in the research of depression. Accumulating evidence suggests that the glutamatergic and GABAergic system play an important role in the neurobiology and treatment of this disease. Multiple studies have shown that serotonin (5-HT) could modulate the neurotransmission of glutamic acid (Glu) and gamma-aminobutyric acid (GABA). The orbitofrontal cortex (OFC), which is involved in the pathophysiology and treatment of depression, plays a critical role in the control of higher brain functions and it mainly receives a dense 5-HT innervation from the dorsal raphe nucleus. There exist some 5-HT1A receptors on glutamatergic neurons and GABAergic neurons in the OFC. The purpose of this research was to elucidate the modulatory action of 5-HT1A receptor on the functions of Glu and GABA, which are the principal neurotransmitters mediating excitatory and inhibitory signals in the OFC respectively, in a well-established animal model of depression induced by chronic unpredictable mild stress (CUMS). We used CUMS in rat to mimic the core symptoms in human. Using the pharmacology approaches by microinjecting of 5-HT1A receptor agonist 8-OH-DPAT and its antagonist WAY100635 to the OFC, we detected behavioral changes by using behavior tests including sucrose preference test, open field test and tail suspension test. In addition, high-performance liquid chromatography (HPLC) was used to detect the level of neurotransmitters such as 5-HT, Glu and GABA in the OFC, respectively. CUMS group showed a variety of behavioral characteristics of depression, including a significant reduction in the sucrose preference, and locomotion, rearing and grooming in the open field test, and a significant increase in

  6. 音乐治疗对慢性应激大鼠脑内5-羟色胺及微管蛋白的影响%Effects of the music therapy on the serotonin and tubulin in brain tissue of chronic unpredictable mild stress rats

    Institute of Scientific and Technical Information of China (English)

    吴涵; 牟晓洁

    2014-01-01

    目的 探讨音乐治疗对慢性轻度不可预测性应激(CUMS)大鼠脑内前额叶、海马、下丘脑等脑区5-羟色胺及微管蛋白的水平及可能作用机制.方法 随机将24只SD雄性大鼠分为音乐治疗应激组(n=8)、应激组(n=8)和正常对照组(n=8).采用慢性轻度不可预测性应激(CUMS)模型连续刺激大鼠21 d,音乐治疗应激组在应激的同时给予音乐治疗.实验结束后对每组大鼠进行行为学观察,然后处死大鼠,检测下丘脑、海马和前额叶皮质中5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)的含量和微管蛋白的表达.结果 旷场试验的中央格停留时间比较,应激组大鼠显著低于对照组(P<0.01),而音乐治疗应激组与对照组相比差异无统计学意义(P>0.05).与应激组相比,对照组和音乐治疗应激组的海马、前额叶中5-HT及5-HIAA含量均显著升高(P<0.01);但三组下丘脑中5-HT及5-HIAA含量差异无统计学意义(P>0.05).与应激组相比,对照组和音乐治疗应激组的海马中乙酰化微管蛋白表达均显著降低(P<0.01),酪氨酸化微管蛋白表达均显著升高(P<0.01);但三组的前额叶和下丘脑中乙酰化微管蛋白、酪氨酸化微管蛋白表达差异无统计学意义(P>0.05).结论 音乐治疗能改善应激所致的前额叶、海马5-羟色胺水平的低下和海马微管蛋白的降低.%Objective To study the effect of the music therapy on the serotonin and tubulin in frontal cortex,hippocampus and hypothalamus of chronic unpredictable mild stress (CUMS) rats,and to explore the neurobiology of the music therapy on stress disorders.Methods Twenty-four male Sprague-Dawley rats were randomly divided equally to music therapy stress group(n=8),stress group(n=8) and normal control group(n=8).Mild chronic unpredictable stress was used for 21 days in a continuous stimulation pattern to establish the CUMS model.The 5-HT,5-HIAA and tubulin levels in the the frontal cortex

  7. Sex differences in the chronic mild stress model of depression.

    Science.gov (United States)

    Franceschelli, Anthony; Herchick, Samantha; Thelen, Connor; Papadopoulou-Daifoti, Zeta; Pitychoutis, Pothitos M

    2014-09-01

    A large volume of clinical and experimental evidence documents sex differences in brain anatomy, chemistry, and function, as well as in stress and drug responses. The chronic mild stress model (CMS) is one of the most extensively investigated animal models of chronic stress. However, only a limited number of studies have been conducted in female rodents despite the markedly higher prevalence of major depression among women. Herein, we review CMS studies conducted in rats and mice of both sexes and further discuss intriguing sex-dependent behavioral and neurobiological findings. The PubMed literature search engine was used to find and collect all relevant articles analyzed in this review. Specifically, a multitermed search was performed with 'chronic mild stress', 'chronic unpredictable stress' and 'chronic variable stress' as base terms and 'sex', 'gender', 'females' and 'depression' as secondary terms in various combinations. Male and female rodents appear to be differentially affected by CMS application, depending on the behavioral, physiological, and neurobiological indices that are being measured. Importantly, the CMS paradigm, despite its limitations, has been successfully used to assess a constellation of interdisciplinary research questions in the sex differences field and has served as a 'silver bullet' in assessing the role of sex in the neurobiology of major depression.

  8. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    刘丽琴; 罗艳; 张瑞睿; 郭建友

    2011-01-01

    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  9. Effects of Chronic Unpredictable Mild Stress with Different Time Courses on Neuroplasticity-related Proteins Expression in Rat Hippocampus%不同时程的慢性不可预计温和应激对大鼠海马神经可塑性相关蛋白水平的影响

    Institute of Scientific and Technical Information of China (English)

    肖玲; 舒畅; 唐记华; 王晓萍; 王高华

    2013-01-01

    Objective:To explore the effect of different time courses of chronic unpredictable mild stress on neu-roplasticity-related proteins expression in the adult rat hippocampus. Methods:Twenty-four rats were randomly divided into four groups with 6 rats in each group:the control group, rats without stress;M1 group in which rats were subjected to CUMS for 1 week; M2 group, in which rats were subjected to CUMS for 2 weeks; and M3 group in which rats were subjected to CUMS for 3 weeks. The levels of brain-derived neurotrophic factor (BD-NF), cAMP response element binding protein (CREB), B-cell lymphoma-2 (Bcl-2) protein in the hippocampus were detected using Weston blot. Results:when compared to the expression of BDNF, CREB, and Bcl-2 proteins in the controlled group, those in the M1 and M3 groups were significantly decreased ( <0.05), and there was no different changes in those protein in the M2 group. The amounts of BDNF, CREB, and Bcl-2 protein showed no significant difference between the M1 group and M3 group. Conclusion:Different time courses of CUMS might affect the expression of proteins implicated in neuroplasticity, providing insight into the role of neuroplasticity-related proteins in the depression.%目的:探讨不同时程的慢性不可预计温和应激对大鼠海马区神经可塑性相关蛋白水平的影响。方法:24只大鼠随机分为4组,各6只:正常对照组、应激1周组、应激2周组、应激3周组,分别给予应激0、1、2、 3周。采用Western blot 方法检测海马脑源性神经营养因子(BDNF)、cAMP 反应元件结合蛋白(CREB)、B 淋巴细胞瘤-2(Bcl-2)的蛋白水平。结果:与正常对照组对比,应激1周组、应激3周组的BDNF、CREB、 Bcl-2的蛋白水平较低(<0.05),应激2周组无明显差异;应激1周组和应激3周组之间的BDNF、CREB、 Bcl-2蛋白水平无明显差异。结论:海马区的神经可塑性相关蛋白BDNF、CREB、Bcl-2的水平变化可能

  10. CUMS抑郁模型大鼠脑组织DA、5-HT及其代谢产物的浓度变化%Concentration change of DA, 5-HT and their metabolites in brain tissue of depression models rat treated with chronic unpredicted mild stress

    Institute of Scientific and Technical Information of China (English)

    唐亚梅; 陈春梅; 刘勇

    2012-01-01

    Objective We explored the related neurobiochemistry pathomechanism by the comparison of concentration of dopamine(DA), 5-hydroxytryptamine (5-HT) and their metabolites in brain tissue in the Chronic unpredicted mild stress (CUMS)depression model rats. Methods 24 male Spragur-Dawley (SD) rats were randomly assigned to 3 groups: control group, model group and fluoxetine group. CUMS with solitary condition was taken to manufacture depression rat model. After separated the brains tissues of CUMS depression rats, the levels of DA, 5-HT and their metabolites of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray Electrochemic detection for high performance liquid chromatogram (HPLC) technique. Results Compared to contronl group, the levels of DA, homovanillic acid (HVA), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the mPFC of depression model rats have significantly decreased(P<0.01 or 0.05), and the levels of DA, HVA and 5-HT in hippocampus have significantly decreased (P<0.01 or 0.05); Compared to model group, the levels of DA, HVA and 5 -HT in the mPFC of fluoxetine group rats have significantly increased (P<0.01 or 0.05), and the levels of DA, 5 -HT and 5 -HIAA in hippocampus have significantly increased (P <0.05). Conclusion The activity of DA and 5 -HT systems in the mPFC and hippocampus were decreased in CUMS depression model rats.%目的:通过分析抑郁模型大鼠脑组织DA、5-HT及其代谢产物的浓度变化,探讨抑郁症发病的神经生化机制.方法:将24只雄性SD大鼠随机分成对照组、模型组和氟西汀组3组;采用慢性轻度不可预见性应激(CUMS)结合孤养建立抑郁大鼠模型,随后取脑并分离内侧前额皮质(mPFC)和海马,采用库仑阵列电化学高效液相色谱法测定上述脑区DA、5-HT及其代谢产物的浓度.结果:与对照组比较,模型组大鼠mPFC区DA、高香草酸(HVA)、5-HT及5-羟吲哚乙酸(5-HIAA

  11. The effect of repetitive transcranial magnetic stimulation on the changes of depressive like behaviors in chronic unpredictable mild stress model rats and its possible mechanism%重复经颅磁刺激对抑郁模型大鼠行为的改善作用及机制

    Institute of Scientific and Technical Information of China (English)

    刘高华; 陈冠婕; 陈怡环; 杨帆; 张瑞国; 彭正午; 谭庆荣

    2013-01-01

    Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the depressive like behaviors and expression of brain derived neurotrophic factor (BDNF),IL-1β and NF-κB of hippocampal in chronic unpredictable mild stress (CUMS) rats.Methods Thirty-two adult male rats were randomly divided into four groups (n =8):Control group,Control + rTMS group,CUMS group and CUMS + rTMS group.The sucrose preference test,forced swim test and open field test were used to evaluate depressive like behaviors for each groups.In addition,the expression of BDNF,NF-κB and IL-1 β in hippocampal were detected by western blot and ELISA after behavioral test,respectively.Results 1.The effects of rTMS on depressive like behaviors of CUMS rats:in the sucrose preference test,the sucrose preference rate of CUMS rats (0.67 ± 0.06) was significantly lower than Control group (0.91 ± 0.04),which was higher in the CUMS + rTMS group (0.83 ±0.08).In the forced swim test,the immobility time of CUMS group ((26.88 ± 11.33) s) was longer than Control group ((15.22 ± 6.75) s) and CUMS + rTMS group ((18.41 ± 6.95) s).In the open field test,both the total distance travelled and number of central area entry times of CUMS group((849.165 ± 769.01) cm,(7.42 ± 5.68))were significantly shorter ((6224.81 ± 1403.2) cm) and smaller (22.86 ± 3.72) than Control group,and those of the CUMS + rTMS were longer ((4105.57 ± 1516.92)cm) and larger (21.25 ± 3.45).All the behavioral results were statistically significant (P< 0.05).And of all the aforementioned behavioral parameters,there were no significant differences between Control group and Control + rTMS group(P>0.05).2.The effects of rTMS on the hippocampal expressions of BDNF,NF-κB and IL-1β in CUMS rats:compared with Control group,the hippocampal expression of BDNF in CUMS rats was significantly decreased,while the expressions of NF-κB and IL-1β in the hippocampus were significantly increased (P< 0.05).Compared

  12. Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.

    Science.gov (United States)

    Bhatia, Nitish; Jaggi, Amteshwar Singh; Singh, Nirmal; Anand, Preet; Dhawan, Ravi

    2011-07-01

    The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.

  13. 高脂血症叠加慢性不可预见性应激模型大鼠open-field行为学特征分析%Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model

    Institute of Scientific and Technical Information of China (English)

    胡华; 张迎春; 许烨勍; 刘春风; 王立伟

    2015-01-01

    Objective To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS).Methods A total of 40 rats were randomly divided into control (CON),control feed for 9 weeks followed by CUMS for 4 weeks (CON + CUMS),high fat diet (HFD) and high lipid feed for 9 weeks followed by CUMS for 4 weeks (HFD + CUMS) (n =10 each).Open-field test was individually measured at baseline,week 9 and week 13.Results (1) Serum lipids:total cholesterol [(2.67 ± 0.04) mmol/L,(2.68 ± 0.02) mmol/L] and low density lipoprotein [(1.08 ± 0.03) mmol/L,(1.06 ± 0.01) mmol/L] of HFD and HFD + CUMS were both significantly higher than those of CON and CON + CUMS [(1.78 ± 0.12) mmol/L,(0.79 ± 0.04) mmol/L;(1.76 ±0.09)mmol/L,(0.76 ±0.06)mmol/L,all P <0.01].(2) Open-field test:at week 13,compared to CON rats,CON + CUMS rats exhibited enhanced locomotor activity during the first minute,reduced activity in the center squares and rearing,and increased the number of grooming and defecation (all P < 0.05).In comparison to the CON rats,a decrease in total squares in 5 min,central squares and peripheral squares was observed in HFD rats at week 13 (all P < 0.05).However,compared with HFD,CON,CON + CUMS rats,when high lipid feed for 9 weeks combined with depression,significant decrease activities in total squares in 5 min,central squares and peripheral squares were observed in HFD + CUMS rats at week 13.Besides these,the number of rearing was reduced,however,locomotor activity during the first minute and the number of grooming and defecation was significantly increased (all P < 0.001).Conclusion Under uncontrolled hyperlipidemia,severe depressive symptoms will present more early once exposure to a series of chronic stressors followed by significant autonomic nervous dysfunctional symptoms.%目的 观察高脂血症叠加抑郁症大鼠open-field行为学特征.方法 40只SD大鼠按随机数字表法

  14. Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lan-lan; MING Liang; MA Chuan-geng; CHENG Yan; JIANG Qin

    2005-01-01

    Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

  15. Effect on the Expression of IL-1β,IL-6 in Hippocampus and Serum of Depressive Rats with Chronic Unpredictable Mild Stress Treated by Different Electro-acupuncture Treatment%不同电针对慢性应激抑郁模型大鼠海马及血清细胞因子 IL-1β、IL-6表达的影响

    Institute of Scientific and Technical Information of China (English)

    莫雨平; 李志刚; 邓晓丰; 纪倩; 滕金艳; 姚海江; 宋洪涛; 唐银杉; 许安萍; 张淑静

    2014-01-01

    Objective:To investigate the effect on the expression of IL -1β, IL-6 in the hippocampus and ser-um of rats with chronic unpredictable mild stress treated by different electro -acupuncture(EA) treatment, to elucidate the possible role of IL -1β, IL-6 in the development of experimental depression and the effect of different EA for them .Methods:Adult male SD rats were randomly divided into normal control group ( n=12 ) , model group ( n=12 ) , pulsed EA group ( n=12 ) , music EA group ( n=12 ) and fluoxetine group ( n=12 ) . Depressive models were established by lonely raising and chronic unpredictable mild stress for 21 days. Open-field test was performed to test the behavior of rats .The expression of hippocampus and serum IL -1β, IL-6 was detected by using immunohistochemistry and enzyme linked immunosorbent assay ( ELISA ) techniques respectively .Results:The cross and rear score of model group was significantly lower than that in normal control group , while pulsed EA group , music EA group and fluoxetine group could reverse it .The ex-pression of hippocampus and serum IL -1β, IL-6 in model group increased significantly .The three kinds of treatment could improve these pathological change , but there was no difference among these effects of treat-ment .Conclusion:The levels of IL-1β, IL-6 in hippocampus and serum of depressive rats are higher than those in the normal group .EA treatment may have antagonism against depression by lowering the levels of IL-1β, IL-6 in hippocampus and serum ,and there is no difference between the effects of pulsed EA treat-ment and music EA treatment for depression .%目的:观察不同电针对慢性应激抑郁模型( chronic unpredictable mild stress ,CUMS)大鼠海马及血清中细胞因子IL-1β、IL-6表达的影响,探讨IL-1β、IL-6在大鼠实验性抑郁症发病过程中的作用机制及不同电针干预对其影响。方法:将雄性清洁健康级SD大鼠60只,随机分为正常组、模型组

  16. Predictable chronic mild stress improves mood, hippocampal neurogenesis and memory.

    Science.gov (United States)

    Parihar, V K; Hattiangady, B; Kuruba, R; Shuai, B; Shetty, A K

    2011-02-01

    Maintenance of neurogenesis in adult hippocampus is important for functions such as mood and memory. As exposure to unpredictable chronic stress (UCS) results in decreased hippocampal neurogenesis, enhanced depressive- and anxiety-like behaviors, and memory dysfunction, it is believed that declined hippocampal neurogenesis mainly underlies the behavioral and cognitive abnormalities after UCS. However, the effects of predictable chronic mild stress (PCMS) such as the routine stress experienced in day-to-day life on functions such as mood, memory and hippocampal neurogenesis are unknown. Using FST and EPM tests on a prototype of adult rats, we demonstrate that PCMS (comprising 5 min of daily restraint stress for 28 days) decreases depressive- and anxiety-like behaviors for prolonged periods. Moreover, we illustrate that decreased depression and anxiety scores after PCMS are associated with ~1.8-fold increase in the production and growth of new neurons in the hippocampus. Additionally, we found that PCMS leads to enhanced memory function in WMT as well as NORT. Collectively, these findings reveal that PCMS is beneficial to adult brain function, which is exemplified by increased hippocampal neurogenesis and improved mood and cognitive function.

  17. Predictable chronic mild stress in adolescence increases resilience in adulthood.

    Science.gov (United States)

    Suo, Lin; Zhao, Liyan; Si, Jijian; Liu, Jianfeng; Zhu, Weili; Chai, Baisheng; Zhang, Yan; Feng, Jiajia; Ding, Zengbo; Luo, Yixiao; Shi, Haishui; Shi, Jie; Lu, Lin

    2013-07-01

    Stress in adolescence has been widely demonstrated to have a lasting impact in humans and animal models. Developmental risk and protective factors play an important role in the responses to stress in adulthood. Mild-to-moderate stress in adolescence may resist the negative impacts of adverse events in adulthood. However, little research on resilience has been conducted. In this study, we used a predictable chronic mild stress (PCMS) procedure (5 min of daily restraint stress for 28 days) in adolescent rats (postnatal days (PNDs) 28-55) to test the resilience effect of PCMS on depressive-like behavior in the sucrose preference test and forced swim test and anxiety-like behavior in the novelty-suppressed feeding test and elevated plus maze in adulthood. We also investigated the role of mammalian target of rapamycin (mTOR) signaling in the brain during the PCMS procedure in adolescence. Moreover, we investigated the effect of PCMS in adolescence on subsequent responses to chronic unpredictable stress (CUS; PNDs 63-83) in adulthood. The results demonstrated that PCMS during adolescence produced antidepressant- and anxiolytic-like effects and increased mTOR signaling activity in the prefrontal cortex in early adulthood. Either systemic administration or intra-PFC infusion of the mTOR inhibitor rapamycin completely blocked the behavioral effects produced by PCMS in adolescence. PCMS during adolescence resisted depressive- and anxiety-like behavior caused by CUS in adulthood. These findings indicate that PCMS in adolescence can contribute to resilience against depression and anxiety caused by stress in adulthood.

  18. Chronic Mild Prenatal Stress Exacerbates the Allergen-Induced Airway Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Paulo J. Nogueira

    1999-01-01

    Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

  19. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders;

    2010-01-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core...

  20. Does Chronic Unpredictable Stress during Adolescence Affect Spatial Cognition in Adulthood?

    Directory of Open Access Journals (Sweden)

    Lauren E Chaby

    Full Text Available Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner.

  1. Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

    Science.gov (United States)

    Fokos, S; Panagis, G

    2010-05-01

    Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behaviour, the reinforcing attributes of these subjective effects are difficult to define in experimental animals. The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats. Male rats were exposed to either 10 days of CUS or no stressor. Alterations in brain reward function were assessed with the intracranial self-stimulation (ICSS) paradigm, and anxiety responses were measured with the elevated plus maze. CUS did not affect baseline brain stimulation reward thresholds. Delta(9)-THC did not exhibit reinforcing actions in the ICSS paradigm neither in nonstressed nor in stressed animals. More importantly, in nonstressed animals, both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects. In stressed animals, however, only the high dose of THC induced an anxiolytic-like response, whereas the low dose induced anxiogenic effects. The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals, and indicate that environmental conditions, such as stressful experiences, do not alter the behavioural effects of Delta( 9)-THC in the ICSS paradigm.

  2. Does Chronic Unpredictable Stress during Adolescence Affect Spatial Cognition in Adulthood?

    Science.gov (United States)

    Chaby, Lauren E; Sheriff, Michael J; Hirrlinger, Amy M; Lim, James; Fetherston, Thomas B; Braithwaite, Victoria A

    2015-01-01

    Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner.

  3. Learning, memory, and glial cell changes following recovery from chronic unpredictable stress.

    Science.gov (United States)

    Bian, Yanqing; Pan, Zhuo; Hou, Ziyuan; Huang, Cui; Li, Wei; Zhao, Baohua

    2012-08-01

    Previous research has indicated that chronic stress induces inflammatory responses, cognitive impairments, and changes in microglia and astrocytes. However, whether stress-induced changes following recovery are reversible is unclear. The present study examined the effects of chronic unpredictable stress (CUS) following recovery on spatial learning and memory impairments, changes in microglia and astrocytes, and interleukine-1β (IL-1β) and glial-derived neurotrophic factor (GDNF) levels. Mice were randomly divided into control, stress, and recovery groups, and CUS was applied to mice in the stress and recovery groups for 40 days. Following the application of CUS, the recovery group was allowed 40 days without stress. The results of the Morris water maze illustrated that CUS-induced spatial learning and memory impairments could be reversed or even improved by a period of recovery. Immunohistochemical tests revealed that CUS-induced alterations in microglia could dissipate with time in the CA3 region of the hippocampus and prelimbic areas. However, CUS-induced activation of astrocytes was sustained in the CA3 area following recovery. Western blot analyses revealed that CUS induced a significant increase of GDNF and a significant decrease in IL-1β. Additionally, increased GDNF levels were sustained in the hippocampus during recovery. In conclusion, this study provides evidence that CUS-induced learning and memory impairments could be reversible following recovery. However, activated astrocytes and increased GDNF levels in the hippocampus remained elevated after recovery, suggesting that activated astrocytes and increased GDNF play important roles in the adaptation of the brain to CUS and in repairing CUS-induced impairments during recovery.

  4. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    Science.gov (United States)

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

  5. The chronic mild stress (CMS) model of depression: History, evaluation and usage.

    Science.gov (United States)

    Willner, Paul

    2017-02-01

    Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

  6. Effects of fluoxetine on protein expression of potassium ion channels in the brain of chronic mild stress rats

    OpenAIRE

    Chunlin Chen; Ling Wang; Xianfang Rong; Weiping Wang; Xiaoliang Wang

    2015-01-01

    The purpose of this study is to investigate the expression of major potassium channel subtypes in the brain of chronical mild stress (CMS) rats and reveal the effects of fluoxetine on the expression of these channels. Rats were exposed to a variety of unpredictable stress for three weeks and induced anhedonia, lower sucrose preference, locomotor activity and lower body weight. The protein expressions were determined by Western blot. CMS significantly increased the expression of Kv2.1 channel ...

  7. Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence

    Directory of Open Access Journals (Sweden)

    Lauren eChaby

    2013-07-01

    Full Text Available Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid stress hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g. isolation, crowding, cage tilt were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias (F1,12 = 5.000, P < 0.05, altered coping response (T1,14 = 2.216, P = 0.04, and accelerated decision making (T1,14 = 3.245, P = 0.01. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object (T1,14 = 2.240, P = 0.04; T1,14 = 2.419, P = 0.03, respectively. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions. Stress during adolescence also induced short-term changes in the way animals moved around a novel environment.

  8. Octreotide ameliorates gastric lesions in chronically mild stressed rats

    Institute of Scientific and Technical Information of China (English)

    Noha N Nassar; Mona F Schaalan; Hala F Zaki; Dalaal M Abdallah

    2011-01-01

    AIM: To evaluate the effect of chronic mild stress (CMS) on the emergence of gastric ulcers and possible modulation by octreotide, a synthetic somatostatin analogue. METHODS: Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d, a multifactorial interactional animal model for CMS. Octreotide was administered daily for 21 d at two dose levels (50 and 90 μg/kg) before exposure to stress procedure. Macro-and microscopical assessments were made, in addition to quantification of plasma corticosterone and gastric mucosal inflammatory, oxidative stress, and apoptotic biomarkers. RESULTS: Exposure to CMS elevated plasma corticosterone (28.3 ± 0.6 μg/dL, P = 0.002), an event that was accompanied by gastric lesions (6.4 ± 0.16 mm,P = 0.01) and confirmed histopathologically. Moreover, the insult elevated gastric mucosal lipid peroxides (13 ± 0.5 nmol/g tissue, P = 0.001), tumor necrosis factor-α(3008.6 ± 78.18 pg/g tissue, P < 0.001), prostaglandin E2 (117.1 ± 4.31 pg/g tissue, P = 0.002), and caspase-3 activity (2.4 ± 0.14 OD/mg protein, P = 0.002). Conversely, CMS mitigated interleukin-10 (627.9 ± 12.82 pg/g tissue, P = 0.001). Furthermore, in animals exposed to CMS, octreotide restored plasma corticosterone (61% and 71% from CMS, P = 0.002) at both dose levels. These beneficial effects were associated with a remarkable suppression of gastric lesions (38% and 9% from CMS, P = 0.01) and reversal of derangements in gastric mucosa. CONCLUSION: The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant, anti-inflammatory, and anti-apoptotic actions.

  9. Chronic mild stress impact: are females more vulnerable?

    Science.gov (United States)

    Dalla, C; Antoniou, K; Drossopoulou, G; Xagoraris, M; Kokras, N; Sfikakis, A; Papadopoulou-Daifoti, Z

    2005-01-01

    Despite the knowledge that women are more susceptible than men to stress-related mental illness, such as major depression, there is no comprehensive estimation of the role of gender in the detrimental effects of chronic stress that might cause depression. Sex differences regarding the association of behavioral parameters with serotonergic and hypothalamic-pituitary-adrenal axis activities were investigated in the chronic mild stress model of depression. Additionally, the impact of chronic mild stress exposure on an additional/novel short-term stressful procedure, such as the forced swim test was examined in male and female rats. Female rats were found to be more vulnerable to chronic mild stress and that was depicted with disruption of sucrose intake, decreases in open field activity, increased corticosterone levels, alteration in estrous cycle and decreased serotonergic activity in hippocampus and hypothalamus. On the contrary, in males the current chronic mild stress protocol elicited only behavioral changes, such as disruption in sucrose intake and decreased open field activity. Interestingly, in response to forced swim test, females previously subjected to chronic mild stress, were found to cope better by exhibiting increased active behavior in the second forced swim test session and higher hypothalamic serotonergic activity in comparison with corresponding males. On the other hand, males were more affected by previous chronic mild stress exposure and that was manifested by decreased active behavior in the first forced swim test session and increased corticosterone levels following second forced swim test session. These data indicate that although females are more vulnerable in the application of chronic mild stress than males, in response to an additional-novel stressor (forced swim test) they show better response. Therefore, both sex/gender and combination of stressful procedures should be carefully considered in the study of the pathophysiology of stress

  10. Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats

    Institute of Scientific and Technical Information of China (English)

    YIN Yan-yan; MING Liang; ZHENG Li-fang; KAN Hong-wei; LI Chun-ru; LI Wei-ping

    2007-01-01

    Background A bioactive compound from Paecilomyces tenuipes (BGPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress(CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.Methods The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21.Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone(CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.Results Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.Conclusions BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.

  11. Predictable Chronic Mild Stress in Adolescence Increases Resilience in Adulthood

    OpenAIRE

    Suo, Lin; Zhao, Liyan; Si, Jijian; Liu, Jianfeng; Zhu, Weili; Chai, Baisheng; Zhang, Yan; Feng, Jiajia; Ding, Zengbo; Luo, Yixiao; Shi, Haishui; Shi, Jie; Lu, Lin

    2013-01-01

    Stress in adolescence has been widely demonstrated to have a lasting impact in humans and animal models. Developmental risk and protective factors play an important role in the responses to stress in adulthood. Mild-to-moderate stress in adolescence may resist the negative impacts of adverse events in adulthood. However, little research on resilience has been conducted. In this study, we used a predictable chronic mild stress (PCMS) procedure (5 min of daily restraint stress for 28 days) in a...

  12. Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced...... anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d...... changes in CMS rat brains and these parameters might have value in clinical diagnosis of depression and for evaluation of treatment efficacy....

  13. 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.

  14. Reversion of BDNF, Akt and CREB in Hippocampus of Chronic Unpredictable Stress Induced Rats: Effects of Phytochemical, Bacopa Monnieri

    Science.gov (United States)

    Hazra, Somoday; Kumar, Sourav; Saha, Goutam Kumar

    2017-01-01

    Objective The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. Methods We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). Results Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. Conclusion These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior. PMID:28096878

  15. Sex differences in response to chronic mild stress and congenital serotonin deficiency.

    Science.gov (United States)

    Sachs, Benjamin D; Ni, Jason R; Caron, Marc G

    2014-02-01

    Women exhibit a nearly twofold increased risk of developing depression and anxiety disorders when compared to men, a fact that has been hypothesized to result in part from increased stress susceptibility. Here, we used the tryptophan hydroxylase-2 R439H knock-in mouse (Tph2KI) and the chronic unpredictable mild stress (CMS) model to examine sex differences in response to congenital 5-HT deficiency and chronic stress. Our results demonstrate that female mice, but not 5-HT-deficient animals, exhibit significantly increased susceptibility to CMS-induced despair-like behavior in the forced swim test. In addition, female 5-HT-deficient mice exhibit anhedonia-like behavior in the sucrose preference test, whereas male 5-HT-deficient animals do not, suggesting that females exhibit increased sensitivity to at least some of the effects of congenital 5-HT deficiency. Although CMS did not reduce cell proliferation in the hippocampus, low levels of brain 5-HT were associated with increased hippocampal cell proliferation, an effect that was predominantly observed in females. Overall, these results highlight the importance of interactions between psychiatric disease risk factors such as sex, chronic stress and congenital 5-HT deficiency in the development of aberrant emotional behavior.

  16. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment.

    Science.gov (United States)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders; Sandi, Carmen

    2010-10-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core symptom of depression, was assessed by measuring consumption of a palatable solution. Exposure to CUS reduced intake of a palatable solution and this effect was prevented by chronic antidepressant treatment. Moreover, chronic antidepressant treatment decreased depressive-like behavior in a modified forced swim test in stressed rats. Present evidence suggests a role for brain-derived neurotrophic factor (BDNF) in depression. BDNF mRNA levels in the ventral and dorsal hippocampus were assessed by in situ hybridization. Exposure to CUS was not correlated with a decrease but rather with an increase in BDNF mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity.

  17. Influence of housing on the consequences of chronic mild stress in female rats.

    Science.gov (United States)

    Baker, S; Bielajew, C

    2007-08-01

    The chronic mild stress (CMS) paradigm was developed to model anhedonia in animals. The repeated administration of a series of unpredictable, mild stressors attempts to mimic the daily stress associated with the onset of clinical depression in humans. Male animals are predominantly used in these investigations despite significant, well-documented sex differences in human depression. In this study, the CMS procedure was modified to be more ecologically relevant to female animals. The effects of stress on sucrose preference, social interaction, rate of weight gain, and regularity of the estrous cycle in female Sprague-Dawley (SD) rats were evaluated in both single- and paired-housed rats, during 3 weeks each of baseline, CMS, and post-CMS phases. The results indicate that only single-housed rats exposed to stressors have a reduced rate of weight gain, significantly attenuated sucrose preference levels, and increased social interaction scores during the CMS phase of the study. Housing condition more than exposure to stress appeared to contribute to the disruption of estrous cycling in some animals. These data suggest that housing affords some protection from the negative consequences of CMS, at least in female rats, and that lack of social interaction in the single-housing condition may render females more vulnerable to stress-related illnesses. The development of paradigms that model human depression should emphasize sex-specific differences.

  18. Testosterone has antidepressant-like efficacy and facilitates imipramine-induced neuroplasticity in male rats exposed to chronic unpredictable stress.

    Science.gov (United States)

    Wainwright, Steven R; Workman, Joanna L; Tehrani, Amir; Hamson, Dwayne K; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

    2016-03-01

    Hypogonadal men are more likely to develop depression, while testosterone supplementation shows antidepressant-like effects in hypogonadal men and facilitates antidepressant efficacy. Depression is associated with hypothalamic-pituitary-adrenal (HPA) axis hyperactivity and testosterone exerts suppressive effects on the HPA axis. The hippocampus also plays a role in the feedback regulation of the HPA axis, and depressed patients show reduced hippocampal neuroplasticity. We assessed the antidepressant-like effects of testosterone with, or without, imipramine on behavioral and neural endophenotypes of depression in a chronic unpredictable stress (CUS) model of depression. A 21-day CUS protocol was used on gonadectomized male Sprague-Dawley rats treated with vehicle, 1mg of testosterone propionate, 10mg/kg of imipramine, or testosterone and imipramine in tandem. Testosterone treatment reduced novelty-induced hypophagia following CUS exposure, but not under non-stress conditions, representing state-dependent effects. Further, testosterone increased the latency to immobility in the forced swim test (FST), reduced basal corticosterone, and reduced adrenal mass in CUS-exposed rats. Testosterone also facilitated the effects of imipramine by reducing the latency to immobility in the FST and increasing sucrose preference. Testosterone treatment had no significant effect on neurogenesis, though the combination of testosterone and imipramine increased PSA-NCAM expression in the ventral dentate gyrus. These findings demonstrate the antidepressant- and anxiolytic-like effects of testosterone within a CUS model of depression, and provide insight into the mechanism of action, which appears to be independent of enhanced hippocampal neurogenesis.

  19. 3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

    Directory of Open Access Journals (Sweden)

    Laura Andrea León A

    2013-01-01

    Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

  20. Chronic post-traumatic headache after mild head injury

    DEFF Research Database (Denmark)

    Kjeldgaard, Dorte; Forchhammer, Hysse; Teasdale, Tom

    2014-01-01

    to or above the cut-off score for having post-traumatic stress disorder (PTSD) according to the HTQ. In terms of demographics and headache, the groups were comparable except the CPTH group were more often without affiliation to the labour market ( P ...BACKGROUND: The aetiology behind chronic post-traumatic headache (CPTH) after mild head injury is unclear and management is complicated. In order to optimize treatment strategies we aimed to characterize a CPTH population. METHODS: Ninety patients with CPTH and 45 patients with chronic primary...... headaches were enrolled from the Danish Headache Center. All patients were interviewed about demographic and headache data. They completed the Harvard Trauma Questionnaire (HTQ), Rivermead Post Concussion Symptoms Questionnaire, SF-36 and a headache diary. RESULTS: The CPTH group experienced more cognitive...

  1. Cannabinoid modulation of chronic mild stress-induced selective enhancement of trace fear conditioning in adolescent rats.

    Science.gov (United States)

    Reich, Christian G; Iskander, Anthony N; Weiss, Michael S

    2013-10-01

    History of stress is considered a major risk factor for the development of major depression and posttraumatic stress disorder (PTSD). Elucidating the neurobiological mechanisms of Pavlovian fear conditioning may provide insight into the etiology of PTSD. In the current study, adolescent male Sprague-Dawley rats were exposed to 3 weeks of a chronic-mild-unpredictable stress (CMS) protocol. Immediately following the CMS, the animals were subjected to hippocampal-dependent (trace and contextual) and hippocampal-independent (delay) fear conditioning. CMS exposure enhanced trace freezing behavior compared to non-stress controls. This effect was not observed in contextual or delay conditioned animals. Given that the endocannabinoid system is negatively affected by CMS procedures, separate groups of stressed rats were administered the CB1 receptor agonist, ACEA (0.1 mg/kg), prior to trace fear conditioning or a memory-recall test. Regardless of administration time, ACEA significantly reduced freezing behavior in stressed animals. Furthermore, when administered during the first memory recall test, ACEA enhanced long-term extinction in both stress and non-stress groups. The results demonstrate that chronic unpredictable stress selectively enhances hippocampal-dependent episodic fear memories. Pathologies of the episodic memory and fear response may increase the susceptibility of developing PTSD. Reduction in fear responses via exogenous activation of the CB1 receptor suggests that a deficiency in the endocannabinoid system contributes to this pathology.

  2. Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

    Science.gov (United States)

    Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

    2015-04-01

    Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory.

  3. Differential effects of tianeptine on the dorsal hippocampal volume of rats submitted to maternal separation followed by chronic unpredictable stress in adulthood.

    Science.gov (United States)

    Pollano, Antonella; Zalosnik, María I; Durando, Patricia E; Suárez, Marta M

    2016-11-01

    Early maternal separation (MS) may produce lasting effects in the dorsal hippocampus (DH) that can change its response to chronic stress in adulthood. Chronic stress affects DH morphology and function, but tianeptine (an anti-depressant) can reverse the stress-induced morphological impairments. Morphologic alterations of hippocampus can affect contextual memory. Therefore, we evaluated the effect of tianeptine in MS and chronically stressed rats on: 1) volume of the DH and its areas using stereology and 2) hippocampal-dependent memory using a fear conditioning test. Male Wistar rats were subjected to daily MS for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50 and 74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle, providing eight groups: AFR-unstressed/vehicle (n = 5 for stereology, n = 18 for fear conditioning test); AFR unstressed/tianeptine (n = 6 and n = 10); AFR-chronic stress/vehicle (n = 6 and n = 14); AFR-chronic stress/tianeptine (n = 6 and n = 10), MS-unstressed/vehicle (n = 5 and n = 19), MS-unstressed/tianeptine (n = 6 and n = 10), MS-chronic stress/vehicle (n = 6 and n = 18), and MS-chronic stress/tianeptine (n = 6 and n = 10). MS-chronic stress/tianeptine rats showed a diminished CA1 area than the corresponding MS-unstressed/tianeptine rats. The combination of stressors produced a freezing response similar to those of the control group during postconditioning. During retrieval, MS led to a diminished freezing response compared to the AFR-unstressed groups. Tianeptine had no effect on freezing behavior. Our results show that tianeptine can affect the CA1 area volume differently depending on the nature and quantity of stressors but cannot alter freezing to context.

  4. Region-specific changes in activities of cell death-related proteases and nitric oxide metabolism in rat brain in a chronic unpredictable stress model.

    Science.gov (United States)

    Tishkina, Anna; Rukhlenko, Alexey; Stepanichev, Mikhail; Levshina, Irina; Pasikova, Natalia; Onufriev, Mikhail; Moiseeva, Yulia; Piskunov, Alexey; Gulyaeva, Natalia

    2012-12-01

    Effects of a chronic combined unpredictable stress on activities of two cell death-related proteases, calpain and cathepsin B, were studied along with indices of nitrergic system in rat brain structures. Male Wistar rats were subjected to a 2-week-long combined stress (combination of unpaired flash light and moderate footshock associated with a white noise session). Stress resulted in a significant loss in the body and thymus weight and increased defecation in the open field test, though neither motor and exploratory activity, nor plasma corticosterone differed from the respective control levels. Decreased calpain activity and increased cathepsin B activity were demonstrated in the hippocampus of stressed rats (previously we have shown that caspase-3 activity was significantly suppressed in the brain of rats subjected to same type of stress). A significant reduction in the number of NOS-containing neurons was accompanied by a chronic stressinduced decline in NOS activity in the neocortex. Similar changes were observed in the hippocampus. However, levels of NO metabolites were elevated in both structures. Thus, stress-induced structural modifications in the brain may be mediated by disturbances in the nitrergic system and increased lysosomal proteolysis.

  5. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  6. Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

    Science.gov (United States)

    Zhao, Jing; Jung, Yang-Hee; Jang, Choon-Gon; Chun, Kwang-Hoon; Kwon, Sung Won; Lee, Jeongmi

    2015-03-01

    Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

  7. Chronic effect of ketanserin in mild to moderate essential hypertension.

    Science.gov (United States)

    Woittiez, A J; Wenting, G J; van den Meiracker, A H; Ritsema van Eck, H J; Man in't Veld, A J; Zantvoort, F A; Schalekamp, M A

    1986-02-01

    Ketanserin, an antagonist highly selective for 5-hydroxytryptamine (serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate essential hypertension. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate essential hypertension.

  8. Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappaB in the frontal cortex and hippocampus via glucocorticoid secretion.

    Science.gov (United States)

    Munhoz, Carolina Demarchi; Lepsch, Lucilia B; Kawamoto, Elisa Mitiko; Malta, Marília Brinati; Lima, Larissa de Sá; Avellar, Maria Christina Werneck; Sapolsky, Robert M; Scavone, Cristoforo

    2006-04-01

    Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. The transcription factor nuclear factor-kappaB (NF-kappaB), which is inhibited by GCs, regulates numerous genes central to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (LPS)-induced activation of NF-kappaB in the brain were investigated. One day after chronic unpredictable stress (CUS), nonstressed and CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated the increase in LPS-induced activation of NF-kappaB in frontal cortex and hippocampus but not in the hypothalamus. This stress effect was blocked by pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA receptor antagonist, also reduced the effect of LPS in all three brain regions. However, the combined antagonism of both GC and NMDA receptors produced no further reduction in NF-kappaB activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-kappaB activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs.

  9. The Relation of Mild Traumatic Brain Injury to Chronic Lapses of Attention

    Science.gov (United States)

    Pontifex, Matthew B.; Broglio, Steven P.; Drollette, Eric S.; Scudder, Mark R.; Johnson, Chris R.; O'Connor, Phillip M.; Hillman, Charles H.

    2012-01-01

    We assessed the extent to which failures in sustained attention were associated with chronic mild traumatic brain injury (mTBI) deficits in cognitive control among college-age young adults with and without a history of sport-related concussion. Participants completed the ImPACT computer-based assessment and a modified flanker task. Results…

  10. Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats

    DEFF Research Database (Denmark)

    Hougaard, K.S.; Mandrup, Karen; Kjaer, S.L.;

    2011-01-01

    from dams exposed to chronic mild stress (CMS) during gestation. In humans, decreased PPI has been reported to be associated with anxiety. Because of its potential translational value across species, the modulation of startle reactivity may be a useful tool in examining altered emotional reactivity...

  11. Clinical Studies on Treatment of Chronic Prostatitis with Acupuncture and Mild Moxibustion

    Institute of Scientific and Technical Information of China (English)

    Yu Yang; Kang Jingli; Duan Shumin

    2005-01-01

    To observe the therapeutic effect of acupuncture and mild moxibustion on chronic prostatitis and to probe into the mechanism of the therapy. Two hundred patients with chronic prostatitis were randomly divided into two groups so as to observe respectively the changes in clinical symptoms, count of WBC and lecithin corpuscles in succus prostaticus, prostatic capcules and internal echo, tenderness and elasticity of prostate by palpation before and after treatment. After treatment, a remarkable improvement was found in clinical symptoms, succus prostaticus test and ultrasonic examination in the treatment group with a statistically significant difference (P<0.05) as compared to the control group. The treatment of chronic prostatitis with acupuncture and mild moxibustion can remove the stagnation of succus prostaticus, improve the blood circulation in prostate, inhibit or kill the pathogenic micro-organisms, strengthen or regulate the immune function of the patients, improve local blood circulation, eliminate the accumulation of secretion and relieve the obstruction of the prostatic ducts.

  12. Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen long-fin zebrafish: stronger effects in the resting phase than in the active phase.

    Science.gov (United States)

    Manuel, Remy; Gorissen, Marnix; Zethof, Jan; Ebbesson, Lars O E; van de Vis, Hans; Flik, Gert; van den Bos, Ruud

    2014-11-01

    Zebrafish (Danio rerio Hamilton) are increasingly used as a model to study the effects of chronic stress on brain and behaviour. In rodents, unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than during the resting phase. Here, we applied UCS during the daytime (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house-reared Tuebingen long-fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3 day protocol where fish learn to avoid swimming from a white to a black compartment where they will receive a 3 V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon were quantified. Following 14 days of UCS during the day, inhibitory avoidance learning decreased (lower latencies on days 2 and 3); minor effects were found following 7 days of UCS. Following 7 nights of UCS, inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared with controls (100%) from 7 days of UCS (139%), to 14 days of UCS (174%) to 7 nights of UCS (231%), suggestive of an increasing stress load. Only in the 7 nights of UCS group did expression levels of corticoid receptor genes (mr, grα, grβ) and of bdnf increase. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and as being indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress axis-related genes, especially grβ; in mammals this receptor has been implicated in

  13. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    Institute of Scientific and Technical Information of China (English)

    Massimo; Sartori; Silvano; Andorno; Angelo; Rossini; Renzo; Boldorini; Cristina; Bozzola; Stefania; Carmagnola; Mario; Del; Piano; Emanuele; Albano

    2010-01-01

    AIM:To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C(CHC). METHODS:We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to,or unsuitable for,antiviral therapy who underwent mild iron depletion(ferritin≤70 ng/mL) by long-term phlebotomy.Histological improvement,as defined by at least one point reduction in the staging score or,in case...

  14. Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain.

    Science.gov (United States)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove; Kroenke, Christopher D; Nyengaard, Jens R; Hansen, Brian; Jespersen, Sune Nørhøj

    2016-11-15

    Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d-MRI) analyses, such as neurite density and diffusion kurtosis imaging (DKI), are able to capture microstructural changes and are considered to be robust tools in preclinical and clinical imaging. The present study utilized d-MRI analyzed with a neurite density model and the DKI framework to investigate microstructure in the hippocampus, prefrontal cortex, caudate putamen and amygdala regions of CMS rat brains by comparison to brains from normal controls. To validate findings of CMS induced microstructural alteration, histology was performed to determine neurite, nuclear and astrocyte density. d-MRI based neurite density and tensor-based mean kurtosis (MKT) were significantly higher, while mean diffusivity (MD), extracellular diffusivity (Deff) and intra-neurite diffusivity(DL) were significantly lower in the amygdala of CMS rat brains. Deff was also significantly lower in the hippocampus and caudate putamen in stressed groups. Histological neurite density corroborated the d-MRI findings in the amygdala and reductions in nuclear and astrocyte density further buttressed the d-MRI results. The present study demonstrated that the d-MRI based neurite density and MKT can reveal specific microstructural changes in CMS rat brains and these parameters might have value in clinical diagnosis of depression and for evaluation of treatment efficacy.

  15. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  16. Contextual fear induced by unpredictability in a human fear conditioning preparation is related to the chronic expectation of a threatening US

    NARCIS (Netherlands)

    Vansteenwegen, D.; Iberico, C.; Vervliet, B.; Hermans, D.

    2008-01-01

    The present study was set up to investigate cued and contextual fear in situations of (un)predictability in a human fear conditioning paradigm. Forty-nine participants were presented with two different contexts (switching on and off the central lighting of the experimental room). In the predictable

  17. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats.

    Science.gov (United States)

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6-7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.

  18. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats.

    Directory of Open Access Journals (Sweden)

    María del Consuelo Figueroa-García

    Full Text Available It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6-7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.

  19. Cognitive deficits in the rat chronic mild stress model for depression: relation to anhedonic-like responses

    DEFF Research Database (Denmark)

    Henningsen, Kim; Andreasen T., Jesper; Bouzinova, Elena V.

    2009-01-01

    The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviours in laboratory rats. The aim of the present study was to examine the effects of chronic stress on cognitive performance. About 70% of rats exposed to 7 weeks of chronic mild stress showed a gradual reduction...... in consumption of a sucrose solution, indicating an anhedonic-like state. The remaining rats did not reduce their sucrose intake, but appeared resilient to the stress-induced effects on sucrose intake. Cognitive profiling of the CMS rats revealed that chronic stress had a negative effect on performance...

  20. Diagnosis of mild chronic pancreatitis (Cambridge classification): Comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the usefulness of secretin injection MRCP for the diagnosis of mild chronic pancreatitis. METHODS: Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. RESULTS: The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44%and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. CONCLUSION: Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

  1. Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Bødtkjer, Donna Marie Briggs; Kudryavtseva, Olga;

    2014-01-01

    OBJECTIVE: Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including......-like response) was reduced in anhedonic rats (p depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed...... endothelium-dependent hyperpolarization-like relaxation despite up-regulation of the NO and COX-2-dependent pathways in rat mesenteric arteries. These changes could affect peripheral resistance and organ perfusion in major depression....

  2. Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress

    DEFF Research Database (Denmark)

    Henningsen, K; Woldbye, D P D; Wiborg, O

    2013-01-01

    Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown...... to reverse a depression-like state in the chronic mild stress model of depression (CMS), but the effect of ECS on cognition has not previously been investigated. In this study the CMS model was used to induce a depressive-like condition in rats. The study was designed to investigate the acute effect of ECS...

  3. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

    DEFF Research Database (Denmark)

    Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L;

    1995-01-01

    /I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...

  4. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

    DEFF Research Database (Denmark)

    Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L

    1995-01-01

    Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml.min-1.1.73 m-2 (11-43) (median, range) and 15 sex, age, and body mass index matched....../I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...

  5. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    Science.gov (United States)

    Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

    2010-01-01

    AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

  6. Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

    OpenAIRE

    Giusti B; Marini M; Rossi L; Lapini I; Magi A; Capalbo A; Lapalombella R; di Tullio S; Samaja M; Esposito F; Margonato V; Boddi M; Abbate R; Velcsteinas A

    2009-01-01

    Abstract: Background: Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after ...

  7. Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

    OpenAIRE

    Esposito Fabio; Samaja Michele; di Tullio Simona; Lapalombella Rosa; Capalbo Andrea; Magi Alberto; Lapini Ilaria; Rossi Luciana; Marini Marina; Giusti Betti; Margonato Vittoria; Boddi Maria; Abbate Rosanna; Veicsteinas Arsenio

    2009-01-01

    Abstract Background Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after th...

  8. Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain.

    Science.gov (United States)

    Li, Ruipeng; Wang, Xiangxiang; Qin, Tingting; Qu, Rong; Ma, Shiping

    2016-01-01

    Increasing evidence suggests that inflammation and oxidative stress may contribute to the development of major depressive disorder (MDD). Apigenin, a type of bioflavonoid widely found in citrus fruits, has a number of biological actions including anti-inflammatory and antioxidant effects. Although apigenin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study aims to investigate the effects of apigenin on behavioral changes and inflammatory responses induced by chronic unpredictable mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor, was administered 30 min before apigenin. We found that treatment with apigenin (20mg/kg, intragastrically) for three weeks remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased locomotor activity and reduced sucrose consumption. In response to oxidative stress, the NLRP3 inflammasome was activated and IL-1β secretion increased in the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated PPARγ expression and downregulated the expression of NLRP3, which subsequently downregulated the production of IL-1β. In addition, GW9662 diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In conclusion, our results demonstrate that apigenin exhibits antidepressant-like effects in CUMS rats, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression via the up-regulation of PPARγ expression.

  9. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.

  10. DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

    Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...... validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian...

  11. Treatment of a mild chronic case of ciguatera fish poisoning with intravenous mannitol, a case study.

    Science.gov (United States)

    Mitchell, Gary

    2005-03-01

    This article describes a recent case of ciguatera poisoning treated with intravenous mannitol. Mannitol has been used with good effect in non-controlled studies in acutely severely poisoned patients, but is not described in the treatment of chronic or milder poisoning. Our patient was a 35-year-old Niuean man who had eaten a ciguatoxic fish two weeks previously. His symptoms were not severe but were very unpleasant and restricted his ability to work. He was given a single dose of mannitol (0.66g/kg) as an intravenous infusion over two hours. His symptoms dramatically improved within 24 hours, and within a few days he felt virtually back to his former self. He experienced no side effects to the mannitol. It is suggested that intravenous mannitol may prove to be a useful treatment for mild to moderate ciguatera poisoning, and for patients who present late for treatment.

  12. Cardiac response to exercise in mild-to-moderate chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    Hao-Yan Wang; Qiu-Fen Xu; Yao Xiao

    2009-01-01

    Objective Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular problem.The symptom of dyspnea on exertion may be associated with pulmonary dysfunction or heart failure, or both. The study objective was to determine whether cardiac dysfunction adds to the mechanism of dyspnea caused mainly by impaired lung function in patients with mild-to-moderate COPD. Methods Patients with COPD and healthy controls performed incremental and constant work rate exercise testing. Venous blood samples were collected in 19 COPD patients and 10 controls before and during constant work exercise for analysis of N-terminal-pro-BNP (NT-pro-BNP). Results Peak oxygen uptake and constant work exercise time (CWET) were significantly lower in COPD group than in control group (15.81±3.65 vs 19.19a±6.16 ml/min kg, P=0.035 and 7.78±6.53 rain vs 14.77±7.33 min, P=0.015, respectively). Anaerobic threshold, oxygen pulse and heart rate reserve were not statistically significant between COPD group and control group. The NT-pro-BNP levels both at rest and during constant work exercise were higher in COPD group compared to control group, but without statistical significance. The correlations between CWET and NT-proBNP at rest or during exercise in patients with COPD were not statistically significant. Conclusions Heart failure does not contribute to exercise intolerance in mild-to-moderate COPD.

  13. Association between macular degeneration and mild to moderate chronic kidney disease

    Science.gov (United States)

    Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen

    2017-01-01

    Abstract Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264–1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218–1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients. PMID:28296786

  14. Chronic mild stress alters circadian expressions of molecular clock genes in the liver.

    Science.gov (United States)

    Takahashi, Kei; Yamada, Tetsuya; Tsukita, Sohei; Kaneko, Keizo; Shirai, Yuta; Munakata, Yuichiro; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Hasegawa, Yutaka; Sawada, Shojiro; Oka, Yoshitomo; Katagiri, Hideki

    2013-02-01

    Chronic stress is well known to affect metabolic regulation. However, molecular mechanisms interconnecting stress response systems and metabolic regulations have yet to be elucidated. Various physiological processes, including glucose/lipid metabolism, are regulated by the circadian clock, and core clock gene dysregulation reportedly leads to metabolic disorders. Glucocorticoids, acting as end-effectors of the hypothalamus-pituitary-adrenal (HPA) axis, entrain the circadian rhythms of peripheral organs, including the liver, by phase-shifting core clock gene expressions. Therefore, we examined whether chronic stress affects circadian expressions of core clock genes and metabolism-related genes in the liver using the chronic mild stress (CMS) procedure. In BALB/c mice, CMS elevated and phase-shifted serum corticosterone levels, indicating overactivation of the HPA axis. The rhythmic expressions of core clock genes, e.g., Clock, Npas2, Bmal1, Per1, and Cry1, were altered in the liver while being completely preserved in the hypothalamic suprachiasmatic nuculeus (SCN), suggesting that the SCN is not involved in alterations in hepatic core clock gene expressions. In addition, circadian patterns of glucose and lipid metabolism-related genes, e.g., peroxisome proliferator activated receptor (Ppar) α, Pparγ-1, Pparγ-coactivator-1α, and phosphoenolepyruvate carboxykinase, were also disturbed by CMS. In contrast, in C57BL/6 mice, the same CMS procedure altered neither serum corticosterone levels nor rhythmic expressions of hepatic core clock genes and metabolism-related genes. Thus, chronic stress can interfere with the circadian expressions of both core clock genes and metabolism-related genes in the liver possibly involving HPA axis overactivation. This mechanism might contribute to metabolic disorders in stressful modern societies.

  15. Mild and moderate pre-dialysis chronic kidney disease is associated with increased coronary artery calcium

    Directory of Open Access Journals (Sweden)

    Budoff M

    2011-12-01

    Full Text Available Sion K Roy, Albert Cespedes, Dong Li, Tae-Young Choi, Matthew J BudoffDivision of Cardiology, Department of Medicine, Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center, Torrance, California, USABackground: It is increasingly evident that patients with chronic kidney disease (CKD are more likely to die from heart disease than kidney failure. This study evaluated whether pre-dialysis CKD is an independent risk factor for coronary artery calcium (CAC.Methods: A total of 544 consecutive patients who underwent CAC scoring were analyzed. Eleven patients requiring hemodialysis were excluded. Patients were divided into three groups: normal glomerular filtration rate (GFR (GFR > 90 mL/min/1.73 m2, mild CKD (90 ≥ GFR > 60 mL/min/1.73 m2, and moderate CKD (60 ≥ GFR > 30 mL/min/1.73 m2. Continuous and categorical variables were compared using analysis of variance and the χ2 statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting the presence of CAC (>10 was performed and odds of incidence of CAC (>10 were calculated among the three GFR subgroups.Results: After adjustment for covariates, patients with mild CKD had mean CAC scores 175 points higher than those with the referent normal GFR (P = 0.048, while those with moderate CKD had mean CAC scores 693 points higher than the referent (P < 0.001. After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95% confidence interval 1.3–3.7, P = 0.004 and patients with moderate CKD were 6.4 times more likely (95% confidence interval 2.9–14.3, P < 0.001 to have incident CAC compared with the group with normal GFR.Conclusion: Mild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC

  16. Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism Pooled Analysis of Five Prospective General Population Cohorts

    NARCIS (Netherlands)

    Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.; Naess, Inger Anne; Lutsey, Pamela L.; Braekkan, Sigrid K.; Veeger, Nic J. G. M.; Brodin, Ellen E.; Meijer, Karina; Sang, Yingying; Matsushita, Kunihiro; Hallan, Stein I.; Hammerstrom, Jens; Cannegieter, Suzanne C.; Astor, Brad C.; Coresh, Josef; Folsom, Aaron R.; Hansen, John-Bjarne; Cushman, Mary

    2012-01-01

    Background-Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. Methods and Results-We poole

  17. Undefined and unpredictable responsibility

    DEFF Research Database (Denmark)

    Bove, Dorthe Gaby; Zakrisson, Ann-Britt; Midtgaard, Julie;

    2016-01-01

    AIMS AND OBJECTIVES: To explore how spouses of patients with severe chronic obstructive pulmonary disease experience their role as informal caregiver. BACKGROUND: Informal caregiver spouses are of pivotal importance in the way that patients with chronic obstructive pulmonary disease cope...... with their daily life, including their opportunity to stay at home and avoid hospitalisations in the last stages of the disease. However, caregiving is associated with increased morbidity and mortality among caregivers. Further understanding of the role as an informal caregiver spouse of patients with severe...... chronic obstructive pulmonary disease is needed to develop supportive interventions aimed at reducing the caregiver burden. DESIGN: The study had a qualitative exploratory design. The data collection and analysis were based on framework method. Framework method is a thematic methodology and consists...

  18. Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mithun Diwakar

    2015-01-01

    Full Text Available A barrier in the diagnosis of mild traumatic brain injury (mTBI stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS, and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG, which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition. MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and

  19. The effect of chronic mild hyponatremia on bone mineral loss evaluated by retrospective national Danish patient data

    DEFF Research Database (Denmark)

    Kruse, Christian; Eiken, Pia; Verbalis, Joseph;

    2016-01-01

    PURPOSE: To evaluate the effect of chronic mild hyponatremia ([Na+]=130-137mmol/L) on bone mineral content (BMC) and bone mineral density (BMD) loss through multiple, serial dual-energy X-ray absorptiometry (DXA) scans. METHODS: Utilizing biochemical and DXA scan data from two Danish regions...... between 2004 and 2011, supplemented with national Danish patient diagnosis and prescription reimbursement databases, a retrospective cohort study was performed. All subjects with more than one DXA scan were included, then stratified into "normonatremia" ([Na(+)]=[137.00-147.00] mmol/L) and "mild...

  20. Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain.

    Science.gov (United States)

    Gong, Yu; Chai, Yi; Ding, Jian-Hua; Sun, Xiu-Lan; Hu, Gang

    2011-01-13

    Increasing evidence implicates mitochondrial failure as a crucial factor in the pathogenesis of mental disorders, such as depression. The aim of the present study was to investigate the effects of exposure to chronic mild stress (CMS), a paradigm developed in the late 1980s as an animal model of depression, on the mitochondrial function and mitochondrial ultrastructure in the mouse brain. The results showed that the CMS regime induced depressive-like symptoms in mice characterized by reduced sucrose preference and body weight. Moreover, CMS exposure was associated with a significant increase in immobility time in the tail suspension test. Exposure to the CMS paradigm inhibited mitochondrial respiration rates and dissipated mitochondrial membrane potential in hippocampus, cortex and hypothalamus of mice. In addition, we found a damaged mitochondrial ultrastructure in brains of mice exposed to CMS. These findings provide evidence for brain mitochondrial dysfunction and ultrastructural damage in a mouse model of depression. Moreover, these findings suggest that mitochondrial malfunction-induced oxidative injury could play a role in stress-related disorders such as depression.

  1. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

    Directory of Open Access Journals (Sweden)

    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

  2. Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress.

    Science.gov (United States)

    Lin, Pao-Yen; Chang, Alice Y W; Lin, Tsu-Kung

    2014-09-01

    Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4 weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.

  3. Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

    Science.gov (United States)

    Briet, M; Bozec, E; Laurent, S; Fassot, C; London, G M; Jacquot, C; Froissart, M; Houillier, P; Boutouyrie, P

    2006-01-01

    Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; Pelastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

  4. In utero programming alters adult response to chronic mild stress: part 3 of a longitudinal study.

    Science.gov (United States)

    Baker, Stephanie L; Mileva, Guergana; Huta, Veronika; Bielajew, Catherine

    2014-11-07

    Exposure to stress before birth may lay the foundation for the development of sensitivities or protection from psychiatric disorders while later stress exposure may trigger either their expression or suppression. This report, part three of a longitudinal study conducted in our laboratory, aimed to examine the interaction between early and adult stress and their effects on measures of anxiety and depression. In parts one and two, we reported the effects of gestational stress (GS) in Long Evans rat dams and their juvenile and young adult offspring. In this third and final installment, we evaluated the effects of GS and chronic mild stress (CMS) in the adult female offspring at 6 month and 12 month time-points. The two by two design included a combination of GS and CMS and the appropriate control groups. Using Hierarchical Linear Modeling, main effects of GS on corticosterone level at the 12 month time-point was found while main effects of CMS were seen in body weight, sucrose preference, and corticosterone, and significant interactions between group at the 6 and 12 month time-points. The GS group had the lowest sucrose preference during CMS at 6 months supporting a cumulative effect of early and later life stress. The GS/CMS group showed lower corticosterone at 12 months than the GS/noCMS group indicating a possible mismatch between prenatal programming and later life stress. These results highlight the importance of early life factors in exerting potentially protective effects in models involving later life stress.

  5. Effect of mild aerobic training on the myocardium of mice with chronic Chagas disease

    Directory of Open Access Journals (Sweden)

    Preto E

    2015-09-01

    Full Text Available Emerson Preto,1 Nathalia EA Lima,1 Lucila Simardi,2 Fernando Luiz Affonso Fonseca,2,3 Abílio Augusto Fragata Filho,4 Laura Beatriz Mesiano Maifrino1,41Universidade São Judas Tadeu, São Paulo, 2Faculdade de Medicina do ABC, Santo André, 3Universidade Federal de São Paulo, Diadema, 4Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, BrazilBackground: Chronic chagasic heart disease represents extensive remodeling of the cardiovascular system, manifested as cardiac denervation, interstitial mononuclear infiltrate, myocyte and vascular degenerative changes, fibrosis, and hypertrophy. Moreover, aerobic exercises are widely indicated for the treatment of various disorders of the cardiovascular system.Purpose: To evaluate the right and left ventricles of BALB/c mice with chronic Chagas disease, undergoing mild exercise, by using morphometric and stereological methods.Materials and methods: A total of 20 male mice at 4 months of age were used for experiments. The animals were divided into four groups (n=5 in each group: untrained control, trained control, untrained infected (UI, and trained infected (TI. Animals of UI and TI groups were inoculated with 1,000 trypomastigote forms of Trypanosoma cruzi (Y strain, and after 40 days, animals entered chronic phase of the disease. Physical exercise, which included swimming, was performed for 30 minutes daily, five times a week for 8 consecutive weeks at a bath temperature of 30°C. After the trial period, euthanasia and subsequent withdrawal of the heart were done. The organ was prepared by histological staining procedures with hematoxylin–eosin and picrosirius red.Results: We found that the physical training used in our experimental model promoted increase in volume density of capillaries and decrease in volume density of collagen fibers and cross-sectional area of cardiomyocytes in chagasic animals (TI group. By histopathological analysis, we found differences in the inflammatory infiltrate

  6. Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression.

    Science.gov (United States)

    Sakr, H F; Abbas, A M; Elsamanoudy, A Z; Ghoneim, F M

    2015-08-01

    Our objective was to investigate the effects of chronic unpredictable mild stress (CUMS) with or without selective serotonin reuptake inhibitor (fluoxetine) and anti-oxidant (resveratrol) on testicular functions and oxidative stress in rats. Fifty male rats were divided into 2 groups; control and CUMS. CUMS group was further subdivided into 4 subgroups administered water, fluoxetine, resveratrol and both. Sucrose intake, body weight gain, serum corticosterone, serotonin and testosterone levels, sperm count and motility, testicular malondialdehyde, superoxide dismutase (SOD), catalase, glutathione (GSH), and gene expression of steroidogenic acute-regulatory (StAR) protein and cytochrome P450 side chain cleavage (P450scc) enzyme were evaluated. CUMS decreased sucrose intake, weight gain, anti-oxidants (SOD, catalase, GSH), testosterone, serotonin, StAR and cytochrome P450scc gene expression, sperm count and motility and increased malondialdehyde and corticosterone. Fluoxetine increased malondialdehyde, sucrose intake, weight gain, serotonin and decreased anti-oxidants, StAR and cytochrome P450scc gene expression, sperm count and motility, testosterone, corticosterone in stressed rats. Administration of resveratrol increased anti-oxidants, sucrose intake, weight gain, serotonin, StAR and cytochrome P450scc gene expression, testosterone, sperm count and motility, and decreased malondialdehyde and corticosterone in stressed rats with or without fluoxetine. In conclusion, CUMS induces testicular dysfunctions and oxidative stress. While treatment of CUMS rats with fluoxetine decreases the depressive behavior, it causes further worsening of testicular dysfunctions and oxidative stress. Administration of resveratrol improves testicular dysfunctions and oxidative stress that are caused by CUMS and further worsened by fluoxetine treatment.

  7. Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury PCS and PTSD

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-10-1-0962 TITLE: Hyperbaric Oxygen therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury...Annual 3. DATES COVERED (From – To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0962 Hyperbaric Oxygen therapy in...post- hyperbaric oxygen treatment. Four additional subjects have been screened in October 2015 and nine are awaiting first appointment for

  8. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid.

    Science.gov (United States)

    Chen, Jiao; Wang, Zhen-zhen; Zuo, Wei; Zhang, Shuai; Chu, Shi-feng; Chen, Nai-hong

    2016-02-01

    Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors.

  9. Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity.

    Science.gov (United States)

    Reich, C G; Mihalik, G R; Iskander, A N; Seckler, J C; Weiss, M S

    2013-12-03

    Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity.

  10. Chronic mild stress (CMS in mice: of anhedonia, 'anomalous anxiolysis' and activity.

    Directory of Open Access Journals (Sweden)

    Martin C Schweizer

    Full Text Available BACKGROUND: In a substantial proportion of depressed patients, stressful life events play a role in triggering the evolution of the illness. Exposure to stress has effects on different levels in laboratory animals as well and for the rat it has been shown that chronic mild stress (CMS can cause antidepressant-reversible depressive-like effects. The adoption of the model to the mouse seems to be problematic, depending on the strain used and behavioural endpoint defined. Our aim was to evaluate the applicability of CMS to mice in order to induce behavioural alterations suggested to reflect depression-like symptoms. METHODOLOGY/PRINCIPAL FINDINGS: A weekly CMS protocol was applied to male mice of different mouse strains (D2Ola, BL/6J and BL/6N and its impact on stress-sensitive behavioural measures (anhedonia-, anxiety- and depression-related parameters and body weight was assessed. Overnight illumination as commonly used stressor in CMS protocols was particularly investigated in terms of its effect on general activity and subsequently derived saccharin intake. CMS application yielded strain-dependent behavioural and physiological responses including 'paradox' anxiolytic-like effects. Overnight illumination was found to be sufficient to mimic anhedonic-like behaviour in BL/6J mice when being applied as sole stressor. CONCLUSIONS/SIGNIFICANCE: The CMS procedure induced some behavioural changes that are compatible with the common expectations, i.e. 'anhedonic' behaviour, but in parallel behavioural alterations were observed which would be described as 'anomalous' (e.g. decreased anxiety. The results suggest that a shift in the pattern of circadian activity has a particular high impact on the anhedonic profile. Changes in activity in response to novelty seem to drive the 'anomalous' behavioural alterations as well.

  11. Web-based support for daily functioning of people with mild intellectual disabilities or chronic psychiatric disorders: A feasibility study in routine practice

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    Jessica de Wit

    2015-05-01

    Conclusion: The initial results of the use of web-based support for this client population seem promising and justify further research on online support for clients with mild intellectual disabilities or chronic psychiatric disorders.

  12. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  13. Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study.

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    Christiane Drechsler

    Full Text Available BACKGROUND: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD. METHODS: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19 using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. RESULTS: Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min, 2.64±1.06 µmol/L (GFR 60-90 ml/min, 2.52±1.24 µmol/L (GFR 30-60 ml/min and 2.05±0.78 µmol/L (GFR<30 ml/min, respectively (p = 0.002. The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005. This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01, and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06. CONCLUSIONS: Homoarginine concentrations are directly correlated with kidney function and are significantly

  14. 百事乐胶囊对慢性应激抑郁模型大鼠海马DG、CA3区神经元再生相关蛋白的影响%Effects of Baishile Capsules on Neurogenesis Related Protein in Hippocampal DG and CA3 ;Area of Model Rats with Chronic Unpredicted Mile Stress Depression

    Institute of Scientific and Technical Information of China (English)

    张秀丽; 孟盼; 王宇红; 向韵; 刘林; 韩远山

    2015-01-01

    目的:探讨百事乐胶囊对慢性应激抑郁模型大鼠海马神经再生相关cAMP-CREB-BDNF信号通路的影响。方法将SD大鼠随机分为空白组、模型组、氟西汀组及百事乐高、中、低剂量组,除空白组外,采用慢性温和不可预见性应激加孤养的方式建立大鼠抑郁模型,各组给予相应药物灌胃,连续21 d。开野实验、糖水消耗实验、定位航行实验及空间搜索实验检测大鼠行为学的变化,ELISA检测大鼠血浆中皮质酮含量,免疫组化检测海马DG、CA3区蛋白激酶A(PKA)、脑源性神经营养因子(BDNF)、环磷腺苷效应元件结合蛋白(CREB)的表达。结果与模型组比较,百事乐高、中剂量组大鼠水平或垂直活动次数及蔗糖偏食度升高(P<0.05,P<0.01),百事乐高剂量组大鼠逃避潜伏期、目标象限潜伏时间缩短(P<0.05),百事乐高、中、低剂量组血浆皮质酮浓度降低(P<0.05),百事乐高剂量组海马DG、CA3区PKA、CREB、BDNF表达升高(P<0.05)。结论百事乐胶囊可能通过cAMP-CREB-BDNF信号通路促进海马神经元再生而实现抗抑郁的作用。%Objective To investigate effects of Baishile Capsules on cAMP-CREB-BDNF signal pathway about hippocampal neurogenesis in model rats with chronic unpredicted stress depression. Methods SD rats were randomly divided into blank group, model group, fluoxetine hydrochloride group, and Baishile Capsules high, medium, and low dose groups. Chronic stress depression rat model was established by chronic and mild unpredictable stressors. All groups were given relevant medicine for 21 days. The open-field test, sugar consumption experiment, place navigation test, and space searching experiment were used to detect behavior changes of the rats. ELISA was used to detect content of corticosterone in plasma. The protein expressions of PKA, BDNF, and CREB were detected by immunohistochemical method. Results Compared with model group, Baishile Capsules high

  15. The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

    DEFF Research Database (Denmark)

    Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J

    2008-01-01

    mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

  16. SMFM Statement: benefit of antihypertensive therapy for mild-to-moderate chronic hypertension during pregnancy remains uncertain.

    Science.gov (United States)

    2015-07-01

    Chronic hypertension is present in up to 5% of pregnant women and constitutes a major cause of maternal and neonatal morbidity and mortality. The purpose of this document is to summarize the current recommendations regarding use of antihypertensive medications during pregnancy for women with mild-to-moderate chronic hypertension in the setting of the recently published Control of Hypertension in Pregnancy Study (CHIPS). The recently published CHIPS trial was a multicenter international randomized controlled trial comparing "less tight control" to "tight control" of blood pressure for pregnant women with hypertension. The most updated recommendations regarding management of pregnant women with hypertension are found from the American Congress of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy, which are endorsed by the Society of Maternal-Fetal Medicine (SMFM). SMFM recommends that clinicians continue to follow existing guidelines for management of pregnant women with mild-to-moderate chronic hypertension due to the fact that the benefits and risks of pharmacologic treatment for these women remain uncertain, and adequately powered randomized controlled trials are needed to address the less common but clinically significant nonsurrogate perinatal outcomes.

  17. Chronic unpredictable stress before pregnancy reduce the expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor in hippocampus of offspring rats associated with impairment of memory.

    Science.gov (United States)

    Huang, Yuejun; Shi, Xuechuan; Xu, Hongwu; Yang, Hanhua; Chen, Tian; Chen, Sihong; Chen, Xiaodong

    2010-07-01

    To investigate the effect of stress before pregnancy on memory function and serum corticosterone (COR) levels, as well as the expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate (NMDA) 2A (NR2A) and 2B (NR2B) receptors in the hippocampus of the offspring rats when they were 2 months postnatally. Adult female Sprague-Dawley (SD) rats were divided randomly into two groups: control group (n = 8) and chronic unpredictable stress (CUS) group (n = 12). All rats were tested in the open field test and sucrose intake test before and after CUS. The memory function of their offspring were tested in the Morris water maze. Serum COR levels were determined by using a standard radioimmunoassay kit. The expression of BDNF, NR2A and NR2B in the hippocampus of the offspring rats were studied by immunoreactivity quantitative analysis and real-time RT-PCR. (1) Following CUS, reduced open field test activity and decreased sucrose consumption were observed relative to controls. (2) The Morris water maze task demonstrated increased escape latency in the offspring rats of CUS group relative to controls (P BDNF and NR2B in the offspring of CUS group was decreased in the CA3 and DG regions of the hippocampus compared to the control group offspring, but NR2A levels were not altered between the offspring of the two groups. (5) Real-time RT-PCR demonstrated that BDNF and NR2B mRNAs were significantly decreased in the offspring of the CUS group compared with the control group (P BDNF and NR2B in the hippocampus of offspring. These alterations are associated with impairment of memory in the adult offspring. These data suggest that, stress before pregnancy might have a profound influence on brain development of offspring, that may persist into and be manifested in adulthood.

  18. Do epigenetic events take place in the vastus lateralis of patients with mild chronic obstructive pulmonary disease?

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    Ester Puig-Vilanova

    Full Text Available Muscle dysfunction is a major comorbidity in Chronic Obstructive Pulmonary Disease (COPD. Several biological mechanisms including epigenetic events regulate muscle mass and function in models of muscle atrophy. Investigations conducted so far have focused on the elucidation of biological mechanisms involved in muscle dysfunction in advanced COPD. We assessed whether the epigenetic profile may be altered in the vastus lateralis of patients with mild COPD, normal body composition, and mildly impaired muscle function and exercise capacity. In vastus lateralis (VL of mild COPD patients with well-preserved body composition and in healthy age-matched controls, expression of DNA methylation, muscle-enriched microRNAs, histone acetyltransferases (HTAs and deacetylases (HDACs, protein acetylation, small ubiquitin-related modifier (SUMO ligases, and muscle structure were explored. All subjects were clinically evaluated. Compared to healthy controls, in the VL of mild COPD patients, muscle function and exercise capacity were moderately reduced, DNA methylation levels did not differ, miR-1 expression levels were increased and positively correlated with both forced expiratory volume in one second (FEV1 and quadriceps force, HDAC4 protein levels were increased, and muscle fiber types and sizes were not different. Moderate skeletal muscle dysfunction is a relevant feature in patients with mild COPD and preserved body composition. Several epigenetic events are differentially expressed in the limb muscles of these patients, probably as an attempt to counterbalance the underlying mechanisms that alter muscle function and mass. The study of patients at early stages of their disease is of interest as they are a target for timely therapeutic interventions that may slow down the course of the disease and prevent the deleterious effects of major comorbidities.

  19. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...... amygdala of the same brain hemispheres is also included with three different stains: DiI and Hoechst stained microscopic images (confocal microscopy) andALDH1L1 antibody based immunohistochemistry.These stains may be used to evaluate neurite density (DiI), nuclear density (Hoechst) and astrocytic density...

  20. [Long-term effect of inhaled budesonide in patients with mild to moderate chronic obstructive lung disease. The Osterbro Study].

    Science.gov (United States)

    Vestbo, J; Sørensen, T; Lange, P; Brix, A; Torre, P; Viskum, K

    2000-01-24

    We compared the effect of inhaled budesonide with placebo on decline in lung function and respiratory symptoms in a three-year study of patients with chronic obstructive pulmonary disease (COPD). We used a parallel-group, randomized, double-blind, placebo-controlled design, nested in an ongoing epidemiological survey. Patients were non-asthmatic subjects with a decreased ratio between forced expiratory volume in one second (FEV1) and vital capacity (VC); i.e., FEV1/VC longterm inhaled corticosteroids in the treatment of mild-moderate COPD.

  1. Actual Therapeutic Indication of an Old Drug: Urea for Treatment of Severely Symptomatic and Mild Chronic Hyponatremia Related to SIADH

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    Guy Decaux

    2014-09-01

    Full Text Available Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.

  2. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury : Acute versus chronic disturbances?

    NARCIS (Netherlands)

    Metting, Zwany; Spikman, Jacoba M.; Rodiger, Lars A.; van der Naalt, Joukje

    2014-01-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully unde

  3. White Matter Abnormalities are Associated with Chronic Postconcussion Symptoms in Blast-Related Mild Traumatic Brain Injury

    Science.gov (United States)

    Miller, Danielle R.; Hayes, Jasmeet P.; Lafleche, Ginette; Salat, David H.; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI−LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  4. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    Science.gov (United States)

    Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

  5. Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

    Directory of Open Access Journals (Sweden)

    Esposito Fabio

    2009-07-01

    Full Text Available Abstract Background Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after the exercise cessation. Rats were trained at mild intensity on a treadmill: 25 m/min, 10%incline, 1 h/day, 3 days/week, 10 weeks; about 60% of the maximum aerobic power. By Affymetrix technology, we investigated the gene expression profile induced by exercise training in the left ventricle (LV of trained (n = 10 and control (n = 10 rats. Cardioprotection was investigated by ischemia/reperfusion experiments (n = 10 trained vs. n = 10 control rats. Results Mild exercise did not induce cardiac hypertrophy and was cardioprotective as demonstrated by the decreased infarct size (p = 0.02 after ischemia/reperfusion experiments in trained with respect to control rats. Ten genes and 2 gene sets (two pathways resulted altered in LV of exercised animals with respect to controls. We validated by real-time PCR the increased expression of four genes: similar to C11orf17 protein (RGD1306959, caveolin 3, enolase 3, and hypoxia inducible factor 1 alpha. Moreover, caveolin 3 protein levels were higher in exercised than control rats by immunohistochemistry and Western Blot analysis. Interestingly, the predicted gene similar to C11orf17 protein (RGD1306959 was significantly increased by exercise. This gene has a high homology with the human C11orf17 (alias: protein kinase-A interacting protein 1 or breast cancer associated gene 3. This is the first evidence that this gene is involved in the response to the exercise training. Conclusion Our data indicated that few, but significant

  6. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M;

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

  7. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  8. Respiratory Consequences of Mild-to-Moderate Obesity: Impact on Exercise Performance in Health and in Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Denis E. O'Donnell

    2012-01-01

    Full Text Available In many parts of the world, the prevalence of obesity is increasing at an alarming rate. The association between obesity, multiple comorbidities, and increased mortality is now firmly established in many epidemiological studies. However, the link between obesity and exercise intolerance is less well studied and is the focus of this paper. Although exercise limitation is likely to be multifactorial in obesity, it is widely believed that the respiratory mechanical constraints and the attendant dyspnea are important contributors. In this paper, we examined the evidence that critical ventilatory constraint is a proximate source of exercise limitation in individuals with mild-to-moderate obesity. We first reviewed existing information on exercise performance, including ventilatory and perceptual response patterns, in obese individuals who are otherwise healthy. We then considered the impact of obesity in patients with preexisting respiratory mechanical abnormalities due to chronic obstructive pulmonary disease (COPD, with particular reference to the effect on dyspnea and exercise performance. Our main conclusion, based on the existing and rather sparse literature on the subject, is that abnormalities of dynamic respiratory mechanics are not likely to be the dominant source of dyspnea and exercise intolerance in otherwise healthy individuals or in patients with COPD with mild-to-moderate obesity.

  9. Association between macular degeneration and mild to moderate chronic kidney disease: A nationwide population-based study.

    Science.gov (United States)

    Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen

    2017-03-01

    Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264-1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218-1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients.

  10. Clinical Management of a Patient with Chronic Recurrent Vertigo Following a Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Eric G. Johnson

    2009-01-01

    Full Text Available Vertigo, was provoked and right torsional up-beat nystagmus was observed in a 47-year-old patient when she was placed into the right Hallpike-Dix test position using infrared goggle technology. The clinical diagnosis was benign paroxysmal positional vertigo (BPPV, specifically right posterior canalithiasis, resulting from a mild traumatic brain injury (TBI suffered approximately six-months earlier. Previous medical consultations did not include vestibular system examination, and Meclizine was prescribed to suppress her chief complaint of vertigo. Ultimately, the patient was successfully managed by performing two canalith repositioning maneuvers during a single clinical session. The patient reported 100% resolution of symptoms upon reexamination the following day, and the Hallpike-Dix test was negative. Continued symptom resolution was subjectively reported 10 days postintervention via telephone consultation. This case report supports previous publications concerning the presence of BPPV following TBI and the need for inclusion of vestibular system examination during medical consultation.

  11. Mild moxibustion at Tianshu (ST 25) decreases expression of prokineticin-1 and prokineticin receptor-1 in colon tissue of rats with chronic visceral hyperalgesia

    Institute of Scientific and Technical Information of China (English)

    Luyi Wu; Chunhui Bao; Linbao Ge; Cili Zhou; Huirong Liu; Li Qi; Tao Yi; Huangan Wu; Xiaomei Wang

    2011-01-01

    Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu (ST 25) decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.

  12. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study

    OpenAIRE

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-01-01

    Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study correspondence: Corresponding author. Tel.: +43 5129003 70560; fax: +43 5129003 73560or73561. (Kronenberg, Florian) (Kronenberg, Florian) Division of Genetic Epidemiology; Department of Medical Genetics, Molecular and Clinical Pharmacology; Innsbruck Medical University - AUSTRIA (Stur...

  13. Chronic mild stress and imipramine treatment elicit opposite changes in behavior and in gene expression in the mouse prefrontal cortex.

    Science.gov (United States)

    Erburu, M; Cajaleon, L; Guruceaga, E; Venzala, E; Muñoz-Cobo, I; Beltrán, E; Puerta, E; Tordera, R M

    2015-08-01

    Many studies suggest that the prefrontal cortex (PFC) is a target limbic region for stress response because a dysfunction here is linked to anhedonia, a decrease in reactivity to rewards, and to anxiety. It is suggested that stress-induced persistent molecular changes in this brain region could bring some light on the mechanisms perpetuating depressive episodes. In order to address this issue, here we have studied the long-term PFC gene expression pattern and behavioral effects induced by a chronic mild stress (CMS) model and antidepressant treatment in mice. CMS was applied to mice for six weeks and imipramine (10mg/kg, i.p.) or saline treatment was administered for five weeks starting from the third week of CMS. Mice were sacrificed one month after CMS and following two weeks after the discontinuation of drug treatment and the PFC was dissected and prepared for gene (mRNA) and protein expression studies. Using the same experimental design, a separate group of mice was tested for anhedonia, recognition memory, social interaction and anxiety. CMS induced a long-term altered gene expression profile in the PFC that was partially reverted by imipramine. Specifically, the circadian rhythm signaling pathway and functions such as gene expression, cell proliferation, survival and apoptosis as well as neurological and psychiatric disorders were affected. Of these, some changes of the circadian rhythm pathway (Hdac5, Per1, and Per2) were validated by RT-PCR and western-blot. Moreover, CMS induced long-lasting anhedonia that was reverted by imipramine treatment. Impaired memory, decreased social interaction and anxiety behavior were also induced by chronic stress. We have identified in the PFC molecular targets oppositely regulated by CMS and imipramine that could be relevant for chronic depression and antidepressant action. Among these, a possible candidate for further investigation could be the circadian rhythm pathway.

  14. Chronic Mild Hyperglycemia in GCK-MODY Patients Does Not Increase Carotid Intima-Media Thickness

    Directory of Open Access Journals (Sweden)

    Stepanka Pruhova

    2013-01-01

    Full Text Available Aim. GCK-MODY is an autosomal dominant form of diabetes caused by heterozygous mutations in the glucokinase gene leading to a lifelong mild hyperglycemia. The risk of macrovascular complications is considered low, but studies are limited. We, therefore, investigated the carotid intima-media thickness (CIMT as an indicator of macrovascular complications in a group of patients with GCK-MODY. Methods. Twenty-seven GCK mutation carriers and 24 controls recruited among their first-degree relatives were compared, all aging over 35 years. The CIMT was tested using a high-resolution B-mode carotid ultrasonography. Medical history, anthropometry, and biochemical blood workup were obtained. Results. The mean CIMT was 0.707 ± 0.215 mm (mean ± SD in GCK mutation carriers and 0.690 ± 0.180 mm in control individuals. When adjusted for age, gender, and family status, the estimated mean difference in CIMT between the two groups increased to 0.049 mm (P=0.19. No difference was detected for other characteristics, with the exception of fasting blood glucose (GCK-MODY 7.6 mmol/L ± 1.2 (136.4 mg/dL; controls 5.3 mmol/L ± 0.3 (95.4 mg/dL; P<0.0001 and glycated hemoglobin HbA1c (GCK-MODY 6.9% ± 1.0%, 52 mmol/mol ± 10; controls 5.7% ± 0.4%, 39 mmol/mol ± 3; P<0.0001. The frequency of myocardial infarction and ischemic stroke did not differ between groups. Conclusion. Our data indicate that the persistent hyperglycemia in GCK-MODY is associated with a low risk of developing diabetic macrovascular complications.

  15. Skin Autofluorescence and Subclinical Atherosclerosis in Mild to Moderate Chronic Kidney Disease: A Case-Control Study

    Science.gov (United States)

    Sánchez, Enric; Betriu, Àngels; Arroyo, David; López, Carolina; Hernández, Marta; Rius, Ferran; Fernández, Elvira

    2017-01-01

    Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, p2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4–6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, p<0.001) and LDL-cholesterol (r = -0.269, p = 0.001), and positively correlated with age (r = 0.472, p<0.001), pulse pressure (r = 0.238, p = 0.002), and SCORE risk (r = 0.451, p<0.001). A stepwise multivariate regression analysis showed that age and glomerular filtration rate independently predicted skin AF (R2 = 0.289, p<0.001). Skin AF is elevated in patients with mild-to-moderate CKD compared with control subjects. This finding may be independently associated with the glomerular filtration rate and the presence of subclinical atheromatous disease. Therefore, the use of skin AF may help to accurately evaluate the real cardiovascular risk at the

  16. Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

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    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2010-02-01

    Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

  17. Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model.

    Science.gov (United States)

    Yan, Shuo; You, Zi-Li; Zhao, Qiu-Ying; Peng, Cheng; He, Gang; Gou, Xiao-Jun; Lin, Bin

    2015-12-01

    Natural products have been widely reported as effective therapeutic alternatives for treatment of depression. Sanyuansan is a compound recipe composed of ginseng total saponins, fish oil, and valeriana. The aims of this study were to validate whether Sanyuansan has antidepressant-like effects through acute behavioral tests including the forced swimming test (FST), tail suspension test (TST), locomotor activity test, and chronic mild stress (CMS) mice model of depression. C57BL/6 mice were given oral administration of 30 mg/kg imipramine, Sanyuansan, and saline, respectively. The acute behavioral tests including the TST, FST, and locomotor activity test were done after the administration of drugs for consecutively three times (24 hours, 1 hour, and 0.5 hour prior to the tests). Furthermore, the sucrose preference and the serum corticosterone level of mice in the CMS model were examined. Sanyuansan only at 900 mg/kg markedly reduced immobility time in the TST compared with the saline-treated group of mice. Sanyuansan at doses of 225 mg/kg, 450 mg/kg, and 900 mg/kg significantly reduced immobility time of mice in the FST. Sanyuansan reversed the CMS-induced anhedonia and hyperactivation of the hypothalamus-pituitary-adrenal axis. In addition, our results showed that neither imipramine nor Sanyuansan at any dosage increased spontaneous motor activity. These results suggested that Sanyuansan induced significant antidepressant-like effects in mice in both acute and chronic animal models, which seemed unlikely to be attributed to an increase in locomotor activities of mice, and had no sedative-like effects.

  18. Concussion/mild traumatic brain injury-related chronic pain in males and females: A diagnostic modelling study

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    Mollayeva, Tatyana; Cassidy, J. David; Shapiro, Colin M.; Mollayeva, Shirin; Colantonio, Angela

    2017-01-01

    Abstract Pain is an unpleasant, complex, and perceived experience that places a significant burden on patients and clinicians. Its severity may be mediated by emotion, attitude, and environmental influences, and pain may be expressed differently in males and females. Traumatic brain injury (TBI) is frequently associated with chronic pain. This diagnostic modeling study examined sex differences in the construct of chronic pain in patients with delayed recovery from concussion/mild traumatic brain injury (mTBI). Data were collected from standardized questionnaires, neuroimaging records, and comprehensive clinical assessments. Bivariate associations were calculated using the Spearman correlation coefficient or analysis of variance. We established sex-specific stepwise multivariate linear regression models of factors associated with pain. Of the 94 participants diagnosed with mTBI (the mean age was 45.20 ± 9.94 years; 61.2% were males; the median time since injury was 197 days [interquartile range 139–416]), head/neck, and bodily pain were reported by 93% and 64%, respectively. No sex differences were identified in pain frequencies or severity. Pain was significantly associated with certain socio-demographic, injury-related, behavioral, and clinical variables. In the multivariable regression analysis, several determinants explained 60% of the pain variance in males and 46% in females. Pain is common in patients with delayed recovery from mTBI and is significantly associated with potentially modifiable clinical and nonclinical variables. Examining the multidimensional construct of pain in concussion/mTBI through a sex lens garners new directions for future longitudinal research on the pain mechanisms involved in postconcussion syndrome. PMID:28207508

  19. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

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    Charles W. Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  20. Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

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    Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

    2015-11-01

    It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the

  1. Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

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    Kim, Yu Ri; Kim, Ha Neui; Hong, Ki Whan; Shin, Hwa Kyoung; Choi, Byung Tae

    2017-01-01

    The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB) was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects. PMID:28208711

  2. Iptakalim confers an antidepressant effect in a chronic mild stress model of depression through regulating neuro-inflammation and neurogenesis.

    Science.gov (United States)

    Lu, Ming; Yang, Jing-Zhe; Geng, Fan; Ding, Jian-Hua; Hu, Gang

    2014-09-01

    Depression is a serious mental disorder in the world, but the underlying mechanisms remain unclear and the effective cures are scarce. Iptakalim (Ipt), an ATP-sensitive potassium (K-ATP) channel opener that can cross the blood-brain barrier freely, has been demonstrated to inhibit neuro-inflammation and enhance adult hippocampal neurogenesis. But it is unknown whether Ipt is beneficial to therapy of depression by modulating neurogenesis and neuro-inflammation. This study aimed to determine the potential antidepressant efficacy of Ipt in a chronic mild stress (CMS) mouse model of depression. We showed that treatment with Ipt (10 mg/kg/day, i.p) for 4 wk restored the decrease of sucrose preference and shortened the immobile time in forced swimming tests (FST) and tail suspension tests (TST) in CMS model mice. We further found that Ipt reversed the CMS-induced reduction of the adult hippocampal neurogenesis and improved cerebral insulin signalling in the CMS mice. Furthermore, Ipt negatively regulated nod-like receptor protein 3 (NLRP3) expression and, in turn, inhibited microglia-mediated neuro-inflammation by suppressing the activation of NLRP3-inflammasome/caspase-1/interleukin 1β axis in the hippocampus of CMS mice. Taken together, our findings demonstrate that Ipt plays a potential antidepressant role in CMS model mice through regulating neuro-inflammation and neurogenesis, which will provide potential for Ipt in terms of opening up novel therapeutic avenues for depression.

  3. The neurogenic effects of an enriched environment and its protection against the behavioral consequences of chronic mild stress persistent after enrichment cessation in six-month-old female Balb/C mice.

    Science.gov (United States)

    Vega-Rivera, Nelly Maritza; Ortiz-López, Leonardo; Gómez-Sánchez, Ariadna; Oikawa-Sala, Julian; Estrada-Camarena, Erika Monserrat; Ramírez-Rodríguez, Gerardo Bernabé

    2016-03-15

    Because stress may underlie the presence of depressive episodes, strategies to produce protection against or to reverse the effects of stress on neuroplasticity and behavior are relevant. Preclinical studies showed that exposure to stimuli, such as physical activity and environmental enrichment (ENR), produce beneficial effects against stress causing antidepressant-like effects in rodents. Additionally, ENR induces positive effects on neuroplasticity, neurochemistry and behavior at any age of rodents tested. Here, we analyzed whether ENR exposure prevents the development of depressive-like behavior produced by unpredictable, chronic mild stress (CMS) exposure as well as changes in hippocampal neurogenesis in a six-month-old female Balb/C mice, strain that shows low baseline levels of hippocampal neurogenesis. Mice were assigned to one of four groups: (1) normal housing-normal housing (NH-NH), (2) NH-CMS, (3) ENR-NH, or (4) ENR-CMS. The animals were exposed over 46 days to ENR or NH and subsequently to NH or CMS for 4 weeks. ENR induces long-term effects protecting against CMS induction of anhedonia and hopelessness behaviors. Independent of housing conditions, ENR increased the number of proliferative cells (Ki67), and CMS decreased the number of proliferative cells. ENR increased the newborn cells (BrdU) and mature phenotypes of neurons; these effects were not changed by CMS exposure. Similarly, the number of doublecortin-positive cells was not affected by CMS in ENR mice, which showed more cells with complex dendrite arborizations. Our study suggests that ENR induces protection against the effects of CMS on behavior and neuroplasticity in six-month-old Balb/C mice.

  4. Unpredictability and the transmission of numbers

    CERN Document Server

    Myers, John M

    2015-01-01

    Curiously overlooked in physics is its dependence on the transmission of numbers. For example the transmission of numerical clock readings is implicit in the concept of a coordinate system. The transmission of numbers and other logical distinctions is often achieved over a computer-mediated communications network in the face of an unpredictable environment. By unpredictable we mean something stronger than the spread of probabilities over given possible outcomes, namely an opening to unforeseeable possibilities. Unpredictability, until now overlooked in theoretical physics, makes the transmission of numbers interesting. Based on recent proofs within quantum theory that provide a theoretical foundation to unpredictability, here we show how regularities in physics rest on a background of channels over which numbers are transmitted. As is known to engineers of digital communications, numerical transmissions depend on coordination reminiscent of the cycle of throwing and catching by players tossing a ball back and...

  5. Antidepressant-like activity of magnesium in the chronic mild stress model in rats: alterations in the NMDA receptor subunits.

    Science.gov (United States)

    Pochwat, Bartłomiej; Szewczyk, Bernadeta; Sowa-Kucma, Magdalena; Siwek, Agata; Doboszewska, Urszula; Piekoszewski, Wojciech; Gruca, Piotr; Papp, Mariusz; Nowak, Gabriel

    2014-03-01

    Recent data suggests that the glutamatergic system is involved in the pathophysiology and treatment of major depressive disorder (MDD) and that the N-methyl-D-aspartate (NMDA) receptor is a potential target for antidepressant drugs. The magnesium ion blocks the ion channel of the NMDA receptor and prevents its excessive activation. Some preclinical and clinical evidence suggests also that magnesium may be useful in the treatment of depression. The present study investigated the effect of magnesium treatment (10, 15 and 20 mg/kg, given as magnesium hydroaspartate) in the chronic mild stress (CMS) model of depression in rats. Moreover, the effect of CMS and magnesium (with an effective dose) on the level of the proteins related to the glutamatergic system (GluN1, GluN2A, GluN2B and PSD-95) in the hippocampus, prefrontal cortex (PFC) and amygdala were examined. A significant reduction in the sucrose intake induced by CMS was increased by magnesium treatment at a dose of 15 mg/kg, beginning from the third week of administration. Magnesium did not affect this behavioural parameter in the control animals. CMS significantly increased the level of the GluN1 subunit in the amygdala (by 174%) and GluN2A in the hippocampus (by 191%), both of which were significantly attenuated by magnesium treatment. Moreover, magnesium treatment in CMS animals increased the level of GluN2B (by 116%) and PSD-95 (by 150%) in the PFC. The present results for the first time demonstrate the antidepressant-like activity of magnesium in the animal model of anhedonia (CMS), thus indicating the possible involvement of the NMDA/glutamatergic receptors in this activity.

  6. Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood

    Directory of Open Access Journals (Sweden)

    Charlis eRaineki

    2014-02-01

    Full Text Available Individuals exposed to alcohol during gestation show higher rates of psychopathologies. The hyperresponsivity to stress induced by prenatal alcohol exposure may be related to this increased rate of psychopathologies, especially because this population is more likely to be exposed to stressful environments throughout life. However, alcohol-induced changes in the overlapping neurocircuitries that underlie stress and the expression of psychopathologies are not fully understood. Here, we performed a comprehensive analysis of the neural activity within central areas known to play key roles in both emotional and stress regulation. Adult male and female offspring from prenatal alcohol exposure (PAE, pair-fed, and ad libitum-fed control conditions were exposed to chronic mild stress (CMS. Following CMS, the neural activity (c-fos mRNA of the amygdala, ventral hippocampal formation, medial prefrontal cortex (mPFC, and paraventricular nucleus of hypothalamus (PVN was assessed in response to an acute stress (elevated plus maze. Our results demonstrate that, overall, PAE decreased neural activity within the amygdala and hippocampal formation in males and increased neural activity within the amygdala and mPFC in females. CMS reduced neural activity within the mPFC and PVN in PAE males, but reduced activity in all areas analyzed in control males. By contrast, CMS reduced neural activity in the mPFC in PAE females and had no effects in control females. Furthermore, the constrained principal component analysis revealed that these patterns of neural activity resulted in differential activation of functional neural networks in males compared to females, indicating sexually dimorphic effects of PAE and CMS. Importantly, the altered networks of brain activation in PAE animals may underlie the hyperresponsivity to stress and increased psychopathologies observed among individuals prenatally exposed to alcohol.

  7. Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.

    Science.gov (United States)

    Marco, Eva M; Ballesta, Javier Antonio; Irala, Carlos; Hernández, María-Donina; Serrano, María Elisa; Mela, Virginia; López-Gallardo, Meritxell; Viveros, María-Paz

    2017-01-01

    Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression

  8. Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression.

    Science.gov (United States)

    Ge, Lin; Zhu, Ming-Ming; Yang, Jing-Yu; Wang, Fang; Zhang, Rong; Zhang, Jing-Hai; Shen, Jing; Tian, Hui-Fang; Wu, Chun-Fu

    2015-04-01

    Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide. Rats were exposed to 10weeks of CMS or control conditions and were then subsequently treated with 2weeks of daily oleamide (5mg/kg, i.p.), fluoxetine (10mg/kg, i.p.), or vehicle. Protein extracts from the hippocampus were then collected, and hippocampal maps were generated by way of two-dimensional gel electrophoresis (2-DE). Altered proteins induced by CMS and oleamide were identified through mass spectrometry and database searches. Compared to the control group, the CMS rats exhibited significantly less body weight gain and decreased sucrose consumption. Treatment with oleamide caused a reversal of the CMS-induced deficit in sucrose consumption. In the proteomic analysis, 12 protein spots were selected and identified. CMS increased the levels of adenylate kinase isoenzyme 1 (AK1), nucleoside diphosphate kinase B (NDKB), histidine triad nucleotide-binding protein 1 (HINT1), acyl-protein thioesterase 2 (APT-2), and glutathione S-transferase A4 (GSTA4). Compared to the CMS samples, seven spots changed significantly following treatment with oleamide, including GSTA4, glutathione S-transferase A6 (GSTA6), GTP-binding nuclear protein Ran (Ran-GTP), ATP synthase subunit d, transgelin-3, small ubiquitin-related modifier 2 (SUMO2), and eukaryotic translation initiation factor 5A-1 (eIF5A1). Of these seven proteins, the level of eIF5A1 was up-regulated, whereas the remaining proteins were down-regulated. In conclusion, oleamide has antidepressant

  9. Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

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    Cabrera R.J.

    1999-01-01

    Full Text Available Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS during pregnancy (prenatal stress; PS group. Control pregnant rats (C group were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36 while the other PS pups were cross-fostered with C dams (PSF group, N = 47 and the other C pups were cross-fostered with PS dams (CF group, N = 58. Pups were undisturbed until weaning (postnatal day 28. The male offspring underwent motor activity tests (day 28, enriched environment tests (day 37 and social interaction tests (day 42 in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, P<0.05. The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; c2 test, P<0.05 and lower body weight than controls at days 28 and 60 (Duncan's test, P<0.05 and P<0.01, respectively. The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, P<0.01 for PS group and P<0.05 for CF and PSF groups. In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, P<0.05. Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, P<0.05. In fact, CVS treatment during gestation plus

  10. Sex-specific effects of prenatal chronic mild stress on adult spatial learning capacity and regional glutamate receptor expression profiles.

    Science.gov (United States)

    Wang, Yan; Ma, Yuchao; Hu, Jingmin; Zhang, Xinxin; Cheng, Wenwen; Jiang, Han; Li, Min; Ren, Jintao; Zhang, Xiaosong; Liu, Mengxi; Sun, Anji; Wang, Qi; Li, Xiaobai

    2016-07-01

    Both animal experiments and clinical studies have demonstrated that prenatal stress can cause cognitive disorders in offspring. To explore the scope of these deficits and identify potential underlying mechanisms, we examined the spatial learning and memory performance and glutamate receptor (GluR) expression patterns of adult rats exposed to prenatal chronic mild stress (PCMS). Principal component analysis (PCA) was employed to reveal the interrelationships among spatial learning indices and GluR expression changes. Female PCMS-exposed offspring exhibited markedly impaired spatial learning and memory in the Morris water maze (MWM) task compared to control females, while PCMS-exposed males showed better initial spatial learning in the MWM compared to control males. PCMS also altered basal and post-MWM glutamate receptor expression patterns, but these effects differed markedly between sexes. Male PCMS-exposed offspring exhibited elevated basal expression of NR1, mGluR5, and mGluR2/3 in the prefrontal cortex (PFC), whereas females showed no basal expression changes. Following MWM training, PCMS-exposed males expressed higher NR1 in the PFC and mammillary body (MB), higher mGluR2/3 in PFC, and lower NR2B in the hippocampus (HIP), PFC, and MB compared to unstressed MWM-trained males. Female PCMS-exposed offspring showed strongly reduced NR1 in MB and NR2B in the HIP, PFC, and MB, and increased mGluR2/3 in PFC compared to unstressed MWM-trained females. This is the first report suggesting that NMDA subunits in the MB are involved in spatial learning. Additionally, PCA further suggests that the NR1-NR2B form is the most important for spatial memory formation. These results reveal long-term sex-specific effects of PCMS on spatial learning and memory performance in adulthood and implicate GluR expression changes within HIP, PFC, and MB as possible molecular mechanisms underlying cognitive dysfunction in offspring exposed to prenatal stress.

  11. Cut-off points for mild, moderate, and severe pain on the visual analogue scale for pain in patients with chronic musculoskeletal pain.

    Science.gov (United States)

    Boonstra, Anne M; Schiphorst Preuper, Henrica R; Balk, Gerlof A; Stewart, Roy E

    2014-12-01

    The aim of this study was to find the cut-off points on the visual analogue scale (VAS) to distinguish among mild, moderate, and severe pain, in relation to the following: pain-related interference with functioning; verbal description of the VAS scores; and latent class analysis for patients with chronic musculoskeletal pain. A total of 456 patients were included. Pain was assessed using the VAS and verbal rating scale; functioning was assessed using the domains of the Short Form (36) Health Survey (SF-36). Eight cut-off point schemes were tested using multivariate analysis of variance (MANOVA), ordinal logistic regression, and latent class analysis. The study results showed that VAS scores ⩽ 3.4 corresponded to mild interference with functioning, whereas 3.5 to 6.4 implied moderate interference, and ⩾ 6.5 implied severe interference. VAS scores ⩽ 3.4 were best described for patients with chronic musculoskeletal pain as mild pain, 3.5 to 7.4 as moderate pain, and ⩾ 7.5 as severe pain. Latent class analysis found that a 3-class solution fitted best, resulting in the classes 0.1 to 3.8, 3.9 to 5.7, and 5.8 to 10 cm. Findings from our study agree with those of some other studies, although many other studies found different optimal cut-off point schemes. As there appear to be no universally accepted cut-off points, and in view of the low-to-moderate associations between VAS scores and functioning and between VAS and verbal rating scale scores, the correct classification of VAS scores as mild, moderate. or severe in clinical practice seems doubtful.

  12. Assessing the Impact of Post Traumatic Stress Symptoms on Resting State Function Networks in a Military Chronic Mild Traumatic Brain Injury Sample.

    Science.gov (United States)

    Nathan, Dominic E; Bellgowan, Julie F; French, Louis M; Wolf, Jonathan P; Oakes, Terry; Mielke, Jeannine B; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

    2017-03-19

    The relationship between post traumatic stress disorder (PTSD) and chronic symptoms of mild traumatic brain injury (mTBI) is difficult to discern and poorly understood. An accurate differential diagnosis, assessment and treatment of mTBI and PTSD is challenging due to significant symptom overlap and the absence of clearly established biomarkers. The objective of this work is to examine how post traumatic stress influences task-free brain networks in chronic mTBI subjects. Control subjects (N=44) were compared with chronic mTBI subjects with low (N=58, PCLC totalpost traumatic stress symptoms (PTSS). The results indicate significant differences in Brodmann area 10 for all mTBI subject groups, indicating potential mTBI related disruptions with regulation of emotions and decision-making. The effects of PTSS were observed in the anterior cingulate, and parahippocampus suggesting possible disruptions pertaining to memory regulation, encoding and retrieval. The overall results indicate the presence of aberrant connectivity patterns between controls and chronic mTBI subjects with low, medium and high PTSS. Furthermore, the findings suggest a disruption in attention relating to a network of brain regions involved with emotional regulation and memory coding, rather than a fear related response. Taken together, the results suggest these regions form a network that could be a target for future research pertaining to PTSD and chronic mTBI. Furthermore, the use of clinical measures, task based imaging studies or multimodal imaging could help further elucidate specific neural correlates of PTSS and mTBI.

  13. Predictability and unpredictability in optical system optimization

    NARCIS (Netherlands)

    Van Turnhout, M.; Bociort, F.

    2007-01-01

    Local optimization algorithms, when they are optimized only for speed, have in certain situations an unpredictable behavior: starting points very close to each other lead after optimization to different minima. In these cases, the sets of points, which, when chosen as starting points for local optim

  14. Effect of intravenous human immunoglobulin G on hippocampal function of depressive model rats subjected to chronic unpredictable stress%静脉输注人免疫球蛋白G对慢性不可预料应激抑郁模型大鼠海马功能的影响

    Institute of Scientific and Technical Information of China (English)

    王晟; 徐丽芳

    2014-01-01

    目的:探讨静脉输注人免疫球蛋白G(IgG)对慢性不可预料应激抑郁模型大鼠海马功能的影响。方法对慢性不可预料应激抑郁模型大鼠分别给予静脉输注人IgG+应激( IgG组)和单纯应激( CUS组)处理,对照组不行任何处理。分别采用悬尾实验、糖水偏好实验、强迫游泳实验、自主活动实验和5-溴脱氧尿嘧啶核苷(BrdU)标记海马齿状回神经元,检测神经元再生情况。结果 IgG组及对照组糖水偏好消耗显著大于 CUS 组( P均<0.01);悬尾实验、强迫游泳实验和自主活动实验不动时间IgG组及对照组显著小于CUS组(P均<0.01);IgG组海马区域BrdU阳性细胞数与CUS组比较有统计学差异( P<0.01)。结论静脉输注人IgG对慢性不可预料应激造成的大鼠抑郁样行为具有改善作用;可保护海马的神经元再生功能。%Objective To investigate the effect of intravenous human immunoglobulin G ( IgG) on depressive model rats subjected to chronic unpredictable stress .Methods Depressive model rats subjected to chronic unpredictable stress were randomly divided into 3 groups: intravenous immunoglobulin G ( IVIG) +stress group ( IVIG group), stress-only group ( CUS group) and the control group without any treatment .Tail suspension test , sucrose preference test , forces swimming test, locomotor activity and BrdU labeling neuron of hippocampal dentate gyrus based neurogenesis were used to analyze the effect of IVIG on depressive model rats .Results Sucrose consumption in the IVIG group and control group was significantly less than that of the CUS group (P<0.01), while duration of immobility of tail suspension test , forced swimming test and lo-comotor activity was significantly shorter than that of the CUS group (all P<0.01).The difference of BrdU positive cell number in the hippocampus between the two groups was significant (P<0.01).Conclusion IVIG can improve the depres

  15. The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress.

    Science.gov (United States)

    First, Maya; Gil-Ad, Irit; Taler, Michal; Tarasenko, Igor; Novak, Nurit; Weizman, Abraham

    2013-05-01

    Chronic mild stress (CMS) in rats is an established rodent depression model. Antidepressants attenuate the depression-like symptoms and prevent the biochemical changes caused by stress. In the present study, we examined the effect of CMS and the selective norepinephrine reuptake inhibitor (NRI) reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal and cortical neurotrophic factors. Male Sprague Dawley rats were exposed for 5 weeks to a variety of mild stressors. REB (5 mg/kg/i.p.) was daily injected to half of the stressed and unstressed groups. Animal behavior following CMS was tested using the Morris Water Maze (MWM) cognitive paradigm and by monitoring sucrose intake and weight gain. After 5 weeks of CMS, stressed rats showed decreased sucrose intake, and REB treatment normalized this decrease. CMS reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, and REB treatment reversed this alteration and increased BDNF receptor (TrkB) levels. REB elevated hippocampal extracellular signal-regulated kinase (ERK) phosphorylation of both stressed and unstressed rats. In conclusion, our study shows that BDNF, its receptor TrkB, and ERK participate in the neurobiological response to chronic stress and in the molecular and cellular activities of REB in the hippocampus.

  16. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury

    OpenAIRE

    Radouil Tzekov; Clint Dawson; Megan Orlando; Benoit Mouzon; Jon Reed; James Evans; Gogce Crynen; Michael Mullan; Fiona Crawford

    2016-01-01

    Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue w...

  17. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Sørensen, T; Lange, Peter;

    1999-01-01

    for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat. FINDINGS: The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year...... recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD....

  18. Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

    Science.gov (United States)

    Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

    2015-11-01

    Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis

  19. A systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury. Results of the International Collaboration on MTBI Prognosis (ICoMP)

    DEFF Research Database (Denmark)

    Godbolt, Allison; Cancelliere, Carol; Hincapié, Cesar A

    2014-01-01

    -defined criteria. Peer-reviewed reports in six languages were considered. Study selection: Systematic reviews, meta-analyses, randomized controlled trials (RCTs), cohorts and case-control studies, with a minimum of 30 MTBI cases in subjects of any age, assessing the risk of dementia or CCI after MTBI were selected...... synthesis: Evidence from accepted studies was synthesized qualitatively according to modified SIGN criteria and prognostic information was prioritized as exploratory or confirmatory, according to design. Of 77 914 records screened, 304 articles were eligible and reviewed. Methodological quality......Objective: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI), following mild traumatic brain injury (MTBI). Data sources: MEDLINE and other databases were searched (2001–2012), using a previously published search strategy and pre...

  20. Chronic ultra-mild stress improves locomotor performance of B6D2F1 mice in a motor risk situation.

    Science.gov (United States)

    Negroni, Julia; Venault, Patrice; Pardon, Marie Christine; Pérez-Diaz, Fernando; Chapouthier, Georges; Cohen-Salmon, Charles

    2004-12-06

    Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established.

  1. Effects of Ning Shen Ling Granule(宁神灵冲剂)and Dehydroepiandrosterone on Cognitive Function in Mice Undergoing Chronic Mild Stress

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao; DONG Yi-long; YANG Nan; LIU Yan-yong; GAO Rui-feng; ZUO Ping-ping

    2007-01-01

    Objective:To investigate the changes of spontaneous and cognitive behavior,and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS),and to determine the effect of Ning Shen Ling Granule (宁神灵冲剂,NSL) and dehydroepiandrosterone (DHEA) on them.Methods:CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources,and they were medicated for 1 week beginning at the 3rd week of modeling.The changes in behavior were determined by Morris Water Maze and spontaneous movement test,and M-receptor binding activity in cerebral cortex,hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.Results:(1)The spontaneous movement in CMS model mice was significantly reduced,with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01),and these abnormal changes in behavior were improved in those treated with NSL and DHEA.(2)The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05),but could be restored to the normal level after intervention with NSL or DHEA.Conclusion:The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress,and that may be related to the low activity of central cholinergic M-receptors.Both NSL and DHEA could effectively alleviate the above-mentioned changes.

  2. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

    Directory of Open Access Journals (Sweden)

    Radouil Tzekov

    Full Text Available Repetitive mild traumatic brain injury (r-mTBI results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL, tubulin (TUBB2A, TUBA4A, microtubule-associated proteins (MAP1A, MAP1B, collagen (COL6A1, COL6A3 and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1, APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC, including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the

  3. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

    Science.gov (United States)

    Tzekov, Radouil; Dawson, Clint; Orlando, Megan; Mouzon, Benoit; Reed, Jon; Evans, James; Crynen, Gogce; Mullan, Michael; Crawford, Fiona

    2016-01-01

    Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of

  4. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress

    Directory of Open Access Journals (Sweden)

    Muhammad Farhan

    2016-09-01

    Full Text Available Background: Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI, has been proposed to be more effective as an antidepressive drug as compared to other SSRIs. After chronic SSRI administration, the increase in synaptic levels of 5-HT leads to desensitization of somatodentritic 5-HT autoreceptors in the raphe nuclei. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Methods: Twenty four male rats were used in this study. Animals of CMS group were exposed to CMS. Animals of stressed and unstressed group were administrated with fluoxetine at dose of 1.0 mg/kg s well as 5.0 mg/kg repeatedly for 07 days 1 h before exposed to CMS. The objective of the present study was to evaluate that repeated treatment with fluoxetine could attenuate CMS-induced behavioral deficits. Results: Treatment with fluoxetine attenuated CMS-induced behavioral deficits. Fluoxetine administration induced hypophagia in unstressed as well as CMS rats. Acute and repeated administration of fluoxetine increased motor activity in familiar environment but only repeated administration increased exploratory activity in open field. Anxiolytic effects of fluoxetine were greater in unstressed rats. These anxiolytic effects were produced as result of repeated administration not on acute administration of fluoxetine at 1.0 mg/kg as well as 5.0 mg/kg. Conclusion: The present study demonstrated that CMS exposure resulted into behavioral deficits and produced depressive-like symptoms. Fluoxetine, an SSRI, administration attenuated behavioral deficits induced by CMS. Anxiolytic effects of repeated fluoxetine administration were greater in unstressed than CMS animals.

  5. Diffusion kurtosis imaging and high-resolution MRI demonstrate structural aberrations of caudate putamen and amygdala after chronic mild stress.

    Science.gov (United States)

    Delgado y Palacios, Rafael; Verhoye, Marleen; Henningsen, Kim; Wiborg, Ove; Van der Linden, Annemie

    2014-01-01

    The pathophysiology of major depressive disorder (MDD) and other stress related disorders has been associated with aberrations in the hippocampus and the frontal brain areas. More recently, other brain regions, such as the caudate nucleus, the putamen and the amygdala have also been suggested to play a role in the development of mood disorders. By exposing rats to a variety of stressors over a period of eight weeks, different phenotypes, i.e. stress susceptible (anhedonic-like) and stress resilient animals, can be discriminated based on the sucrose consumption test. The anhedonic-like animals are a well validated model for MDD. Previously, we reported that in vivo diffusion kurtosis imaging (DKI) of the hippocampus shows altered diffusion properties in chronically stressed rats independent of the hedonic state and that the shape of the right hippocampus is differing among the three groups, including unchallenged controls. In this study we evaluated diffusion properties in the prefrontal cortex, caudate putamen (CPu) and amygdala of anhedonic-like and resilient phenotypes and found that mean kurtosis in the CPu was significantly different between the anhedonic-like and resilient animals. In addition, axial diffusion and radial diffusion were increased in the stressed animal groups in the CPu and the amygdala, respectively. Furthermore, we found that the CPu/brain volume ratio was increased significantly in anhedonic-like animals as compared with control animals. Concurrently, our results indicate that the effects of chronic stress on the brain are not lateralized in these regions. These findings confirm the involvement of the CPu and the amygdala in stress related disorders and MDD. Additionally, we also show that DKI is a potentially important tool to promote the objective assessment of psychiatric disorders.

  6. Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response.

    Science.gov (United States)

    Havranek, Michael M; Bolliger, Bianca; Roos, Sophie; Pryce, Christopher R; Quednow, Boris B; Seifritz, Erich

    2016-01-01

    According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 × 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity.

  7. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease

    DEFF Research Database (Denmark)

    Pitt, Bertram; Kober, Lars; Ponikowski, Piotr;

    2013-01-01

    Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroida......Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non......-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD)....

  8. Antidepressant-like action of AGN 2979, a tryptophan hydroxylase activation inhibitor, in a chronic mild stress model of depression in rats.

    Science.gov (United States)

    Gittos, M W; Papp, M

    2001-10-01

    Chronic mild stress (CMS) procedure was used to study an antidepressant-like activity of AGN 2979, a selective inhibitor of tryptophan hydroxylase (TH) activation. At the dose of 4 mg/kg, AGN 2979 fully reversed the CMS-induced reduction in the consumption of 1% sucrose solution. This effect was maintained for at least 1 week after cessation of treatment and no signs of withdrawal were observed in either stressed or control animals receiving AGN 2979. The lower (1 mg/kg) and higher (16 mg/kg) doses were ineffective. The magnitude of action of AGN 2979 in the CMS model was comparable to that of imipramine (10 mg/kg) but its onset of action appears to be faster since the inhibition of sucrose intake in stressed animals was already reversed after the 1st week of AGN 2979 administration while imipramine required 3 weeks of treatment to cause similar effect. These results provide support for the hypothesis that inhibition of TH activation may result in a potent antidepressant activity.

  9. Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats' response to chronic mild stress and the effects of Notch signaling.

    Directory of Open Access Journals (Sweden)

    Shaohua Wang

    Full Text Available Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO. Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl]-S-phenyl-glycine t-butyl ester. We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells' synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.

  10. Young-Adult Male Rats' Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors

    Science.gov (United States)

    José Jaime, Herrera-Pérez; Venus, Benítez-Coronel; Graciela, Jiménez-Rubio; Tania, Hernández-Hernández Olivia

    2016-01-01

    In a previous study, we found that chronic mild stress (CMS) paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal's vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals' body weight and sucrose preference (indicator of anhedonia) were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests); meanwhile, others were used to measure serum corticosterone. We found that CMS (1) did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2) decreased body weight gain; and (3) increased the rat's entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats' vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors. PMID:27433469

  11. Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS).

    Science.gov (United States)

    Chandrasekhar, Y; Ramya, E M; Navya, K; Phani Kumar, G; Anilakumar, K R

    2017-02-01

    Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i.p.) and TC (25, 50 and 100mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder.

  12. Effects of Chronic Mild Stress on the Development of Atherosclerosis and Expression of Toll-Like Receptor 4 Signaling Pathway in Adolescent Apolipoprotein E Knockout Mice

    Directory of Open Access Journals (Sweden)

    Hongfeng Gu

    2009-01-01

    Full Text Available Here, we investigated the effect of chronic mild stress (CMS on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs signaling pathway in adolescent apolipoprotein E knockout (apoE-/- mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88, and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factor κB (NF-κB, MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

  13. Neuroplastic Correlates in the mPFC Underlying the Impairment of Stress-Coping Ability and Cognitive Flexibility in Adult Rats Exposed to Chronic Mild Stress during Adolescence

    Science.gov (United States)

    Zhang, Yu; Shao, Feng; Wang, Qiong; Xie, Xi

    2017-01-01

    Using a valid chronic mild stress (CMS) model of depression, we found that adolescent (postnatal days [PND] 28–41) CMS induced transient alterations in anhedonia that did not persist into adulthood after a 3-week recovery period. Previously stressed adult rats exhibited more immobility/despair behaviors in the forced swimming test and a greater number of trials to reach criterion in the set-shifting task, suggesting the impaired ability to cope with stressors and the cognitive flexibility that allows adaptation to dynamic environments during adulthood. In addition, adult rat exposure to adolescent CMS had a relatively inhibited activation in ERK signaling and downstream protein expression of phosphorylated cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex. Further correlation analysis demonstrated that immobility and set-shifting performance were positively correlated with the inhibition of ERK signaling. These results indicated adolescent CMS can be used as an effective stressor to model an increased predisposition to adult depression. PMID:28182105

  14. Effectiveness of a minimal psychological intervention to reduce mild to moderate depression and chronic fatigue in a working population: the design of a randomized controlled trial

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    Aelfers Ed

    2013-02-01

    Full Text Available Abstract Background In a working population, common mental complaints like depressed mood and chronic fatigue are highly prevalent and often result in further deterioration of mental health and consequently absence from work. In a large occupational health setting, we will evaluate the (cost- effectiveness of a Minimal Psychological Intervention (MPI, in reducing symptoms of depression and chronic fatigue in a working population. The MPI is also evaluated regarding its appreciation by worker, nurse, and occupational health physician (process evaluation. The tailor-made intervention is administered by nurses, who are trained in the principles of cognitive behavioural therapy and self-management. Methods/design The presented WoPaCoM study (Work Participation of Workers with Common Mental complaints is a two-armed randomized controlled trial, comparing MPI with usual care. A total number of 124 workers suffering from (chronic mental fatigue or mild to moderate depression will be included. A stratified and block randomization will be applied, stratifying by customer organisation, income, and gender, using a block size of four. It will include a baseline measurement and subsequently follow up measurements after 4, 6 and 12 months. The primary outcome measures are symptoms of either fatigue (using the Checklist Individual Strength and/or depression (using the Beck Depression Inventory and secondary outcome measures include sickness absence, self efficacy, costs and quality of life. Analysis will include both univariate and multivariate techniques and data will be analysed according to the intention to treat principle. Discussion Patient recruitment in an occupational setting proves to be complicated and time consuming. Shift work for instance proved to be an obstacle for making appointments for consultation with the nurse. Furthermore, economic developments might have created job insecurity which negatively influenced participation in the study, with

  15. 慢性不可预见性应激易感性差异的5-羟色胺转运体和5-羟色胺受体机制研究%Mechanisms of serotonin transporter and serotonin 1A receptor in the different susceptibility of chronic unpredictable stress

    Institute of Scientific and Technical Information of China (English)

    刘杰; 王瑛; 贾梅志; 王晓慧; 张尚荣; 尚士渲

    2013-01-01

    Objective To investigate the expression of serotonin transporter (5-HTT) and serotonin 1A treceptor (5-HT1 A R) located in the chronic unpredictable stress (CUS)-relative brain areas (mPFC,VTA,NAc) in high and low CUS susceptibility rats,thus to unveil the possible mechanism lead to the different CUS susceptibility.Methods One hundred and fifty male Sprague-Dawley rats were randomly assigned into experiment group (n =120) and control group (n =30).Rats in experiment group were trained according to established CUS procedure.OFT and FST were used to assess the different susceptibility to CUS:high susceptibility group (H group)and low susceptibility group (L group).After the model was established,rats were scarified and cardio-perfused,and the brains were removed and sliced up coronarily.The sections including ventral tegmental area (VTA),nucleus accumben (NAc),medial prefrontal cortex (mPFC) were selected.The mRNA levels of 5-HTT and 5-HT1AR in the regions were estimated with in situ hybridization.Results The expression of 5-HTT in H group were significantly lower than that of in the control and L group in all regions (mPFC:169.20 ± 8.23 vs 143.53 ±5.31 ; Nac:177.41 ± 5.68 vs 158.65 ± 5.24 ; VTA:174.16 ± 5.61 vs 158.65 ± 4.85),and the difference between the H and L group was significant(P<0.01) ;however,the expression of 5-HT1AR in H group were significantly higher than that of in the control and L group in all regions (mPFC:113.98 ± 7.46 vs 125.90 ± 3.30 ; Nac:112.11± 5.50 vs 125.06 ± 3.97 ;VTA:103.11 ± 6.05 vs 115.57 ± 3.19),and the difference between the H and L group was significant (P< 0.01).Conclusion The overexpression of 5-HT1AR and down regulation of 5-HTT in the circuit of VTA-NAc-mPFC may be the basis of the high susceptibility to CUS.%目的 探讨大鼠慢性不可预见性应激(Chronic Unpredictable Stress,CUS)易感性差异的中脑边缘系统5-羟色胺转运体(5-HTT)和5-羟色胺1A受体(5-HT1AR)机制.方法 150只雄性Sprague

  16. Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air

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    Lopez Ivan A

    2009-05-01

    Full Text Available Abstract Background The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO exposure (25 parts per million subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5 to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO. At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS, neuronal (nNOS, and endothelial (eNOS nitric oxide synthases. Results Superoxide dismutase-1 (SOD1, SOD2, and hemeoxygenase-1 (HO-1 immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein, synapsin-1 (functional protein, and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA, were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained

  17. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression.

    Science.gov (United States)

    Han, X; Shao, W; Liu, Z; Fan, S; Yu, J; Chen, J; Qiao, R; Zhou, J; Xie, P

    2015-07-09

    Major depressive disorder (MDD) is a prevalent psychiatric mood illness and a major cause of disability and suicide worldwide. However, the underlying pathophysiology of MDD remains poorly understood due to its heterogenic nature. Extensive pre-clinical research suggests that many molecular alterations associated with MDD preferentially localize to the postsynaptic density (PSD). Here, we used a rodent chronic mild stress (CMS) model to generate susceptible and unsusceptible subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass spectrometry was performed to identify differentially expressed proteins in enriched PSD preparations from the hippocampi of different groups. More than 1500 proteins were identified and quantified, and 74 membrane proteins were differentially expressed. Of these membrane proteins, 51 (69%) were identified by SynaptomeDB search as having a predicted PSD localization. The unbiased profiles identified several PSD candidate proteins that may be related to CMS vulnerability or insusceptibility, and these two CMS phenotypes displayed differences in the abundance of several types of proteins. A detailed protein functional analysis pointed to a role for PSD-associated proteins involved in signaling and regulatory functions. Within the PSD, the N-methyl-D-aspartate (NMDA) receptor subunit NR2A and its downstream targets contribute to CMS susceptibility. Further analysis of disease relevance indicated that the PSD contains a complex set of proteins of known relevance to mental illnesses including depression. In sum, these findings provide novel insights into the contribution of PSD-associated proteins to stress susceptibility and further advance our understanding of the role of hippocampal synaptic plasticity in MDD.

  18. 7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress

    Science.gov (United States)

    Chang, Hsin-An; Wang, Ying-Hsiu; Tung, Che-Se; Yeh, Chin-Bin

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. Methods SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. Results Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. Conclusion 7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.

  19. Brainstem white matter integrity is related to loss of consciousness and postconcussive symptomatology in veterans with chronic mild to moderate traumatic brain injury.

    Science.gov (United States)

    Delano-Wood, L; Bangen, K J; Sorg, S F; Clark, A L; Schiehser, D M; Luc, N; Bondi, M W; Werhane, M; Kim, R T; Bigler, E D

    2015-09-01

    We investigated associations between DTI indices of three brainstem white matter tracts, traumatic brain injury (TBI) injury characteristics, and postconcussive symptomatology (PCS) in a well-characterized sample of veterans with history of mild to moderate TBI (mTBI). 58 military veterans (mTBI: n = 38, mean age = 33.2, mean time since injury = 90.9 months; military controls [MC]; n = 20; mean age = 29.4) were administered 3T DTI scans as well as a comprehensive neuropsychiatric evaluation including evaluation of TBI injury characteristics and PCS symptoms (e.g., negative mood, dizziness, balance and coordination difficulties). Tractography was employed by seeding ROIs along 3 brainstem white matter tracts (i.e., medial lemniscus-central tegmentum tract [ML-CTT]; corticospinal tracts [CST], and pontine tegmentum [PT]), and mean DTI values were derived from fractional anisotropic (FA) maps. Results showed that there were no significant difference in FA between the MC and TBI groups across the 3 regions of interest; however, among the TBI group, CST FA was significantly negatively associated with LOC duration. Additionally, lower FA of certain tracts-most especially the PT-was significantly associated with increased PCS symptoms (i.e., more severe vestibular symptoms, poorer physical functioning, and greater levels of fatigue), even after adjusting for PTSD symptoms. Our findings show that, in our sample of veterans with mTBI, tractography-based DTI indices of brainstem white matter tracts of interest are related to the presence and severity of PCS symptoms. Findings are promising as they show linkages between brainstem white matter integrity and injury severity (LOC), and they raise the possibility that the pontine tegmentum in particular may be a useful marker of PCS symptoms. Collectively, these data point to important neurobiological substrates of the chronic and complex constellation of symptoms following the 'signature injury' of our

  20. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

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    Udaiyappan Janakiraman

    Full Text Available Parkinson's disease (PD is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS, a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt. with probenecid (250 mg/kg, s.c. (MPTP/p induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor impairments, levels and expressions of dopamine (DA, serotonin (5-HT, DAergic markers such as tyrosine hydroxylase (TH, dopamine transporter (DAT, vesicular monoamine transporters-2 (VMAT 2 and α-synuclein in nigrostriatal (striatum (ST and substantia nigra (SN and extra-nigrostriatal (hippocampus, cortex and cerebellum tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  1. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study.

    Science.gov (United States)

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-04-01

    The kidney is one of the organs most prominently affected by aging. This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons resulting in hyperfiltration, hypertrophy and elevations in glomerular pressure. The factors influencing aging of the kidney are not fully elucidated. Epidemiological, experimental and interventional studies resulted in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease (CKD). Therefore, we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18-65 years with primary non-diabetic CKD of various degrees of renal impairment. Of them, 177 completed a prospective follow-up of 7 years. Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and/or terminal renal failure. Patients who reached a progression endpoint (n =6 5) were significantly older, had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate (GFR). Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis. Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters. As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished. In summary, our prospective 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression.

  2. [Unpredictable risk and damage compensation in civil process].

    Science.gov (United States)

    Vayre, P

    1998-04-01

    UNPREDICTABLE RISK DEFINITION: Any medical or surgical action with diagnostic or therapeutic purpose involves a potential risk of complication, unrelated to the initial pathology or a technical error, but could lead to death or disability. Proof of unpredictable risk without initial fault requires a careful examination of each case by a judicial expert in order to eliminate the complications related to an unskilled surgeon or to poor postoperative care. UNPREDICTABLE RISK COMPENSATION: Conclusions of the Academy: In current French common law, damage compensation can only be obtained in cases where all possible medical means are not implemented and professional fault can be proven. It is illogical to extend the civil responsibility of the practitioner to an obligation of procedural result. In the absence of fault, damage compensation does not come under the civil responsibility of the surgeon. A special insurance system for unpredictable risk has to be created using the principles of mutual insurance.

  3. Chronic Mild Cold Conditioning Modulates the Expression of Hypothalamic Neuropeptide and Intermediary Metabolic-Related Genes and Improves Growth Performances in Young Chicks.

    Directory of Open Access Journals (Sweden)

    Phuong Nguyen

    Full Text Available Low environmental temperatures are among the most challenging stressors in poultry industries. Although landmark studies using acute severe cold exposure have been conducted, still the molecular mechanisms underlying cold-stress responses in birds are not completely defined. In the present study we determine the effect of chronic mild cold conditioning (CMCC on growth performances and on the expression of key metabolic-related genes in three metabolically important tissues: brain (main site for feed intake control, liver (main site for lipogenesis and muscle (main site for thermogenesis.80 one-day old male broiler chicks were divided into two weight-matched groups and maintained in two different temperature floor pen rooms (40 birds/room. The temperature of control room was 32°C, while the cold room temperature started at 26.7°C and gradually reduced every day (1°C/day to reach 19.7°C at the seventh day of the experiment. At day 7, growth performances were recorded (from all birds and blood samples and tissues were collected (n = 10. The rest of birds were maintained at the same standard environmental condition for two more weeks and growth performances were measured.Although feed intake remained unchanged, body weight gain was significantly increased in CMCC compared to the control chicks resulting in a significant low feed conversion ratio (FCR. Circulating cholesterol and creatine kinase levels were higher in CMCC chicks compared to the control group (P<0.05. CMCC significantly decreased the expression of both the hypothalamic orexigenic neuropeptide Y (NPY and anorexigenic cocaine and amphetamine regulated transcript (CART in chick brain which may explain the similar feed intake between the two groups. Compared to the control condition, CMCC increased the mRNA abundance of AMPKα1/α2 and decreased mTOR gene expression (P<0.05, the master energy and nutrient sensors, respectively. It also significantly decreased the expression of fatty

  4. Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

    Science.gov (United States)

    Franceschelli, A; Sens, J; Herchick, S; Thelen, C; Pitychoutis, P M

    2015-04-02

    During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice.

  5. A New Arbiter PUF for Enhancing Unpredictability on FPGA.

    Science.gov (United States)

    Machida, Takanori; Yamamoto, Dai; Iwamoto, Mitsugu; Sakiyama, Kazuo

    2015-01-01

    In general, conventional Arbiter-based Physically Unclonable Functions (PUFs) generate responses with low unpredictability. The N-XOR Arbiter PUF, proposed in 2007, is a well-known technique for improving this unpredictability. In this paper, we propose a novel design for Arbiter PUF, called Double Arbiter PUF, to enhance the unpredictability on field programmable gate arrays (FPGAs), and we compare our design to conventional N-XOR Arbiter PUFs. One metric for judging the unpredictability of responses is to measure their tolerance to machine-learning attacks. Although our previous work showed the superiority of Double Arbiter PUFs regarding unpredictability, its details were not clarified. We evaluate the dependency on the number of training samples for machine learning, and we discuss the reason why Double Arbiter PUFs are more tolerant than the N-XOR Arbiter PUFs by evaluating intrachip variation. Further, the conventional Arbiter PUFs and proposed Double Arbiter PUFs are evaluated according to other metrics, namely, their uniqueness, randomness, and steadiness. We demonstrate that 3-1 Double Arbiter PUF archives the best performance overall.

  6. A New Arbiter PUF for Enhancing Unpredictability on FPGA

    Directory of Open Access Journals (Sweden)

    Takanori Machida

    2015-01-01

    Full Text Available In general, conventional Arbiter-based Physically Unclonable Functions (PUFs generate responses with low unpredictability. The N-XOR Arbiter PUF, proposed in 2007, is a well-known technique for improving this unpredictability. In this paper, we propose a novel design for Arbiter PUF, called Double Arbiter PUF, to enhance the unpredictability on field programmable gate arrays (FPGAs, and we compare our design to conventional N-XOR Arbiter PUFs. One metric for judging the unpredictability of responses is to measure their tolerance to machine-learning attacks. Although our previous work showed the superiority of Double Arbiter PUFs regarding unpredictability, its details were not clarified. We evaluate the dependency on the number of training samples for machine learning, and we discuss the reason why Double Arbiter PUFs are more tolerant than the N-XOR Arbiter PUFs by evaluating intrachip variation. Further, the conventional Arbiter PUFs and proposed Double Arbiter PUFs are evaluated according to other metrics, namely, their uniqueness, randomness, and steadiness. We demonstrate that 3-1 Double Arbiter PUF archives the best performance overall.

  7. Effects of exercise on behavior and serum cortisol in depression due to chronic mild stress%不同时程游泳运动对抑郁症模型大鼠行为及血清皮质醇的影响

    Institute of Scientific and Technical Information of China (English)

    何松彬; 王小同; 唐闻捷

    2008-01-01

    目的 观察不同时程游泳运动对抑郁症模型大鼠行为及血清皮质醇的影响.方法 选取48只SD大鼠随机分为3个大组,每个大组各设3个亚组(每个亚组6只大鼠),第一大组观察造模时运动对大鼠的影响(造模伴运动组),包括空白对照组、造模对照组、造模伴运动组;第二大组观察造模后运动对大鼠的影响(造模后运动组),包括空白对照组、造模对照组、造模后运动组;第三大组观察造模前运动对大鼠的影响(造模前运动组),包括空白对照组、造模对照组、造模前运动组(造模后运动组与造模前运动组为同一组).所有造模大鼠均给予21 d慢性轻度不可预见性应激,记录大鼠旷野试验、糖水试验相关数据,用放射免疫法测定血清皮质醇含量.结果 造模可使大鼠出现糖水摄入减少、糖水偏爱度降低,在旷野试验中水平运动能力减弱、垂直运动能力减弱、排粪便数增加.造模伴运动组大鼠上述现象得到抑制,造模前运动组及造模后运动组的大鼠均未能显示抑制现象,造模可使大鼠血皮质醇含量升高,造模伴运动组及造模前运动组能有效降低血清皮质醇含量,其中造模伴运动组尤为明显.结论 不同时程的游泳运动对抑郁症模型大鼠行为学及血清皮质醇具有不同的影响作用;运动可以降低血清皮质醇含量,并且具有一定的累积效应;运动对抑郁症状的改变以即刻作用为主,没有长期累积作用.%Objective To investigate the effects of exercise on behavior and serum cortisol levels in depression caused by chronic,unpredictable,mild stress(CUMS).Methods Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups:A,B and C.Each group was then divided into 3 subgroups:a blank control subgroup,a model subgroup,and an intervention subgroup.CUMS such as unpredictable forced swimming in cold water,electric stimulation of the animals'feet and shaking of the

  8. Expression of microtubule associated protein-2 in hippocampus and effect of fluoxetine combine with enrich environment in chronic unpredictable stress rats%慢性刺激大鼠海马微管相关蛋白-2的表达及氟西汀联合丰富环境的作用

    Institute of Scientific and Technical Information of China (English)

    刘聪; 王长虹; 闫福林; 韩金红; 谷景阳; 翟飞; 单筱雯

    2015-01-01

    Objective To discuss the change of the expression level of microtubule associated protein-2 (MAP-2) in hippocampus and the effect of fluoxetine combine with enrich environment in chronic unpredictable stress (CUS) rat.Methods Divided 30 male Sprague-Dawle (SD) rats into CUS group,normal group,CUS + fluoxetine group,CUS + enrich environment group,and CUS + fluoxetine + enrich environment group averagely and randomly according to random number table (n=6 each).Rats in CUS group were all fed lonely and received CUS for 6 weeks.Rats in normal group were fed in groups (3 rats in every cage) in standard environment for 6 weeks.Rats in CUS+fluoxetine group,CUS+enrich environment group,and CUS + fluoxetine + enrich environment group received CUS for 6 weeks and had a lavage with fluoxetine,an intervention of enrich environment,a lavage with fluoxetine + an intervention of enrich environment respectively during the last 3 weeks every day.Every rat went a behavioral assessment before and after CUS and after intervention.Behavioral assessment included sucrose water consumption test,weight measurement,and open field test (horizontal moving distance,number of vertical,number of faece).Measured the level of MAP-2 expressed in hippocampus with immunohistochemistry at last.Results (1) Behavioral assessment before CUS:there was no significant difference between CUS group,normal group,CUS + fluoxetine group,CUS + enrich environment group and CUS + fluoxetine + enrich environment group in sucrose water consumption test,weight measurement,horizontal moving distance,number of vertical and number of faece.(2) Behavioral assessment after CUS:consumption of sucrose water,gain of body weight,distance of horizontal moving of rats in CUS group,CUS + fluoxetine group,CUS + enrich environment group,and CUS+fluoxetine+enrich environment group were all less than rats in normal group (all P<0.05).(3)Behavioral assessment after intervention:consumption of sucrose water,gain of body weight

  9. Cut-off points for mild, moderate, and severe pain on the visual analogue scale for pain in patients with chronic musculoskeletal pain

    NARCIS (Netherlands)

    Boonstra, Anne M.; Schiphorst Preuper, Henrica R. Schiphorst; Balk, Gerlof A.; Stewart, Roy E.

    2014-01-01

    The aim of this study was to find the cut-off points on the visual analogue scale (VAS) to distinguish among mild, moderate, and severe pain, in relation to the following: pain-related interference with functioning; verbal description of the VAS scores; and latent class analysis for patients with ch

  10. Effects of TCM compound of resolving stagnation for tranquilization on neurotransmitters and brain-derived neurotrophic factors in depression rat model by chronic unpredictable stress%解郁安神中药对抑郁模型大鼠神经递质及脑源性神经营养因子的影响

    Institute of Scientific and Technical Information of China (English)

    邹海艳; 王蕾; 张弛; 张秋霞; 杨亦龙; 屠蘅菁; 姚晓泉; 王雅丽; 刘思思; 欧阳俊; 王海征; 赵晖

    2015-01-01

    目的:观察解郁安神中药对慢性不可预见性应激( CUS)抑郁大鼠模型神经递质及脑源性神经营养因子( BDNF)的影响,探讨其抗抑郁的作用机制。方法雄性SD大鼠随机分为正常组,模型组,解郁安神中药小、中、大剂量组(8.2、16.3、32.7 g/kg),盐酸氟西汀组(10 mg/kg)。应激刺激开始的同时连续灌胃药物35 d。通过敞箱实验、新奇抑制摄食实验观察药物对大鼠行为学的影响;采用HPLC法测定药物对大鼠海马、皮层的多巴胺( DA)、5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)、去甲肾上腺素(NE)含量的影响;利用Western blot观察药物对大鼠海马BNDF的表达。结果模型组大鼠体重增长缓慢,在行为学测试中表现出自主活动减少;皮层的5-HT和NE的含量明显降低( P<0.05),海马5-HT及5-HIAA、NE的水平亦显著降低( P<0.05), BDNF的表达显著下降(P<0.05)。与模型组比较,解郁安神中药各剂量均可不同程度改善CUS抑郁大鼠自发活动的减少;中药中、大剂量及盐酸氟西汀可显著提高皮层5-HT、NE的含量( P<0.05),中药小、大剂量组可显著提高海马NE的含量( P<0.05),中药各剂量可显著提高海马5-HT、5-HIAA的含量(P<0.05);中药大剂量及盐酸氟西汀可上调海马BDNF的表达(P<0.05)。结论解郁安神中药抗抑郁的作用机制可能与其对神经递质的影响及上调脑源性神经营养因子有关。%Objective To observe the effect of TCM compound of resolving stagnation for tranquilization ( RST) on neurotransmitters and brain derived neurotrophic factors ( BNDF ) in depression rat model induced by chronic unpredictable stress ( CUS) , and to reveal the mechanism of RST on the treatment of depression.Methods Altogether 60 male SD rats were randomly divided into normal group, model group, high-, mid-and low-dose RST

  11. 母鼠妊娠前慢性不可预见性应激对胎鼠大脑5-羟色胺1A受体表达的影响%Effect of Pregestational Chronic Unpredictable Stress on Expression of 5-Hydroxytryptamine 1A Receptor of Brain in Fetal Rats

    Institute of Scientific and Technical Information of China (English)

    黄月君; 史雪川; 许宏武; 杨汉华; 陈思红; 陈晓东

    2011-01-01

    Objective To investigate the effect of chronic unpredictable stress(CUS) before pregnancy on serum cortisol(COR) level of maternal rats and the expression of 5 - hydroxytryptamine 1A(5 - HT1 A) of brain in fetal rats.Methods Adult female SD rats were divided randomly into 2 groups: control group (n = 8 )and C US model group( n = 12).All rats were tested in the open field test and sucrose intake test before and after CUS protocol.All maternal rats were sacrificed in embryonic day 20.Serum COR level of maternal rats was determined by using a standard radioimmunoassay kit.The expression levels of 5 - HT1A receptor mRNA in hippocampus, hypothalamus and prefrontal cortex of fetal rats were studied by reverse transcription polymerase chain reaction ( RT - PCR).Results 1.After CUS, the total distance, central distance and peripheral distance in the open field test and sucrose consumption in sucrose intake test of CUS group decreased compared with those before CUS and control group.2.CUS induced a significant increase in cortisol levels of the maternal rats( 190.2 ± 19.8 ) μg · L-1,compared with the control group[( 155.3 ± 14.4) μg · L-1].3.The body weight and brain weight between the fetal rats of 2 groups had no statistic significance.4.RT - PCR showed that the level of 5 - HT1 A receptor mRNA in the hippocampus of CUS group( 0.228 ± 0.132 ) less than in control group(0.286 ± 0.025 ), as well as in prefrontal cortex of CUS group(0.249 ± 0.027 )compared with control group (0.266 ±0.028 ) (Pa < 0.01 ), but it had no effect in hypothalamus( P > 0.05 ).Conclusion Progestational CUS reduced the expression of 5 - HT1 A receptor in corresponding brain of the fetus which related with COR.%目的 观察母鼠妊娠前接受慢性不可预见性应激(CUS)后皮质醇(COR)水平改变对胎鼠大脑不同区域5-羟色胺1A(5-HT1A)受体表达的影响.方法 SD成年健康雌性大鼠20只随机分为正常对照母鼠组(8只)和CUS母鼠组(12只).采用11种

  12. Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms.

    NARCIS (Netherlands)

    Zannad, Faiez; McMurray, John J. V.; Krum, Henry; van Veldhuisen, Dirk J.; Swedberg, Karl; Shi, Harry; Vincent, John; Pocock, Stuart J.; Pitt, Bertram

    2011-01-01

    Background: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. Methods: In this randomized,

  13. Functional states of rat cortical circuits during the unpredictable availability of a reward-related cue.

    Science.gov (United States)

    Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García, José M

    2016-11-21

    Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly.

  14. Unpredictable feeding impairs glucose tolerance in growing lambs.

    Directory of Open Access Journals (Sweden)

    Anne L Jaquiery

    Full Text Available Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24 or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21. Intravenous glucose tolerance tests (IVGTT, insulin tolerance tests (ITT, and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18 ± 2%; U 16 ± 2% of initial body weight. Glucose area under the curve (AUC was unchanged in C (AUC pre 818 ± 34, post 801 ± 33 mmol.min.l(-1, but increased by 20% in U (pre 830 ± 25, post 1010 ± 19 mmol.min.l(-1; p<0.0001, with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes post intervention C 1.49 ± 0.04 vs U 1.36 ± 0.04 ng.min.ml(-1; p = 0.03. Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism.

  15. CPG Control for Biped Hopping Robot in Unpredictable Environment

    Institute of Scientific and Technical Information of China (English)

    Tingting Wang; Wei Guo; Mantian Li; Fusheng Zha; Lining Sun

    2012-01-01

    A CPG control mechanism is proposed for hopping motion control of biped robot in unpredictable environment.Based on analysis of robot motion and biological observation of animal's control mechanism,the motion control task is divided into two simple parts:motion sequence control and output force control.Inspired by a two-level CPG model,a two-level CPG control mechanism is constructed to coordinate the drivers of robot joint,while various feedback information are introduced into the control mechanism.Interneurons within the control mechanism are modeled to generate motion rhythm and pattern promptly for motion sequence control; motoneurons are modeled to control output forces of joint drivers in real time according to feedbacks.The control system can perceive changes caused by unknown perturbations and environment changes according to feedback information,and adapt to unpredictable environment by adjusting outputs of neurons.The control mechanism is applied to a biped hopping robot in unpredictable environment on simulation platform,and stable adaptive motions are obtained.

  16. The advantages of being unpredictable: How emotional inconsistency extracts concessions in negotiation

    NARCIS (Netherlands)

    Sinaceur, M.; Adam, H.; van Kleef, G.A.; Galinsky, A.D.

    2013-01-01

    Integrating recent work on emotional communication with social science theories on unpredictability, we investigated whether communicating emotional inconsistency and unpredictability would affect recipients' concession-making in negotiation. We hypothesized that emotional inconsistency and unpredic

  17. Macrophage-related serum biomarkers soluble CD163 (sCD163) and soluble mannose receptor (sMR) to differentiate mild liver fibrosis from cirrhosis in patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Andersen, E S; Rødgaard-Hansen, S; Moessner, B;

    2014-01-01

    with hepatitis C virus (HCV). Forty patients with chronic hepatitis C were included from two hospital clinics. On the day of inclusion, transient elastography (TE) was performed to assess the fibrosis stage, and blood samples were collected for the measurement of sCD163 and sMR. The plasma concentrations of both...... biomarkers were significantly higher in patients infected with HCV and with cirrhosis compared to those with no/mild liver fibrosis (5.77 mg/l vs. 2.49 mg/l and 0.44 mg/l vs. 0.30 mg/l for sCD163 and sMR, respectively). The best separation between groups was obtained by sCD163 [area under the receiver...

  18. Lingmao Formula Combined with Entecavir for HBeAg-Positive Chronic Hepatitis B Patients with Mildly Elevated Alanine Aminotransferase: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Zhu

    2013-01-01

    Full Text Available Objective. To determine the efficacy and safety of Lingmao Formula combined with entecavir for HBeAg-positive chronic hepatitis B patients with mildly elevated alanine aminotransferase (ALT. Methods. 301 patients were randomly assigned to receive Lingmao Formula combined with entecavir (treatment group or placebo combined with entecavir (control group for 52 weeks. The outcomes of interest included the reduction of serum HBV DNA level, HBeAg loss, HBeAg seroconversion, ALT normalization, and histological improvement. Results. The mean decrease of serum HBV DNA level from baseline and the percentage of patients who had reduction in serum HBV DNA level ≥2 lg copies/mL in treatment group were significantly greater than that in control group (5.5 versus 5.4 lg copies/mL, P=0.010; 98.5% versus 92.6%, P=0.019. The percentage of HBeAg loss in treatment group was 22.8%, which was much higher than a percentage of 12.6% in control group (P=0.038. There was no significant difference between the two groups in histological improvement. Safety was similar in the two groups. Conclusions. The combination of Lingmao Formula with entecavir could result in significant decrease of serum HBV DNA and increase of HBeAg loss for HBeAg-positive chronic hepatitis B patients with mildly elevated ALT without any serious adverse events. Clinical trial registration number is ChiCTR-TRC-09000594.

  19. Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Bisgaard, Christina; Jayatissa, Magdalena N; Enghild, Jan J

    2007-01-01

    of depression, by exposing rats to a series of mild stressors for 7 weeks, with antidepressant treatment during the last 4 weeks. In the CMS model, animals were split into six different groups at the end of treatment; unchallenged control escitalopram (n = 12), unchallenged control vehicle (n = 12), CMS vehicle...... (n = 12), CMS escitalopram responders (n = 11), CMS escitalopram non-responders (n = 13) and CMS resilient (stress resistant) (n = 12). Protein levels in the ventral rat hippocampus were compared between the groups to provide putative markers of anhedonia, escitalopram resistance, and stress...... resilience. Twenty-eight candidate protein spots were selected, of which 13 were successfully identified using tandem mass spectrometry. DRP-2 (dihydropyrimidinase-related protein-2) was a potential marker for escitalopram resistance, whereas alpha-SNAP and beta-SNAP were associated with stress resilience...

  20. 温和灸对慢性疲劳大鼠肠道菌群的影响%Influence of Mild Moxibustion on Intestinal Microflora of Chronic Fatigue Rats

    Institute of Scientific and Technical Information of China (English)

    成泽东; 陈以国; 张涛

    2013-01-01

    目的 观察温和灸对慢性疲劳大鼠肠道菌群的影响,并探讨其机理.方法 40只大鼠随机分为正常组、模型组、人参皂苷组、温和灸组.除正常组外,其他大鼠用饮食失节加冷水游泳制备慢性疲劳模型.正常组和模型组不给予任何治疗,温和灸组灸关元,人参皂苷组给予人参皂苷水溶液灌胃,每日1次.21d后,被迫采取粪便,采用厌氧及需氧菌选择性培养基测定各组大鼠粪便中典型菌群数量.结果 与正常组比较,模型组菌群数量明显减少(P<0.05);与模型组比较,温和灸组和人参皂苷组菌群数量明显增加(P<0.05);温和灸组与人参皂苷组比较差异无统计学意义(P>0.05).结论 关元灸可有效升高肠道中双歧杆菌、乳酸杆菌2种厌氧菌及大肠杆菌、肠球菌2种需氧菌的菌群数量,调整肠道菌群失调.%Objective To study influence of mild moxibustion on intestinal microflora of chronic fatigue rats, and explore its mechanism. Methods Forty rats were randomly divided into normal group, model group, ginsenoside group and mild moxibustion group. Rat model of chronic fatigue was made by disorder diet and cold-water swimming. Normal group and model group were not given any treatment, mild moxibustion group was given moxibustion at Guanyuan point, ginsenoside group was intragastrically given ginsenoside solution, once a day. After 21 days, forced to take dung, anaerobic and aerobic bacteria were cultured with selective media and determined the number of typical flora. Results Compared with the normal group, the number of bacteria of model group reduced significantly (P0.05). Conclusion Guanyuan moxibustion can improve symptoms of rats with diarrhea, adjust the intestinal flora: increase the number of two kinds of anaerobic bacteria (bifidobacteria, lactobacilli) and two kinds of aerobic bacteria (enterobacter, intestinal bacteria).

  1. Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing

    Science.gov (United States)

    Boonstra, Anne M.; Stewart, Roy E.; Köke, Albère J. A.; Oosterwijk, René F. A.; Swaan, Jeannette L.; Schreurs, Karlein M. G.; Schiphorst Preuper, Henrica R.

    2016-01-01

    Objectives: The 0–10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate, and severe pain in terms of pain-related interference with functioning in patients with chronic musculoskeletal pain, to measure the variability of the optimal cut-off points, and to determine the influence of patients’ catastrophizing and their sex on these cut-off points. Methods: 2854 patients were included. Pain was assessed by the NRS, functioning by the Pain Disability Index (PDI) and catastrophizing by the Pain Catastrophizing Scale (PCS). Cut-off point schemes were tested using ANOVAs with and without using the PSC scores or sex as co-variates and with the interaction between CP scheme and PCS score and sex, respectively. The variability of the optimal cut-off point schemes was quantified using bootstrapping procedure. Results and conclusion: The study showed that NRS scores ≤ 5 correspond to mild, scores of 6–7 to moderate and scores ≥8 to severe pain in terms of pain-related interference with functioning. Bootstrapping analysis identified this optimal NRS cut-off point scheme in 90% of the bootstrapping samples. The interpretation of the NRS is independent of sex, but seems to depend on catastrophizing. In patients with high catastrophizing tendency, the optimal cut-off point scheme equals that for the total study sample, but in patients with a low catastrophizing tendency, NRS scores ≤ 3 correspond to mild, scores of 4–6 to moderate and scores ≥7 to severe pain in terms of interference with functioning. In these optimal cut-off schemes, NRS scores of 4 and 5 correspond to moderate interference with functioning for patients with low catastrophizing tendency and to mild interference for patients with high catastrophizing tendency. Theoretically one would therefore expect that among the patients with NRS scores 4 and 5 there would be a higher average PDI score for those with low

  2. 舒郁散对慢性应激抑郁大鼠行为及海马糖皮质激素受体表达的影响%Effect of Suyusan on the Behavior and Glucocorticoid Receptor Expression in Hippocampus with Chronic Unpredictable Mild Stress induced Depression Rats

    Institute of Scientific and Technical Information of China (English)

    陈利平; 王发渭; 段冬梅; 孙志高; 许成勇

    2014-01-01

    目的 观察舒郁散对慢性不可预见性应激(CUMS)抑郁大鼠的行为变化及对大鼠脑组织肿瘤坏死因子-α (TNF-α)含量、海马内糖皮质激素受体表达的影响.方法 50只Wistar大鼠随机分为正常对照组、模型组、百忧解组、舒郁散小剂量组、舒郁散大剂量组.对大鼠进行21 d的CUMS刺激,采用糖水实验、悬尾实验观察大鼠的行为改变,用ELISA法测大鼠脑组织TNF-α含量,免疫组化观察大鼠海马GR表达.结果 百忧解组、舒郁散大剂量组大鼠的尾悬不动时间明显延长、糖水消耗百分率明显下降,与模型组比差异显著(P<0.01).百忧解、舒郁散大剂量治疗组大鼠悬尾不动时间明显减少,糖水消耗量明显增加,与模型组比差异显著(P< 0.05).百忧解、舒郁散大剂量治疗组大鼠脑组织TNF-α含量显著降低,与模型组比差异显著(P<0.05).模型组海马GR免疫反应阳性神经元数目明显减少,百忧解组、舒郁散大剂量组海马GR免疫反应阳性神经元数目明显增加,平均光密度明显增强,与模型组比差异显著(P<0.05).结论 动物行为学显示舒郁散具有抗抑郁作用,这种作用与降低CUMS抑郁大鼠脑组织TNF-α含量,增强海马糖皮质激素受体表达有关,上述作用与其剂量呈正相关.

  3. Effects of pentoxifylline, 7-nitroindazole, and imipramine on tumor necrosis factor-α and indoleamine 2,3-dioxygenase enzyme activity in the hippocampus and frontal cortex of chronic mild-stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Mohamed BMSA

    2013-05-01

    Full Text Available Bassim MSA Mohamed,1,6 Sawsan Aboul-Fotouh,2,5 Eman A Ibrahim,3 Hanan Shehata,4 Amal A Mansour,4 Nemat AZ Yassin,1 Wafaa El-Eraky,1 Ahmed M Abdel-Tawab2,5 1Department of Pharmacology, National Research Centre, Cairo, Egypt; 2Department of Pharmacology, 3Department of Pathology, 4Department of Medical Biochemistry and Molecular Biology, 5Clinical Pharmacology Unit, Ain Shams University, Cairo, Egypt; 6Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO enzyme, and hence serotonin availability in chronic mild stress (CMS, an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P < 0.05. Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05 reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01 reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF

  4. 米邦塔仙人掌果胶对慢性不可预知温和应激小鼠绝望症状的改善作用%Study on the improvement of milpa alta cactus pectin on desperate symptoms in mice exposed to chronic unpreditc able mild stress

    Institute of Scientific and Technical Information of China (English)

    肖同楚; 黄朝明; 杨兴娥; 湛进进; 郭莲军

    2015-01-01

    目的:研究米邦塔仙人掌果胶( MCP)对慢性不可预知温和应激( CUMS)小鼠绝望症状的改善作用。方法雄性昆明种小鼠随机分为空白对照组、模型组、MCP低剂量组(50 mg/kg)、MCP中剂量组(100 mg/kg)、MCP高剂量组(200 mg/kg)。除空白对照组不进行任何应激处理外,其余组均进行CUMS,各MCP组均在进行CUMS期间每天灌胃相应剂量MCP。造模结束24 h后进行悬尾实验,48 h后进行强迫游泳实验。结果模型组悬尾实验潜伏期显著短于空白对照组(P<0.01),累计不动时间显著长于空白对照组(P<0.01);MCP高剂量组潜伏期显著长于模型组(P<0.05),MCP中、高剂量组累计不动时间显著短于模型组(P均<0.01)。模型组强迫游泳实验潜伏期显著短于空白对照组(P<0.01),累计不动时间显著长于空白对照组(P<0.01);MCP各给药组潜伏期与空白对照组比较差异均无统计学意义(P均>0.05),而MCP高剂量组累计不动时间显著短于模型组(P<0.05)。结论 MCP能较好地缓解CMS小鼠的行为绝望症状。%Objetc ive It is to investigate the effect of milpa alta cactus pectin ( MCP) on desperate symptoms in mice ex-posed to chronic unpredictable mild stress ( CUMS) .Methods The male Kunming mice were randomly divided into 5 groups such as control group, CUMS+Vehicle group, CUMS+MCP 50 mg/kg group, CUMS+MCP 100 mg/kg group, and CUMS+MCP 200 mg/kg group.Except the control group, the other groups were exposed to CUMS for 6 weeks.And during this peri-od, the animals were treated with corresponding drug by intragastric administration.While the ends of the model, the tail sus-pension test ( TST) was carried out after 24 hours, and the forced swimming test ( FST) were conducted after 48 hours.Re-sults In TST, the latency of the CUMS+Vehicle group was significantly shorter (P0.05), and the immobility time of the

  5. Managing the continuum certainty, uncertainty, unpredictability in large engineering projects

    CERN Document Server

    Caron, Franco

    2013-01-01

    The brief will describe how to develop a risk analysis applied to a project , through a sequence of steps: risk management planning, risk identification, risk classification, risk assessment, risk quantification, risk response planning, risk monitoring and control, process close out and lessons learning. The project risk analysis and management process will be applied to large engineering projects, in particular related to the oil and gas industry. The brief will address the overall range of possible events affecting the project moving from certainty (project issues) through uncertainty (project risks) to unpredictability (unforeseeable events), considering both negative and positive events. Some quantitative techniques (simulation, event tree, Bayesian inference, etc.) will be used to develop risk quantification. The brief addresses a typical subject in the area of project management, with reference to large engineering projects concerning the realization of large plants and infrastructures. These projects a...

  6. Trailing the unpredictable pathways of European Union lifelong learning policy

    DEFF Research Database (Denmark)

    Cort, Pia

    2014-01-01

    actors from different sites to make a ‘European Area of Lifelong Learning a Reality’ (EU Commission, 2001). The changes challenge policy research and its traditional analytical units of the nation-state and the EU as a supranational organization. As stated in the introduction of the book, decision......Since 2000 the concept of Europeanization has gained importance as a way of conceptualizing the changes in education and training policy in the European Union. Not least the introduction of the Open Method of Coordination in education and training has launched important policy processes through...... which the usual distinctions between policy-making, policy decision and policy implementation are changing. Policy pathways have become unpredictable as ‘transnational flows and networks of people, ideas and practices across European borders’ (Lawn & Grek, 2012, p. 8) have intensified and drawn together...

  7. Silkwood vs. Kerr-McGee Corporation: unpredicted fallout

    Energy Technology Data Exchange (ETDEWEB)

    Silvestrini, L.V.F.

    1985-01-01

    The Silkwood suit is extolled as important precedent because it arguably gives states and private citizens acting as jurors the right to establish de facto nuclear regulatory policy. The Court's rationale in allowing punitive damages based on state tort law principles to be awarded against a private nuclear developer for injuries caused by the release of hazardous radioactive material from its plant is inconsistent with that used in a case involving Pacific Gas and Electric the year before. The author reviews the doctrine of preemption, discusses the legal and factural setting of the Silkwood case, and concludes that the Court could have provided a test similar to that invoked in labor law disputes to determine the available exceptions to total federal preemption of nuclear safety. Without such a test, the results of future litigation over nuclear safety concerns are unpredictable.

  8. Hyperhomocysteinemia is a result, rather than a cause, of depression under chronic stress.

    Directory of Open Access Journals (Sweden)

    Shen Chengfeng

    Full Text Available BACKGROUND: Although the accumulation of homocysteine (Hcy has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear. The present study was designed to clarify whether increased Hcy plays an important role in stress-induced depression. RESULTS: We employed the chronic unpredictable mild stress model (CUMS of depression for 8 weeks to observe changes in the plasma Hcy level in the development of depression. The results showed that Wistar rats exposed to a series of mild, unpredictable stressors for 4 weeks displayed depression-like symptoms such as anhedonia (decreased sucrose preferences and a decreased 5-Hydroxy Tryptophan (5-HT concentration in the hippocampus. At the end of 8 weeks, the plasma Hcy level increased in the CUMS rats. The anti-depressant sertraline could decrease the plasma Hcy level and improve the depression-like symptoms in the CUMS rats. RhBHMT, an Hcy metabolic enzyme, could decrease the plasma Hcy level significantly, although it could not improve the depressive symptoms in the CUMS rats. CONCLUSIONS: The results obtained from the experiments did not support the hypothesis that the increased Hcy concentration mediated the provocation of depression in CUMS rats, and the findings suggested that the increased Hcy concentration in the plasma might be the result of stress-induced depression.

  9. 1,2,3,4-Tetrahydroisoquinoline produces an antidepressant-like effect in the forced swim test and chronic mild stress model of depression in the rat: Neurochemical correlates.

    Science.gov (United States)

    Możdżeń, Edyta; Papp, Mariusz; Gruca, Piotr; Wąsik, Agnieszka; Romańska, Irena; Michaluk, Jerzy; Antkiewicz-Michaluk, Lucyna

    2014-04-15

    1,2,3,4-Tetrahydroisoquinoline (TIQ) is an exo- and endogenous amine naturally present in mammalian brain which displays antidepressant-like effect in various animal models: the forced swim test (FST) and chronic mild stress (CMS) paradigm in rats. To elucidate this action we compared the effects of TIQ with imipramine, a classic antidepressant drug and one of the most clinically effective. Applied behavioral tests showed that TIQ produced an antidepressant-like effect with a potency comparable to that of imipramine. TIQ (25-50mg/kg i.p.), similarly to imipramine (10-30mg/kg i.p.), reduced the immobility time in FST and completely reversed the decrease in sucrose intake caused by CMS in the rat. In addition, in order to avoid the possible psychostimulating effect of TIQ we examined the influence of its administration on locomotor activity in rats. TIQ, like imipramine, produced a reduction in horizontal locomotor activity. This suggested that TIQ did not have psychostimulant properties and that prolonged swimming in the FST was a result of an increased motivation to escape from the stressful situation. The biochemical analyses have shown that TIQ activates monoaminergic systems as a reversible monoamine oxidase (MAO) inhibitor and free radical scavenger. Beyond the activation of noradrenaline and serotonin systems, TIQ also moderately affects the dopamine system. On the basis of the presented behavioral and biochemical studies we suggest that TIQ is a potential new antidepressant which may be effective for the depression therapy in a clinical setting.

  10. Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats.

    Science.gov (United States)

    Li, Min; Li, Xiaobai; Zhang, Xinxin; Ren, Jintao; Jiang, Han; Wang, Yan; Ma, Yuchao; Cheng, Wenwen

    2014-06-01

    Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain.

  11. Effects of the chronic restraint stress induced depression on reward-related learning in rats.

    Science.gov (United States)

    Xu, Pan; Wang, Kezhu; Lu, Cong; Dong, Liming; Chen, Yixi; Wang, Qiong; Shi, Zhe; Yang, Yanyan; Chen, Shanguang; Liu, Xinmin

    2017-03-15

    Chronic mild or unpredictability stress produces a persistent depressive-like state. The main symptoms of depression include weight loss, despair, anhedonia, diminished motivation and mild cognition impairment, which could influence the ability of reward-related learning. In the present study, we aimed to evaluate the effects of chronic restraint stress on the performance of reward-related learning of rats. We used the exposure of repeated restraint stress (6h/day, for 28days) to induce depression-like behavior in rats. Then designed tasks including Pavlovian conditioning (magazine head entries), acquisition and maintenance of instrumental conditioning (lever pressing) and goal directed learning (higher fixed ratio schedule of reinforcement) to study the effects of chronic restraint stress. The results indicated that chronic restraint stress influenced rats in those aspects including the acquisition of a Pavlovian stimulus-outcome (S-O) association, the formation and maintenance of action-outcome (A-O) causal relation and the ability of learning in higher fixed ratio schedule. In conclusion, depression could influence the performances in reward-related learning obviously and the series of instrumental learning tasks may have potential as a method to evaluate cognitive changes in depression.

  12. A diferença na qualidade de vida de pacientes com doença venosa crônica leve e grave Differences in the quality of life of patients with mild and severe chronic venous disease

    Directory of Open Access Journals (Sweden)

    Raymundo Fagner Farias Novais dos Santos

    2009-06-01

    Full Text Available CONTEXTO: A doença venosa crônica atinge os indivíduos em sua fase mais produtiva da vida, acarretando dor, perda de mobilidade e afastamento de atividades, podendo interferir diretamente na qualidade de vida. Seus sintomas clínicos decorrem de um estado de hipertensão venosa, causada por refluxo e/ou obstrução venosa. OBJETIVO: Determinar a diferença na qualidade de vida de pacientes com doença venosa crônica leve e grave. MÉTODOS: Foi realizado estudo transversal analítico comparativo na unidade de saúde durante 8 meses. A amostra foi calculada em 88 pacientes e dividida em dois grupos: Grupo A (CEAP clínico 1, 2 e 3 e Grupo B (CEAP clínico 4, 5 e 6. Foi usado o questionário genérico Medical Outcomes Study - 36-Item Short-Form Health Survey (SF-36. A análise estatística para verificar se havia diferença foi através do teste t de Student, com intervalo de confiança de 95% e p BACKGROUND: Chronic venous disease afflicts individuals in their most productive years, resulting in pain and loss of mobility and independence in performing routine daily activities, which may directly interfere with the patient's quality of life. Clinical symptoms result from venous hypertension caused by reflux and/or venous blockage. OBJECTIVE: To determine differences in the quality of life of patients with mild and severe chronic venous disease. METHODS: A cross-sectional comparative study was conducted in a health care facility during an 8-month period. The sample was composed of 88 patients divided into two groups: group A (clinical CEAP class 1, 2 and 3 and group B (clinical CEAP class 4, 5 and 6. The Medical Outcomes Study - 36-Item Short-Form Health Survey (SF-36 questionnaire was used. Statistical analysis was conducted using the Student t test, with a 95% confidence interval and a level of significance set at p < 0.05. RESULTS: We analyzed 88 subjects, 47 in group A and 41 in group B. Of the total, 87.5% (77 were women and 34% (30 were

  13. Disease in a more variable and unpredictable climate

    Science.gov (United States)

    McMahon, T. A.; Raffel, T.; Rohr, J. R.; Halstead, N.; Venesky, M.; Romansic, J.

    2014-12-01

    Global climate change is shifting the dynamics of infectious diseases of humans and wildlife with potential adverse consequences for disease control. Despite this, the role of global climate change in the decline of biodiversity and the emergence of infectious diseases remains controversial. Climate change is expected to increase climate variability in addition to increasing mean temperatures, making climate less predictable. However, few empirical or theoretical studies have considered the effects of climate variability or predictability on disease, despite it being likely that hosts and parasites will have differential responses to climatic shifts. Here we present a theoretical framework for how temperature variation and its predictability influence disease risk by affecting host and parasite acclimation responses. Laboratory experiments and field data on disease-associated frog declines in Latin America support this framework and provide evidence that unpredictable temperature fluctuations, on both monthly and diurnal timescales, decrease frog resistance to the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Furthermore, the pattern of temperature-dependent growth of the fungus on frogs was inconsistent with the pattern of Bd growth in culture, emphasizing the importance of accounting for the host-parasite interaction when predicting climate-dependent disease dynamics. Consistent with our laboratory experiments, increased regional temperature variability associated with global El Niño climatic events was the best predictor of widespread amphibian losses in the genus Atelopus. Thus, incorporating the effects of small-scale temporal variability in climate can greatly improve our ability to predict the effects of climate change on disease.

  14. Changes in proinflammatory cytokines and white matter in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    Yang P

    2015-03-01

    Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

  15. Metabolic characteristics of mild chronic pancreatitis in Bama miniature swine%巴马小型猪轻度慢性胰腺炎代谢特征分析

    Institute of Scientific and Technical Information of China (English)

    孙高峰; 左长京; 汪建华; 张建; 马超; 李晓栋; 彭烨; 潘桂霞; 茅娟莉

    2013-01-01

    Objective To investigate the metabolic characteristics of early stage of obstructive chronic pancreatitis (CP) in swine by high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy.Methods A total of 39 Bama miniature swine were randomly divided into CP group and control group.The pancreatic main duct (PMD) of the swine in the experimental group underwent partial proximal ligation procedure.The swine in the control group underwent opening the abdomen and rubbing the pancreas and intestine.At the 4th,8th and 12th week after the operation,the swine were sacrificed to harvest the pancreas tissue for pathologically examination,which were classified as mild,moderate and severe according to the degree of fibrosis.The metabolic profiles from the pancreas of normal swine and mild CP swine were examined by using HR-MAS NMR spectroscopy.Results CP model was successfully established in 24 Bama miniature swine,and pathologically examination showed 10 was mild,5 was moderate and 7 was severe.Among the metabolites in mild CP,HR-MAS NMR analysis suggested that the peak of choline,glycine,betaine,lactate,fatty acid,phosphorylcholine/choline glycerophosphate was different with those in normal pancreas,and only the difference of choline was statistically significant (5.02 ± 1.96 vs 1.56 ± 0.79,P < 0.O1),while the difference of other 5 metabolites was not statistically significant.Conclusions Compared with control group,mild CP in Bama miniature swine shows significantly increased choline,and this may be a marker for discrimination of normal and early CP.%目的 应用高分辨魔角旋转磁共振(HR-MAS NMR)波谱分析巴马小型猪阻塞性慢性胰腺炎(CP)早期的代谢变化特征.方法 39头巴马小型猪按随机数字表法分为对照组和CP组.采用主胰管近端不全结扎法制备CP模型,对照组仅开腹翻动胰腺及肠道后关腹.造模后第4、8、12周分批处死动物,获取胰腺组

  16. Intrusions of a drowsy mind: Neural markers of phenomenological unpredictability

    Directory of Open Access Journals (Sweden)

    Valdas eNoreika

    2015-03-01

    Full Text Available The transition from a relaxed to a drowsy state of mind is often accompanied by hypnagogic experiences: most commonly, perceptual imagery, but also linguistic intrusions, i.e. the sudden emergence of unpredictable anomalies in the stream of inner speech. This study has sought to describe the contents of such intrusions, to verify their association with the progression of sleep onset, and to investigate the electroencephalographic processes associated with linguistic intrusions as opposed to more common hypnagogic perceptual imagery. A single participant attended 10 experimental sessions in the EEG laboratory, where he was allowed to drift into a drowsy state of mind, while maintaining metacognition of his own experiences. Once a linguistic intrusion or a noticeable perceptual image occurred, the participant pressed a button and reported it verbally. An increase in the EEG-defined depth of drowsiness as assessed by the Hori system of sleep onset was observed in the last 20 sec before a button press. Likewise, EEG Dimension of Activation values decreased before the button press, indicating that the occurrence of cognitively incongruous experiences coincides with the rapid change of EEG predictability patterns. EEG hemispheric asymmetry analysis showed that linguistic intrusions had a higher alpha and gamma power in the left hemisphere electrodes, whereas perceptual imagery reports were associated with a higher beta power over the right hemisphere. These findings indicate that the modality as well as the incongruence of drowsiness-related hypnagogic experiences is strongly associated with distinct EEG signatures in this participant. Sleep onset may provide a unique possibility to study the neural mechanisms accompanying the fragmentation of the stream of consciousness in healthy individuals.

  17. Impact and Effect of Preoperative Short-term Pulmonary Rehabilitation Training on 
Lung Cancer Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease: 
A Randomized Trial

    Directory of Open Access Journals (Sweden)

    Yutian LAI

    2016-11-01

    Full Text Available Background and objective Pulmonary rehabilitation (PR is proposed as an effective strategy to decrease surgical morbidity. However, appropriate rehabilitation plan, initiation time, and optimal duration of PR remain unclear. Lung cancer patients with chronic obstructive pulmonary disease (COPD are considered high-risk population for postoperative pulmonary complications (PPCs because of poor lung fitness and cardiopulmonary endurance. This study aims to assess the impact of a one-week, systematic and highly-intensive rehabilitation on surgical lung cancer patients with mild to moderate COPD. Methods A randomized controlled trial with 48 subjects was conducted (24 patients each for the intervention and groups. The intervention group received seven days of systematic, integrated and highly-intensive PR before surgical treatment, including: pharmacotherapy with atomizing terbutaline, pulmicort and infusion of ambroxol; and physical rehabilitation with respiratory training and endurance training. The control group underwent standard preoperative care. Results For the intervention group, the postoperative length of stay was shorter [(6.17±2.91 d vs (8.08±2.21 d; P=0.013]; likewise for the duration of antibiotics use [(3.61±2.53 d vs (5.36±3.12 d; P=0.032]. No significant difference was found between the groups in total in-hospital cost [(46,455.6±5,080.9 ¥ vs (45,536.0±4,195.8 ¥, P=0.498], medicine cost [(7,760.3±2,366.0 vs (6,993.0±2,022.5, P=0.223], and material cost [(21,155.5±10,512.1 ¥ vs (21,488.8±3,470.6 ¥, P=0.883]. In the intervention group, peak expiratory flow [(268.40±123.94 L/min vs (343.71±123.92 L/min; P<0.001], 6-min walk distance (6-MWD [(595.42±106.74 m vs (620.90±99.27 m; P=0.004], and energy consumption [(59.93±10.61 kcal vs (61.03±10.47 kcal; P=0.004] were statistically different after the seven-day exercise, compared with those on the first day. Finally, for the intervention group the incidence of PPCs (8

  18. Mild Traumatic Brain Injury

    Science.gov (United States)

    ... Videos mild Traumatic Brain Injury 94447 reads Please Log in You must be logged in to access ... Brain Injury (DCoE) to promote the processes of building resilience, facilitating recovery and supporting reintegration of returning ...

  19. Chronic mild stress induces depression-like behavior of rats%慢性应激性刺激对大鼠行为的影响——抑郁症模型的建立

    Institute of Scientific and Technical Information of China (English)

    姚莉红; 成翔; 张蕾; 衣昕; 郭玉秀; 秦建兵; 金国华; 张新化

    2013-01-01

    目的:以慢性应激性刺激(chronic mild stress,CMS)制作抑郁症动物模型,并以多种方式检测模型鼠的行为学变化,以期获得理想的动物模型.方法:对SD大鼠给予不可预知的慢性应激性刺激,包括:日夜颠倒;笼子弄脏;将笼子倾斜45°;限制它的活动;夜间不给予充足的食物;停止或减少对其水的供应等.每项刺激持续时间≥20 min,每2次刺激间隔时间≥16h,为时5周.在刺激结束后,立即进行行为学测试,包括悬尾实验(tail suspension test,TST);强迫游泳实验(forced swim test,FST);蔗糖饮水实验(sucrose preference test,SPT).结果:经过CMS处理的大鼠在悬尾试验中的不动时间明显大于未经过CMS实验处理的大鼠的不动时间(P<0.05).在强迫游泳实验中,经过CMS处理的大鼠不动次数大于未经CMS实验的大鼠的次数,游泳的次数明显少于未经CMS实验处理的大鼠的游泳次数.未经CMS实验的大鼠蔗糖摄入百分比为(72.10±5.24)%,而经过CMS实验大鼠的摄入蔗糖水百分比为(52.98± 11.14)%,明显低于对照组(P<0.05).结论:不可预知的缓慢刺激长时间施加到啮齿类动物,可以模拟出类似抑郁症的相关症状.

  20. Antidepressant- like effects of BCEF0083 in the chronic unpredictable stress models

    Institute of Scientific and Technical Information of China (English)

    LanlanZhou; LiangMING; ChuangengMa; YanCheng; QinJiang

    2004-01-01

    AIM: Depression is a complicated disease, There are no satisfactory drugs to therapy depression so far. BCEF is a new type of bioactive compounds from entomogenous fungi. Depression animal models are effective to evaluate the antidepressant property of drugs. Several animal models of depression have been inn'oduced, however, only a few have been

  1. The Chronic Illness Initiative: Supporting College Students with Chronic Illness Needs at DePaul University

    Science.gov (United States)

    Royster, Lynn; Marshall, Olena

    2008-01-01

    College students with chronic illness find it difficult to succeed in traditional degree programs due to disruptions caused by relapses and unpredictable waxing and waning symptoms. College disability offices are often unable to help, both because their standard supports are not appropriate and because students with chronic illness frequently do…

  2. Impact of unpredictability on chaos synchronization of vertical-cavity surface-emitting lasers with variable-polarization optical feedback.

    Science.gov (United States)

    Xiang, Shuiying; Pan, Wei; Yan, Lianshan; Luo, Bin; Zou, Xihua; Jiang, Ning; Yang, Lei

    2011-09-01

    The effects of unpredictability degree on the chaos synchronization properties of vertical-cavity surface-emitting lasers with variable-polarization optical feedback are investigated numerically. For variable-polarization optical injection, only low-unpredictability chaos can be well synchronized, while high-unpredictability chaos cannot be synchronized even with large injection strength. On the other hand, for the polarization-preserved optical injection, the synchronization quality is hardly affected by the unpredictability degree, and high-quality synchronization can be achieved for both low- and high-unpredictability chaos due to injection locking.

  3. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    ... stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It can involve problems with memory, language, thinking and judgment that are greater than normal age-related changes. If you have mild cognitive impairment, you may ...

  4. Mild induced hypothermia

    DEFF Research Database (Denmark)

    Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

    2014-01-01

    INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled tr...

  5. Effects of Chronic Stress on Cognition in Male SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    2016-08-01

    Full Text Available Background/Aims: Chronic stress can lead to cognitive impairment. Senescence-accelerated mouse prone 8 (SAMP8 is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. Methods: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1 mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95 and synaptophysin (SYN, which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR and western blotting analysis of SYN and PSD95. Results: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. Conclusion: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic

  6. FCJ-178 Network Affordances: The unpredictable parameters of a Hong Kong SPEED SHOW

    Directory of Open Access Journals (Sweden)

    Audrey Samson

    2015-06-01

    Full Text Available This paper examines the notion of network affordance within the context of network art. We expand on the notion of affordances, (Gibson, 1977; Gaver, 1996 to include ecological and computational parameters of unpredictability. We illustrate the notion of unpredictability by considering four specific works that were included in a network art exhibition, SPEED SHOW [2.0] Hong Kong (2013. The paper discusses how the artworks are contingent upon the parametric relations (Parisi, 2013 of the network. We introduce network affordance as a dynamic framework that could articulate the experience of tension arising from the (visible symbolic representation of computational processes and its hidden occurrences.

  7. How to create a health care organization that can succeed in an unpredictable future.

    Science.gov (United States)

    Olden, Peter C; Haynos, Jessika

    2013-01-01

    For those who manage organizations, it has been said that success does not come from predicting the future but instead comes from creating an organization that can succeed in an unpredictable future. Managers are responsible for creating such an organization. To do that, managers can apply management-related principles and methods. This article explains selected principles of organization structure, human resources, culture, decision making, and change management and how to apply them to health care organizations. If done well, that will help such organizations succeed in an unpredictable future.

  8. [Predicting suicide or predicting the unpredictable in an uncertain world: Reinforcement Learning Model-Based analysis].

    Science.gov (United States)

    Desseilles, Martin

    2012-01-01

    In general, it appears that the suicidal act is highly unpredictable with the current scientific means available. In this article, the author submits the hypothesis that predicting suicide is complex because it results in predicting a choice, in itself unpredictable. The article proposes a Reinforcement learning model-based analysis. In this model, we integrate on the one hand, four ascending modulatory neurotransmitter systems (acetylcholine, noradrenalin, serotonin, and dopamine) with their regions of respective projections and afferences, and on the other hand, various observations of brain imaging identified until now in the suicidal process.

  9. Long term sex-dependent psychoneuroendocrine effects of maternal deprivation and juvenile unpredictable stress in rats.

    Science.gov (United States)

    Llorente, R; Miguel-Blanco, C; Aisa, B; Lachize, S; Borcel, E; Meijer, O C; Ramirez, M J; De Kloet, E R; Viveros, M P

    2011-04-01

    We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent

  10. Effect of chronic stress and mifepristone treatment on voltage-dependent Ca2+ currents in rat hippocampal dentate gyrus.

    NARCIS (Netherlands)

    van Gemert, N.G.; Joëls, M.

    2006-01-01

    Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the presen

  11. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    Science.gov (United States)

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress.

  12. Fat or lean: adjustment of endogenous energy stores to predictable and unpredictable changes in allostatic load

    Science.gov (United States)

    Schultner, Jannik; Kitaysky, Alexander S.; Welcker, Jorg; Hatch, Scott

    2013-01-01

    1. The ability to store energy endogenously is an important ecological mechanism that allows animals to buffer predictable and unpredictable variation in allostatic load. The secretion of glucocorticoids, which reflects changes in allostatic load, is suggested to play a major role in the adjustment of endogenous stores to these varying conditions.

  13. Beyond Cumulative Risk: Distinguishing Harshness and Unpredictability as Determinants of Parenting and Early Life History Strategy

    Science.gov (United States)

    Belsky, Jay; Schlomer, Gabriel L.; Ellis, Bruce J.

    2012-01-01

    Drawing on life history theory, Ellis and associates' (2009) recent across- and within-species analysis of ecological effects on reproductive development highlighted two fundamental dimensions of environmental variation and influence: harshness and unpredictability. To evaluate the unique contributions of these factors, the authors of present…

  14. EXTENDED MILD-SLOPE EQUATION

    Institute of Scientific and Technical Information of China (English)

    黄虎; 丁平兴; 吕秀红

    2001-01-01

    The Hamiltonian formalism for surface waves and the mild-slope approximation were empolyed in handling the case of slowly varying three-dimensional currents and an uneven bottom, thus leading to an extended mild-slope equation. The bottom topography consists of two components: the slowly varying component whose horizontal length scale is longer than the surface wave length, and the fast varying component with the amplitude being smaller than that of the surface wave. The frequency of the fast varying depth component is, however, comparable to that of the surface waves. The extended mild- slope equation is more widely applicable and contains as special cases famous mild-slope equations below: the classical mild-slope equation of Berkhoff , Kirby' s mild-slope equation with current, and Dingemans' s mild-slope equation for rippled bed. The extended shallow water equations for ambient currents and rapidly varying topography are also obtained.

  15. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    Science.gov (United States)

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

  16. Chronic stress induced cognitive impairment in APP/PS-1 double transgenic mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Bing HAN

    2015-08-01

    Full Text Available Objective  To observe the effect of chronic unpredictable mild stress (CUMS on the cognitive function and brain morphological changes in APP/PS-1 mice, one of the genetic mouse models of Alzheimer's disease (AD, and to investigate the possible role of environmental factors in genetic mouse model of AD. Methods  There were 22-week-old wild-type C57BL/6 male mice (control group, N = 15 and APP/PS-1 double transgenic male mice [N = 27: AD group (N = 13 and AD + CUMS group (N = 14] tested in this study. Morris water maze test was used to evaluate spatial learning and memory of the mice. Amyloid deposition in the hippocampus was determined by Congo red staining. The ultrastructure of neurons in hippocampal CA1 region was observed by transmission electron microscope (TEM.  Results  Compared with control group, AD + CUMS group had significantly longer fifth-day escape latency [(33.14 ± 14.37 s vs (21.22 ± 12.16 s; t = -2.701, P = 0.045], and significantly shortened time spent in platform quadrant [(9.74±1.35 s vs (15.02 ± 1.33 s; t = 2.639, P = 0.012] in Morris water maze test. Compared with AD group, the percentage of amyloid plaque area in hippocampal area was increased in AD + CUMS group [(0.59 ± 0.03% vs (0.04 ± 0.03%; t = -2.900, P = 0.005]. The ultrastructure of hippocampal neurons in AD group was slightly damaged: cellular membrane was intact; cell matrix was uniform; intracelluar lipofuscin could be seen; the structure of nucleus and nuclear membrane had no obvious changes; mild fusion of cristae and membrane was seen in mitochondria; Golgi apparatus was partially indistinct; endoplasmic reticulum was mildly expanded. The ultrastructure of hippocampal neurons in AD + CUMS group was obviously damaged, including blurred cell membrane, reduced low-density and high-density granules in cytoplasm, uneven cell matrix, reduced number of organelles, lipofuscin and autophagosome deposition, obvious condensation of chromatin distributing over

  17. Combat Veterans with PTSD after Mild TBI Exhibit Greater ERPs from Posterior-medial Cortical Areas While Appraising Facial Features

    Science.gov (United States)

    2014-01-01

    within the past 30 days; (2) life- time history of bipolar disorder , attention deficit hyperactivity disorder , or psychotic disorder ; or (3) acute medical...Arbisi, P.A., Thuras, P., 2011. Longitudinal effects of mild traumatic brain injury and posttraumatic stress disorder comorbidity on postdeployment...The effects of temporal unpredictability in anticipation of negative events in combat veterans with PTSD. J. Affect. Disord . 146, 426–432. Simmons, A.N

  18. Pharmacotherapy for mild hypertension

    Directory of Open Access Journals (Sweden)

    Diana Diao

    Full Text Available BACKGROUND: People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population. The benefits and harms of treating mild hypertension in primary prevention patients are not known at present. This review examines the existing randomized controlled trial (RCT evidence. OBJECTIVE: Primary objective: To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension (systolic blood pressure (BP 140-159 mmHg and/or diastolic BP 90-99 mmHg and without cardiovascular disease. METHODS: Search: We searched CENTRAL (2011, Issue 1, MEDLINE (1948 to May 2011, EMBASE (1980 to May 2011 and reference lists of articles. The Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE were searched for previous reviews and meta-analyses of anti-hypertensive drug treatment compared to placebo or no treatment trials up until the end of 2011. Selection criteria: RCTs of at least 1 year duration. Data collection and analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD, total cardiovascular events (CVS, and withdrawals due to adverse effects. MAIN RESULTS: Of 11 RCTs identified 4 were included in this review, with 8,912 participants. Treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15. In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57, stroke (RR 0.51, 95% CI 0.24, 1.08, or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32. Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95% CI 4.14, 5.57, ARR 9%. AUTHORS' CONCLUSIONS: Antihypertensive drugs used in the treatment of adults (primary prevention with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg have not been

  19. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    is tested on matched employer-employee data from the entire Danish population. The analysis reveals that self-employed stay longer in their employment status compared to individuals in paid-employment. This effect is not explained by reduced attractiveness to the wage sector (lock-in effect). We interpret...... this finding by crafting a theory in which entrepreneurship may resolve mismatches of individuals in the labor market and may inherently increase the value of non-monetary benefits, namely independence. This counterintuitive finding – self-employment yields greater stability, all else equal – has fundamental...

  20. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    2014-01-01

    Is entrepreneurship a more stable career choice for high employment turnover individuals? We find that a transition to entrepreneurship induces a shift towards stayer behavior and identify job matching, job satisfaction and lock-in effects as main drivers. These findings have major implications...

  1. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    Does entrepreneurship lower individuals? employment turnover rates? The paper offers two reasons why this is the case - a matching mechanism and a lock-in effect. The paper offers theoretical justifications and seeks to empirically disentangle the two mechanisms. A matched employer-employee data...... due to reduced attractiveness in the wage sector and sunk costs related lock-in effects. Results, however, also indicate that entrepreneurship may resolve mismatches of individuals in the labor market. This counterintuitive finding - self-employment yields greater employment stability - has...... fundamental implications for the understanding of the returns (labor market outcomes) to entrepreneurship....

  2. Brain dysfunction in mild to moderate hypoxia.

    Science.gov (United States)

    Gibson, G E; Pulsinelli, W; Blass, J P; Duffy, T E

    1981-06-01

    Hypoxia is commonly invoked to explain alterations in mental function, particularly in patients with cardiac pulmonary failure. The effects of acute graded hypoxia or higher integrative functions are well documented experimentally in man. Hypoxia in experimental animal models demonstrates that the pathophysiology is complex. In mild to moderate hypoxia, in contrast to severe hypoxia and to ischemia, the supply of energy for the brain is not impaired; cerebral levels of adenosine triphosphate (ATP) and adenylate energy charge are normal. In contrast, the turnover of several neurotransmitters is altered by mild hypoxia. For example, acetylcholine synthesis is reduced proportionally to the reduction in carbohydrate oxidation. This relationship holds in vitro and with several in vivo models of hypoxia. Pharmacologic and physiologic studies in man and experimental animals are consistent with acetylcholine having an important role in mediating the cerebral effects of mild hypoxia. These observations raise the possibility that treatments directed to cholinergic or other central neurotransmitter systems may benefit patients with cerebral syndromes secondary to chronic hypoxia.

  3. Distinct state anxiety after predictable and unpredictable fear training in mice.

    Science.gov (United States)

    Seidenbecher, Thomas; Remmes, Jasmin; Daldrup, Thiemo; Lesting, Jörg; Pape, Hans-Christian

    2016-05-01

    Sustained fear paradigms in rodents have been developed to monitor states of anxious apprehension and to model situations in patients suffering from long-lasting anxiety disorders. A recent report describes a fear conditioning paradigm, allowing distinction between phasic and sustained states of conditioned fear in non-restrained mice. However, so far no prospective studies have yet been conducted to elucidate whether induction of phasic or sustained fear can affect states of anxiety. Here, we used CS (conditioned stimulus) and US (unconditioned stimulus) pairing with predictable and unpredictable timing to induce phasic and sustained fear in mice. State anxiety during various fear response components was assessed using the elevated plus-maze test. Training with unpredictable CS-US timing resulted in CS-evoked sustained components of fear (freezing), while predictable CS-US timing resulted in rapid decline. Data suggested the influence of training procedure on state anxiety which is dependent on progression of conditioned fear during fear memory retrieval. Animals trained with unpredictable CS-US timing showed an unchanged high anxiety state throughout behavioral observation. In contrast, mice trained with predictable CS-US timing showed anxiolytic-like behavior 3 min after CS onset, which was accompanied by a fast decline of the fear conditioned response (freezing). Further systematic studies are needed to validate the phasic/sustained fear model in rodents as translational model for anxiety disorders in humans.

  4. Environmental Unpredictability in Childhood Is Associated With Anxious Romantic Attachment and Intimate Partner Violence Perpetration.

    Science.gov (United States)

    Barbaro, Nicole; Shackelford, Todd K

    2016-03-27

    Human life history theory describes how resources are allocated among conflicting life tasks, including trade-offs concerning reproduction. The current research investigates the unique importance of environmental unpredictability in childhood in association with romantic attachment, and explores whether objective or subjective measures of environmental risk are more informative for testing life history hypotheses. We hypothesize that (1) unpredictability in childhood will be associated with greater anxious attachment, (2) anxious attachment will be associated with intimate partner violence (IPV) perpetration, and (3) anxious attachment will mediate the relationship between unpredictability in childhood and IPV perpetration. In two studies (totaln= 391), participants in a heterosexual, romantic relationship completed self-report measures of childhood experiences, romantic attachment, and IPV perpetration. Study 1 provides support for Hypothesis 1. Hypothesis 1 is replicated only for men, but not women, in Study 2. Results of Study 2 provide support for Hypothesis 2 for men and women, and Hypothesis 3 was supported for men but not women. The findings contribute to the literature addressing the association of environmental risk in childhood on adult romantic relationship outcomes.

  5. Defensive activation to (un)predictable interoceptive threat: The NPU respiratory threat test (NPUr).

    Science.gov (United States)

    Schroijen, Mathias; Fantoni, Simona; Rivera, Carmen; Vervliet, Bram; Schruers, Koen; van den Bergh, Omer; van Diest, Ilse

    2016-06-01

    Potentially life-threatening interoceptive sensations easily engage the behavioral defensive system. Resulting fear and anxiety toward interoceptive threat are functionally distinct states that are hypothesized to play a prominent role in the etiology of panic disorder. The present study aimed to investigate whether fear- and anxiety-potentiated startle responses occur to predictable and unpredictable interoceptive threat, respectively. Therefore, we modified the NPU threat test (Schmitz & Grillon, ) and replaced the aversive electrocutaneous stimulus with an aversive interoceptive stimulus (a breathing occlusion, making it briefly impossible to breathe). Healthy participants (N = 48) underwent three instructed conditions. A visual cue signaled the occlusion in the predictable condition (P), whereas another cue was unrelated to the occurrence of the occlusion in the unpredictable condition (U). The safe condition (N) also had a visual cue, but no occlusion. Both fear- and anxiety-potentiated startle blink responses were observed in response to predictable and unpredictable respiratory threat, respectively. The current study presents and validates the NPU respiratory threat test (NPUr) as an ecologically valid paradigm to study both anxiety and fear in response to a panic-relevant interoceptive threat. The paradigm allows future testing of contextual generalization, investigation of different clinical groups, and more explicit comparisons of defensive responding to interoceptive versus exteroceptive threats.

  6. Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

    Science.gov (United States)

    Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

    2017-02-01

    The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

  7. Mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Pavlović Dragan M.

    2009-01-01

    Full Text Available Mild cognitive impairment (MCI is a syndrome that spans the area between normal ageing and dementia. It is classified into amnestic and non-amnestic types, both with two subtypes: single domain and multiple domains. Prevalence of MCI depends on criteria and population and can vary from 0.1 to 42% persons of older age. In contrast to dementia, cognitive deterioration is less severe and activities of daily living are preserved. Most impaired higher cognitive functions in MCI are memory, executive functions, language, visuospatial functions, attention etc. Also there are depression, apathy or psychomotor agitation, and signs of psychosis. Aetiology of MCI is multiple, mostly neurodegenerative, vascular, psychiatric, internistic, neurological, traumatic and iatrogenic. Persons with amnestic MCI are at a higher risk of converting to Alzheimer's disease, while those with a single non-memory domain are at risk of developing frontotemporal dementia. Some MCI patients also progress to other dementia types, vascular among others. In contrast, some patients have a stationary course, some improve, while others even normalize. Every suspicion of MCI warrants a detailed clinical exploration to discover underlying aetiology, laboratory analyses, neuroimaging methods and some cases require a detailed neuropsychological assessment. At the present time there is no efficacious therapy for cognitive decline in MCI or the one that could postpone conversion to dementia. The treatment of curable causes, application of preventive measures and risk factor control are reasonable measures in the absence of specific therapy.

  8. Cognitive Processing in Mild Disabilities.

    Science.gov (United States)

    Al-Hilawani, Yasser A.; Poteet, James A.

    Research regarding the cognitive processing of students with learning disabilities, mild mental handicap, and emotional handicap is reviewed. In considering cognitive processing for students with mild mental handicap, research attention has been directed to the issues of memory and learning, acquisition and retrieval deficits, inefficient…

  9. Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Gonglin Hou; Mingming Tang

    2011-01-01

    There is evidence that the expression of members of the fibroblast growth factor (FGF) protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 (FGF2) and fibroblast growth factor receptor-1 (FGFR1) protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

  10. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Zhong, Xiao-Ming; Xian, Yan-Fang; Ip, Siu-Po

    2014-03-15

    Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine.

  11. Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6

    Directory of Open Access Journals (Sweden)

    Kersting S

    2013-02-01

    Full Text Available Sabine Kersting,1 Kirstin Reinecke,2 Christoph Hilgert,1 Monika S Janot,1 Elisabeth Haarmann,1 Martin Albrecht,1 Annette M Müller,3 Thomas Herdegen,2 Ulrich Mittelkötter,1 Waldemar Uhl,1 Ansgar M Chromik11Department of General and Visceral Surgery, St Josef Hospital, Ruhr-University of Bochum, Bochum, Germany; 2Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Campus Kiel, Germany; 3Department of Pediatric Pathology, Rheinische Friedrich-Wilhems-University of Bonn, Bonn, GermanyIntroduction: The c-Jun N-terminal kinases (JNKs are involved in signal transduction of inflammatory bowel diseases. The aim of this study was to examine the function of JNKs by using a low-dose dextran sulfate sodium (DSS model in JNK1 knockout mice (Mapk8–/–, JNK2 knockout mice (Mapk9–/–, and wild-type controls (WT1, WT2.Methods: The animals were evaluated daily using a disease activity index. After 30 days, the intestine was evaluated histologically with a crypt damage score. CD4+ and CD8+ cells were quantified using immunofluorescence. Analysis of tumor necrosis factor-a (TNFα, interleukin-6 (IL-6, and transforming growth factor ß1 (TGFB1 expression was carried out using LightCycler® real-time polymerase chain reaction.Results: Cyclic administration of low-dose DSS (1% was not able to induce features of chronic colitis in Mapk8–/– WT2 mice. By contrast, DSS administration significantly increased the disease activity index in WT1 and Mapk9–/– mice. In Mapk9–/– mice, the crypt damage score and the number of CD4+ and CD8+ cells as features of chronic colitis/inflammation were also significantly elevated. Expression of TNFα, IL-6, and TGFB1 was not altered by the JNK knockout.Conclusion: Administering DSS at a defined low concentration that is unable to induce colitis in WT animals leads to clinically and histologically detectable chronic colitis in Mapk9–/– mice. The reason for this disease

  12. Potential antiinflammatory effects of acupuncture in a chronic stress model of depression in rats.

    Science.gov (United States)

    Lu, Jun; Shao, Run-Hui; Hu, Li; Tu, Ya; Guo, Jian-You

    2016-04-08

    Accumulating evidence indicates that inflammation may contribute to the pathophysiology of depression. Acupuncture in traditional Chinese medicine has been considered an effective treatment for depression. However, whether the mechanisms that underlie the antidepressant effect of acupuncture are related to its antiinflammatory properties remains unclear. In the present study, rats were exposed to chronic unpredictable mild stress (CUMS) for 28 days to induce depressive-like behavior. Body weight, sucrose preference, and locomotor activity in the open field were measured. After the behavioral tests, reverse transcription polymerase chain reaction was used to determine the mRNA expression of proinflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), and enzyme-linked immunosorbent assay was used to detect cytokine concentrations. CUMS rats exhibited decrease in body weight, sucrose preference, and locomotor activity in the open field test. Chronic acupuncture and fluoxetine treatment reversed CUMS-induced depressive-like behavior. Compared with control rats, the mRNA and protein expression of IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex and cytokine concentrations in serum significantly increased in CUMS rats. Acupuncture and fluoxetine treatment significantly decreased the levels of proinflammatory cytokines in the hippocampus, prefrontal cortex, and serum. These results suggest that acupuncture has antidepressant-like effects, and its mechanism of action appears to involve the inhibition of proinflammatory cytokines.

  13. Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

    Science.gov (United States)

    Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

    2010-12-17

    Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects.

  14. Coping with uncertainty: breeding adjustments to an unpredictable environment in an opportunistic raptor.

    Science.gov (United States)

    Sergio, Fabrizio; Blas, J; López, L; Tanferna, A; Díaz-Delgado, R; Donázar, J A; Hiraldo, F

    2011-05-01

    No environment is truly constant in time. As a result, animals have evolved multiple adjustments to cope with such fluctuations. However, the allocation of effort to costly activities that imply long-term commitments, such as breeding, may be extremely challenging when future resources change constantly and unpredictably, a context that has received little investigation. To fill this gap, we studied the breeding response by a wetland-dependent raptor, the black kite Milvus migrans, to within and between-years fluctuations in resource availability (inundation levels). The breeding performance of the population was decomposed into reproductive components expressed in a sequence of successive tasks along the breeding cycle (e.g. timing of laying, clutch size, hatching success, brood reduction). Variation in each component was related to resource levels observed at different key dates of the season in order to test whether and when population-level reproduction was adjusted to available resources. Along a 22-year time-series, inundation levels fluctuated unpredictably within and among years, and mostly affected the later components of kites' reproduction, such as hatching success and the incidence of brood reduction, which were the main determinants of the population yearly breeding output. Results were consistent with multiple adjustments to cope with uncertainty. As the season progressed and resources became easier to assess, a bet-hedging waiting strategy based on a conservatively small, invariant and asynchronous clutch gave way to real-time resource-tracking mechanisms mediated by progressive adjustments to current prey availability, so that population-level breeding rates were determined and tuned to resources rather late in the season. Such adjustments were the likely outcome of the interaction between parental tactics and environmental constraints. Behavioural flexibility, such as dietary opportunism, probably promoted further resistance to resource

  15. Tropes And Tools Of Creativity: The Ontology Of Image And Its Unpredictable Operations

    DEFF Research Database (Denmark)

    Isar, Nicoletta

    2016-01-01

    as an essential rather than episodic constituent of our art historical consciousness,” and with the help of other anthropologists (Lévi-Strauss) and theorists of the image (Belting), I hope to understand why the “archaic” never died in ourselves. Focus will be on the artistic expressions of Brancusi’s work...... and some of his Avant-garde contemporary, trying to define the mechanism of the creative process as a mythopoetic activity, a mode of “communication” between the model, the materials, and the user, a collective or authorless event, indeed, a revelation: a play of unpredictable operations....

  16. Experimental study of inequality and unpredictability in an artificial cultural market.

    Science.gov (United States)

    Salganik, Matthew J; Dodds, Peter Sheridan; Watts, Duncan J

    2006-02-10

    Hit songs, books, and movies are many times more successful than average, suggesting that "the best" alternatives are qualitatively different from "the rest"; yet experts routinely fail to predict which products will succeed. We investigated this paradox experimentally, by creating an artificial "music market" in which 14,341 participants downloaded previously unknown songs either with or without knowledge of previous participants' choices. Increasing the strength of social influence increased both inequality and unpredictability of success. Success was also only partly determined by quality: The best songs rarely did poorly, and the worst rarely did well, but any other result was possible.

  17. Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome.

    Science.gov (United States)

    Singh, Jyotsna; Majumdar, Kaushik; Gupta, Rahul; Batra, Vineeta Vijay

    2015-01-01

    Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course.

  18. Expression and clinical significance of MMP-2 and TIMP-2 in liver tissues of patients with mild chronic hepatitis B%轻度慢性乙型肝炎患者肝组织中MMP-2和TIMP-2的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    诸葛璐; 潘陈为; 林巍; 方佩佩; 方周溪; 周光耀; 吕夕明; 金玲湘

    2013-01-01

    目的 探讨轻度慢性乙型肝炎(CHB)患者肝组织中的基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶抑制剂-2(TIMP-2)的表达及临床意义.方法 选取2006年12月至2011年12月温州医学院附属第二医院感染内科收治入院的慢性HBV感染者68例为研究对象,将其分为轻度慢性乙型肝炎(CHB)组(35例)和慢性HBV携带组(33例).采集患者血清,行HBV血清学标志物、HBVDNA、肝纤维化血清学指标检测及肝穿刺活检,光镜下观察肝组织.采用免疫组织化学染色法检测MMP-2和TIMP-2的表达,并进行阳性表达评分及肝组织纤维化分级.用SPSS 17.0软件进行统计学分析.结果 轻度CHB组和慢性HBV携带者组血清肝纤维化指标透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型胶原(PC Ⅲ)和Ⅳ型胶原(CⅣ)的差异无统计学意义(t=1.35,1.65,1.88和1.89,P>0.05).轻度CHB组肝组织中MMP-2和TIMP-2评分分别为(4.42±1 37)和(3.89±1.12)分,慢性HBV携带组分别为(3.61 ±1.23)和(3.31±1.07)分,差异有统计学意义(t=2.56和2.18,P<0.05).CHB组的MMP-2/TIMP-2比值为1.15±0.17,而慢性HBV携带组为1.08-±0.11,两组比较差异有统计学意义(t=2.04,P<0.05).MMP-2和TIMP-2评分与纤维化分级的相关系数分别为0.372(P =0.002)和0.439(P =0.000).结论 轻度CHB患者的肝组织中MMP-2和TIMP-2表达增加,且与纤维化分级具有相关性,可用于评估患者肝纤维化的程度.%Objective To investigate the expression and clinical significance of matrix metalloprotein-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2) in liver tissues of patients with mild chronic hepatitis B.Methods A total of 68 subjects with chronic hepatitis B virus (HBV) infections admitted to the Second Affiliated Hospital of Wenzhou Medical College during December 2006 and December 2011 were enrolled in the study,including 35 cases of mild chronic hepatitis B (CHB) and 33 carriers.Serum samples were collected,and serum HBV markers

  19. Implementing unpredictability in feeding enrichment for Malayan sun bears (Helarctos malayanus).

    Science.gov (United States)

    Schneider, Marion; Nogge, Gunther; Kolter, Lydia

    2014-01-01

    Bears in the wild spend large proportions of time in foraging activities. In zoos their time budgets differ markedly from those of their wild counterparts. Feeding enrichment has been documented to increase foraging behavior and to reduce stereotypies. But in general these procedures have no long-term effects and result in habituation. As can be expected by the predictions of the optimal foraging theory, foraging activities are restricted as long as the availability of food is predictable. To quantify the effect of spatial unpredictability, three feeding methods have been designed to stimulate functional foraging behavior in captive Malayan sun bears in the long-term. In order to examine if habituation occurs, the most effective method was tested for 12 consecutive days. Activities of four adult sun bears at the Cologne Zoo were recorded by focal animal recording of foraging behaviors and time sampling of activities for a total of 360 hr. Implementing unpredictability significantly increased the time the bears spent foraging and led to a higher diversity of foraging behaviors. The effects lasted throughout the entire day and no habituation occurred in the course of 12 consecutive days. The study shows how functional species typical behavior in captive Malayan sun bears can be stimulated in the long-term by simulating natural characteristics of food availability.

  20. Controllability modulates the neural response to predictable but not unpredictable threat in humans.

    Science.gov (United States)

    Wood, Kimberly H; Wheelock, Muriah D; Shumen, Joshua R; Bowen, Kenton H; Ver Hoef, Lawrence W; Knight, David C

    2015-10-01

    Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

  1. The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae.

    Directory of Open Access Journals (Sweden)

    Selene S C Nogueira

    Full Text Available Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari, a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3 and unpredictable feeding phases (U1- signaled and U2- non-signaled. The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2 than during the other two predictable phases (C1 and C3. The peccaries also spent less time feeding during the signaled unpredictable phase (U1 and the following control phase (C2 than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2, also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

  2. The Effects of Feeding Unpredictability and Classical Conditioning on Pre-Release Training of White-Lipped Peccary (Mammalia, Tayassuidae)

    Science.gov (United States)

    Nogueira, Selene S. C.; Abreu, Shauana A.; Peregrino, Helderes; Nogueira-Filho, Sérgio L. G.

    2014-01-01

    Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari), a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3) and unpredictable feeding phases (U1- signaled and U2- non-signaled). The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2) than during the other two predictable phases (C1 and C3). The peccaries also spent less time feeding during the signaled unpredictable phase (U1) and the following control phase (C2) than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2), also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild. PMID:24475072

  3. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... alcohol abuse over many years. Repeated episodes of acute ... chronic pancreatitis. Genetics may be a factor in some cases. ...

  4. Should mild COPD be treated? Evidence for early pharmacological intervention.

    Science.gov (United States)

    Elbehairy, Amany F; Webb, Katherine A; Neder, J Alberto; Alberto Neder, J; O'Donnell, Denis E

    2013-12-01

    Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways that is both preventable and treatable. It is well established that those with mild-to-moderate disease severity represent the majority of patients with COPD, yet this subpopulation is relatively under-studied. Because of an insidious pre-clinical phase, COPD is both under-diagnosed and under-treated. Recent studies have confirmed that even patients with mild, grade 1 COPD [i.e. those with a reduced forced expiratory volume in one second (FEV1)/forced vital capacity ratio but normal FEV1], have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with non-smoking healthy controls. Beyond the imperative of smoking cessation-the pivotal intervention in all COPD stages-the role of pharmacotherapy for prevention of disease progression has yet to be established. The main objective of this review is to provide a concise overview of the heterogeneous pathophysiology of COPD with only mild airway obstruction on spirometry and obstacles for early diagnosis. We emphasize that the absence of sufficiently powered trials involving a large number of patients precludes definitive recommendations in support of (or against) long-term pharmacological treatment in mild COPD. Despite these limitations, we present a rationale for earlier pharmacological intervention derived from recent physiological studies performed in symptomatic patients with mild COPD.

  5. The Spectrum of Disease in Chronic Traumatic Encephalopathy

    Science.gov (United States)

    McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

    2013-01-01

    Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

  6. An Overview of Multiple Sclerosis: Medical, Psychosocial, and Vocational Aspects of a Chronic and Unpredictable Neurological Disorder

    Science.gov (United States)

    Rumrill, Phillip D., Jr.; Roessler, Richard T.

    2015-01-01

    This article presents an overview of multiple sclerosis (MS), one of the most common neurological disorders in the western hemisphere. Medical and psychosocial aspects of the disease such as causes and risk factors, diagnosis, incidence and prevalence, symptoms, courses, and treatment are described. Existing research regarding the employment…

  7. Mild mental stress in diabetes

    DEFF Research Database (Denmark)

    Hildebrandt, P; Mehlsen, J; Sestoft, L;

    1985-01-01

    A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements......--increase in blood-pressure was observed in both groups. In conclusion, we found that even mild mental strain influences SBF in both normal subjects and in diabetics. The induced alterations in the two groups are different, probably because of a slight parasympathetic dysfunction in the diabetics....

  8. [Impact and Effect of Preoperative Short-term Pulmonary Rehabilitation Training on 
Lung Cancer Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease: 
A Randomized Trial].

    Science.gov (United States)

    Lai, Yutian; Su, Jianhua; Yang, Mei; Zhou, Kun; Che, Guowei

    2016-11-20

    背景与目的 围术期肺康复训练计划能够加速肺癌手术患者的术后快速康复,但是其应用方案、时间等仍未统一。肺癌合并慢性阻塞性肺病(chronic obstructive pulmonary disease, COPD)的手术患者,由于其相对较差的肺功能及心肺耐力,一直以来,都是肺部相关并发症的高危人群。本研究旨在探讨术前短期综合肺康复训练对肺癌合并轻中度COPD手术患者的影响。方法 前瞻性分析2015年3月11日至2015年11月31日四川大学华西医院胸外科行肺叶切除的原发性非小细胞癌合并轻中度COPD患者48例,随机分成实验组和对照组;实验组患者术前完成一周短期综合肺康复方案,包括以雾化吸入普米克令舒、博利康尼和沐舒坦静脉滴注为主的药物康复以及呼吸训练+耐力训练(Nustep)的物理康复;而对照组患者按常规术前准备进行。结果 最终24例患者纳入实验组,24例患者纳入对照组:实验组患者的术后住院时间[(6.17±2.91) d vs (8.08±2.21) d; P=0.013]和术后抗生素使用时间[(3.61±2.53) d vs (5.36±3.12) d; P=0.032]低于对照组,总住院费用[(46,455.6±5,080.9) ¥ vs (45,536.0±4,195.8) ¥, P=0.498]、住院材料费用[(21,155.5±10,512.1) ¥ vs (21,488.8±3,470.6) ¥, P=0.883]、住院药物费用[(7,760.3±2,366.0) ¥ vs (6,993.0±2,022.5) ¥, P=0.223]在两组间均无统计学差异;实验组患者对比训练前后,最大峰值流速(peak expiratory flow, PEF)[(268.40±123.94) L/min vs (343.71±123.92) L/min; Ppulmonary complications, PPCs)发生率(8.3%, 2/24 vs 20.8%, 5/24, P=0.416)差异无统计学意义。结论 术前短期综合肺康复训练能够提高肺癌合并轻中度慢性阻塞性肺病患者心肺耐力,加速患者术后快速康复,可作为术前快速康复计划的重要部分。.

  9. GLOBALISATION AND THE UNPREDICTABILITY OF CRISIS EPISODES: AN EMPIRICAL ANALYSIS OF COUNTRY RISK INDEXES

    Directory of Open Access Journals (Sweden)

    San-Martín-Albizuri, Nerea

    2012-05-01

    Full Text Available The ongoing globalisation process has not put an end to international financial crises. On the contrary, it seems to have contributed to their appearance and to accentuating their degrees of unpredictability. In this context, the main objective of the present study is to establish whether the values of the best-known and most widely used country risk indexes, namely, the Euromoney index and the International Country Risk Group (ICRG, and the values of their representative variables could have forecasted well in advance the crises that took place between 1994 and 2002, a period which is herein termed the ‘globalisation era’. The results show that, although the selected indexes and their representative variables were able to identify certain vulnerabilities, they could not accurately identify the political, economic, and/or financial factors that developed prior to these crisis episodes.

  10. Phenotypic plasticity is not affected by experimental evolution in constant, predictable or unpredictable fluctuating thermal environments.

    Science.gov (United States)

    Manenti, T; Loeschcke, V; Moghadam, N N; Sørensen, J G

    2015-11-01

    The selective past of populations is presumed to affect the levels of phenotypic plasticity. Experimental evolution at constant temperatures is generally expected to lead to a decreased level of plasticity due to presumed costs associated with phenotypic plasticity when not needed. In this study, we investigated the effect of experimental evolution in constant, predictable and unpredictable daily fluctuating temperature regimes on the levels of phenotype plasticity in several life history and stress resistance traits in Drosophila simulans. Contrary to the expectation, evolution in the different regimes did not affect the levels of plasticity in any of the traits investigated even though the populations from the different thermal regimes had evolved different stress resistance and fitness trait means. Although costs associated with phenotypic plasticity are known, our results suggest that the maintenance of phenotypic plasticity might come at low and negligible costs, and thus, the potential of phenotypic plasticity to evolve in populations exposed to different environmental conditions might be limited.

  11. Community health nursing practices in contexts of poverty, uncertainty and unpredictability: a systematization of personal experiences.

    Science.gov (United States)

    Laperrière, Hélène

    2007-01-01

    Several years of professional nursing practices, while living in the poorest neighbourhoods in the outlying areas of Brazil's Amazon region, have led the author to develop a better understanding of marginalized populations. Providing care to people with leprosy and sex workers in riverside communities has taken place in conditions of uncertainty, insecurity, unpredictability and institutional violence. The question raised is how we can develop community health nursing practices in this context. A systematization of personal experiences based on popular education is used and analyzed as a way of learning by obtaining scientific knowledge through critical analysis of field practices. Ties of solidarity and belonging developed in informal, mutual-help action groups are promising avenues for research and the development of knowledge in health promotion, prevention and community care and a necessary contribution to national public health programmers.

  12. Trafficking of endoplasmic reticulum-retained recombinant proteins is unpredictable in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Thomas eDe Meyer

    2014-09-01

    Full Text Available A wide variety of recombinant proteins has been produced in the dicot model plant, Arabidopsis thaliana. Many of these proteins are targeted for secretion by means of an N terminal endoplasmic reticulum (ER signal peptide. In addition, they can also be designed for ER retention by adding a C terminal H/KDEL-tag. Despite extensive knowledge of the protein trafficking pathways, the final protein destination, especially of such H/KDEL-tagged recombinant proteins, is unpredictable. In this respect, glycoproteins are ideal study objects. Microscopy experiments reveal their deposition pattern and characterization of their N-glycans aids in elucidating the trafficking. Here, we combine microscopy and N glycosylation data generated in Arabidopsis leaves and seeds, and highlight the lack of a decent understanding of heterologous protein trafficking.

  13. Preexposure to (un)predictable shock modulates discriminative fear learning between cue and context: an investigation of the interaction between fear and anxiety.

    Science.gov (United States)

    Meulders, Ann; Vervliet, Bram; Fonteyne, Riet; Baeyens, Frank; Hermans, Dirk; Vansteenwegen, Debora

    2012-05-01

    It has been suggested that prior experiences with unpredictable/uncontrollable stressors facilitate subsequent fear learning and the development of anxiety disorders. However, animal research documents that preexposure to unpredictable stressors (USs) impede later fear conditioning with that US. These differential predictions were tested in a human experimental model of clinical anxiety. One (US-only) group was preexposed to unpredictable shocks, a second (Unpaired) group received explicitly unpaired presentations of a neutral shape and the shock, and a third (Paired) group received paired shape-shock presentations. Next, all groups received training with a novel shape, using the same shock (50% reinforcement). Fear responding was assessed through startle modulation and online shock-expectancy ratings. Results showed retarded fear learning in the unpredictable groups compared to the predictable group. We argue that prior experiences of unpredictability may still contribute to the development of clinical anxiety, by impeding adaptive fear learning and perpetuating the perception of unpredictability/uncontrollability.

  14. Activity restriction in mild COPD: a challenging clinical problem

    Directory of Open Access Journals (Sweden)

    O'Donnell DE

    2014-06-01

    Full Text Available Denis E O'Donnell,1 Kevin B Gebke2 1Division of Respiratory and Critical Care Medicine, Respiratory Investigation Unit, Queen's University and Kingston General Hospital, Kingston, ON, Canada; 2Primary Care Sports Medicine Program, Indiana University School of Medicine, Indianapolis, IN, USA Abstract: Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD. However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the

  15. Mild maternal stress disrupts associative learning and increases aggression in offspring.

    Science.gov (United States)

    Eaton, L; Edmonds, E J; Henry, T B; Snellgrove, D L; Sloman, K A

    2015-05-01

    Maternal stress has been shown to affect behaviour of offspring in a wide range of animals, but this evidence has come from studies that exposed gestating mothers to acute or severe stressors, such as restraint or exposure to synthetic stress hormones. Here we show that exposure of mothers to even a mild stressor reduces associative learning and increases aggression in offspring. Female guppies were exposed to routine husbandry procedures that produced only a minimal, non-significant, elevation of the stress hormone cortisol. In contrast to controls, offspring from mothers that experienced this mild stress failed to learn to associate a colour cue and food reward, and showed a greater amount of inter-individual variation in behaviour compared with control offspring. This mild stress also resulted in offspring that were more aggressive towards their own mirror image than controls. While it is possible that these results could represent the transmission of beneficial maternal characteristics to offspring born into unpredictable environments, the potential for mild maternal stress to affect offspring performance also has important implications for research into the trans-generational effects of stress.

  16. 甘丙肽2型受体激动剂对慢性温和应激模型大鼠抑郁样行为的影响%Effects of Galanin Receptor 2 Agonist on Depression-like Behavior in Chronic Mild Stress Model Rats

    Institute of Scientific and Technical Information of China (English)

    张攀; 刘博; 王彤; 李慧; 杨予涛; 徐志卿

    2016-01-01

    Objective To explore the effect of intracerebroventricular injection of AR-M1896, a galanin receptor 2 agonist, on depres-sion-like behavior in rat chronic mild stress (CMS) model. Methods 48 Sprague-Dawley rats were randomly assigned into control group, CMS group, CMS artificial cerebrospinal fluid (aCSF) group and CMS AR-M1896 group equally. The control group received no interven-tion, and the other groups were established chronic mild stress model. After six-week of stress, forced swim test and sucrose preference test were conducted to identify the CMS rats. AR-M1896 or aCSF was injected into the lateral ventricle of CMS AR-M1896 group and CMS aC-SF group, respectively. The immobility time and climbing time in the forced swim test were analysed, and the sucrose consumption percent-age in the sucrose preference test was measured. Results The immobility time decreased (F=11.998, P<0.01), climbing time increased (F=8.268, P<0.05), and the sucrose consumption percentage increased (F=10.352, P<0.01) in CMS AR-M1896 group, compared with CMS aC-SF group. Conclusion Intracerebroventricular administration of galanin receptor 2 agonist AR-M1896 is effective on depression in CMS model rats.%目的 侧脑室注射甘丙肽2型受体(GalR2)激动剂AR-M1896,探讨其对慢性温和应激模型(CMS)大鼠抑郁样行为的影响.方法 48只Sprague-Dawley大鼠随机等分为对照组、CMS组、CMS人工脑脊液(aCSF)组、CMS AR-M1896组.对照组不作任何处理,其他3组制备大鼠慢性温和应激模型.应激6周后,通过强迫游泳及糖水偏好实验验证抑郁样行为;挑选造模成功大鼠,CMS aCSF组和CMS AR-M1896组侧脑室分别注射aCSF和AR-M1896.观察强迫游泳实验中的不动时间、攀爬时间,以及糖水偏好实验中的糖水饮用百分比.结果 与CMS aCSF组相比,CMS AR-M1896组不动时间明显缩短(F=11.998,P<0.01),攀爬时间延长(F=8.268,P<0.05),糖水饮用百分比明显增加(F=10.352,P<0.01).结论

  17. Hippocampal BDNF signaling restored with chronic asiaticoside treatment in depression-like mice.

    Science.gov (United States)

    Luo, Liu; Liu, Xiao-Long; Mu, Rong-Hao; Wu, Yong-Jing; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

    2015-05-01

    Brain-derived neurotrophic factor (BDNF) plays a key role in the regulation of depression in the brain. Recently, increasing studies have focused on the antidepressant-like mechanism of BDNF and its downstream signaling pathway. A previous study has shown that asiaticoside produced an antidepressant-like action in the mouse tail suspension test and forced swimming test. However, the neurotrophic mechanism that is affected by asiaticoside is unclear. Our present study aimed to verify whether asiaticoside produces an antidepressant-like effect through the activation of BDNF signaling in chronic unpredictable mild stress (CUMS). The results showed that mice treated with asiaticoside for four weeks reversed the decreased sucrose preference and increased immobility time that was observed in CUMS mice. In addition, we found that asiaticoside up-regulated BDNF, PSD-95 and synapsin I expression only in the hippocampus but not in the frontal cortex in both non-stressed and CUMS mice. However, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), completely abolished the antidepressant-like effect of asiaticoside. Moreover, the expression of hippocampal BDNF, PSD-95 and synapsin I that had increased with asiaticoside also declined with K252a pretreatment. In conclusion, our study implies that it is possible that asiaticoside exerts its antidepressant-like action by activating BDNF signaling in the hippocampus.

  18. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    Energy Technology Data Exchange (ETDEWEB)

    Yang, C.; Guo, X. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wang, G.H. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wuhan University, Institute of Neuropsychiatry, Wuhan, China, Institute of Neuropsychiatry, Wuhan University, Wuhan (China); Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China)

    2014-03-03

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  19. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    Directory of Open Access Journals (Sweden)

    C. Yang

    2014-03-01

    Full Text Available Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD. In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  20. Effect of Mild Moxibustion on Macrophage Number and Collagen Expression of Raw Surface Tissue in Chronic Refractory Skin Ulcer Rats%温和灸对大鼠慢性难愈性创面组织巨噬细胞及胶原表达的影响

    Institute of Scientific and Technical Information of China (English)

    孙立虹; 梁玉磊; 孙彦辉; 孙永辉; 张会珍; 李晓峰; 马红利; 赵振栓; 蒋海涛

    2012-01-01

    目的:研究温和灸对慢性难愈性创面组织表面巨噬细胞及Ⅰ、Ⅲ型胶原含量的影响,探讨温和灸干预难愈性创面瘢痕形成的效果及可能作用机制.方法:在80只雄性SD大鼠中随机取72只,在其背部制造全层皮肤损伤开放性创面.予以肌肉注射氢化可的松琥珀酸钠,建立慢性难愈性创面动物模型,随机分为模型组、温灸组、TDP组,每组24只.不予任何干预的8只大鼠作为正常组.TDP组、温灸组取创面局部及双侧“肾俞”“足三里”穴,分别以TDP照射或艾条温灸,每穴15 min,每日1次.以HE染色法检测治疗第7、10、14天修复组织表面巨噬细胞数,以免疫组化法检测治疗第7、10、14天修复组织Ⅰ、Ⅲ型胶原的含量.结果:温灸组、TDP组、模型组创面修复组织巨噬细胞数均明显较正常组增多(P<0.05);在治疗第7天,温灸组表面巨噬细胞数多于模型组(P<0.05);在治疗第10天,温灸组、TDP组表面巨噬细胞数均多于模型组(P<0.05),且温灸组多于TDP组(P<0.05);在治疗第14天,温灸组、TDP组表面巨噬细胞数均较模型组减少(P<0.05),且温灸组少于TDP组(P<0.05).大鼠创面修复组织Ⅰ、Ⅲ型胶原蛋白表达的平均吸光度,在治疗第7、14天,温灸组、TDP组均较模型组高(P<0.05,P<0.01);第14天温灸组高于TDP组(P<0.01).温灸组、TDP组胶原蛋白Ⅰ/Ⅲ值均较模型组接近正常组;在第14天,温灸组优于TDP组(P<0.05).结论:温和灸能促进创面愈合,且可降低瘢痕形成,其机制可能与调节不同时间内创面组织巨噬细胞数和Ⅰ、Ⅲ型胶原含量及其比值有关.%To observe the effect of mild moxibustion on the number of macrophages and contents of collagen I and Ⅲ in the raw surface tissue in chronic skin ulcer rats so as to study its mechanism underlying promoting scar formation. Methods Eighty male SD rats were randomly divided into normal (n = 8), model (n = 24), TDP (n = 24

  1. A New Tool for Assessing Context Conditioning Induced by US-Unpredictability in Humans: The Martians Task Restyled

    Science.gov (United States)

    Meulders, Ann; Vervliet, Bram; Vansteenwegen, Debora; Hermans, Dirk; Baeyens, Frank

    2011-01-01

    Unpredictability of an unconditioned stimulus (US) typically produces context conditioning in animals and humans. We modified the Martians task--a computer game measuring learning of Pavlovian associations through conditioned suppression--for assessing context conditioning in humans. One between-subjects and one within-subjects study are reported.…

  2. Mild Head Trauma and Chronic Headaches in Returning US Soldiers

    Science.gov (United States)

    2009-04-01

    multiple headache diagnoses. Two of the soldiers with migraine were also diagnosed with occipital neuralgia . One of these soldiers was diag- nosed with...13 (27) Occipital neuralgia 5 (15) 3 (6) Medication overuse headache 4 (12) 0 (0) Headache NOS 7 (21) 7 (14) Multiple headache types 10 (30) 16 (33

  3. 逍遥散抗慢性心理应激海马神经元凋亡的机理研究%Mechanism of Xiaoyao Powder in Counteracting Apoptosis of Hippocampus Neurons Caused by Chronic Psychological Stress

    Institute of Scientific and Technical Information of China (English)

    王文竹; 杨忠华; 徐志伟; 苏俊芳

    2011-01-01

    Objective To investigate the effect of Xiaoyao Powder(XP) on apoptosis of hippocampus neurons and glucocorticoid receptor(GR) mRNA expression caused by chronic psychological stress. Methods Wistar rats were randomized to 3 groups: normal group(without any stimulation,gastric gavage of 2 mL normal saline per day), model group( chronic mild unpredictable stress, gastric gavage of 2 mL normal saline per day) and XP group(gastric gavage of 2 mL XP one hour before stress). The changes of body weight and sucrose preference were observed. The apoptotic rate of hippocampal neurons were detected by PI staining method and GR mRNA expression by in-situ hybridization.Results After treatment with chronic mild unpredictable stress for 21 days, the body weight as well as the weight gain was lower in the model group and XP group than that in the normal group(P < 0.01 ), and the sucrose preference was decreased in the model group (P < 0.01 ). In the model group, the apoptotic rate of hippocampal neurons was increased(P < 0.05), and GR mRNA expression was decreased(P < 0.01 ). XP decreased the apoptotic rate (P < 0.05) and increased GR mRNA expression(P < 0.01 ). Conclusion Chronic mild unpredictable stress can significantly decrease sucrose preference. XP can counteract the decrease of sucrose preference and significantly improve the apoptosis of hippocampus neurons caused by chronic psychological stress, which mechanism maybe related to the regulation of GR mRNA expression.%目的 观察逍遥散抗慢性心理应激海马神经元凋亡及糖皮质激素受体(GR)表达的影响.方法 Wistar 大鼠按体重分为正常组、模型组、逍遥散组.正常组及模型组灌胃等量生理盐水,逍遥散组给予逍遥散7.02g/kg.观察实验前后大鼠体重及糖水偏爱度的变化,采用PI法检测大鼠海马神经元凋亡,原位杂交法检测GR mrRNA表达.结果 经过21 d慢性轻度不可预计应激(CMUS)造模后,模型组、逍遥散组体重及

  4. Love stories can be unpredictable: Jules et Jim in the vortex of life.

    Science.gov (United States)

    Dercole, Fabio; Rinaldi, Sergio

    2014-06-01

    Love stories are dynamic processes that begin, develop, and often stay for a relatively long time in a stationary or fluctuating regime, before possibly fading. Although they are, undoubtedly, the most important dynamic process in our life, they have only recently been cast in the formal frame of dynamical systems theory. In particular, why it is so difficult to predict the evolution of sentimental relationships continues to be largely unexplained. A common reason for this is that love stories reflect the turbulence of the surrounding social environment. But we can also imagine that the interplay of the characters involved contributes to make the story unpredictable-that is, chaotic. In other words, we conjecture that sentimental chaos can have a relevant endogenous origin. To support this intriguing conjecture, we mimic a real and well-documented love story with a mathematical model in which the environment is kept constant, and show that the model is chaotic. The case we analyze is the triangle described in Jules et Jim, an autobiographic novel by Henri-Pierre Roché that became famous worldwide after the success of the homonymous film directed by François Truffaut.

  5. HYBRID SYSTEM BASED FUZZY-PID CONTROL SCHEMES FOR UNPREDICTABLE PROCESS

    Directory of Open Access Journals (Sweden)

    M.K. Tan

    2011-07-01

    Full Text Available In general, the primary aim of polymerization industry is to enhance the process operation in order to obtain high quality and purity product. However, a sudden and large amount of heat will be released rapidly during the mixing process of two reactants, i.e. phenol and formalin due to its exothermic behavior. The unpredictable heat will cause deviation of process temperature and hence affect the quality of the product. Therefore, it is vital to control the process temperature during the polymerization. In the modern industry, fuzzy logic is commonly used to auto-tune PID controller to control the process temperature. However, this method needs an experienced operator to fine tune the fuzzy membership function and universe of discourse via trial and error approach. Hence, the setting of fuzzy inference system might not be accurate due to the human errors. Besides that, control of the process can be challenging due to the rapid changes in the plant parameters which will increase the process complexity. This paper proposes an optimization scheme using hybrid of Q-learning (QL and genetic algorithm (GA to optimize the fuzzy membership function in order to allow the conventional fuzzy-PID controller to control the process temperature more effectively. The performances of the proposed optimization scheme are compared with the existing fuzzy-PID scheme. The results show that the proposed optimization scheme is able to control the process temperature more effectively even if disturbance is introduced.

  6. The effect of unpredicted visual feedback on activation in the secondary somatosensory cortex during movement execution

    Directory of Open Access Journals (Sweden)

    Wasaka Toshiaki

    2012-11-01

    Full Text Available Abstract Background A mechanism that monitors the congruence between sensory inputs and motor outputs is necessary to control voluntary movement. The representation of limb position is constantly updated on the basis of somatosensory and visual information and efference copy from motor areas. However, the cortical mechanism underlying detection of limb position using somatosensory and visual information has not been elucidated. This study investigated the influence of visual feedback on information processing in somatosensory areas during movement execution using magnetoencephalography. We used an experimental condition in which the visual information was incongruent despite the motor execution and somatosensory feedback being congruent. Subjects performed self-paced bimanual movements of both thumbs, either symmetric or asymmetric, under normal visual and mirrored conditions. The mirror condition provided a visual feedback by showing a reflection of the subject’s right hand in place of the left hand. Therefore, in the Asymmetric task of the Mirror condition, subjects saw symmetric movements despite performing asymmetric movements. Results Activation in the primary somatosensory area (SI revealed inhibition of neural activity and that in the secondary somatosensory area (SII showed enhancement with voluntary movement. In addition, the SII contralateral to the side of stimulation was significantly enhanced in the Asymmetric task of the Mirror condition, which provided non-veridical visual feedback. Conclusions These results suggested that visual information influenced the neuronal activity concerning sensorimotor interaction in the SII during motor execution. The SII contributes to the detection of unpredicted visual feedback of movement execution.

  7. [A model of bipedal walking adaptable to an unpredictably dynamic environment].

    Science.gov (United States)

    Yano, Masafumi; Tomita, Nozomi; Makino, Yoshinari

    2010-11-01

    Modern science has been developed through concept of subject-object separation. That is, nature has been cordoned off from human beings and objectified. We have attempted to discover ideal world laws wherein we can consider nature as homogeneous. The real world, however, is by far more complicated than what natural sciences have so far been able to decipher. There are many problems that cannot be effectively addressed with the existing scientific technology. Because the real world is so unpredictable and dynamic, it is impossible to objectify it in advance and apply traditional methodology. This real world problem arises especially in information processing systems, that is, the recognition and the motion control systems coping with the real world. The current information systems can only handle explicit and complete information. Life is an intrinsic part of nature. To be both pliant and sturdy in a complex environment requires autonomy capable of creating the information needed to control the self. It forms the premise for the cognizance and control of life systems that exist in reality. To "live," a life system must independently forge a harmonious relationship with an unlimited environment. It requires that the life system be capable of creating the information necessary for self-control. It is this autonomy that clearly distinguishes the world of life systems from the physical world. Here, we will show an example of adaptive bipedal walking under an indefinite environment.

  8. Controllable uncertain opinion diffusion under confidence bound and unpredicted diffusion probability

    Science.gov (United States)

    Yan, Fuhan; Li, Zhaofeng; Jiang, Yichuan

    2016-05-01

    The issues of modeling and analyzing diffusion in social networks have been extensively studied in the last few decades. Recently, many studies focus on uncertain diffusion process. The uncertainty of diffusion process means that the diffusion probability is unpredicted because of some complex factors. For instance, the variety of individuals' opinions is an important factor that can cause uncertainty of diffusion probability. In detail, the difference between opinions can influence the diffusion probability, and then the evolution of opinions will cause the uncertainty of diffusion probability. It is known that controlling the diffusion process is important in the context of viral marketing and political propaganda. However, previous methods are hardly feasible to control the uncertain diffusion process of individual opinion. In this paper, we present suitable strategy to control this diffusion process based on the approximate estimation of the uncertain factors. We formulate a model in which the diffusion probability is influenced by the distance between opinions, and briefly discuss the properties of the diffusion model. Then, we present an optimization problem at the background of voting to show how to control this uncertain diffusion process. In detail, it is assumed that each individual can choose one of the two candidates or abstention based on his/her opinion. Then, we present strategy to set suitable initiators and their opinions so that the advantage of one candidate will be maximized at the end of diffusion. The results show that traditional influence maximization algorithms are not applicable to this problem, and our algorithm can achieve expected performance.

  9. Ecohydrology of managed ecosystems: Linking rainfall unpredictability, agronomic performance, and sustainable water use

    Science.gov (United States)

    Vico, Giulia; Porporato, Amilcare

    2014-05-01

    The field of ecohydrology, traditionally focusing on natural ecosystems, can offer the necessary quantitative tools to assess and compare the sustainability of agriculture across climates, soil types, crops, and irrigation strategies, including rainfall unpredictability. In particular, irrigation is one of the main strategies to enhance and stabilize agricultural productivity, but represents a cost in terms of often scarce water resources. Here, the sustainability of irrigated and rainfed agriculture is assessed by means of water productivity (defined as the ratio between yield and total supplied water), yields, water requirements, and their variability. These indicators are quantified using a probabilistic description of the soil water balance and crop development. Employing this framework, we interpret changes in water productivity as total water input is altered, in two staple crops (maize and wheat) grown under different soils, climates, and irrigation strategies. Climate change scenarios are explored by using the same approach and altering the rainfall statistics. For a given irrigation strategy, intermediate rainfall inputs leads to the highest variability in yield and irrigation water requirement - it is under these conditions that water management is most problematic. When considering the contrasting needs of limiting water requirements while ensuring adequate yields, micro-irrigation emerges as the most sustainable strategy at the field level, although consideration should be given to its profitability and long-term environmental implications.

  10. Mild hypoxia affects synaptic connectivity in cultured neuronal networks.

    Science.gov (United States)

    Hofmeijer, Jeannette; Mulder, Alex T B; Farinha, Ana C; van Putten, Michel J A M; le Feber, Joost

    2014-04-01

    Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity.

  11. Ethical Implications of the Mild Encephalitis Hypothesis of Schizophrenia

    Science.gov (United States)

    Riedmüller, Rita; Müller, Sabine

    2017-01-01

    Schizophrenia is a serious mental disease with a high mortality rate and severe social consequences. Due to insufficient knowledge about its etiopathogenesis, curative treatments are not available. One of the most promising new research concepts is the mild encephalitis hypothesis of schizophrenia, developed mainly by Karl Bechter and Norbert Müller. According to this hypothesis, a significant subgroup of schizophrenia patients suffer from a mild, but chronic, form of encephalitis with markedly different etiologies ranging from viral infections, traumas to autoimmune diseases. This inflammatory process is thought to occur in the beginning or during the course of the disease. In this article, we investigate the consequences of the mild encephalitis hypothesis of schizophrenia for the scientific community, and evaluate these consequences ethically. The mild encephalitis hypothesis implies that schizophrenia would no longer be considered an incurable psychiatric disorder. Instead, it would be considered a chronic, but treatable, neurological disease. This paradigm shift would doubtlessly have significant consequences: (1) major reforms would be necessary in the theoretical conceptualization of schizophrenia, which would challenge the psychiatric diagnostic systems, Diagnostic and Statistical Manual of Mental Disorders version 5 and ICD-10. (2) Psychotic patients should be treated in interdisciplinary teams, optimally in neuropsychiatric units; additionally, specialists for endocrinology, diabetology, and cardiology should be consulted for the frequently occuring somatic comorbidities. (3) Current diagnostic procedures and (4) therapies would have to be modified significantly. (5) There might be repercussions for the pharmaceutical industry as well: first, because old drugs with expired patent protection could partly replace expensive drugs and, second, because there would be a demand for the development of new anti-inflammatory drugs. (6) Legal evaluation of

  12. Mild chronic kidney disease independently predicts adverse outcomes in women with symptoms and signs of ischemia%中度肾功能不全是女性冠心病患者不良预后独立预测因素

    Institute of Scientific and Technical Information of China (English)

    张涛; 王松涛; 刘月红

    2015-01-01

    Objective:To investigate mild chronic kidney disease( CKD)independently predicts adverse outcomes in women with symptoms and signs of ischemia. Methods:To categorize 269 women referred for clinically indicated coronary angi-ography according to estimated glomerular filtration rate(eGFR). Time to death from all - cause and cardiovascular causes and major adverse outcomes were assessed by multivariate regression adjusted for baseline covariates. Results:Obstructive coronary artery disease(CAD)was present only in few patients(41% ). Even after adjusting for CAD severity,renal function remained a strong independent predictor of all - cause and cardiac mortality(P ﹤ 0. 001). Every 10 - unit decrease in eGFR was associ-ated with a 13% increased risk of all - cause mortality,17% increased risk of cardiovascular mortality,and 8% increased risk of adverse cardiovascular events. Conclusion:Even mild CKD is a strong independent predictor of all - cause and cardiac mor-tality in women with symptoms/ signs of ischemia.%目的:探讨中度慢性肾病(CKD)作为有心肌缺血症状女性患者不良预后的独立预测因素的可行性。方法:连续选择269例住院接受冠脉造影的女性患者,根据其肾小球滤过率(eGFR)进行分组。采用调整基线变量的多变量回归分析研究入组患者全因病死率、心血管疾病病死率及主要不良事件的发生率。结果:阻塞性冠状动脉疾病( CAD)患者仅占41%。在调整了CAD严重程度评分后,肾功能仍是对全因及心血管病死率的可靠独立预测因素(P ﹤0.001)。评估肾小球滤过率(eGFR),eGFR 每降低10 U,全因病死率增加13%,心血管疾病病死率增加17%,不良心血管事件的发生增加8%。结论:仅中等程度的 CKD 可作为有或无心肌缺血症状的女性患者全因及因心血管疾病死亡的独立预测因素。

  13. Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli:A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Julia eMossbridge

    2012-10-01

    Full Text Available This meta-analysis of 26 reports published between 1978 and 2010 tests an unusal hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: 1 randomly presented arousing vs. neutral stimuli, or 2 guessing tasks with feedback (correct vs. incorrect. Dependent variables included: electrodermal activity, heart rate, blood volume, pupil dilation, electroencephalographic activity (EEG, and blood oxygenation level dependent (BOLD activity. To avoid including data hand-picked from multiple different analyses, no post-hoc experiments are considered. The results reveal a significant overall effect with a small effect size (random effects: overall [weighted] ES=0.21, 95%CI=0.13-0.29, z=5.3, p<5.7x10-8; fixed effects: overall ES=0.21, 95%CI=0.15-0.27, z=6.9, p<2.7x10-12. Higher quality experiments produce a quantitately larger effect size and a greater level of significance than lower quality studies. The number of contrary unpublished reports that would be necessary to reduce the level of significance to chance (p>0.05 was conservatively calculated to be 87 reports. We explore alternative explanations and examine the potential linkage between this unexplained anticipatory activity and other results demonstrating meaningful pre-stimulus activity preceding behaviourally relevant events. Multiple replications arising from different laboratories using the same methods are necessary to further examine this currently unexplained anticipatory activity. The cause of this anticipatory activity, which undoubtedly lies within the realm of natural physical processes (as opposed to supernatural or paranormal ones, remains to be determined.

  14. Resilience of imperilled headwater stream fish to an unpredictable high-magnitude flood

    Directory of Open Access Journals (Sweden)

    Bruce R. Ellender

    2015-03-01

    Full Text Available Headwater stream fish communities are increasingly becoming isolated in headwater refugia that are often cut off from other metapopulations within a river network as a result of nonnative fish invasions, pollution, water abstraction and habitat degradation downstream. This range restriction and isolation therefore makes them vulnerable to extinction. Understanding threats to isolated fish populations is consequently important for their conservation. Following a base-flow survey, a high-magnitude flood (peak flow of 1245 m-3s-1 provided an opportunity to investigate the response of endangered Eastern Cape redfin Pseudobarbus afer populations to a natural disturbance in the Waterkloof and Fernkloof streams, two relatively pristine headwater tributaries of the Swartkops River system within the Groendal Wilderness Area, Eastern Cape Province, South Africa. Pseudobarbus afer had limited distributions, occupying 3 km in both the Fernkloof and Waterkloof streams. Fish population assessments before and after the flood event indicated that there were no longitudinal trends in P. afer abundance before or after the flood, but overall abundance post-flooding in the Fernkloof stream was higher. There were no noticeable changes in P. afer size structure pre- and post-flood. Pseudobarbus afer showed resilience to a major flooding event most likely related to evolution in river systems characterised by environmental stochasticity.Conservation implications: This research provides insight into the population level responses of native headwater stream fishes to unpredictable natural disturbance. Of particular relevance is information on their ability to withstand natural disturbances, which provides novel information essential for their conservation and management especially as these fishes are already impacted by multiple anthropogenic stressors.

  15. The effect of a concurrent cognitive task on cortical potentials evoked by unpredictable balance perturbations

    Directory of Open Access Journals (Sweden)

    Staines W Richard

    2004-05-01

    Full Text Available Abstract Background Although previous studies suggest that postural control requires attention and other cognitive resources, the central mechanisms responsible for this relationship remain unclear. To address this issue, we examined the effects of altered attention on cortical activity and postural responses following mechanical perturbations to upright stance. We hypothesized that cortical activity would be attenuated but not delayed when mechanical perturbations were applied during a concurrent performance of a cognitive task (i.e. when attention was directed away from the perturbation. We also hypothesized that these cortical changes would be accompanied by alterations in the postural response, as evidenced by increases in the magnitude of anteroposterior (AP centre of pressure (COP peak displacements and tibialis anterior (TA muscle activity. Healthy young adults (n = 7 were instructed to continuously track (cognitive task or not track (control task a randomly moving visual target using a hand-held joystick. During each of these conditions, unpredictable translations of a moving floor evoked cortical and postural responses. Scalp-recorded cortical activity, COP, and TA electromyographic (EMG measures were collected. Results Results revealed a significant decrease in the magnitude of early cortical activity (the N1 response, the first negative peak after perturbation onset during the tracking task compared to the control condition. More pronounced AP COP peak displacements and EMG magnitudes were also observed for the tracking task and were possibly related to changes in the N1 response. Conclusion Based on previous notions that the N1 response represents sensory processing of the balance disturbance, we suggest that the attenuation of the N1 response is an important central mechanism that may provide insight into the relationship between attention and postural control.

  16. Predicting the unpredictable: Critical analysis and practical implications of predictive anticipatory activity

    Directory of Open Access Journals (Sweden)

    Julia eMossbridge

    2014-03-01

    Full Text Available A recent meta-analysis of experiments from seven independent laboratories (n=26 published since 1978 indicates that the human body can apparently detect randomly delivered stimuli occurring 1-10 seconds in the future (Mossbridge, Tressoldi, & Utts, 2012. The key observation in these studies is that human physiology appears to be able to distinguish between unpredictable dichotomous future stimuli, such as emotional vs. neutral images or sound vs. silence. This phenomenon has been called presentiment (as in feeling the future. In this paper we call it predictive anticipatory activity or PAA. The phenomenon is predictive because it can distinguish between upcoming stimuli; it is anticipatory because the physiological changes occur before a future event; and it is an activity because it involves changes in the cardiopulmonary, skin, and/or nervous systems. PAA is an unconscious phenomenon that seems to be a time-reversed reflection of the usual physiological response to a stimulus. It appears to resemble precognition (consciously knowing something is going to happen before it does, but PAA specifically refers to unconscious physiological reactions as opposed to conscious premonitions. Though it is possible that PAA underlies the conscious experience of precognition, experiments testing this idea have not produced clear results. The first part of this paper reviews the evidence for PAA and examines the two most difficult challenges for obtaining valid evidence for it: expectation bias and multiple analyses. The second part speculates on possible mechanisms and the theoretical implications of PAA for understanding physiology and consciousness. The third part examines potential practical applications.

  17. Changes in cortical activity associated with adaptive behavior during repeated balance perturbation of unpredictable timing.

    Science.gov (United States)

    Mierau, Andreas; Hülsdünker, Thorben; Strüder, Heiko K

    2015-01-01

    The compensation for a sudden balance perturbation, unpracticed and unpredictable in timing and magnitude is accompanied by pronounced postural instability that is suggested to be causal to falls. However, subsequent presentations of an identical perturbation are characterized by a marked decrease of the amplitude of postural reactions; a phenomenon called adaptation or habituation. This study aimed to identify cortical characteristics associated with adaptive behavior during repetitive balance perturbations based on single-trial analyses of the P1 and N1 perturbation-evoked potentials. Thirty-seven young men were exposed to ten transient balance perturbations while balancing on the dominant leg. Thirty two-channel electroencephalography (EEG), surface electromyography (EMG) of the ankle plantar flexor muscles and postural sway (i.e., Euclidean distance of the supporting platform) were recorded simultaneously. The P1 and N1 potentials were localized and the amplitude/latency was analyzed trial by trial. The best match sources for P1 and N1 potentials were located in the parietal (Brodmann area (BA) 5) and midline fronto-central cortex (BA 6), respectively. The amplitude and latency of the P1 potential remained unchanged over trials. In contrast, a significant adaptation of the N1 amplitude was observed. Similar adaptation effects were found with regard to postural sway and ankle plantarflexors EMG activity of the non-dominant (free) leg; i.e., an indicator for reduced muscular co-contraction and/or less temporary bipedal stance to regain stability. Significant but weak correlations were found between N1 amplitude and postural sway as well as EMG activity. These results highlight the important role of the midline fronto-central cortex for adaptive behavior associated with balance control.

  18. Changes in cortical activity associated with adaptive behavior during repeated balance perturbation of unpredictable timing

    Directory of Open Access Journals (Sweden)

    Andreas eMierau

    2015-10-01

    Full Text Available The compensation for a sudden balance perturbation, unpracticed and unpredictable in timing and magnitude is accompanied by pronounced postural instability that is suggested to be causal to falls. However, subsequent presentations of an identical perturbation are characterized by a marked decrease of the amplitude of postural reactions; a phenomenon called adaptation or habituation. This study aimed to identify cortical characteristics associated with adaptive behavior during repetitive balance perturbations based on single-trial analyses of the P1 and N1 perturbation-evoked potentials. Thirty-seven young men were exposed to ten transient balance perturbations while balancing on the dominant leg. 32-channel EEG, surface EMG of the ankle plantar flexor muscles and postural sway (i.e. Euclidean distance of the supporting platform were recorded simultaneously. The P1 and N1 potentials were localized and the amplitude/latency was analyzed trial by trial. The best match sources for P1 and N1 potentials were located in the parietal (Brodmann area 5 and midline fronto-central cortex (Brodmann area 6, respectively. The amplitude and latency of the P1 potential remained unchanged over trials. In contrast, a significant adaptation of the N1 amplitude was observed. Similar adaptation effects were found with regard to postural sway and m. peroneus longus EMG activity of the non-dominant (free leg; an indicator reduced muscular co-contraction and/or less temporary bipedal stance to regain stability. Significant but weak correlations were found between N1 amplitude and postural sway as well as EMG activity. These results highlight the important role of the midline fronto-central cortex for adaptive behavior associated with balance control.

  19. Observation and Early Intervention in Mild Idiopathic Scoliosis via Corrective Exercises in Growing Children.

    Science.gov (United States)

    Sy, Ng

    2016-01-01

    Idiopathic scoliosis afflicts 2-3% of the population. For mild curvatures, observation is the treatment of choice. Though this passive "wait and see" approach has been used for many years, the practice is inconsistent among different countries. In Anglo-Saxon countries where scoliosis specific exercises are not practised, observation is indicated for curvatures below 25° in growing children and adolescents. In countries, such as France, Germany, Italy and Poland where scoliosis specific corrective exercises are employed, only patients with no signs of maturity and with curvatures below 15° are treated by observation. Patients with curvatures between 15 - 25° are treated by scoliosis specific exercises. In view of the unpredictability of the progression of scoliosis curvatures in immature patients and the lack of knowledge of long term biomechanical repercussions of mild idiopathic scoliosis on lumbar spine and lower extremities, it is proposed that active intervention through scoliosis specific exercises rather than passive observation be employed in the treatment of mild adolescent idiopathic scoliosis.

  20. Troubling practices of control: re-visiting Hannah Arendt's ideas of human action as praxis of the unpredictable.

    Science.gov (United States)

    Kohlen, Helen

    2015-07-01

    In this article, Hannah Arendt's concept of action will be used to problematize current transformations of the health care sector and examine some responses by ethicists in light of those transformations. The sphere of human interaction that should typify health care work is identified as an action of unpredictable praxis in contrast to controllable procedures and techniques which increasingly take place in the health care sector.

  1. Offset-Control Attenuates Context Conditioning Induced by US-unpredictability in a Human Conditioned Suppression Paradigm

    Directory of Open Access Journals (Sweden)

    Ann Meulders

    2013-03-01

    Full Text Available We investigated whether offset-control of the unconditioned stimulus (US reduces context conditioning induced by US-unpredictability within a human conditioned suppression preparation. We also examined lack of control 'vs'. loss of control. Three groups (No Controllability, NC; Controllability, C; Loss of Controllability, LC received unsignaled USs during two learning phases (ACQ1-2. The NC group, never had offset-control, whereas the C group, always had offset-control. The LC group, had offset-control during ACQ1, but not during ACQ2. Results indicated that US-unpredictability led to contextual conditioned suppression during ACQ1, only when participants did not have offset-control; when they did, no context conditioning was established. From ACQ1 to ACQ2, contextual conditioned suppression increased in the LC group, but it was not more pronounced than in the NC group. These data suggest that offset-control attenuates context conditioning induced by US-unpredictability and – at least in this paradigm – loss of control is not worse than lack of control.

  2. Reminiscence and adaptation to critical life events in older adults with mild to moderate depressive symptoms

    NARCIS (Netherlands)

    Korte, Jojanneke; Bohlmeijer, Ernst T.; Westerhof, Gerben J.; Pot, Anne Margriet

    2011-01-01

    Objectives: The role of reminiscence as a way of adapting to critical life events and chronic medical conditions was investigated in older adults with mild to moderate depressive symptoms. Reminiscence is the (non)volitional act or process of recollecting memories of one's self in the past. Method:

  3. Dessaturação noturna: preditores e influência no padrão do sono de pacientes portadores de doença pulmonar obstrutiva crônica com hipoxemia leve em vigília Nocturnal desaturation: predictors and the effect on sleep patterns in patients with chronic obstructive pulmonary disease and concomitant mild daytime hypoxemia

    Directory of Open Access Journals (Sweden)

    Renata Claudia Zanchet

    2006-06-01

    Full Text Available OBJETIVO: Verificar o padrão da oximetria noturna em portadores de doença pulmonar obstrutiva crônica sem apnéia do sono e com hipoxemia leve em vigília, identificar prováveis parâmetros diurnos capazes de predizer a dessaturação noturna e verificar sua influência no padrão de sono. MÉTODOS: Avaliaram-se 25 pacientes, divididos em dois grupos: com e sem dessaturação noturna. RESULTADOS: Comparando-se o primeiro grupo (52% com o segundo observou-se: idade, 63 ± 5 versus 63 ± 6 anos; volume expiratório forçado no primeiro segundo, 53 ± 31% versus 56 ± 19% do previsto; relação entre volume expiratório forçado no primeiro segundo e capacidade vital forçada, 49 ± 14% versus 52 ± 10%; pressão parcial de oxigênio no sangue arterial, 68 ± 8mmHg versus 72 ± 68mmHg; saturação arterial de oxigênio, 93 ± 2% versus 94 ± 1%. O grupo com dessaturação noturna apresentou menores valores de saturação arterial de oxigênio diurna e saturação periférica de oxigênio noturna. Não houve diferença no padrão de sono entre os grupos. Houve correlação da relação entre o volume expiratório forçado no primeiro segundo e a capacidade vital forçada, pressão parcial de oxigênio no sangue arterial e saturação arterial de oxigênio diurnas, e saturação periférica de oxigênio no exercício com os níveis de saturação periférica de oxigênio noturna, porém somente a saturação arterial de oxigênio diurna foi preditora da dessaturação noturna. CONCLUSÃO: A única variável capaz de predizer dessaturação noturna foi a saturação arterial de oxigênio diurna. A dessaturação noturna não influencia o padrão de sono de portadores de doença pulmonar obstrutiva crônica com hipoxemia diurna leve.OBJECTIVE: To determine the nocturnal oximetry pattern in chronic obstructive pulmonary disease patients having no sleep apnea and presenting mild daytime hypoxemia, to identify probable daytime parameters capable of

  4. Understanding mild persistent asthma in children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Szefler, Stanley J

    2005-01-01

    Limitations in asthma prevalence studies and difficulties in diagnosing pediatric asthma lead to uncertainty over the full extent of mild persistent asthma in children and adolescents. Although recent surveys have reported that the majority of pediatric patients with asthma in the United States...... and Europe have symptoms consistent with mild disease, these surveys have limitations in design. Thus, the true prevalence of mild asthma remains unknown. It is unclear whether children with mild persistent asthma progress to more severe asthma, but the risk of severe asthma exacerbations seems...... to be unrelated to the symptom severity. Clinical studies restricted to pediatric patients with mild asthma are limited, but available data do suggest substantial morbidity of mild persistent asthma in this population and support inhaled corticosteroid intervention. There is a need for further investigation...

  5. Unpredictable, unpreventable and impersonal medicine: global disaster response in the 21st century.

    Science.gov (United States)

    Andrews, Russell J; Quintana, Leonidas M

    2015-01-01

    The United Nations has recognized the devastating consequences of "unpredictable, unpreventable and impersonal" disasters-at least US $2 trillion in economic damage and more than 1.3 million lives lost from natural disasters in the last two decades alone. In many disasters (both natural and man-made) hundreds-and in major earthquakes, thousands-of lives are lost in the first days following the event because of the lack of medical/surgical facilities to treat those with potentially survivable injuries. Disasters disrupt and destroy not only medical facilities in the disaster zone but also infrastructure (roads, airports, electricity) and potentially local healthcare personnel as well. To minimize morbidity and mortality from disasters, medical treatment must begin immediately, within minutes ideally, but certainly within 24 h (not the days to weeks currently seen in medical response to disasters). This requires that all resources-medical equipment and support, and healthcare personnel-be portable and readily available; transport to the disaster site will usually require helicopters, as military medical response teams in developed countries have demonstrated. Some of the resources available and in development for immediate medical response for disasters-from portable CT scanners to telesurgical capabilities-are described. For immediate deployment, these resources-medical equipment and personnel-must be ready for deployment on a moment's notice and not require administrative approvals or bureaucratic authorizations from numerous national and international agencies, as is presently the case. Following the "trauma center/stroke center" model, disaster response incorporating "disaster response centers" would be seamlessly integrated into the ongoing daily healthcare delivery systems worldwide, from medical education and specialty training (resident/registrar) to acute and subacute intensive care to long-term rehabilitation. The benefits of such a global disaster

  6. Opioid rotation in the management of chronic pain: where is the evidence?

    NARCIS (Netherlands)

    Vissers, K.C.P.; Besse, K.; Hans, G.; Devulder, J.; Morlion, B.

    2010-01-01

    The management of chronic pain remains a challenge because of its complexity and unpredictable response to pharmacological treatment. In addition, accurate pain management may be hindered by the prejudice of physicians and patients that strong opioids, classified as step 3 medications in the World H

  7. Opioid Rotation in the Management of Chronic Pain : Where Is the Evidence?

    NARCIS (Netherlands)

    Vissers, K. C. P.; Besse, K.; Hans, G.; Devulder, J.; Morlion, B.

    2010-01-01

    The management of chronic pain remains a challenge because of its complexity and unpredictable response to pharmacological treatment. In addition, accurate pain management may be hindered by the prejudice of physicians and patients that strong opioids, classified as step 3 medications in the World H

  8. Chronic endometritis and infertility

    Science.gov (United States)

    Park, Hyun Jong; Kim, You Shin; Yoon, Tae Ki

    2016-01-01

    Chronic endometritis (CE) is a condition involving the breakdown of the peaceful co-existence between microorganisms and the host immune system in the endometrium. A majority of CE cases produce no noticeable signs or mild symptoms, and the prevalence rate of CE has been found to be approximately 10%. Gynecologists and pathologists often do not focus much clinical attention on CE due to the time-consuming microscopic examinations necessary to diagnose CE, its mild clinical manifestations, and the benign nature of the disease. However, the relationship between CE and infertility-related conditions such as repeated implantation failure and recurrent miscarriage has recently emerged as an area of inquiry. In this study, we reviewed the literature on the pathophysiology of CE and how it may be associated with infertility, as well as the literature regarding the diagnosis and treatment of CE. In addition, we discuss the value of hysteroscopic procedures in the diagnosis and treatment of CE. PMID:28090456

  9. Intestinal pseudo-obstruction:An uncommon condition with heterogeneous etiology and unpredictable outcome

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Intestinal pseudo-obstruction (IPO) either acute or chronic is a condition including features of intestinal ileus in absence of mechanical obstruction.Our paper presents such a rare case of idiopathic IPO in a 53-year-old male patient with recurrent episodes of pseudo-obstruction,whicb were successfully resolved by anticholinesterase agents,motilin agonists or colonic decompression.However,the patient finally underwent total colectomy.Huge colonic dilatation was identified intraoperatorily,while histology showed a neuropathic variant of chronic intestinal pseudo-obstruction.Etiologic mechanisms and current therapeutic methods are reviewed in this paper,which concludes that IPO is a condition in which conservative treatment usually fails.Total colectomy with ileoanal pouch may be the only solution in these situations.

  10. An accuracy analysis of Cyberknife tumor tracking radiotherapy according to unpredictable change of respiration

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Jung Min; Lee, Chang Yeol; Huh, Hyun Do; Kim, Wan Sun [Dept. of Radiation Oncology, Inha university hospital, Incheon (Korea, Republic of)

    2015-12-15

    Cyber-Knife tumor tracking system, based on the correlation relationship between the position of a tumor which moves in response to the real time respiratory cycle signal and respiration was obtained by the LED marker attached to the outside of the patient, the location of the tumor to predict in advance, the movement of the tumor in synchronization with the therapeutic device to track real-time tumor, is a system for treating. The purpose of this study, in the cyber knife tumor tracking radiation therapy, trying to evaluate the accuracy of tumor tracking radiation therapy system due to the change in the form of unpredictable sudden breathing due to cough and sleep. Materials and Methods : Breathing Log files that were used in the study, based on the Respiratory gating radiotherapy and Cyber-knife tracking radiosurgery breathing Log files of patients who received herein, measured using the Log files in the form of a Sinusoidal pattern and Sudden change pattern. it has been reconstituted as possible. Enter the reconstructed respiratory Log file cyber knife dynamic chest Phantom, so that it is possible to implement a motion due to respiration, add manufacturing the driving apparatus of the existing dynamic chest Phantom, Phantom the form of respiration we have developed a program that can be applied to. Movement of the phantom inside the target (Ball cube target) was driven by the displacement of three sizes of according to the size of the respiratory vertical (Superior-Inferior) direction to the 5 mm, 10 mm, 20 mm. Insert crosses two EBT3 films in phantom inside the target in response to changes in the target movement, the End-to-End (E2E) test provided in Cyber-Knife manufacturer depending on the form of the breathing five times each. It was determined by carrying. Accuracy of tumor tracking system is indicated by the target error by analyzing the inserted film, additional E2E test is analyzed by measuring the correlation error while being advanced. If the target

  11. Study of C57 mice depression model induced by chronic stress and separation%慢性应激联合孤养C57小鼠抑郁模型的研究

    Institute of Scientific and Technical Information of China (English)

    姚丽华; 陈建新; 王晓萍; 王惠玲; 王高华; 刘忠纯

    2014-01-01

    目的 探讨C57小鼠慢性不可预见性温和应激(chronic unpredictable mild stress,GUMS)联合孤养建立抑郁模型的可行性和有效性.方法 将30只雄性C57小鼠随机分为CUMS+孤养组、CUMS+孤养+氟西汀组、对照组各10只,前两组CUMS+孤养致抑郁模型3周,3周后对CUMS+孤养+氟西汀组进行氟西汀干预,观察小鼠应激前、应激后及干预后的摄食量/体质量、旷场实验和液体消耗实验变化.结果 与对照组比较,建模21d后CUMS+孤养组和CUMS+孤养+氟西汀组小鼠摄食量/体质量、糖水偏好、旷场总行程显著下降(P<0.05);经氟西汀干预14 d后摄食量/体质量、旷场总行程与对照组比较无明显差异(P>0.05),但糖水消耗量明显提高(P<0.05),与CUMS+孤养组比较也有明显改善(P<0.05).结论 C57小鼠CUMS联合孤养制作抑郁模型的效果肯定,是研究抑郁症较为理想的动物模型.%Objective To investigate the feasibility and effectiveness of C57 mice depression model established by chronic unpredictable mild stress (CUMS) and separation.Methods 30 male C57 mice were randomly divided into three groups:CUMS + separation group (group CS),CUMS + separation + fluoxetine group (group CSF),and control group (group C).The mice of group CS and group CSF were fed with chronic unpredictable mild stress (CUMS) and separation for 3 weeks.Then,the mice of group CSF were given fluoxetine.To record the food intake/body weight,liquid consumption and field test of the mice at relevant time point.Results Compared with control group,the food intake/body weight,total route in the field test,and the sucrose solution consumption in liquid consumption test of group CS and group CSF decreased significantly (P<0.05) at the 21th days.But after giving fluoxetine for 14 days,group CSF had no significant differences with group C except sucrose solution consumption.Although the difference of sucrose solution preferences was significant compared with

  12. Should we treat mild subclinical/mild hyperthyroidism? No.

    Science.gov (United States)

    Vanderpump, Mark P J

    2011-08-01

    The management of a patient with subclinical hyperthyroidism or mild thyroid over-activity is controversial. Subclinical hyperthyroidism is defined as a serum thyrotrophin (TSH) below the reference range but a normal thyroxine (T4) and triiodothyronine (T3) level in a patient who is either asymptomatic or has only non-specific symptoms. Epidemiological studies report an overall prevalence of approximately 3%, with men and women over 65 years and those in iodine deficient regions having the highest prevalence. Approximately 50% of subjects are taking levothyroxine. The aetiology for those with endogenous subclinical hyperthyroidism is Graves' disease, toxic nodular goitre or rarely a solitary toxic adenoma or thyroiditis. Non-thyroidal illness is an important cause of false positive low serum TSH test results. Subjects with low but detectable serum TSH values (0.1-0.4 mU/L) usually recover spontaneously when re-tested. It has been estimated that in those with an undetectable serum TSH (hyperthyroidism occurs at a rate up to 5% per year. Advocates of intervening for subclinical hyperthyroidism argue that early treatment might reduce mortality, prevent the later development of atrial fibrillation, osteoporotic fractures, and overt hyperthyroidism but data supporting improvement in outcomes are sparse. No appropriately powered prospective, randomised, controlled, double-blinded trial of intervention for subclinical hyperthyroidism exists. For the vast majority of patients adopting a "wait and see" policy rather than intervention may avoid unnecessary treatment or the potential for harm. Any potential benefits of therapy in subclinical hyperthyroidism must be weighed against the significant morbidity associated with the treatment of hyperthyroidism.

  13. 不同强度有氧训练对轻中度慢性阻塞性肺疾病的作用%Effect of aerobic exercises in different intensities on patients with mild to moderate chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    姜文君; 鲍军; 王磊; 张洪斌; 陆甘; 丁明; 刘剑南

    2012-01-01

    Objective: To compare the effects of high-intensity and low-intensity aerobic exercises on pulmonary ventilation function and exercise endurance of patients with mild to moderate chronic obstructive pulmonary disease (COPD). Method: Sixty patients with COPD were divided into high-intensity (with 70% peak power) aerobic exercise group (n=20) , low-intensity (with 50% peak power) aerobic exercise group (n=20) and control group (n=20). All patients administered cardiopulmonary exercise test(CPET) before and after training period, aerobic exercise duration was 8 weeks, 3 times every week. High intensity group did exercise for 40min per time with 4 sections,and each section lasted 5min with 5min interval,while low-intensity group administered 20min continuously exercise every time.Result:There was no significant difference(P>0.05) in all variables in three groups before training. After training, compared with before training the differences of exercise endurance duration, peak power and peak VO2 among three groups were significantly different (P0.05),but significant difference between high-intensity group and other groups(P<0.05). Anaerobic threshold (AT) of high-intensity group increased more than that of control group(P<0.05).Conclusion:Comparing with lower-intensity aerobic exercise, high-intensity interval aerobic exercise can significant-ly improve the pulmonary ventilation function and exercise endurance in patients with mild to moderate COPD.%目的:比较不同强度有氧训练对轻中度稳定期慢性阻塞性肺疾病(COPD)患者肺的通气功能和运动耐力的影响.方法:将60例轻中度稳定期COPD患者随机分为高强度(峰值功率的70%)有氧训练组20例、低强度(峰值功率的50%)有氧训练组20例、对照组20例,所有患者训练前后均进行心肺运动试验(CPET)评估,高强度与低强度有氧训练组均进行8周训练,每周3次,高强度训练组每次训练4组,每组以5min训练、5min休息

  14. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  15. The Influence of Causal Explanations and Diagnostic Labeling on Psychology Students' Beliefs About Treatments, Prognosis, Dangerousness and Unpredictability in Schizophrenia.

    Science.gov (United States)

    Magliano, Lorenza; Read, John; Rinaldi, Angela; Costanzo, Regina; De Leo, Renata; Schioppa, Giustina; Petrillo, Miriam

    2016-04-01

    This study explored views of 566 Italian psychology students about schizophrenia. The most frequently cited causes were psychological traumas (68 %) and heredity (54 %). Thirty-three percent of students firmly believed that people with the condition could recover. Reporting heredity among the causes, and identifying schizophrenia were both associated with prognostic pessimism, greater confidence in pharmacological treatments and lower confidence in psychological treatments. Schizophrenia labeling was also associated with higher perception of unpredictability and dangerousness. Compared to first year students, fourth/fifth year students more frequently reported heredity among the causes, and were more pessimistic about schizophrenia recovery. Stigma topics should be included in future psychologists' education.

  16. Location and acquisition of objects in unpredictable locations. [a teleoperator system with a computer for manipulator control

    Science.gov (United States)

    Sword, A. J.; Park, W. T.

    1975-01-01

    A teleoperator system with a computer for manipulator control to combine the capabilities of both man and computer to accomplish a task is described. This system allows objects in unpredictable locations to be successfully located and acquired. By using a method of characterizing the work-space together with man's ability to plan a strategy and coarsely locate an object, the computer is provided with enough information to complete the tedious part of the task. In addition, the use of voice control is shown to be a useful component of the man/machine interface.

  17. Self-rated health in patients with mild Alzheimer's disease: baseline data from the Danish Alzheimer Intervention Study

    DEFF Research Database (Denmark)

    Waldorff, Frans Boch; Nielsen, Anni B S; Waldemar, Gunhild

    2010-01-01

    , but the validity and the influence on other factors on SRH among cognitively impaired persons remain unknown. This study reports how patients with mild Alzheimer's disease (AD) report SRH and which factors influence SRH. The study was based on baseline data from 321 home living patients with mild AD who...... participated in the Danish Alzheimer Intervention Study (DAISY). Analysis using the generalized estimating equation (GEE) models revealed that good/excellent SRH among patients with mild AD were associated with longer education, lack of other chronic conditions, higher scores of quality of life (QOL), lower...

  18. Mild fetal cerebral ventriculomegaly as a prenatal sonographic marker for Kartagener syndrome.

    Science.gov (United States)

    Wessels, Marja W; den Hollander, Nicolette S; Willems, Patrick J

    2003-03-01

    Primary ciliary dyskinesia (PCD), also referred to as immotile-cilia syndrome or Kartagener syndrome, is a group of genetic disorders caused by defective cilia leading to chronic sinupulmonary infection, situs inversus and reduced fertility. Some PCD patients also have cerebral ventriculomegaly or hydrocephalus. We report here two fetuses and one newborn with mild cerebral ventriculomegaly and a suspected and/or confirmed diagnosis of PCD. These cases demonstrate that mild fetal cerebral ventriculomegaly can be a prenatal sonographic marker of PCD, certainly in fetuses with situs inversus or a history of a previous sib with PCD.

  19. Simple processes drive unpredictable differences in estuarine fish assemblages: Baselines for understanding site-specific ecological and anthropogenic impacts

    Science.gov (United States)

    Sheaves, Marcus

    2016-03-01

    Predicting patterns of abundance and composition of biotic assemblages is essential to our understanding of key ecological processes, and our ability to monitor, evaluate and manage assemblages and ecosystems. Fish assemblages often vary from estuary to estuary in apparently unpredictable ways, making it challenging to develop a general understanding of the processes that determine assemblage composition. This makes it problematic to transfer understanding from one estuary situation to another and therefore difficult to assemble effective management plans or to assess the impacts of natural and anthropogenic disturbance. Although system-to-system variability is a common property of ecological systems, rather than being random it is the product of complex interactions of multiple causes and effects at a variety of spatial and temporal scales. I investigate the drivers of differences in estuary fish assemblages, to develop a simple model explaining the diversity and complexity of observed estuary-to-estuary differences, and explore its implications for management and conservation. The model attributes apparently unpredictable differences in fish assemblage composition from estuary to estuary to the interaction of species-specific, life history-specific and scale-specific processes. In explaining innate faunal differences among estuaries without the need to invoke complex ecological or anthropogenic drivers, the model provides a baseline against which the effects of additional natural and anthropogenic factors can be evaluated.

  20. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    Science.gov (United States)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  1. [Mild brain injuries in emergency medicine].

    Science.gov (United States)

    Liimatainen, Suvi; Niskakangas, Tero; Ohman, Juha

    2011-01-01

    Diagnostics and correct classification of mild brain injuries is challenging. Problems caused by insufficient documentation at the acute phase become more obvious in situations in which legal insurance issues are to be considered. A small proportion of patients with mild brain injury suffer from prolonged symptoms. Medical recording and classification of the brain injury at the initial phase should therefore be carried out in a structured manner. The review deals with the diagnostic problems of mild brain injuries and presents a treatment protocol for adult patients at the acute phase, aiming at avoiding prolonged problems.

  2. Dysregulation of the hypothalamus-pituitary-adrenal axis predicts some aspects of the behavioral response to chronic fluoxetine: association with hippocampal cell proliferation

    Directory of Open Access Journals (Sweden)

    Wahid eKhemissi

    2014-09-01

    Full Text Available In depressed patients, antidepressant resistance has been associated with dysregulation of the hypothalamus-pituitary-adrenal (HPA axis but the underlying mechanisms are poorly understood. The scope of this study was to try to create HPA-related antidepressant resistance in mice and to investigate adult hippocampal neurogenesis as a putative mechanism of antidepressant resistance. Mice were subjected to a 9 week Unpredictable Chronic Mild Stress (UCMS. After a 2 weeks drug-free period, mice were segregated in two groups, according to the percentage of corticosterone suppression after dexamethasone injection: High suppression (HS and Low suppression (LS mice. From the 5thweek onwards, fluoxetine at a dose of 15 mg/kg (i.p. was administered daily and at the end of 8th week, a battery of behavioral tests assessing the emotional, cognitive, and motor aspects of UCMS-induced depressive-like behavior was applied. Results show that fluoxetine-induced antidepressant effects were observed with higher amplitude in HS when compared to LS on various behavioral phenotypes, like coat state, novelty suppression of feeding, splash test and nest test. The same profile was found concerning the immunohistochimical analysis of ki-67 positive cells in the dentate gyrus of the hippocampus, which is a marker of neuronal proliferation, but not for doublecortin labelling. This suggests that the failure of fluoxetine to induce antidepressant effects may be associated to the poor ability of the compound to stimulate cell proliferation in the hippocampus.

  3. Nonsurgical interventions after mild traumatic brain injury

    DEFF Research Database (Denmark)

    Nygren-de Boussard, Catharina; Holm, Lena W; Cancelliere, Carol;

    2014-01-01

    OBJECTIVE: To synthesize the best available evidence regarding the impact of nonsurgical interventions on persistent symptoms after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) with terms including "rehabilitation." Inclusion criteria wer...

  4. Brief RU 38486 Treatment Normalizes the Effects of Chronic Stress on Calcium Currents in Rat Hippocampal CA1 Neurons.

    NARCIS (Netherlands)

    Karst, H.; Joëls, M.

    2007-01-01

    Chronic stress alters many properties in rat brain, like serotonin responsiveness and dendritic morphology. In the present study, we examined (i) whether unpredictable stress during 21 days affects calcium (Ca) currents of CA1 pyramidal neurons recorded on day 22; and (ii) if so, whether this change

  5. Mild perinatal adversities moderate the association between maternal harsh parenting and hair cortisol: Evidence for differential susceptibility.

    Science.gov (United States)

    Windhorst, Dafna A; Rippe, Ralph C A; Mileva-Seitz, Viara R; Verhulst, Frank C; Jaddoe, Vincent W V; Noppe, Gerard; van Rossum, Elisabeth F C; van den Akker, Erica L T; Tiemeier, Henning; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2017-03-13

    It has been shown that following exposure to mild perinatal adversity, children have greater susceptibility to both the negative and positive aspects of their subsequent environment. In a large population-based cohort study (N = 1,776), we investigated whether mild perinatal adversity moderated the association between maternal harsh parenting and children's hair cortisol levels, a biomarker of chronic stress. Mild perinatal adversity was defined as late preterm birth (gestational age at birth of 34-37 weeks, 6 days) or small for gestational age (birth weight between the 2.5th and 10th percentile for full term gestational age). Harsh parenting was assessed by maternal self-report at 3 years. Children's hair cortisol concentrations were measured from hair samples collected at age 6. There were no significant bivariate associations between mild perinatal adversities and harsh parenting and hair cortisol. However, mild perinatal adversities moderated the association between maternal harsh parenting and hair cortisol levels. Children with mild perinatal adversity had lower cortisol levels if parented more harshly and higher cortisol levels in the absence of harsh parenting than children who did not experience mild perinatal adversity. These results provide further evidence that mild perinatal adversity is a potential marker of differential susceptibility to environmental influences.

  6. Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

    Directory of Open Access Journals (Sweden)

    Bing Han

    2017-03-01

    Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

  7. Chronic cholecystitis

    Science.gov (United States)

    Cholecystitis - chronic ... Most of the time, chronic cholecystitis is caused by repeated attacks of acute (sudden) cholecystitis. Most of these attacks are caused by gallstones in the gallbladder. These ...

  8. Chronic Pain

    Science.gov (United States)

    ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. × ... pain. Psychotherapy, relaxation and medication therapies, biofeedback, and behavior modification may also be employed to treat chronic pain. ...

  9. Chronic Pain

    Science.gov (United States)

    ... a problem you need to take care of. Chronic pain is different. The pain signals go on ... there is no clear cause. Problems that cause chronic pain include Headache Low back strain Cancer Arthritis ...

  10. Short- and Long-Term Effects of Unpredictable Repeated Negative Stimuli on Japanese Quail's Fear of Humans

    Science.gov (United States)

    Laurence, Agathe; Lumineau, Sophie; Calandreau, Ludovic; Arnould, Cécile; Leterrier, Christine; Boissy, Alain; Houdelier, Cécilia

    2014-01-01

    Numerous aversive events occur in poultry production, and if repeated and unpredictable, can result in an impaired welfare. Some events such as handling can be perceived negatively and it is of interest to understand how humans' behaviour could affect poultry's behaviours and especially its avoidance of humans. Our aim was to evaluate short- and long-lasting effects of a 3-week procedure involving unpredictable repeated negative stimuli (URNS) applied during the post-juvenile period on quail's reactivity to humans. We compared the reactions of two sets of quail: URNS was applied to one set (treated quail) and the other set was left undisturbed (control quail). When two weeks old, treated quail were exposed to a variety of negative stimuli, either applied automatically or involving human presence. One and seven weeks after the termination of the procedure, the reactivity of control and treated quail to a passive human being was evaluated. Furthermore, the experimenter with her hand on a trough containing a mealworm assessed the propensity of quail of both groups to habituate to feed close to a human being. In the presence of a seated observer, treated quail were more inhibited and more alert than control quail. Likewise, seven weeks after the end of the URNS procedure, more treated than control quail adopted a fear posture. Moreover, whereas control quail spent as much time in the different areas of their cages, treated quail spent more time in the rear part of their cages. Finally, whereas control quail habituated gradually to feed near the experimenter's hand, treated quail did not. All these tests evidence negative short- and long-term effects on treated quail's reactivity to a passive human being and on their habituation to a human being when her presence is positively reinforced. This highlights the importance of young poultry's experience with humans in production. PMID:24668017

  11. Short- and long-term effects of unpredictable repeated negative stimuli on Japanese quail's fear of humans.

    Science.gov (United States)

    Laurence, Agathe; Lumineau, Sophie; Calandreau, Ludovic; Arnould, Cécile; Leterrier, Christine; Boissy, Alain; Houdelier, Cécilia

    2014-01-01

    Numerous aversive events occur in poultry production, and if repeated and unpredictable, can result in an impaired welfare. Some events such as handling can be perceived negatively and it is of interest to understand how humans' behaviour could affect poultry's behaviours and especially its avoidance of humans. Our aim was to evaluate short- and long-lasting effects of a 3-week procedure involving unpredictable repeated negative stimuli (URNS) applied during the post-juvenile period on quail's reactivity to humans. We compared the reactions of two sets of quail: URNS was applied to one set (treated quail) and the other set was left undisturbed (control quail). When two weeks old, treated quail were exposed to a variety of negative stimuli, either applied automatically or involving human presence. One and seven weeks after the termination of the procedure, the reactivity of control and treated quail to a passive human being was evaluated. Furthermore, the experimenter with her hand on a trough containing a mealworm assessed the propensity of quail of both groups to habituate to feed close to a human being. In the presence of a seated observer, treated quail were more inhibited and more alert than control quail. Likewise, seven weeks after the end of the URNS procedure, more treated than control quail adopted a fear posture. Moreover, whereas control quail spent as much time in the different areas of their cages, treated quail spent more time in the rear part of their cages. Finally, whereas control quail habituated gradually to feed near the experimenter's hand, treated quail did not. All these tests evidence negative short- and long-term effects on treated quail's reactivity to a passive human being and on their habituation to a human being when her presence is positively reinforced. This highlights the importance of young poultry's experience with humans in production.

  12. Short- and long-term effects of unpredictable repeated negative stimuli on Japanese quail's fear of humans.

    Directory of Open Access Journals (Sweden)

    Agathe Laurence

    Full Text Available Numerous aversive events occur in poultry production, and if repeated and unpredictable, can result in an impaired welfare. Some events such as handling can be perceived negatively and it is of interest to understand how humans' behaviour could affect poultry's behaviours and especially its avoidance of humans. Our aim was to evaluate short- and long-lasting effects of a 3-week procedure involving unpredictable repeated negative stimuli (URNS applied during the post-juvenile period on quail's reactivity to humans. We compared the reactions of two sets of quail: URNS was applied to one set (treated quail and the other set was left undisturbed (control quail. When two weeks old, treated quail were exposed to a variety of negative stimuli, either applied automatically or involving human presence. One and seven weeks after the termination of the procedure, the reactivity of control and treated quail to a passive human being was evaluated. Furthermore, the experimenter with her hand on a trough containing a mealworm assessed the propensity of quail of both groups to habituate to feed close to a human being. In the presence of a seated observer, treated quail were more inhibited and more alert than control quail. Likewise, seven weeks after the end of the URNS procedure, more treated than control quail adopted a fear posture. Moreover, whereas control quail spent as much time in the different areas of their cages, treated quail spent more time in the rear part of their cages. Finally, whereas control quail habituated gradually to feed near the experimenter's hand, treated quail did not. All these tests evidence negative short- and long-term effects on treated quail's reactivity to a passive human being and on their habituation to a human being when her presence is positively reinforced. This highlights the importance of young poultry's experience with humans in production.

  13. Chronic prostatitis

    OpenAIRE

    Le, Brian; Schaeffer, Anthony J.

    2011-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome [CP/CPPS]). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  14. Chronic prostatitis

    OpenAIRE

    Erickson, Bradley A.; Schaeffer, Anthony J.; Le, Brian

    2008-01-01

    Chronic prostatitis can cause pain and urinary symptoms, and usually occurs without positive bacterial cultures from prostatic secretions (known as chronic abacterial prostatitis or chronic pelvic pain syndrome, CP/CPPS). Bacterial infection can result from urinary tract instrumentation, but the cause and natural history of CP/CPPS are unknown.

  15. The relationship between inspiratory lung function parameters and airway hyper-responsiveness in subjects with mild to moderate COPD

    NARCIS (Netherlands)

    S.K. Ramlal (Sunil); F.J. Visser (Frank); W.C.J. Hop (Wim); B. Staffhorst (Bas); P.N.R. Dekhuijzen (Richard); Y.F. Heijdra (Yvonne)

    2012-01-01

    textabstractBackground: The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV 1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (C

  16. VA/DoD Clinical Practice Guideline for Management of Concussion/Mild Traumatic Brain Injury (mTBI)

    Science.gov (United States)

    2009-04-01

    chronic pain: preliminary findings Archives of Clinical Neuropsychology , Volume 15, Issue 8, , November 2000, Pages 831-832 Borczuk, P.: Mild head...G, Zielinski RE, Fichera S, Rayls KR. Cognitive-behavioral prevention of postconcussion syndrome. Archives of Clinical Neuropsychology 1996;11(2):139

  17. Left Atrial Volume as Predictor of Valve Replacement and Cardiovascular Events in Patients with Asymptomatic Mild to Moderate Aortic Stenosis

    DEFF Research Database (Denmark)

    Dalsgaard, Morten; Egstrup, Kenneth; Wachtell, Kristian

    2013-01-01

    Left atrial (LA) size is known to increase with chronically increased left ventricular (LV) filling pressure. We hypothesized that LA volume was predictive of aortic valve replacement (AVR) and cardiovascular events in a large cohort of patients with asymptomatic mild to moderate aortic valve...... stenosis....

  18. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    -20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter......Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema...... in causing airway narrowing, the latter most likely due to loss of elastic recoil of surrounding tissue....

  19. Pain Catastrophizing Correlates with Early Mild Traumatic Brain Injury Outcome

    Science.gov (United States)

    Chaput, Geneviève; Lajoie, Susanne P.; Naismith, Laura M.; Lavigne, Gilles

    2016-01-01

    Background. Identifying which patients are most likely to be at risk of chronic pain and other postconcussion symptoms following mild traumatic brain injury (MTBI) is a difficult clinical challenge. Objectives. To examine the relationship between pain catastrophizing, defined as the exaggerated negative appraisal of a pain experience, and early MTBI outcome. Methods. This cross-sectional design included 58 patients diagnosed with a MTBI. In addition to medical chart review, postconcussion symptoms were assessed by self-report at 1 month (Time 1) and 8 weeks (Time 2) after MTBI. Pain severity, psychological distress, level of functionality, and pain catastrophizing were measured by self-report at Time 2. Results. The pain catastrophizing subscales of rumination, magnification, and helplessness were significantly correlated with pain severity (r = .31 to .44), number of postconcussion symptoms reported (r = .35 to .45), psychological distress (r = .57 to .67), and level of functionality (r = −.43 to −.29). Pain catastrophizing scores were significantly higher for patients deemed to be at high risk of postconcussion syndrome (6 or more symptoms reported at both Time 1 and Time 2). Conclusions. Higher levels of pain catastrophizing were related to adverse early MTBI outcomes. The early detection of pain catastrophizing may facilitate goal-oriented interventions to prevent or minimize the development of chronic pain and other postconcussion symptoms. PMID:27445604

  20. Pain Catastrophizing Correlates with Early Mild Traumatic Brain Injury Outcome

    Directory of Open Access Journals (Sweden)

    Geneviève Chaput

    2016-01-01

    Full Text Available Background. Identifying which patients are most likely to be at risk of chronic pain and other postconcussion symptoms following mild traumatic brain injury (MTBI is a difficult clinical challenge. Objectives. To examine the relationship between pain catastrophizing, defined as the exaggerated negative appraisal of a pain experience, and early MTBI outcome. Methods. This cross-sectional design included 58 patients diagnosed with a MTBI. In addition to medical chart review, postconcussion symptoms were assessed by self-report at 1 month (Time 1 and 8 weeks (Time 2 after MTBI. Pain severity, psychological distress, level of functionality, and pain catastrophizing were measured by self-report at Time 2. Results. The pain catastrophizing subscales of rumination, magnification, and helplessness were significantly correlated with pain severity (r=.31 to .44, number of postconcussion symptoms reported (r=.35 to .45, psychological distress (r=.57 to .67, and level of functionality (r=-.43 to -.29. Pain catastrophizing scores were significantly higher for patients deemed to be at high risk of postconcussion syndrome (6 or more symptoms reported at both Time 1 and Time 2. Conclusions. Higher levels of pain catastrophizing were related to adverse early MTBI outcomes. The early detection of pain catastrophizing may facilitate goal-oriented interventions to prevent or minimize the development of chronic pain and other postconcussion symptoms.

  1. Efficacy of Cellex in patients with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    B. A. Abusueva

    2016-01-01

    Full Text Available Background. Cognitive disorders may often lead to professional invalidisation and increasing dependence on the external assistance in every day life. Identification of patients with preserved intellectual status and social adaptation but with mild cognitive impairment (MCI is considered to be an effective measure. MCI detection and timely initiation of treatment in most patients is essential to delay the onset of severe dementia.Objective. Investigating influence of Cellex in patients with chronic cerebral ischemia and MCI.Materials and methods. As a part of non-interventional observational comparative study we evaluated the results of Cellex administration in 90 patients with MCI. Patients were divided into 2 groups. Patients from both groups received 1 course of 10 subcutaneous injections of Cellex drug at the dose of 1 mL, and patients from group 2 received two identical courses with an interval of two months. The survey, which included psychometric testing by using special questionnaires (Mini-Mental State Examination, “Frontal Assessment Battery” and “Clock Drawing” tests, Schulte test was performed before treatment, and at months 1 and 2 after its completion.Results. Neuropsychological examination revealed improvement in the patients state, more pronounced after the 2nd course of therapy.Discussion. Our results provide a basis for using Cellex in patients with chronic cerebral ischemia and MCI, allowing to proceede with further studies on the optimal dosage of that drug.

  2. Neuropsychological function following mild exposure to pentaborane

    Energy Technology Data Exchange (ETDEWEB)

    Hart, R.P.; Silverman, J.J.; Garrettson, L.K.; Schulz, C.; Hamer, R.M.

    1984-01-01

    Neuropsychological tests and self-report personality inventories were administered to 14 workers and rescue squad personnel approximately 2 months following mild exposure to pentaborane, a highly toxic volatile liquid boron hydride. Performance decrements were evident on 5 of 11 neuropsychological tests, including Block Design and measures of sustained attention and recent memory. Neuropsychological deficits were not related to emotional changes reported on the Hopkins Symptom Checklist nor to the presence of CT scan abnormality. These results indicate mild residual brain dysfunction following pentaborane intoxication, including possible dysfunction in subcortical regions mediating memory processes and in cortical areas mediating visuo-spatial abilities.

  3. Mild disintegration of green microalgae and macroalgae

    NARCIS (Netherlands)

    Postma, Richard

    2016-01-01

    An increased worldwide protein demand for food and feed and the necessity to release the water soluble proteins in the first stage of the cascade biorefinery require the development of mild protein extraction technologies. Cell disintegration is the first hurdle and is considered as one of the most

  4. Learning Strategies for Adolescents with Mild Disabilities

    Science.gov (United States)

    Conderman, Greg; Koman, Kara; Schibelka, Mary; Higgin, Karen; Cooper, Cody; Butler, Jordyn

    2013-01-01

    Learning strategy instruction is an evidence-based practice for teaching adolescents with mild disabilities. However, researchers have not developed strategies for every content area or skill. Therefore, teachers need to be able develop strategies based on the needs of their students. This article reviews the process for developing and teaching…

  5. Mild hyperthermia influence on Herceptin (R) properties

    NARCIS (Netherlands)

    Escoffre, JM; Deckers, RHR; Sasaki, Noboru; Bos, Clemens; Moonen, Chrit

    2015-01-01

    Background. Mild hyperthermia (mHT) increases the tumor perfusion and vascular permeability, and reduces the interstitial fluid pressure, resulting in better intra-tumoral bioavailability of low molecular weight drugs. This approach is potentially also attractive for delivery of therapeutic macromol

  6. Mild Traumatic Brain Injury – Case Report

    Directory of Open Access Journals (Sweden)

    2015-06-01

    Full Text Available A mild traumatic brain injury or a concussion represents the majority of all traumatic brain injuries. The consequences show on physical, cognitive, and emotional functioning and even though the injury classifies as mild, it can have a significant effect on a patient, patient’s family and their quality of life. Defects are often overlooked as objective clinical methods are lacking. Neuropsychological evaluation can aid in appraisal of the defect magnitude and determine factors that influence the outcome of the injured. The following case report addresses the importance of neuropsychological evaluation in treating cognitive defects along with the Cognitive Behavioral therapy approach toward emotional and behavioral disorders treatment in mild traumatic brain injury. It has been shown how important it is to find possible causes for slow recovery. The annuity tendencies have been noted as an important factor for prolongation of the post-concussion syndrome. We can detect the symptom simulation with appropriate psychological instruments. Described is a case of 38-year-old man who suffered a mild traumatic brain injury.

  7. Surgical strategy for mild ischemic mitral insufficiency

    Institute of Scientific and Technical Information of China (English)

    GU Cheng-xiong; WEI Hua; YU Yang

    2010-01-01

    @@ To the Editor: We read with the interest the article by FAN Hong-guang and colleagues~1 having obtained outstanding early and long-term clinical outcomes of left ventricular restoration for the patients with postinfarction ventricular aneurysm and low left ventricular ejection fraction (LVEF) of mean 37.7%. We would like to comment on surgical strategy for mild ischemic mitral insufficiency.

  8. Sleep deprivation does not affect neuronal susceptibility to mild traumatic brain injury in the rat

    Directory of Open Access Journals (Sweden)

    Caron AM

    2015-06-01

    Full Text Available Aimee M Caron, Richard Stephenson Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada Abstract: Mild and moderate traumatic brain injuries (TBIs (and concussion occur frequently as a result of falls, automobile accidents, and sporting activities, and are a major cause of acute and chronic disability. Fatigue and excessive sleepiness are associated with increased risk of accidents, but it is unknown whether prior sleep debt also affects the pathophysiological outcome of concussive injury. Using the “dark neuron” (DN as a marker of reversible neuronal damage, we tested the hypothesis that acute (48 hours total sleep deprivation (TSD and chronic sleep restriction (CSR; 10 days, 6-hour sleep/day affect DN formation following mild TBI in the rat. TSD and CSR were administered using a walking wheel apparatus. Mild TBI was administered under anesthesia using a weight-drop impact model, and the acute neuronal response was observed without recovery. DNs were detected using standard bright-field microscopy with toluidine blue stain following appropriate tissue fixation. DN density was low under home cage and sleep deprivation control conditions (respective median DN densities, 0.14% and 0.22% of neurons, and this was unaffected by TSD alone (0.1%. Mild TBI caused significantly higher DN densities (0.76%, and this was unchanged by preexisting acute or chronic sleep debt (TSD, 0.23%; CSR, 0.7%. Thus, although sleep debt may be predicted to increase the incidence of concussive injury, the present data suggest that sleep debt does not exacerbate the resulting neuronal damage. Keywords: sleep deprivation, concussion, traumatic brain injury, dark neuron, neurodegeneration, rat cortex

  9. Models of acute and chronic pancreatitis.

    Science.gov (United States)

    Lerch, Markus M; Gorelick, Fred S

    2013-06-01

    Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

  10. Dormant stages of crustaceans as a mechanism of propagation in the extreme and unpredictable environment in the Crimean hypersaline lakes

    Science.gov (United States)

    Shadrin, Nickolai V.; Anufriieva, Elena V.; Amat, Francisco; Eremin, Oleg Yu.

    2015-11-01

    A pool of dormant stages of planktonic organisms in saline lakes is a substantial component in the plankton communities; we need to take it into account to understand plankton dynamics. Hypersaline water bodies in Crimea, the largest peninsula in the Black Sea, constitute a very characteristic and peculiar habitat type in the region. We examined the presence of crustacean resting stages in sediments of dried up sites of the Crimean hypersaline lakes. Sediment samples were taken in 9 different lakes. Experiments performed on the hatching of these resting stages showed the presence of Moina salina (Cladocera), parthenogenetic Artemia and Artemia urmiana (Anostraca), Eucypris mareotica ( inflata) (Ostracoda), and Cletocamptus retrogressus (Harpacticoida). Comparing the experimental results obtained with clean dried brine shrimp cysts and those kept in sediment samples, it was noted that clean cysts hatched much faster than those from sediments did. Some components in bottom sediments slow down and desynchronize hatching from resting eggs in different groups of crustaceans. The sediments of different lakes inhibited the nauplii output from Artemia and ostracod resting eggs to different degrees. More data are needed before we can discuss the reasons of this inhibition. The nonsynchronous output of active stages from the bottom resting ones may be an adaptation that allows crustacean species to exist in extreme and unpredictably changing environments, avoiding the risk that all may emerge at once under unsuitable conditions.

  11. Prenatal stress effects in a wild, long-lived primate: predictive adaptive responses in an unpredictable environment

    Science.gov (United States)

    Heistermann, Michael; Schülke, Oliver; Ostner, Julia

    2016-01-01

    Prenatal maternal stress affects offspring phenotype in numerous species including humans, but it is debated whether these effects are evolutionarily adaptive. Relating stress to adverse conditions, current explanations invoke either short-term developmental constraints on offspring phenotype resulting in decelerated growth to avoid starvation, or long-term predictive adaptive responses (PARs) resulting in accelerated growth and reproduction in response to reduced life expectancies. Two PAR subtypes were proposed, acting either on predicted internal somatic states or predicted external environmental conditions, but because both affect phenotypes similarly, they are largely indistinguishable. Only external (not internal) PARs rely on high environmental stability particularly in long-lived species. We report on a crucial test case in a wild long-lived mammal, the Assamese macaque (Macaca assamensis), which evolved and lives in an unpredictable environment where external PARs are probably not advantageous. We quantified food availability, growth, motor skills, maternal caretaking style and maternal physiological stress from faecal glucocorticoid measures. Prenatal maternal stress was negatively correlated to prenatal food availability and led to accelerated offspring growth accompanied by decelerated motor skill acquisition and reduced immune function. These results support the ‘internal PAR’ theory, which stresses the role of stable adverse internal somatic states rather than stable external environments. PMID:27655764

  12. [Chronicity, chronicization, systematization of delusions].

    Science.gov (United States)

    Trapet, P; Fernandez, C; Galtier, M C; Gisselmann, A

    1984-05-01

    Chronicity in psychopathology is indicative of a term, a decay. Chronicization only leads the way to this term. Here, chronicization is taken literally as an inscription in the time course of delusions. The mechanism of systematization seems to be a central mark in the approach to chronic delusions. It is not an alienation or an irreversible closing but an attempted accommodation with reality in the life of psychotic subjects, irrespective of the delusional structure. The role of therapy and drug treatment as a follow-up may in that case assume another meaning.

  13. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Froeling, Fieke EM

    2008-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas owing to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects 3–9 people in 100,000; 70% of cases are alcohol-induced.

  14. Chronic pancreatitis

    OpenAIRE

    Kocher, Hemant M.; Kadaba, Raghu

    2011-01-01

    Chronic pancreatitis is characterised by long-standing inflammation of the pancreas due to a wide variety of causes, including recurrent acute attacks of pancreatitis. Chronic pancreatitis affects between 3 and 9 people in 100,000; 70% of cases are alcohol-induced.

  15. Metastatic Renal Cell Carcinoma to the Parotid Gland in the Setting of Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Robert Deeb

    2012-01-01

    Full Text Available Renal cell carcinoma (RCC is infamous for its unpredictable behavior and metastatic potential. We report a case of a patient with a complex history of multifocal renal cell carcinoma and chronic lymphocytic leukemia (CLL, who subsequently developed a parotid mass. Total parotidectomy revealed this mass to be an additional site of metastasis which had developed 19 years after his initial diagnosis of RCC.

  16. Early supported discharge following mild stroke

    DEFF Research Database (Denmark)

    Lou, Stina; Carstensen, Kathrine; Møldrup, Marie;

    2016-01-01

    BACKGROUND: Early supported discharge (ESD) allows mild-to-moderate stroke patients to return home as soon as possible and continue rehabilitation at their own pace in familiar surroundings. Thus, the main responsibility for continued rehabilitation is in the hands of patients and their partners......, who must collaborate to adjust to poststroke everyday life. However, couples' joint experiences of stroke, early discharge and rehabilitation at home remain minimally investigated. AIM: To investigate how mild stroke patients' and their partners' experience and manage everyday life in a context of ESD....... METHODS: We conducted qualitative interviews with a purposive sample of 22 ESD patients and 18 partners. Interviews were conducted 3-6 weeks after stroke, and we used thematic analysis to analyse the data. FINDINGS: The analysis identified three themes. First, 'Home as a healing place' involved...

  17. An Extended Mild-Slope Equation

    Institute of Scientific and Technical Information of China (English)

    PAN Junning; HONG Guangwen; ZUO Qihua

    2000-01-01

    On the assumption that the vortex and the vertical velocity component of the current are small, a mild-slope equation for wave propagation on non-uniform flows is deduced from the basic hydrodynamic equations, with the terms of ( h h)2 and /2h h included in the equation. The terms of bottom friction, wind energy input and wave nonlinearity are also introduced into the equation. The wind energy input functions for wind waves and swells are separately considered by adopting Wen′s (1989) empirical formula for wind waves and Snyder′s observation results for swells. Thus, an extended mild-slope equation is obtained, in which the effects of refraction, diffraction, reflection, current, bottom friction, wind energy input and wave nonlinearity are considered synthetically.

  18. A mild form of Proteus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hauer, M.P.; Allmann, K.H.; Langer, M. [Abteilung Roentgendiagnostik, Radiologische Universitaetsklinik, Albert-Ludwigs-Universitaet Freiburg (Germany); Uhl, M. [Sektion Kinderradiologie, Albert-Ludwigs-Universitaet (Germany); Darge, K. [Radiologische Universitaetsklinik, Abteilung Kinderradiologie, Universitaet Heidelberg (Germany)

    1998-05-01

    Proteus syndrome is a rare congenital hamartomatous syndrome. We report on the clinical and radiological appearances of a boy in order to illustrate the typical signs which include subcutaneous masses, in mild forms partial gigantism of hands and feet, hemihypertrophy, and bony abnormalities. We discuss how to make the definitive diagnosis on the basis of using a known rating scale, important aspects of differential diagnosis and clinical features, and diagnostic management. (orig.) With 3 figs., 1 tab., 14 refs.

  19. Perinatal Risk Factors for Mild Motor Disability

    Science.gov (United States)

    Hands, Beth; Kendall, Garth; Larkin, Dawne; Parker, Helen

    2009-01-01

    The aetiology of mild motor disability (MMD) is a complex issue and as yet is poorly understood. The aim of this study was to identify the prevalence of perinatal risk factors in a cohort of 10-year-old boys and girls with (n = 362) and without (n = 1193) MMD. Among the males with MMD there was a higher prevalence of postpartum haemorrhage,…

  20. Predicting the unpredictable.

    Science.gov (United States)

    Bonabeau, Eric

    2002-03-01

    The collective behavior of people in crowds, markets, and organizations has long been a mystery. Why, for instance, do employee bonuses sometimes lead to decreases in productivity? Why do some products generate tremendous buzz, seemingly out of nowhere, while others languish despite multimillion-dollar marketing campaigns? How could a simple clerical error snowball into a catastrophic loss that bankrupts a financial institution? Traditional approaches like spreadsheet and regression analyses have failed to explain such "emergent phenomena," says Eric Bonabeau, because they work from the top down, trying to apply global equations and frameworks to a particular situation. But the behavior of emergent phenomena, contends Bonabeau, is formed from the bottom up--starting with the local interactions of individuals who alter their actions in response to other participants. Together, the myriad interactions result in a group behavior that can easily elude any top-down analysis. But now, thanks to "agent-based modeling," some companies are finding ways to analyze--and even predict--emergent phenomena. Macy's, for instance, has used the technology to investigate better ways to design its department stores. Hewlett-Packard has run agent-based simulations to anticipate how changes in its hiring strategy would affect its corporate culture. And Société Générale has used the technology to determine the operational risk of its asset management group. This article discusses emergent phenomena in detail and explains why they have become more prevalent in recent years. In addition to providing real-world examples of companies that have improved their business practices through agent-based modeling, Bonabeau also examines the future of this technology and points to several fields that may be revolutionized by its use.

  1. Complex and Unpredictable Cardano

    CERN Document Server

    Ekert, Artur

    2008-01-01

    This purely recreational paper is about one of the most colorful characters of the Italian Renaissance, Girolamo Cardano, and the discovery of two basic ingredients of quantum theory, probability and complex numbers. The paper is dedicated to Giuseppe Castagnoli on the occasion of his 65th birthday. Back in the early 1990s, Giuseppe instigated a series of meetings at Villa Gualino, in Torino, which brought together few scattered individuals interested in the physics of computation. By doing so he effectively created and consolidated a vibrant and friendly community of researchers devoted to quantum information science. Many thanks for that!

  2. Complex and unpredictable Cardano

    Science.gov (United States)

    Ekert, Artur

    2008-08-01

    This purely recreational paper is about one of the most colorful characters of the Italian Renaissance, Girolamo Cardano, and the discovery of two basic ingredients of quantum theory, probability and complex numbers.

  3. Decisions under unpredictable losses

    Directory of Open Access Journals (Sweden)

    Ali Ahmed

    2007-10-01

    Full Text Available An experimental test of the descriptive adequacy of the extit{restated diversification principle} is presented. The principle postulates that risk-averse utility maximizers will pool risks for their mutual benefit, even if information is missing about the probabilities of losses. It is enough for people to assume that they face equal risks when they pool risks. The results of the experiment support the principle.

  4. Mild obstructive sleep apnea: beyond the AHI

    Directory of Open Access Journals (Sweden)

    Lee-Iannotti J

    2014-07-01

    Full Text Available No abstract available. Article truncated at 150 words. A common conundrum faced by sleep medicine practitioners is how to manage the large group of patients with mild sleep apnea. Many patients are referred for sleep evaluation, with symptoms thought to be due to obstructive sleep apnea (OSA. Often polysomnography demonstrates only mild sleep apnea, and the clinician and patient are faced with the dilemma of whether to use continuous positive airway pressure (CPAP therapy or an oral appliance. In making this important decision the clinician incorporates the commonly used definition of mild sleep apnea as an apnea-hypopnea index of between 5 and 14 apneas or hypopneas per hour of sleep. Moderate sleep apnea is defined as 15-29 events per hour, and severe is 30 and above events per hour. These arbitrary thresholds originated in the early 1980s when knowledge of this condition was in its infancy and little was known about the long term health effects. The definition ...

  5. Coping with unpredictability: dopaminergic and neurotrophic responses to omission of expected reward in Atlantic salmon (Salmo salar L..

    Directory of Open Access Journals (Sweden)

    Marco A Vindas

    Full Text Available Comparative studies are imperative for understanding the evolution of adaptive neurobiological processes such as neural plasticity, cognition, and emotion. Previously we have reported that prolonged omission of expected rewards (OER, or 'frustrative nonreward' causes increased aggression in Atlantic salmon (Salmo salar. Here we report changes in brain monoaminergic activity and relative abundance of brain derived neurotrophic factor (BDNF and dopamine receptor mRNA transcripts in the same paradigm. Groups of fish were initially conditioned to associate a flashing light with feeding. Subsequently, the expected food reward was delayed for 30 minutes during two out of three meals per day in the OER treatment, while the previously established routine was maintained in control groups. After 8 days there was no effect of OER on baseline brain stem serotonin (5-HT or dopamine (DA activity. Subsequent exposure to acute confinement stress led to increased plasma cortisol and elevated turnover of brain stem DA and 5-HT in all animals. The DA response was potentiated and DA receptor 1 (D1 mRNA abundance was reduced in the OER-exposed fish, indicating a sensitization of the DA system. In addition OER suppressed abundance of BDNF in the telencephalon of non-stressed fish. Regardless of OER treatment, a strong positive correlation between BDNF and D1 mRNA abundance was seen in non-stressed fish. This correlation was disrupted by acute stress, and replaced by a negative correlation between BDNF abundance and plasma cortisol concentration. These observations indicate a conserved link between DA, neurotrophin regulation, and corticosteroid-signaling pathways. The results also emphasize how fish models can be important tools in the study of neural plasticity and responsiveness to environmental unpredictability.

  6. Anticipatory postural adjustments and anticipatory synergy adjustments: preparing to a postural perturbation with predictable and unpredictable direction.

    Science.gov (United States)

    Piscitelli, Daniele; Falaki, Ali; Solnik, Stanislaw; Latash, Mark L

    2017-03-01

    We explored two aspects of feed-forward postural control, anticipatory postural adjustments (APAs) and anticipatory synergy adjustments (ASAs) seen prior to self-triggered unloading with known and unknown direction of the perturbation. In particular, we tested two main hypotheses predicting contrasting changes in APAs and ASAs. The first hypothesis predicted no major changes in ASAs. The second hypothesis predicted delayed APAs with predominance of co-contraction patterns when perturbation direction was unknown. Healthy subjects stood on the force plate and held a bar with two loads acting in the forward and backward directions. They pressed a trigger that released one of the loads causing a postural perturbation. In different series, the direction of the perturbation was either known (the same load released in all trials) or unknown (the subjects did not know which of the two loads would be released). Surface electromyograms were recorded and used to quantify APAs, synergies stabilizing center of pressure coordinate (within the uncontrolled manifold hypothesis), and ASA. APAs and ASAs were seen in all conditions. APAs were delayed, and predominance of co-contraction patterns was seen under the conditions with unpredictable direction of perturbation. In contrast, no significant changes in synergies and ASAs were seen. Overall, these results show that feed-forward control of vertical posture has two distinct components, reflected in APAs and ASAs, which show qualitatively different adjustments with changes in predictability of the direction of perturbation. These results are interpreted within the recently proposed hierarchical scheme of the synergic control of motor tasks. The observations underscore the complexity of the feed-forward postural control, which involves separate changes in salient performance variables (such as coordinate of the center of pressure) and in their stability properties.

  7. Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment.

    LENUS (Irish Health Repository)

    O'Caoimh, Rónán

    2012-09-01

    differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen.

  8. A review of oral labetalol and nifedipine in mild to moderate hypertension in pregnancy.

    Science.gov (United States)

    Clark, Shannon M; Dunn, Holly E; Hankins, Gary D V

    2015-11-01

    Hypertension is the most commonly encountered medical condition in pregnancy, contributing significantly to maternal and perinatal morbidity and mortality. Mild to moderate hypertension in pregnancy is defined as systolic blood pressure of 140-159 mmHg or diastolic blood pressure of 90-109 mmHg (7-9% of pregnancies). When treating hypertension in pregnancy, not only do physiologic changes of pregnancy have an effect on the pharmacokinetics and pharmacodynamics of the drugs used, but the pathophysiology of hypertensive disorders of pregnancy also have an effect. To date, evidence is lacking on the pharmacokinetics and pharmacodynamics of commonly used antihypertensive drugs, which often times leads to suboptimal treatment of hypertensive pregnant women. When considering which agents to use for treatment of mild to moderate hypertension, specifically in gestational and chronic hypertension, oral labetalol and nifedipine are valid options. An overview of the profile for use, safety, and current pharmacokinetic data for each agent is presented here.

  9. Ear infection - chronic

    Science.gov (United States)

    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... up. When this happens, infection can occur. A chronic ear infection develops when fluid or an infection ...

  10. A comparison of long-term postconcussive symptoms between university students with and without a history of mild traumatic brain injury or orthopedic injury.

    Science.gov (United States)

    Ettenhofer, Mark L; Barry, David M

    2012-05-01

    Mild traumatic brain injury (mild TBI) is often associated with postconcussive symptoms such as headache, memory problems, and irritability. However, high rates of similar symptoms in groups without a history of TBI raise questions about the clinical validity of the postconcussive syndrome. This study was conducted to address these issues through systematic examination of symptoms reported by those with and without a history of mild TBI or orthopedic injury. Responses to the Postconcussion Syndrome Checklist (PCSC), demographic information, and medical history were collected via online questionnaire from 3027 non-referred university students (2280 without a history of mild TBI or orthopedic injury, 491 with a history of orthopedic injury, and 256 with post-acute mild TBI). Although the mild TBI group reported higher mean levels of symptoms, confirmatory factor analyses demonstrated that symptoms clustered into parallel cognitive, somatic, affective, and sensory factors in all three groups. Despite modestly higher mean symptoms among those with a history of mild TBI, symptom clusters did not differ from non-TBI groups. These findings cast doubts about the clinical validity of the "postconcussive syndrome" and raise questions about pathways by which mild TBI and other factors may influence the expression of chronic symptoms.

  11. 海马NMDA受体经SP-NK1受体通路参与慢性应激诱发的抑郁样行为%Hippocampal NMDA Receptor is involved in Chronic Stress Induced Depressive-Like Behaviors via SP-NK1 Receptor Pathway

    Institute of Scientific and Technical Information of China (English)

    董素平; 徐畅; 原婷婷; 安书成

    2011-01-01

    为探讨海马N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体与P物质(Substance P,SP)及其神经激肽1 (neurokinin1,NK1)受体在慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)中的作用及其关系,通过建立CUMS动物模型,大鼠海马微量注射给药,测量大鼠体重,并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测,运用高效液相色谱(HPLC)法分析大鼠海马组织中SP和谷氨酸(glutamate,Glu)的含量变化.结果显示,CUMS诱发大鼠表现出明显的抑郁样行为,海马组织中SP和Glu水平显著增加;海马注射NMDA,大鼠表现出与CUMS/SAL组相似的抑郁样行为,且海马组织中SP的含量比正常对照组显著增加;微量注射NK1受体阻断剂CP-96345和/或NMDA受体阻断剂MK-801后,大鼠抑郁样行为明显改善,且MK-801使CUMS导致的大鼠海马P物质水平升高得到明显控制,而CP-96345没有明显改变CUMS引起的海马Glu水平升高;CP-96345使NMDA引起的抑郁样行为得到极显著改善.以上结果表明,慢性应激引起大鼠海马Glu过量释放,通过激活NMDA受体,促进P物质合成释放增加,激活NK1受体,是导致抑郁样行为发生的重要途径之一.%Stressors markedly influence central neurochemical and hormonal processes and thus play a pivotal role in the occurrence of depressive illnesses. As the center for stress response and the potential target for stressful provocation, hippocampus is becoming a focus in depression research. Although a large number of behavioral paradigms have been proposed as animal models of depression, only a few are considered as potentially useful research tools with sufficient validity. The most accepted one is chronic unpredictable mild stress rodent model, in which rats were subjected chronically and unpredictably to a variety of stressors including immersion in cold water, tail pinch, day and night reversed and so on. There are several

  12. Thyroid disorders in mild iodine deficiency

    DEFF Research Database (Denmark)

    Laurberg, P; Nøhr, S B; Pedersen, K M

    2000-01-01

    endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine...... in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately...

  13. Mild cognitive impairment: safe to drive?

    Science.gov (United States)

    Olsen, Kirsty; Taylor, John-Paul; Thomas, Alan

    2014-06-01

    Driving is an important aspect of daily living and for many older people provides autonomy and psycho-social benefits. Cognitive impairment has been found to impact driving skills at the level of dementia, however, uncertainty remains around the impact of a diagnosis of the pre-dementia condition mild cognitive impairment. Current official guidelines are unclear, and assessment of fitness to drive can be problematical. This editorial examines current official guidance available to the clinician and problems with existing assessment as well as the current position of research specifically into MCI and driving, and considers future direction for research in this field.

  14. Mild cognitive impairment in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    LUO Xiao-guang

    2013-08-01

    Full Text Available Cognitive impairment is one of the most common non-motor symptoms of Parkinson's disease (PD and a major influencing factor on patients' daily living ability. Mild cognitive impairment (MCI is a cognitive state between normal aging and dementia, and the living capability of MCI patients relatively remains. MCI often occurs in PD, with its clinical features presenting as the impairment in working memory and (or attention, executive function, language ability, memory and visuospatial function. Here we try to depict the general picture of PD-MCI from the view of epidemiology, pathology, clinical presentation, imaging and diagnostic criteria.

  15. Mild Traumatic Brain Injury in Translation

    OpenAIRE

    Levin, Harvey S.; Robertson, Claudia S.

    2013-01-01

    This Introduction to a Special Issue on Mild Traumatic Brain Injury (mTBI) highlights the methodological challenges in outcome studies and clinical trials involving patients who sustain mTBI. Recent advances in brain imaging and portable, computerized cognitive tasks have contributed to protocols that are sensitive to the effects of mTBI and efficient in time for completion. Investigation of civilian mTBI has been extended to single and repeated injuries in athletes and blast-related mTBI in ...

  16. Semiautomatic MDF deburring tool. [Mild detonating fuse

    Energy Technology Data Exchange (ETDEWEB)

    Simonton, W.L.

    1976-03-31

    A device for semiautomatically deburring the ends of lengths of MDF (mild detonating fuse) was developed by the Automation Development group at Mound Laboratory. The device performs the deburring function by cutting a 0.002 in. x 0.002 in. chamfer on the MDF with small rotating blades. This air-operated, semiautomatic device provides improvement over the manual method of removing burrs by reduction in time and operator strain. A time study is underway to determine the time saved which is expected to be about 75 percent.

  17. Chronic pain after childhood groin hernia repair

    DEFF Research Database (Denmark)

    Aasvang, Eske Kvanner; Kehlet, Henrik

    2007-01-01

    BACKGROUND: In contrast to the well-described 10% risk of chronic pain affecting daily activities after adult groin hernia repair, chronic pain after childhood groin hernia repair has never been investigated. Studies of other childhood surgery before the age of 3 months suggest a risk of increased...... pain responsiveness later in life, but its potential relationship to chronic pain in adult life is unknown. METHODS: This was a nationwide detailed questionnaire study of chronic groin pain in adults having surgery for a groin hernia repair before the age of 5 years (n = 1075). RESULTS: The response...... the age of 3 months (n = 122) did not report groin pain more often or with higher intensity than other patients did. CONCLUSIONS: Groin pain in adult patients operated on for a groin hernia in childhood is uncommon and usually mild and occurs in relation to physical activity. Operation before the age of 3...

  18. Chronic stress, cognitive functioning and mental health.

    Science.gov (United States)

    Marin, Marie-France; Lord, Catherine; Andrews, Julie; Juster, Robert-Paul; Sindi, Shireen; Arsenault-Lapierre, Geneviève; Fiocco, Alexandra J; Lupien, Sonia J

    2011-11-01

    This review aims to discuss the evidence supporting the link between chronic stress, cognitive function and mental health. Over the years, the associations between these concepts have been investigated in different populations. This review summarizes the findings that have emerged from older populations as well as from populations suffering from pathological aging, namely Mild Cognitive Impairment and Alzheimer's Disease. Although older adults are an interesting population to study in terms of chronic stress, other stress-related diseases can occur throughout the lifespan. The second section covers some of these stress-related diseases that have recently received a great deal of attention, namely burnout, depression, and post-traumatic stress disorder. Given that chronic stress contributes to the development of certain pathologies by accelerating and/or exacerbating pre-existing vulnerabilities that vary from one individual to the other, the final section summarizes data obtained on potential variables contributing to the association between chronic stress and cognition.

  19. Chronic stress effects in contralateral medial pterygoid muscle of rats with occlusion alteration.

    Science.gov (United States)

    Loyola, Bruno Melo; Nascimento, Glauce Crivelaro; Fernández, Rodrigo Alberto Restrepo; Iyomasa, Daniela Mizusaki; Pereira, Yamba Carla Lara; Leite-Panissi, Christie Ramos Andrade; Issa, João Paulo Mardegan; Iyomasa, Mamie Mizusaki

    2016-10-01

    Temporomandibular disorder (TMD) has a high prevalence in our society, characterized by a severe pain condition of the masticatory muscles and temporomandibular joint. Despite the indication of multiple factor initiators of TMD, there is still controversy about its etiology and its pathophysiology is poorly understood. Using rats as experimental animals we investigated the effect of unpredictable chronic stress with or without unilateral molar extraction on the contralateral medial pterygoid muscle. Our hypothesis is that these two factors induce changes in morphology, oxidative metabolism and oxidative stress of muscle fibers. Young adult male Wistar rats (±200g) were divided into four groups: a group with extraction and unpredictable chronic stress (E+US); with extraction and without stress (E+C); without extraction and with unpredictable chronic stress (NO+US); and a control group without either extraction or stress (NO+C). The animals were subjected to unilateral extraction of the upper left molars, under intraperitoneal anesthesia with 4% Xylazine (10mg/kg) and 10% Ketamine (80mg/kg) on day zero. The rats of groups E+US and NO+US were submitted to different protocols of stress, from the 14th day after the extraction. The protocols were different every day for five consecutive days, which were repeated from the 6th day for five days more. Contralateral medial pterygoid muscles were obtained on the 24th day after the start of the experiment for morphological, metabolic, capillary density, and oxidative stress analysis. The data from capillary density showed a decrease of capillaries in animals subjected to dental extraction, compared with those without extraction and an increase of laminin expression in the group submitted to the unpredictable chronic stress when compared to the unexposed to stress. SDH test revealed a decrease of light fibers in the group submitted to unilateral extraction of molars, compared with this area in the control group. In E+US and NO

  20. [Chronic hepatitis].

    Science.gov (United States)

    Figueroa Barrios, R

    1995-01-01

    Medical literature about chronic hepatitis is reviewed. This unresolving disease caused by viruses, drugs or unknown factors may progress to in cirrhosis and hepatocarcinoma. A classification based on liver biopsy histology into chronic persistent and chronic active types has been largely abandoned and emphasis is placed on recognizing the etiology of the various types. One is associated with continuing hepatitis B virus infection; another is related to chronic hepatitis C virus infection and the third is termed autoinmune, because of the association with positive serum autoantibodies. A fourth type with similar clinical functional and morphologic features is found with some drug reactions. Long term corticoesteroid therapy is usually successful in autoinmune type. Associations between antibodies to liver-kidney microsomes and the hepatitis C virus can cause diagnostic difficulties. Antiviral treatment of chronic hepatitis B and C with interpheron alfa is employed, controlling symptoms and abnormal biochemistry and the progression to cirrhosis and liver cancer in 30 to 40% patients. Alternative therapies or combinations with interpheron are being evaluated waiting for final results.

  1. Mild behavioral impairment and risk of dementia

    Science.gov (United States)

    Taragano, FE; Allegri, RF; Krupitzki, H; Sarasola, D; Serrano, CM; Loñ, L; Lyketsos, CG

    2009-01-01

    Background Mild cognitive impairment (MCI) is a transitional state between normal ageing and dementia, at least for some patients. Behavioral symptoms in MCI are associated with a higher risk of dementia, but their association with dementia risk in patients without MCI is unknown. Mild Behavioral Impairment (MBI) refers to a late life syndrome with prominent psychiatric and related behavioral symptoms in the absence of prominent cognitive symptoms, which may also be a dementia prodrome. Objective To compare MCI and MBI patients and to estimate the risk of dementia development in these two groups. Method A consecutive series of 358 patients (239 with MCI; and 119 with MBI) presenting to an outpatient general hospital specialty clinic were followed for up to 5 years until conversion to dementia or censoring. Results 34% of MCI patients and over 70% of patients with MBI developed dementia (Logrank p=0.011). MBI patients without cognitive symptoms were more likely to develop dementia (Logrank p<0.001). MBI patients were more likely to develop dementia due to frontotemporal degeneration (FTD) as opposed to Alzheimer’s dementia (AD). Conclusion MBI appears to be a transitional state between normal ageing and dementia. MBI (specifically those without cognitive symptoms) may confer a higher risk for dementia than MCI and is likely an FTD prodrome in many cases. These findings have implications for the early detection, prevention, and treatment of patients with dementia in late life, by focusing on the emergence of new behavioral symptoms. PMID:19323967

  2. DESIGN AND DEVELOPMENT OF MILD COMBUSTION BURNER

    Directory of Open Access Journals (Sweden)

    M.M. Noor

    2013-12-01

    Full Text Available This paper discusses the design and development of the Moderate and Intense Low oxygen Dilution (MILD combustion burner using Computational Fluid Dynamics (CFD simulations. The CFD commercial package was used to simulate preliminary designs for the burner before the final design was sent to the workshop for fabrication. The burner is required to be a non-premixed and open burner. To capture and use the exhaust gas, the burner was enclosed within a large circular shaped wall with an opening at the top. An external EGR pipe was used to transport the exhaust gas which was mixed with the fresh oxidant. To control the EGR and exhaust flow, butterfly valves were installed at the top opening as a damper to close the exhaust gas flow at a certain ratio for EGR and exhaust out to the atmosphere. High temperature fused silica glass windows were installed to view and capture images of the flame and analyze the flame propagation. The burner simulation shows that MILD combustion was achieved for the oxygen mole fraction of 3-13%. The final design of the burner was fabricated and ready for the experimental validation.

  3. Pregnancy management and outcome in women with chronic kidney disease

    OpenAIRE

    Bili, E; Tsolakidis, D; Stangou, S; Tarlatzis, B.

    2013-01-01

    An increasing number of pregnancies occur in the presence of chronic kidney diseases (CKD), mainly including chronic glomerulonephritis (GN), diabetic nephropathy (DN), and lupus nephritis (LN). The most important factor affecting fetal and maternal prognosis is the degree of renal function at conception. In the majority of patients with mild renal function impairment, and well-controlled blood pressure, pregnancy is usually successful and does not alter the natural course of maternal renal d...

  4. Comparison of Low Resolution Electromagnetic Tomography Imaging Between Subjects With Mild and Severe Obstructive Sleep Apnea Syndrome: A Preliminary Study

    OpenAIRE

    Lee, Hyun-Kwon; Park, Doo-Heum; Shin, Hyun-Sil; Hong, Seok-Chan

    2008-01-01

    Objective The purpose of this study was to identify the regions of the brain associated with recurrent nocturnal chronic hypoxic episodes in patients with untreated obstructive sleep apnea syndrome (OSAS) using low-resolution electromagnetic tomography (LORETA) and quantitative electroencephalography (QEEG). Methods Nocturnal polysomnograph (NPSG) and subsequent morning electroencephalograph (EEG) were measured in 20 subjects with OSAS. Mild (n=10 ages 39.5±12.1 years) and severe (n=10 ages 4...

  5. Proteomics portrait of archival lesions of chronic pancreatitis.

    Directory of Open Access Journals (Sweden)

    Sheng Pan

    Full Text Available Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL, mild chronic pancreatitis (MCP, severe chronic pancreatitis (SCP and pancreatic ductal adenocarcinoma (PDAC were subjected to proteomic analysis using a "label-free" comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma.

  6. Swimming and Persons with Mild Persistant Asthma

    Directory of Open Access Journals (Sweden)

    Mirjana Arandelovic

    2007-01-01

    Full Text Available The aim of our study was to analyze the effect of recreational swimming on lung function and bronchial hyperresponsiveness (BHR in patients with mild persistent asthma. This study included 65 patients with mild persistent asthma, who were divided into two groups: experimental group A (n = 45 and control group B (n = 20. Patients from both groups were treated with low doses of inhaled corticosteroids (ICS and short-acting β2 agonists salbutamol as needed. Our program for patients in group A was combined asthma education with swimming (twice a week on a 1-h basis for the following 6 months. At the end of the study, in Group A, we found a statistically significant increase of lung function parameters FEV1 (forced expiratory volume in 1 sec (3.55 vs. 3.65 (p < 0.01, FVC (forced vital capacity (4.27 vs. 4.37 (p < 0.05, PEF (peak expiratory flow (7.08 vs. 7.46 (p < 0.01, and statistically significant decrease of BHR (PD20 0.58 vs. 2.01 (p < 0.001. In Group B, there was a statistically significant improvement of FEV1 3.29 vs. 3.33 (p < 0.05 and although FVC, FEV1/FVC, and PEF were improved, it was not significant. When Groups A and B were compared at the end of the study, there was a statistically significant difference of FVC (4.01 vs. 4.37, FEV1 (3.33 vs. 3.55, PEF (6.79 vs.7.46, and variability (p <0.001, and statistically significantly decreased BHR in Group A (2.01 vs. 1.75 (p < 0.001. Engagement of patients with mild persistent asthma in recreational swimming in nonchlorinated pools, combined with regular medical treatment and education, leads to better improvement of their parameters of lung function and also to more significant decrease of their airway hyperresponsiveness compared to patients treated with traditional medicine

  7. Pervasive Developmental Disorder Behavior in Adolescents with Intellectual Disability and Co-Occurring Somatic Chronic Diseases

    Science.gov (United States)

    Oeseburg, B.; Groothoff, J. W.; Dijkstra, G. J.; Reijneveld, S. A.; Jansen, D. E. M. C.

    2010-01-01

    Evidence on the association between somatic chronic diseases in ID-adolescents and the full range of pervasive developmental disorder behavior (PDD behavior) is scarce. The aim of the present study is to assess the association between somatic chronic diseases in ID-adolescents and mild PDD behavior. We obtained data on 1044 ID-adolescents, aged…

  8. Autonomic dysfunction in patients with mild heart failure and coronary artery disease and the effects of add-on beta-blockade

    NARCIS (Netherlands)

    Szabo, BM; van Wijk, LM; Brouwer, J; Tio, RA; Crijns, HJGM; van Veldhuisen, DJ

    2001-01-01

    Aim: Autonomic impairment is related to the incidence of sudden death in chronic heart failure (CHF). Our objective was to study autonomic profiles in patients with mild CHF due to coronary artery disease, and to investigate the value of add-on P-blockade. Methods and results: Measures of autonomic

  9. Chronic gastritis.

    Science.gov (United States)

    Sipponen, Pentti; Maaroos, Heidi-Ingrid

    2015-06-01

    Prevalence of chronic gastritis has markedly declined in developed populations during the past decades. However, chronic gastritis is still one of the most common serious pandemic infections with such severe killing sequelae as peptic ulcer or gastric cancer. Globally, on average, even more than half of people may have a chronic gastritis at present. Helicobacter pylori infection in childhood is the main cause of chronic gastritis, which microbial origin is the key for the understanding of the bizarre epidemiology and course of the disease. A life-long and aggressive inflammation in gastritis results in destruction (atrophic gastritis) of stomach mucosa with time (years and decades). The progressive worsening of atrophic gastritis results subsequently in dysfunctions of stomach mucosa. Atrophic gastritis will finally end up in a permanently acid-free stomach in the most extreme cases. Severe atrophic gastritis and acid-free stomach are the highest independent risk conditions for gastric cancer known so far. In addition to the risks of malignancy and peptic ulcer, acid-free stomach and severe forms of atrophic gastritis may associate with failures in absorption of essential vitamins, like vitamin B12, micronutrients (like iron, calcium, magnesium and zinc), diet and medicines.

  10. Chronic Bronchitis

    Science.gov (United States)

    ... breathing. You may also have other tests. Chronic bronchitis is a long-term condition that keeps coming back or never goes away completely. If you smoke, it is important to quit. Treatment can help with your symptoms. It often includes ...

  11. Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7.

    Science.gov (United States)

    Xu, Chang; Ma, Xin-Ming; Chen, Hui-Bin; Zhou, Meng-He; Qiao, Hui; An, Shu-Cheng

    2016-10-01

    Neuroimaging studies show that patients with major depression have reduced volume of the orbitofrontal cortex (OFC). Although the serotonin (5-HT) 2A receptor, which is abundant in the OFC, has been implicated in depression, the underlying mechanisms in the development of stress-induced depression remain unclear. Kalirin-7 (Kal7) is an essential component of mature excitatory synapses for maintaining dendritic spines density, size and synaptic functions. The aim of this study was to investigate the role of orbitofrontal 5-HT and 5-HT2A receptors in depressive-like behaviors and their associations with Kal7 and dendritic spines using chronic unpredictable mild stress (CUMS), an established animal model of depression. CUMS had no effect on the levels of 5-HT or the 5-HT2A receptor in the OFC. However, CUMS or microinjection of the 5-HT2A/2C receptor agonist (±)-1-(2, 5-Dimethoxy-4-iodophenyl)- 2-aminopropane hydrochloride (DOI, 5 μg/0.5 μL) into the OFC induced depressive-like behaviors, including anhedonia in the sucrose preference test and behavioral despair in the tail suspension test, a significant reduction in body weight gain and locomotor activity in the open field test, which were accompanied by decreased expression of Kal7 and PSD95 as well as decreased density of dendritic spines in the OFC. These alterations induced by CUMS were reversed by pretreatment with the 5-HT2A receptor antagonist Ketanserin (Ket, 5 μg/0.5 μL into the OFC). These results suggest that CUMS alters structural plasticity through activation of the orbital 5-HT2A receptor and is associated with decreased expression of Kal7, thereby resulting in depressive-like behaviors in rats, suggesting an important role of Kal7 in the OFC in depression.

  12. Mild cognitive impairment in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Shu-hua LI

    2016-06-01

    Full Text Available Cognitive dysfunction is common non-motor symptom (NMS in Parkinson's disease (PD, which affects the patients' quality of life and increases the burden of caregivers. Cognitive dysfunction in PD can be mild cognitive impairment (MCI or dementia. MCI presents in the early stage of PD and the incidence rate is increasing with the disease progression. In some cases it can advance to dementia. The diagnosis of MCI in PD includes inclusion criteria, exclusion criteria and damage level evaluation. Non-pharmacological therapy, such as exercise and cognitive behavior therapy (CBT can improve the symptoms of MCI in PD, while the pharmacological treatment remains to be further studied. DOI: 10.3969/j.issn.1672-6731.2016.06.002

  13. Mild desalination of various raw water streams.

    Science.gov (United States)

    Groot, C K; van den Broek, W B P; Loewenberg, J; Koeman-Stein, N; Heidekamp, M; de Schepper, W

    2015-01-01

    For chemical industries, fresh water availability is a pre-requisite for sustainable operation. However, in many delta areas around the world, fresh water is scarce. Therefore, the E4 Water project (www.e4water.eu) comprises a case study at the Dow site in Terneuzen, The Netherlands, which is designed to develop commercial applications for mild desalination of brackish raw water streams from various origins to enable reuse in industry or agriculture. This study describes an effective two-stage work process, which was used to narrow down a broad spectrum of desalination technologies to a selection of the most promising techniques for a demonstration pilot at 2-4 m³/hour. Through literature study, laboratory experiments and multi-criteria analysis, nanofiltration and electrodialysis reversal were selected, both having the potential to attain the objectives of E4Water at full scale.

  14. Delayed epidural hematoma after mild head injury

    Directory of Open Access Journals (Sweden)

    Radulović Danilo

    2005-01-01

    Full Text Available Background. Traumatic delayed epidural hematoma (DEH can be defined as insignificant or not seen on the initial CT scan performed after a trauma but seen on the subsequent CT scan as a “massive” epidural bleeding. Case report. We presented two cases of traumatic DEH after mild head injury. Both patients were conscious and without neurological deficit on the admission. Initial CT scan did not reveal intracranial hematoma. Repeated CT scan, that was performed after neurological deterioration, revealed epidural hematoma in both cases. The patients were operated with a favorable surgical outcome. Conclusion. Traumatic DEH could occur in the patients with head injuries who were conscious on the admission with a normal initial CT scan finding. Early detection of DEH and an urgent surgical evacuation were essential for a good outcome.

  15. Mild Cognitive Impairment Status and Mobility Performance

    DEFF Research Database (Denmark)

    Pedersen, Mette; Holt, Nicole E; Grande, Laura

    2014-01-01

    BACKGROUND: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. METHODS......MCI), nonmemory domains (naMCI), and multiple domains (mdMCI). Linear regression models were used to assess the association between MCI status and mobility performance in the Habitual Gait Speed, Figure of 8 Walk, Short Physical Performance Battery, and self-reported Late Life Function and Disability Instrument......). All MCI subtypes performed significantly worse than No-MCI on all mobility measures (p Figure of 8 Walk (p = .054) and Basic Lower Extremity (p = .11). Moreover, compared with aMCI, mdMCI manifested worse performance on the Figure of 8 Walk and Short...

  16. Mission Connect Mild TBI Translational Research Consortium

    Science.gov (United States)

    2010-08-01

    increased chronic inflammation we saw increased IBA 1 and ATF3 with decreased BDNF . Figure 10. Vimentin, like GFAP, appears upregulated in astrocytes...moderate TBI and/or stroke ) we also assessed the presence of blood borne proteins in brain at 18 days post-trauma. When we stained for albumin and...Yi and Hazell. 2004. J. Stroke Cerebrovasc. Dis. 13:129-137. Appendices None

  17. Impact of chronic kidney disease on long-term ischemic and bleeding outcomes in medically managed patients with acute coronary syndromes

    DEFF Research Database (Denmark)

    Melloni, Chiara; Cornel, Jan H; Hafley, Gail

    2016-01-01

    AIMS: We aimed to study the relationship of chronic kidney disease stages with long-term ischemic and bleeding outcomes in medically managed acute coronary syndrome patients and the influence of more potent antiplatelet therapies on platelet reactivity by chronic kidney disease stage. METHODS...... disease vs. normal/mild chronic kidney disease were estimated. Platelet reactivity at 30 days was assessed in a subset of patients (n = 1947). The majority of patients were in the normal/mild chronic kidney disease group (67%), followed by moderate chronic kidney disease (29%) and severe chronic kidney.......26; 95% confidence interval 1.09-1.46; severe vs. normal/mild: hazard ratio 1.60; 95% confidence interval 1.25-2.04). Platelet reactivity was lower in patients treated with prasugrel compared with clopidogrel, across all three chronic kidney disease stages. CONCLUSIONS: Among medically managed acute...

  18. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... Information > Children/Pediatric > Chronic Pancreatitis in Children test Chronic Pancreatitis in Children What symptoms would my child ... pancreatitis will develop diabetes in adolescence. Who gets chronic pancreatitis? Those at risk for chronic pancreatitis are ...

  19. Chronic Beryllium Disease

    Science.gov (United States)

    ... Science Education & Training Home Conditions Chronic Beryllium Disease Chronic Beryllium Disease Make an Appointment Find a Doctor ... MD, MSPH, FCCP (February 01, 2016) What is chronic beryllium disease (CBD)? Chronic beryllium disease (CBD) is ...

  20. Chronic motor tic disorder

    Science.gov (United States)

    Chronic vocal tic disorder; Tic - chronic motor tic disorder ... Chronic motor tic disorder is more common than Tourette syndrome . Chronic tics may be forms of Tourette syndrome. Tics usually start ...

  1. Chronic Pelvic Pain

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Chronic Pelvic Pain Home For Patients Search FAQs Chronic Pelvic Pain ... Pelvic Pain FAQ099, August 2011 PDF Format Chronic Pelvic Pain Gynecologic Problems What is chronic pelvic pain? What ...

  2. Comparing Cognitive Profiles of Licensed Drivers with Mild Alzheimer’s Disease and Mild Dementia with Lewy Bodies

    Directory of Open Access Journals (Sweden)

    Stephanie Yamin

    2016-01-01

    Full Text Available Purpose. Alzheimer’s disease (AD and dementia with Lewy Bodies (DLB constitute two of the most common forms of dementia in North America. Driving is a primary means of mobility among older adults and the risk of dementia increases with advanced age. The purpose of this paper is to describe the cognitive profile of licensed drivers with mild AD and mild DLB. Method. Licensed drivers with mild AD, mild DLB, and healthy controls completed neuropsychological tests measuring general cognition, attention, visuospatial/perception, language, and cognitive fluctuations. Results. The results showed differences between healthy controls and demented participants on almost all neuropsychological measures. Participants with early DLB were found to perform significantly worse on some measures of attention and visuospatial functioning in comparison with early AD. Discussion. Future research should examine the relationship between neuropsychological measures and driving outcomes among individuals with mild AD and mild DLB.

  3. Mallory-Denk Bodies in chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Metin Basaranoglu; Nesrin Turhan; Abdullah Sonsuz; G(o)kcen Basaranoglu

    2011-01-01

    Mallory-Denk Bodies (MDB) are important as investigators, suggesting MDB as an indicator of the histologic severity of chronic hepatitis, causes of which include hepatitis C, primary biliary cirrhosis (PBC), and nonalcoholic fatty liver disease (NAFLD). Matteoni et al scored MDB in patients with NAFLD as none, rare and many, and reported that MDB plays a prominent role in this classification scheme in an earlier classification system. In this study, we evaluated 258 patients with chronic hepatitis due to metabolic, autoimmune and viral etiologies. Liver biopsy samples were evaluated with hematoxylin and eosin, periodic acid-Schiff-diastase, Gordon and Sweet's reticulin, Masson's trichrome, and iron stains. Both staging and grading were performed. Additionally, MDB were evaluated and discussed for each disease. We examined patients with nonalcoholic steatohepatitis (NASH;50 patients), alcoholic hepatitis (10 patients), PBC (50 patients), Wilson disease (WD;20 patients), hepatitis B (50 patients), hepatitis C (50 pati patients) and hepatocellular carcinoma (HCC;30 patients). Frequency of MDB was as follows;NASH: 10 patients with mild in 60% and moderate in 40% and observed in every stage of the disease and frequently seen in zone 3. PBC: 11 patients with mild in 10%, moderate in 70%, and cirrhosis in 20%, and frequently seen in zone 1. WD: 16 patients with moderate and severe in 60% and cirrhosis in 40% and frequently seen in zone 1. Hep B: 3 patients with mild in 66% and severe in 34%. Hep C: 7 patients with mild in 40% and moderate in 60% and observed in every stage. HCC: 3 patients with hep B in 2 patients. We found that there is no relationship between MDB and any form of chronic hepatitis regarding histologic severity such as alcoholic steatohepatitis and NAFLD and variable zone distribution by etiology.

  4. Chronic thyroiditis (Hashimoto disease)

    Science.gov (United States)

    Hashimoto thyroiditis; Chronic lymphocytic thyroiditis; Autoimmune thyroiditis; Chronic autoimmune thyroiditis; Lymphadenoid goiter - Hashimoto; Hypothyroidism - Hashimoto; Type 2 polyglandular autoimmune ...

  5. A case of constitutional trisomy 3 mosaicism in a teenage patient with mild phenotype.

    Science.gov (United States)

    Kekis, Mariana; Hashimoto, Sayaka; Deeg, Carol; Calloway, Inga; McKinney, Aimee; Shuss, Christine; Hickey, Scott; Astbury, Caroline

    2016-11-01

    Constitutional mosaicism for trisomy 3 is extremely rare, with only a few postnatally diagnosed cases reported in the literature. We report a case of constitutional trisomy 3 mosaicism in a 16-year-old female, who presented with chronic joint pain, easy bruising, joint hypermobility and dysmorphic features, including long, thin facies, over-folded dysplastic ears, and Pierre-Robin sequence (PRS) with cleft palate. The patient was small at birth, had cleft palate repair, developed chronic joint pain at age 12, and has a history of mild leukopenia and mild thrombocytopenia. Microarray analysis was consistent with a mosaic gain of an entire chromosome 3. FISH analysis of peripheral blood and buccal cells showed the presence of the supernumerary chromosome 3 in a low percentage of cells in both tissues, suggesting that the nondisjunction event occurred prior to the germ cell layer differentiation. Since trisomy 3 has been observed somatically in lymphoma, a Hematology/Oncology consultation was provided for the patient. The oncologist's evaluation for malignancy was unremarkable. A review of findings from other trisomy 3 patients reported in the literature reveals a diverse phenotypic spectrum and does not show a correlation between the proportion of abnormal cells observed in peripheral blood and the patients' clinical features or severity. This case demonstrates that the clinical presentation of an individual with trisomy 3 is highly individualized and the clinical course is difficult to predict.

  6. Memory complaints in subjective cognitive impairment, amnestic mild cognitive impairment and mild Alzheimer's disease.

    Science.gov (United States)

    Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun

    2016-12-01

    Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.

  7. Mental fatigue after mild traumatic brain injury: a 3D-ASL perfusion study.

    Science.gov (United States)

    Liu, Kai; Li, Bo; Qian, Shaowen; Jiang, Qingjun; Li, Li; Wang, Wei; Zhang, Gaiyun; Sun, Yajuan; Sun, Gang

    2016-09-01

    Our purpose was to evaluate mental fatigue associated with mild traumatic brain injury (MTBI) and investigate the underlying neurological mechanisms. We used a 20-min psychomotor vigilance test (PVT) related ASL-fMRI to evaluate mental fatigue in 25 MTBI patients in acute phase, 21 MTBI patients in chronic phase, and 20 healthy subjects. Mental fatigue in patients in acute phase was more severe than in chronic phase patients and healthy controls. The first 5-min-PVT increased CBF of patients in acute phase in "bottom-up" and "top-down" attention areas, and decreased CBF in default mode network (DMN) areas. Twenty-min-PVT results showed that sustained attention of patients was more fragile than in healthy subjects, while sustained attention in the acute phase was less stable than that in the chronic phase. CBF results showed that in patients in the acute phase, the second, third, and last 5-min-PVT decreased CBF in DMN areas, increased CBF of "bottom-up" and "top-down" areas; in the chronic phase, the third and last 5-min-PVT increased CBF of "bottom-up" and "top-down" cortex, while the second 5-min-PVT only increased CBF of the "top-down" cortex. Mental fatigue of MTBI patients persists for more than 12 months, and can be mitigated partly within the first year after injury. The "bottom-up" and "top-down" deficits result in mental fatigue of MTBI patients.

  8. Molecular mechanisms of increased cerebral vulnerability after repeated mild blast-induced traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Alaa Kamnaksh

    2014-06-01

    Full Text Available The consequences of a mild traumatic brain injury can be especially severe if it is repeated within the period of increased cerebral vulnerability (ICV that follows the initial insult. To better understand the molecular mechanisms that contribute to ICV, we exposed rats to different levels of mild blast overpressure (5 exposures; total pressure range: 15.54–19.41 psi or 107.14–133.83 kPa at a rate of 1 per 30 min, monitored select physiological parameters, and assessed behavior. Two days post-injury or sham, we determined changes in protein biomarkers related to various pathologies in behaviorally relevant brain regions and in plasma. We found that oxygen saturation and heart rate were transiently depressed following mild blast exposure and that injured rats exhibited significantly increased anxiety- and depression-related behaviors. Proteomic analyses of the selected brain regions showed evidence of substantial oxidative stress and vascular changes, altered cell adhesion, and inflammation predominantly in the prefrontal cortex. Importantly, these pathological changes as well as indications of neuronal and glial cell loss/damage were also detected in the plasma of injured rats. Our findings illustrate some of the complex molecular changes that contribute to the period of ICV in repeated mild blast-induced traumatic brain injury. Further studies are needed to determine the functional and temporal relationship between the various pathomechanisms. The validation of these and other markers can help to diagnose individuals with ICV using a minimally invasive procedure and to develop evidence-based treatments for chronic neuropsychiatric conditions.

  9. 低剂量茶碱联合噻托溴铵对轻中度稳定期慢性阻塞性肺疾病患者肺功能及生命质量的影响%The effects of low-dose theophylline and tiotropium on lung function and quality of life in patients with mild-moderate stable chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    陈宇清; 廖若敏; 徐红冰; 周新

    2015-01-01

    溴铵治疗可能是轻中度稳定期COPD治疗的一种经济有效的选择.%Objective To observe the effects of low-dose theophylline and tiotropium on lung function and quality of life in patients with mild-moderate stable chronic obstructive pulmonary disease (COPD) and evaluate its safety.Methods This was a randomized,parallel-group,controlled trial.A total of 115 patients with mild-moderate stable COPD were divided into tiotropium group (37 cases),slow-release theophylline group (40 cases) and the combination of slow-release theophylline and tiotropium group (38 cases) by random digits table method.Thirty-eight patients without cardiopulmonary diseases were enrolled in control group.Observation period was 12 months.The lung function,6 min walking test distance (6MWD),modified British Medical Research Council Scale (mMRC),and COPD assessment test (CAT) were monitored before treatment and after treatment for 12 months.Results Of 115 patients,107 patients (35cases in tiotropium group,36 cases in slow-release theophylline group and 36 cases in combination of slowrelease theophylline and tiotropium group) completed the study.No significant difference was found in spirometry parameters reflecting airflow limitation after 12 months treatment compared with that before treatment in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group (P > 0.05),such as the percentage of forced expiratory volume in 1 second (FEV1) over the expected value (FEV1%) and FEV1/forced vital capacity (FVC).The percentage of mid expiratory flow over the expected value (FEF25~75%) was improved in all groups,but the increment of FEF25~75 % was much higher in tiotropium group and the combination of slow-release theophylline and tiotropium group than that in slow-release theophylline group:(39.23 ± 7.77)%,(39.99 ± 8.25)% vs.(34.91 ± 9.50)%,there were significant differences (P < 0.05).Similar changes were

  10. Compulsive masturbation and chronic penile lymphedema.

    Science.gov (United States)

    Calabrò, Rocco Salvatore; Galì, Alessandro; Marino, Silvia; Bramanti, Placido

    2012-06-01

    Chronic penile lymphedema arises from the abnormal retention of lymphatic fluid in the subcutaneous tissues and may be secondary to local and systemic medical conditions such as sexually transmitted diseases, filariasis, malignancy, local radiotherapy, and surgery. This case report aims to consider compulsive masturbation as a possible cause of chronic penile edema. A 40-year-old man was referred to our institute for behavioral disturbance, including compulsive masturbation. Neuropsychiatric evaluation showed moderate mental retardation, mild dysarthria and limb incoordination, anxiety, depressed mood, and impulse dyscontrol. Brain MRI pointed out diffuse white matter lesions. Urogenital examination revealed an uncircumcised penis with non-tender edema of the shaft and prepuce with areas of lichenification. Since the most common local and systemic causes of edema were excluded, chronic penile edema due to compulsive masturbation was diagnosed and the compulsive behavior treated with an antidepressant and low-dose neuroleptics. Compulsive masturbation should be taken into account when counselling patients with penile edema.

  11. Generation of polarization-resolved wideband unpredictability-enhanced chaotic signals based on vertical-cavity surface-emitting lasers subject to chaotic optical injection.

    Science.gov (United States)

    Chen, Jian-Jun; Wu, Zheng-Mao; Tang, Xi; Deng, Tao; Fan, Li; Zhong, Zhu-Qiang; Xia, Guang-Qiong

    2015-03-23

    A system framework is proposed and analyzed for generating polarization-resolved wideband unpredictability-enhanced chaotic signals based on a slave vertical-cavity surface-emitting laser (S-VCSEL) driven by an injected optical chaos signal from a master VCSEL (M-VCSEL) under optical feedback. After calculating the time series outputs from the M-VCSEL under optical feedback and the S-VCSEL under chaotic optical injection by using the spin-flip model (SFM), the unpredictability degree (UD) is evaluated by permutation entropy (PE), and the bandwidth of the polarization-resolved outputs from the M-VCSEL and S-VCSEL are numerically investigated. The results show that, under suitable parameters, both the bandwidth and UD of two polarization components (PCs) outputs from the S-VCSEL can be enhanced significantly compared with that of the driving chaotic signals output from the M-VCSEL. By simulating the influences of the feedback and injection parameters on the bandwidth and UD of the polarization-resolved outputs from S-VCSEL, related operating parameters can be optimized.

  12. Probabilistic Sequence Learning in Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Dezso eNemeth

    2013-07-01

    Full Text Available Mild Cognitive Impairment (MCI causes slight but noticeable disruption in cognitive systems, primarily executive and memory functions. However, it is not clear if the development of sequence learning is affected by an impaired cognitive system and, if so, how. The goal of our study was to investigate the development of probabilistic sequence learning, from the initial acquisition to consolidation, in MCI and healthy elderly control groups. We used the Alternating Serial Reaction Time task (ASRT to measure probabilistic sequence learning. Individuals with MCI showed weaker learning performance than the healthy elderly group. However, using the reaction times only from the second half of each learning block – after the reactivation phase - we found intact learning in MCI. Based on the assumption that the first part of each learning block is related to reactivation/recall processes, we suggest that these processes are affected in MCI. The 24-hour offline period showed no effect on sequence-specific learning in either group but did on general skill learning: the healthy elderly group showed offline improvement in general reaction times while individuals with MCI did not. Our findings deepen our understanding regarding the underlying mechanisms and time course of sequence acquisition and consolidation.

  13. Mild-split SUSY with flavor

    CERN Document Server

    Eliaz, Latif; Gudnason, Sven Bjarke; Tsuk, Eitan

    2013-01-01

    In the framework of a gauge mediated quiver-like model, the standard model flavor texture can be naturally generated. The model - like the MSSM - has furthermore a region in parameter space where the lightest Higgs mass is fed by heavy stop loops, which in turn sets the average squark mass scale near 10-20 TeV. We perform a careful flavor analysis to check whether this type of mild-split SUSY passes all flavor constraints as easily as envisioned in the original type of split SUSY. Interestingly, it turns out to be on the border of several constraints, in particular, the branching ratio of mu -> e gamma and, if order one complex phases are assumed, also epsilon_K neutron and electron EDM. Furthermore, we consider unification as well as dark matter candidates, especially the gravitino. Finally, we provide a closed-form formula for the soft masses of matter in arbitrary representations of any of the gauge groups in a generic quiver-like model with a general messenger sector.

  14. Heterogeneity in executive impairment in patients with very mild Alzheimer's

    DEFF Research Database (Denmark)

    Stokholm, J.; Gade, Anders; Vogel, A.

    2006-01-01

    The presence of executive impairment in mild Alzheimer's disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe...

  15. The transition of mild to severe wear of ceramics

    NARCIS (Netherlands)

    Pasaribu, H.R.; Sloetjes, J.W.; Schipper, D.J.

    2004-01-01

    The transition of mild to severe wear of ceramics depends on the operating conditions (normal load, velocity and temperature) and material properties (like grain size, mechanical and thermal material properties). Adachi et al. [Wear 203¿204 (1997) 291] introduced the transition of mild to severe wea

  16. Gerstmann's syndrome associated with chronic subdural haematoma: a case report.

    Science.gov (United States)

    Maeshima, S; Okumura, Y; Nakai, K; Itakura, T; Komai, N

    1998-08-01

    We report a patient who exhibited Gerstmann's syndrome in association with a chronic subdural haematoma. A 71-year-old right-handed woman presented with mild right arm and leg weakness that began 2 weeks prior to admission. Neurological examination on admission revealed a mild right hemiparesis. Neuropsychological examination revealed right-left disorientation, finger agnosia, agraphia, and acalculia, but no language disturbance. A computerized tomographic (CT) scan revealed a large left frontoparietal, extra-axial hypodense fluid collection containing scattered hypodense foci. A left parietal evacuation of the haematoma was performed. Following surgery the patient dramatically improved. We suggest that the direct compression by the chronic subdural haematoma or a hemispheric pressure difference caused Gerstmann's syndrome. This is an unusual report of a Gerstmann's syndrome following chronic subdural haematoma.

  17. Neural Control of Chronic Stress Adaptation

    Directory of Open Access Journals (Sweden)

    James eHerman

    2013-08-01

    Full Text Available Stress initiates adaptive processes that allow the organism to physiologically cope with prolonged or intermittent exposure to real or perceived threats. A major component of this response is repeated activation of glucocorticoid secretion by the hypothalamo-pituitary-adrenocortical (HPA axis, which promotes redistribution of energy in a wide range of organ systems, including the brain. Prolonged or cumulative increases in glucocorticoid secretion can reduce benefits afforded by enhanced stress reactivity and eventually become maladaptive. The long-term impact of stress is kept in check by the process of habituation, which reduces HPA axis responses upon repeated exposure to homotypic stressors and likely limits deleterious actions of prolonged glucocorticoid secretion. Habituation is regulated by limbic stress-regulatory sites, and is at least in part glucocorticoid feedback-dependent. Chronic stress also sensitizes reactivity to new stimuli. While sensitization may be important in maintaining response flexibility in response to new threats, it may also add to the cumulative impact of glucocorticoids on the brain and body. Finally, unpredictable or severe stress exposure may cause long-term and lasting dysregulation of the HPA axis, likely due to altered limbic control of stress effector pathways. Stress-related disorders, such as depression and PTSD, are accompanied by glucocorticoid imbalances and structural/ functional alterations in limbic circuits that resemble those seen following chronic stress, suggesting that inappropriate processing of stressful information may be part of the pathological process.

  18. Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Qi-Kui Chen; Zhong-Lin Yu; Shi-Zheng Yuan; Zhuo-Fu Wen; Ying-Qiang Zhong; Cu-Jun Li; Hui-Sheng Wu; Can-Rong Mai; Peng-Yan Xie; Yu-Min Lu

    2005-01-01

    AIM: To investigate the characteristics and short-term efficacy of sulfasalazine (SASP) in patients with mildly and moderately active ulcerative colitis (UC).METHODS: Two hundred and twenty-eight patients with mildly and moderately active UC were recruited, 106patients in 1993-1995, and 122 patients in 2000-2002,they were assigned as the 1990s group (n = 106) and the 2000s group (n = 122), prospectively. The general characteristics, clinical manifestations, colonoscopic and histological data were compared between the two groups.The short-term efficacy and safety of SASP 3 g per d were evaluated.RESULTS: Between 2000s and 1990s groups, the gender ratio of men to women was 1:1.18 and 1:1.04, 57.4%and 50.9% of the patients were between 30 and 49 years old. The gender ratio and age of UC patients were not significantly different. The total course of 50.0% and 37.1% of UC patients was less than 1 year (P<0.05), 10.6% and 31.2% of the cases had a duration of more than 5 years (P<0.05) in 2000s and 1990s groups, respectively. The most common clinical type was first episode in 2000s group and chronic relapse in 1990s group. The patients showed a higher frequency of abdominal pain and tenderness in 1990s group than in 2000s group. Erosions were found in 84.4% and 67.9% of patients in 2000s and 1990s groups (P<0.05). Rough and granular mucosa (67.9%vs43.4%, P<0.05)and polyps (47.2% vs 32.8%, P<0.05)were identified in 1990s group more than in 2000s group.There were no significant differences in clinical, colonoscopic and histological classifications. After SASP (1 g thrice per d) treatment for 6 wk, the clinical, colonoscopic and histological remission rates were 71.8%, 21.8% and 16.4%,respectively. In 79 patients with clinical remission, 58.2%and 67.1% remained grade 1 in colonoscopic and histological findings, respectively. The overall effects in first episode type (complete remission in 10, 18.9%, partial remission in 28, 52.8%, and improvement in 9, 17.0%) were

  19. Time estimation in mild Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Nichelli Paolo

    2009-07-01

    Full Text Available Abstract Background Time information processing relies on memory, which greatly supports the operations of hypothetical internal timekeepers. Scalar Expectancy Theory (SET postulates the existence of a memory component that is functionally separated from an internal clock and other processing stages. SET has devised several experimental procedures to map these cognitive stages onto cerebral regions and neurotransmitter systems. One of these, the time bisection procedure, has provided support for a dissociation between the clock stage, controlled by dopaminergic systems, and the memory stage, mainly supported by cholinergic neuronal networks. This study aimed at linking the specific memory processes predicted by SET to brain mechanisms, by submitting time bisection tasks to patients with probable Alzheimer's disease (AD, that are known to present substantial degeneration of the fronto-temporal regions underpinning memory. Methods Twelve mild AD patients were required to make temporal judgments about intervals either ranging from 100 to 600 ms (short time bisection task or from 1000 to 3000 ms (long time bisection task. Their performance was compared with that of a group of aged-matched control participants and a group of young control subjects. Results Long time bisection scores of AD patients were not significantly different from those of the two control groups. In contrast, AD patients showed increased variability (as indexed by increased WR values in timing millisecond durations and a generalized inconsistency of responses over the same interval in both the short and long bisection tasks. A similar, though milder, decreased millisecond interval sensitivity was found for elderly subjects. Conclusion The present results, that are consistent with those of previous timing studies in AD, are interpreted within the SET framework as not selectively dependent on working or reference memory disruptions but as possibly due to distortions in different

  20. Unpredicted Sudden Death due to Recurrent Infratentorial Hemangiopericytoma Presenting as Massive Intratumoral Hemorrhage: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Toshihide Tanaka

    2014-01-01

    Full Text Available Unpredicted sudden death arising from hemangiopericytoma with massive intracranial hemorrhage is quite rare. We encountered a patient with recurrent infratentorial hemangiopericytoma presenting as life-threatening massive intracerebral hemorrhage. A 43-year-old man who had undergone craniotomy for total resection of an infratentorial hemangiopericytoma 17 months earlier presented with morning headache and generalized convulsions. Computed tomography revealed a massive hematoma in the right infratentorial region causing tonsillar herniation and emergency surgery was performed to evacuate the hematoma. Histological findings revealed hemangiopericytoma with hemorrhage. Neurological status remained unimproved and brain death was confirmed postoperatively. Hemangiopericytoma presenting as massive hemorrhage is quite rare. Since the risk of life-threatening massive hemorrhage should be considered, careful postoperative long-term follow-up is very important to identify tumor recurrences, particularly in the posterior cranial fossa, even if the tumor is completely removed.

  1. Unpredicted Sudden Death due to Recurrent Infratentorial Hemangiopericytoma Presenting as Massive Intratumoral Hemorrhage: A Case Report and Review of the Literature.

    Science.gov (United States)

    Tanaka, Toshihide; Kato, Naoki; Hasegawa, Yuzuru; Murayama, Yuichi

    2014-01-01

    Unpredicted sudden death arising from hemangiopericytoma with massive intracranial hemorrhage is quite rare. We encountered a patient with recurrent infratentorial hemangiopericytoma presenting as life-threatening massive intracerebral hemorrhage. A 43-year-old man who had undergone craniotomy for total resection of an infratentorial hemangiopericytoma 17 months earlier presented with morning headache and generalized convulsions. Computed tomography revealed a massive hematoma in the right infratentorial region causing tonsillar herniation and emergency surgery was performed to evacuate the hematoma. Histological findings revealed hemangiopericytoma with hemorrhage. Neurological status remained unimproved and brain death was confirmed postoperatively. Hemangiopericytoma presenting as massive hemorrhage is quite rare. Since the risk of life-threatening massive hemorrhage should be considered, careful postoperative long-term follow-up is very important to identify tumor recurrences, particularly in the posterior cranial fossa, even if the tumor is completely removed.

  2. Chronic inflammatory demyelinating polyneuropathy

    Science.gov (United States)

    Polyneuropathy - chronic inflammatory; CIDP; Chronic inflammatory polyneuropathy; Guillain-Barré - CIDP ... Health care providers also consider CIDP as the chronic form of Guillain-Barré syndrome. The specific triggers ...

  3. Dealing with chronic cancer

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000933.htm Dealing with chronic cancer To use the sharing features on this ... be controlled for a period of time. Controlling Chronic Cancer When you have a chronic cancer, the ...

  4. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.;

    2005-01-01

    function due to CMS were observed. In the present experimental setting, there was no indication of the two exposures potentiating each other with respect to adverse effects on the nervous system. However, the effects of prenatal CMS indicate that stress during fetal life may interfere with the development...

  5. Agomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress

    NARCIS (Netherlands)

    Dagyte, Girstaute; Crescente, Ilaria; Postema, Folkert; Seguin, Laure; Gabriel, Cecilia; Mocaer, Elisabeth; Den Boer, Johan A.; Koolhaas, Jaap M.; Dagytė, Girstautė

    2011-01-01

    The antidepressant agomelatine is a MT1/MT2 receptor agonist and 5-HT2C antagonist. Its antidepressant activity is proposed to result from the synergy between these sets of receptors. Agomelatine-induced changes in the brain have been reported under basal conditions. Yet, little is known about its e

  6. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    OpenAIRE

    Khedr LH; Nassar NN; El-Denshary ES; Abdel-tawab AM

    2015-01-01

    Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chro...

  7. Systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury

    DEFF Research Database (Denmark)

    Godbolt, Alison K; Cancelliere, Carol; Hincapié, Cesar A

    2014-01-01

    criteria. Peer-reviewed reports in 6 languages were considered. STUDY SELECTION: Systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case-control studies, with a minimum of 30 MTBI cases in subjects of any age, assessing the risk of dementia or CCI after MTBI were selected....... Methodological quality was acceptable for 101 (34%) articles, of which 1 article considered dementia and 7 articles considered CCI. The study examining the risk of dementia after MTBI did not find an association. One randomized controlled trial found that being informed about possible cognitive dysfunction after....... CONCLUSIONS: There is a lack of evidence of an increased risk of dementia after MTBI. In children, objective evidence of CCI exists only for complicated MTBI. More definitive studies are needed to inform clinical decisions, assessment of prognosis, and public health policy....

  8. Chronic Exposure to Extremely Low Frequency Electromagnetic Field Induces Mild Renal Damages in Rats

    Directory of Open Access Journals (Sweden)

    T.S. Javadifar

    2011-01-01

    Full Text Available The kidney is a major potential route for the absorption of hazardous materials encountered in the environment. The aim of this study was to evaluate the influence of ELFEMF on function and structure of kidney in rats. Experimental adult male Wistar rats were exposed to a 50 Hz ELFEMF, 1 mT (emitted from solenoid for 24 h daily during 135 days. The sham rats were subjected to sham exposure and the control rats were kept in animal room. In final, blood samples collected for the determination of the creatinine, urea nitrogen, albumin, globulin and total protein concentration in the plasma. The kidney was examined using light microscopy. Results showed that in EMF exposed group plasma concentration of creatinine and urea nitrogen was increased (p<0.001 which was accompanied by marked vascular congestion in the renal cortex and reduction in red blood cell count in glomerular capillaries but there were no changes in total protein, albumin and globulin levels. In conclusion, long term exposure to ELFEMF impacts renal function by influencing the perfusion of kidney.

  9. Chronic psychosocial stress induces visceral hyperalgesia in mice.

    Science.gov (United States)

    Tramullas, Mónica; Dinan, Timothy G; Cryan, John F

    2012-05-01

    Experimental and clinical evidence has shown that chronic stress plays an important role in the onset and/or exacerbation of symptoms of functional gastrointestinal disorders. Here, we aimed to investigate whether exposure to a chronic and temporally unpredictable psychosocial stressor alters visceral and somatic nociception as well as anxiety-related behaviour. In male C57BL/6J mice, chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. Visceral and somatic nociception was evaluated by colorectal distension and a hot plate, respectively. The social interaction test was used to assess social anxiety. Mice exposed to psychosocial stress developed visceral hyperalgesia and somatic hypoalgesia 24 h following the last stress session. SD/OC mice also exhibited social anxiety-like behaviour. All these changes were also associated with physiological alterations, measured as a decreased faecal pellet output and hypothalamic-pituitary-adrenal (HPA) axis disruption. Taken together, these data confirm that this mouse model of chronic psychosocial stress may be useful for studies on the pathophysiological mechanisms underlying such stress-associated disorders and to further test potential therapies.

  10. Inferential reading abilities of mildly mentally retarded and nonretarded students.

    Science.gov (United States)

    Bos, C S; Tierney, R J

    1984-07-01

    The inferential operations of mildly mentally retarded students reading at the intermediate level were investigated using methods based on discourse comprehension theory. We hypothesized that problems encountered in reading by these students are related to difficulties in generating logical inferences. Mildly retarded junior-high students and nonretarded third-grade students of the same reading comprehension level read and recalled a descriptive expository and a narrative passage. On the expository passage mildly retarded students generated the same quantity of inferences as did nonretarded students, but the inferences were qualitatively inferior. On the narrative passage the differences between the two groups were not significant. These findings were discussed in relation to the cognitive functioning of mildly retarded students.

  11. Timing of cholecystectomy after mild biliary pancreatitis: a systematic review.

    NARCIS (Netherlands)

    Baal, M.C.P.M. van; Besselink, M.G.; Bakker, O.J.; Santvoort, H.C. van; Schaapherder, A.F.; Nieuwenhuijs, V.B.; Gooszen, H.G.; Ramshorst, B. van; Boerma, D.

    2012-01-01

    OBJECTIVES: To determine the risk of recurrent biliary events in the period after mild biliary pancreatitis but before interval cholecystectomy and to determine the safety of cholecystectomy during the index admission. BACKGROUND: Although current guidelines recommend performing cholecystectomy earl

  12. Skip the Antibiotics for Mild Eczema in Kids

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_164083.html Skip the Antibiotics for Mild Eczema in Kids Skin condition cleared ... March 14, 2017 (HealthDay News) -- Despite widespread use, antibiotics are not an effective treatment for milder cases ...

  13. Kids' Mild Brain Injury Can Have Long-Term Effects

    Science.gov (United States)

    ... Brain Injury Can Have Long-Term Effects Early head trauma linked to psychiatric, financial issues as adults, study ... HealthDay News) -- Young people who suffer even mild head trauma are more likely to have serious issues later ...

  14. Chronic mucus hypersecretion

    DEFF Research Database (Denmark)

    Harmsen, L; Thomsen, S F; Sylvan Ingebrigtsen, Truls;

    2010-01-01

    Chronic mucus hypersecretion (CMH) is a common condition in patients with chronic respiratory diseases. Little is known about the incidence, prevalence and determinants of CMH in younger individuals....

  15. PSYCHOSENSORIMOTOR DEVELOPMENT OF PRESCHOOLERS WITH MILD CASE OF PSEUDOBULBAR DYSARTHRIA

    OpenAIRE

    2012-01-01

    The article covers the research of connection between mental, sensor and motor development, sensorimotor, ideomotor and emotional-motor reactions and also their variations by preschoolers with mild case of pseudobulbar dysarthria. The aim of the research is in theoretical study of specification of psychosensorimotor development of preschoolers with mild case of pseudobulbar dysarthria. Novelty of the research is in substantiation of the theoretical importance of studying psychosensorimotor de...

  16. The role of invasive ventilation in exacerbations of chronic obstructive pulmonary disease causing respiratory failure.

    Science.gov (United States)

    Kosky, Christopher; Turton, Charles

    2006-01-01

    Acute hypercapnic respiratory failure in chronic obstructive pulmonary disease can usually be managed initially with medical treatment and non- invasive ventilation. In circumstances where non- invasive ventilation cannot be used or has failed, intubation and invasive ventilation may be lifesaving. The outcome of patients with an exacerbation of COPD requiring invasive ventilation is better than often thought, with a hospital survival of 70-89%. Decisions regarding invasive ventilation made by physicians and patients with COPD are unpredictable and vary with the individual. This article reviews the role of invasive ventilation in exacerbations of COPD to assist decision making.

  17. Development of Zn50 Brazing Alloy for Joining Mild Steel to Mild Steel (SAE1018

    Directory of Open Access Journals (Sweden)

    S.C. Nwigbo

    2014-09-01

    Full Text Available This work has developed new brazing alloys for joining mild steel to mild steel (SAE1018 at a lower temperature. The alloys blends and error analysis were done by experimental design software (Design Expert 8.0.7.1. Design of experiments was done by Scheffe quadratic mixture method. The liquidus temperatures were predicted by calculation of phase diagrams of the alloying metals. The brazing alloys were produced by gravity technique and melted using silicon carbide graphite crucible. The quality of the brazing alloys was analyzed by optical microscopy (OM, atomic absorption spectroscopy (AAS and fourier transform infrared spectroscopy (FT-IR. Brazed joints were produced by torch method with a commercial flux. Brazing temperatures (liquidus were tracked by a digital infrared/laser pyrometer. Some mechanical properties studied were tensile strength and hardness. Finally, brazed joints produced from the developed brazing alloys were compared to that produced from muntz brass. Six (6 brazing alloys were successfully developed. Zinc and manganese were the main components, to which were added; 3 to 4 %wt silver and 11 to15 %wt modifying element. The microstructure showed a typical eutectic structure with zinc-rich phase distributed uniformly in the matrix with a combination of different sizes of dendrite, rounded blocks of compounds and hypoeutectic structures. AAS results indicated minimal out-gassing of zinc and FT-IR results indicated very low presence of atmospheric gas. The range of brazing temperature for best results was recorded from 690.90 to 735.10 0C. The joints produced from the developed brazing alloys had acceptable strengths with improved stress-strain behaviour compared to muntz brass.

  18. Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects.

    Science.gov (United States)

    Caetano, Lílian A; Jorge, Alexander A L; Malaquias, Alexsandra C; Trarbach, Ericka B; Queiroz, Márcia S; Nery, Márcia; Teles, Milena G

    2012-11-01

    Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance, early onset of hyperglycemia, and defects of insulin secretion. MODY subtypes described present genetic, metabolic, and clinical differences. MODY 2 is characterized by mild asymptomatic fasting hyperglycemia, and rarely requires pharmacological treatment. Hence, precise diagnosis of MODY is important for determining management and prognosis. We report two heterozygous GCK mutations identified during the investigation of short stature. Case 1: a prepubertal 14-year-old boy was evaluated for constitutional delay of growth and puberty. During follow-up, he showed abnormal fasting glucose (113 mg/dL), increased level of HbA1c (6.6%), and negative β-cell antibodies. His father and two siblings also had slightly elevated blood glucose levels. The mother had normal glycemia. A GCK heterozygous missense mutation, p.Arg191Trp, was identified in the proband. Eighteen family members were screened for this mutation, and 11 had the mutation in heterozygous state. Case 2: a 4-year-old boy investigated for short stature revealed no other laboratorial alterations than elevated glycemia (118 mg/dL); β-cell antibodies were negative. His father, a paternal aunt, and the paternal grandmother also had slightly elevated glycemia, whereas his mother had normal glycemia. A GCK heterozygous missense mutation, p.Glu221Lys, was identified in the index patient and in four family members. All affected patients had mild elevated glycemia. Individuals with normal glycemia did not harbor mutations. GCK mutation screening should be considered in patients with chronic mild early-onset hyperglycemia, family history of impaired glycemia, and negative β-cell antibodies.

  19. Modulatory Effects of Mild Carbon Monoxide Exposure in the Developing Mouse Cochlea.

    Science.gov (United States)

    Lopez, Ivan A; Acuna, Dora; Edmond, John

    2017-01-01

    Carbon monoxide (CO) is well known as a highly toxic poison at high concentrations, yet in physiologic amounts it is an endogenous biological messenger in organs such as the internal ear and brain. In this study we tested the hypothesis that chronic very mild CO exposure at concentrations 25-ppm increases the expression of oxidative stress protecting enzymes within the cellular milieu of the developing inner ear (cochlea) of the normal CD-1 mouse. In addition we tested also the hypothesis that CO can decrease the pre-existing condition of oxidative stress in the mouse model for the human medical condition systemic lupus erythematosus by increasing two protective enzymes heme-oxygenase-1 (HO-1), and superoxide dismutase-2 (SOD-2). CD-1 and MRL/lpr mice were exposed to mild CO concentrations (25 ppm in air) from prenatal only and prenatal followed by early postnatal day 5 to postnatal day 20. The expression of cell markers specific for oxidative stress, and related neural/endothelial markers were investigated at the level of the gene products by immunohistochemistry, proteomics and mRNA expression (quantitative real time-PCR). We found that in the CD-1 and MRL/lpr mouse cochlea SOD-2 and HO-1 were upregulated. In this mouse model of autoimmune disease defense mechanism are attenuated, thus mild CO exposure is beneficial. Several genes (mRNA) and proteins detected by proteomics involved in cellular protection were upregulated in the CO exposed CD-1 mouse and the MRL/lpr mouse.

  20. Chronic urticaria

    Directory of Open Access Journals (Sweden)

    Sandeep Sachdeva

    2011-01-01

    Full Text Available Chronic urticaria (CU is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the ′idiopathic′ forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.

  1. Sport and nonsport etiologies of mild traumatic brain injury: similarities and differences.

    Science.gov (United States)

    Rabinowitz, Amanda R; Li, Xiaoqi; Levin, Harvey S

    2014-01-01

    Mild traumatic brain injury (mTBI) has recently gained appreciation as a significant public health problem, which has highlighted just how little is known about its proximal and long-term effects. A major challenge in the study of mTBI is the heterogeneity of the condition. Research on mTBI has historically separated sport and nonsport etiologies, and the extent to which research from one of these samples translates to the other is unclear. This review examines the literature on mTBI, with a focus on comparing sport and nonsport etiologies with regard to the latest research on biomechanics, pathophysiology, neurocognitive effects, and neuroimaging. Issues of particular relevance to sports injuries, such as exercise, repetitive injuries, subconcussive blows, and chronic injury effects, are also reviewed.

  2. Modeling community integration in workers with delayed recovery from mild traumatic brain injury

    DEFF Research Database (Denmark)

    Mollayeva, T.; Shapiro, C. M.; Mollayeva, S.

    2015-01-01

    Background: Delayed recovery in persons after mild traumatic brain injury (mTBI) is poorly understood. Community integration (CI) is endorsed by persons with neurological disorders as an important outcome. We aimed to describe CI and its associated factors in insured Ontario workers with delayed...... recovery following mTBI. Methods: A cross-sectional study of insured workers in the chronic phase following mTBI was performed at a rehabilitation hospital in Ontario, Canada. Sociodemographic, occupational, injury-related, clinical, and claim-related data were collected from self-reports, medical...... assessments, and insurers' referral files. Community Integration Questionnaire (CIQ) scores were compared using analysis of variance or Spearman's correlation tests. Stepwise multivariable linear regression models were used to evaluate the associations with CI. Results: Ninety-four workers with mTBI (45...

  3. Are NSAIDs useful to treat Alzheimer's disease or mild cognitive impairment?

    Directory of Open Access Journals (Sweden)

    Bruno P Imbimbo

    2010-05-01

    Full Text Available Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4 against the onset of Alzheimer’s disease (AD. The biological mechanism of this protection is not completely understood and may involve the anti-inflammatory properties of NSAIDs or their ability of interfering with the β-amyloid (Aβ cascade. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and cyclooxygenase-2 (COX-2 selective inhibitors in mild-to-moderate AD patients produced negative results. A secondary prevention study with rofecoxib, a COX-2 selective inhibitor, in patients with mild cognitive impairment was also negative. A primary prevention study (ADAPT trial of naproxen (a non-selective COX inhibitor and celecoxib (a COX-2 selective inhibitor in cognitively normal elderly subjects with a family history of AD was prematurely interrupted for safety reasons after a median period of treatment of 2 years. Although both drugs did not reduce the incidence of dementia after two years of treatment, a 4-year follow up assessment surprisingly revealed that subjects previously exposed to naproxen were protected from the onset of AD by 67% compared to placebo. Thus, it could be hypothesized that the chronic use of NSAIDs may be beneficial only in the very early stages of the AD process in coincidence of initial Aβ deposition, microglia activation and consequent release of pro-inflammatory mediators. When the Aβ deposition process is already started, NSAIDs are no longer effective and may even be detrimental because of their inhibitory activity on chronically activated microglia that on long-term may mediate Aβ clearance. The research community should conduct long-term trials with NSAIDs in cognitively normal APOE ε4 carriers.

  4. Chronic 'speech catatonia' with constant logorrhea, verbigeration and echolalia successfully treated with lorazepam: a case report.

    Science.gov (United States)

    Lee, Joseph W Y

    2004-12-01

    Logorrhea, verbigeration and echolalia persisted unremittingly for 3 years, with occasional short periods of motoric excitement, in a patient with mild intellectual handicap suffering from chronic schizophrenia. The speech catatonic symptoms, previously refractory to various antipsychotics, responded promptly to lorazepam, a benzodiazepine with documented efficacy in the treatment of acute catatonia but not chronic catatonia. It is suggested that pathways in speech production were selectively involved in the genesis of the chronic speech catatonic syndrome, possibly a rare form of chronic catatonia not previously described.

  5. MILD BLEEDERS: DIAGNOSIS IS ELUSIVE IN LARGE NUMBER OF PATIENTS

    Directory of Open Access Journals (Sweden)

    Mrinalini kotru

    2016-10-01

    Full Text Available Abstract. Background: Bleeding is a common clinical presentation. Even patients with mild bleeding disorders are extensively investigated for ascertaining the cause. The present study was conducted in order to evaluate the extent of the possibility of diagnosis in mild bleeding disorders. Material and Methods: This was a prospective study of patients referred for work up of mild bleeding for a period of 13 months. A complete blood count, peripheral smear examination, Prothrombin time, Partial Thromboplastin time and Thrombin Time, Platelet Aggregometry test, tests for von Willebrand’s disease and Platelet function 3 availability were measured. Results: 164 patients presented with mild bleeding, in 114 of the  patients a single site of bleeding was present. Epistaxis was the most common presentation (39%. Cutaneous bleeding (petechiae and purpura was the next common site. History of a major bleeding tendency in the family was present only in 11 patients. The investigations showed that VWD (17/164, followed by clotting disorders (CD mainly mild hemophilia (15/164 were the most common diagnosable cause. There were also 4 cases of hypofibrinogenemia. The disorders of platelets (Platelet function defects/PFD were the least common (9/164. Rest 123 (75% patients could not be diagnosed on the basis of these investigations and were labeled as  Bleeding disorders – Unclassified (BDC. Conclusion: n our study, 75% of the patients with mild bleeding remained undiagnosed even after extensive laboratory workup, thus raising a very pertinent question that is it necessary that all mild bleeders submit to a broad battery of investigations, as the diagnosis continues to be elusive despite extensive workup.

  6. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B.; Nikolajsen, L.; Kehlet, H.;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies Udgivelsesdato: 2008/3...

  7. Chronic pain after hysterectomy

    DEFF Research Database (Denmark)

    Brandsborg, B; Nikolajsen, L; Kehlet, Henrik;

    2008-01-01

    BACKGROUND: Chronic pain is a well-known adverse effect of surgery, but the risk of chronic pain after gynaecological surgery is less established. METHOD: This review summarizes studies on chronic pain following hysterectomy. The underlying mechanisms and risk factors for the development of chronic...... post-hysterectomy pain are discussed. RESULTS AND CONCLUSION: Chronic pain is reported by 5-32% of women after hysterectomy. A guideline is proposed for future prospective studies. Udgivelsesdato: 2008-Mar...

  8. Biomarkers for dementia and mild cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Delgado-Alvarado, Manuel; Gago, Belén; Navalpotro-Gomez, Irene; Jiménez-Urbieta, Haritz; Rodriguez-Oroz, María C

    2016-06-01

    Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well-established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin-like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society.

  9. Palliative care in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Lilly, Evan J; Senderovich, Helen

    2016-10-01

    Chronic obstructive pulmonary disease (COPD) is the only major worldwide cause of mortality that is currently increasing in prevalence. Furthermore, COPD is incurable, and the only therapy that has been shown to increase survival is oxygen therapy in selected patients. Compared to patients with cancer, patients with COPD experience similar levels of pain, breathlessness, fatigue, depression, and anxiety and have a worse quality of life but have comparatively little access to palliative care. When these patients do receive palliative care, they tend to be referred later than patients with cancer. Many disease, patient-, and provider-related factors contribute to this phenomenon, including COPD's unpredictable course, misperceptions of palliative care among patients and physicians, and lack of advance care planning discussions outside of crisis situations. A new paradigm for palliative care would introduce palliative treatments alongside, rather than at the exclusion of disease-modifying interventions. This integrated approach would circumvent the issue of difficult prognostication in COPD, as any patient would receive individualized palliative interventions from the time of diagnosis. These points will be covered in this review, which discusses the challenges in providing palliative care to COPD patients, the strategies to mitigate the challenges, management of common symptoms, and the evidence for integrated palliative care models as well as some suggestions for future development.

  10. Comparison Of Levocetirizine And Cetirizine In Chronic Idiopathic Urticaria

    Directory of Open Access Journals (Sweden)

    Rathi Sanjay K

    2004-01-01

    Full Text Available The aim of the study was to compare efficacy, onset of action, and sedative effects of cetirizine (CTZ and levocetirizine (levoCTZ in chronic idiopathic urtcaria with fifteen patients in each group. They were found to be equipotent and the onset of action was almost same. Twenty percent in CTZ and 13.33% in levoCTZ exhibited mild sedation.

  11. DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF IBOPAMINE AND DIGOXIN IN PATIENTS WITH MILD-TO-MODERATE HEART-FAILURE - RESULTS OF THE DUTCH IBOPAMINE MULTICENTER TRIAL (DIMT)

    NARCIS (Netherlands)

    VANVELDHUISEN, DJ; MANINTVELD, AJ; DUNSELMAN, PHJM; LOK, DJA; DOHMEN, HJM; POORTERMANS, JC; WITHAGEN, AJAM; PASTEUNING, WH; BROUWER, J; LIE, KI

    1993-01-01

    Objectives. This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo. Backgroun

  12. [Chronic otitis mediaChronic Otitis Media].

    Science.gov (United States)

    Kohles, N; Schulz, T; Eßer, D

    2015-11-01

    There are 2 different kinds of chronic otitis media: Otitis media chronica mesotympanalis and otitis media chronica epitympanalis (cholesteatoma). The incidence of chronic otitis media as reported in literature differs in a wide range. The incidence rates vary between 0.45 and 46%. Both, otitis media chronica mesotympanalis and cholesteatoma, lead to eardrum perforation due to lengthy and recurring inflammations. Furthermore, chronic otitis media is characterized by frequently recurring otorrhea and conductive hearing loss.

  13. Efficacy of psychosocial intervention in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Waldorff, F B; Buss, D V; Eckermann, A

    2012-01-01

    OBJECTIVE: To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers. DESIGN: Multicentre, randomised, controlled, rater blinded trial. SETTING: Primary care and memory clinics in five...... Danish districts. PARTICIPANTS: 330 outpatients with mild Alzheimer's disease and their 330 primary care givers. INTERVENTIONS: Participating dyads (patient and primary care giver) were randomised to control support during follow-up or to control support plus DAISY intervention (multifaceted and semi...... for attrition (P = 0.0146 and P = 0.0103 respectively). CONCLUSIONS: The multifaceted, semi-tailored intervention with counselling, education, and support for patients with mild Alzheimer's disease and their care givers did not have any significant effect beyond that with well structured follow-up support at 12...

  14. Simulation of MILD combustion using Perfectly Stirred Reactor model

    KAUST Repository

    Chen, Z.

    2016-07-06

    A simple model based on a Perfectly Stirred Reactor (PSR) is proposed for moderate or intense low-oxygen dilution (MILD) combustion. The PSR calculation is performed covering the entire flammability range and the tabulated chemistry approach is used with a presumed joint probability density function (PDF). The jet, in hot and diluted coflow experimental set-up under MILD conditions, is simulated using this reactor model for two oxygen dilution levels. The computed results for mean temperature, major and minor species mass fractions are compared with the experimental data and simulation results obtained recently using a multi-environment transported PDF approach. Overall, a good agreement is observed at three different axial locations for these comparisons despite the over-predicted peak value of CO formation. This suggests that MILD combustion can be effectively modelled by the proposed PSR model with lower computational cost.

  15. Chronic stress disrupts neural coherence between cortico-limbic structures

    Directory of Open Access Journals (Sweden)

    João Filipe Oliveira

    2013-02-01

    Full Text Available Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP and the medial prefrontal cortex (mPFC in rats subjected to short term (STS and chronic unpredictable stress (CUS. CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

  16. The C-Terminal RpoN Domain of sigma54 Forms an unpredictedHelix-Turn-Helix Motif Similar to domains of sigma70

    Energy Technology Data Exchange (ETDEWEB)

    Doucleff, Michaeleen; Malak, Lawrence T.; Pelton, Jeffrey G.; Wemmer, David E.

    2005-11-01

    The ''{delta}'' subunit of prokaryotic RNA-polymerase allows gene-specific transcription initiation. Two {sigma} families have been identified, {sigma}{sup 70} and {sigma}{sup 54}, which use distinct mechanisms to initiate transcription and share no detectable sequence homology. Although the {sigma}{sup 70}-type factors have been well characterized structurally by x-ray crystallography, no high-resolution structural information is available for the {sigma}{sup 54}-type factors. Here we present the NMR derived structure of the C-terminal domain of {sigma}{sup 54} from Aquifex aeolicus. This domain (Thr323 to Gly389), which contains the highly conserved RpoN box sequence, consists of a poorly structured N-terminal tail followed by a three-helix bundle, which is surprisingly similar to domains of the {sigma}{sup 70}-type proteins. Residues of the RpoN box, which have previously been shown to be critical for DNA binding, form the second helix of an unpredicted helix-turn-helix motif. This structure's homology with other DNA binding proteins, combined with previous biochemical data, suggest how the C-terminal domain of {sigma}{sup 54} binds to DNA.

  17. Comparison between characteristics of mild slope equations and Boussinesq equations

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Boussinesq-type equations and mild-slope equations are compared in terms of their basic forms and characteristics. It is concluded that linear mild-slope equations on dispersion relation are better than non-linear Boussinesq equations. In addition, Berkhoff experiments are computed and compared by the two models, and agreement between model results and available experimental data is found to be quite reasonable, which demonstrates the two models' capacity to simulate wave transformation. However they can deal with different physical processes respectively, and they have their own characteristics.

  18. Farmakologisk behandling af mild ukompliceret hypertension i almen praksis

    DEFF Research Database (Denmark)

    Paulsen, Maja Skov; Christensen, Bo; Søndergaard, Jens

    2013-01-01

    Hypertension is an important risk factor for cardiovascular disease. In Denmark, patients with hypertension are primarily managed in primary care. A recent Cochrane review concluded that pharmacotherapy of patients with mild hypertension (systolic blood pressure 140-159 mmHg; diastolic blood...... pressure 90-99 mmHg; no diabetes or cardiovascular disease) did not reduce mortality or morbidity. The evidence for pharmacotherapy in patients having mild/uncomplicated hypertension is weak. However, current Danish guidelines have taken this into consideration in their recommendations of pharmacotherapy...

  19. A mouse model of human repetitive mild traumatic brain injury

    OpenAIRE

    Kane, Michael J; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

    2011-01-01

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an imp...

  20. Prognosis in patients with cirrhosis and mild portal hypertension

    DEFF Research Database (Denmark)

    Ytting, Henriette; Møller, Søren; Henriksen, Jens Henrik

    2006-01-01

    HVPG has been sparse. In this study, long-term survival and the risk of complications in mild portal hypertension were analysed. MATERIAL AND METHODS: Sixty-one patients with cirrhosis and HVPG below 10 mmHg were included in the study. Data were collected from medical files and National Patient...... with that in the background population. CONCLUSIONS: The frequency of complications in patients with mild portal hypertension is considerable, and guidelines for follow-up or medical prophylaxis are warranted. The risk of bleeding from oesophageal varices is low and bleeding-related deaths rare....

  1. Finding even more anthropogenic indicators in mildly prepared sediment samples

    DEFF Research Database (Denmark)

    Enevold, Renée; Odgaard, Bent Vad

    2016-01-01

    NPPs in anthropogenic soils and archaeological samples are often numerous in types as well as in abundance. Preparing these soil samples with methods based on acid digestion holds the potential of severe bias leaving the NPP assemblages devoid of acid vulnerable NPPs. In many cases it might...... be worth the effort to prepare the NPP samples with as mild a preparation method as possible. We have mildly prepared NPP samples from a small forest hollow, Tårup Lund, Denmark. From the recovered NPP assemblages we attempt identifying anthropogenic indicators by comparing to the environmental information...... indicators, pastoral/agricultural activity...

  2. Perforated Hepatic Hydatid Cyst into the Peritoneum with Mild Symptoms

    Directory of Open Access Journals (Sweden)

    A. Dirican

    2008-11-01

    Full Text Available Rupture into the abdominal cavity is a rare but serious complication of hydatid disease that necessitates emergency surgical intervention. We present herein a case with mild abdominal symptoms due to hydatid cyst rupture into the peritoneum after trauma. A 24-year-old man was admitted to the emergency room with mild abdominal pain. His symptoms had started after a fall four days earlier. Ultrasonography and computed tomography showed cystic lesions in the liver and peritoneum with intraabdominal free fluid. He was treated surgically with partial cystectomy and falciformoplasty. Postoperative albendazole therapy was given for two months. There was not recurrence four months postoperatively at control computed tomography.

  3. [Adults with mild mental retardation and intelligence tests].

    Science.gov (United States)

    Roivainen, Eka

    2015-01-01

    One of the criteria for mild mental retardation is a total level of less than 70 IQ points measured by an intelligence test. The results of intelligence tests are approximate. There are differences in the norms of test versions, and measurement error must be taken into account in individual testing. A total level of 80 measured by adult tests utilized in Finland does not exclude the possibility of mild mental retardation, and a total level of 60 does not confirm it. The test performance should be compared with other measures, such as school and work history, practical functional capacity and previous test results.

  4. Lumbar Discectomy of a Patient of Mitral Stenosis with Chronic Atrial Fibrillation Under Epidural Anaesthesia

    Directory of Open Access Journals (Sweden)

    Vinaya R Kulkarni

    2008-01-01

    Full Text Available A 60-year-old female patient posted for discectomy of lumbar region L 3 -L 4 was accidently diagnosed to have chronic atrial fibrillation of rheumatic aetiology.This is a case report of this patient of critical mitral stenosis with mild mitral regurgitation with chronic atrial fibrillation managed successfully under lower thoracic epidural anaesthesia,in prone position without any compli-cation.

  5. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    Science.gov (United States)

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention.

  6. Alcohol consumption and mortality in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Berntsen, Sine; Kragstrup, Jakob; Siersma, Volkert

    2015-01-01

    OBJECTIVE: To investigate the association between alcohol consumption and mortality in patients recently diagnosed with mild Alzheimer's disease (AD). DESIGN: A post hoc analysis study based on a clinical trial population. SETTING: The data reported were collected as part of the Danish Alzheimer...

  7. Awareness of deficits in mild cognitive impairment and Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Stokholm, Jette; Gade, Anders

    2004-01-01

    In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...

  8. Music Enhances Autobiographical Memory in Mild Alzheimer's Disease

    Science.gov (United States)

    El Haj, Mohamad; Postal, Virginie; Allain, Philippe

    2012-01-01

    Studies have shown that the "Four Seasons" music may enhance the autobiographical performance of Alzheimer's disease (AD) patients. We used a repeated measures design in which autobiographical recall of 12 mild AD patients was assessed using a free narrative method under three conditions: (a) in "Silence," (b) after being exposed to the opus "Four…

  9. Human Capability, Mild Perfectionism and Thickened Educational Praxis

    Science.gov (United States)

    Walker, Melanie

    2008-01-01

    This paper argues for a mild perfectionism in applying Amartya Sen's capability approach for an education transformative of student agency and well-being. Key to the paper is the significance of education as a process of being and becoming in the future, and education's fundamental objective of a positively changed human being. The capability…

  10. The Gross Motor Skills of Children with Mild Learning Disabilities

    Science.gov (United States)

    Nonis, Karen P.; Jernice, Tan Sing Yee

    2014-01-01

    Many international studies have examined the gross motor skills of children studying in special schools while local studies of such nature are limited. This study investigated the gross motor skills of children with Mild Learning Disabilities (MLD; n = 14, M age = 8.93 years, SD = 0.33) with the Test of Gross Motor Development-2 (TGMD-2, Ulrich,…

  11. Numerical Magnitude Processing in Children with Mild Intellectual Disabilities

    Science.gov (United States)

    Brankaer, Carmen; Ghesquiere, Pol; De Smedt, Bert

    2011-01-01

    The present study investigated numerical magnitude processing in children with mild intellectual disabilities (MID) and examined whether these children have difficulties in the ability to represent numerical magnitudes and/or difficulties in the ability to access numerical magnitudes from formal symbols. We compared the performance of 26 children…

  12. FAST Science: Teaching Science to Adolescents with Mild Disabilities.

    Science.gov (United States)

    Sasaki, Joyce; Serna, Loretta A.

    1995-01-01

    FAST I (Foundational Approach to Science Teaching I) is an inquiry and inductive-reasoning approach to learning physical science, ecology, and relational study. The program was successfully adapted for middle school students with mild disabilities. Teacher preparation, classroom groupings, behavior management procedures, evaluation, and…

  13. Care Partner Responses to the Onset of Mild Cognitive Impairment

    Science.gov (United States)

    Blieszner, Rosemary; Roberto, Karen A.

    2010-01-01

    Purpose: We examined characteristics, responses, and psychological well-being of care partners who support and assist older adults recently diagnosed with mild cognitive impairment (MCI). Design and Methods: Based on a sample of 106 care partners of community residents diagnosed with MCI at memory clinics, we conducted face-to-fa